[Characteristics of Soil Spectral Reflectance and Estimation of Soil Parameters in Fuxin Opencast Coal Mine]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Dec, 2009  |  Pubmed ID: 20210171

The surface soil samples of Fuxin opencast coal overburden dumps were collected in the field and the spectral reflectance and characteristic parameters of the soil samples, such as moisture content, pH, electrical conductivity (EC), available potassium (K+) content, and soil organic matter content (SOM), were measured. The Analysis results indicated that the curves of the soil spectral reflectance decreased with increasing the laid years. The possible reasons were the influences of soil texture and color. Although the valleys of the spectral reflectance appeared at 1 420, 1 910 and 2 210 nm, they were not conspicuous on the lime soil and mixture soil reflectance curves at 1 420 and 2 210 nm. With discussing the spectral reflectance of different types of soil texture, it's easy to find that the reflectance of fine grained soil was higher than the rough grained soil. Correlations between soil spectral reflectance and soil parameters were analyzed. The results showed that there was a positive relation between reflectance and pH, and correlation coefficient decreased with the wavelength increasing. There was no relationship between spectral reflectance and EC, and negative relations were observed between spectral reflectance and soil parameters, K+ and SOM, respectively. A high correlation coefficient was found between spectral reflectance and SOM, and the highest correlation coefficient reached -0. 76. The exponential correlation was found between sol spectral reflectance and soil moisture content to analyze all samples. According to different years and textures, more detail was described about the correlation between spectral reflectance of characteristic wavelength (1 910 and 1 943 nm) and soil moisture content. Meanwhile, the linear correlations were found under different conditions and higher correlation coefficients were obtained. In order to estimate SOM, five wavelengths (1 350, 1 602, 1 862, 2 160 and 2 227 nm) were selected based on principal component analysis to build a multiple linear regression model. The multiple correlation coefficient of calibration model (R2(C)) was 0.737 4, and the multiple correlation coefficient of validation (R2(V)) was 0.682 4. It indicated that the model was able to meet the needs of monitoring SOM in Fuxin opencast coal mine.

[Vestibular Testing Abnormalities in Individuals with Motion Sickness]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Aug, 2009  |  Pubmed ID: 20041604

To evaluate the vestibular function of motion sickness.

Quantitative Characterization of Optical and Physiological Parameters in Normal Breasts Using Time-resolved Spectroscopy: in Vivo Results of 19 Singapore Women

Journal of Biomedical Optics. Nov-Dec, 2009  |  Pubmed ID: 20059242

We report the quantitative measurements of optical and physiological parameters of normal breasts from 19 Singapore women by using time-resolved diffuse optical spectroscopy. Intrinsic absorption coefficient (mu(a)) and reduced scattering coefficients (mu(s) (')) of breasts were calculated from the time-resolved photon migration data. Physiology of breasts was characterized using the concentrations of oxyhemoglobin, deoxyhemoglobin, total hemoglobin (THC), and oxygenation saturation. On average, the experiment results showed that the mu(a) of young women (below 40 years old) was 36 to 38% greater than that of older women (above 40 years old) and that parameter THC was approximately 42% greater. Results also showed that the THC of premenopausal women was 24.3 microMol/L, which was approximately 69% larger than that of postmenopausal women at 14.1 microMol/L. Meanwhile, the mu(a) of premenopausal women was approximately 60% larger than that of postmenopausal women. Correlation analysis further showed that the optical and physiological parameters of breasts were strongly influenced by changes in the women's age, menopausal states, and body mass index. These in vivo experiment results will contribute to the breast tissue diagnosis between healthy and diseased breast tissues.

Evaluation of LOXL1 Polymorphisms in Exfoliation Syndrome in a Chinese Population

Molecular Vision. 2009  |  Pubmed ID: 19936304

To evaluate the association profiles of the lysyl oxidase-like 1 (LOXL1) gene polymorphisms with exfoliation syndrome in a Chinese population.

Syntheses, Crystal and Electronic Structures, and Physical Properties of Two Quaternary Chalcogenides: La(4)FeSb(2)Q(10) (Q = S, Se)

Inorganic Chemistry. Dec, 2009  |  Pubmed ID: 20000645

Two new quaternary chalcogenides, La(4)FeSb(2)S(10) and La(4)FeSb(2)Se(10), have been synthesized from the stoichiometric mixture of elements by solid-state reactions at 1100 degrees C. The compounds crystallize in the orthorhombic space group Pbcm with a = 15.066(4) A, b = 7.590(2) A, c = 13.341(4) A, and Z = 4 and a = 15.596(5) A, b = 7.869(2) A, c = 13.960(4) A, and Z = 4, respectively. These structures represent an unique three-dimensional network, in which SbQ(3) trigonal pyramids (Sb-S < 2.60 A, Sb-Se < 2.80 A) are connected via a relatively weak Sb-Q bond (Sb-S approximately 2.90 A, Sb-Se approximately 3.00 A) in a novel teeter-totter (SbQ(4))(n) chain motif. The theoretical studies confirm the Sb-Q bonding interactions within such teeter-totter chains. Their optical band gaps are measured to be 1.00 and 0.85 eV. At room temperature, their electrical conductivities are about 10(-4) S/cm. Both compounds display antiferromagnetic interactions between Fe centers, and their effective magnetic moments are 5.25 and 6.17 micro(B), respectively.

An Agarose-gel Based Method for Transporting Cell Lines

Current Chemical Genomics. 2009  |  Pubmed ID: 20161836

Cryopreserved cells stored in dry ice or liquid nitrogen is the classical method for transporting cells between research laboratories in different cities around the world in order to maintain cell viability. An alternative method is to ship the live cells in flasks filled with cell culture medium. Both methods have limitations of either a requirement on special shipping container or short times for the cells to survive on the shipping process. We have recently developed an agarose gel based method for directly transporting the live adherent cells in cell culture plates or dishes in ambient temperature. This convenient method simplifies the transportation of live cells in long distance that can maintain cells in good viability for several days.

[Altered Expression of L-type Calcium Channel Alpha1C and Alpha1D Subunits in Colon of Rats with Diarrhea-predominant Irritable Bowel Syndrome]

Zhonghua Yi Xue Za Zhi. Oct, 2009  |  Pubmed ID: 20137275

To investigate the molecular identities of L-type calcium channel alpha1C subunit (Cav1.2) and alpha1D subunit (Cav1.3) responsible for motor dysfunction of diarrhea-predominant irritable bowel syndrome (D-IBS).

[Lipid Frofile and Hemorheology in Obstructive Sleep Apnea-hypopnea Syndrome.]

Zhonghua Jie He He Hu Xi Za Zhi = Zhonghua Jiehe He Huxi Zazhi = Chinese Journal of Tuberculosis and Respiratory Diseases. Dec, 2009  |  Pubmed ID: 20193354

To investigate whether there was a correlation between lipid level, hemorheology and the obstructive sleep apnea hypopnea syndrome.

Mechanisms Mediating CCK-8S-induced Contraction of Proximal Colon in Guinea Pigs

World Journal of Gastroenterology : WJG. Mar, 2010  |  Pubmed ID: 20205277

To investigate the effects of sulfated cholecystokinin octapeptide (CCK-8S) on the contractile activity of guinea-pig proximal colon.

Volatile Organic Acid Adsorption and Cation Dissociation by Porphyritic Andesite for Enhancing Hydrolysis and Acidogenesis of Solid Food Wastes

Bioresource Technology. Jul, 2010  |  Pubmed ID: 20156676

Volatile organic acid adsorption, cation dissociation by porphyritic andesite, and their effects on the hydrolysis and acidogenesis of solid food wastes were evaluated through batch experiments. The acetic acid adsorption experiments show that pH was mainly regulated by H(+) adsorption. The mono-layer and multi-layer adsorption were found under the low (8.3-83.2 mmol/L) and high (133.22-532.89 mmol/L) initial acetic acid concentration, respectively. The dissociated cations concentration in acidic solution showed the predominance of Ca(2+). Porphyritic andesite addition elevated the pH levels and accelerated hydrolysis and acidogenesis in the batch fermentation experiment. Leachate of porphyritic andesite addition achieved the highest hydrolysis constant of 22.1 x 10(-3)kgm(-2)d(-1) and VS degradation rates of 3.9 g L(-1)d(-1). The highest activity of microorganisms represented by specific growth rate of ATP, 0.16d(-1), and specific consumption rate of Ca(2+), 0.18d(-1), was obtained by adding leachate of porphyritic andesite.

Transgenic Plasmodium That Expresses HIV-1 Gag Elicits Immunity and Protects Mice Against Vaccinia Virus-gag and Malarial Parasites

Vaccine. Nov, 2010  |  Pubmed ID: 20933565

Malaria and human immunodeficiency virus type 1 (HIV-1) infection overlap in many regions of the world. Our goal was to determine the feasibility of developing transgenic Plasmodium berghei that expresses HIV-1 Gag, PbGAG, as a conceptual bivalent vaccine against both HIV-1 infection and malaria. Immunization of mice with PbGAG induced specific responses to the HIV-1 Gag. Importantly, mice vaccinated with PbGAG were significantly protected from challenge with vaccinia virus-gag (VV-gag) with an average 30-fold reduction in titer (P<0.05). In addition, mice immunized with PbGAG developed Plasmodium-specific immune responses and the immunized animals were protected from challenges with blood-stage P. berghei NK65 and Plasmodium yoelii 17XL. We demonstrated a novel vaccination strategy that uses a live transgenic protozoan parasite-based bivalent vaccine to immunize mice and confer significant levels of protection against VV-gag and malarial parasite challenges. These observations have important implications for the development of a new form of bivalent vaccine against both HIV-1 and malaria.

Nonmotor Symptoms Are Independently Associated with Impaired Health-related Quality of Life in Chinese Patients with Parkinson's Disease

Movement Disorders : Official Journal of the Movement Disorder Society. Dec, 2010  |  Pubmed ID: 20945434

We performed a cross-sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18-month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health-related quality of life (Hr-QoL). The patients' NMS, Hr-QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39-item Parkinson's Disease Questionnaire (PDQ-39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's r(S) = 0.276, P = 0.012), H&Y (r(S) = 0.230, P = 0.038), and UPDRS III (r(S) = 0.350, P = 0.001). Similarly, the PDQ-39 SI significantly associated with the disease duration (r(S) = 0.258, P = 0.019), H&Y (r(S) = 0.340, P = 0.002), and UPDRS III (r(S) = 0.453, P < 0.001). NMS domains that influenced the PDQ-39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr-QoL. NMSS explains more of the variability in Hr-QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R² change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr-QoL in PD and that improving NMS should be viewed as an important part in the management of PD.

The Na+/Ca2+ Exchanger-1 Mediates Left Ventricular Dysfunction in Mice with Chronic Intermittent Hypoxia

Journal of Applied Physiology (Bethesda, Md. : 1985). Dec, 2010  |  Pubmed ID: 20947716

Chronic intermittent hypoxia (CIH) and cardiovascular dysfunction occur in patients with obstructive sleep apnea. We hypothesized that the Na(+)/Ca(2+) exchanger-1 (NCX1) mediates, at least partially, left ventricular (LV) dysfunction in CIH. Four groups of mice (N = 15-17 per group), either cardiac-specific NCX1 knockouts (KO) or wild types (WT), were exposed to either CIH or normoxia [i.e., handled controls (HC)] 10 h/day for 8 wk. As expected, myocardial expression of NCX1 was greater in WT than in KO animals, both in HC and CIH-exposed groups. In both CIH groups (WT or KO), but not the HC groups, blood pressure increased by 10% at week 1 over their baseline and remained elevated for all 8 wk, with no differences between WT and KO. LV dilation (increased diastolic and systolic dimension) and hypertrophy (increased left heart weight), along with LV dysfunction (greater end-diastolic pressure and lower ejection fraction), were observed in the WT animals compared with the KO following CIH exposure. Compared with HC, CIH exposure was associated with apoptosis (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling and caspase-3) in WT, but not KO, mice. We conclude that myocardial NCX1 does not mediate changes in blood pressure, but is one of the mediators for LV global dysfunction and cardiomyocyte injury in CIH.

[Effect of Lovastatin and Rosiglitazone on Cholesterol Reverse Transportation in Foam Cell]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Aug, 2010  |  Pubmed ID: 20979792

This study was designed to explore the function of ATP binding cassette transporter 1 (ABCA1) and Apolipoprotein A-I (ApoA-I) in cholesterol reverse transportation (RCT), the influence of lovastatin and rosiglitazone on the concentration of cholesterol (CHO) in THP-1 (human monocytic leukemia cell line) derived foam cells.

[Progress of Research on Exfoliation Syndrome]

[Zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology. Jun, 2010  |  Pubmed ID: 21055204

Exfoliation syndrome is an age-related systemic disorder of extracellular matrix, which is associated with a rapid progress of cataract resulting in the increased incidence of complications during operation and post-operation of cataract. The exact pathogenesis of exfoliation syndrome is still unclear. The purpose of this review is to discuss the recent progress in the clinical diagnosis, cell biology, molecular biology, and an improved knowledge of genetics, which will provide a better understanding of the mechanism behind this disorder.

Mycoplasma Hyorhinis Infection in Gastric Carcinoma and Its Effects on the Malignant Phenotypes of Gastric Cancer Cells

BMC Gastroenterology. 2010  |  Pubmed ID: 21062494

Mycoplasma hyorhinis infection has been postulated to play a role in the development of several types of cancer, but the direct evidence and mechanism remained to be determined.

A Preclinical 188Re Tumor Therapeutic Investigation Using MORF/cMORF Pretargeting and an AntiTAG-72 Antibody CC49

Cancer Biology & Therapy. Oct, 2010  |  Pubmed ID: 21099368

The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in 3 out of the 5 animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.

DHEA Prevents Aβ25-35-impaired Survival of Newborn Neurons in the Dentate Gyrus Through a Modulation of PI3K-Akt-mTOR Signaling

Neuropharmacology. Sep-Oct, 2010  |  Pubmed ID: 20167228

Infusion (i.c.v.) of beta-amyloid 25-35 (Abeta(25-35)) stimulates proliferation of progenitor cells in the hippocampal dentate gyrus (DG) of adult male mice, but a large population of the newborn cells will die in the 2nd week after birth, a critical period for neurite growth. Neurosteroid dehydroepiandrosterone (DHEA) has been demonstrated to promote neurite growth. Herein, we report that the DHEA-treatment on 6-12 days after BrdU-injection (BrdU-D(6-12)) dose-dependently attenuates the loss of newborn neurons induced by Abeta(25-35)-infusion. The DHEA-neuroprotection was blocked by the sigma(1) receptor antagonist NE100 and mimicked by the sigma(1) receptor agonist PRE084 when administered on BrdU-D(6-12). The DHEA-action was sensitive to the PI3K inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. The Abeta(25-35)-infusion decreased the levels of Akt, mTOR and p70S6k phosphorylation, which could be rescued by DHEA-treatment in a sigma(1) receptor-dependent manner. Furthermore, the Abeta(25-35)-infusion led to a decrease in the dendritic density and length of doublecortin positive cells in the DG, which also was improved by the DHEA-treatment on BrdU-D(6-12). These findings suggest that DHEA prevents the Abeta(25-35)-impaired survival and dendritic growth of newborn neurons through a sigma(1) receptor-mediated modulation of PI3K-Akt-mTOR-p70S6k signaling.

Knockout of Na+/Ca2+ Exchanger in Smooth Muscle Attenuates Vasoconstriction and L-type Ca2+ Channel Current and Lowers Blood Pressure

American Journal of Physiology. Heart and Circulatory Physiology. May, 2010  |  Pubmed ID: 20173044

Mice with smooth muscle (SM)-specific knockout of Na(+)/Ca(2+) exchanger type-1 (NCX1(SM-/-)) and the NCX inhibitor, SEA0400, were used to study the physiological role of NCX1 in mouse mesenteric arteries. NCX1 protein expression was greatly reduced in arteries from NCX1(SM-/-) mice generated with Cre recombinase. Mean blood pressure (BP) was 6-10 mmHg lower in NCX1(SM-/-) mice than in wild-type (WT) controls. Vasoconstriction was studied in isolated, pressurized mesenteric small arteries from WT and NCX1(SM-/-) mice and in heterozygotes with a global null mutation (NCX1(Fx/-)). Reduced NCX1 activity was manifested by a marked attenuation of responses to low extracellular Na(+) concentration, nanomolar ouabain, and SEA0400. Myogenic tone (MT, 70 mmHg) was reduced by approximately 15% in NCX1(SM-/-) arteries and, to a similar extent, by SEA0400 in WT arteries. MT was normal in arteries from NCX1(Fx/-) mice, which had normal BP. Vasoconstrictions to phenylephrine and elevated extracellular K(+) concentration were significantly reduced in NCX1(SM-/-) arteries. Because a high extracellular K(+) concentration-induced vasoconstriction involves the activation of L-type voltage-gated Ca(2+) channels (LVGCs), we measured LVGC-mediated currents and Ca(2+) sparklets in isolated mesenteric artery myocytes. Both the currents and the sparklets were significantly reduced in NCX1(SM-/-) (vs. WT or NCX1(Fx/-)) myocytes, but the voltage-dependent inactivation of LVGCs was not augmented. An acute application of SEA0400 in WT myocytes had no effect on LVGC current. The LVGC agonist, Bay K 8644, eliminated the differences in LVGC currents and Ca(2+) sparklets between NCX1(SM-/-) and control myocytes, suggesting that LVGC expression was normal in NCX1(SM-/-) myocytes. Bay K 8644 did not, however, eliminate the difference in myogenic constriction between WT and NCX1(SM-/-) arteries. We conclude that, under physiological conditions, NCX1-mediated Ca(2+) entry contributes significantly to the maintenance of MT. In NCX1(SM-/-) mouse artery myocytes, the reduced Ca(2+) entry via NCX1 may lower cytosolic Ca(2+) concentration and thereby reduce MT and BP. The reduced LVGC activity may be the consequence of a low cytosolic Ca(2+) concentration.

Cytotoxic T Lymphocyte Epitopes from Human Heparanase Can Elicit a Potent Anti-tumor Immune Response in Mice

Cancer Immunology, Immunotherapy : CII. Jul, 2010  |  Pubmed ID: 20182872

Heparanase is expressed in almost all advanced tumors, and therefore it may serve as a potential target for tumor therapy. Our previous study has shown that heparanase can serve as a potential universal tumor-associated antigen (TAA) for the immunotherapy of advanced tumors. Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro. The present study was designed to investigate whether the above peptides could induce immune responses in mice. Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched. We also found that these peptide-specific CTLs did not lyse autologous lymphocytes that had low heparanase activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-gamma-producing T cells as compared to a negative peptide. These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice. Because heparanase is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide-based vaccines may be useful for the immunotherapy of patients with advanced tumors.

The Immune Protein CD3zeta is Required for Normal Development of Neural Circuits in the Retina

Neuron. Feb, 2010  |  Pubmed ID: 20188655

Emerging evidence suggests that immune proteins regulate activity-dependent synapse formation in the central nervous system (CNS). Mice with mutations in class I major histocompatibility complex (MHCI) genes have incomplete eye-specific segregation of retinal ganglion cell (RGC) axon projections to the CNS. This effect has been attributed to causes that are nonretinal in origin. We show that a key component of MHCI receptor, CD3zeta, is expressed in RGCs. CD3zeta-deficient mice have reduced RGC dendritic motility, an increase in RGC dendritic density, and a selective defect of glutamate-receptor-mediated synaptic activity in the retina. Disrupted RGC synaptic activity and dendritic motility is associated with a failure of eye-specific segregation of RGC axon projections to the CNS. These results provide direct evidence of an unrecognized requirement for immune proteins in the developmental regulation of RGC synaptic wiring and indicate a possible retinal origin for the disruption of eye-specific segregation found in immune-deficient mice.

Impact of the Japanese Diagnosis Procedure Combination-based Payment System in Japan

Journal of Medical Systems. Feb, 2010  |  Pubmed ID: 20192060

In the health insurance system of Japan, a fee-for-service system has been applied to individual treatment services since 1958. This system involves a structural problem of causing an increase in examination and drug administration. A flat-fee payment system called DPC was introduced in April 2003 to solve the problems of the fee-for-service system. Based on the data of 2003 and 2004, we assessed the impact of DPC in Japan, and obtained the following conclusions: First, the introduction of DPC in Japan could not decrease the absolute value of medical costs; second, the internal efficiency of the institutions was improved, for example, by reducing the mean length of hospitalizations; third, the DPC-based diagnosis classification is considered to be effective for simplifying the medical fee system within the framework of EBM and for providing patients with information; and fourth, after introduction of the DPC, structural problems remain in the flat-fee payment system, such as examination and treatment of low quality, selection of patients and up coding. Its introduction should thus be performed with sufficient caution. We will make greater efforts to establish a better medical fee system by evaluating these problems.

Removal of Vestibular Schwannoma and Facial Nerve Preservation Using Small Suboccipital Retrosigmoid Craniotomy

Chinese Medical Journal. Feb, 2010  |  Pubmed ID: 20193244

Vestibular schwannoma, the commonest form of intracranial schwannoma, arises from the Schwann cells investing the vestibular nerve. At present, the surgery for vestibular schwannoma remains one of the most complicated operations demanding for surgical skills in neurosurgery. And the trend of minimal invasion should also be the major influence on the management of patients with vestibular schwannomas. We summarized the microsurgical removal experience in a recent series of vestibular schwannomas and presented the operative technique and cranial nerve preservation in order to improve the rates of total tumor removal and facial nerve preservation.

CDNA Cloning and Expression Analysis of Wheat (Triticum Aestivum L.) Phytoene and ζ-carotene Desaturase Genes

Molecular Biology Reports. Oct, 2010  |  Pubmed ID: 20013057

Carotene desaturation, an essential step in the carotenoid biosynthesis pathway, is catalyzed by two carotene desaturases, phytoene desaturase (PDS) and ζ-carotene desaturase (ζ-carotene desaturase, ZDS). Full-length cDNAs designated TaPDS and TaZDS were cloned from wheat (Triticum aestivum cv. Chinese Spring) respectively, using the rapid amplification of cDNA ends (RACE) approach. The cDNA of TaPDS sequence was 2076 bp long, containing a 1731 bp open reading frame (ORF) which deduced protein having 576 amino acid residues with predicted molecular mass of 64.3 kDa and having a putative transit sequence for plastid targeting in the N-terminal region. While the cDNA sequence of TaZDS was 2150 bp long, contained an ORF sequence of 1707 bp, and encoded a putative protein of 568 amino acid residues with an estimated molecular mass of 62.5 kDa. Phylogenetic analysis demonstrated that TaPDS and TaZDS showed high homology with other PDSs and ZDSs in higher plant species, respectively. Moreover, sequences analysis also showed a high degree of conservation among plant PDSs and ZDSs. The deduced TaPDS and TaZDS protein both have the dinucleotide binding domain and conserved regions characteristic of other carotene desaturases. Analysis of the expression pattern of wheat TaPDS and TaZDS in different tissues revealed that the transcripts levels were higher in leaves and flowers petals, followed by in inflorescences, and were nearly absent in the roots and seeds. Southern analysis of genomic DNA indicated that the wheat TaPDS and TaZDS probably belong to a low-copy-number gene family.

Clinicopathologic Characteristics of Pleomorphic Carcinoma of the Breast

Virchows Archiv : an International Journal of Pathology. Jan, 2010  |  Pubmed ID: 20013346

Pleomorphic carcinoma of the breast is considered a rare variant of high-grade ductal NOS carcinoma (NOS-IDC), and the prognosis is poor. However, its clinicopathologic features are not well-characterized. Using the criteria delineated in the World Health Organization breast tumor classification of 2003, ten cases of pleomorphic carcinoma were identified from 9794 NOS-IDC in our archived materials that were originally diagnosed as high-grade infiltrating ductal carcinoma of breast. To investigate the clinicopathologic characteristics and to elucidate the histologic diagnosis and differential diagnosis of this entity, we reviewed the pathology manifestations and clinical features of these cases and examined the tumor expression of ER, PR, PCNA, AE(1)/AE(3), p53, S-100, C-erbB-2, EMA, p63, and Bcl-2 by immunohistochemistry.

Differential Expression of CHS7 and CHS8 Genes in Soybean

Planta. Feb, 2010  |  Pubmed ID: 20016991

Chalcone synthase (CHS) catalyzes the first reaction specific for flavonoid and isoflavonoid biosynthesis. The soybean genome consists of nine copies of CHS genes (CHS1-CHS9) and a duplicate copy of CHS1. Even though the soybean CHS gene family members share a high degree of sequence similarity, they play different roles during plant development or in response to environmental stimuli. Our previous work on the comparison of a global gene expression in two soybean cultivars that differ in the level of total isoflavonoid accumulation has denoted the involvement of CHS7 and CHS8 genes in isoflavonoid synthesis. We have extended our effort to understand expression patterns of these two genes in soybean and in transgenic Arabidopsis. Promoter regions of CHS7 and CHS8 genes were isolated and in silico analysis performed to investigate potential transcription factor binding sites (TFBSs). The TFBSs were verified by DNase I footprint analysis. Some unique and several common TFBSs were identified in CHS7 and CHS8 promoters. We cloned beta-glucuronidase (GUS) under CHS7 and CHS8 promoters and monitored the tissue-specific GUS expression in transformed Arabidopsis. Differential GUS activity was observed in young leaves, roots, and mature pod walls of transgenic CHS7 promoter-GUS and CHS8 promoter-GUS plants. The tissue-specific expression patterns of CHS7 and CHS8 genes were determined in soybean by quantitative RT-PCR. Both CHS7 and CHS8 genes were expressed at higher levels in roots; however, overall expression pattern of these genes varied in different tissues. The results suggest that the structural diversity within CHS7 and CHS8 promoters may lead into differential activation of these genes by different inducers as well as developmental stage- and tissue-specific differences in gene expression.

Antibodies Directed to Alpha6beta4 Highlight the Adhesive and Signaling Functions of the Integrin in Breast Cancer Cell Lines

Cancer Biology & Therapy. Mar, 2010  |  Pubmed ID: 20061819

Integrin alpha6beta4 signaling interactions have been implicated in tumor progression, and beta4 expression has been linked to poor prognosis in certain breast cancer subtypes. We generated human antibodies to alpha6beta4 to further evaluate its role in tumor cell signaling. Biochemical characterization indicated these antibodies are specific for alpha6beta4, recognize distinct epitopes and have low nanomolar affinities for both human and murine protein. The antibodies demonstrated differing effects on alpha6beta4-mediated cellular adhesion, highlighting the existence of different functional epitopes on alpha6beta4. Interestingly however both antibodies blocked adhesion-independent growth in a panel of breast cancer cell lines. Antibody induced apoptosis and inhibition of phosphoinositide 3-kinase (PI3K) signaling were also observed within the context of matrix adhesion. Enhanced inhibitory effects were observed when the alpha6beta4 antibodies were used in combination with antibodies to epidermal growth factor receptor (EGFR) or erythoblastic leukemia viral oncogene homolog 2 (ErbB2). These findings illustrate a role for both the adhesive and signaling functions of alpha6beta4 in breast cancer cell survival. The antibodies and data generated herein advance our understanding of alpha6beta4 in regulating tumorigenic processes, and suggest that combination therapies involving alpha6beta4 may be therapeutically effective in breast cancer.

Thermoelectric Properties of Eu(Zn(1-x)Cd(x))2Sb2

Dalton Transactions (Cambridge, England : 2003). Jan, 2010  |  Pubmed ID: 20066197

The thermoelectric performance of EuZn(2)Sb(2) and EuCd(2)Sb(2) was optimized by mixed occupation of the transition metal position. Samples in the solid solution Eu(Zn(1-x)Cd(x))(2)Sb(2) with the CaAl(2)Si(2)-type crystal structure (space group Pm1) were prepared from the elements for compositions with x = 0, 0.1, 0.3, 0.5 and 1. The thermoelectric properties were investigated after densification of the products by spark plasma sintering (SPS). The samples show low electrical resistivity, high thermopower and a low lattice thermoconductivity. The highest ZT value of 1.06 at 650 K is obtained for x = 0.1.

Treatment with Progesterone After Focal Cerebral Ischemia Suppresses Proliferation of Progenitor Cells but Enhances Survival of Newborn Neurons in Adult Male Mice

Neuropharmacology. May, 2010  |  Pubmed ID: 20079361

Stroke stimulates cell proliferation in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG) in adult rodents and humans. However, most newborn cells will die within 1-2 weeks. We recently have revealed that progesterone (P4) promotes the survival of newborn neurons in the DG and improves the neurological dysfunction after cerebral ischemia. The aim of this study was to further explore the effects of P4 on the ischemia-induced neurogenesis in the DG, SVZ and striatum. Bromodeoxyuridine (BrdU) was used to label proliferating cells on day 3 after middle cerebral artery occlusion (MCAO). P4 (4 mg/kg) was injected for 3 consecutive days at BrdU-D(-1 to 1) (from one day before to one day after BrdU-injection) or BrdU-D(4-6) (4-6 days after BrdU-injection). The P4-treatment at BrdU-D(-1 to 1) attenuated the increase in the density of 24-h-old BrdU(+) cells in MCAO-DG and -SVZ, which was blocked by the 5alpha-reductase inhibitor finasteride. The P4-treatment at BrdU-D(4-6) significantly increased the density of 28-day-old BrdU(+) cells in MCAO-DG without changing the population ratios of BrdU(+)/NeuN(+) and BrdU(+)/GFAP(+) cells, which was sensitive to the blockade of P4 receptor and extracellular signal-regulated kinase (ERK). In addition, the P4-treatment at BrdU-D(4-6) produced approximately 2-fold increase in the density of 28-day-old BrdU(+) cells in MCAO-striatum. This study provides evidence that the P4-treatment after stroke suppresses ischemia-stimulated proliferation of progenitor cells but improves the poor survival of ischemia-induced newborn cells.

Epithelial Uptake of [18F]1-(2'-deoxy-2'-arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice

Gastroenterology. Apr, 2010  |  Pubmed ID: 20080095

Uptake of [18F]1-(2'-deoxy-2'-arabinofuranosyl)cytosine (D-FAC) is a trait of activated lymphocytes; its biodistribution predominates in the spleen, thymus, and bone marrow. In addition, D-FAC is taken up at high levels by the intestine. We analyzed the regional specificity of uptake and cell types that mediate it.

MicroRNAs Reduce Tumor Growth and Contribute to Enhance Cytotoxicity Induced by Gefitinib in Non-small Cell Lung Cancer

Chemico-biological Interactions. Mar, 2010  |  Pubmed ID: 20097187

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. An oncogenic or tumor-suppressive miRNA may have potential as a therapeutic target to control cancers. Gefitinib is a tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR). H460 and A549 cells with EGFR receptor-independent over-activation of protein kinase B (Akt) or extracellular signal-regulated kinases (ERK) are significantly resistant to gefitinib. The first aim of this study was to confirm a role for three miRNAs (let-7a, hsa-miR-126, and hsa-miR-145) in the inhibition of proliferation in non-small cell lung cancer (NSCLC) cells. A second aim was to evaluate three miRNAs for their abilities to overcome cellular resistance and enhance the gefitinib cytotoxicity. The expression of miRNAs was estimated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation was examined by sulforhodamine B assay and tumor xenografts were measured in SCID/beige mice. The activation of Akt and ERK was observed by Western blotting. Forced expression of individual miRNA suppressed the growth of two cell lines and xenografts. The effect varied among different miRNAs and cells. Restoration of hsa-miR-126 more obviously inhibited cell growth than did restoration of hsa-miR-145 in both cells, and the suppressive effect was more significant in H460 xenografts than in A549 xenografts. Western blotting revealed that the inhibition of cell proliferation resulted from the inhibition of the activation of Akt and ERK. Moreover, forced expression of miRNAs contributed to enhanced cytotoxicity induced by gefitinib in lung cancer cells; especially in hsa-miR-126, the highest value of half max inhibitory (IC50) was increased sixfold. These findings confirm that tumor-suppressive miRNAs can inhibit the growth of NSCLC cells and enhance the targeted agents cytotoxicity, suggesting novel potential approaches to an improvement in chemotherapy.

Proteomic Analysis of Proteins Involved in Spermiogenesis in Mouse

Journal of Proteome Research. Mar, 2010  |  Pubmed ID: 20099899

Spermiogenesis is a unique process in mammals during which haploid round spermatids mature into spermatozoa in the testis. Its successful completion is necessary for fertilization and its malfunction is an important cause of male infertility. Here, we report the high-confidence identification of 2116 proteins in mouse haploid germ cells undergoing spermiogenesis: 299 of these were testis-specific and 155 were novel. Analysis of these proteins showed many proteins possibly functioning in unique processes of spermiogenesis. Of the 84 proteins annotated to be involved in vesicle-related events, VAMP4 was shown to be important for acrosome biogenesis by in vivo knockdown experiments. Knockdown of VAMP4 caused defects of acrosomal vesicle fusion and significantly increased head abnormalities in spermatids from testis and sperm from the cauda epididymis. Analysis of chromosomal distribution of the haploid genes showed underrepresentation on the X chromosome and overrepresentation on chromosome 11, which were due to meiotic sex chromosome inactivation and expansion of testis-expressed gene families, respectively. Comparison with transcriptional data showed translational regulation during spermiogenesis. This characterization of proteins involved in spermiogenesis provides an inventory of proteins useful for understanding the mechanisms of male infertility and may provide candidates for drug targets for male contraception and male infertility.

Phase I Trial of Non-cytotoxic Suramin As a Modulator of Docetaxel and Gemcitabine Therapy in Previously Treated Patients with Non-small Cell Lung Cancer

Cancer Chemotherapy and Pharmacology. Nov, 2010  |  Pubmed ID: 20107799

In preclinical models, non-cytotoxic suramin (concentrations <50 μM) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer.

Self-rated Health and Comprehensive Geriatric Functions in Community-living Older Adults in Japan

Journal of the American Geriatrics Society. Jan, 2010  |  Pubmed ID: 20122074

Polybrominated Diphenyl Ethers in Background Surface Soils from the Yangtze River Delta (YRD), China: Occurrence, Sources, and Inventory

Environmental Science and Pollution Research International. May, 2010  |  Pubmed ID: 20127420

Very few data for polybrominated diphenyl ethers (PBDEs) were available in the Yangtze River Delta (YRD), one of the most developed and urbanized region in China. In this study, Chongming Island, located at the estuary of the Yangtze River, was selected as background area to investigate the occurrence, sources, and inventory of PBDEs.

DMXB (GTS-21) Ameliorates the Cognitive Deficits in Beta Amyloid(25-35(-) ) Injected Mice Through Preventing the Dysfunction of Alpha7 Nicotinic Receptor

Journal of Neuroscience Research. Jun, 2010  |  Pubmed ID: 20127813

Intracerebroventricular injection of beta-amyloid(25-35) (Abeta(25-35)) in mice leads to cognitive deficits with the dysfunction of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) within 1-2 weeks in a dose-dependent manner. The present study focused on the effect of DMXB, a selective alpha7nAChR agonist, on Abeta(25-35) (3 nmol)-impaired spatial memory and alpha7nAChR function. We found that the treatment with DMXB on days 1-10 after Abeta(25-35) injection dose-dependently prevented Abeta(25-35)-induced impairment of acquisition performance and probe trail test in Morris water maze. Importantly, the treatment with DMXB (1 mg/kg) perfectly prevented Abeta(25-35)-induced depression of alpha7nAChR response, which was associated with improving the probability of presynaptic glutamate release and the induction of high-frequency stimulation (HFS)-dependent long-term potentiation (LTP) in hippocampal Schaffer collaterale-CA1 synapse. Furthermore, although either the basal level of extracellular signal-regulated kinase 2 (ERK2) or its phosphorylation in the hippocampus had no difference between control and Abeta(25-35) mice, the Abeta(25-35) injection significantly attenuated HFS-triggered increase in ERK2 phosphorylation. The treatment with DMXB also rescued the ERK2 phosphorylation triggered by HFS in Abeta(25-35) mice that is required for LTP induction. This study firstly provides in vivo evidence that the anti-amnesic effect of DMXB is likely due to preventing the Abeta(25-35)-induced dysfunction of alpha7nAChR.

Visuospatial Attention Deficit in Patients with Local Brain Lesions

Brain Research. Mar, 2010  |  Pubmed ID: 20132799

The disability of visuospatial attention can lead to poor volitional movement and functional recovery in patients with brain lesions. However, the accurate clinical method to assess visuospatial attention is limited. The frontoparietal network including the posterior parietal cortex and the frontal eye fields has been shown to involve in visuospatial attention. The Attention Network Test provided measures for three different components of visuospatial attention: alerting, orienting and executive control. This study was to probe the deficit and relationship of visuospatial attention using Attention Network Test paradigm in patients with frontoparietal network lesions. During this task, patients responded significantly slower on each cue condition and target type than controls, and showed deficits in the alerting and orienting networks. The efficiency of resolving conflict was decreased in patients with frontal lesions whereas this was increased in patients with parietal lesions. These findings suggest that the frontoparietal network is involved in the alerting and orienting attentional function and the executive function is possibly selectively associated with the frontal lobe. The Attention Network Test paradigm produces sensitive, valid and reliable subject estimates of visuospatial attention function in patients with brain lesions, and may be useful for clinical rehabilitation strategy selection for patients with the frontoparietal network lesions.

Multistage Inversion Algorithm for Biological Tissue Imaging

Journal of Biomedical Optics. Jan-Feb, 2010  |  Pubmed ID: 20210453

A new inversion method for diffuse optical tomography is proposed. This is a multistage algorithm, that uses a signal subspace-based method to simplify the inverse problem and proposes a guided iterative inversion process to improve the imaging. First, subspace-based analysis is used to determine the voxels that definitely belong to the background and exclude them from further consideration. Then, the pseudo-inverse technique is applied for reconstruction. In the final stage, the reconstruction is improved iteratively by finding and excluding more voxels belonging to background. The method reduces the ill-posedness of the image reconstruction problem iteratively such that good imaging results are obtained for multiple heterogeneities having complicated geometries even in the presence of 3% additive white noise.

Expression of HAb18G is Associated with Tumor Progression and Prognosis of Breast Carcinoma

Breast Cancer Research and Treatment. Dec, 2010  |  Pubmed ID: 20213083

HAb18G is a recently identified hepatoma-associated antigen and its association with tumor growth, invasion, and angiogenesis has been studied in a variety of tumors. However, its role in the tumor progression of breast cancer has not been explored. HAb18G expression was examined by immunohistochemistry in pathological sections of 1,637 breast tissue samples and by in situ hybridization in 41 cases of invasive breast carcinomas (BC). While not detected in any cases of tumor-like conditions or benign tumors of breast, and only rarely in normal tissue (4.4%), HAb18G expression was gradually up-regulated from atypical ductal hyperplasia (27.3%), to ductal carcinoma-in situ (59.8%), and to BC (61.4%) (P < 0.01). Its expression in BC was correlated positively with C-erbB-2 expression and histologic grade (P < 0.001), and negatively with the expression of estrogen and progesterone receptors (P < 0.001). Significant differences of expression were also identified among the subgroups of BC examined: in decreasing order from invasive micropapillary carcinoma, ductal carcinoma, lobular carcinoma, papillary carcinoma, medullary carcinoma, to mucinous adenocarcinoma (P = 0.001), corresponding to their known clinical aggressiveness. In an expanded group of 186 BC patients with proper follow up, our previous findings were confirmed: HAb18G expression was significantly associated with local recurrence, distant metastasis and tumor mortality (P < 0.01). We also demonstrated that up-regulated tumor expression of HAb18G was a significant predictor of reduced disease progression-free survival rate and a shorter overall survival, independent of systemic therapies. In conclusion, this study suggests that HAb18G expression is associated with BC progression and prognosis. Further evaluation of this new marker in breast cancer is indicated.

Induction of Balance and Breadth in the Immune Response is Beneficial for the Control of SIVmac239 Replication in Rhesus Monkeys

The Journal of Infection. May, 2010  |  Pubmed ID: 20227437

The aim of this study was to induce cellular and humoral responses with enhanced breadth and more balanced magnitude as a possible approach for an effective HIV vaccine.

An Optimized Telomerase-specific Lentivirus for Optical Imaging of Tumors

Cancer Research. Apr, 2010  |  Pubmed ID: 20233877

Advances in medical imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography, have made great progress in detecting tumors. However, these imaging techniques are unable to differentiate malignant tumors from benign ones. Recently developed optical imaging of tumors in small animals provides a useful method to distinguish malignant tumors from their surrounding normal tissues. Human telomerase reverse transcriptase (hTERT) is normally inactivated in most somatic cells, whereas it is commonly reactivated in many cancer cells. In this study, we constructed a lentiviral vector that expresses green fluorescent protein (GFP) driven by an optimized hTERT promoter to create a noninvasive tumor-specific imaging methodology. The activity of this optimized hTERT promoter was found to be equal to the activity of SV40 and cytomegalovirus promoters. In vitro experiments showed that GFP was only expressed in telomerase-positive tumor cells infected with this lentivirus, whereas there was no GFP expression in telomerase-negative tumor cells or normal somatic cells. We also found that subcutaneous telomerase-positive tumors could be visualized 24 hours after an intratumoral injection with this lentivirus by using a charge-coupled device (CCD) camera. In contrast, telomerase-negative tumors could not be imaged after an intratumoral injection even for 30 days. These results suggest that infection with lentivirus containing this optimized hTERT promoter might be a useful diagnostic tool for the real-time visualization of macroscopically invisible tumor tissues using a highly sensitive CCD imaging system.

E-selectin Targeting to Visualize Tumors in Vivo

Contrast Media & Molecular Imaging. Mar-Apr, 2010  |  Pubmed ID: 20235150

Generally angiogenic factors induce the expression of E-selectin in vascular endothelial cells in the tumors. In this study, we employed an anti-E-selectin monoclonal antibody to target tumors in vivo and evaluated an optical imaging reagent to visualize tumor regions. The anti-E-selectin antibody was conjugated on the surface of liposomes, which encapsulated the near-infrared fluorescent substances Cy3 or Cy5.5. The liposomes efficiently recognized human umbilical vein endothelial cells only when E-selectin was induced by angiogenic factors such as TNF-alpha in vitro. Cy5.5 encapsulated into liposomes that were conjugated with an anti-E-selectin antibody successfully visualized Ehrlich ascites tumor cells when transplanted into mice. Thus, E-selectin targeting with liposomes containing a near-infrared fluorescent dye was found effective in visualizing tumors in vivo. This strategy should be extremely useful as a method to identify sentinel lymphatic nodes and angiogenic tumors as well as use for drug delivery to tumor cells.

Differential Expression of MRNAs Encoding BMP/Smad Pathway Molecules in Antral Follicles of High- and Low-fecundity Hu Sheep

Animal Reproduction Science. Jul, 2010  |  Pubmed ID: 20303683

The Hu sheep is world-famous for its hyper-prolificacy and the bone morphogenetic protein (BMP)/Smad pathway and several other closely related molecules (GDF9, TGF-betaRI) have been shown to have a close relationship with reproduction in sheep. In order to investigate the mechanism of high fecundity in Hu sheep and its relationship with the BMP/Smad pathway, 147 Hu sheep were blood sampled for detection of the FecB mutation (A746G) in the BMPRIB gene by PCR-SSCP, and sixteen adult Hu ewes classified as either high-fecundity (HF) or low-fecundity (LF) animals were sacrificed for tissue and antral follicle sampling. The tissue distribution patterns of mRNAs encoding BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP15), BMP receptors (BMPRIA, BMPRIB and BMPRII), intracellular transducers (Smad1, Smad5 and Smad4) and closely related molecules (GDF9 and TGF-betaRI) were detected by RT-PCR and the gene expression levels in antral follicles were investigated by real-time PCR. The results showed that all experimental animals were homozygous for the BMPRIB (A746G) mutation, and all detected genes related to the BMP/Smad pathway and GDF9 and TGF-betaRI were expressed in the ovary. In addition, BMP4, BMPRIB, BMPRII, Smad4, GDF9 and TGF-betaRI mRNAs were more abundant in the antral follicles of HF animals than those of LF animals (P<0.05), but BMP15 mRNA was less abundant (P<0.01). This suggests that there could be an unidentified genetic mutation in BMPRIB, or other unidentified genes and unknown factors, which controls ovarian number by changing the expression patterns of genes known to regulate ovulation rate via the BMP/Smad pathway and closely related molecules (GDF9 and TGF-betaRI).

[Enclosure Experiments About the Hydrodynamics Effects on the Plankton]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Jan, 2010  |  Pubmed ID: 20329518

To explore the effects of hydrodynamics on plankton, four kinds of surface flow enclosure experiments were done from August, 2007 to July, 2008. The flow velocity were 0.002, 0.10, 0.15 and 0.30 m x s(-1) respectively. Under 0.15 and 0.30 m x s(-1) surface velocity conditions, it was revealed that Spirogyra biomasses were 2.3 times and 31.3 times of the ones under static state respectively. Under 0.10, 0.15 and 0.30 m x s(-1) conditions, Chl-a concentrations were 45%, 54% and 26% of the ones under statistic state while zooplankton biomasses were 38%, 27% and 6% respectively. The mechanism is that a certain flow velocity stimulates Spirogyra growth may be for the shear stress generated by the surface flow can help the vegetative reproduction. Shear stress and turbulence may also bring the phytoplankton to the light limited area by force. Besides, as Spirogyra grows well, it can inhibit the phytoplankton growth by excretion or some symbiotic microorganism. When shear stress or water turbulence exceeds a certain value, crustacean zooplankton successful grazing rate may also be depressed.

ATP Depletion-induced Actin Rearrangement Reduces Cell Adhesion Via P38 MAPK-HSP27 Signaling in Renal Proximal Tubule Cells

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2010  |  Pubmed ID: 20332631

Ischemia causes desquamation of proximal tubular epithelial cells leading to acute renal failure. However, the molecular mechanisms underlying the detachment of proximal tubule cells remain unknown. In this study, we reported that ATP depletion resulted in actin polymerization, a shift of filamentous actin from web-like structure to fragmented parallel stress fibers, followed by a reduction of cellular adhesion ability. The pre-treatment with Jasplakinolide, an actin stabilizer, prevented ATP depletion-induced actin polymerization and reduction of cell adhesion, indicating that the cytoskeleton reorganization decreased the cellular adhesion ability. Furthermore, the ATP depletion markedly increased the levels of p38MAPK and HSP27 phosphorylation with enhanced translocation of phosphorylated HSP27 from cytoskeleton to cytoplasm. The inhibition of p38MAPK by SB203580 blocked the ATP depletion to induce HSP27 phosphorylation and actin polymerization. These findings suggest that ischemia remodels filamentous actin leading to desquamation of proximal tubular epithelial cells through p38 MAPK-HSP27 signaling.

Dissipation and Evaluation of Hexaflumuron Residues in Chinese Cabbage Grown in Open Fields

Journal of Agricultural and Food Chemistry. Apr, 2010  |  Pubmed ID: 20345168

The dissipation and residue behavior of hexaflumuron in Chinese cabbage ( Brassica pekinensis ) under different treatments were investigated at two main cabbage-growing areas in China. The dissipation rates of hexaflumuron in cabbages and soils fit a first-order decay process very well. The dissipation times for 50% of the hexaflumuron in cabbage and soil were 3.37 and 3.01 days from Hunan province and 5.58 and 3.68 days in Tianjin, respectively, when Chinese cabbage was treated with 180 g of active ingredient (ai)/ha. Hexaflumuron residual times in cabbage and soil were influenced strongly by the application rate and frequency. The application regimen of hexaflumuron in the cabbage field, a rate of 120 g of ai/ha with two applications at a 7 day interval and a 21 day preharvest interval, was recommended from the point of view of ensuring food safety. The residual levels of hexaflumuron in cabbages were lower than the standards of the "Positive List System for Agricultural Chemical Residues in Foods" based on the recommended application regimen.

A Histone-fold Complex and FANCM Form a Conserved DNA-remodeling Complex to Maintain Genome Stability

Molecular Cell. Mar, 2010  |  Pubmed ID: 20347428

FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF. We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. In the cell, FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. In vertebrates, FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. Yeast orthologs of these proteins function together to resist MMS-induced DNA damage and promote gene conversion at blocked replication forks. Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human.

Protective Effects of Xyloketal B Against MPP+-induced Neurotoxicity in Caenorhabditis Elegans and PC12 Cells

Brain Research. May, 2010  |  Pubmed ID: 20347725

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population over age 65years. Mitochondrial defect and oxidative stress actively participate in the dopaminergic (DA) neuron degeneration in PD. Xyloketal B is a novel marine compound with unique chemical structure isolated from mangrove fungus Xylaria sp. (no. 2508). Recently, we have demonstrated that Xyloketal B can directly scavenge DPPH free radicals and protects mitochondria against oxidative insult. In the present study, we investigate the neuroprotective action of xyloketal B against MPP+-induced neurotoxicity in Caenorhabditis elegans and PC12 cells. The viability and DA neurodegeneration was assessed in C. elegans selectively expressing green fluorescent protein (GFP) in DA neurons. PC12 cell damage was measured using MTT and nuclear morphology. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential and total GSH were assessed. Xyloketal B dose-dependently protected against MPP+-induced loss of viability and DA neurodegeneration in C. elegans. Similar neuroprotection was replicated in MPP+ PC12 cell model. In addition, xyloketal B attenuated MPP+-induced intracellular ROS accumulation, loss of mitochondrial membrane potential and restored total GSH level in PC12 cells. All together, the present study demonstrates that xyloketal B protects against MPP+-induced neurotoxicity in C. elegans and PC12 cells mainly through its antioxidant property and restoration of total GSH level.

Effect of Atorvastatin on Dendritic Cells of Tubulointerstitium in Diabetic Rats

BMB Reports. Mar, 2010  |  Pubmed ID: 20356459

Inflammatory reactology has become increasingly important in diabetic kidney disease. In this study, we estabilished STZ-induced diabetic rat model to investigate whether dendritic cells (DCs) mediated tubulointerstitial damages, and whether the effects by DCs were mediated by P-selectin expression and can be inhibited by atorvastatin. The study demonstrated that there was an accumulation of DCs in diabetic rats mediated by P-selectin. It also showed the accumulation of DCs and expression of P-selectin was closely correlated with the degree of renal tubulointerstitial injury. These effects were markedly attenuated by atorvastatin. Thus, DCs play a role in tubulointerstitial damages, atorvasttin can prevent renal tubulointerstitium from damage by inhibiting the P-selectin expression and DCs migration.

RpoB Gene Mutation Profile in Rifampicin-resistant Mycobacterium Tuberculosis Clinical Isolates from Guizhou, One of the Highest Incidence Rate Regions in China

The Journal of Antimicrobial Chemotherapy. Jun, 2010  |  Pubmed ID: 20356906

Expression and Function of Matrix Gla Protein in Human Peritoneal Mesothelial Cells

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. Oct, 2010  |  Pubmed ID: 20368306

Chronic peritoneal dialysis (PD) is associated with peritoneal calcification. Studies in vascular tissue suggest that ectopic calcification is not merely a passive but a regulated process resembling bone mineralization. We investigated whether peritoneal calcification is controlled by matrix Gla protein (MGP) secreted by peritoneal mesothelial cells.

Identification of Hits As Matrix-2 Protein Inhibitors Through the Focused Screening of a Small Primary Amine Library

Journal of Medicinal Chemistry. May, 2010  |  Pubmed ID: 20394375

Although amantadine derivatives are the only M2 drugs for influenza virus A, their use is limited in the U.S. because of drug resistance. Here we report the identification of multiple M2 inhibitors that were rapidly generated through focused screening of a small primary amine library that was designed using a scaffold-hopping strategy based on amantadine. These compounds are as active as amantadine and might be hits for further lead generation processes.

JAAD Grand Rounds Quiz. Hemorrhagic Nodule on the Abdomen

Journal of the American Academy of Dermatology. May, 2010  |  Pubmed ID: 20398828

Ultrathin Diamond-like Carbon Film Coated Silver Nanoparticles-based Substrates for Surface-enhanced Raman Spectroscopy

ACS Nano. May, 2010  |  Pubmed ID: 20433194

We have demonstrated that by coating with a thin dielectric layer of tetrahedral amorphous carbon (ta-C), a biocompatible and optical transparent material in the visible range, the Ag nanoparticle-based substrate becomes extremely suitable for surface-enhanced Raman spectroscopy (SERS). Our measurements show that a 10 A or thicker ta-C layer becomes efficient to protect the oxygen-free Ag in air and prevent Ag ionizing in aqueous solutions. Furthermore, the Ag nanoparticles substrate coated with a 10 A ta-C film shows a higher enhancement of Raman signals than the uncoated substrate. These observations are further supported by our numerical simulations. We suggest that biomolecule detections in analytic assays could be easily realized using ta-C-coated Ag-based substrate for SERS especially in the visible range. The coated substrate also has higher mechanical stability, chemical inertness, and technological compliance, and may be useful, for example, to enhance TiO(2) photocatalysis and solar-cell efficiency by the surface plasmons.

A Novel Role for 14-3-3sigma in Regulating Epithelial Cell Polarity

Genes & Development. May, 2010  |  Pubmed ID: 20439433

The loss of epithelial polarity is thought to play an important role during mammary tumor progression. Using a unique transgenic mouse model of ErbB2-induced mammary tumorigenesis, we demonstrated previously that amplification of ErbB2 is frequently accompanied by loss of the 14-3-3sigma gene. Here, we demonstrate that ectopic expression of 14-3-3sigma results in restoration of epithelial polarity in ErbB2-transformed mammary tumor cells. We further demonstrate that targeted deletion of 14-3-3sigma within primary mammary epithelial cells increases their proliferative capacity and adversely affects their ability to form polarized structures. Finally, we show that 14-3-3sigma can specifically form complexes with Par3, a protein that is essential for the maintenance of a polarized epithelial state. Taken together, these observations suggest that 14-3-3sigma plays a critical role in retaining epithelial polarity.

Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen

Journal of Medicinal Chemistry. Jun, 2010  |  Pubmed ID: 20481602

A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 muM. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.

The Apical Transmembrane Protein Crumbs Functions As a Tumor Suppressor That Regulates Hippo Signaling by Binding to Expanded

Proceedings of the National Academy of Sciences of the United States of America. Jun, 2010  |  Pubmed ID: 20498073

The Hippo signaling pathway regulates organ size and tissue homeostasis from Drosophila to mammals. At the core of the Hippo pathway is a kinase cascade extending from the Hippo (Hpo) tumor suppressor to the Yorkie (Yki) oncoprotein. The Hippo kinase cascade, in turn, is regulated by apical membrane-associated proteins such as the FERM domain proteins Merlin and Expanded (Ex), and the WW- and C2-domain protein Kibra. How these apical proteins are themselves regulated remains poorly understood. Here, we identify the transmembrane protein Crumbs (Crb), a determinant of epithelial apical-basal polarity in Drosophila embryos, as an upstream component of the Hippo pathway in imaginal disk growth control. Loss of Crb leads to tissue overgrowth and target gene expression characteristic of defective Hippo signaling. Crb directly binds to Ex through its juxtamembrane FERM-binding motif (FBM). Loss of Crb or mutation of its FBM leads to mislocalization of Ex to basolateral domain of imaginal disk epithelial cells. These results shed light on the mechanism of Ex regulation and provide a molecular link between apical-basal polarity and tissue growth. Furthermore, our studies implicate Crb as a putative cell surface receptor for Hippo signaling by uncovering a transmembrane protein that directly binds to an apical component of the Hippo pathway.

High-efficiency Transduction of Fibroblasts and Mesenchymal Stem Cells by Tyrosine-mutant AAV2 Vectors for Their Potential Use in Cellular Therapy

Human Gene Therapy. Nov, 2010  |  Pubmed ID: 20507237

Adeno-associated virus 2 (AAV2) vectors transduce fibroblasts and mesenchymal stem cells (MSCs) inefficiently, which limits their potential widespread applicability in combinatorial gene and cell therapy. We have reported that AAV2 vectors fail to traffic efficiently to the nucleus in murine fibroblasts. We have also reported that site-directed mutagenesis of surface-exposed tyrosine residues on viral capsids leads to improved intracellular trafficking of the mutant vectors, and the transduction efficiency of the single tyrosine-mutant vectors is ∼10-fold higher in human cells. In the current studies, we evaluated the transduction efficiency of single as well as multiple tyrosine-mutant AAV2 vectors in murine fibroblasts. Our results indicate that the Y444F mutant vectors transduce these cells most efficiently among the seven single-mutant vectors, with >30-fold increase in transgene expression compared with the wild-type vectors. When the Y444F mutation is combined with additional mutations (Y500F and Y730F), the transduction efficiency of the triple-mutant vectors is increased by ∼130-fold and the viral intracellular trafficking is also significant improved. Similarly, the triple-mutant vectors are capable of transducing up to 80-90% of bone marrow-derived primary murine as well as human MSCs. Thus, high-efficiency transduction of fibroblasts with reprogramming genes to generate induced pluripotent stem cells, and the MSCs for delivering therapeutic genes, should now be feasible with the tyrosine-mutant AAV vectors.

Rb(16)Cd(25.39(3))sb(36): an Electron-deficient Zintl Phase Containing Infinite Dodecahedron Chains

Inorganic Chemistry. Jul, 2010  |  Pubmed ID: 20509601

A novel ternary antimonide Rb(16)Cd(25.39(3))Sb(36) has been synthesized by a solid-state reaction of the appropriate amount of elements in a welded niobium tube at 530 degrees C. The compound crystallizes in orthorhombic space group Cmcm (No. 63) with a = 16.499(5) A, b = 12.391(4) A, c = 12.400(4) A, and Z = 1. The structure features a new 3D network constructed of chains of Rb(+)-centered dodecahedra running along [001]. The atomic distribution of the Cd(8)Sb(12) dodecahedron presents an energetically favored pattern without any Cd-Cd bonding. The formation of the phase and the occurrence of a very narrow phase width of Rb(16)Cd(24+x)Sb(36) [0.94(2) < or = x < or = 1.47(3)] have been studied in detail. The Fermi level of the title compound is expected to be located between those of the hypothetical models of "[Rb(16)Cd(24)Sb(36)](0)" (I, poor metallic) and "[Rb(16)Cd(24)Sb(36)] + 4e" (II, narrow-band-gap semiconductor), which agrees well with the experimental measurements. In the temperature range of 300-473 K, the as-synthesized Rb(16)Cd(25.39(3))Sb(36) exhibits p-type semiconductor behavior and shows temperature-independent thermal conductivities (around 0.49 W/m.K). The electrical conductivity, Seebeck coefficient, and figure of merit (ZT) of Rb(16)Cd(25.39(3))Sb(36) are temperature-dependent; these values are 57.4 S/cm, +81.4 microV/K, and 0.04, respectively, at 466 K.

Syntheses, Crystal and Electronic Structures, and Physical Properties of Quaternary Semiconductors: Ln2Mn3Sb4S12 (Ln = Pr, Nd, Sm, Gd)

Inorganic Chemistry. Jul, 2010  |  Pubmed ID: 20509606

Four new quaternary lanthanide antimony sulfides: Ln(2)Mn(3)Sb(4)S(12) (Ln = Pr, Nd, Sm, Gd) have been synthesized from a stoichiometric element mixture at 1373 K by conventional solid state reactions. These compounds crystallize in the monoclinic space group C2/m with the unit cell parameters of a = 19.928(2)-19.9672(6) A, b = 3.9323(4)-3.8803(2) A, c = 14.921(2)-14.9011(1) A, V = 938.5(2)-925.63(6) A(3), and Z = 2 on going from Ln = Pr to Gd. Their structure represents a novel wavy MnS(6) octahedron layer decorated on both sides by chains of an SbS(5) square pyramid via strong Sb-S bonding interactions (< 3.0 A). Such a MnS(6) octahedron layer consists of chains of an edge-sharing [Mn1S(6)](2) dimer extending along [010] that are interconnected by single strings of an edge-sharing Mn2S(6) octahedron at axial S apexes. Sm(2)Mn(3)Sb(4)S(12) displays spin-canted antiferromagnetic interactions between Sm(2+) and Mn(2+) centers and an optical gap of 1.50 eV. The DFT study indicates an indirect band gap with an electronic transfer excitation of S 3p to Sb 5p orbital electrons.

Incidence of Chemotherapy-induced Amenorrhea Associated with Epirubicin, Docetaxel and Navelbine in Younger Breast Cancer Patients

BMC Cancer. 2010  |  Pubmed ID: 20540745

The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.

Human Hepatocyte Growth Factor Receptor is a Cellular Coreceptor for Adeno-associated Virus Serotype 3

Human Gene Therapy. Dec, 2010  |  Pubmed ID: 20545554

Adeno-associated viruses (AAVs) use a variety of cellular receptors/coreceptors to gain entry into cells. A number of AAV serotypes are now available, and the cognate receptors/coreceptors for only a handful of those have been identified thus far. Of the 10 commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells in general. However, in our more recent studies, we observed that AAV3 vectors transduced human liver cancer cells remarkably well, which led to the hypothesis that AAV3 uses hepatocyte growth factor receptor (HGFR) as a cellular coreceptor for viral entry. AAV3 infection of human liver cancer cell lines was strongly inhibited by hepatocyte growth factor, HGFR-specific small interfering RNA, and anti-HGFR antibody, which corroborated this hypothesis. However, AAV3 vectors failed to transduce murine hepatocytes, both in vitro and in vivo, suggesting that AAV3 specifically uses human HGFR, but not murine HGFR, as a cellular coreceptor for transduction. AAV3 may prove to be a useful vector for targeting human liver cancers for the potential gene therapy.

In Vivo Assessment of Artery Smooth Muscle [Ca2+]i and MLCK Activation in FRET-based Biosensor Mice

American Journal of Physiology. Heart and Circulatory Physiology. Sep, 2010  |  Pubmed ID: 20622107

The cellular mechanisms that control arterial diameter in vivo, particularly in hypertension, are uncertain. Here, we report a method that permits arterial intracellular Ca(2+) concentration ([Ca(2+)](i)), myosin light-chain kinase (MLCK) activation, and artery external diameter to be recorded simultaneously with arterial blood pressure (BP) in living mice under 1.5% isofluorane anesthesia. The method also enables an assessment of local receptor activity on [Ca(2+)](i), MLCK activity, and diameter in arteries, uncomplicated by systemic effects. Transgenic mice that express, in smooth muscle, a Ca(2+)/calmodulin-activated, Förster resonance energy transfer (FRET)-based "ratiometric", exogenous MLCK biosensor were used. Vasoactive substances were administered either intravenously or locally to segments of exposed femoral or cremaster arteries. In the basal state, mean BP was approximately 90 mmHg, femoral arteries were constricted to 65% of their passive diameter, MLCK fractional activation was 0.14, and [Ca(2+)](i) was 131 nM. Phenylephrine (300 ng/g wt iv) elevated mean BP transiently to approximately 110 mmHg, decreased heart rate, increased femoral artery [Ca(2+)](i) to 244 nM and fractional MLCK activation to 0.24, and decreased artery diameter by 23%. In comparison, local application of 1.0 muM phenylephrine raised [Ca(2+)](i) to 279 nM and fractional MLCK activation to 0.26, and reduced diameter by 25%, but did not affect BP or heart rate. Intravital FRET imaging of exogenous MLCK biosensor mice permits quantification of changes in [Ca(2+)](i) and MLCK activation that accompany small changes in BP. Based on the observed variance of the FRET data, this method should enable the detection of a difference in basal [Ca(2+)](i) of 29 nM between two groups of 12 mice with a significance of P < 0.05.

Quantification of Circulating Cell-free DNA in the Serum of Patients with Obstructive Sleep Apnea-hypopnea Syndrome

Lung. Dec, 2010  |  Pubmed ID: 20668869

Serum cell-free DNA concentrations have been reported to increase in many acute diseases as well as in some chronic conditions such as cancer and autoimmune diseases. The aim of this study was to examine whether serum DNA concentrations were elevated in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). The effects of nasal continuous positive airway pressure (nCPAP) on serum DNA were also investigated. One hundred twenty-seven people diagnosed with OSAHS by polysomnography (PSG) were admitted into the OSAHS group, and 52 subjects without OSAHS were recruited for the control group. The OSAHS group was further divided into mild, moderate, and severe OSAHS subgroups based on their apnea-hypopnea index (AHI) during sleep. Ten patients with moderate and severe OSAHS were treated with nCPAP. Serum DNA, interleukin-6 (IL-6), and malonaldehyde (MDA) concentrations were measured and were found to be significantly higher in patients with moderate and severe OSAHS groups than those in the mild OSAHS and control groups (p < 0.05). Univariate analysis showed that serum DNA correlated positively with AHI, oxygen desaturation index (ODI), IL-6, and MDA, and negatively correlated with minimal oxygen saturation (miniSaO(2)) (all p < 0.05). In stepwise multiple regression analysis, only MDA and miniSaO(2) were suggested as significant independent predictors for the serum DNA concentrations. After 6 months of nCPAP therapy, serum concentrations of DNA, IL-6, and MDA were significantly decreased (p < 0.05). The increasing concentration of serum DNA in patients with OSAHS was positively correlated with disease severity. Serum DNA may become an important parameter for monitoring the severity of OSAHS and effectiveness of therapy.

[Analysis and Comparison of the Masking and TRT for Patients with Subjective Tinnitus]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. May, 2010  |  Pubmed ID: 20669657

To compare the effect of tinnitus masking and tinnitus retraining therapy (TRT) in patients with subjective tinnitus, and to analyze the effect of TRT within the positive or negative group of tinnitus masking test.

Treatment of Oral Florid Papillomatosis with Systemic Administration of Photocarcinorin: an Effective Photodynamic Therapy

Photomedicine and Laser Surgery. Dec, 2010  |  Pubmed ID: 20673139

To evaluate the safety and effect of systemic administration of photosensitizer Photocarcinorin (PsD-007) in the treatment of oral florid papillomatosis (OFP).

Synthesis, Crystal and Electronic Structures, and Physical Properties of Caged Ternary Cu-rich Antimonide: BaCu(7.31(3))Sb5

Inorganic Chemistry. Aug, 2010  |  Pubmed ID: 20690758

A new caged Cu-rich antimonide, BaCu(7.31(3))Sb(5), was obtained from a direct combination of the elements in a graphite crucible under a high vacuum by a solid state reaction, and the structure was determined by the single-crystal X-ray diffraction method to be hexagonal P6(3)/mmc (No.194), with a = 7.0154(4) A, c = 12.5423(14) A, V = 534.58(7) A(3), and Z = 2. BaCu(7.31(3))Sb(5) is the first antimonide member of the BaNi(9)P(5)-type barium copper pnictides with a Cu2 site occupancy of 43.7(9)%, and the structure building unit is a 30-vertex Cu(18)Sb(12) cage centered by a Ba atom. The Cu(18)Sb(12) cages form chains along the c axis by sharing the opposite hexagonal (Cu2)(3)(Sb2)(3) faces. Such a cage chain shares (Cu1)(2)(Sb1)(2) rhomboidal faces with six neighboring chains along the [100], [010], and [110] directions to generate a 3D condensed metallic network. The electronic structure calculations by CASTEP indicate the metallic nature, which matches well with the metallic electrical conductivity, small Seebeck coefficient, and Pauli paramagnetism. The calculated formation energies indicate that BaCu(7.5)Sb(5)[triple bond]Ba(2)Cu(15)Sb(10) with the Cu2 site half occupied is the energetically favorable stoichiometry compared with Ba(2)Cu(12)Sb(10) (empty Cu2 site) and Ba(2)Cu(18)Sb(10) (fully occupied Cu2 site).

Hemoglobin H Disease Due to a De Novo Mutation at the α2-globin Gene and an Inherited Common α-thalassemia Deletion Found in a Chinese Boy

Blood Cells, Molecules & Diseases. Oct, 2010  |  Pubmed ID: 20691621

Hemoglobin (Hb) H disease is a moderate form of α-thalassemia resulting from various genetic defects. A novel frameshift mutation cd 43/44(-C) at the α2-globin gene was identified in a Chinese boy with hemoglobin H disease by sequencing. The proband's mother carries a common α-thalassemia deletion while his father was normal both in the hematological phenotype and α-globin genotype, which suggested that it occurred as a de novo mutation. Molecular studies revealed a compound heterozygote for the Southeast Asian α-thalassemia deletion and this novel spontaneous mutation (-/α(T)α) and the patient exhibited the clinical manifestation of classic hemoglobin H disease. Based on the results of excluding the possibility of a somatic mosaicism of a point mutation in the α2-globin gene, we progress that this de novo single-base deletion should have arisen during the spermatogenic process or earlier embryonic stage. The present study provides information in determining a supplementary model of inheritance for α-thalassemia, which should be useful in genetic counseling.

High-efficiency Transduction and Correction of Murine Hemophilia B Using AAV2 Vectors Devoid of Multiple Surface-exposed Tyrosines

Molecular Therapy : the Journal of the American Society of Gene Therapy. Dec, 2010  |  Pubmed ID: 20736929

Elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer with adeno-associated virus type 2 (AAV2) vectors. Here, combinations of mutations in the seven potentially relevant Y residues were evaluated for further augmentation of transduction efficiency. These mutant capsids packaged viral genomes to similar titers and retained infectivity. A triple-mutant (Y444+500+730F) vector consistently had the highest level of in vivo gene transfer to murine hepatocytes, approximately threefold more efficient than the best single-mutants, and ~30-80-fold higher compared with the wild-type (WT) AAV2 capsids. Improvement of gene transfer was similar for both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors, indicating that these effects are independent of viral second-strand DNA synthesis. Furthermore, Y730F and triple-mutant vectors provided a long-term therapeutic and tolerogenic expression of human factor IX (hF.IX) in hemophilia B (HB) mice after administration of a vector dose that only results in subtherapeutic and transient expression with WT AAV2 encapsidated vectors. In summary, introduction of multiple tyrosine-mutations into the AAV2 capsid results in vectors that yield at least 30-fold improvement of transgene expression, thereby lowering the required therapeutic dose and potentially vector-related immunogenicity. Such vectors should be attractive for treatment of hemophilia and other genetic diseases.

Anti-JC Virus Antibodies: Implications for PML Risk Stratification

Annals of Neurology. Sep, 2010  |  Pubmed ID: 20737510

A study was undertaken to establish an enzyme-linked immunosorbent assay (ELISA) to detect JC virus (JCV)-specific antibodies in multiple sclerosis (MS) patients, and to evaluate its potential utility for identifying patients at higher or lower risk (ie, risk stratification) of developing progressive multifocal leukoencephalopathy (PML).

Auger-mediated Cytotoxicity of Cancer Cells in Culture by an 125I-antisense Oligomer Delivered As a Three-component Streptavidin Nanoparticle

Journal of Biomedical Nanotechnology. Apr, 2010  |  Pubmed ID: 20738069

We reported recently that a three-component nanoparticle, consisting of a targeting antibody, a transfecting peptide and an 111In-antiRIalpha MORF antisense oligomer, provided Auger electron-mediated, antisense-mediated, cytotoxicity of cells in culture. We have now measured the cytotoxicity of the nanoparticle in culture with the 111In replaced by 125I, another attractive Auger electron emitter. The nanoparticle consisted of streptavidin linking the 125I labeled antiRIalpha mRNA antisense MORF oligomer, the tat transfecting peptide and the anti-Her2 Trastuzumab antibody. Cytotoxicity was evaluated by a clonogenic survival assay in BT-474 (Her2+) human breast cancer cells. In a dose escalation study, as measured by the surviving fraction, the cytotoxicity of tumor cells to the 125I-labeled antisense nanoparticle was significantly higher than that for the identical sense control. When compared with our previous study with 111In as label, a similar level of cytotoxicity was achieved but the observed minimal therapeutic dose for the 125I-labeled nanoparticle in BT-474 cells was lower than that for 111In-labeled nanoparticle in SK-BR-3 cells. Thus, a radiolabeled antisense MORF oligomer delivered into cells by a three-component nanoparticle is an effective vehicle for Auger radiotherapy when radiolabeled with 111In or 125I.

Pb2B5O9I: an Iodide Borate with Strong Second Harmonic Generation

Journal of the American Chemical Society. Sep, 2010  |  Pubmed ID: 20738133

The combination of lone-pair effects on Pb(2+) cations and the smaller electronegativity of I(-) anions into the pentaborate framework generates a phase-matchable material, Pb(2)B(5)O(9)I, with the largest powder SHG response among borates, about 13.5 times that of KDP (KH(2)PO(4)), and transparency over the near-UV to middle-IR region. DFT calculations on electronic structure and cutoff-energy-dependent SHG coefficients confirm these origins.

Inhibition of Tankyrase 1 in Human Gastric Cancer Cells Enhances Telomere Shortening by Telomerase Inhibitors

Oncology Reports. Oct, 2010  |  Pubmed ID: 20811689

Telomere stability is believed to be related to aging and tumorigenesis. Besides telomerase, telomere length is also regulated by several telomere-specific binding proteins. Tankyrase 1, a telomeric poly(ADP-ribose) polymerase (PARP), elongates telomere length by inhibiting TRF1 binding to telomeres. In order to study the synergistic action of tankyrase 1 and telomerase in the maintenance of telomere length in mammalian cells, we constructed anti-sense tankyrase 1 (aTNKS) eukaryotic expression vectors and then transfected them into the SGC-7901 human gastric cancer cell line, as well as SGC-7901 cells that had been transfected with antisense hTR (7901-ahTR) and antisense hTERT (7901-ahTERT) with DOTAP liposomes. The activity of telomerase, telomere length and telomerase-associated protein activities were measure by TRAP-ELISA, Southern blot and western blot analysis, respectively, in aTNKS transfected and untransfected cells. The results demonstrated that telomere length was significantly shorter in cells with concomitant tankyrase 1 and telomerase inhibition than by either tankyrase 1 or telomerase inhibition alone, in SGC-7901 cells. We also found that aTNKS had no effect on telomerase activity. These results reveal that inhibition of tankyrase 1 could shorten telomere length and play a synergistic role with telomerase inhibitors in telomere length shortening in the SGC-7901 gastric cancer cell line. Co-inhibition of tankyrase 1 and telomerase activity may be a rational strategy for telomere-directed gastric cancer therapeutics.

Proteomic Analysis of Testis Biopsies in Men Treated with Transient Scrotal Hyperthermia Reveals the Potential Targets for Contraceptive Development

Proteomics. Oct, 2010  |  Pubmed ID: 20815088

Mild testicular heating safely and reversibly suppresses spermatogenesis. In this study, we attempted to clarify the underlying molecular mechanism(s) involved in heat-induced spermatogenesis suppression in human testis. We conducted global proteomic analyses of human testicular biopsies before, and at 2 and 9 wk after heat treatment. Thirty-one and Twenty-six known proteins were identified with significant differential expression at 2 and 9 wk after heat treatment, respectively. These were used to characterize the cellular and molecular events in the testes when seminiferous epithelia became damaged (2 wk) and recovered (9 wk). At 2 wk post-treatment, the changed expression of a series of proteins could promote apoptosis or suppress proliferation and cell survival. At 9 wk post-treatment, the changed expression of proteins mainly promoted cell proliferation, differentiation and survival, but resisted cell apoptosis. Among those heat-regulated proteins, HNRNPH1 was selected for the further functional study. We found that HNRNPH1 was an anti-apoptosis protein that could regulate the expression of other heat-induced proteins. In conclusion, heat-induced reversible suppression of spermatogenesis occurred by modulating the expression of proteins related to proliferation, differentiation, apoptosis and cell survival pathways. These differentially expressed proteins were found to be key molecular targets affecting spermatogenesis after heat treatment.

Generation of Replication-competent Recombinant Influenza A Viruses Carrying a Reporter Gene Harbored in the Neuraminidase Segment

Journal of Virology. Nov, 2010  |  Pubmed ID: 20826692

Replication-competent influenza viruses carrying reporter genes are of great use for basic research, screening of antiviral drugs, and neutralizing of antibodies. In this study, two recombinant influenza A viruses with a neuraminidase (NA) segment harboring enhanced green fluorescent protein (EGFP) in the background of A/PR/8/34 (PR8) were generated. The viral RNA (vRNA)-specific packaging signals for NA were largely retained for efficient packaging. An "autocleave" 2A peptide sequence, which was inserted at the N terminus or the COOH terminus of NA to link with EGFP, enabled NA and EGFP to be expressed monocistronically. Further analysis demonstrated that both viruses, named rPR8-EGFP+NA and rPR8-NA+EGPF, although with some characteristic differences in growth and EGFP expression, could replicate in noncomplementary cells and propagate to large quantities while maintaining genome stability after multiple passages in embryonated eggs. These replication-competent influenza viruses carrying reporter genes are a great addition to the tool set for developing antiviral therapeutics and vaccines and for in vivo studies of viral dissemination and pathogenicity.

[Comparison of Two Tracing Method of Transplanted Mouse Embryonic Stem Cell]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. Aug, 2010  |  Pubmed ID: 20868608

To trace the embryonic stem (ES) cells transplanted into rat brain by labeling the cells with green fluorescent protein (GFP) and by mouse neuronal specific antibody Thy-1 and compare their features.

Pseudo-random Single Photon Counting: a High-speed Implementation

Biomedical Optics Express. 2010  |  Pubmed ID: 21258444

Pseudo-random single photon counting (PRSPC) is a new time-resolved optical measurement method which combines the spread spectrum time-resolved method with single photon counting. A pseudo-random bit sequence is used to modulate a continuous wave laser diode, while single photon counting is used to build up the optical signal in response to the modulated excitation. Periodic cross-correlation is performed to obtain the temporal profile of the subject of interest. Compared with conventional time-correlated single photon counting (TCSPC), PRSPC enjoys many advantages such as low cost and high count rate without compromising the sensitivity and time-resolution. In this paper, we report a PRSPC system that can be used for high-speed acquisition of the temporal point spread function of diffuse photons. It can reach a photon count rate as high as 3 Mcps (counts per second). Phantom experiments have been conducted to demonstrate the system performance.

[The Effects of Oxymatrine on Expression of Interleukin-6 and Interleukin-1beta MRNA of Human Periodontal Ligament Cell Stimulated by Lipopolysaccharides]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Dec, 2010  |  Pubmed ID: 21365847

To observe the effects of oxymatrine on the expression of interleukin-6 (IL-6), interleukin-1beta (IL-1beta) mRNA of human periodontal ligament cell (PDLC) stimulated by lipopolysaccharides (LPS), and to discuss oxymatrine's inhibition mechanism on periodontal inflammation stimulated by LPS.

Growth and Photosynthesis Responses of Phaeodactylum Tricornutum to Dissolved Organic Matter from Salt Marsh Plant and Sediment

Journal of Environmental Sciences (China). 2010  |  Pubmed ID: 21179964

The effects of allochthonous dissolved organic matter (DOM) on the growth and photosynthesis of Phaeodactylum tricornutum were investigated. P. tricornutum incubated in f/2 medium was exposed to DOM additives, which were extracted from the plant and sediment samples of a salt marsh in North Branch of the Yangtze estuary, China. During 12 days incubation, the chlorophyll fluorescence parameters of P tricornutum were measured by a Phyto-PAM phytoplankton analyzer. Spectral properties of DOM in algae filtrates were also observed. The concentrations of chlorophyll a, active chlorophyll a, and the maximum quantum yield of photosystem II significantly decreased after four days of incubation, suggesting that the growth and photosynthetic efficiency of P. tricornutum were inhibited. After adding sediment-DOM extract, both a250/a365 (the ratio of the absorption coefficients at 250 and 365 nm) and S values (spectral slope coefficients) of algae filtrates declined in the first two days, which demonstrated a loss of low molecular weight DOM. Parallel factor analysis of fluorescence spectra of DOM in algae filtrates revealed that DOM could be classified into two humic-like and two protein-like components. The fluorescence intensity of tyrosine-like component originating from algae increased significantly during incubation. This study supports the hypothesis that allochthonous DOM derived from salt marsh plant and sediment have a strong influence on the adjacent aquatic ecosystems.

Adding a Clearing Agent to Pretargeting Does Not Lower the Tumor Accumulation of the Effector As Predicted

Cancer Biotherapy & Radiopharmaceuticals. Dec, 2010  |  Pubmed ID: 21204772

Clearing agents are often used in pretargeting despite the potential for decreased tumor accumulation of the effector. However, according to the authors' semiempirical model, a clearing agent should not necessarily decrease tumor accumulation. In this study, the authors have added a clearing step to their model-morpholino phosphorodiamidate oligomer (MORF)/complement MORF (cMORF) pretargeting system-to confirm this prediction. The CC49 antibody was conjugated with both biotin and an 18 mer MORF. The influence of avidin on antibody clearance was first evaluated in normal mice in which each animal received 30 μg of MORF-CC49-biotin, 0-70 μg of avidin 1 day later, and 1.2 μg of ⁹⁹(m)Tc-cMORF 3 hours later, with sacrifice at 3 hours. Thereafter, a pretargeting study in mice bearing an LS174T tumor was performed at a 34 μg avidin dosage. In normal mice, the blood level of ⁹⁹(m)Tc-cMORF fell by 60% at an avidin dosage of 10 μg or higher. In tumored mice, avidin produced a similar reduction in blood but had no influence on tumor level, which remained at 6.30% ID/g as predicted. In conclusion, in addition to the expected reduced effector levels in blood and normal tissues, a reduction in tumor accumulation was avoided when adding a clearing agent as predicted.

Abnormal Neurogenesis in the Dentate Gyrus of Adult Mice Lacking 1,25-dihydroxy Vitamin D(3) (1,25-(OH)(2)D(3))

Hippocampus. Dec, 2010  |  Pubmed ID: 21125584

In this study, we employed 1α-hydroxylase knockout (1α-(OH)ase(-/-)) mice to investigate the influence of 1,25-dihydroxy vitamin D(3) (1,25-(OH)(2)D(3)) deficiency on the adult neurogenesis in the hippocampal dentate gyrus (DG). The numbers of both 24-hr-old BrdU(+) cells and proliferating cell nuclear antigen positive cells in 8-week-old 1α-(OH)ase(-/-) mice increased approximately twofold compared with wild-type littermates. In contrast, the numbers of 7- and 28-day-old BrdU(+) cells in 1α-(OH)ase(-/-) mice decreased by 50% compared with wild-type mice, while the proportion of BrdU(+)/NeuN(+) cells in BrdU(+) population showed no difference between 1α-(OH)ase(-/-) and wild-type mice. Apoptotic cells in the subgranular zone (SGZ) of DG markedly increased in 1α-(OH)ase(-/-) mice. Replenishment of 1,25-(OH)(2)D(3), but not correction of serum calcium and phosphorus levels, completely prevented changes in the neurogenesis in 1α-(OH)ase(-/-) mice. The absence of 1,25-(OH)(2)D(3) led to an increase in the expression of L-type voltage-gated calcium channel (L-VGCC) and a decrease in the nerve growth factor (NGF) mRNA level. Treatment with the L-VGCC inhibitor nifedipine blocked the increased cell proliferations by 1,25-(OH)(2)D(3) deficiency. Administration of NGF significantly attenuated the loss of newborn neurons in 1α-(OH)ase(-/-) mice. © 2010 Wiley-Liss, Inc.

Rhegmatogenous Retinal Detachment Due to Paravascular Linear Retinal Breaks over Patchy Chorioretinal Atrophy in Pathologic Myopia

Archives of Ophthalmology. Dec, 2010  |  Pubmed ID: 21149778

To characterize posterior paravascular linear retinal breaks over areas of patchy chorioretinal atrophy as a cause of retinal detachment among patients with pathologic myopia.

Hepatocyte Nuclear Factor-4 Alpha Regulates Liver Triglyceride Metabolism in Part Through Secreted Phospholipase A(2) GXIIB

Hepatology (Baltimore, Md.). Nov, 2010  |  Pubmed ID: 21225646

Hepatocyte nuclear factor-4 alpha (HNF-4α) is an important transcription factor governing the expression of genes involved in multiple metabolic pathways. Secreted phospholipase A(2) GXIIB (PLA(2)GXIIB) is an atypical member of a class of secreted phospholipases A(2). We establish in this study that PLA(2)GXIIB is an HNF-4α target gene. We demonstrate that HNF-4α binds to a response element on the PLA(2)GXIIB promoter. Moreover, HNF-4α agonists induce PLA(2)GXIIB expression in human hepatocarcinoma cells. Importantly, PLA(2)GXIIB-null mice accumulate triglyceride, cholesterol, and fatty acids in the liver and develop severe hepatosteatosis resembling some of the phenotypes of liver-specific HNF-4α-null mice. These defects are in part due to compromised hepatic very low-density lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4α elevates serum triglyceride level in wild-type but not PLA(2)GXIIB-null mice. Conclusion: Collectively, these evidences suggest that HNF-4α is a key physiological PLA(2)GXIIB transcriptional regulator and that PLA(2)GXIIB is a novel mediator of triglyceride metabolism in the liver. (HEPATOLOGY 2011;).

[Reaction of NO with Metal Oxides and Urea Supported on Activated Carbons at Low Temperature]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Nov, 2010  |  Pubmed ID: 21250435

The catalysts were prepared by activated carbon fiber (ACF) loaded different contents of NiO and NiO-CeO2, Urea was loaded on the prepared catalysts as reductant. The experiments of selective catalytic reductions (SCR) of NO were carried out from 30 to 120 degrees C. The experiments of SEM, BET and XRD of the samples were also carried out selectively to study the catalysts properties, respectively. The experimental results showed that the loaded mass fraction of NiO could greatly affect the catalytic activity of the catalysts. 10% NiO catalyst activity and activity stability were both higher than that of the others, and it could yield about 50% removal efficiency of NO at 90 degrees C. With the loaded mass increasing, the catalytic activity was obviously decreased. And furthermore, the catalyst of 5% NiO-5% CeO2/ACF had the best catalytic activities on SCR NO and stability among the prepared NiO-CeO2/ACF catalysts, and its NO removal efficiency was over 55% at 110 degrees C. When the loaded mass increased, the similar phenomenon was observed, which was due to the decreasing of specific surface area of the catalysts. The metal oxides, loaded on ACF, were the catalytic centers in this study. Moreover, 5% CeO2-5% NiO/ACF had the highest catalytic activity than 10% CeO2/ACF and 10% NiO/ ACF. Therefore, there should be synergistic effect between CeO2 and NiO. Finally, the catalytic mechanism of SCR on NO at low temperature was discussed.

Cyclo-Tetra-kis(μ-naphthalene-1,8-dicarboxyl-ato)tetra-kis-[diaqua-(2,2'-bipyridine)-manganese(II)] Tetra-hydrate

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21589355

In the title centrosymmetric tetra-nuclear complex, [Mn(4)(C(12)H(6)O(4))(4)(C(10)H(8)N(2))(4)(H(2)O)(8)]·4H(2)O, two independent Mn(II) ions are coordinated in a slightly disorted octa-hedral environment by two aqua ligands, two naphthalene-1,8-dicarboxyl-ate (1,8-nap) ligands and one bis-chelating 2,2'-bipyridine (2,2'-bipy) ligand. In the crystal, mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds into chains along [100]. These chains are further linked by weak π-π inter-actions with centroid-centroid distances in the range of 3.609 (2)-3.758 (1) Å, forming a three-dimensional supra-molecular network.

Contribution of Disulfide S2(2-) Anions to the Crystal and Electronic Structures in Ternary Sulfides, Ba12In4S19, Ba4M2S8 (M=Ga, In)

Inorganic Chemistry. Jun, 2011  |  Pubmed ID: 21599031

Three semiconducting ternary sulfides have been synthesized from the mixture of elements with about 20% excess of sulfur (to establish oxidant rich conditions) by solid-state reactions at high temperature. Ba(12)In(4)S(19) ≡ (Ba(2+))(12)(In(3+))(4)(S(2-))(17)(S(2))(2-), 1, crystallizes in the trigonal space group R ̅3 with a = 9.6182(5) Å, b = 9.6182(5) Å, c = 75.393(7) Å, and Z = 6, with a unique long period-stacking structure of a combination of monometallic InS(4) tetrahedra, linear dimeric In(2)S(7) tetrahedra, disulfide S(2)(2-) anions, and isolated sulfide S(2-) anions that is further enveloped by Ba(2+) cations. Ba(4)In(2)S(8) ≡ (Ba(2+))(4)(In(3+))(2)(S(2-))(6)(S(2))(2-), 2, crystallizes in the triclinic space group P ̅1̅ with a = 6.236(2) Å, b = 10.014(4) Å, c = 13.033(5) Å, α = 104.236(6)°, β = 90.412(4)°, γ = 91.052(6)°, and Z = 2. Ba(4)Ga(2)S(8) ≡ (Ba(2+))(4)(Ga(3+))(2)(S(2-))(6)(S(2))(2-), 3, crystallizes in the monoclinic P2(1)/c with a = 12.739(5) Å, b = 6.201(2) Å, c = 19.830(8) Å, β = 104.254(6)° and Z = 4. Compounds 2 and 3 represent the first one-dimensional (1D) chain structure in ternary Ba/M/S (M = In, Ga) systems. The optical band gaps of 1 and 3 are measured to be around 2.55 eV, which agrees with their yellow color and the calculation results. The CASTEP calculations also reveal that the disulfide S(2)(2-) anions in 1-3 contribute mainly to the bottom of the conduction bands and the top of valence bands, and thus determine the band gaps.

[Effects of Cholecystokinin Octapeptide on the Contractile Activity of Guinea-pig Colonic Smooth Muscles, L-type Calcium Currents and Membrane Potentials of Myocytes]

Zhonghua Yi Xue Za Zhi. Mar, 2011  |  Pubmed ID: 21600166

To investigate the effects and mechanism of cholecystokinin octapeptide (CCK-8S) on the contractile activity of smooth muscles, L-type calcium current and membrane potentials of proximal colon myocytes in guinea pig.

The Expression Pattern of Polycomb Group Protein Ezh2 During Mouse Embryogenesis

Anatomical Record (Hoboken, N.J. : 2007). Jul, 2011  |  Pubmed ID: 21630475

The Polycomb group (PcG) family proteins are required for the stability of homeotic selector genes and other genes related to the regulation of mammalian development through their roles in the modulation of chromatin domains. Among them, the mammalian enhancer zeste homologue 2 (Ezh2) contributes to the transcriptional repression of these genes. Previous studies tracked the Ezh2 expression at cDNA and mRNA levels during mouse development. However, little information is known about the expression patterns of Ezh2 at the protein levels. In this study, the embryos (E6.5-E18.5) obtained through timed matings of strain Kunming mice were inserted into paraffin blocks. Tissue microarrays were constructed and followed by subsequent immunohistochemical staining. The positive cells were identified and scored based on both the percentage of stained cells and their staining intensities. Ezh2 protein expression was found throughout the embryonic tissues including the nerves, intestine epithelial, liver, pancreas, renal tubule, and lungs. Its expression level was higher at early embryonic developmental stages. However, the nerve fibers and myocardium showed weak or no immunostaining reactivities. Ezh2 protein was moderately expressed in the nuclei of renal tubule epithelial cells at E14.5. In contrast, it was weakly expressed in the fetal kidneys at E18.5 and the protein was localized in the cytoplasm of the renal tubule epithelial cells. Our data confirmed that Ezh2 protein was expressed in mouse embryos and its expression exhibited tissue specificity and dependence on the stages of embryo development. thus providing new information helpful for understanding the possible roles of Ezh2 in embryogenesis.

Resolution of Redundant Semantic Type Assignments for Organic Chemicals in the UMLS

Artificial Intelligence in Medicine. Jul, 2011  |  Pubmed ID: 21646001

The Unified Medical Language System (UMLS) integrates terms from different sources into concepts and supplements these with the assignment of one or more high-level semantic types (STs) from its Semantic Network (SN). For a composite organic chemical concept, multiple assignments of organic chemical STs often serve to enumerate the types of the composite's underlying chemical constituents. This practice sometimes leads to the introduction of a forbidden redundant ST assignment, where both an ST and one of its descendants are assigned to the same concept. A methodology for resolving redundant ST assignments for organic chemicals, better capturing the essence of such composite chemicals than the typical omission of the more general ST, is presented.

Probing Near-surface Nanoscale Mechanical Properties of Low Modulus Materials Using a Quartz Crystal Resonator Atomic Force Microscope

Nanotechnology. Jul, 2011  |  Pubmed ID: 21685557

We describe the development of a technique for making indentations on the top 5-20 nm of the surfaces of relatively low modulus materials using a high spatial and force sensitivity atomic force microscope (AFM) whose optical cantilever has been replaced by a quartz crystal resonator (QCR). Unlike conventional optical-cantilever-based AFMs, the accuracy of this technique is not compromised by the compliance of the loading system due to the high stiffness of the QCR. To obtain material modulus values from the indentation results, we find the commonly used Oliver-Pharr model to be unsuitable because of our use of a sharp tip and relatively deep indentation. Instead, we develop a new analysis that may be more appropriate for the geometry we use as well as the non-linear constitutive behavior exhibited by the materials we examined. We calculated values for the moduli of several different materials, which we find to be consistent with the range of published data.

Curcumin Prevents Corticosterone-induced Neurotoxicity and Abnormalities of Neuroplasticity Via 5-HT Receptor Pathway

Journal of Neurochemistry. Sep, 2011  |  Pubmed ID: 21689105

Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT(1A), 5-HT(2A) and 5-HT(4), but 5-HT(1B,) 5-HT(2B), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT(1A) and 5-HT(4) receptors, but not for the 5-HT(2A) receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT(1A) receptor antagonist p-MPPI or 5-HT(4) receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.

Anti-vascular Endothelial Growth Factor Monotherapy Versus Combination Treatment with Photodynamic Therapy for Subfoveal Choroidal Neovascularization Secondary to Causes Other Than Age-related Macular Degeneration

Retina (Philadelphia, Pa.). Nov, 2011  |  Pubmed ID: 21691258

To compare the visual outcomes and retreatment rates of monotherapy with intravitreal bevacizumab versus combination with photodynamic therapy for choroidal neovascularization secondary to causes other than age-related macular degeneration.

[Experimental Research of Purification NO-containing Gas by Aqueous Oxidation with UV/H2O2]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Apr, 2011  |  Pubmed ID: 21717731

The influence of some experimental factors on removal efficiency of nitric oxide (NO) under the condition of liquid-phase oxidation with UV/H2O2, such as H2O2 concentration, solution temperature, initial pH, NO concentration, illumination condition, O2 content and gas flow rate, were investigated by employing orthogonal experiments and single factor experiments. The results showed that NO could be efficiently removed by the aqueous oxidation technology with UV/H2O2 system, and the highest NO removal rate was about 80%. Moreover, H2O2 concentration, temperature and initial pH had varying degree effects on purifying NO-containing gas, whereas NO removal rate were more affected by H2O2 concentration and temperature. The single factor experimental results showed that high NO removal rate could be obtained when H2O2 concentration was 0.2 mol/L and the initial pH was 6-7. H2O2 concentration and initial pH should be maintained at an appropriate level or the production of *OH could be restricted, which would result in lower NO removal rate. The optimum operation temperature was 40 degrees C, which is lower than common operating temperature (50 degrees) for the wet scrubber. Enlarging the illumination strength and O2 content could improve the NO removal rate. Furthermore, the NO removal rate was also controlled by the area and coefficient of gas-liquid mass transfer.

Enhancement of Gag-Specific But Reduction of Env- and Pol-Specific CD8(+) T Cell Responses by Simian Immunodeficiency Virus Nonstructural Proteins In Mice

AIDS Research and Human Retroviruses. Sep, 2011  |  Pubmed ID: 21736424

Abstract Accessory and regulatory proteins (nonstructural proteins) have received increasing attention as components in novel HIV/SIV vaccine design. However, the complicated interactions between nonstructural proteins and structural proteins remain poorly understood, especially their effects on immunogenicity. In this study, the immunogenicity of structural proteins in the presence and absence of nonstructural proteins was compared. First, a series of recombinant plasmids and adenoviral vectors carrying various SIVmac239 nonstructural and structural genes was constructed. Then mice were primed with DNA plasmids and boosted with corresponding Ad5 vectors of different combinations, and the resulting immune responses were measured. Our results demonstrated that when the individual Gag, Pol, or Env gene products were coimmunized with the whole repertoire of nonstructural proteins, the Gag-specific CD8(+) T response was greatly enhanced, while the Env- and Pol-specific CD8(+) T responses were significantly reduced. The same pattern was not observed in CD4(+) T cell responses. Antibody responses against both the Gag and Env proteins were elicited more effectively when these structural antigens were immunized together with nonstructural antigens. These findings may provide helpful insights into the development of novel HIV/SIV vaccines.

Cocaine- and Amphetamine-regulated Transcript Promotes the Differentiation of Mouse Bone Marrow-derived Mesenchymal Stem Cells into Neural Cells

BMC Neuroscience. 2011  |  Pubmed ID: 21756347

Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells) seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present.

[Malignant Hyperthermia After the Operation Under General Anesthesia: a Case Report]

Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. Jan, 2011  |  Pubmed ID: 21251395

LRRK2 R1398H Polymorphism is Associated with Decreased Risk of Parkinson's Disease in a Han Chinese Population

Parkinsonism & Related Disorders. May, 2011  |  Pubmed ID: 21159540

A Simple Method to Increase the Transduction Efficiency of Single-stranded Adeno-associated Virus Vectors in Vitro and in Vivo

Human Gene Therapy. May, 2011  |  Pubmed ID: 21219084

We have recently shown that co-administration of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors with self-complementary (sc) AAV2-protein phosphatase 5 (PP5) vectors leads to a significant increase in the transduction efficiency of ssAAV2 vectors in human cells in vitro as well as in murine hepatocytes in vivo. In the present study, this strategy has been further optimized by generating a mixed population of ssAAV2-EGFP and scAAV2-PP5 vectors at a 10:1 ratio to achieve enhanced green fluorescent protein (EGFP) transgene expression at approximately 5- to 10-fold higher efficiency, both in vitro and in vivo. This simple coproduction method should be adaptable to any ssAAV serotype vector containing transgene cassettes that are too large to be encapsidated in scAAV vectors.

Nanoparticle-mediated Delivery of Pitavastatin into Lungs Ameliorates the Development and Induces Regression of Monocrotaline-induced Pulmonary Artery Hypertension

Hypertension. Feb, 2011  |  Pubmed ID: 21220711

Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.

High Prevalence of Multidrug-resistant Tuberculosis in Zunyi, Guizhou Province of China

The Journal of Antimicrobial Chemotherapy. Oct, 2011  |  Pubmed ID: 21795258

Impairment of Spatial Learning and Memory in Transgenic Mice Overexpressing Human Fibroblast Growth Factor-23

Brain Research. Sep, 2011  |  Pubmed ID: 21824606

Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. Effects of FGF-23 on skeleton, phosphate homeostasis, and cardiovascular system have been investigated; however, the effect of FGF-23 on the central nervous system (CNS) is unknown. To assess whether FGF-23 influences the function and structure of the CNS and whether the effect of FGF-23 on the CNS is mediated by FGF receptors directly or by hypophosphatemia indirectly, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet containing a normal diet plus 1.25% phosphate in drinking water from weaning for 5weeks and the phenotypes of the CNS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet showed impaired spatial learning and memory. Furthermore, these mice exhibited the impairment of long-term potentiation in hippocampal CA1 region, and the reduction of hippocampal adenosine-triphosphate content and of choline acetyltransferase-positive neurons in basal forebrain, possibly as pathogenetic factors contributing to the cognitive deficit. The central nervous phenotypes of transgenic mice were rescued following improved hypophosphatemia by the high-phosphate diet intake. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CNS mediated by the secondary severe hypophosphatemia.

Structure-activity Relationships of Neuritogenic Gentiside Derivatives

ChemMedChem. Nov, 2011  |  Pubmed ID: 21834095

Improving the Quantitation Accuracy in Noninvasive Small Animal Single Photon Emission Computed Tomography Imaging

Nuclear Medicine and Biology. Aug, 2011  |  Pubmed ID: 21843780

Noninvasive imaging of small animals to measure biodistributions and pharmacokinetics of radiolabeled agents is increasingly seen as an effective alternative to external counting of tissues obtained by sacrifice and dissection. However, we have observed important disagreements in measuring the accumulation of (111)In-labeled antibodies in organs such as liver and kidneys when comparing imaging to ex vivo counting in the same animals. This study was conducted to establish whether this discrepancy could be minimized by selecting the region of interest (ROI) in images at the appropriate color threshold and by correcting for the estimated radioactivity within the blood pool of these organs during imaging.

Silica Nanorattle-doxorubicin-anchored Mesenchymal Stem Cells for Tumor-tropic Therapy

ACS Nano. Sep, 2011  |  Pubmed ID: 21854047

Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle-doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody-antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity.

Sensitive Competitive Flow Injection Chemiluminescence Immunoassay for IgG Using Gold Nanoparticle As Label

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Nov, 2011  |  Pubmed ID: 21862396

A sensitive competitive flow injection chemiluminescence (CL-FIA) immunoassay for immunoglobulin G (IgG) was developed using gold nanoparticle as CL label. In the configuration, anti-IgG antibody was immobilized on a glass capillary column surface by 3-(aminopropyl)-triethoxysilane and glutaraldehyde to form immunoaffinity column. Analyte IgG and gold nanoparticle labeled IgG were passed through the immunoaffinity column mounted in a flow system and competed for the surface-confined anti-IgG antibody. CL emission was generated from the reaction between luminol and hydrogen peroxide in the presence of Au (III), generated from chemically oxidative dissolution of gold nanoparticle by an injection of 0.10 mol L(-1) HCl-0.10 mol L(-1) NaCl solution containing 0.10 mmol L(-1) Br(2). The concentration of analyte IgG was inversely related to the amount of bound gold nanoparticle labeled IgG and the CL intensity was linear with the concentration of analyte IgG from 1.0 ng mL(-1) to 40 ng mL(-1) with a detection limit of 5.2×10(-10) gm L(-1). The whole assay time including the injections and washing steps was only 30 min for one sample, which was competitive with CL immunoassays based on a gold nanoparticle label and magnetic separation. This work demonstrates that the CL immunoassay incorporation of nanoparticle label and flow injection is promising for clinical assay with sensitivity and high-speed.

Comparing Two TAG-72 Binding Peptides Previously Identified by Phage Display As Potential Imaging Agents

Nuclear Medicine Communications. Oct, 2011  |  Pubmed ID: 21876403

To evaluate the targeting property in vitro and in vivo of two tumor-associated glycoprotein 72 (TAG-72) binding peptides, previously identified in this laboratory by phage selection using different elution conditions.

[The Semi-quantitative Method for Evaluating Lipid Accumulation in Pancreas of Diabetic Mice]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Jun, 2011  |  Pubmed ID: 21882526

To investigate the semi-quantitative method for evaluating the lipid accumulation in pancreas, the KKAy mice, a classical type 2 diabetes mellitus model mice, were used and treated with rosiglitazone (Rosi); and the age-matched C57BL/6J mice were used as normal control. Pancreas was fixed quickly for histological examination with HE staining. For the estimation of the lipid accumulation in pancreas, semi-quantitative method was designed: the number and the size of islet, lipid accumulation in islet and in exocrine gland were observed and the integrative score calculated under the microscope, separately. In KKAy mice, the characteristics of the increased amount of islet, the enlarged area of islet, an abundance of large vacuolations, lipid droplets, and fat proliferation were exposed frequently, and the integrative score increased 2.1 folds compared with that in C57BL/6J mice. Meanwhile, the levels of serum glucose, insulin, and triglyceride (TG) were 1.7, 18.0, and 9.0 times as those in C57BL/6J mice, respectively. With the rosiglitazone (10 mg x kg(-1)) treatment, compared with that in KKAy mice, the pancreatic pathological changes were ameliorated significantly, and the integrative score in KKAy + Rosi mice decreased by 28.9%; and the levels of serum glucose, insulin, and triglyceride decreased by 48.3%, 81.3% and 64.1%, respectively. It showed there is a correlation between the pancreatic pathological semi-quantitative score and the values of serum parameters. In conclusion, this semi-quantitative scoring method is simple and objective for the evaluation of lipid accumulation in pancreas of mice.

Polybrominated Diphenyl Ethers in Sewage Sludge from Shanghai, China: Possible Ecological Risk Applied to Agricultural Land

Chemosphere. Oct, 2011  |  Pubmed ID: 21885085

Ideally, agricultural use is a treatment for the sewage sludge generated from municipal wastewater. However, this treatment probably causes ecological risks due to the occurrence of organic contaminants in sludge, which has attracted rising concerns recently. To assess the possible ecological risk, in this study, sewage sludge samples were collected from 28 wastewater treatment plants (WWTPs) in Shanghai, China for exploring the level and profile of polybrominated diphenyl ethers (PBDEs). The mean concentration of Σ18PBDE (sum of all target analytes except for BDE-209) was at the low end of global range. However, we found the highest reported BDE-209 levels (34,900 ng g(-1) dw) in sewage sludge/biosoilds to date. The annual mass loadings of penta-BDE, octa-BDE, and deca-BDE were 3.6, 0.6, and 763 kg through sludge, respectively. Following sludge application in agricultural land, the concentrations of penta-BDE, octa-BDE, and deca-BDE in soil were 0.19, 0.03, and 39.5 ng g(-1), respectively. Preliminary results indicate that the ecological risk of soil in organisms exposed to PBDEs was relatively low. Nevertheless, further studies are needed to explore the fate of PBDEs in sewage sludge due to no restriction on the usage and production of PBDEs products in China currently.

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model Through Induction of Innate and Adaptive Immunity

PloS One. 2011  |  Pubmed ID: 21931708

Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer.

Dielectric and Ferroelectric Properties of Bi(Zn1/2Ti1/2)O3-PbTiO3-PbZrO3 Ternary Ceramics

IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. Sep, 2011  |  Pubmed ID: 21937321

Ceramics of a new ternary solid solution system, xBi(Zn(1/2)Ti(1/2))O(3-yPbTiO(3)z)PbZrO(3) (xBZT-yPT-zPZ), with compositions along the solubility limit curve are prepared by solid-state reaction and sintering technique. Two morphotropic phase boundaries (MPBs) separating the orthorhombic and tetragonal (MPB(O-T)) phases and the tetragonal and rhombohedral (MPB(T-R)) phases, respectively, are observed with increasing z (0.10 ≤ x ≤ 0.21; 0 ≤ y ≤ 0.49). It is found that the transition from the ferroelectric to paraelectric phase becomes more diffuse with the addition of BZT into the PZT solid solution. Enhanced dielectric and ferroelectric properties appear at MPB(R-T), which exists over a wide composition region (0.45 ≤ z ≤ 0.6), as revealed by X-ray diffraction and dielectric measurements. The dielectric constant reaches a maximum value (ε' = 1250) on the tetragonal majority side of the MPB. The highest remnant polarization (P(r) = 34.2 μC/cm(2)) is found in the composition at the center of the MPB, where the rhombohedral and tetragonal phases coexist in almost equal quantities.

Identification and Expressional Analysis of Two Cathepsins from Half-smooth Tongue Sole (Cynoglossus Semilaevis)

Fish & Shellfish Immunology. Dec, 2011  |  Pubmed ID: 21939771

Cathepsins are a family of lysosomal proteases that play an important role in protein degradation, antigen presentation, apoptosis, and inflammation. Cathepsins are divided into three groups, i.e., cysteine protease, serine protease, and aspartic protease. Cathepsin D and cathepsin L, which are aspartic protease and cysteine protease respectively, have been identified in a number of teleosts; however, the immunological relevance of fish cathepsins is largely unknown. In this study, we cloned and analyzed the expression profiles of a cathepsin D (CsCatD) and a cathepsin L (CsCatL) homologs from half-smooth tongue sole (Cynoglossus semilaevis). CsCatD is composed of 396 amino acid residues and shares 67.6-88.4% overall sequence identities with fish and human cathepsin D. Structurally CsCatD possesses an aspartic endopeptidase domain, which contains two conserved aspartic acid residues that form the catalytic site. CsCatL is 336 residues in length and shares 64.7-90.2% overall sequence identities with fish and human cathepsin L. CsCatL has an N-terminal cathepsin propeptide inhibitor domain followed by a Papain family cysteine protease domain, the latter containing four conserved catalytic residues: Gln-133, Cys-139, His-279, and Asn-303. Recombinant CsCatL purified from Escherichia coli exhibited apparent protease activity. Quantitative real time RT-PCR analysis detected constitutive expression of CsCatD and CsCatL in multiple tissues, with the lowest level found in heart and the highest level found in liver. Experimental challenge of tongue sole with the bacterial pathogen Vibrio anguillarum and megalocytivirus caused significant inductions of both CsCatD and CsCatL expression in kidney and spleen in time-dependent manners. Immunization of the fish with a subunit vaccine also enhanced CsCatD and CsCatL expression in the first week post-vaccination. These results suggest involvement of CsCatD and CsCatL in host immune reactions to bacterial and viral infections and in the process of antigen-induced immune response.

Interconversion Between [5]pseudorotaxane and [3]pseudorotaxane by Pasting/detaching Two Axle Molecules

The Journal of Organic Chemistry. Oct, 2011  |  Pubmed ID: 21942572

An acceptor-donor-acceptor-type linear molecule 1(2+) containing one electron-rich naphthoxy (NP) unit and two monocharged viologen (MCV) units was synthesized. Through the noncovalent interaction of cucurbit[8]uril (CB[8]) with one NP and one MCV in 1(2+), we first obtained a [2]pseudorotaxane ([1(2+)]⊂CB[8]), and the excess CB[8] included simultaneously the two bare MCV units of two [2]pseudorotaxanes to form a [5]pseudorotaxane ([1(2+)](2)⊂[CB[8]](3)). Its transformation to [3]pseudorotaxane was achieved through detaching the two axle molecules in the presence of acid, and then the addition of base may result in a reversible switch between two different pseudorotaxanes. This novel methodology elongating reversibly linear molecules by noncovalent interactions will benefit the development of stimuli-responsive functional molecular devices.

Self-rated Happiness is Associated with Functional Ability, Mood, Quality of Life and Income, but Not with Medical Condition in Community-dwelling Elderly in Japan

Geriatrics & Gerontology International. Oct, 2011  |  Pubmed ID: 21951778

N-1-(2-mercaptoethyl)thymine Modification of Gold Nanoparticles: a Highly Selective and Sensitive Colorimetric Chemosensor for Hg2+

The Analyst. Nov, 2011  |  Pubmed ID: 21952711

An approach for mercury ions (Hg(2+)) sensing based on the Hg(2+)-induced aggregation of thymine (T)-SH-functionalized gold nanoparticles (AuNPs) has been reported. The T-SH ligands that we synthesized can easily be coupled to the surface of AuNPs through the Au-S bond and can recognize Hg(2+) with high selectivity by forming a T-Hg-T complex with strong affinity. For the T-SH-functionalized AuNPs (T-S-AuNPs) sensor, upon addition of Hg(2+), the formation of the T-Hg-T complex induces aggregation of T-S-AuNPs and results in a significant change of color and UV-Vis absorption spectra. Thus, our method can be used for the rapid, easy and reliable screening of Hg(2+) in aqueous solution, with high sensitivity (2.8 nM) and selectivity over competing analytes. The developed method is successfully applied to the sensing of Hg(2+) in real environmental samples.

Ultra-short Plasmonic Splitters and Waveguide Cross-over Based on Coupled Surface Plasmon Slot Waveguides

Optics Express. Jan, 2011  |  Pubmed ID: 21369076

Composite metal-dielectric-metal (MDM) surface plasmon polariton (SPP) structures are first proposed to realize the ultra-short optical splitters with simplified designs. The operation mechanism is based on the contra-directional coupling achieved in composite plasmonic slot waveguides. In certain cases, the switching function can also be realized. It is further shown that based on the same physical mechanism multi-dielectric-core composite MDM structures could serve as a novel plasmonic waveguide crossover component with low cross talk and high throughput.

In-phase Alignments of Asymmetric Building Units in Ln4GaSbS9 (Ln = Pr, Nd, Sm, Gd-Ho) and Their Strong Nonlinear Optical Responses in Middle IR

Journal of the American Chemical Society. Mar, 2011  |  Pubmed ID: 21370830

New noncentrosymmetric rare-earth metal gallium thioantimonates, Ln(4)GaSbS(9) were synthesized from stoichiometric element mixtures at 950 °C by high-temperature solid-state reactions. These compounds crystallize in orthorhombic space group Aba2 (no.41) with a = 13.799(3)-13.427(5) Å, b = 14.187(3)-13.756(5) Å, c = 14.323(3)-13.954(5) Å, V = 2804(2)-2577 (2) Å(3), and Z = 8 on going from Ln = Pr to Ho. The asymmetric building units, bimetallic polar (Sb(2)S(5)) units, and dimeric (GaS(4))(2) tetrahedra are in-phase aligned as an infinite single anionic chain of {[(Ga(2)S(6))(Sb(2)S(5))](10-)}(∞) that is further packed in a noncentrosymmetric pseudolayer motif perpendicular to the c axis. Three of the title compounds show large powder second harmonic generation (SHG) effects at 2.05 μm, and two of them also exhibit large transparency ranges (1.75 or 0.75 to 25 μm) in the middle-IR region. Significantly, the Sm-member exhibits the strongest SHG response among sulfides to date with intensity approximately 3.8 times that of the benchmark AgGaS(2). The band structures, indirect band gap nature, bonding strengths, and lone pair effects around Sb have also been studied by Vienna ab initio simulation package calculations.

Mechanical and Water-holding Properties and Microstructures of Soy Protein Isolate Emulsion Gels Induced by CaCl2, Glucono-δ-lactone (GDL), and Transglutaminase: Influence of Thermal Treatments Before And/or After Emulsification

Journal of Agricultural and Food Chemistry. Apr, 2011  |  Pubmed ID: 21381784

The mechanical properties, water-holding capacities (WHC), and microstructures of emulsion gels, induced by glucono-δ-lactone (GDL), CaCl(2), and microbial transglutaminase (MTGase) from unheated and heated soy protein isolate (SPI)-stabilized emulsions (at protein concentration 5%, w/v; oil volume fraction, 20%, w/v), were investigated and compared. The influence of thermal pretreatments (at 90 °C for 5 min) before and/or after emulsification was evaluated. Considerable differences in mechanical, water-holding, and microstructural properties were observed among various emulsion gels. The thermal pretreatment after emulsification increased the strength of the emulsion gels induced by GDL and CaCl(2), whereas in the case of MTGase, thermal pretreatments before and/or after emulsification on the contrary greatly inhibited gel network formation. The application of the enzyme coagulant exhibited much higher potential to form SPI-stabilized emulsion gels with higher mechanical strength than that of the other two coagulants. The WHC of the emulsion gels seemed to be not directly related to their gel network strength. Confocal laser scanning microscope analyses indicated that the network microstructure of the formed emulsion gels, mainly composed of aggregated protein-stabilized oil droplets and protein aggregate clumps, varied with the type of applied coagulants and emulsions. The differences in microstructure were basically consistent with the differences in mechanical properties of the gels. These results could provide valuable information for the formation of cold-set soy protein-stabilized emulsion gels.

Anticolchicine Cytotoxicity Enhanced by Dan Gua-Fang, a Chinese Herb Prescription in ECV304 in Mediums

Chinese Journal of Integrative Medicine. Feb, 2011  |  Pubmed ID: 21390579

To study the effect of anticolchicine cytotoxicity of Dan Gua-Fang, a Chinesea Chinese), a Chinese herbal compound prescription on endothelial cells of vein (ECV304) cultivated in mediums of different glucose concentrations as well as the proliferation of those cells in the same conditions, in order to reveal the value of Dan Gua-Fang in preventing and treating endothelial damage caused by hyperglycemia in diabetes mellitus.

Efficient Degradation of Tetrabromobisphenol A by Heterostructured Ag/Bi5Nb3O15 Material Under the Simulated Sunlight Irradiation

Journal of Hazardous Materials. May, 2011  |  Pubmed ID: 21397395

Heterostructured metallic silver-layered bismuth niobate two-component system (Ag/Bi(5)Nb(3)O(15)) was developed for the first time by a mild hydrothermal method combined with photodeposition. The Ag/Bi(5)Nb(3)O(15) exhibited single-crystalline orthorhombic structure with small particle size (50-200 nm) and octahedral as well as sheet-like shape; additionally, it possessed photoresponse in both UV and visible region. As a novel alternative photocatalysts to TiO(2), the photocatalytic activity of the Ag/Bi(5)Nb(3)O(15) was evaluated by the degradation of tetrabromobisphenol A, a member from the family of the brominated flame retardant, under solar simulating Xe lamp irradiation, and enhanced photocatalytic activity in compared to Bi(5)Nb(3)O(15) itself and Degussa P25 was obtained.

Combined Core Needle Biopsy and Fine-needle Aspiration with Ancillary Studies Correlate Highly with Traditional Techniques in the Diagnosis of Nodal-based Lymphoma

American Journal of Clinical Pathology. Apr, 2011  |  Pubmed ID: 21411774

Core needle biopsy (CNB) and fine-needle aspiration (FNA) are increasingly replacing excisional lymph node biopsy in the diagnosis of lymphomas. However, evaluation of CNB and FNA remains challenging owing to limited architectural information and the more detailed subclassification of lymphomas required by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Our study is the largest study to assess diagnostic accuracy of CNB and FNA in conjunction with ancillary studies. We analyzed 263 cases and a diagnosis was established in 237, of which 193 were completely subclassified. In cases in which excisional biopsy was available as a reference for comparison, CNB and FNA had a sensitivity of 96.5%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 90%. CNB and FNA with ancillary studies represent a viable alternative in the diagnosis of lymphoma, as long as the number and size of cores for morphologic studies are not compromised.

Coexistent Dowling-Degos Disease and Reticulate Acropigmentation of Kitamura with Progressive Seborrheic Keratosis

Cutis; Cutaneous Medicine for the Practitioner. Feb, 2011  |  Pubmed ID: 21416772

[Significant Improvement of Motor Symptoms by Deep Brain Stimulation of Bilateral Subthalamic Nucleus in Patients with Moderate or Advanced Parkinson's Disease]

Zhonghua Yi Xue Za Zhi. Feb, 2011  |  Pubmed ID: 21419000

To study the effects of deep brain stimulation (DBS) of bilateral subthalamic nucleus (STN) on the motor and non-motor symptoms in moderate or advanced Parkinson's disease (PD) patients.

Small Intestine CD11c+ CD8+ T Cells Suppress CD4+ T Cell-induced Immune Colitis

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jun, 2011  |  Pubmed ID: 21436315

The large (LI) and small intestine (SI) differ in patterns of susceptibility to chronic mucosal inflammation. In this study, we evaluated whether this might, in part, reflect differences in resident mucosal CD11c(+) T cells. These cells comprised 39-48% (SI) and 12-17% (LI) of the intraepithelial compartment, most of which were T-cell receptor-αβ(+). In the SI, the majority of these cells were CD103(+) CD8(+) NK1.1(-), whereas the opposite phenotype prevailed in the LI. In transfer models of CD4(+) T cell-induced colitis, small numbers (2.5 × 10(5)) of SI CD11c(+) CD8(+) T cells suppressed proinflammatory cytokine-producing CD4(+) T cells in mesenteric lymph nodes and mucosa-associated lymphoid compartments (SI and LI) and protected mice from chronic inflammation. On a per-cell basis, the regulatory function of SI CD11c(+) T cells in CD4(+) T cell colitis was potent compared with other reported regulatory CD4(+) or CD8(+) T cells. In contrast, neither LI CD11c(+) T cells nor SI CD11c(-) T cells were effective in such immunoregulation. SI CD11c(+) CD8(+) T cells were similarly effective in suppressing CD4(+)CD45RB(hi) T cell colitis, as evidenced by inhibition of intracellular proinflammatory cytokine expression and histological inflammation. These findings indicate that SI CD11c(+) CD8(+) T cells are a distinct intestinal T cell population that plays an immunoregulatory role in control of proinflammatory CD4(+) T cells and maintenance of intestinal mucosal homeostasis.

Epidemiology of Adenovirus Type 5 Neutralizing Antibodies in Healthy People and AIDS Patients in Guangzhou, Southern China

Vaccine. May, 2011  |  Pubmed ID: 21447314

Recombinant adenovirus serotype 5 (Ad5) viruses have been extensively explored as vectors for vaccination or gene therapy. However, one major obstacle to their clinical application is the high prevalence of preexisting anti-Ad5 immunity resulting from natural infection. It has been reported that there are geographic variations in the prevalence of natural adenovirus infection. In the present study, we investigated the seroprevalence of Ad5 in Guangzhou, southern China by measuring the Ad5 neutralizing antibodies in blood samples collected from several sites. The seroprevalence was 77.34% in the general healthy population. The seroprevalence and antibody titers increased with age, with the older population (41-72 years old) having the highest seropositivity (84.8%) and percentage (54.4%) of high Ad5 neutralizing antibody titers (>1000). The dynamics of Ad5 neutralizing antibodies were stable and persistent over the course of eight months. Furthermore, the seroprevalence of Ad5 in the HIV-infected AIDS patients was investigated and there was no significant difference from the general healthy population. Our survey provides useful insights for the future development of Ad5-based vaccination and gene therapy.

Optimization of Source and Detector Configurations Based on Cramer-Rao Lower Bound Analysis

Journal of Biomedical Optics. Mar, 2011  |  Pubmed ID: 21456862

Optimization of source and detector (SD) arrangements in a diffuse optical tomography system is helpful for improving measurements' sensitivity to localized changes in imaging domain and enhancing the capacity of noise resistance. We introduced a rigorous and computationally efficient methodology and adapt it into the diffuse optics field to realize the optimizations of SD arrangements. Our method is based on Cramer-Rao lower bound analysis, which combines the diffusion-forward model and a noise model together. This method can be used to investigate the performance of the SD arrangements through quantitative estimations of lower bounds of the standard variances of the reconstructed perturbation depths and values. More importantly, it provides direct estimations of parameters without solving the inverse problem. Simulations are conducted in the reflection geometry to validate the effectiveness of the method on selections of the optimized SD sets, with a fixed number of sources and detectors, from an SD group on a planar probe surface. The impacts of different noise levels and target perturbation depths are considered in the simulations. It is demonstrated that the SD sets selected by this method afford better reconstructed images. This methodology can be adapted to other probe surfaces and other imaging geometries.

Occurrence of Polybrominated Diphenyl Ethers in Soil from the Central Loess Plateau, China: Role of Regional Range Atmospheric Transport

Chemosphere. May, 2011  |  Pubmed ID: 21459410

Very few studies were conducted in highland and depositional areas in studying the transport and behavior of polybrominated diphenyl ethers (PBDEs). In this study, surface soils were collected from Huan County to investigate the level, profile, and potential influence of PBDEs via regional range atmospheric transport in the central part of the Loess Plateau (CLP) of China, one of the most extensive areas of loess deposition in the world. PBDEs were ubiquitous and log-normally distributed in soils from the CLP with mean concentrations of 0.91 and 0.54 ng g(-1) for ΣPBDEs (sum of PBDE congeners except for BDE-209) and BDE-209, respectively. BDE-209 was predominated congener (43.5%), followed by BDE-47 (15.7%), 99 (10.7%), and 153 (7.5%). Further principal component analysis on congener profiles showed that PBDEs in the CLP originated from similar source(s). Additionally, significant differences in the ratios of BDE-47 to 99 and BDE-153 to 154 were found between soil samples and commercial products, indicating that they have undergone fractionation during the process of regional range atmospheric transport. The deposition of PBDEs in the CLP could be influenced by the sources from surrounding regions. For example, Xi'an may have potential influence to the CLP based on geographical analysis and concentrations comparison of PBDEs in gaseous. Therefore, more studies are needed to clarify the atmospheric transport and fate of PBDEs in this region.

Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis Via Negative Interaction with Cathepsin D and SDF-1

Carcinogenesis. Jul, 2011  |  Pubmed ID: 21470957

The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through regulating cell autophagy by targeting cathepsin D, as OLFM4 reduced cathepsin D protein levels and enzymatic activity and attenuated cathepsin D-induced cancer cell proliferation. In addition, overexpression of OLFM4 abrogated stromal cell derived factor-1 (SDF-1)-induced PC-3 cell invasiveness in a Matrigel invasion assay, partially through blocking SDF-1-mediated AKT phosphorylation. Coimmunoprecipitation and immunofluorescence staining studies in OLFM4-expressing PC-3 cells demonstrated a direct interaction between OLFM4 and cathepsin D or SDF-1. Taken together, these results suggest that OLFM4 negatively interacts with cathepsin D and SDF-1 and inhibits prostate cancer growth and bone metastasis.

DHEAS Induces Short-term Potentiation Via the Activation of a Metabotropic Glutamate Receptor in the Rat Hippocampus

Hippocampus. Apr, 2011  |  Pubmed ID: 21484933

The neurosteroid dehydroepiandrosterone-sulfate (DHEAS) is a positive modulator of synaptic transmission in mammalian brains; however, the underlying molecular mechanisms are not fully understood. This report describes the acute effects of DHEAS on the synaptic transmission in the hippocampal dentate gyrus of rat brain slices. The application of DHEAS for 10 min augmented the optically recorded EPSP (op-EPSP) in a dose dependent manner. The effect became visible at 1 nM and saturated at 100 nM. We focused on the effect of DHEAS at 100 nM, where the op-EPSP amplitude was increased by 30%, and gradually decreased to the basal level in 30 min after wash out of the drug (short-term potentiation by DHEAS; STP(DHEAS) ). DHEAS did not alter the presynaptic properties including the presynaptic fiber volley (PSFV) and paired pulse facilitation (PPF), thus indicating that the acute DHEAS effect is of postsynaptic origin. The involvement of putative DHEAS targets, GABA(A) , NMDA, and σ1 receptors in STP(DHEAS) was also investigated; however, antagonists to these receptors only partially inhibited the acute effect of DHEAS. By contrast, STP(DHEAS) was totally inhibited by either the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP (10 μM) or the ryanodine receptor (RyR) inhibitors (ryanodine and ruthenium red), but not by the mGluR1 antagonist LY367385 and the IP3R antagonist 2-APB, suggesting that STP(DHEAS) is mediated by an mGluR5-RyR cascade in postsynaptic neurons. Consistent with this finding, the selective agonist for mGluR5 CHPG nearly perfectly mimicked the DHEAS effect. This is the first demonstration of mGluR involvement in the DHEAS action in regard to hippocampal synaptic transmission. © 2011 Wiley-Liss, Inc.

Diagnostic and Therapeutic Challenges

Retina (Philadelphia, Pa.). Jul-Aug, 2011  |  Pubmed ID: 21487339

Fibroblast Growth Factor 23 Overexpression Impacts Negatively on Dentin Mineralization and Dentinogenesis in Mice

Clinical and Experimental Pharmacology & Physiology. Jun, 2011  |  Pubmed ID: 21488937

1. Though previous studies have shown that fibroblast growth factor 23 (FGF23) mRNA expression localizes in ameloblasts and odontoblasts in teeth, it is unclear what effect FGF23 overexpression has on dentin mineralization and dentinogenesis. Toward this end, the phenotypes of mandibles and teeth were compared between 6-week-old FGF23 transgenic mice and their wild-type littermates by radiography, microcomputed tomography scanning, histology, histochemistry and immunohistochemistry. 2. The mineral density was reduced in all teeth, including molars and incisors, and in the mandible, and the mineralized tooth volume in incisor and molars, and the mineralized cortical and alveolar bone volume in mandibles were decreased in FGF23 transgenic mice compared with their wild-type littermates. The dental volume, reparative dentin area, the expression of dentin sialoprotein in dentin, and the deposition of type I collagen and osteocalcin in the dental matrix were significantly reduced. However, the predentin volume and the expression of biglycan in dentin were increased in FGF23 transgenic mice compared with their wild-type littermates. 3. The results of the present study show that FGF23 overexpression plays a negative regulatory role on dentin mineralization and dentinogenesis.

Hypotonicity Modulates Tetrodotoxin-sensitive Sodium Current in Trigeminal Ganglion Neurons

Molecular Pain. 2011  |  Pubmed ID: 21496300

Voltage-gated sodium channels (VGSCs) play an important role in the control of membrane excitability. We previously reported that the excitability of nociceptor was increased by hypotonic stimulation. The present study tested the effect of hypotonicity on tetrodotoxin-sensitive sodium current (TTX-S current) in cultured trigeminal ganglion (TG) neurons. Our data show that after hypotonic treatment, TTX-S current was increased. In the presence of hypotonicity, voltage-dependent activation curve shifted to the hyperpolarizing direction, while the voltage-dependent inactivation curve was not affected. Transient Receptor Potential Vanilloid 4 receptor (TRPV4) activator increased TTX-S current and hypotonicity-induced increase was markedly attenuated by TRPV4 receptor blockers. We also demonstrate that inhibition of PKC attenuated hypotonicity-induced inhibition, whereas PKA system was not involved in hypotonic-response. We conclude that hypotonic stimulation enhances TTX-S current, which contributes to hypotonicity-induced nociception. TRPV4 receptor and PKC intracellular pathway are involved in the increase of TTX-S current by hypotonicity.

Multiple Antigenic Peptides of Human Heparanase Elicit a Much More Potent Immune Response Against Tumors

Cancer Prevention Research (Philadelphia, Pa.). Aug, 2011  |  Pubmed ID: 21505182

Peptide vaccination for cancer immunotherapy requires an ideal immune response induced by epitope peptides derived from tumor-associated antigens (TAA). Heparanase is broadly expressed in various advanced tumors. Accumulating evidence suggests that heparanase can serve as a universal TAA for tumor immunotherapy. However, due to the low immunogenicity of peptide vaccines, an ideal immune response against tumors usually cannot be elicited in patients. To increase the immunogenicity of peptide vaccines, we designed three 4-branched multiple antigenic peptides (MAP) on the basis of the human leukocyte antigen (HLA)-A2-restricted cytotoxic T lymphocyte (CTL) epitopes of human heparanase that we identified previously as antigen carriers. Our results show that MAP vaccines based on the HLA-A2-restricted CLT epitopes of human heparanase were capable of inducing HLA-A2-restricted and heparanase-specific CTL in vitro and in mice. Moreover, compared with their corresponding linear peptides, heparanase MAP vaccines elicited much stronger lysis of tumor cells by activating CD8(+) T lymphocytes and increasing the releasing of IFN-γ. However, these heparanase-specific CTLs did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirm the safety of these MAP vaccines. Therefore, our findings indicate that MAP vaccines based on CTL epitopes of human heparanase can be used as potent immunogens for tumor immunotherapy because of advantages such as broad spectrum, high effectiveness, high specificity, and safety.

The 712A/G Polymorphism of Brain-derived Neurotrophic Factor is Associated with Parkinson's Disease but Not Major Depressive Disorder in a Chinese Han Population

Biochemical and Biophysical Research Communications. May, 2011  |  Pubmed ID: 21510922

Background: Overlaps in clinical, pathological and molecular characteristics of Parkinson's disease (PD) and Major Depressive Disorder (MD-D) have promoted association studies in search of common genetic risk factors that may predispose or modify this spectrum of disorders. Experimental and clinical data suggest that genetic variations in Brain-derived neurotrophic factor (BDNF) gene may increase the risk for PD and MD-D. Methods: Two hundred and sixty-six PD, 83 MD-D and 400 controls were recruited for this study, assessed using a battery of neuropsychological tests, and genotyped for 11757C/G, 712A/G, 196A/G, and 270C/T in BDNF gene. Results: 712A/G was associated with 2.50-fold time risk of PD. By combining genotypes AG/AA with 712 GG genotype as reference (OR=1) in stratification analysis, AG/AA genotypes were associated with PD (OR=2.94, 95% CI=1.88-4.61). Accordingly, the A allele was significantly overrepresented in PD compared with the G allele (OR=3.16, 95% CI=2.08-4.81). This distribution in females and males were similar. Conclusion: Our results suggested a novel association between BDNF 712A/G AG/AA genotypes and PD in a Chinese Han population.

An Oral Colon-targeting Controlled Release System Based on Resistant Starch Acetate: Synthetization, Characterization, and Preparation of Film-coating Pellets

Journal of Agricultural and Food Chemistry. May, 2011  |  Pubmed ID: 21513356

An oral colon-targeting controlled release system based on resistant starch acetate (RSA) as a film-coating material was developed. The RSA was successfully synthesized, and its digestion resistibility could be improved by increasing the degree of substitution (DS), which was favorable for the colon-targeting purpose. As a delivery carrier material, the characteristics of RSA were investigated by polarized light microscopy, FTIR spectroscopy, and X-ray diffraction. The results revealed a decrease of the crystallinity of RSA and a change of its crystalline structure from B + V hydrid type to V type. To evaluate the colon-targeting release performance, the RSA film-coated pellets loaded with different bioactive components were prepared by extrusion-spheronization and then by fluid bed coating. The effects of the DS, plasticizer content, and coating thickness of the RSA film and those of the content and molecular weight of the loaded bioactive component on the colon-targeting release performance of the resulting delivery system were investigated. By adjusting the DS, the coating thickness, and the plasticizer content of the RSA film, either the pellets loaded with a small molecular bioactive component such as 5-aminosalicylic acid or those with a macromolecular bioactive peptide or protein such as bovine serum albumin, hepatocyte growth-promoting factor, or insulin showed a desirable colon-targeting release performance. The release percentage was less than 12% in simulated upper gastrointestinal tract and went up to 70% over a period of 40 h in simulated colonic fluid. This suggests that the delivery system based on RSA film has an excellent colon-targeting release performance and the universality for a wide range of bioactive components.

CXCL8 of Scophthalmus Maximus: Expression, Biological Activity and Immunoregulatory Effect

Developmental and Comparative Immunology. Oct, 2011  |  Pubmed ID: 21530579

CXCL8, or interleukin-8, is a CXC chemokine that promotes neutrophil migration in response to inflammatory stimuli. In this study, we identified and analyzed a CXCL8 orthologue, SmCXCL8, from turbot (Scophthalmus maximus). The deduced amino acid sequence of SmCXCL8 is 99-residue in length and shares 52-83% overall identities with the lineage 1 CXCL8 of a number of teleost. SmCXCL8 possesses a CXC chemokine domain that contains the conserved CXC motif preceded by the tripeptide sequence EMH. Purified recombinant SmCXCL8 (rSmCXCL8) induced chemotaxis in peripheral blood neutrophils and, to lesser extents, head kidney (HK) lymphocytes and macrophages in a dose-dependent manner. Mutation of the EMH motif by alanine substitution reduced the chemoattractive effect of rSmCXCL8. Expression of SmCXCL8 as determined by quantitative real time RT-PCR (qRT-PCR) was detected mainly in immune organs under normal physiological conditions and was upregulated by experiment challenges with bacterial pathogen and poly(I:C). In addition, SmCXCL8 expression was also induced to significant extents following vaccination of turbot with a subunit vaccine. When rSmCXCL8 was added to the cell cultures of peripheral blood leukocytes and HK lymphocytes and macrophages, it stimulated the proliferation of these cells and enhanced cellular resistance against intracellular bacterial survival. qRT-PCR analysis showed that rSmCXCL8 induced the expression of TNF-α and suppressor of cytokine signaling 3 in HK lymphocytes in different time frames. On the other hand, SmCXCL8 expression was also upregulated by TNF-α. Taken together, these results indicate that SmCXCL8 is a functional CXC chemokine with immunomodulatory effect and plays a role in inflammatory response induced by bacterial infection.

RGS22, a Novel Cancer/testis Antigen, Inhibits Epithelial Cell Invasion and Metastasis

Clinical & Experimental Metastasis. Aug, 2011  |  Pubmed ID: 21533872

RGS22 is a novel testis specific gene. It is located within chromosome 8q22.2, which shows high relevance with tumor chromosomal aberrations. We investigated the potential role of RGS22 in human tumorigenesis. We examined the level of RGS22 expression by tumor tissue arrays, immunohistochemistry and by analyzing the expression levels of four human esophageal cancer cell lines with different metastatic potential using western blot. In addition, we examined the role of RGS22 over-expression in the processes of invasion and metastasis using a highly metastatic cancer cell line. We show that RGS22 are expressed in many tumor types, but specific to cancers with epithelial origin and associated with cancer metastasis. In addition, we identified the association of RGS22 to tumor invasion in cancer cell lines. Over-expression of RGS22 in a highly metastatic esophageal cancer cell line causes decrease in cell migration and reduction in the invasive potential of the cells. RGS22 is over-expressed in low metastatic epithelial cancers and involved in the processes of cell migration and invasion in esophageal cancer cell lines. Therefore, RGS22 may be an important tumor suppressor gene in tumorigenesis, a potential new diagnostic and prognostic biomarker for metastasis and may translate to therapeutic opportunities for the preventive treatment of epithelial cancer metastasis.

Thermal and Rheological Properties of Breadfruit Starch

Journal of Food Science. Jan-Feb, 2011  |  Pubmed ID: 21535676

The thermal and rheological properties of breadfruit starch were studied using DSC and 2 different rheometers. It was found that the gelatinization temperature of starch with excess moisture content (>70%) was at approximately 75 °C. A new endotherm was detected at about 173 °C when the moisture content was lower than required for full gelatinization of the starch. A detailed examination revealed that this endotherm represented the melting of amylose-lipid complexes. Breadfruit starch paste exhibited shear-thinning fluid characteristics, and good thermal and pH stability. The setback viscosity of the breadfruit starch was lower than that of potato and corn starches. The rheological properties of the breadfruit starch paste was well described by the Herschel-Bulkley model at a shear rate of 0 to 100 s(-1), where R(2) is greater than 0.95, and it behaved like a yield-pseudoplastic fluid. Both the storage modulus and loss modulus of the paste initially increased sharply, then dropped after reaching the gelatinization peak. Breadfruit starch gel showed both flexibility and viscosity. Suspension with 6% starch content exhibited very weak gel rigidity; however, this increased significantly at starch contents above 20%.

Toremifene is an Effective and Safe Alternative to Tamoxifen in Adjuvant Endocrine Therapy for Breast Cancer: Results of Four Randomized Trials

Breast Cancer Research and Treatment. Aug, 2011  |  Pubmed ID: 21553116

Compared to tamoxifen, the efficacy and side effects of toremifene in adjuvant endocrine therapy for breast cancer were not very clear. This meta-analysis was conducted to give a more precise estimation of the efficacy and severe side effects of toremifene given in the adjuvant setting in comparison to tamoxifen. The electronic database PubMed was searched for randomized trials comparing toremifene with tamoxifen as adjuvant therapies. Four randomized trials published in three articles were eligible, including 1,890 pooled cases treated with toremifene and 1,857 cases treated with tamoxifen. Compared to patients in tamoxifen group, patients in toremifene group did not have a significantly different overall survival rate (risk ratio (RR): 1.07, 95% confidence interval (CI): 0.97-1.19, P = 0.994 for heterogeneity) or a disease-free survival (DFS) rate (RR: 1.05, 95% CI: 0.95-1.17, P = 0.431 for heterogeneity) at the end of the follow-up time. The rates of thromboembolic events in toremifene group, including deep vein thrombosis (odds ratio (OR): 0.68, 95% CI: 0.40-1.17, P = 0.926 for heterogeneity), cerebrovascular accident (OR: 0.59, 95% CI: 0.32-1.09, P = 0.438 for heterogeneity), and pulmonary embolism (OR: 0.91, 95% CI: 0.42-2.01, P = 0.618 for heterogeneity), were not significantly different from those in tamoxifen group. The rates of endometrial polyps and endometrial cancer between the two groups were almost the same. This meta-analysis suggested that toremifene was as effective as tamoxifen in the adjuvant setting for both perimenopausal and postmenopausal breast cancer patients with similar severe adverse effects to tamoxifen. Toremifene was a convincing and safe change for tamoxifen in adjuvant endocrine therapy.

PDE4 Inhibitor Suppresses PGE2-induced Osteoclast Formation Via COX-2-mediated P27(KIP1) Expression in RAW264.7 Cells

Die Pharmazie. Mar, 2011  |  Pubmed ID: 21553651

We investigated the effects of phosphodiesterase 3 (PDE3) and PDE4 inhibitors, which are cAMP degrading enzymes, on prostaglandin E2 (PGE2)-induced osteoclast formation. A PDE4 inhibitor decreased PGE2-induced osteoclast formation, whereas a PDE3 inhibitor did not, possibly due to the lack of PDE3 expression in RAW 264.7 cells. Cell cycle analysis revealed that the PDE4 inhibitor stimulated PGE2-induced p27(KIP1) expression, which leads to increased growth arrest at G0/G1 phase. The PDE4 inhibitor increased cyclooxygenase 2 (COX-2) expression in the presence of PGE2. COX-2 overexpression was associated with growth suppression via p27(KIP1) expression in RAW 264.7 cells. Taken together, our data demonstrate that the PDE4 inhibitor enhances PGE2-induced growth arrest of osteoclast precursors via COX-2-mediated p27(KIP1) expression, which in turn negatively regulates osteoclast formation.

Cerebroside-A Provides Potent Neuroprotection After Cerebral Ischaemia Through Reducing Glutamate Release and Ca2+ Influx of NMDA Receptors

The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). May, 2011  |  Pubmed ID: 21557879

Excessive presynaptic glutamate release after cerebral ischaemia leads to neuronal death mainly through excessive calcium entry of N-methyl-d-aspartate receptors (NMDARs). Our recent study reported that cerebroside can open large-conductance Ca2+-activated K+ (BKCa) channels. The present study evaluated the effects of cerebroside-A (CS-A), a single molecule isolated from an edible mushroom, on brain injury after focal or global ischaemia in adult male mice and rats. We herein report that treatment with CS-A after 60-min middle cerebral artery occlusion dose-dependently reduced the cerebral infarction with at least a 6-h efficacious time-window, which was partially blocked by the BKCa channel blocker charybdotoxin (CTX). Treatment with CS-A after 20 min global cerebral ischaemia (four-vessel occlusion) significantly attenuated the death of pyramidal cells in hippocampal CA1 area, which was also sensitive to CTX. CS-A, by opening the BKCa channel, could prevent excessive glutamate release after oxygen-glucose deprivation (OGD). In addition, CS-A could inhibit NMDAR Ca2+ influx, which did not require the activation of the BKCa channel. Furthermore, CS-A blocked the OGD-induced NMDAR-dependent long-term potentiation in hippocampal CA1 region. These findings indicate that treatment with CS-A after stroke exerts potent neuroprotection through prevention of excessive glutamate release and reduction of Ca2+ influx through NMDARs.

Assessment of Limbus and Central Cornea in Patients with Keratolimbal Allograft Transplantation Using in Vivo Laser Scanning Confocal Microscopy: an Observational Study

Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie. May, 2011  |  Pubmed ID: 21267594

Keratolimbal allograft (KLAL) transplantation has been proved to be a useful surgical procedure for limbal stem cell deficiency patients. However, information about in vivo ocular surface changes in those patients is limited, due to the lack of a reliable and non-invasive technique for closely monitoring the changes of KLAL grafts. The aim of this study is to characterize the cellular changes in the limbus and central cornea after KLAL in patients with severe ocular chemical injury, using in vivo laser scanning confocal microscopy (LSCM).

Hepatocyte Nuclear Factor-4 Alpha Regulates Liver Triglyceride Metabolism in Part Through Secreted Phospholipase A₂ GXIIB

Hepatology (Baltimore, Md.). Feb, 2011  |  Pubmed ID: 21274867

Hepatocyte nuclear factor-4 alpha (HNF-4α) is an important transcription factor governing the expression of genes involved in multiple metabolic pathways. Secreted phospholipase A(2) GXIIB (PLA(2) GXIIB) is an atypical member of a class of secreted phospholipases A(2) . We establish in this study that PLA(2) GXIIB is an HNF-4α target gene. We demonstrate that HNF-4α binds to a response element on the PLA(2) GXIIB promoter. Moreover, HNF-4α agonists induce PLA(2) GXIIB expression in human hepatocarcinoma cells. Importantly, PLA(2) GXIIB-null mice accumulate triglyceride, cholesterol, and fatty acids in the liver and develop severe hepatosteatosis resembling some of the phenotypes of liver-specific HNF-4α-null mice. These defects are in part due to compromised hepatic very low-density lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4α elevates serum triglyceride level in wild-type but not PLA(2) GXIIB-null mice. CONCLUSION: Collectively, these evidences suggest that HNF-4α is a key physiological PLA(2) GXIIB transcriptional regulator and that PLA(2) GXIIB is a novel mediator of triglyceride metabolism in the liver.

Evaluation of Severe Subclavian Artery Stenosis by Color Doppler Flow Imaging

Ultrasound in Medicine & Biology. Mar, 2011  |  Pubmed ID: 21276651

This study evaluates the diagnostic value of the hemodynamic parameters of color Doppler flow imaging (CDFI) for severe (70 to 99%) subclavian artery stenosis (SAS) using digital subtraction angiography (DSA) as the reference standard. Two-hundred fifty-two patients with suspected SAS were recruited into the study and examined from June 2005 to December 2009. The degree of stenosis was classified as moderate (50 to 69%) or severe (70 to 99%) stenosis. By using CDFI, the residual diameter (Dr), peak systolic velocity (PSV1) and end diastolic velocity (EDV) at the stenotic vessel segments, as well as the original diameter (Do) and PSV2 of the relative normal segments distal to the stenosis (the segment distal to the poststenotic dilation) were recorded. The diameter stenosis rate (1-Dr/Do) and PSV ratio (PSV1/PSV2) were calculated. Using DSA as the reference standard, the diagnostic values and optimal cutoff values for each parameter for the evaluation of severe (70%-99%) were determined using receiving operating characteristic curve analysis. Among the 252 patients, 109 patients were diagnosed as having severe (70 to 99%) SAS and 143 patients had moderate (50 to 69%) SAS. The optimal cutoff values for PSV1, EDV and the PSV1/PSV2 ratio for evaluating severe (70 to 99%) SAS were PSV1 ≥343 cm/s, EDV ≥60 cm/s and PSV1/PSV2 ≥4.0, respectively. The accuracy for diagnosing SAS with PSV1 (86.1%) was higher than that of EDV (85.7%), PSV1/PSV2 (84.9%) and 1-Dr/Do (80.2%). In addition, when PSV1 was used in combination with EDV and 1-Dr/Do, the accuracy for diagnosing SAS increased from 86.1% to 87.3%. When PSV1 was used in combination with EDV and PSV1/PSV2, the accuracy for diagnosing SAS reached 95.8%. In conclusion, the CDFI hemodynamic parameters of PSV1, EDV and PSV1/PSV2 show good consistency with DSA for diagnosing severe (70 to 99%) SAS, and a combination of these three parameters can ensure even greater accuracy for diagnosing SAS.

Abnormal Synaptic Plasticity in Basolateral Amygdala May Account for Hyperactivity and Attention-deficit in Male Rat Exposed Perinatally to Low-dose Bisphenol-A

Neuropharmacology. Apr, 2011  |  Pubmed ID: 21277317

If the pregnant and lactating female rats are exposed to environmental levels of bisphenol-A (BPA), their male offspring will display hyperactivity and attention-deficit. In patients with attention-deficit/hyperactivity disorder (ADHD), the size of the amygdala is reported to be reduced. This study examined functional alterations in the basolateral amygdala (BLA) of the postnatal 28-day-old male offspring exposed perinatally to BPA (BPA-rats). We specifically focused on the synaptic properties of GABAergic/dopaminergic systems in the BLA. A single electrical stimulation of the capsule fibers evoked multispike responses with an enhanced primary population spikes (1st-PS) in the BPA-rats. A single train of high-frequency stimulation of the fibers induced NMDA receptor (NMDAR) dependent long-term potentiation (LTP) in BPA-rats, but not in control rats. Also, paired-pulse inhibition (PPI, GABA-dependent) in control rats was reversed to paired-pulse facilitation (PPF) in BPA-rats. Perfusion of slices obtained from BPA-rats with the GABA(A) receptor (GABA(A)R) agonist muscimol blocked the multispike responses and LTP, and recovered PPI. By contrast, the dopamine D1 receptor antagonist SCH23390 abolished LTP and attenuated the increased amplitude of 1st-PS in BPA-rats. Conversely, blockade of GABA(A)R by bicuculline could produce the multispike responses and PPF in BLA in control rats. Furthermore, in BLA the infusion of SCH23390, muscimol or the NMDAR blocker MK801 ameliorated the hyperactivity and improved the deficits in attention. These findings suggest that the perinatal exposure to BPA causes GABAergic disinhibition and dopaminergic enhancement, leading to an abnormal cortical-BLA synaptic transmission and plasticity, which may be responsible for the hyperactivity and attention-deficit in BPA-rats. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

Alteration of Synaptic Plasticity in Rat Dorsal Striatum Induced by Chronic Ethanol Intake and Withdrawal Via ERK Pathway

Acta Pharmacologica Sinica. Feb, 2011  |  Pubmed ID: 21293469

The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity.

Exposure to PCBs, Through Inhalation, Dermal Contact and Dust Ingestion at Taizhou, China--a Major Site for Recycling Transformers

Chemosphere. Apr, 2011  |  Pubmed ID: 21295325

Air samples containing gaseous and particulate phases were collected from e-waste workplaces and residential areas of an intensive e-waste recycling area and compared with a reference site. The highest total concentration of PCBs was detected at transformer recycling workshops (17.6 ng m(-3)), followed by the residential area (3.37 ng m(-3)) at Taizhou, and the lowest was obtained at the residential area of the reference site, Lin'an (0.46 ng m(-3)). The same trend was also observed with regards to PCB levels in dust samples. The highest average PCBs level of 2824 ng g(-1) (dry wt) was found in the transformer recycling workshops, and was significantly higher than that of residential areas of Taizhou (572 ng g(-1) dry wt) and Lin'an (42.4 ng g(-1) dry wt). WHO-PCB-TEQ level in the workshops of Taizhou was 2216 pg TEQ(1998)g(-1) dry wt or 2159 pg TEQ(2005)g(-1) dry wt, due to the high abundance of PCB 126 (21.5 ng g(-1) dry wt), which contributed 97% or 99% of WHO-PCB-TEQs. The estimated intake of PCBs via dust ingestion and dermal absorption by transformer recycling workers were 77.5×10(-5) and 36.0×10(-5) pg WHO-PCB-TEQ(1998)kg(-1)d(-1), and 67.3×10(-5) and 31.3×10(-5) pg WHO-PCB-TEQ(2005)kg(-1)d(-1), respectively.

Genetic Polymorphisms of Glutathione S-transferases Are Associated with Ulcerative Colitis in Central China

Cell Biochemistry and Biophysics. Jul, 2011  |  Pubmed ID: 21301992

The present study aimed to investigate the association between genetic polymorphisms of glutathione S-transferases (GSTs) and susceptibility to ulcerative colitis (UC) in central China. The prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms were examined using polymerase chain reaction methods in 270 consecutive UC patients and 623 age- and sex-matched healthy controls. The frequencies of the GSTM1(null) and GSTT1(null) as well as GSTP1 (Val/Val) genotypes were significantly higher in UC patients than in the controls (70.74% vs. 41.74%, P = 0.0001; 64.82% vs. 47.19%, P = 0.0001; and 48.89% vs. 34.35%, P = 0.0004, respectively). When the UC patients were stratified according to clinical features, we found that the frequencies of the GSTT1(null) and GSTP1 (Val/Val) genotypes but not the GSTM1(null) genotype were significantly higher in patients with distal colitis than in extensive colitis (P = 0.0007, P = 0.001, and P = 0.271, respectively). However, these variant GST genotypes were not significantly linked to severity of the disease (P > 0.05). GST variant genotypes are strongly correlated with prevalence and extent but not with severity of UC in the Hubei Han population in central China.

Mechanistic Distinction Between Activation and Inhibition of (Na(+)+K(+))-ATPase-mediated Ca2+ Influx in Cardiomyocytes

Biochemical and Biophysical Research Communications. Mar, 2011  |  Pubmed ID: 21303662

(Na(+)+K(+))-ATPase (NKA) mediates positive inotropy in the heart. Extensive studies have demonstrated that the reverse-mode Na(+)/Ca(2+)-exchanger (NCX) plays a critical role in increasing intracellular Ca(2+) concentration through the inhibition of NKA-induced positive inotropy by cardiac glycosides. Little is known about the nature of the NCX functional mode in the activation of NKA-induced positive inotropy. Here, we examined the effect of an NKA activator SSA412 antibody on (45)Ca influx in isolated rat myocytes and found that KB-R7943, a NCX reverse-mode inhibitor, fails to inhibit the activation of NKA-induced (45)Ca influx, suggesting that the Ca(2+) influx via the reverse-mode NCX does not mediate this process. Nifedipine, an L-type Ca(2+) channel (LTCC) inhibitor, completely blocks the activation of NKA-induced (45)Ca influx, suggesting that the LTCC is responsible for the moderate increase in intracellular Ca(2+). In contrast, the inhibition of NKA by ouabain induces 4.7-fold (45)Ca influx compared with the condition of activation of NKA. Moreover, approximately 70% of ouabain-induced (45)Ca influx was obstructed by KB-R7943 and only 30% was impeded by nifedipine, indicating that both the LTCC and the NCX contribute to the rise in intracellular Ca(2+) and that the NCX reverse-mode is the major source for the (45)Ca influx induced by the inhibition of NKA. This study provides direct evidence to demonstrate that the activation of NKA-induced Ca(2+) increase is independent of the reverse-mode NCX and pinpoints a mechanistic distinction between the activation and inhibition of the NKA-mediated Ca(2+) influx path ways in cardiomyocytes.

Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-induced LH-surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A

Endocrinology. Apr, 2011  |  Pubmed ID: 21303948

Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.

Characterization of Apoptosis and Proliferation in Esophageal Carcinoma EC109 Cells Following SiRNA-induced Down-regulation of TRAF6

Molecular and Cellular Biochemistry. Jun, 2011  |  Pubmed ID: 21312055

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an activator of the NF-κB transcription factor. NF-κB is involved in a variety of inflammatory, anti-apoptotic, and gene regulatory pathways and was recently found to be over-expressed in esophageal cancer cells. Here we investigated the function of TRAF6 in the esophageal cancer cell line EC109. siRNA targeting TRAF6 was introduced into EC109 cells and TRAF6 mRNA and protein levels were subsequently examined via RT-PCR and western blotting. Rates of apoptosis and cell proliferation were also measured using flow cytometry, ethynyl deoxyuridine (EdU), and CCK-8 (Cell Counting Kit-8) assays. The real-time PCR array was applied to profile the expression of TRAF6 related genes. TRAF6-siRNA reduced TRAF6 mRNA and protein expressions. NF-κB p65 protein expression was decreased in TRAF6-targeting siRNA-transfected cells compared to cells of the negative control. TRAF6-siRNA also significantly inhibited proliferation and enhanced apoptosis of EC109 cells. These studies suggested that TRAF6 was required for NF-κB activation in EC109 cells and it may be a good molecular target for suppressing the survival and proliferation of esophageal cancer cells.

Unexpected Side Products in the Conjugation of an Amine-derivatized Morpholino Oligomer with P-isothiocyanate Benzyl DTPA and Their Removal

Nuclear Medicine and Biology. Feb, 2011  |  Pubmed ID: 21315270

In connection with pretargeting, an amine-derivatized morpholino phosphorodiamidate oligomer (NH(2)-cMORF) was conjugated conventionally with p-isothiocyanate benzyl-DTPA (p-SCN-Bn-DTPA). However, after (111)In radiolabeling, unexpected label instability was observed. To understand this instability, the NH(2)-cMORF and, as control, the native cMORF without the amine were conjugated in the conventional manner. Surprisingly, the (111)In labeling of the native cMORF conjugate was equally effective as that of the NH(2)-cMORF conjugate (>95%) despite the absence of the amine group. Furthermore, heating the radiolabeled NH(2)-cMORF and native cMORF conjugates resulted in a 35% loss and a complete loss of the label, respectively. Since the (111)In labeled DTPA is known to be stable, the instability in both cases must be due to some unstable association of DTPA to the cMORF, presumably unstable association to some endogenous sites in cMORF. Based on this assumption, a postconjugation-prepurification heating step was introduced, and labeling efficiency and stability were again investigated. By introducing the heating step, the side products were dissociated, and after purification and labeling, the NH(2)-cMORF conjugate provided a stable label and high labeling efficiency with no need for postlabeling purification. The biodistribution of this radiolabeled conjugate in normal mice showed significantly lower backgrounds compared with the labeled unstable native cMORF conjugate. In conclusion, the conventional conjugation procedure to attach the p-SCN-Bn-DTPA to NH(2)-cMORF resulted in side product(s) that were responsible for the (111)In label instability. Adding a postconjugation-prepurification heating step dissociated the side products, improved the label stability and lowered tissue backgrounds in mice.

Enhanced Internalization of ErbB2 in SK-BR-3 Cells with Multivalent Forms of an Artificial Ligand

Journal of Cellular and Molecular Medicine. Nov, 2011  |  Pubmed ID: 21323863

Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

Paclitaxel Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy

The Journal of Urology. Apr, 2011  |  Pubmed ID: 21334664

We have noted that inadequate drug delivery to tumor cells is a major cause of failed intravesical therapy for nonmuscle invading bladder cancer, partly due to the dilution of drug concentration by urine production during treatment. To address this problem we developed gelatin nanoparticles of paclitaxel designed to yield constant drug concentrations. The hypothesis that a constant, therapeutic concentration in urine, bladder tissue and tumors can be attained was evaluated in dogs.

Redox-responsive Photochromism and Fluorescence Modulation of Two 3D Metal-organic Hybrids Derived from a Triamine-based Polycarboxylate Ligand

Chemistry (Weinheim an Der Bergstrasse, Germany). Mar, 2011  |  Pubmed ID: 21337438

Determinants of TRPV4 Activity Following Selective Activation by Small Molecule Agonist GSK1016790A

PloS One. 2011  |  Pubmed ID: 21339821

TRPV4 (Transient Receptor Potential Vanilloid 4) channels are activated by a wide range of stimuli, including hypotonic stress, non-noxious heat and mechanical stress and some small molecule agonists (e.g. phorbol ester 4α-PDD). GSK1016790A (GSK101) is a recently discovered specific small molecule agonist of TRPV4. Its effects on physical determinants of TRPV4 activity were evaluated in HeLa cells transiently transfected with TRPV4 (HeLa-TRPV4). GSK101 (10 nM) causes a TRPV4 specific Ca(2+) influx in HeLa-TRPV4 cells, but not in control transfected cells, which can be inhibited by ruthenium red and Ca(2+)-free medium more significantly at the early stage of the activation rather than the late stage, reflecting apparent partial desensitization. Western blot analysis showed that GSK101 activation did not induce an increase in TRPV4 expression at the plasma membrane, but caused an immediate and sustained downregulation of TRPV4 on the plasma membrane in HeLa-TRPV4 cells. Patch clamp analysis also revealed an early partial desensitization of the channel which was Ca(2+)-independent. FRET analysis of TRPV4 subunit assembly demonstrated that the GSK101-induced TRPV4 channel activation/desensitization was not due to alterations in homotetrameric channel formation on the plasma membrane. It is concluded that GSK101 specifically activates TRPV4 channels, leading to a rapid partial desensitization and downregulation of the channel expression on the plasma membrane. TRPV4 subunit assembly appears to occur during trafficking from the ER/Golgi to the plasma membrane and is not altered by agonist stimulation.

Expression of the Integrin-linked Kinase in a Rat Kidney Model of Chronic Allograft Nephropathy

Cell Biochemistry and Biophysics. Sep, 2011  |  Pubmed ID: 21350838

The purpose of this study was to investigate the expression and significance of integrin-linked kinase (ILK) in the pathogenesis of chronic allograft nephropathy (CAN) in rats. For this, kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. ILK protein expression was determined by Western-blot and immunohistological assays, and mRNA by RT-PCR. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts showed markedly increased mononuclear cells infiltration and presented with severe interstitial fibrosis and tubular atrophy at 16 and 24 weeks. ILK expression (protein/mRNA) was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. ILK expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and interstitial fibrosis. Therefore, it was concluded that ILK overexpression was the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and interstitial fibrosis and allograft nephroangiosclerosis at later stage of CAN pathogenesis in rats.

Squamous Cell Cancer of the Head and Neck with Distant Metastasis at Presentation

Head & Neck. May, 2011  |  Pubmed ID: 20872838

Current literature reports widely different rates of distant metastasis at presentation for squamous cell carcinoma of the head and neck (SCCHN). We used the Surveillance Epidemiology and End Results (SEER) database to determine the rate of and risk factors for distant metastasis.

Comparative Immunogenicity of Recombinant Adenovirus-vectored Vaccines Expressing Different Forms of Hemagglutinin (HA) Proteins from the H5 Serotype of Influenza A Viruses in Mice

Virus Research. Jan, 2011  |  Pubmed ID: 20883733

Recent outbreaks of highly pathogenic avian influenza (HPAI) H5N1 viruses in poultry and their subsequent transmission to humans have highlighted an urgent need to develop preventive vaccines in the event of a pandemic. In this paper we constructed recombinant adenovirus (rAd)-vectored influenza vaccines expressing different forms of H5 hemagglutinin (HA) from the A/Vietnam/1194/04 (VN/1194/04) virus, a wild-type HA, a sequence codon-optimized HA and a transmembrane (TM) domain-truncated HA. Compared to the rAd vectors expressing the wild-type HA (rAd-04wtHA) and the TM-truncated form of HA (rAd-04optHA-dTM), the rAd vectored vaccine with the sequence codon-optimized HA (rAd-04optHA) showed a tendency to induce much higher hemagglutinin inhibition (HI) antibody titers in mice immunized with a prime-boost vaccine. Furthermore, administration of the rAd-04optHA vaccine to mice could elicit cross-reactive immune responses against the antigenically distinct HK/482/97 virus. Additionally, we constructed another vector containing the codon-optimized HA of the A/Hong Kong/482/97 (HK/482/97) virus. Administration of a bivalent immunization formulation including the rAd-04optHA and rAd-97optHA vaccines to mice induced a stronger immune response against HK/482/97 virus than the monovalent formulation. Taken together, these findings may have some implications for the development of rAd-vectored vaccines in the event of the pandemic spread of HPAI.

The Highly Potent and Selective Dipeptidyl Peptidase IV Inhibitors Bearing a Thienopyrimidine Scaffold Effectively Treat Type 2 Diabetes

European Journal of Medicinal Chemistry. Jan, 2011  |  Pubmed ID: 21106276

New dipeptidyl peptidase IV inhibitors were designed based on Alogliptin using a scaffold-hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound 10d exhibited subnanomolar (IC(50)=0.33nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of 10d may lead to a new class of clinical candidate DPP-IV inhibitors.

Occurrence, Sources, and Inventory of Hexabromocyclododecanes (HBCDs) in Soils from Chongming Island, the Yangtze River Delta (YRD)

Chemosphere. Jan, 2011  |  Pubmed ID: 21111446

Hexabromocyclododecanes (HBCDs) is a concern due to their large usage combining with physico-chemical properties and toxicity to wildlife and human. However, very limited data were reported on HBCDs in soils, especially from rural area. In this study, 22 soil samples were collected from Chongming Island at estuary of the Yangtze River Delta, to investigate the level, diasteroisomer profile, potential sources, and mass inventory of HBCDs. The total concentrations ranged from not detected to 93.8pgg(-1) dry weight (dw) with a mean of 23.3pgg(-1)dw, which was at the low end of the global levels. The wide distribution of HBCDs in soils suggested that the local emissions of HBCD-containing materials and/or the inputs via atmospheric transport from other regions were two possible sources. Variation of HBCDs levels was observed in different types of soils. Woodland, tideland and road soils contained slightly higher HBCDs than those of farmland and grassland. Overall, γ-HBCD was the dominant diasteroisomer in soils, followed by α-HBCD and β-HBCD. Significant but weak correlations were only found between α-HBCD and β-HBCD versus TOC content in soils. Currently, the mass inventory of HBCDs in soils of Chongming Island was 5.3kg. Based on these data, we gave perspective on human intake of HBCDs via soil ingestion by age. Local resident's intakes ranged from 15.5 to 97.8fgkg body weight(-1)d(-1), in which children are exposed more than adults.

Pregnenolone Sulfate Enhances Survival of Adult-generated Hippocampal Granule Cells Via Sustained Presynaptic Potentiation

Neuropharmacology. Feb-Mar, 2011  |  Pubmed ID: 21111750

Synaptic input activity affects the neurogenesis in adult hippocampal dentate gyrus (DG), while the input activity is potentiated by neurosteroid pregnenolone sulfate (PREGS). This study focused on exploring the effects of PREGS on the survival of newborn neurons in the DG of adult male mice. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and injection (i.c.v.) of PREGS (3 nmol for two successive days) was made on various paired days from 0-1 to 20-21 after BrdU-injection. PREGS given on day 11-12 or 15-16, roughly corresponding to the prophase of synaptogenesis, produced an approximately 2-fold increase in the number of 22-day-old BrdU(+) cells. Hippocampal slices, which were prepared 60 min after the in vivo PREGS-injection and followed by 60 min perfusion with artificial cerebrospinal fluid (ACSF), showed a sustained (>60 min) increase in the presynaptic glutamate release at perforant path-granule cell synapses. PREGS-inducted presynaptic potentiation required a co-activation of α7 nicotinic acetylcholine receptor (α7nAChR), NMDA receptor (NMDAr) and sigma-1 receptor (σ1R), while its maintenance after PREGS-washout depended only on NMDAr and neuronal NO synthase (nNOS) activation. PREGS enhanced the NMDAr-mediated nNOS expression to increase presynaptic glutamate release via a retrograde NO signaling. The sustained presynaptic potentiation was critical to keep the PREGS-enhanced survival of newborn neurons in an NMDAr-dependent manner. These results for the first time provide in vivo evidence that PREGS enhances the survival of newborn neurons in adult animals through the potentiation of synaptic input activity.

Short Communication: Enhancement of Immunogenicity of Replication-defective Adenovirus-based Human Immunodeficiency Virus Vaccines in Rhesus Monkeys

AIDS Research and Human Retroviruses. Jun, 2011  |  Pubmed ID: 21083437

Adenovirus (Ad) is still under extensive investigation as a vector for HIV vaccination; however, one possible explanation for the failure of Merck's STEP trial is the relatively weak immunogenicity of replication-defective Ad vectors. In this study, a novel strategy to enhance the immunogenicity of replication-defective Ad-based HIV vaccines was developed. First, a recombinant plasmid expressing adenoviral E1 protein (pVAX-E1) was constructed to complement the E1-deleted replication-defective Ad vectors in trans. Then, the immunogenicity of the vaccine regimen of Ad5-HIV gag plus pVAX-E1 plasmid was assessed in rhesus macaques. Compared with traditional administration of Ad-based vectors alone, the results showed that our strategy elicited a more sustained and robust HIV gag-specific cellular response and enhanced long-term proliferation of CD4(+) and CD8(+) T lymphocytes. This strategy represents a proof-of-concept that enhances the immunogenicity of replication-defective Ad-based vectors, and it exemplifies the useful implications for Ad-based HIV vaccines and other vaccines.

Identification of a High Affinity TAG-72 Binding Peptide by Phage Display Selection

Cancer Biology & Therapy. Jan, 2011  |  Pubmed ID: 20980835

Phage display was used to select novel peptides that specifically bind the TAG-72 antigen and with properties suitable for imaging TAG-72 positive cancers.

Microsurgical Management of Tuberculum Sellae Meningiomas by the Frontolateral Approach: Surgical Technique and Visual Outcome

Clinical Neurology and Neurosurgery. Jan, 2011  |  Pubmed ID: 20947247

The aim of this study was to evaluate visual outcome in patients with tuberculum sellae meningioma (TSM) treated microsurgically using the frontolateral or fronto-orbital approach and optic canal unroofing to resect tumor involvement of the optic canal.

Bidirectional Immunoregulation of Calcineurin Inhibitor Tacrolimus on FOXP3 Transcription?

Medical Hypotheses. Feb, 2011  |  Pubmed ID: 20937549

The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.

Noninvasive and Real-time Monitoring of the Therapeutic Response of Tumors in Vivo with an Optimized HTERT Promoter

Cancer. Aug, 2011  |  Pubmed ID: 22009660

BACKGROUND: Telomerase is commonly recognized as an effective anticancer target. The human telomerase reverse transcriptase (hTERT), the rate-limiting component of telomerase, is expressed in most malignant tumors, but it is not found in most normal somatic cells. Here, we report a real-time and noninvasive method to monitor tumor response to a lentivirus-based hTERT-conditional suicidal gene therapy. METHODS: In this study, we constructed a lentivirus system in which an optimized hTERT promoter was used to drive the expression of the cytosine deaminase (CD) gene, one of the suicide genes, and a green fluorescent protein (GFP) reporter gene (pLenti-CD/GFP). The lentivirus was used to infect telomerase-positive or telomerase-negative cell lines. In vitro and in vivo experiments were conducted to analyze the dynamic processes of exogenous gene expression noninvasively in cell culture and living animals in real time via optical imaging. RESULTS: The lentivirus was able to express the CD gene and GFP in telomerase-positive tumor cells and significantly decrease cell proliferation after the use of prodrug 5-flucytosine. However, it could not express GFP and CD in telomerase-negative cell lines, nor could it induce any suicidal effect in those cells. The in vivo study showed that telomerase-positive tumors can be visualized after intratumor injection of the lentivirus in tumor-bearing nude mice via an optical imaging system. Significant tumor growth suppression was observed in telomerase-positive tumors. CONCLUSIONS: Collectively, this technology provides a valuable, noninvasive method to evaluate the real-time therapeutic response of tumors in vivo. Cancer 2011;. © 2011 American Cancer Society.

[Progress and Prospect of Electrospun Silk Fibroin in Construction of Tissue-engineering Scaffold]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. Jun, 2011  |  Pubmed ID: 22034811

Silk fibroin is a natural macromolecular fibroin. It has broad prospects in tissue engineering application due to its good physical and mechanical properties and good biocompatibility. This paper reviews its chemistry structure, property, the usage as matrix of tissue-engineering scaffold using electrospinning technology, and the influence on growth, proliferation and function of vascular endothelial cell, smooth muscle cell, keratinocyte and fibroblast. It also addresses the advantages and disadvantages of silk fibroin applied in tissue engineering study like artificial vascular, skin, bone stent etc. The potential applications on esophageal tissue engineering and regenerative medicine were discussed.

How NaCl Raises Blood Pressure: A New Paradigm for the Pathogenesis of Salt-dependent Hypertension

American Journal of Physiology. Heart and Circulatory Physiology. Nov, 2011  |  Pubmed ID: 22058154

Excess dietary salt (NaCl) is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na(+) and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid (CSF) [Na(+)]. This leads, via the Na(+)-sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction . Plasma levels of endogenous ouabain (EO), the Na(+) pump ligand, also become elevated. Remarkably, high CSF [Na(+)]-evoked, locally-secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na(+) channels, EO, ouabain-sensitive α2 Na(+) pumps and angiotensin II. The EO increases (e.g.) hypothalamic angiotensin type-1 receptor and NADPH oxidase, and decreases neuronal NOS protein expression. The Aldo-ENaC-EO-α2 Na(+) pump-Ang II pathway modulates the activity of brain cardiovascular control centers that regulate the BP 'set point' and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex enhances vasoconstriction directly via an EO-α2 Na(+) pump- Na/Ca exchanger (NCX)-Ca(2+) signaling pathway. Importantly, circulating EO also activates an EO-α2 Na(+) pump-Src kinase signaling cascade. This increases expression of the NCX-transient receptor potential cation channel (TRPC) Ca(2+) signaling pathway in arterial smooth muscle, but decreases expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may participate directly in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP.

Okadaic Acid Induces Apoptosis Through the PKR, NF-κB and Caspase Pathway in Human Osteoblastic Osteosarcoma MG63 Cells

Toxicology in Vitro : an International Journal Published in Association with BIBRA. Dec, 2011  |  Pubmed ID: 21964477

Okadaic acid (OA) is the major component of diarrheic shellfish poisoning toxins and a potent inhibitor of protein phosphatase 1 and 2A. However, the underlying regulatory mechanisms involved in OA-induced cell death are not well understood. In the present study, we examined the effects of OA on apoptosis of MG63 cells by characterizing apoptotic morphological changes of the cells and DNA fragmentation. The roles of double-stranded RNA-dependent protein kinase (PKR), nuclear factor-κB (NF-κB) and caspase in OA-mediated apoptosis in MG63 cells were also examined. Results showed that OA induced cytotoxicity and apoptosis in MG63 cells at IC50 of 75 nM. A functional PKR pathway is required to induce apoptosis in response to OA treatment. Blockade of NF-κB by ammonium pyrrolidinedithiocarbamate (PDTC) resulted in down-regulation of apoptosis. The caspase-3 and caspase-8 inhibitors blocked apoptosis in MG63 cells. In conclusion, our results imply that OA can induce MG63 cell apoptosis through the PKR, NF-κB and caspase pathway.

Colorimetric Detection of Trace Copper Ions Based on Catalytic Leaching of Silver-coated Gold Nanoparticles

ACS Applied Materials & Interfaces. Nov, 2011  |  Pubmed ID: 21970438

A colorimetric, label-free, and nonaggregation-based silver coated gold nanoparticles (Ag/Au NPs) probe has been developed for detection of trace Cu(2+) in aqueous solution, based on the fact that Cu(2+) can accelerate the leaching rate of Ag/Au NPs by thiosulfate (S(2)O(3)(2-)). The leaching of Ag/Au NPs would lead to dramatic decrease in the surface plasmon resonance (SPR) absorption as the size of Ag/Au NPs decreased. This colorimetric strategy based on size-dependence of nanoparticles during their leaching process provided a highly sensitive (1.0 nM) and selective detection toward Cu(2+), with a wide linear detection range (5-800 nM) over nearly 3 orders of magnitude. The cost-effective probe allows rapid and sensitive detection of trace Cu(2+) ions in water samples, indicating its potential applicability for the determination of copper in real samples.

Herpesvirus Entry Mediator Regulates Hypoxia-inducible Factor-1α and Erythropoiesis in Mice

The Journal of Clinical Investigation. Dec, 2011  |  Pubmed ID: 22080867

Erythropoiesis, the production of red blood cells, must be tightly controlled to ensure adequate oxygen delivery to tissues without causing thrombosis or stroke. Control of physiologic and pathologic erythropoiesis is dependent predominantly on erythropoietin (EPO), the expression of which is regulated by hypoxia-inducible factor (HIF) activity in response to low oxygen tension. Accumulating evidence indicates that oxygen-independent mediators, including inflammatory stimuli, cytokines, and growth factors, also upregulate HIF activity, but it is unclear whether these signals also result in EPO production and erythropoiesis in vivo. Here, we found that signaling through herpesvirus entry mediator (HVEM), a molecule of the TNF receptor superfamily, promoted HIF-1α activity in the kidney and subsequently facilitated renal Epo production and erythropoiesis in vivo under normoxic conditions. This Epo upregulation was mediated by increased production of NO by renal macrophages. Hvem-deficient mice displayed impaired Epo expression and aggravated anemia in response to erythropoietic stress. These data reveal that HVEM signaling functions to promote HIF-1α activity and Epo production, and thus to regulate erythropoiesis. Furthermore, our findings suggest that this molecular mechanism could represent a therapeutic target for Epo-responsive diseases, including anemia.

Structure Change Induced by Terminal Sulfur in Noncentrosymmetric La2Ga2GeS8 and Eu2Ga2GeS7 and Nonlinear-optical Responses in Middle Infrared

Inorganic Chemistry. Dec, 2011  |  Pubmed ID: 22087584

Two new noncentrosymmetric quaternary sulfides, La(2)Ga(2)GeS(8) (1) and Eu(2)Ga(2)GeS(7) (2), have been synthesized by high-temperature solid-state reactions. The structure change on going from 1 to 2 to the known Li(2)Ga(2)GeS(6) (3) nicely shows that the reduced cation charge-compensation requirement causes a decrease in the number of terminal S atoms per formula, which is a key to determining the connectivity of the GaS(4) and GeS(4) building units. Powder sample 2 exhibits a strong second-harmonic-generation (SHG) response of about 1.6 times the benchmark AgGaS(2) at 2.05 μm laser radiation, a non type I phase-matchable behavior, and a comparable transparency region. The SHG intensities of these compounds originate from the electronic transitions from S 3p states to La/Eu/Li-S, Ga-S, and Ge-S antibonding states according to Vienna ab initio simulation package studies.

Effect of Resistant Starch Film Properties on the Colon-targeting Release of Drug from Coated Pellets

Journal of Controlled Release : Official Journal of the Controlled Release Society. Nov, 2011  |  Pubmed ID: 22195920

A Novel Oral Colon-targeting Drug Delivery System Based on Resistant Starch Acetate

Journal of Controlled Release : Official Journal of the Controlled Release Society. Nov, 2011  |  Pubmed ID: 22195921

Sturge-weber Syndrome

Annals of Dermatology. Nov, 2011  |  Pubmed ID: 22148033

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome, characterized by the association of facial port-wine hemangiomas in the trigeminal nerve distribution area, with vascular malformation(s) of the brain (leptomeningeal angioma) with or without glaucoma. Herein, we reported Sturge-Weber syndrome in a 50-year-old man, who presented port-wine hemangiomas and epilepsy. In this case, the patient's epilepsy episodes from his first year of life had been ignored and separated from the entity of SWS by his physicians, which led to delayed treatment. This case illustrates the importance of careful examination of patients of any age with hemangiomas in the trigeminal nerve with concomitant episodes of epilepsy. In such cases, there should be yearly neuroimaging screenings to guaranteed early interdisciplinary interventions from the time of definite diagnosis.

Potent Neutralization of Influenza A Virus by a Single-domain Antibody Blocking M2 Ion Channel Protein

PloS One. 2011  |  Pubmed ID: 22164266

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

Effects of Ultraviolet Radiation Exposure on FOXP3+ Infiltration in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma

Photodermatology, Photoimmunology & Photomedicine. Dec, 2011  |  Pubmed ID: 22092733

To analyze the prevalence and significance of FOXP3+ infiltration into (pre)malignant skin carcinomas following ultraviolet radiation (UVR) exposure. The possible pathways that UVR impacts on FOXP3 are to be discussed.

Topographic Characterization and Protein Quantification of Esophageal Basement Membrane for Scaffold Design Reference in Tissue Engineering

Journal of Biomedical Materials Research. Part B, Applied Biomaterials. Jan, 2012  |  Pubmed ID: 22102566

Basement membrane (BM) has been investigated widely and applied in the field of bio-synthesized scaffold design in tissue engineering. However, this respect of investigation has seen scarcely in the field of esophageal tissue engineering. This study reports BM's basic topographic characters and quantification of structural and major proteins involving collagen IV, laminin, entactin, proteoglycans of porcine esophagus. Several methods were adopted to strip epithelium from mucosa tissue. For example, ethylene diamine tetraacetic acid, sonication, dithiothreitol, cold sodium chloride (NaCl), mechanical force of glass coverslip, and cold trypsin and so forth. Assessed experimental results under different conditions, the optimal condition to isolate epithelium from BM was established. After the reaction of cold trypsin at 4°C for 15 h, the BM was isolated from epithelium and exposed integratedly. Hematoxylin and eosin staining and immunohistochemical staining verified the effectiveness of epithelium removal and the integrity of BM. The topographic features of the exposed BM were observed under transmission electron microscopy and scanning electron microscopy. It displayed a rugged surface and 3-D topography consisting of pores and fibers with sub-100 nm range via ImageJ software. The major proteins existing in BM were quantitatively analyzed by enzyme-linked immune sorbent assay. All these results will provide references for the design of synthesized scaffolds and protein modification in esophageal tissue-engineering research.

Hypertonic Stimulation Inhibits Synaptic Transmission in Hippocampal Slices Through Decreasing Pre-synaptic Voltage-gated Calcium Current

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22172932

Acute changes in the cerebrospinal fluid osmotic pressure modulate the brain excitability. The present study investigated the effect of hypertonic stimulation on the synaptic transmission in hippocampal slices. It was found that the slope of excitatory postsynaptic potential (EPSP) in hippocampal CA1 area was inhibited after the hypertonic treatment. Accompanied with the inhibition in EPSP slope, the paired-pulse facilitation (PPF) was increased by hypertonicity. Transient receptor potential vanilloid 4 (TRPV4 receptor) antagonists did not block hypertonicity-action. High voltage-gated calcium current (I(HVA)) in hippocampal CA3 neurons was decreased by hypertonicity, whereas the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced current in hippocampal CA1 neurons was unaffected. Additionally, inhibition of phosphatidylinositol 3-kinase (PI3K) or protein kinase A (PKA) markedly attenuated hypertonicity-induced decrease of I(HVA), whereas antagonism of phosphorylated ERK1/2 mitogen-activated protein kinase (pERK1/2) had no effect. We conclude that hypertonic stimulation inhibits synaptic transmission in hippocampal slices through decreasing pre-synaptic voltage-gated calcium current.

Identification of New Delhi Metallo-β-lactamase Gene (NDM-1) from a Clinical Isolate of Acinetobacter Junii in China

Canadian Journal of Microbiology. Jan, 2012  |  Pubmed ID: 22181044

New Delhi metallo-β-lactamase-1 (NDM-1) is a novel type of metallo-β-lactamase (MBL) responsible for bacterial resistance to β-lactam antibiotics. Acinetobacter junii was previously shown to possess a MBL phenotype; however, the genes responsible for this phenotype were not identified. In this study, we reported the identification of NDM-1 gene in a clinical isolate of A. junii from a child patient in China, which was resistant to all β-lactams except aztreonam but sensitive to aminoglycosides and quinolones. The cloned NDM-1 gene contained an open reading frame of 813 bp and had a nucleotide sequence 99.9% identical (812/813) to reported NDM-1 genes carried by Acinetobacter baumannii , Enterococcus faecium , Escherichia coli , and Klebsiella pneumoniae . Recombinant NDM-1 protein was successfully expressed in E. coli BL21, and antibiotic sensitivities of the NDM-1-producing E. coli were largely similar to the A. junii 1454 isolate. The findings of this study raise attention to the emergence and spread of NDM-1-carrying bacteria in China.

Promoter Methylation Analysis of Seven Clock Genes in Parkinson's Disease

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22193177

The expression of clock genes is altered in leukocytes from patients with Parkinson's disease (PD). However, the underlying mechanisms are unknown. To determine whether abnormal CpG methylation contributes to the dysregulated expression of these genes, the methylation status of the promoters of seven major human clock genes, PER1, PER2, CRY1, CRY2, Clock, NPAS2, and BMAL1, was examined using methylation-specific PCR (MSP) and sequencing in 206 PD patients and 181 healthy controls. This analysis revealed that most clock gene promoters were devoid of methylation. Methylation was only detectable in the CRY1 and NPAS2 promoters. Interestingly, the methylation frequency of the NPAS2 promoter was significantly decreased in PD patients. These results suggest that altered promoter methylation may contribute to the abnormal expression of clock genes in PD.

Hypotonicity-induced TRPV4 Function in Renal Collecting Duct Cells: Modulation by Progressive Cross-talk with Ca(2+)-activated K(+) Channels

Cell Calcium. Feb, 2012  |  Pubmed ID: 22204737

The mouse cortical collecting duct (CCD) M-1 cells were grown to confluency on coverslips to assess the interaction between TRPV4 and Ca(2+)-activated K(+) channels. Immunocytochemistry demonstrated strong expression of TRPV4, along with the CCD marker, aquaporin-2, and the Ca(2+)-activated K(+) channels, the small conductance SK3 (K(Ca)2.3) channel and large conductance BKα channel (K(Ca)1.1). TRPV4 overexpression studies demonstrated little physical dependency of the K(+) channels on TRPV4. However, activation of TRPV4 by hypotonic swelling (or GSK1016790A, a selective agonist) or inhibition by the selective antagonist, HC-067047, demonstrated a strong dependency of SK3 and BK-α activation on TRPV4-mediated Ca(2+) influx. Selective inhibition of BK-α channel (Iberiotoxin) or SK3 channel (apamin), thereby depolarizing the cells, further revealed a significant dependency of TRPV4-mediated Ca(2+) influx on activation of both K(+) channels. It is concluded that a synergistic cross-talk exists between the TRPV4 channel and SK3 and BK-α channels to provide a tight functional regulation between the channel groups. This cross-talk may be progressive in nature where the initial TRPV4-mediated Ca(2+) influx would first activate the highly Ca(2+)-sensitive SK3 channel which, in turn, would lead to enhanced Ca(2+) influx and activation of the less Ca(2+)-sensitive BK channel.

Genetic Diversity and Drug Susceptibility of Mycobacterium Tuberculosis Isolates from Zunyi, One of the Highest Incidence Rate Areas in China

Journal of Clinical Microbiology. Jan, 2012  |  Pubmed ID: 22205809

M. tuberculosis isolates from Zunyi were found more diversified but clustered less frequently to Beijing family compared to other areas of China. These observations, on top of the fact that Zunyi area has a high prevalence of MDR-TB, support the notion that Beijing-family isolates may not be linked to MDR-TB.

E2F1: a Potential Negative Regulator of HTERT Transcription in Normal Cells Upon Activation of Oncogenic C-Myc

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Jan, 2012  |  Pubmed ID: 22207128

Previous studies have revealed that the link between c-Myc and E2F1 pathway plays a pivotal role in regulating cell growth and death. Human telomerase reverse transcriptase (hTERT), activation of which is required for cell immortalization and transformation, has been confirmed to be a direct transcriptional target of c-Myc. It is of note that E2F1, which is also a direct transcriptional target of c-Myc, can bind the hTERT promoter and repress its expression. Thus, although oncogene c-Myc can be activated in normal cells, for the subsequent induction of E2F1, it may still be insufficient to trigger the expression of hTERT. This negative feedback regulation, if it exists, may be another mechanism for normal cells to control the transmission of c-Myc-mediated oncogenic signals. In this article, we reviewed current knowledge about the crosstalk among c-Myc, E2F1 and hTERT, with an emphasis on the hypothesis that E2F1 negatively regulates c-Myc-induced hTERT transcription. Additionally, we postulated that the miR-17-92 cluster-mediated regulation of c-Myc and E2F1 expression may be of particular importance for the repression of hTERT transcription.

Detection of Human Enterovirus 71 and Coxsackievirus A16 in Children with Hand, Foot and Mouth Disease in China

Molecular Medicine Reports. Apr, 2012  |  Pubmed ID: 22218731

The aims of the present study were to investigate the genetic characteristics of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) strains in China and to evaluate the relationship between the genotypes of CVA16 and EV71 and their geographical distribution. A total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (HFMD) in Zhejiang Province. The presence of enteroviruses was determined using reverse transcription-semi-nested PCR targeted to the VP1 gene of all human enteroviruses and DNA sequencing. EV71 and CVA16, the major etiological agents of HFMD, were detected in 38.4% (38/99) and 35.4% (35/99) of HEV-A species-positive cases, respectively. Based on the phylogenetic analysis of the VP1 gene, EV71 strains identified in this study belong to subgenotype C4, and CVA16 strains herein were classified into clusters B2a and B2b within the genotype B2. Taking into consideration other published data, we conclude that the genetic characteristics of enteroviruses in China reflect the pattern of the endemic circulation of the subgenotype C4 to EV71 and clusters B2a and B2b within genotype B2 to CVA16, which have been continuously circulating in China since 1997. This observation indicates that the genetic characteristics of enteroviruses in China seem to depend on their special geographical and climatical features allowing them to be sustained with little external effect.

Noncentrosymmetric Inorganic Open-Framework Chalcohalides with Strong Middle IR SHG and Red Emission: Ba(3)AGa(5)Se(10)Cl(2) (A = Cs, Rb, K)

Journal of the American Chemical Society. Feb, 2012  |  Pubmed ID: 22239154

Novel SHG effective inorganic open-framework chalcohalides, Ba(3)AGa(5)Se(10)Cl(2) (A = Cs, Rb and K), have been synthesized by high temperature solid state reactions. These compounds crystallize in the tetragonal space group I4̅ (No.82) with a = b = 8.7348(6) - 8.6341(7) Å, c = 15.697(3) - 15.644(2) Å, V = 1197.6(3) - 1166.2(2) Å(3) on going from Cs to K. The polar framework of (3)(∞)[Ga(5)Se(10)](5-) is constructed by nonpolar GaSe(4)(5- )tetrahedron (T1) and polar supertetrahedral cluster Ga(4)Se(10)(8-) (T2) in a zinc-blende topological structure with Ba/A cations and Cl anions residing in the tunnels. Remarkably, Ba(3)CsGa(5)Se(10)Cl(2) exhibits the strongest intensity at 2.05 μm (about 100 times that of the benchmark AgGaS(2) in the particle size of 30-46 μm) among chalcogenides, halides, and chalcohalides. Furthermore, these compounds are also the first open-framework compounds with red photoluminescent emissions. The Vienna ab initio theoretical studies analyze electronic structures and linear and nonlinear optical properties.

Strong Kleinman-Forbidden Second Harmonic Generation in Chiral Sulfide: La(4)InSbS(9)

Journal of the American Chemical Society. Feb, 2012  |  Pubmed ID: 22239538

A new chiral sulfide family, Ln(4)InSbS(9) (Ln = La, Pr, Nd), with its own structure type in space group P4(1)2(1)2 or its enantiomorph P4(3)2(1)2 has been synthesized by solid-state reaction. Remarkably, the La member shows the strongest Kleinman-forbidden second harmonic generation to date, with an intensity 1.5 times that of commercial AgGaS(2) at a laser wavelength of 2.05 μm, and exhibits type-I phase-matchable behavior. Density functional theory calculations and ab initio molecular dynamics simulations suggest that lattice vibrations may be responsible for the origin and magnitude of the strong SHG effect.

Cinobufocini Inhibits NF-κB and COX-2 Activation Induced by TNF-α in Lung Adenocarcinoma Cells

Oncology Reports. Jan, 2012  |  Pubmed ID: 22267101

The aim of the present study was to investigate the effects of cinobufocini on nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and the production of cytokines induced by tumor necrosis factor-α (TNF-α) in the A549 cell line. A549 cells were incubated with cinobufocini at different concentrations for 24, 48 or 72 h. Cell proliferation was examined by the WST-8 assay. The expression of NF-κB, COX-2 and inhibitor κBα (IκBα) was studied by western blotting. The NF-κB-dependent luciferase rporter (3xκB-luc) was transfected for 24 h, the cells were treated with the reagents for 24 h, and the transcriptional activity of the NF-κB promoter was detected by a luciferase assay. The levels of IL-6 and IL-8 mRNA were detected by reverse transcription-polymerase chain reaction. We found that cinobufocini inhibited NF-κB p65 expression and the transcriptional activity of the NF-κB promoter induced by TNF-α compared with the control in the nuclei of A549 cells. Moreover, induced COX-2 expression was blocked by cinobufocini and was correlated with a reduction in the activated p65 subunit of NF-κB. Additionally, the levels of IL-6 and IL-8 mRNA induced by TNF-α were significantly suppressed by the addition of cinobufocini. In conclusion, these results suggest that the anti-inflammatory effects of cinobufocini are dependent on the NF-κB/COX-2 pathway in A549 cells, thereby providing a possible anticancer mechanism for the compound.

[Treatment of Peripheral Facial Paralysis with Acupuncture at Renying (ST 9) Mainly Cooperated with Stellate Ganglion Block: a Randomized Controlled Trial]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Jan, 2012  |  Pubmed ID: 22295815

To explore the better therapy for peripheral facial paralysis.

Construction of a Cellulase Hyper-expression System in Trichoderma Reesei by Promoter and Enzyme Engineering

Microbial Cell Factories. Feb, 2012  |  Pubmed ID: 22314137

ABSTRACT: BACKGROUND: Trichoderma reesei is the preferred organism for producing industrial cellulases. However, a more efficient heterologous expression system for enzymes from different organism is needed to further improve its cellulase mixture. The strong cbh1 promoter of T. reesei is frequently used in heterologous expression, however, the carbon catabolite repressor CREI may reduce its strength by binding to the cbh1 promoter at several binding sites. Another crucial point to enhance the production of heterologous enzymes is the stability of recombinant mRNA and the prevention of protein degradation within the endoplasmic reticulum, especially for the bacteria originated enzymes. In this study, the CREI binding sites within the cbh1 promoter were replaced with the binding sites of transcription activator ACEII and the HAP2/3/5 complex to improve the promoter efficiency. To further improve heterologous expression efficiency of bacterial genes within T. reesei, a flexible polyglycine linker and a rigid alpha-helix linker were tested in the construction of fusion genes between cbh1 from T. reesei and e1, encoding an endoglucanase from Acidothermus cellulolyticus. RESULTS: The modified promoter resulted in an increased expression level of the green fluorescent protein reporter by 5.5-fold in inducing culture medium and 7.4-fold in repressing culture medium. The fusion genes of cbh1 and e1 were successfully expressed in T. reesei under the control of promoter pcbh1m2. The higher enzyme activities and thermostability of the fusion protein with rigid linker indicated that the rigid linker might be more suitable for the heterologous expression system in T. reesei. Compared to the parent strain RC30-8, the FPase and CMCase activities of the secreted enzyme mixture from the corresponding transformant R1 with the rigid linker increased by 39% and 30% at 60degreesC, respectively, and the reduced sugar concentration in the hydrolysate of pretreated corn stover (PCS) was dramatically increased by 40% at 55degreesC and 169% at 60degreesC when its enzyme mixture was used in the hydrolysis. CONCLUSIONS: This study shows that optimizations of the promoter and linker for hybrid genes can dramatically improve the efficiency of heterologous expression of cellulase genes in T. reesei.

Toxicity Features of High Glucose on Endothelial Cell Cycle and Protection by Dan Gua-Fang () in ECV-304 in High Glucose Medium

Chinese Journal of Integrative Medicine. Feb, 2012  |  Pubmed ID: 22331440

OBJECTIVE: To study the toxicity features of high glucose on the endothelial cell cycle and the: influence of Dan Gua-Fang (), a Chinese herbal compound prescription, on the reproductive cycle of vascular endothelial cells cultivated under a high glucose condition; to reveal the partial mechanisms of Dan Gua-Fang in the prevention and treatment of endothelial injury caused by hyperglycemia in diabetes mellitus (DM); and offer a reference for dealing with the vascular complications of DM patients with long-term high blood glucose. METHODS: Based on the previous 3-(4,5)-dimethylthiahiazo (z-y1)-3-5-diphenytetrazoliumromide (MTT) experiment,: under different medium concentrations of glucose and Dangua liquor, the endothelial cells of vein-304 (ECV-304) were divided into 6 groups as follows: standard culture group (Group A, 5.56 mmol/L glucose); 1/300 herb-standard group (Group B); high glucose culture group (Group C, 16.67 mmol/L glucose); 1/150 herb-high glucose group (Group D); 1/300 herb-high glucose group (Group E); and 1/600 herb-high glucose group (Group F). The cell cycle was assayed using flow cytometry after cells were cultivated for 36, 72 and 108 h, respectively. RESULTS: (1): The percentage of cells in the G(0)/G(1) phase was significantly increased in Group C compared with that in Group A (P<0.05), while the percentage of S-phase (S%) cells in Group C was significantly reduced compared with Group A (P<0.05); the latter difference was dynamically related to the length of growing time of the endothelial cells in a high glucose environment. (2) The S% cells in Group A was decreased by 30.25% (from 40.23% to 28.06%) from 36 h to 72 h, and 12.33% (from 28.06% to 24.60%) from 72 h to 108 h; while in Group C, the corresponding decreases were 23.05% and 21.87%, respectively. The difference of S% cells between the two groups reached statistical significance at 108 h (P<0.05). (3) The percentage difference of cells in the G(2)/M phase between Group C and Group A was statistically significant at 72 h (P<0.01). (4) 1/300 Dan Gua-Fang completely reversed the harmful effect caused by 16.67 mmol/L high glucose on the cell cycle; moreover it did not disturb the cell cycle when the cell was cultivated in a glucose concentration of 5.56 mmol/L. CONCLUSIONS: High glucose produces an independent: impact on the cell cycle. Persistent blocking of the cell cycle and its arrest at the G(0)/G(1) phase are toxic effects of high glucose on the endothelial cell cycle. The corresponding variation of the arrest appears in the S phase. 1/300 Dan Gua-Fang completely eliminates the blockage of high glucose on the endothelial cell cycle.

Sensitive Electrochemical Immunosensor Array for the Simultaneous Detection of Multiple Tumor Markers

The Analyst. Jan, 2012  |  Pubmed ID: 22091469

A novel electrochemical immunosensor array for the simultaneous detection of multiple tumor markers was developed by incorporating electrochemically addressing immobilization and one signal antibody strategy. As a proof-of-principle, an eight-electrode array including six carbon screen-printed working electrodes was used as a base array for the analysis of two important tumor markers, carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) and a horseradish peroxidase-labeled antibody was employed as a signal antibody. The immunosensor in the array was fabricated in sequence by covalently coupling the capture antibody onto the surface of the desired working electrode, which was firstly electrochemically addressably grafted with an aminophenyl group by reduction of in situ generated aminophenyl diazonium cation generated from p-phenylenediamine, using glutaraldehyde as cross-linker. This allowed the selective immobilization of the capture antibody at the desired position on a single array via an electrochemical operation. The immunoassay in sandwich mode was performed by specifically binding the targets, second antibodies and one signal antibody to the immunosensor array. The result showed that the steady current density was directly proportional to the concentration of target CEA/AFP in the range from 0.10 to 50 ng mL(-1) with a detection limit of 0.03 ng mL(-1) for CEA and 0.05 ng mL(-1) for AFP (S/N = 3), respectively. This work demonstrates that the employment of an electrochemically addressing method for the fabrication of an immunosensor array and one signal antibody is a promising approach for the determination of multiple tumor markers in clinical samples.

Cognitive Impairment is Common in Parkinson's Disease Without Dementia in the Early and Middle Stages in a Han Chinese Cohort

Parkinsonism & Related Disorders. Feb, 2012  |  Pubmed ID: 21975261

Cognitive impairments have been reported to be common in Parkinson's disease (PD) without dementia, which occur not only in the late stages of PD, but also in the early and middle stages. Until now, no reports on the profile of cognitive impairment in Chinese non-demented PD population have been published yet. Different ethnic groups should be assessed to improve evaluation of cognitive impairment in clinical practice. The aims of this study are to estimate the frequencies and profile of cognitive impairments and to explore the risk factors of cognitive impairments in Han Chinese non-demented PD patients at early and middle stages.

Ruscogenin Inhibits Lipopolysaccharide-induced Acute Lung Injury in Mice: Involvement of Tissue Factor, Inducible NO Synthase and Nuclear Factor (NF)-κB

International Immunopharmacology. Jan, 2012  |  Pubmed ID: 22079591

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0mg/kg 1h prior to LPS challenge (30mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis.

Comparing the Intracellular Fate of Components Within a Noncovalent Streptavidin Nanoparticle with Covalent Conjugation

Nuclear Medicine and Biology. Jan, 2012  |  Pubmed ID: 21958854

Auger radiotherapy requires adequate tumor delivery and high nuclear accumulation and retention. We hypothesize that the noncovalent nature of a streptavidin/biotin three-component nanoparticle possessing these qualities may be required for dissociation of the radiolabeled oligomer and its accumulation into the cell nucleus.

Cathepsin B of Cynoglossus Semilaevis: Identification, Expression, and Activity Analysis

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. Jan, 2012  |  Pubmed ID: 21959146

Cathepsin B (EC 3.4.22.1) is a member of the papain family cysteine protease and in mammals is known to be involved in protein degradation and other biological functions. However, very little is known about the function of cathepsin B in fish. In this study, we identified and analyzed a cathepsin B homologue (CsCatB) from tongue sole (Cynoglossus semilaevis, Pleuronectiformes), an economic fish species cultured in China. CsCatB is composed of 322 amino acid residues and shares 70-81.3% overall sequence identities with its counterpart in teleosts and humans. CsCatB possesses typical cathepsin B structural features including the propeptide region and the papain family cysteine protease domain, the latter containing the four catalytic residues (Q101, C107, H277, and N297) that are conserved in lower and higher vertebrates. Quantitative real time RT-PCR analysis showed that CsCatB expression occurred in multiple tissues and was positively regulated by bacterial infection and by immunization with a subunit vaccine. Recombinant CsCatB purified from Escherichia coli exhibited apparent protease activity, which was optimal at 35 °C and pH 5.5. In contrast, a mutant CsCatB bearing glutamic acid substitution at H277 was dramatically reduced in proteolytic activity. These results indicate that CsCatB is a biologically active protease that is likely to be involved in host immune response during bacterial infection and vaccination.

Bloody Nipple Discharge is a Predictor of Breast Cancer Risk: a Meta-analysis

Breast Cancer Research and Treatment. Feb, 2012  |  Pubmed ID: 21947751

Nipple discharge is a common complaint of patients with breast disease. The color of nipple discharge is always the first alarming symptom for patients. It is controversial whether the discharge color is an indicator of an underlying malignancy. The electronic database PubMed was searched for relevant articles. A meta-analysis about the association between the color of nipple discharge and breast cancer risk was conducted. Eight studies, including 3,110 patients, were eligible for this meta-analysis. Compared with patients in non-bloody nipple discharge group (179/1,478), patients in bloody nipple discharge group (404/1,632) had a markedly higher breast cancer risk (OR: 2.27, 95% CI: 1.32-3.89, P < 0.001 for heterogeneity). Compared with patients in clear/serous group (71/575), patients in bloody nipple discharge group (326/1,271) also had a higher risk (OR: 2.49, 95% CI: 1.25-4.93, P = 0.011 for heterogeneity). Furthermore, compared with patients in the colored group (55/448), patients in bloody nipple discharge group (296/1,124) (OR: 2.00, 95% CI: 0.74-5.45, P = 0.009 for heterogeneity) had no significant difference. Besides, there was no significant difference between patients in colored group (55/448) and clear/serous group (61/470) (OR: 1.35, 95% CI: 0.83-2.18, P = 0.707 for heterogeneity). Therefore, bloody nipple discharge could be a predictor of breast cancer risk among different colors of discharges. The symptom of bloody nipple discharge is helpful to the stratification of preoperative patients.

Melatonin Protects Against Rotenone-induced Cell Injury Via Inhibition of Omi and Bax-mediated Autophagy in Hela Cells

Journal of Pineal Research. Jan, 2012  |  Pubmed ID: 21883444

Parkinson's disease is the second most common neurodegenerative disease, and environmental toxins such as rotenone play an important role in causing degeneration of dopaminergic neurons. Melatonin, a major secretory product of pineal, is recently reported to protect against rotenone-induced cell death in animal models. Yet, the mechanism involved in this protection needs to be elucidated. Here, we report that rotenone treatment (0-100 μM) decreased cell survival of Hela cells in a dose-dependent manner. At concentrations ranging from 0.1 to 100 μM, rotenone induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a protein associated with the autophagosomal membrane. Knockdown of Bax or Omi using shRNA inhibited 1 μM rotenone-induced autophagy. To determine whether melatonin would protect cells against rotenone-induced cell death and autophagy, we pretreated Hela cells with 250 μM melatonin for 24 hr in the presence of rotenone. Melatonin inhibited Bax expression and the release of the omi/HtrA2 into the cytoplasm induced by 1 μM rotenone. Melatonin 250 μM treatment also suppressed cell death induced by 0.1-100 μM rotenone and protected against the formation of LC3-II in cells exposed to 1 μM rotenone. This work demonstrates a novel role for melatonin as a neuroprotective agent against rotenone.

Three Genetic Polymorphisms of Homocysteine-metabolizing Enzymes and Risk of Coronary Heart Disease: a Meta-analysis Based on 23 Case-control Studies

DNA and Cell Biology. Feb, 2012  |  Pubmed ID: 21780915

Many epidemiological studies have explored the relationships between three genetic polymorphisms of genes encoding homocysteine-metabolizing enzymes (methionine synthase [MTR] A2756G, methionine synthase reductase [MTRR] A66G, and N(5),N(10)-methylenetetrahydrofolate reductase [MTHFR] A1298C) and risk of coronary heart disease (CHD), but no conclusive results were obtained. Therefore, we performed a meta-analysis of 23 case-control studies. Odds ratio (OR) and 95% confidence interval (95% CI) were used to examine the strength of the associations. Among those primary studies, 22 studies were for Europeans, and one study focused on the MTR A2756G polymorphism in Asians. The results of combined analyses of the MTR A2756G polymorphism suggested that the G allele was associated with increased risk of CHD and myocardial infarction (MI) especially for Europeans (GG vs. AA for CHD: OR [95% CI]=1.63 [1.18-2.25], p(z)(-test)=0.001, p(heterogeneity)=0.274; GG+AG vs. AA for MI: OR [95% CI]=1.44 [1.08-1.93], p(z)(-test)=0.014, p(heterogeneity)=0.611). In addition, the G allele was also associated with higher risk CHD based on population-based case-control studies (PCC) (GG vs. AA: OR [95% CI]=1.75 [1.24-2.49], p(z)(-test)=0.002, p(heterogeneity)=0.316). The results suggested that the MTRR A66G polymorphism was not associated with risk of CHD for Europeans (AA vs. GG: OR [95% CI]=1.07 [0.59-1.94], p(z)(-test)=0.831, p(heterogeneity)<0.01). The results suggested that the C allele of the MTHFR A1298C polymorphism might be associated with the increased risk of MI for Europeans (CC vs. CA+AA: OR [95% CI]=1.37 [1.03-1.84], p(z)(-test)=0.033, p(heterogeneity)=0.668). However, when subgroup analyses for sources of controls were performed, conflicting results were obtained. The results suggested that the C allele was associated with decreased risk of CHD based on hospital-based case-control studies, but associated with increased risk of CHD based on PCC. This meta-analysis suggests that MTR A2756G polymorphism, but not MTRR A66G and MTHFR A1298C, is associated with risk of CHD for Europeans. Because of limitations and potential bias, more well-designed studies with larger sample size, especially focused on Asians and Africans, should be performed in the future.