Use of UV-C Treatment to Inhibit the Microbial Growth and Maintain the Quality of Yali Pear

Journal of Food Science. Sep, 2010  |  Pubmed ID: 21535563

The effects of UV-C radiation on microbial growth in vitro (Monilinia fruticola) and in inoculated Yali pears (Pyrus bretschneideri Rehd.) were investigated. Moreover, postharvest quality and the activities of defense and antioxidant enzymes were analyzed after the pears were exposed to UV-C irradiation at an energy level of 5 kJ m⁻².The results showed that spore germination of M. fructicola was significantly inhibited by each of the 3 doses (1, 5, and 10 kJ m⁻²) in vitro. In the in vivo assays, lesion diameter on the fruit being inoculated before or after the UV-C treatment was both significantly lower than that on the fruit of control. Meanwhile, the activities of phenylalanine ammonia lyase, β-1,3-glucanase, superoxide dismutase, catalase, and glutathione reductase were induced to high levels by UV-C treatment. We conclude that UV-C treatment could reduce postharvest disease by the germicidal and induced effects and maintain the quality by enhancing the antioxidant enzyme activities. PRACTICAL APPLICATION: UV-C radiation has recently been proposed as a new technology to avoid chemical fungicides. However, there are few studies regarding the effect of UV-C treatment on Yali pear. In this study, we found that 5 kJ m⁻² UV-C irradiation can control postharvest disease and maintain the quality of Yali pear. This method may be applied to reduce the decay of Yali pears during exporting and storage.

Induction of Programmed Cell Death in Arabidopsis and Rice by Single-wall Carbon Nanotubes

American Journal of Botany. Oct, 2010  |  Pubmed ID: 21616795

• Premise of the study: Single-walled carbon nanotubes (SWCNTs) have many unique structural and mechanical properties. Their potential applications, especially in biomedical engineering and medical chemistry, have been increasing in recent years, but the toxicological impact of nanoparticles has rarely been studied in plants. • Methods: We exposed Arabidopsis and rice leaf protoplasts to SWCNTs and examined cell viability, DNA damage, reactive oxygen species generation, and related gene expression. We also tested the effects of nanoparticles on Arabidopsis leaves after injecting a SWCNT solution. EM-TUNEL (electron-microscopic terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) and a cerium chloride staining method were used. • Key results: SWCNTs caused adverse cellular responses including cell aggregation, chromatin condensation along with a TUNEL-positive reaction, plasma membrane deposition, and H(2)O(2) accumulation. The effect of SWCNTs on the survival of cells was dose dependent, with 25 μg/mL inducing 25% cell death in 6 h. In contrast, activated carbon, which is not a nano-sized carbon particle, did not induce cell death even 24 h after treatments. The data indicated that the nano-size of the particle is a critical factor for toxicity. Moreover, endocytosis-like structures with cerium chloride deposits formed after SWCNT treatment, suggesting a possible pathway for nanoparticles to traverse the cell membrane. • Conclusions: Consequently, SWCNTs have an adverse effect on protoplasts and leaves through oxidative stress, leading to a certain amount of programmed cell death. Although nanomaterials have great advantages in many respects, the benefits and side effects still need to be assessed carefully.

Efficient Expression of Bioactive Human Leptin in Escherichia Coli in Soluble Fusion Form

Indian Journal of Clinical Biochemistry : IJCB. Jul, 2010  |  Pubmed ID: 21731206

Leptin, a 16 kDa nonglycosylated hormone, is produced by mature adipocytes and functions primarily in the hypothalamus to reduce food intake and body weight. To explore a new approach for high-level expression of human Leptin in Escherichia coli, the human Leptin gene, synthesized according to the published sequence, was cloned into the vector pET32a to construct a fusion expression plasmid: Trx-Leptin/pET32a. Our data showed that more than 40% of the fusion protein Trx-Leptin was expressed in soluble form. After purified by Ni-IDA affinity chromatography, cleaved by enterokinase and applied Ni-IDA affinity chromatography again, purified Leptin with homogeneity over 96% was achieved. The bio-functional experiments of purified Leptin showed a significant reduction in food intake and body weight of female mice treated with Leptin by comparing with control mice, and it indicated that the purified Leptin has full biological activity. In addition, our expression system was a very low-cost and efficient prokaryotic expression system. So taken together, our results demonstrated that our expression system of bio-active Leptin provided a new method for producing Leptin in big scale and would be widely applied in commercial Leptin producing industries.

Chinese Culture, Homosexuality Stigma, Social Support and Condom Use: A Path Analytic Model

Stigma Research and Action. , 2011  |  Pubmed ID: 21731850

PURPOSE: The objective of this study was to examine the interrelationships among individualism, collectivism, homosexuality-related stigma, social support, and condom use among Chinese homosexual men. METHODS: A cross-sectional study using the respondent-driven sampling approach was conducted among 351 participants in Shenzhen, China. Path analytic modeling was used to analyze the interrelationships. RESULTS: The results of path analytic modeling document the following statistically significant associations with regard to homosexuality: (1) higher levels of vertical collectivism were associated with higher levels of public stigma [β (standardized coefficient) = 0.12] and self stigma (β = 0.12); (2) higher levels of vertical individualism were associated with higher levels self stigma (β = 0.18); (3) higher levels of horizontal individualism were associated with higher levels of public stigma (β = 0.12); (4) higher levels of self stigma were associated with higher levels of social support from sexual partners (β = 0.12); and (5) lower levels of public stigma were associated with consistent condom use (β = -0.19). CONCLUSIONS: The findings enhance our understanding of how individualist and collectivist cultures influence the development of homosexuality-related stigma, which in turn may affect individuals' decisions to engage in HIV-protective practices and seek social support. Accordingly, the development of HIV interventions for homosexual men in China should take the characteristics of Chinese culture into consideration.

Multidisciplinary Management of Congenitally Missing Teeth with Osseointegrated Dental Implants: a Long-term Report

The Chinese Journal of Dental Research : the Official Journal of the Scientific Section of the Chinese Stomatological Association (CSA). , 2011  |  Pubmed ID: 21734944

To describe a multidisciplinary approach to ensure optimal treatment and timing of treatment for these patients.

Synergistic Killing of Multidrug-resistant Pseudomonas Aeruginosa at Multiple Inocula by Colistin Combined with Doripenem in an in Vitro Pharmacokinetic/pharmacodynamic Model

Antimicrobial Agents and Chemotherapy. Dec, 2011  |  Pubmed ID: 21911563

Combination therapy may be required for multidrug-resistant (MDR) Pseudomonas aeruginosa. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR P. aeruginosa. Studies were conducted in a one-compartment in vitro pharmacokinetic/pharmacodynamic model for 96 h at two inocula (~10(6) and ~10(8) CFU/ml) against a colistin-heteroresistant reference strain (ATCC 27853) and a colistin-resistant MDR clinical isolate (19147 n/m). Four combinations utilizing clinically achievable concentrations were investigated. Microbiological response was examined by log changes and population analysis profiles. Colistin (constant concentrations of 0.5 or 2 mg/liter) plus doripenem (peaks of 2.5 or 25 mg/liter every 8 h; half-life, 1.5 h) substantially increased bacterial killing against both strains at the low inoculum, while combinations containing colistin at 2 mg/liter increased activity against ATCC 27853 at the high inoculum; only colistin at 0.5 mg/liter plus doripenem at 2.5 mg/liter failed to improve activity against 19147 n/m at the high inoculum. Combinations were additive or synergistic against ATCC 27853 in 16 and 11 of 20 cases (4 combinations across 5 sample points) at the 10(6)- and 10(8)-CFU/ml inocula, respectively; the corresponding values for 19147 n/m were 16 and 9. Combinations containing doripenem at 25 mg/liter resulted in eradication of 19147 n/m at the low inoculum and substantial reductions in regrowth (including to below the limit of detection at ∼50 h) at the high inoculum. Emergence of colistin-resistant subpopulations of ATCC 27853 was substantially reduced and delayed with combination therapy. This investigation provides important information for optimization of colistin-doripenem combinations.

A Role for Protein Kinase Casein Kinase2 α-subunits in the Arabidopsis Circadian Clock

Plant Physiology. Nov, 2011  |  Pubmed ID: 21900482

Circadian rhythms are autoregulatory, endogenous rhythms with a period of approximately 24 h. A wide variety of physiological and molecular processes are regulated by the circadian clock in organisms ranging from bacteria to humans. Phosphorylation of clock proteins plays a critical role in generating proper circadian rhythms. Casein Kinase2 (CK2) is an evolutionarily conserved serine/threonine protein kinase composed of two catalytic α-subunits and two regulatory β-subunits. Although most of the molecular components responsible for circadian function are not conserved between kingdoms, CK2 is a well-conserved clock component modulating the stability and subcellular localization of essential clock proteins. Here, we examined the effects of a cka1a2a3 triple mutant on the Arabidopsis (Arabidopsis thaliana) circadian clock. Loss-of-function mutations in three nuclear-localized CK2α subunits result in period lengthening of various circadian output rhythms and central clock gene expression, demonstrating that the cka1a2a3 triple mutant affects the pace of the circadian clock. Additionally, the cka1a2a3 triple mutant has reduced levels of CK2 kinase activity and CIRCADIAN CLOCK ASSOCIATED1 phosphorylation in vitro. Finally, we found that the photoperiodic flowering response, which is regulated by circadian rhythms, was reduced in the cka1a2a3 triple mutant and that the plants flowered later under long-day conditions. These data demonstrate that CK2α subunits are important components of the Arabidopsis circadian system and their effects on rhythms are in part due to their phosphorylation of CIRCADIAN CLOCK ASSOCIATED1.

Benzo[a]pyrene Exposure Influences the Cardiac Development and the Expression of Cardiovascular Relative Genes in Zebrafish (Daniorerio) Embryos

Chemosphere. Dec, 2011  |  Pubmed ID: 22209252

It is reported that the most abundant polycyclic aromatic hydrocarbons (PAHs) in weathered crude oils are cardiotoxic. However, the action mechanism of PAHs on vertebrate cardiovascular development and disease is unclear. In the present study, the cardiac morphology and functioning of zebrafish embryos exposed to benzo[a]pyrene [B(a)P], as a high-ring PAHs, for 72h were observed and determined. The results showed that B(a)P exposure resulted in cardiac developmental defects in zebrafish embryos. Significant changes in expression level of multiple genes potentially critical for regulating the B(a)P-induced cardiovascular developmental defects were also found. A gene network regulating cardiac development perturbed by B(a)P exposure was identified and established by computational analysis and employment of some databases. The information from the network could provide a clue for further mechanistic studies explaining molecular events regulating B(a)P-mediated cardiovascular defects and consequences.

Evaluation of Sponge Tray-membrane Bioreactor (ST-MBR) for Primary Treated Sewage Effluent Treatment

Bioresource Technology. Dec, 2011  |  Pubmed ID: 22197339

The membrane bioreactor system (MBR) with pre-treatment of sponge tray bioreactor (STB) was evaluated at different operating conditions for treating primary treated sewage (PTS). The result indicated the successful removal of DOC with the efficiency of higher than 95%. The highest nutrient removal efficiency of 83.6% (NH(4)-N) and 75.5% (PO(4)-P) was observed at sludge concentration of 330mg/L. Specific oxygen uptake rate (SOUR) of activated sludge in MBR kept increasing up to 6mgO(2)/gVSSh during stage IV. The sludge volume index (SVI) of less than 100mL/g during the operation indicated the good settling property of the sludge. At highest sludge concentration of 5g/L, trans-membrane pressure (TMP) was increasing dramatically during first 15d up to 25kPa; however it was only 6kPa at lower sludge concentrations. It is concluded that the system showed the highest performance at stage III with sludge concentration of 330mg/L.

Late Gestational Maternal Serum Cortisol is Inversely Associated with Fetal Brain Growth

Neuroscience and Biobehavioral Reviews. Dec, 2011  |  Pubmed ID: 22206902

To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95±7.31), middle (gestational day 160.17±16.12) and late pregnancy (gestational day 268.89±12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R(2)=0.512, p=0.009), late head circumference (R(2)=0.498, p=0.001), middle biparietal diameter (R(2)=0.819, p=0.013), middle cerebellum transverse diameter R(2)=0.76, p=0.014) and early biparietal diameter(R(2)=0.819, p=0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels. In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life.

Endothelial Cell Damage Induces a Blood-alveolus Barrier Breakdown in the Development of Radiation-induced Lung Injury

Asia-Pacific Journal of Clinical Oncology. Dec, 2011  |  Pubmed ID: 22151990

To investigate the role of endothelial cell damage in radiation-induced lung injury.

Organ-sparing Surgery for Penile Cancer: Complications and Outcomes

Urology. Nov, 2011  |  Pubmed ID: 22054385

To evaluate the complications and outcomes of organ-sparing surgery in penile cancer.

A Cross-sectional Study of Menthol Cigarette Preference by 14- to 15-Year-Old Smokers in New Zealand

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Dec, 2011  |  Pubmed ID: 22193580

INTRODUCTION: This study investigates the epidemiology of menthol cigarette preference, its association with smoking initiation, and nicotine addiction measured by loss of autonomy among New Zealand adolescent smokers. METHODS: Data from the 2006-2009 national surveys among New Zealand Year 10 students (14-15 years old) were analyzed using multiple logistic regression. Menthol preference was an outcome variable; demographic factors and smoking status were covariates. Loss of autonomy and menthol preference were examined using multiple linear regression analysis. The Hooked on Nicotine Checklist measured loss of autonomy as an outcome variable. Menthol status, smoking status, and demographic factors were covariates. All analyses were controlled for clustering of data by school. RESULTS: Overall, 17.7% of New Zealand 14- to 15-year-old smokers in this study indicated a preference for menthol cigarette, with greater odds of menthol cigarette preference among girls (odds ratio [OR] = 2.43; 95% CI = 2.15-2.75), ethnic minorities (Māori OR = 1.21; 95% CI = 1.07-1.36, Asians OR = 2.24; 95% CI = 1.79-2.82, Pacific Islanders OR = 1.83; 95% CI = 1.52-2.19), smokers from high socioeconomic status schools (OR = 1.24; 95% CI = 1.03-1.49), when parents smoked (OR = 1.16; 95% CI = 1.03-1.31), and newer smokers (smoked 11-100 cigarettes OR = 1.16; 95% CI = 1.03-1.31, smoking on a monthly OR = 1.17; 95% CI = 1.00-1.37, and a weekly basis OR = 1.29; 95% CI = 1.15-1.44). No significant correlation was found among those who smoked 1-10 cigarettes in total (OR = 1.02; 95% CI = 0.86-1.20) nor was any correlation found between menthol preference and nicotine addiction measured by loss of autonomy (coef. = -.21, p value = .165).Conclusion:This study found inequalities in menthol cigarette preference among New Zealand adolescent smokers, consistent with patterns found in the United States but did not find any significant correlation between menthol preference and loss of autonomy.

An Outbreak of Sheep Pox Associated with Goat Poxvirus in Gansu Province of China

Veterinary Microbiology. Nov, 2011  |  Pubmed ID: 22169434

Three strains of Capripoxviruses (CaPVs) were isolated from an outbreak of sheep pox in Gansu province of China. They were analyzed by P32 gene-based molecular methods and a species-specific PCR based on the RPO30 gene. Two bands which are specific to goat poxvirus (GTPV) were observed after the PCR products of P32 gene were digested with the endonuclease of Hinf I. Moreover, an amplicon of 172bp, which is specific to GTPV, was amplified from the viruses by using the RPO30 gene-based PCR. Sequence analysis of the P32 genes showed that three nucleotide bases for coding residue of aspartic acid which are located at 163-165 position of P32 gene of sheep poxvirus (SPPV) were absent, and six single nucleotide substitutions which are characteristic of GTPV were present. The viruses were genetically closer to GTPV strains and clustered into the GTPV branch of the phylogenetic tree constructed on the basis of the P32 gene. The results characterized the isolated viruses as GTPV. It is the first report of an outbreak of sheep pox associated with GTPV in China.

[Preliminary Comparison Research of Thoracoscopy and Thoracotomy Lobectomy for Clinical N0 and Post-operatively Pathological N2 Non-small Cell Lung Cancer]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2011  |  Pubmed ID: 22178835

To evaluate the safty, thoroughness and efficacy of the video-assisted thoracoscopic surgery compared with open thoracotomy, in treatment of patients with the preoperative staging of lymph node negative and postoperative pathological mediastinal lymph node positive (cN0-pN2) locally advanced non-small cell lung cancer(NSCLC).

[A Retrospective Comparative Study of the Safety, Completeness and Efficacy of Video-assisted Thoracoscopic Lobectomy Versus Open Lobectomy for Non-small-cell Lung Cancer Patients Whose Tumor Size Was Greater Than 5 Cm]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2011  |  Pubmed ID: 22178836

To discuss the feasibility of the completely video-assisted thoracoscopic lobectomy for non-small-cell lung cancer (NSCLC) patients whose tumor size was greater than 5 cm.

[Impacts of Different Nephrostomy Tubes and Their Fixation Ways on Patients with Nephrolithiasis Complicated with Renal Insufficiency After Percutaneous Nephrolithotomy]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2011  |  Pubmed ID: 22178838

To investigate impacts of different nephrostomy tubes and their fixation ways on patients with nephrolithiasis complicated with renal insufficiency after percutaneous nephrolithotomy.

Gate-tuned Normal and Superconducting Transport at the Surface of a Topological Insulator

Nature Communications. , 2011  |  Pubmed ID: 22146394

Three-dimensional topological insulators are characterized by the presence of a bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical phenomena originating from the presence of the Dirac fermions are predicted to occur, and to be experimentally accessible via transport measurements in suitably designed electronic devices. Here we study transport through superconducting junctions fabricated on thin Bi(2)Se(3) single crystals, equipped with a gate electrode. In the presence of perpendicular magnetic field B, sweeping the gate voltage enables us to observe the filling of the Dirac fermion Landau levels, whose character evolves continuously from electron- to hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned, and is minimum at the charge neutrality point determined from the Landau level filling. Our results demonstrate how gated nano-electronic devices give control over normal and superconducting transport of Dirac fermions at an individual surface of a three-dimensional topological insulators.

Effect of Monochromatic Light on Melatonin Secretion and Arylalkylamine N-acetyltransferase MRNA Expression in the Retina and Pineal Gland of Broilers

Anatomical Record (Hoboken, N.J. : 2007). Jul, 2011  |  Pubmed ID: 21618440

The goal of this study is to investigate the effects of various monochromatic lights on plasma melatonin (MT) levels and the expression of arylalkylamine N-acetyltransferase (AANAT) mRNA in the pineal gland and retina. A total of 160 newly hatched (posthatching day 1, P1) broilers, including intact, sham-operated, and pinealectomized groups were exposed to blue light (BL), green light (GL), red light (RL), and white light (WL) by light emitting diode (LED) system for short term (24 hr) or long term (2 weeks), separately. For intact and sham-operated birds, the plasma MT level exhibited marked circadian rhythms at P7 and P14 regardless of short-term and long-term exposure to four monochromatic lights. However, WL and BL showed a faint suppression of MT secretion in contrast to GL and RL at either light or dark time points, with the following rank order: GL < RL < WL < BL. Larger circadian amplitude of MT levels was observed in GL group versus BL group (at P14: 87.70 pg/mL vs. 19.85 pg/mL, respectively). Pinealectomy disturbed the MT rhythm under different light colors, especially in RL. Additionally, consistent with the alteration of plasma MT levels, we observed increased AANAT mRNA expression and immunoreactive cell numbers of proliferating cell nuclear antigen (PCNA) and c-Fos in the pineal gland or retina in GL than that of BL, whereas 5-HT immunoreactive cell number was significantly decreased in GL. These data suggested that GL enhanced chick pinealocytes and retinal cells to express AANAT mRNA and to secrete MT, which may be depended on promoting c-Fos expression and cell proliferation.

Effect of Varying the Length of Soft-tissue Grafts in the Tibial Tunnel in a Canine Anterior Cruciate Ligament Reconstruction Model

Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. Jun, 2011  |  Pubmed ID: 21624677

To investigate the effect of graft length within the bone tunnel on tendon-bone healing at an early stage after anterior cruciate ligament (ACL) reconstruction using Achilles tendon autograft in a canine model.

Comparative Studies of De Novo Assembly Tools for Next-generation Sequencing Technologies

Bioinformatics (Oxford, England). Aug, 2011  |  Pubmed ID: 21636596

MOTIVATION: Several new de novo assembly tools have been developed recently to assemble short sequencing reads generated by next-generation sequencing platforms. However, the performance of these tools under various conditions has not been fully investigated, and sufficient information is not currently available for informed decisions to be made regarding the tool that would be most likely to produce the best performance under a specific set of conditions. RESULTS: We studied and compared the performance of commonly used de novo assembly tools specifically designed for next-generation sequencing data, including SSAKE, VCAKE, Euler-sr, Edena, Velvet, ABySS and SOAPdenovo. Tools were compared using several performance criteria, including N50 length, sequence coverage and assembly accuracy. Various properties of read data, including single-end/paired-end, sequence GC content, depth of coverage and base calling error rates, were investigated for their effects on the performance of different assembly tools. We also compared the computation time and memory usage of these seven tools. Based on the results of our comparison, the relative performance of individual tools are summarized and tentative guidelines for optimal selection of different assembly tools, under different conditions, are provided.

Assessment of Primary Cancers in GH-treated Adult Hypopituitary Patients: an Analysis from the Hypopituitary Control and Complications Study

European Journal of Endocrinology / European Federation of Endocrine Societies. Aug, 2011  |  Pubmed ID: 21646285

GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database.

Small-molecule Anticancer Compounds Selectively Target the Hemopexin Domain of Matrix Metalloproteinase-9

Cancer Research. Jul, 2011  |  Pubmed ID: 21646471

Lack of target specificity by existing matrix metalloproteinase (MMP) inhibitors has hindered antimetastatic cancer drug discovery. Inhibitors that bind to noncatalytic sites of MMPs and disrupt protease signaling function have the potential to be more specific and selective. In this work, compounds that target the hemopexin (PEX) domain of MMP-9 were identified using an in silico docking approach and evaluated using biochemical and biological approaches. Two of the selected compounds interfere with MMP-9-mediated cancer cell migration and proliferation in cells expressing exogenous or endogenous MMP-9. Furthermore, these inhibitors do not modulate MMP-9 catalytic activity. The lead compound, N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1H-pyrimidin-2-yl)sulfanyl]-acetamide, specifically binds to the PEX domain of MMP-9, but not other MMPs. This interaction between the compound and the PEX domain results in the abrogation of MMP-9 homodimerization and leads to blockage of a downstream signaling pathway required for MMP-9-mediated cell migration. In a tumor xenograft model, this pyrimidinone retarded MDA-MB-435 tumor growth and inhibited lung metastasis. Thus, we have shown for the first time that a novel small-molecule interacts specifically with the PEX domain of MMP-9 and inhibits tumor growth and metastasis by reducing cell migration and proliferation.

Helicobacter Pylori Induces Promoter Hypermethylation and Downregulates Gene Expression of IRX1 Transcription Factor on Human Gastric Mucosa

Journal of Gastroenterology and Hepatology. Nov, 2011  |  Pubmed ID: 21649733

Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line.

Anti-oxidative and TNF-α Suppressive Activities of Puerarin Derivative (4AC) in RAW264.7 Cells and Collagen-induced Arthritic Rats

European Journal of Pharmacology. Sep, 2011  |  Pubmed ID: 21651907

Puerarin is a major active ingredient extracted from the root of P. lobata, a traditional Chinese herb, and possesses anti-oxidative and anti-inflammatory activities. However, the low oral bioavailability of puerarin limits its further application. Therefore, we synthesized tetraacetyl puerarin (4AC) through acetylation to improve its liposolubility and bioavailability. In the present investigations, we tested the anti-oxidative and TNF-α suppressive activity of 4AC in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and bovine type II collagen-induced arthritic (CIA) rats. The results showed that 4AC retained the bioactivity of puerarin. And 4AC significantly increased the activity of SOD and reduced the level of MDA both in vitro and in vivo. It also improved the level of GSH-PX and the total antioxidant capacity in vivo. Furthermore, it dramatically decreased TNF-α level in the cultured supernatant of RAW264.7 cells treated with LPS and in the serum of CIA rats. These initial results indicated that 4AC had a potential therapeutic effect on CIA rats through an anti-oxidative and TNF-α suppressive activity. In addition, the molecular mechanism of anti-oxidation of 4AC was explored by testing the MAPKs/NF-κB signaling pathway. The results showed that 4AC significantly inhibited NF-κB expression and down-regulated the levels of p-ERK and p-JNK in LPS-activated RAW264.7 cells. These results indicated that 4AC had bioactive anti-oxidative effects and suggest the potential value of 4AC for the treatment of rheumatoid arthritis.

Observations of Cell Size Dynamics Under Osmotic Stress

Cytometry. Part A : the Journal of the International Society for Analytical Cytology. Jul, 2011  |  Pubmed ID: 21656664

Cultured mammalian cells [e.g., murine hybridomas, Chinese hamster ovary (CHO) cells] used to produce therapeutic and diagnostic proteins often exhibit increased specific productivity under osmotic stress. This increase in specific productivity is accompanied by a number of physiological changes, including cell size variation. Investigating the cell size variation of hyperosmotically stressed cultures may reveal, in part, the basis for increased specific productivity as well as an understanding of some of the cellular defense responses that occur under hyperosmotic conditions. The regulation of cell volume is a critical function maintained in animal cells. Although these cells are highly permeable to water, they are significantly less permeable to ionic solutes. Appropriate cell-water content is actively maintained in these cells by regulation of ion and osmolyte balances. Transport appropriate to extracellular conditions, leading to accrual or release of these species, is activated in response to acute cell volume changes. Osmotically induced regulatory volume increases (RVI) and regulatory volume decreases (RVD) are known to occur under a variety of conditions. We observed the time evolution of size variation in populations of two CHO cell lines under hyperosmotic conditions. Observations were made using multiple instruments, multiple cell lines, and multiple cell culture conditions. Size variation of CHO A1 was gauged by flow cytometry using an LSRII® flow cytometer while CHO B0 cells were quantified using a Cedex® cell analyzer. Hyperosmotic stress had a dose-dependent effect on the regulatory control of cell volume. Stressed cultures of CHO cells grown in suspension exhibited a shift in mean cell diameter. This shift in mean was not due to a change in the whole population, but rather to the emergence of distinct subpopulations of cells with larger cell diameters than those in the bulk of the population.

Temperature Effect on Electrospinning of Nanobelts: the Case of Hafnium Oxide

Nanotechnology. Jul, 2011  |  Pubmed ID: 21659687

Electrospinning is a convenient and versatile method for fabricating different kinds of one-dimensional nanostructures such as nanofibres, nanotubes and nanobelts. Environmental parameters have a great influence on the electrospinning nanostructure. Here we report a new method to fabricate hafnium oxide (HfO(2)) nanobelts. HfO(2) nanobelts were prepared by electrospinning a sol-gel solution with the implementation of heating and subsequent calcination treatment. We investigate the temperature dependence of the products by scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and energy-dispersive x-ray (EDX) spectroscopy. The heating temperature of spinning ambient is found to be crucial to the formation of HfO(2) nanobelts. By tuning the temperature, the morphological transformation of HfO(2) from nanowires to nanobelts was achieved. It was found that the rapid evaporation of solvent played an important role in the formation process of HfO(2) nanobelts. It is shown that nanobelts can only be obtained with the temperature higher than 50 °C and they are in the high quality monoclinic phase. A possible growth mechanism of the nanobelts based on phase separation is proposed. The enhanced photoluminescence (PL) of HfO(2):Eu(3+) nanobelts is also illustrated.

Galanin Antagonist Increases Insulin Resistance by Reducing Glucose Transporter 4 Effect in Adipocytes of Rats

General and Comparative Endocrinology. Aug, 2011  |  Pubmed ID: 21664358

Seeing that galanin increases animal body weight on the conditions of inhibiting insulin secretion and animals with metabolic disorder of galanin easily suffer from diabetes, we postulate that endogenous galanin is necessary to reduce insulin resistance in adipocytes. To test this hypothesis, we compared four groups of rats to examine whether an increase in galanin secretion stimulated by swimming may reduce insulin resistance. The rats from sedentary and trained drug groups were injected by M35, a galanin antagonist. The rats from trained control and trained drug groups swam after each injection for four weeks. We found that exercise significantly elevated plasma galanin contents and glucose transporter 4 (GLUT4) mRNA levels in adipocytes. Meanwhile, M35 treatment reduced GLUT4 and GLUT4 mRNA levels, and glucose infusing rates in euglycemic-hyperinsulinemic clamp tests. The ratios of GLUT4 concentrations at plasma membranes to total cell membranes in both drug groups were lower compared with each control group, respectively. These observations suggest that endogenous galanin reduces insulin resistance by increasing GLUT4 contents and promoting GLUT4 transportation from intracellular membranes to plasma membranes in adipocytes. Galanin is an important hormone to reduce insulin resistance in rats.

Biochemical Characterization of Deblocking Aminopeptidases from the Hyperthermophilic Archaeon Thermococcus Kodakarensis KOD1

Bioscience, Biotechnology, and Biochemistry. , 2011  |  Pubmed ID: 21670507

Deblocking aminopeptidase (DAP) is an exoprotease that can release N-terminal amino acids from blocked peptides. Three DAP homologous (TkDAP1, TkDAP2, and TkDAP3) are annotated in the genome data base of Thermococcus kodakarensis KOD1. TkDAP2 and TkDAP3 were identified as proteins that are overexpressed in response to heat and oxidative stress by two-dimensional electrophoresis. In this study, the TkDAP1 and TkDAP2 genes were cloned and expressed in Escherichia coli. The two proteins were purified homogeneity and analyzed by gel filtration chromatography and electron microscopy. TkDAP1 showed two oligomers, which were identified as an octodecimer and a dodecamer. TkDAP2 produced three native forms: octodecimer, dodecamer, and trimer. Dodecamer assembly was the main form in the two proteins. Finally, TkDAP1 was found to have higher deblocking aminopeptidase activity on the substrates of Ac-Leu-pNA and Ac-Ala-Ala-Ala, while TkDAP2 had higher aminopeptidase activity on the substrates of Leu-pNA and Ala-Ala-Ala-pNA.

Probing Waveforms and Adaptive Receivers for Active Sonar

The Journal of the Acoustical Society of America. Jun, 2011  |  Pubmed ID: 21682389

Active sonar systems involve the transmission and reception of one or more probing sequences, which provide a basis for extraction of target information in a region of interest. The probing sequences at the transmitter and signal processing at the receiver play crucial roles in the overall system performance. In this paper, CAN (cyclic algorithm-new) is employed to synthesize probing sequences with good aperiodic autocorrelation properties. The performance of the CAN sequences will be compared with those of pseudo random noise and random phase sequences. Two adaptive receiver designs, namely the iterative adaptive approach (IAA) and the sparse learning via iterative minimization (SLIM) method, will also be considered. IAA and SLIM will be compared with the conventional matched filter method. The performances of the algorithms will be illustrated via numerical examples, which show that CAN, IAA, and SLIM can contribute to the overall performance improvement of the active sonar systems.

Ezetimibe Restores Biliary Cholesterol Excretion in Mice Expressing Niemann-Pick C1-Like 1 Only in Liver

Biochimica Et Biophysica Acta. Sep, 2011  |  Pubmed ID: 21683156

Niemann-Pick C1-Like 1 (NPC1L1) is highly expressed in the small intestine across mammalian species and is the target of ezetimibe, a potent cholesterol absorption inhibitor. In humans, NPC1L1 is also expressed in the liver. We found that transgenic overexpression of NPC1L1 in the wild-type mouse liver inhibits biliary cholesterol secretion and raises blood cholesterol, which can be reversed by ezetimibe treatment. Unfortunately, the high expression of endogenous NPC1L1 in the intestine hampered a definitive establishment of the role of hepatic NPC1L1 in cholesterol metabolism and ezetimibe action in the liver because intestinal NPC1L1 dramatically influences cholesterol homeostasis and is a target of ezetimibe. To circumvent this obstacle, we crossed liver-specific NPC1L1 transgenic mice to NPC1L1 knockout (L1-KO) mice and created a mouse line expressing no endogenous NPC1L1, but human NPC1L1 in liver only (L1(LivOnly) mice). Compared to L1-KO mice, L1(LivOnly) mice on a 0.2% cholesterol diet showed significantly increased hepatic and plasma cholesterol, and despite a 90% reduction in biliary cholesterol excretion, their fecal cholesterol excretion remained completely unaltered. Remarkably, 4days of ezetimibe treatment significantly restored biliary cholesterol secretion in L1(LivOnly) mice. These findings demonstrated a direct role of hepatic NPC1L1 in regulating biliary cholesterol excretion and hepatic/blood cholesterol levels, and unequivocally established hepatic NPC1L1 as a target of ezetimibe.

Linkage Maps from Multiple Genetic Crosses and Loci Linked to Growth-related Virulent Phenotype in Plasmodium Yoelii

Proceedings of the National Academy of Sciences of the United States of America. Aug, 2011  |  Pubmed ID: 21690382

Plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. Here, we performed 14 genetic crosses between three pairs of P. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. Microsatellite genotypes from the progeny formed 14 linkage groups belonging to the 14 parasite chromosomes, allowing assignment of sequence contigs to chromosomes. Growth-related virulent phenotypes from 25 progeny of one of the crosses were significantly associated with a major locus on chromosome 13 and with two secondary loci on chromosomes 7 and 10. The chromosome 10 and 13 loci are both linked to day 5 parasitemia, and their effects on parasite growth rate are independent but additive. The locus on chromosome 7 is associated with day 10 parasitemia. The chromosome 13 locus spans ~220 kb of DNA containing 51 predicted genes, including the P. yoelii erythrocyte binding ligand, in which a C741Y substitution in the R6 domain is implicated in the change of growth rate. Similarly, the chromosome 10 locus spans ~234 kb with 71 candidate genes, containing a member of the 235-kDa rhoptry proteins (Py235) that can bind to the erythrocyte surface membrane. Atypical virulent phenotypes among the progeny were also observed. This study provides critical tools and information for genetic investigations of virulence and biology of P. yoelii.

Fluorescence in Situ Hybridization on Plant Extended Chromatin DNA Fibers for Single-copy and Repetitive DNA Sequences

Plant Cell Reports. Sep, 2011  |  Pubmed ID: 21695528

The compactness of plant chromosomes and the structure of the plant cell wall and cytoplasm provide a great obstacle to fluorescence in situ hybridization (FISH) for single-copy or low-copy DNA sequences. Consequently, many new methods for improving spatial resolution via chromosomal stretching have been employed to overcome this technical challenge. In this article, a technique for extracting cell-wall free nuclei at mitotic interphase, then using these nuclei to prepare extended DNA fibers (EDFs) by the method of a receding interface, whereby slide-mounted chromatin produces EDFs in concert with gravity-assisted buffer flow, was adopted as a result of the low frequency of EDF damage produced by this procedure. To examine the quality of these EDFs, we used single-copy gene encoding S-locus receptor kinase and multi-copy 5S rDNA (ribosomal DNA) as probes. The resulting EDFs proved suitable for high-resolution FISH mapping for repetitive DNA sequences, and the localization of a single-copy locus.

Overexpression of AtBMI1C, a Polycomb Group Protein Gene, Accelerates Flowering in Arabidopsis

PloS One. , 2011  |  Pubmed ID: 21701597

Polycomb group protein (PcG)-mediated gene silencing is emerging as an essential developmental regulatory mechanism in eukaryotic organisms. PcGs inactivate or maintain the silenced state of their target chromatin by forming complexes, including Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). Three PRC2 complexes have been identified and characterized in Arabidopsis; of these, the EMF and VRN complexes suppress flowering by catalyzing the trimethylation of lysine 27 on histone H3 of FLOWER LOCUS T (FT) and FLOWER LOCUS C (FLC). However, little is known about the role of PRC1 in regulating the floral transition, although AtRING1A, AtRING1B, AtBMI1A, and AtBMI1B are believed to regulate shoot apical meristem and embryonic development as components of PRC1. Moreover, among the five RING finger PcGs in the Arabidopsis genome, four have been characterized. Here, we report that the fifth, AtBMI1C, is a novel, ubiquitously expressed nuclear PcG protein and part of PRC1, which is evolutionarily conserved with Psc and BMI1. Overexpression of AtBMI1C caused increased H2A monoubiquitination and flowering defects in Arabidopsis. Both the suppression of FLC and activation of FT were observed in AtBMI1C-overexpressing lines, resulting in early flowering. No change in the H3K27me3 level in FLC chromatin was detected in an AtBMI1C-overexpressing line. Our results suggest that AtBMI1C participates in flowering time control by regulating the expression of FLC; moreover, the repression of FLC by AtBMI1C is not due to the activity of PRC2. Instead, it is likely the result of PRC1 activity, into which AtBMI1C is integrated.

Divergent Activities of Osteogenic BMP2, and Tenogenic BMP12 and BMP13 Independent of Receptor Binding Affinities

Growth Factors (Chur, Switzerland). Aug, 2011  |  Pubmed ID: 21702718

Ectopic expression of recombinant human bone morphogenetic protein 2 (rhBMP2) induces osteogenesis, while ectopic expression of rhBMP12 and rhBMP13 induces the formation of tendon-like tissue. Despite their different in vivo activities, all three ligands bound to the type I bone morphogenic protein receptors (BMPRs), activin receptor-like kinase (ALK)-3 and ALK6, and to the type II BMPRs, activin receptor type-2A, activin receptor type-2B, and BMPR2, with similar affinities. Treatment of C3H10T1/2 cells with rhBMP2 activated SMAD signaling and induced expression of osteoblast markers including osteocalcin mRNA (Ocn). In contrast, treatment with rhBMP12 or rhBMP13 resulted in a dose-dependent induction of a tendon-specific gene (Thbs4) expression with no detectable activation of SMAD 1, 5, and 8. Differential regulation of Thbs4 and Ocn has potential utility as an in vitro biomarker for induction of tenogenic signaling. Such an assay also permits the ability to distinguish between the activities of different BMPs and may prove useful in studies on the molecular mechanisms of BMP tenogenic activity.

Melatonin Attenuates Colistin-induced Nephrotoxicity in Rats

Antimicrobial Agents and Chemotherapy. Sep, 2011  |  Pubmed ID: 21709095

Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the nephroprotective effect of melatonin against colistin in rats. Rats (n = 7 per group) were treated intravenously twice daily with saline, colistin (at increasing doses from 0.5 to 4.0 mg/kg), melatonin (5 mg/kg), or both melatonin and colistin for 7 days. The severity of renal alteration was examined both biochemically and histologically. The effect of coadministration of melatonin on colistin pharmacokinetics was investigated. Significantly lower urinary N-acetyl-β-d-glucosaminidase excretion was observed from day 1 in the colistin-melatonin group compared to the colistin group (P < 0.0001). Plasma creatinine increased significantly (P = 0.023) only in the colistin group on day 6. Significant histological abnormalities (P < 0.0001) were detected only in the kidneys of the colistin group. Melatonin altered colistin pharmacokinetics; the total body clearance in the colistin-melatonin group (1.82 ± 0.26 ml/min/kg) was lower than in the colistin group (4.28 ± 0.93 ml/min/kg). This is the first study demonstrating the protective effect of melatonin against colistin-induced nephrotoxicity, which indicates that colistin-induced nephrotoxicity is mediated through oxidative stress. It also highlights the potential of coadministering an antioxidant to widen the therapeutic window of this very important last-line antibiotic.

[Spectralsignatures of Nickel and Vanadium Supported Photocatalysts and Their Photocatalytic Properties]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Apr, 2011  |  Pubmed ID: 21714270

Using SiO2, activated carbon (AC) and Al2O3 as supports, the supported photocatalysts Ni-V-O/SiO2, Ni-V-O/AC and Ni-V-O/Al2O3 were prepared by impregnation method, and their spectralsignatures were investigated. The carbonylation of methanol with CO2 under UV irradiation was used as a probe reaction to compare the photocatalytic performance of the prepared catalysts. Integrated with the testing results of carbonylation, the effects of different supports on selectivity for the carbonylation products of methyl formate (MF) and dimethyl carbonate (DMC) were discussed by pyridine-IR and UV-Vis techniques. XRD results showed that the particles of nickel and vanadium supported on SiO2 had the highest degree of dispersion. Results of pyridine-IR indicated that all catalysts retained Lewis acid sites. The acid strength was different from catalyst samples with different supports but with the same active components. The acid strengths could be arranged as follows: Ni-V-O/SiO2 > Ni-V-O/Al2 O3 > Ni-V-O/AC. Different acid strengths exhibited different influence on the selectivity of products MF and DMC of carbonylation. The surface acid strengths of catalysts were the major factor influencing the selectivity of carbonylation products.

SIRT3-dependent Deacetylation Exacerbates Acetaminophen Hepatotoxicity

EMBO Reports. Aug, 2011  |  Pubmed ID: 21720390

Acetaminophen/paracetamol-induced liver failure--which is induced by the binding of reactive metabolites to mitochondrial proteins and their disruption--is exacerbated by fasting. As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we investigated whether deacetylation predisposes mice to toxic metabolite-mediated disruption of mitochondrial proteins. We show that mitochondrial deacetylase SIRT3(-/-) mice are protected from acetaminophen hepatotoxicity, that mitochondrial aldehyde dehydrogenase 2 is a direct SIRT3 substrate, and that its deacetylation increases acetaminophen toxic-metabolite binding and enzyme inactivation. Thus, protein deacetylation enhances xenobiotic liver injury by modulating the binding of a toxic metabolite to mitochondrial proteins.

Regulation of Gene Expression in Human Tendinopathy

BMC Musculoskeletal Disorders. , 2011  |  Pubmed ID: 21539748

Chronic tendon injuries, also known as tendinopathies, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure, yet little is known about the molecular mechanisms leading to tendinopathy.

RTEF-1, an Upstream Gene of Hypoxia-inducible Factor-1α, Accelerates Recovery from Ischemia

The Journal of Biological Chemistry. Jun, 2011  |  Pubmed ID: 21540178

The amount of available hypoxia-inducible factor (HIF)-1α has been considered to be largely a consequence of post-translational modification by multiple ubiquitin-proteasome pathways. However, the role of transcriptional regulation of HIF-1α is less certain, and the mechanisms of transcriptional regulation of HIF-1α require further investigation. Here we report that related transcriptional enhancer factor-1 (RTEF-1), a member of the TEF transcriptional factor family, transcriptionally regulates the HIF-1α gene under normoxic and hypoxic conditions. The expression of HIF-1α mRNA was decreased in endothelial cells in which RTEF-1 was knocked down with siRNA. Sequential deletional analysis of the HIF-1α promoter revealed that the MCAT-like element in the HIF-1α promoter was essential for HIF-1α transcription. Binding of RTEF-1 to the MCAT-like element was confirmed by ChIP. Treatment of endothelial cells with a HIF-1 inhibitor resulted in retardation of RTEF-1-induced proliferation and tube formation. Moreover, increased HIF-1α expression was observed in transgenic mice expressing RTEF-1 under the VE-cadherin promoter (VE-Cad/RTEF-1). VE-Cad/RTEF-1 mice subjected to hindlimb ischemia demonstrated increased levels of HIF-1α, accelerated recovery of blood flow, and increased capillary density compared with littermate controls. These results identify RTEF-1 as a regulator of HIF-1α transcription, which results in up-regulation of HIF-1α and acceleration of recovery from ischemia.

Effects of Oligochitosan on Postharvest Alternaria Rot, Storage Quality, and Defense Responses in Chinese Jujube (Zizyphus Jujuba Mill. Cv. Dongzao) Fruit

Journal of Food Protection. May, 2011  |  Pubmed ID: 21549049

Effects of oligochitosan (OCH) on postharvest rot caused by Alternaria alternata in Chinese jujube (Zizyphus jujuba Mill. cv. Dongzao) fruit were investigated. An in vitro test indicated that mycelial growth of A. alternata was strongly suppressed by OCH at 0.5, 1, 2, 5, 10, 15, or 20 g/liter. The half-inhibition concentration of OCH against this fungus was 0.76 and 1.69 g/liter on days 4 and 6 of incubation, respectively. Lesion area and disease incidence in the jujube fruit inoculated with A. alternata were remarkably reduced by the OCH treatments at concentrations higher than 1 g/liter, but 5 g/liter OCH was considered the optimal treatment for inhibiting disease development. OCH also significantly reduced postharvest natural decay, promoted fruit firmness, delayed decline in soluble solids and loss of ascorbic acid, and increased total phenolic compounds during storage at 0°C and 85 to 95% relative humidity. Biochemical evaluations revealed that the activities of the main defense-related enzymes in the jujube fruit, including phenylalanine ammonia-lyase, peroxidase, chitinase, and β-1,3-glucanase, were significantly enhanced (P < 0.05) by OCH treatment. OCH increased superoxide dismutase activity but decreased catalase activity and, consequently, elevated hydrogen peroxide levels in the fruit. These results suggest that OCH might trigger several defense mechanisms in the jujube fruit for disease control in addition to its direct antifungal activity. OCH could be a viable alternative to conventional control of postharvest diseases of horticultural products.

Comparison of the Planning Target Volume Based on Three-dimensional CT and Four-dimensional CT Images of Non-small-cell Lung Cancer

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. May, 2011  |  Pubmed ID: 21549440

To compare positional and volumetric differences of planning target volumes (PTVs) based on axial three-dimensional CT (3DCT) and four-dimensional CT (4DCT) for the primary tumor of non-small cell lung cancer (NSCLC).

[Effects of Sericine on TGF-beta1/Smad3 Signal Pathway of Diabetic Mephropathy Rats Kidney]

Zhongguo Ying Yong Sheng Li Xue Za Zhi = Zhongguo Yingyong Shenglixue Zazhi = Chinese Journal of Applied Physiology. Feb, 2011  |  Pubmed ID: 21560355

To observe the effects of color silk cocoon extraction-sericine on transforming growth factor-beta1 (TGF-beta1) and Smad3 protein expression in kidney of diabetic nephropathy (DN) rats.

Analysis of Environmental Endocrine Disrupting Activities in Wastewater Treatment Plant Effluents Using Recombinant Yeast Assays Incorporated with Exogenous Metabolic Activation System

Biomedical and Environmental Sciences : BES. Apr, 2011  |  Pubmed ID: 21565684

To measure the endocrine disrupting chemicals (EDCs) in wastewater and evaluate the EDCs removal efficiencies in the municipal wastewater treatment plants (WWTP).

[Porcine Anti-human Lymphocyte Globulin Plus Cyclosporine A Therapy for Severe Aplastic Anemia]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Apr, 2011  |  Pubmed ID: 21569706

To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG) plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA).

Anterior Corpectomy and Reconstruction with Titanium Mesh Cage and Dynamic Cervical Plate for Cervical Spondylotic Myelopathy in Elderly Osteoporosis Patients

Archives of Orthopaedic and Trauma Surgery. Oct, 2011  |  Pubmed ID: 21573884

This retrospective study was to evaluate the relationship between osteoporosis and dynamic cervical plates in screw-plate or screw-bone interface of elderly cervical spondylotic myelopathy (CSM) patients.

Correlation of Sex Hormone and Androgen Receptor with Diabetes Mellitus in Elderly Men

The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. Sep, 2011  |  Pubmed ID: 21574908

To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men.

Overexpression of MiR-22 Reverses Paclitaxel-induced Chemoresistance Through Activation of PTEN Signaling in P53-mutated Colon Cancer Cells

Molecular and Cellular Biochemistry. Nov, 2011  |  Pubmed ID: 21594648

Chemoresistance is a key cause of treatment failure in colon cancer. MiR-22 is a tumor-suppressing microRNA. To explore whether miR-22 is an important player in the development of chemoresistance in colon cancer, we overexpressed miR-22 and subsequently tested its role in cell proliferation, apoptosis, survival, and associated signaling in p53-mutated HT-29 and HCT-15 cells, and p53 wild-type HCT-116 cells. We further investigated the role of miR-22 on cytotoxicity of paclitaxel in both the p53-mutated and p53 wild-type colon cancer cells. Results showed that HT-29 and HCT-15 cells were resistant to paclitaxel-induced cytotoxicity, which normally inhibits cell proliferation and survival, and induces apoptosis. Conversely, HCT-116 was relatively sensitive to the cytotoxicity of paclitaxel. Overexpression of miR-22 significantly decreased cell proliferation and survival, and induced cell apoptosis in the p53-mutated colon cancer cells, but played no role in the p53 wild-type cells. Importantly, miR-22 overexpression enhanced the cytotoxic role of paclitaxel in p53-mutated HT-29 and HCT-15 cells, but not in p53 wild-type HCT-116 cell. We further demonstrated that the tumor-suppressive role of miR-22 in p53-mutated colon cancer cells was mediated by upregulating PTEN expression, which negatively regulated Akt phosphorylation at Ser(473) and MTDH expression, and subsequently increased Bax and active caspase-3 levels. Our study is the first to identify the tumor-suppressive role of miR-22 and its associated signaling in the p53-mutated colon cancer cells and highlighted the chemosensitive role of miR-22.

Syntheses of Spirocyclic Oxindole-butenolides by Using Three-component Cycloadditions of Isocyanides, Allenoates, and Isatins

Chemistry (Weinheim an Der Bergstrasse, Germany). Jun, 2011  |  Pubmed ID: 21598327

DNA Methylation in Peripheral Blood Cells of Pigs Cloned by Somatic Cell Nuclear Transfer

Cellular Reprogramming. Aug, 2011  |  Pubmed ID: 21599517

To date, the genome-wide DNA methylation status of cloned pigs has not been investigated. Due to the relatively low success rate of pig cloning by somatic cell nuclear transfer, a better understanding of the epigenetic reprogramming and the global methylation patterns associated with development in cloned pigs is required. In this study we applied methylation-specific digital karyotyping tag sequencing by Solexa technology and investigated the genome-wide DNA methylation profiles of peripheral blood cells in cloned pigs with normal phenotypes in comparison with their naturally bred controls. In the result, we found that globally there was no significant difference of DNA methylation patterns between the two groups. Locus-specifically, some genes involved in embryonic development presented a generally increased level of methylation. Our findings suggest that in cloned pigs with normal phenotypes, the DNA methylation pattern is quite normal, and that DNA methylation changes in some genomic regions are compatible with normal development.

[Construction of Replication-deficient Recombinant Adenovirus Vector with HTFPI-2 Gene by AdMax System and Expression in U937 Monocytes in Vitro]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Apr, 2011  |  Pubmed ID: 21604496

We tried to construct and identify the recombinant replication-deficient adenovirus vector coding for human tissue factor pathway inhibitor 2 (hTFPI-2) gene by AdMax system in HEK293 cells. Firstly, we obtained hTFPI-2 gene from the recombinant plasmid pIRES2-EGFP-TFPI-2 by PCR using primers with restriction endonuclease site of EcoRI or SacI. After digesting the hTFPI-2 gene and plasmid PDC316-IRES-EGFP shuttle vector, we ligated them with T4 ligase and formed the recombinant shuttle vector PDC316-IRES-EGFP-hTFPI-2. It was confirmed that the ligation product was inserted the gene of hTFPI-2 correctly by sequencing. Then we took cotransfection of HEK293 cells with the recombinant shuttle vector and genomic plasmid pBHGloxdeltaE1,3Cre by liposome lipofectamine2000, and finished the package of recombinant adenovirus Ad-hTFPI-2. The results of the PCR test and restriction endonuclease digestion confirmed the successful construction of the recombinants Ad-hTFPI-2. Furthermore, we measured the titre of Ad-hTFPI-2 with the aid of green fluorescence protein expression after multiplication and purification. The titre was 0.931 x 10(12) pfu/ml. Finally, we infected U937 monocytes by purified Ad-hTFPI-2, and determined the infection efficiency and the TFPI-2's level and activity. The efficiency of Ad-hTFPI-2 infection in U937 cells was 89.33%. After infected by Ad-hTFPI-2, the TFPI-2's level in supernatant increased about 7 fold. Also the TFPI-2 in supernatant had activities of inhibiting trypsin and plasmin. The recombinant adenovirus with the hTFPI-2 gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in antiatherosclerosis.

[Relationship Between Post-stenting Coronary Thrombolysis in Myocardial Infarction Flow and Plasma Von Willebrand Factor and ADAMTS-13 Levels in Patients with ST Segment Elevation Myocardial Infarction]

Zhonghua Xin Xue Guan Bing Za Zhi. Mar, 2011  |  Pubmed ID: 21609524

To investigate the relationship between post-stenting coronary thrombolysis in myocardial infarction (TIMI) flow and plasma von Willebrand factor (vWF) and its cleaving protease (ADAMTS-13) levels in patients with ST segment elevation myocardial infarction (STEMI).

[The Diagnosis and Treatment of Colorectal Non-Hodgkin's Lymphoma 32 Cases]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Apr, 2011  |  Pubmed ID: 21612690

To summarize the clinical features, diagnostic and therapeutic experiences of colorectal Non-Hodgkin's lymphoma (NHL).

Design and Synthesis of Small Molecule RhoA Inhibitors: a New Promising Therapy for Cardiovascular Diseases?

Journal of Medicinal Chemistry. Jul, 2011  |  Pubmed ID: 21615130

RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromolecules, and to our knowledge, small molecular-based inhibitors have not been reported. In this study, a series of first-in-class small molecular RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. Virtual screening of ∼200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level (compounds 1-3). Compound 1 was selected for further structure modifications in considering binding activity and synthesis ease. Fourty-one new compounds (1, 12a-v, 13a-h, and 14a-j) were designed and synthesized accordingly. It was found that eight (12a, 12j, 14a, 14b, 14d, 14e, 14 g, and 14h) showed high RhoA inhibition activities with IC(50) values of 1.24 to 3.00 μM. A pharmacological assay indicated that two compounds (14g and 14 h) demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.

Suction Blister Epidermal Grafting Using a Modified Suction Method in the Treatment of Stable Vitiligo: a Retrospective Study

Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. Jul, 2011  |  Pubmed ID: 21492308

Of various surgical therapies used for the replenishment of melanocytes in recalcitrant and stable vitiligo, suction blister epidermal grafting (SBEG) is one of the simplest and most effective methods.

Co-inheritance of β- and δ-thalassemia Compromising Prenatal Screening in a Chinese Couple Seeking Prevention

Fetal Diagnosis and Therapy. , 2011  |  Pubmed ID: 21494010

Although δ-globin gene mutations have no clinical implications, association of β- and δ-thalassemia may lead to misdiagnosis. We describe the case of a Chinese woman who was assumed to have an α-thalassemia heterozygote, but was later shown to have β-thalassemia with a normal amount of HbA(2) caused by the -77 mutation of the δ-globin gene. This study highlights the importance of considering δ-thalassemia during β-thalassemia screening to avoid false-negative results in the detection of at-risk couples.

Virgatolides A-C, Benzannulated Spiroketals from the Plant Endophytic Fungus Pestalotiopsis Virgatula

Organic Letters. May, 2011  |  Pubmed ID: 21495643

Virgatolides A-C (1-3), unique metabolites with a 3',4',5',6'-tetrahydrospiro[chroman-2,2'-pyran] core, were isolated from cultures of the plant endophytic fungus Pestalotiopsis virgatula. Compounds 1-3 possess two previously undescribed skeletons originating from a benzannulated 6,6-spiroketal and one (2 and 3) and two (1) γ-lactone units, respectively. The structure of 1 was secured by X-ray crystallography.

An Economic Assessment of Astaxanthin Production by Large Scale Cultivation of Haematococcus Pluvialis

Biotechnology Advances. Nov-Dec, 2011  |  Pubmed ID: 21497650

Although natural sources have long been exploited for astaxanthin production, it is still uncertain if natural astaxanthin can be produced at lower cost than that of synthetic astaxanthin or not. In order to give a comprehensive cost analysis of astaxanthin production from Haematococcus, a pilot plant with two large scale outdoor photobioreactors and a raceway pond was established and operated for 2 years to develop processes for astaxanthin production from Haematococcus. The developed processes were scaled up to a hypothetical plant with a production capacity about 900 kg astaxanthin per year, and the process economics was preliminarily assessed. Based on the analysis, the production cost of astaxanthin and microalgae biomass can be as low as $718/kg and $18/kg respectively. The results are very encouraging because the estimated cost might be lower than that of chemically synthesized astaxanthin.

Decreased Mortality in Acute Pancreatitis Related to Early Aggressive Hydration

Pancreas. May, 2011  |  Pubmed ID: 21499208

Early aggressive intravenous hydration is believed to prevent morbidity and mortality by preventing intravascular volume depletion and maintaining perfusion of the pancreas possibly preventing pancreatic necrosis. The following study was initiated to determine the relationship between the observed decrease in mortality and the role of early aggressive hydration.

ARFGAP1 Promotes AP-2-dependent Endocytosis

Nature Cell Biology. May, 2011  |  Pubmed ID: 21499258

COPI (coat protein I) and the clathrin-AP-2 (adaptor protein 2) complex are well-characterized coat proteins, but a component that is common to these two coats has not been identified. The GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), ARFGAP1, is a known component of the COPI complex. Here, we show that distinct regions of ARFGAP1 interact with AP-2 and coatomer (components of the COPI complex). Selectively disrupting the interaction of ARFGAP1 with either of these two coat proteins leads to selective inhibition in the corresponding transport pathway. The role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport.

Identification of Chromosome Aberrations in Sporadic Microsatellite Stable and Unstable Colorectal Cancers Using Array Comparative Genomic Hybridization

Cancer Genetics. Feb, 2011  |  Pubmed ID: 21504706

Colorectal cancer (CRC) is one of the most common cancers in Denmark and in the western world in general, and the prognosis is generally poor. According to the traditional molecular classification of sporadic colorectal cancer, microsatellite stable (MSS)/chromosome unstable (CIN) colorectal cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material comprised fresh samples from 40 MSS tumors and 20 MSI tumors obtained from 60 Danish CRC patients. We identified five small genomic regions (<15 megabases) exhibiting recurrent copy number loss, which, to our knowledge, have not been reported in previously published aCGH studies of CRC: 3p25.3, 3p21.2-p21.31, 5q13.2, 12q24.23-q24.31, and 12q24.23-q24.31. These regions contain several potentially important tumor suppressor genes that may play a role in a significant proportion of both sporadic MSS CRC and MSI CRC. Furthermore, the generated aCGH data are in support of the recently proposed classification of sporadic CRC into MSS CIN+, MSI CIN-, MSI CIN+, and MSS CIN- cancers.

A Three-dimensional Pharmacophore Model for IMPDH Inhibitors

Chemical Biology & Drug Design. Jul, 2011  |  Pubmed ID: 21507206

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo synthesis of guanosine nucleotides. It is considered an important target in the quest for drugs in the immunosuppressive, antiviral, antibacterial and anticancer therapeutic areas. In this study, a chemical feature-based pharmacophore model of IMPDH inhibitors has been firstly developed with the aid of the HypoRefine protocol within Discovery Studio 2.5. The best model for IMPDH inhibitors, Hypo1-1, was characterized by the best correlation coefficient (0.97595) and the lowest RMSD (0.582058). It consisted of one hydrogen-bond donor, one hydrogen-bond acceptor, one aromatic ring and one hydrophobic feature, as well as two excluded volumes. The model was validated using a wide range of test molecules and a cross-validation. Furthermore, the pharmacophore features were confirmed by molecular docking studies. The pharmacophore model could quantitatively predict inhibitor activity and identify highly potent molecules. Therefore, the present results could be valuable for the discovery and development of specific IMPDH inhibitors.

Wingspan Stent for High-Grade Symptomatic Vertebrobasilar Artery Atherosclerotic Stenosis

Cardiovascular and Interventional Radiology. Apr, 2011  |  Pubmed ID: 21516376

PURPOSE: This study was designed to present the treatment outcomes with Wingspan stent angioplasty of high-grade intracranial vertebrobasilar artery (VBA) stenosis in symptomatic patients. METHODS: Between 2007 and 2010, the records of 30 patients with 31 intracranial high-grade VBA stenoses (all≥70%) who underwent elective stenting due to the failure of medical therapy were retrospectively reviewed. Clinical evaluation was performed based on the modified Rankin scale and the National Institutes of Health Stroke Scale. RESULTS: In all cases, the stent deployment was technically successful. The mean stenosis decreased significantly from 82.28 ± 8.02% (range, 72-99%) to 11.18 ± 7.28% (range, 0-25%) after stent-assisted angioplasty (P < 0.05). Periprocedure complications occurred in 3 (10%) of 30 patients; there were 2 cases of perforator strokes and 1 case of transient flow insufficiency with stent overlap. Clinical follow-up (mean, 17.81 ± 11.49 months; range, 5-40 months) was available for 27 patients, and angiographic follow-up (mean, 9.95 ± 5.74 months, range, 5-20 months) was available for 19 patients. Only one case demonstrated recurrent symptoms with restenosis (≥50%). There were no recurrent ischemic events and no cases of restenosis in the other patients. CONCLUSIONS: According to our data, the Wingspan stent for symptomatic intracranial VBA stenoses is a safe and efficacious treatment alternative in cases with recurrent symptoms despite medical therapy. However, the improvement of outcome requires the reduction in the rate of procedure-related complications and long-term outcomes still have to be demonstrated.

Identifying Rare and Subtle Behaviours: A Weakly Supervised Joint Topic Model

IEEE Transactions on Pattern Analysis and Machine Intelligence. Apr, 2011  |  Pubmed ID: 21519099

One of the most interesting and desired capabilities for automated video behaviour analysis is the identification of rarely occurring and subtle behaviours. This is of practical value because dangerous or illegal activities often have few or possibly only one prior example to learn from, and are often subtle. Rare and subtle behaviour learning is challenging for two reasons: (1) contemporary modeling approaches require more data and supervision than may be available and (2) the most interesting and potentially critical rare behaviours are often visually subtle - occurring among more obvious typical behaviours or being defined by only small spatio-temporal deviations from typical behaviours. In this paper we introduce a novel weakly-supervised joint topic model which addresses these issues. Specifically we introduce a multi-class topic model with partially shared latent structure and associated learning and inference algorithms. These contributions will permit modeling of behaviours from as few as one example, even without localisation by the user and when occurring in clutter; and subsequent classification and localisation such behaviours online and in real time. We extensively validate our approach on two standard public-space datasets where it clearly outperforms a batch of contemporary alternatives.

Activities of Colistin- and Minocycline-based Combinations Against Extensive Drug Resistant Acinetobacter Baumannii Isolates from Intensive Care Unit Patients

BMC Infectious Diseases. , 2011  |  Pubmed ID: 21521536

Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB) strains.

Butane-1,4-diaminium 2-(meth-oxy-carbon-yl)benzoate Dihydrate

Acta Crystallographica. Section E, Structure Reports Online. , 2011  |  Pubmed ID: 21522348

In the title compound, C(4)H(14)N(2) (+)·2C(9)H(7)O(4) (-)·2H(2)O, the butane-1,4-diaminium cation lies on an inversion center. In the crystal, inter-molecular N-H⋯O and O-H⋯O hydrogen bonds link the components into layers parallel to (100). Addtional stabilization within these layers is provided by weak inter-molecular C-H⋯O hydrogen bonds.

4-(2-Amino-phen-yl)-10-oxa-4-aza-tricyclo-[5.2.1.0]dec-8-ene-3,5-dione

Acta Crystallographica. Section E, Structure Reports Online. , 2011  |  Pubmed ID: 21522349

In the title compound, C(14)H(12)N(2)O(3), the essentially planar pyrrole ring [maximum deviation = 0.037 (4) Å] and the benzene ring form a dihedral angle of 69.5 (2)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds connect mol-ecules into chains along [001]. Additional stabilization is provided by weak inter-molecular C-H⋯O hydrogen bonds.

Methanaminium 3,4,5,6-tetra-chloro-2-(meth-oxy-carbon-yl)benzoate

Acta Crystallographica. Section E, Structure Reports Online. , 2011  |  Pubmed ID: 21522362

In the crystal structure of the title compound, CH(6)N(+)·C(9)H(3)Cl(4)O(4) (-), the N atom of the methyl-amine mol-ecule is protonated and hydrogen bonded to the carboxyl group of the 3,4,5,6-tetra-chloro-2-(meth-oxy-carbon-yl)benzoate anion. The anions are linked by the cations via inter-molecular N-H⋯O inter-actions into chains extending along the c axis.

Propan-1-aminium 3,4,5,6-tetra-chloro-2-(meth-oxy-carbon-yl)benzoate

Acta Crystallographica. Section E, Structure Reports Online. , 2011  |  Pubmed ID: 21522384

In the anion of the title salt, C(3)H(10)N(+)·C(9)H(3)Cl(4)O(4) (-), the meth-oxy-carbonyl and carboxyl groups are aligned at dihedral angles of 57.8 (3) and 62.5 (3)°, respectively, with the aromatic ring. In the crystal, the cations and anions are linked by N-H⋯O hydrogen bonds, generating chains running aong the c axis.

16-Isopropyl-5,9-dimethyl-tetra-cyclo-[10.2.2.0.0]hexa-dec-15-ene-5,14-dimethanol

Acta Crystallographica. Section E, Structure Reports Online. , 2011  |  Pubmed ID: 21523038

The title compound, C(23)H(38)O(2), a tetra-cyclo-[10.2.2.0(1,10).0(4,9)] hexa-decane structure, crystallized with four independent mol-ecules in the asymmetric unit. In the crystal, these independent mol-ecules are linked by O-H⋯O hydrogen bonds, forming a polymeric chain propagating in [100].

Performance and Scalability of Fourier Domain Optical Coherence Tomography Acceleration Using Graphics Processing Units

Applied Optics. May, 2011  |  Pubmed ID: 21532660

Fourier domain optical coherence tomography (FD-OCT) provides faster line rates, better resolution, and higher sensitivity for noninvasive, in vivo biomedical imaging compared to traditional time domain OCT (TD-OCT). However, because the signal processing for FD-OCT is computationally intensive, real-time FD-OCT applications demand powerful computing platforms to deliver acceptable performance. Graphics processing units (GPUs) have been used as coprocessors to accelerate FD-OCT by leveraging their relatively simple programming model to exploit thread-level parallelism. Unfortunately, GPUs do not "share" memory with their host processors, requiring additional data transfers between the GPU and CPU. In this paper, we implement a complete FD-OCT accelerator on a consumer grade GPU/CPU platform. Our data acquisition system uses spectrometer-based detection and a dual-arm interferometer topology with numerical dispersion compensation for retinal imaging. We demonstrate that the maximum line rate is dictated by the memory transfer time and not the processing time due to the GPU platform's memory model. Finally, we discuss how the performance trends of GPU-based accelerators compare to the expected future requirements of FD-OCT data rates.

The Role of Von Willebrand Factor and ADAMTS13 in the No-reflow Phenomenon: After Primary Percutaneous Coronary Intervention

Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. , 2011  |  Pubmed ID: 22163125

We prospectively studied the correlations between plasma levels of von Willebrand factor and its cleaving protease--a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 (ADAMTS13)--in 126 patients who did or did not develop no-reflow phenomenon after primary percutaneous intervention for acute ST-segment-elevation myocardial infarction. Quantitative plasma levels of von Willebrand factor and ADAMTS13 were measured by immunoturbidometric assay.Angiographic no-reflow was observed in 46 (37%) of the 126 patients. At admission, plasma levels of von Willebrand factor were significantly higher in the no-reflow group (P < 0.001), but levels of ADAMTS13 at admission were similar in the 2 groups (P = 0.143). At logistic regression, after adjustment for serum creatinine, left ventricular ejection fraction, high-sensitivity C-reactive protein, and N-terminal pro B-type natriuretic peptide, plasma von Willebrand factor level at admission (≥ 5,531 mU/mL) was still the predictive factor for the no-reflow phenomenon. The area under the receiver operating characteristics curve was 0.785.Our results suggest that high von Willebrand factor level is related to the no-reflow phenomenon in such a way that it might be a predictor of the phenomenon.

Stress Wave Signal Denoising Using Ensemble Empirical Mode Decomposition and an Instantaneous Half Period Model

Sensors (Basel, Switzerland). , 2011  |  Pubmed ID: 22164032

Stress-wave-based techniques have been proven to be an accurate nondestructive test means for determining the quality of wood based materials and they been widely used for this purpose. However, the results are usually inconsistent, partially due to the significant difficulties in processing the nonlinear, non-stationary stress wave signals which are often corrupted by noise. In this paper, an ensemble empirical mode decomposition (EEMD) based approach with the aim of signal denoising was proposed and applied to stress wave signals. The method defined the time interval between two adjacent zero-crossings within the intrinsic mode function (IMF) as the instantaneous half period (IHP) and used it as a criterion to detect and classify the noise oscillations. The waveform between the two adjacent zero-crossings was retained when the IHP was larger than the predefined threshold, whereas the waveforms with smaller IHP were set to zero. Finally the estimated signal was obtained by reconstructing the processed IMFs. The details of threshold choosing rules were also discussed in the paper. Additive Gaussian white noise was embedded into real stress wave signals to test the proposed method. Butterworth low pass filter, EEMD-based low pass filter and EEMD-based thresholding filter were used to compare filtering performance. Mean square error between clean and filtered stress waves was used as filtering performance indexes. The results demonstrated the excellent efficiency of the proposed method.

Waif1/5T4 Inhibits Wnt/β-catenin Signaling and Activates Noncanonical Wnt Pathways by Modifying LRP6 Subcellular Localization

Developmental Cell. Dec, 2011  |  Pubmed ID: 22100263

Wnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.

Central Nervous System Regulation of Food Intake and Energy Expenditure: Role of Galanin-mediated Feeding Behavior

Neuroscience Bulletin. Dec, 2011  |  Pubmed ID: 22108817

Galanin is a neuropeptide widely expressed in the brain. It is implicated in energy expenditure, feeding, and the regulation of body weight. Numerous studies have revealed that galanin regulates food intake via galanin receptors, 5-HT(1A) receptor and adrenergic α-2 receptor. In this review, we summarize recent findings that reveal the essential role of galanin in increasing food intake as well as body weight and that identify the individual galanin receptor subtypes involved in the brain's modulation of food intake and energy expenditure, to provide a theoretical basis for further studies of different aspects of galanin action.

Characterization of the Interaction Between Surfactants and Enzymes by Fluorescence Probe

Enzyme and Microbial Technology. Sep, 2011  |  Pubmed ID: 22112561

In order to investigate the mechanism of the different stimulatory effects of the biosurfactant rhamnolipid and the chemical surfactant Tween 80 on enzymatic hydrolysis of lignocellulose, the interaction between surfactants and enzymes was analyzed by the fluorescence probe method using pyrene as probe. Based on the evolution law of pyrene fluorescence spectroscopy in the "surfactants-enzymes" systems, the interaction relationship between surfactants and enzymes was analyzed and discussed in this paper. The results show that enzyme molecules bind with rhamnolipid molecules, participate in the formation of rhamnolipid micelles, and increase the inner hydrophobic polarity of micelles, but do not change the properties of rhamnolipid micelles above the CMC (Critical Micelle Concentration). Nevertheless, for Tween 80, enzyme molecules also participate in the forming of micelles, however, they exhibit a stronger interaction with enzymes above the CMC. Both rhamnolipid and Tween 80 bind more strongly with xylanase than cellulase. Considering also previous experimental results, it can be concluded that the interaction between surfactants and enzymes improve enzyme stability and activity, and, therefore, the efficiency of enzymatic hydrolysis of lignocellulose is enhanced. The findings further provide theoretical knowledge about the mechanism of the stimulative effects of surfactants on enzymatic hydrolysis of lignocellulose.

Microautophagy: Lesser-known Self-eating

Cellular and Molecular Life Sciences : CMLS. Nov, 2011  |  Pubmed ID: 22080117

Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics, microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways. The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone-mediated autophagy, and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular bodies and multivesicular lysosomes.

Role of Sexual Transmission of HIV Among Young Noninjection and Injection Opiate Users: a Respondent-driven Sampling Study

Sexually Transmitted Diseases. Dec, 2011  |  Pubmed ID: 22082729

Sexual transmissibility of HIV among young drug users in China has been investigated in few studies. The objective of this study was to examine the role of sexual transmission on HIV infection among injection drug users (IDUs) and noninjection drug users (NIDUs).

Economical Challenges to Microbial Producers of Butanol: Feedstock, Butanol Ratio and Titer

Biotechnology Journal. Nov, 2011  |  Pubmed ID: 22076745

Butanol is an important solvent and transport fuel additive, and can be produced by microbial fermentation. Attempts to generate a superior microbial producer of butanol have been made through different metabolic engineering strategies. However, to date, butanol bio-production is still not economically competitive compared to petrochemical-derived production because of its major drawbacks, such as, high cost of the feedstocks, low butanol concentration in the fermentation broth and the co-production of low-value by-products acetone and ethanol. Here we analyze the main bottlenecks in microbial butanol production and summarize relevant advances from recently reported studies. Further needs and directions for developing real industrially applicable strains in butanol production are also discussed.

Dual Energy Spectral CT Imaging of Insulinoma-Value in Preoperative Diagnosis Compared with Conventional Multi-detector CT

European Journal of Radiology. Dec, 2011  |  Pubmed ID: 22153746

OBJECTIVE: The aim of this study was to investigate the value of dual energy spectral CT (DEsCT) imaging in preoperative diagnosis of insulinomas in comparison with conventional multi-detector CT (MDCT). MATERIALS AND METHODS: Thirty-five patients were included in this study with 14 underwent the conventional dual-phase CT imaging (from March 2009 to January 2010) and 21 underwent the dual-phase DEsCT imaging (from February 2010 to May 2011). CT images were interpreted prospectively by two radiologists in consensus before operation. All the patients had diagnosis confirmed pathologically. The accuracy of preoperative diagnosis of insulinomas between DEsCT imaging and conventional MDCT, and between different kinds of images of DEsCT was compared. RESULTS: There were 39 confirmed lesions among the 35 patients (23 and 16 tumors in the spectral CT group and MDCT group, respectively). MDCT detected 11 of 16 tumors. DEsCT imaging detected 20 of 23 tumors separately with the monochromatic image or the iodine density image, and 22 of 23 tumors with the combination of the two kinds of images. The sensitivity for the preoperative diagnosis of insulinoma was 95.7% with the combination of monochromatic and iodine density images in DEsCT imaging, statistically higher than that with the conventional MDCT (68.8%) (p=0.033). CONCLUSION: Dual energy spectral CT imaging has higher sensitivity in preoperative diagnosis of insulinomas compared with conventional MDCT. The combination of monochromatic image and iodine density image can improve the diagnostic sensitivity of insulinomas.

2-Methyl-propan-2-aminium 2-(meth-oxy-carbon-yl)benzoate

Acta Crystallographica. Section E, Structure Reports Online. Oct, 2011  |  Pubmed ID: 22064965

In the title compound, C(4)H(12)N(+)·C(9)H(7)O(4) (-), two C atoms and the N atom of the cation lie on a mirror plane, while all the atoms of the anion are disordered about a mirror plane. In the crystal, N-H⋯O hydrogen bonds link the components into chains along [010]. In the anion, the mean planes of the methoxycarbonyl and carboxylate groups form dihedral angles of 83.0 (2) and 83.2 (2)°, respectively, with the aromatic ring.

High Efficient Expression of Bioactive Human BMP-14 in E. Coli Using SUMO Fusion Partner

The Protein Journal. Dec, 2011  |  Pubmed ID: 22057545

Bone morphogenetic proteins (BMPs) are cytokines from the TGF-β superfamily, with important roles during embryonic development and in the induction of bone and cartilage tissue differentiation in the adult body. In this contribution, We report here the application of small ubiquitin-related modifier (SUMO) fusion technology to the expression and purification of human BMP-14. The fusion protein expressed in a soluble form was purified to a purity of 90% by Ni-IDA chromatography. After the SUMO-BMP14 fusion protein was cleaved by the SUMO protease at 30 °C for 1 h, the cleaved sample was re-applied to a Ni-IDA. Finally, about 45 mg recombinant hBMP-14 was obtained from 1 litre bacterial culture with no less than 95% purity. The purified hBMP-14 dimer was over 90% purity and could induce the expression of alkaline phosphatase activity in C2C12 cells in a dose-dependent manner. Thus the SUMO-mediated peptide expression and purification system potentially could be employed for the production of other homodimeric proteins.

Effects of Adenovirus Vectors Mediated Human Lactoferrin CDNA on Mice Bearing EMT6 Breast Carcinoma

Die Pharmazie. Sep, 2011  |  Pubmed ID: 22026128

Human lactoferrin (hLTF) is an 80KD iron-binding protein. It has been reported that hLTF exists anti-tumor effects. In this study Adenovirus Vectors Mediated Human Lactoferrin cDNA (ad-rhLTF) was constructed and an antitumor effects of ad-rhLTF were investigated in mice bearing EMT6 breast carcinoma. The results demonstrated that ad-rhLTF (5 x 10(8) and 25 x 10(8) pfu/ml local injection) had high expression in tumor tissues and effectively reduced the weight of EMT6 breast tumors. Compared with the control group, cell cycle assay by flow cytometry showed that ad-rhLTF increased the percentage of tumor cells in the Sub-G1 phase and G0/G1 phase and the apoptotic number reached to 23.2% in ad-rhLTF group (25 x 10(8) pfu/ml). Ad-rhLTF treatment also resulted in a decrease of Bcl-2 and an increase in Bax and caspase 3 expressions, which was demonstrated by immunohistochemical analysis and RT-PCR. These data suggest that the antitumor effects of ad-rhLTF might be associated with arresting tumor cells in the G0/G1 phase, inducing cell apoptosis and regulation of the expression of Bcl-2, Bax and activation of caspase 3.

Serum Levels of TNF-α, IL-1β, COMP, and CTX-II in Patients with Kashin-Beck Disease in Sichuan, China

Rheumatology International. Nov, 2011  |  Pubmed ID: 22068351

The aim of the study was to detect differences in serum levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), cartilage oligomeric matrix protein (COMP), type II collagen (CTX-II) between patients with Kashin-Beck disease (KBD) or osteoarthritis (OA) and to assess the correlation between these differences with the clinical grade of KBD. A total of one hundred fifty adult serum samples were collected; these samples belonged to the KBD group (n = 64), the OA group in KBD-prevalent areas (n = 47) and a healthy control group in non-KBD area (n = 39). Serum levels of TNF-α, IL-1β, COMP, and CTX-II were determined by a sandwich enzyme-linked immunosorbent assay, and the results were compared among the 3 groups (KBD/OA/normal) and between the different grades of KBD as well. The serum levels of IL-1β, TNF-α, COMP, and CTX-II were significantly higher in the KBD and OA group than the healthy adult group (P < 0.001), and TNF-α and IL-1β levels in the KBD group were similar to the OA group (for TNF-α, 14.38 ± 7.42 pg/ml vs. 12.61 ± 4.00 pg/ml, respectively, [P = 0.29]; for IL-1β, 141.53 ± 71.35 pg/ml vs. 135.61 ± 68.60 pg/ml, respectively, [P = 0.63]). However, the COMP level was significantly lower and the CTX-II level was higher in the KBD group than in the OA group (for COMP, 7.03 ± 3.11 ng/ml vs. 9.20 ± 3.51 ng/ml, respectively, [P = 0.003]; for CTX-II, 2.23 ± 0.79 ng/ml vs. 1.80 ± 0.87 ng/ml, respectively, [P = 0.026]). Moreover, no significant correlations were found between clinical grade and serum levels of TNF-α, IL-1β, COMP, and CTX-II for the 3 grades of KBD patients (P = 0.645, 0.481, 0.832, and 0.270, respectively). This study showed that serum levels of COMP in KBD patients decreased and CTX-II levels increased compared with the levels in OA patients, but TNF-α and IL-1β levels in KBD and OA group were similar. In addition, increased serum levels of TNF-α, IL-1β, COMP, and CTX-II were not associated with the KBD grade.

Glioblastoma with PNET-like Components Has a Higher Frequency of Isocitrate Dehydrogenase 1 (IDH1) Mutation and Likely a Better Prognosis Than Primary Glioblastoma

International Journal of Clinical and Experimental Pathology. , 2011  |  Pubmed ID: 22076165

Glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET), a rare variant of glioblastoma, poses both diagnostic and therapeutic challenges. Ten patients with GBM-PNET were investigated with a median age of 51.5 years and the male to female ratio of 4:1. The majority of patients (7 out of 10) showed ring-enhancing lesions on magnetic resonance imaging (MRI), which is classic for GBMs. Restricted diffusion was noted in 7 cases where diffusion weighted imaging (DWI) was performed, which correlates with the presence of PNET-like components. CD56 and vimentin immunostaining made the diagnosis of GBM-PNET much easier. Vimentin strongly and diffusely highlighted the astrocytic components and was negative in PNET-like components, while CD56 was strongly and diffusely positive in both astrocytic and PNET-like components. Seven out of 9 cases were positive for p53 in both astrocytic and PNET-like components. Two out of 8 cases harbored isocitrate dehydrogenase 1 (IDH1) R132H mutation, while IDH2 R172 mutations were not identified. Three out of 10 patients had a median survival time of 17 months while the two patients, whose tumor carried IDH1 mutation, were still alive after 15 and 31 months of follow-up. Compared to primary GBMs, GBM-PNETs might have a better prognosis. Further large scale studies are necessary to confirm this observation.

[Periarthritis of Shoulder Treated with Deep Puncture by Elongated Needle Combined with Spike-hooked Needle and Cupping: a Multicentral Randomized Controlled Study]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Oct, 2011  |  Pubmed ID: 22043668

To assess the clinical efficacy and the safety for periarthritis of shoulder treated with deep puncture by elongated needle combined with spike-hooked needle and cupping.

Translating Human Embryonic Stem Cells from 2-Dimensional to 3-Dimensional Cultures in a Defined Medium on Laminin- and Vitronectin-Coated Surfaces

Stem Cells and Development. Dec, 2011  |  Pubmed ID: 22034857

While defining the environment for human embryonic stem cell (hESC) culture on 2-dimensional (2D) surfaces has made rapid progress, the industrial-scale implementation of this technology will benefit from translating this knowledge into a 3-dimensional (3D) system, thus enabling better control, automation, and volumetric scale-up in bioreactors. The current study describes a system with defined conditions that are capable of supporting the long-term 2D culture of hESCs and the transposing of these conditions to 3D microcarrier (MC) cultures. Vitronectin (VN) and laminin (LN) were chosen as matrices for the long-term propagation of hESCs in a defined culture medium (STEMPRO(®)) for conventional 2D culture. Adsorption of these proteins onto 2D tissue culture polystyrene (TCPS) indicated that surface density saturation of 510 and 850 ng/cm(2) for VN and LN, respectively, was attained above 20 μg/mL deposition solution concentration. Adsorption of these proteins onto spherical (97±10 μm), polystyrene MC followed a similar trend and coating surface densities of 450 and 650 ng/cm(2) for VN and LN, respectively, were used to support hESC propagation. The long-term expansion of hESCs was equally successful on TCPS and MC, with consistently high expression (>90%) of pluripotent markers (OCT-4, MAB-84, and TRA-1-60) over 20 passages and maintenance of karyotypic normality. The average fold increase in cell numbers on VN-coated MC per serial passage was 8.5±1.0, which was similar to LN-coated MC (8.5±0.9). Embryoid body differentiation assays and teratoma formation confirmed that hESCs retained the ability to differentiate into lineages of all 3 germ layers, thus demonstrating the first translation to a fully defined MC-based environment for the expansion of hESCs.

Simvastatin Suppresses Apoptosis in Vulnerable Atherosclerotic Plaques Through Regulating the Expression of P(53), Bcl-2 and Bcl-xL

Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. Oct, 2011  |  Pubmed ID: 22038096

PURPOSE: Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has antioxidant and anti-inflammatory properties that are independent of lipid-lowering abilities. This experiment was carried out to explore the effects of simvastatin on apoptosis in vulnerable atherosclerotic plaques of apoE-deficient mice. METHODS AND RESULTS: Eight weeks-old apoE(-/-) mice were fed a Western-type diet. Vulnerable atherosclerotic lesions were formed in the branchiocephalic artery at the age of 30-weeks, before simvastatin administration for 8 weeks. Simvastatin did neither affect the levels of plasma glucose and lipids, nor the size of atherosclerotic lesions. Analysis of plaque composition showed that simvastatin decreased the area of lipid core and increased the amounts of macrophages and smooth muscle cells in atherosclerotic plaques of apoE(-/-) mice. In addition, simvastatin down-regulated the expression of vascular cell adhesion molecule-1 (VCAM-1) by both inhibition of nuclear factor kappa B (NF-кB) activation and suppression of the expression of the receptor for advanced glycation end products (RAGE). Moreover, we found that simvastatin administration led to reduced TUNEL-positive cells in the aortic root lesions, accompanied by up-regulation of Bcl-2 and Bcl-xL expression, and decreased P(53) expression as shown by Western blot. CONCLUSION: In the present study, we show novel data to suggest that simvastatin could suppress apoptosis in vulnerable atherosclerotic plaques of apoE(-/-) mice by regulating the expression of apoptosis-related proteins, such as p(53), Bcl-2 and Bcl-xL.

Screening for Mutations in the α-globin Genes Leading to Abnormal Hemoglobin Variants with High Resolution Melting Analysis

Clinical Chemistry and Laboratory Medicine : CCLM / FESCC. Oct, 2011  |  Pubmed ID: 22022987

Abstract Background: α-Thalassemia is one of the most commonly inherited single-gene disorders in southern China. It is important to identify non-deletional α-thalassemia in areas where α-thalassemia is prevalent, since non-deletional HbH disease (--/α(T)α or --/αα(T)) is caused by the interaction of a non-deletional α-thalassemia with α-thalassemia-1 trait (--/αα). In this study, we developed an optimized molecular protocol for screening for α-globin gene mutations and validated the feasibility of using it as a rapid detection method. Methods: An approach based on high-resolution melting (HRM) analysis was used. A total of 74 samples, including 54 abnormal α-chain samples and 20 control samples, were tested. Results: All of the 54 samples with point mutations at the exons 1, 2 or 3 of the α-globin genes, including 33 non-deletional α-thalassemia, were successfully detected. Conclusions: HRM has the potential to become an efficient, rapid screening method for non-deletional α-thalassemia.

Comparison of Gene Expression and Genome-wide DNA Methylation Profiling Between Phenotypically Normal Cloned Pigs and Conventionally Bred Controls

PloS One. , 2011  |  Pubmed ID: 22022462

Animal breeding via Somatic Cell Nuclear Transfer (SCNT) has enormous potential in agriculture and biomedicine. However, concerns about whether SCNT animals are as healthy or epigenetically normal as conventionally bred ones are raised as the efficiency of cloning by SCNT is much lower than natural breeding or In-vitro fertilization (IVF). Thus, we have conducted a genome-wide gene expression and DNA methylation profiling between phenotypically normal cloned pigs and control pigs in two tissues (muscle and liver), using Affymetrix Porcine expression array as well as modified methylation-specific digital karyotyping (MMSDK) and Solexa sequencing technology. Typical tissue-specific differences with respect to both gene expression and DNA methylation were observed in muscle and liver from cloned as well as control pigs. Gene expression profiles were highly similar between cloned pigs and controls, though a small set of genes showed altered expression. Cloned pigs presented a more different pattern of DNA methylation in unique sequences in both tissues. Especially a small set of genomic sites had different DNA methylation status with a trend towards slightly increased methylation levels in cloned pigs. Molecular network analysis of the genes that contained such differential methylation loci revealed a significant network related to tissue development. In conclusion, our study showed that phenotypically normal cloned pigs were highly similar with normal breeding pigs in their gene expression, but moderate alteration in DNA methylation aspects still exists, especially in certain unique genomic regions.

Synthesis and Anti-tumor Activities of N'-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone Derivatives

Bioorganic & Medicinal Chemistry Letters. Nov, 2011  |  Pubmed ID: 21986587

A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC(50) values of 10-20 μM on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms.

Salinomycin Can Effectively Kill ALDH(high) Stem-like Cells on Gastric Cancer

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie. Oct, 2011  |  Pubmed ID: 21996439

Salinomycin is a novel identified cancer stem cells (CSCs) killer. Higher ALDH activity represents CSCs characterization. Here, we screened ALDH activities on several gastric cancer cell lines and divided them into ALDH(high) and ALDH(low) gastric cancer groups. ALDH(high) cancer cells (NCI-N87 and SNU-1) disclosed more CSCs characteristics, such as higher levels of Sox2, Nanog and Nestin, more floating spheroid bodies, more colony formation and more resistance to conventional chemotherapeutic drugs 5-Fu and CDDP, compared to these parameters observed in ALDH(low) cancer cells (P<0.01). Importantly, ALDH(high) cancer cells are relatively sensitive to salinomycin when compared to ALDH(low) cancer cells (P<0.01). Our results confirmed ALDH as functional marker of CSCs population on gastric cancer. Salinomycin might be selective therapy for CSCs fraction, which is resistant to conventional anticancer drugs 5-Fu and CDDP.

Ankylosis of Temporomandibular Joint After the Traumatic Brain Injury: a Report of Two Cases

Dental Traumatology : Official Publication of International Association for Dental Traumatology. Oct, 2011  |  Pubmed ID: 22008514

Abstract -  Mouth opening limitation after the neurosurgical procedures is a common complication and usually resolves within 3 months. If limited mouth opening remains unresolved on the long term, an intra-articular ankylosis of temporomandibular joint may develop eventually. The possible mechanisms base on the myositis and atrophy of the masticatory muscles for these craniotomies are often involved in the temporalis. This article reports two unusual cases with the intra-articular ankylosis of temporomandibular joint after the traumatic brain injury, who received a modified surgical treatment for joint ankylosis. Therefore, the early diagnosis and intervention are important to minimize these complications.

Oscillatory-like Relaxation Behavior of Light Transmitted Through Ferrofluids

Applied Optics. Oct, 2011  |  Pubmed ID: 22015404

An oscillatory-like relaxation process in which there are two valleys in the T-t curve is observed when light is transmitted through binary ferrofluids composed of both ferrimagnetic CoFe(2)O(4) nanoparticles and paramagnetic p-MgFe(2)O(4) nanoparticles in the presence of a high magnetic field and through pure (single) CoFe(2)O(4) ferrofluids in a low magnetic field. This relaxation behavior is explained using a model of a bidispersed system based on both chained and unchained particles. In such a bidispersed system, the variation of the transmitted light results mainly from the motion of the chains, with the polarized unchained particles' gas producing the modulation effect. The oscillatory-like relaxation phenomenon depends on the features of both the chained and unchained particle systems. If either the particle volume fraction of chained particles or of unchained particles is very low, or the degree of polarization of the unchained particles gas is very weak, a simple nonlinear relaxation process, giving only a valley in the T-t curve, will appear for the transmitted light. For pure CoFe(2)O(4) ferrofluids, the number of chained and unchained particles does not remain constant under different values of the magnetic field. According to the analysis of the relaxation behavior of transmitted light, it is known that binary ferrofluids based on strong magnetic CoFe(2)O(4) particles and weak magnetic p-MgFe(2)O(4) particles can be much closer to the theoretical bidispersed system than single ferrofluids containing only strong magnetic particles.

Macrophage Migration Inhibitory Factor Homolog from Plasmodium Yoelii Modulates Monocyte Recruitment and Activation in Spleen During Infection

Parasitology Research. Oct, 2011  |  Pubmed ID: 22015474

Macrophage migration inhibitory factor (MIF) has been shown to be involved in the pathogenesis of severe malaria. Malaria parasites express an MIF homolog that may play a role in regulating host immune responses, and a recent study showed that overexpression of MIF reduced parasitemia in a mouse malaria model. Another recent study showed migration of monocytes to the spleen contributed to the control of blood stage infection. However, there are few papers describing the effect of MIF on monocyte recruitment/activation during the infection. We generated recombinant Plasmodium yoelii MIF (rPyMIF) and investigated its function on purified mouse CD11b(+) cells in vitro and monocyte responses in vivo. The result shows that rPyMIF protein bound to mouse CD11b(+) cells and inhibited their random migration in vitro. On the other hand, rPyMIF did not induce cytokine release from the cells directly or modulate lipopolysaccharide-induced cytokine release. Mice immunized with rPyMIF showed transient but significantly lower parasitemia than the control mice at day 3 after lethal Py17XL challenge. The total number of CD11b(+) cells in the spleens was significantly higher in rPyMIF-immunized group. Further investigation revealed that there were significantly higher numbers of recruited and activated monocytes in the spleens of rPyMIF immunization group on day 3. These results indicate that PyMIF potentially modulates monocyte recruitment and activation during infection of P. yoelii erythrocytic stages.

Low Birth Weight and Elevated Head-to-abdominal Circumference Ratio Are Associated with Elevated Fetal Glycated Serum Protein Concentrations

Journal of Hypertension. Sep, 2011  |  Pubmed ID: 21841546

To analyze the association between low birth weight, head-to-abdominal circumference ratio, and insulin resistance in early life.

Induction of Specific Immune Response and Suppression of Fertility by B-cell-epitope-based Mimovirus Vaccine

Reproduction (Cambridge, England). Nov, 2011  |  Pubmed ID: 21908656

SPINLW1 (previously known as eppin (epididymal protease inhibitor)) is a target under intense scrutiny in the study of male contraceptive vaccines. B-cell-dominant epitopes are now recognized as key parts of the induction of humoral immune responses against target antigens. The generation of robust humoral responses in vivo has become a crucial problem in the development of modern vaccines. In this study, we developed a completely novel B-cell-dominant-epitope-based mimovirus vaccine, which is a kind of virus-size particulate antigen delivery system. The mimovirus successfully self-assembled from a cationic peptide containing a cell-penetrating peptide of TAT49-57 and a plasmid DNA encoding both three SPINLW1 (103-115) copies and adjuvant C3d3. The male mice were immunized with the epitope-based mimovirus vaccine, which resulted in a gradual elevation of specific serum IgG antibody levels. These reached a peak at week 4. Mating for the fertility assay showed that the mimovirus vaccine had accomplished a moderate fertility inhibition effect and investigation into the mechanism of action showed that it did so by interfering with the reproductive function of the sperm but that it did not damage the structures of the testes or cause serum testosterone to decline. Our results suggest an ideal protocol for suppressing fertility in mice by an engineered mimovirus vaccine.

Differential Roles of Human Striatum and Amygdala in Associative Learning

Nature Neuroscience. Oct, 2011  |  Pubmed ID: 21909088

Although the human amygdala and striatum have both been implicated in associative learning, only the striatum's contribution has been consistently computationally characterized. Using a reversal learning task, we found that amygdala blood oxygen level-dependent activity tracked associability as estimated by a computational model, and dissociated it from the striatal representation of reinforcement prediction error. These results extend the computational learning approach from striatum to amygdala, demonstrating their complementary roles in aversive learning.

Ancient Antimicrobial Peptides Kill Antibiotic-resistant Pathogens: Australian Mammals Provide New Options

PloS One. , 2011  |  Pubmed ID: 21912615

To overcome the increasing resistance of pathogens to existing antibiotics the 10×'20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes.

Microcystic Meningioma Presenting As a Cystic Lesion with an Enhancing Mural Nodule in Elderly Women: Report of Three Cases

Brain Tumor Pathology. Oct, 2011  |  Pubmed ID: 21863303

Cystic meningioma with an enhancing mural nodule is uncommon and can present as a radiologic and clinical dilemma with wide differential. We report a series of rare and unique presentation of microcystic meningioma in three elderly women aged 76 (case 1), 72 (case 2), and 76 (case 3) years, respectively. The first patient presented with a 3-year history of vertigo and past history of carotid artery stenosis, hypertension, and hypothyroidism. The second patient presented with headache and an acute episode of weakness in her legs. The third patient presented with headache, vomiting, and confusion. Magnetic resonance imaging for these three cases showed a cystic lesion with an enhancing mural nodule in the right frontal lobe. The preoperative differential diagnoses included hemangioblastoma and well-circumscribed gliomas for the first two cases. Glioblastoma and metastatic tumor were the working diagnoses for the third case because of vasogenic brain edema and marked mass effect. The final pathological diagnosis was microcystic meningioma for all three cases. Case reports are mainly of fibrous or meningothelial meningiomas with cystic formation. Male predominance and young age are most commonly reported. Our series is unique because of the rare and unusual clinical-radiologic presentation of microcystic meningioma in elderly women.

Use of Array CGH to Detect Exonic Copy Number Variants Throughout the Genome in Autism Families Detects a Novel Deletion in TMLHE

Human Molecular Genetics. Nov, 2011  |  Pubmed ID: 21865298

Autism is a neurodevelopmental disorder with increasing evidence of heterogeneous genetic etiology including de novo and inherited copy number variants (CNVs). We performed array comparative genomic hybridization using a custom Agilent 1 M oligonucleotide array intended to cover 197 332 unique exons in RefSeq genes; 98% were covered by at least one probe and 95% were covered by three or more probes with the focus on detecting relatively small CNVs that would implicate a single protein-coding gene. The study group included 99 trios from the Simons Simplex Collection. The analysis identified and validated 55 potentially pathogenic CNVs, categorized as de novo autosomal heterozygous, inherited homozygous autosomal, complex autosomal and hemizygous deletions on the X chromosome of probands. Twenty percent (11 of 55) of these CNV calls were rare when compared with the Database of Genomic Variants. Thirty-six percent (20 of 55) of the CNVs were also detected in the same samples in an independent analysis using the 1 M Illumina single-nucleotide polymorphism array. Findings of note included a common and sometimes homozygous 61 bp exonic deletion in SLC38A10, three CNVs found in lymphoblast-derived DNA but not present in whole-blood derived DNA and, most importantly, in a male proband, an exonic deletion of the TMLHE (trimethyllysine hydroxylase epsilon) that encodes the first enzyme in the biosynthesis of carnitine. Data for CNVs present in lymphoblasts but absent in fresh blood DNA suggest that these represent clonal outgrowth of individual B cells with pre-existing somatic mutations rather than artifacts arising in cell culture. GEO accession number GSE23765 (http://www.ncbi.nlm.nih.gov/geo/, date last accessed on 30 August 2011). Genboree accession: http://genboree.org/java-bin/gbrowser.jsp?refSeqId=1868&entryPointId=chr17&from=53496072&to=53694382&isPublic=yes, date last accessed on 30 August 2011.

[Determination of Silver Content in Silver-loaded Coral Hydroxyapatite in Relation to the Biocompatibility]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Aug, 2011  |  Pubmed ID: 21868334

To determine the amount of silver in silver-loaded coral hydroxyapatite (Ag(+)-CHA) bone substitute and its impact on the biocompatibility of this material with mouse embryonic osteoblast cells.

The Antioxidant N-acetylcysteine Promotes Atherosclerotic Plaque Stabilization Through Suppression of RAGE, MMPs and NF-κB in ApoE-deficient Mice

Journal of Atherosclerosis and Thrombosis. , 2011  |  Pubmed ID: 21873804

N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. To explore the mechanisms underlying atherosclerotic plaque stabilization induced by NAC, we examined the effects of NAC administration in apoE-deficient mice on the expression of the receptor of advanced glycation end products (RAGE), matrix metalloproteinases (MMPs) and the activation of nuclear factor kappa B (NF-κB) in atherosclerotic plaques.

Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity Against Multidrug-resistant Pseudomonas Aeruginosa at Multiple Inocula

Antimicrobial Agents and Chemotherapy. Nov, 2011  |  Pubmed ID: 21876058

The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in Pseudomonas aeruginosa. The aim of this study was to systematically investigate in vitro bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (~10(6) and ~10(8) CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 10(6)-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 10(8)-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 10(6)- and 10(8)-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations.

Protective Effects of Diosmetin Extracted from Galium Verum L. on the Thymus of U14-bearing Mice

Canadian Journal of Physiology and Pharmacology. Sep, 2011  |  Pubmed ID: 21851214

Diosmetin (DGVL) extracted from the traditional Chinese herb Galium verum L. has been found to have anticancer activity. In this study, the effects of DGVL on the thymus of U14-bearing mice were investigated. Using flow cytometry, peripheral blood lymphocytes were characterized based on the expression of surface markers for T helper cells (CD4(+)) and T suppressor cells (CD8(+)). Serum levels of tumor necrosis factor α (TNF-α), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGF-β1) and a cell proliferation assay were determined with an enzyme-linked immunosorbent assay. The expression of Fas and Fas ligand (FasL) on the thymus was determined by Western blotting. Our results showed that DGVL inhibited tumor growth and significantly increased the thymus weight compared with the control. Also, DGVL elevated serum levels of IL-2 and significantly reduced levels of TNF-α, TGF-β1, and IL-10 in a dose-dependent manner. Histological study and terminal dUTP nick end labeling staining results showed that DGVL protected thymus tissue against the onslaught of tumor growth by inhibiting thymus lymphocyte apoptosis. The cell proliferation assay revealed that DGVL might promote more thymus lymphocytes towards proliferation. Furthermore, the ratio of CD4(+)/CD8(+) T lymphocytes was significantly increased from 0.69 to 2.29 by treatment with DGVL. Immunoblotting analyses revealed that the expression of Fas and FasL on the thymus was lower in mice in the DGVL treatment group than in the control mice. In conclusion, DGVL can inhibit tumor growth and protect tumor-induced apoptosis of the thymus, and the mechanism is closely associated with reduced cell death in the thymus and a Fas-FasL-dependent pathway.

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling

PloS One. , 2011  |  Pubmed ID: 21858214

GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50(-/-) mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60.

Self-assembly of Copper and Cobalt Complexes with Hierarchical Size and Catalytic Properties for Hydroxylation of Phenol

Nanoscale Research Letters. , 2011  |  Pubmed ID: 21824407

ABSTRACT: A feasible and effective self-assembly method to synthesize different scale coordination polymers in highly dilute solution (from nanocrystals to microcrystals and to bulk crystals) without any blocking agent has been described. The growth of crystalline particles was controlled by removing the particles at different reaction times to interrupt the growth at the desired size. The nano and microscale particles show better catalytic conversions and selectivities in the hydroxylation of phenols than the bulk crystals.

Oxidative Coupling of Porphyrins Using Copper(II) Salts

Chemical Communications (Cambridge, England). Sep, 2011  |  Pubmed ID: 21829800

A method for radical coupling of porphyrins using copper(II) salts as one-electron oxidants was developed. A Zn(II)-porphyrin bearing an aminophenyl group yielded porphyrin oligomers, and two tri-arylporphyrins were oxidized to form doubly and triply linked dimers. Bromination of doubly linked dimers gave macrocycles with twisted skeletons.

Growth Suppression Effects of Recombinant Adenovirus Expressing Human Lactoferrin on Cervical Cancer in Vitro and in Vivo

Cancer Biotherapy & Radiopharmaceuticals. Aug, 2011  |  Pubmed ID: 21834714

Human lactoferrin (hLF) is a multifunctional glycoprotein that can inhibit cancer growth. The molecular mechanism of hLF-induced tumor growth inhibition is incompletely understood. Moreover, the adenovirus vector-mediated hLF (Ad-hLF) gene therapy on cervical cancer has not been yet characterized. In this study, the replication-deficient Ad-hLF was used to explore tumor growth suppression effects on cervical cancer in vitro and in vivo. The results showed that the recombinant adenovirus encoding hLF delivery resulted in a more differential tumor growth inhibition, and this growth arrest was caused by cell cycle inhibition at G2/M phase. In addition, Fas, a death-inducing receptor, and Bax, a member of pro-apoptotic Bcl-2 family, were increased in the sample of cervical cancer tissue treated by Ad-hLF. Further, it was also observed that caspase-3 was activated and the expression of anti-apoptotic Bcl-2 was decreased. These results indicated that the growth inhibitory effects of Ad-hLF on cervical cancer were caused by elevated expression of Fas and decreased the ratio of anti- to pro-apoptotic molecule Bcl-2/Bax.

Dosing of Colistin-back to Basic PK/PD

Current Opinion in Pharmacology. Oct, 2011  |  Pubmed ID: 21835694

The increasing prevalence of multidrug-resistant Gram-negative bacteria worldwide has led to a re-evaluation of the previously discarded antibiotic, colistin. Despite its important role as salvage therapy for otherwise untreatable infections, dosage guidelines for the prodrug colistin methanesulfonate (CMS) are not scientifically based and have led to treatment failure and increased colistin resistance. In this review we summarise the recent progress made in the understanding of the pharmacokinetics of CMS and formed colistin with an emphasis on critically ill patients. The pharmacodynamics of colistin is also reviewed, with special attention given to the relationship between pharmacokinetics and pharmacodynamics and how the emerging data can be used to inform design of optimal dosage regimens. Recent data suggest the current dosage regimens of CMS are suboptimal in many critically ill patients.

Early Prenatal Diagnosis of Thalassemia: the First Report of Experience in Mainland China

Hemoglobin. , 2011  |  Pubmed ID: 21797712

In this study, we report our experience with chorionic villus sampling (CVS) for prenatal diagnosis of thalassemia in mainland China. During a 4-year period, 308 pregnant women chose to have CVS for prenatal diagnosis. Chorionic villus sampling was successful in all cases, and post-CVS abortion was seen in only two cases (0.6%). DNA diagnosis was correctly done in 307 (99.7%) prenatal samples but maternal contamination was found in one (0.3%) subject. In total, 77 pregnancies were found with an affected fetus, and all of the affected pregnancies were terminated within 1 week after the CVS procedure. Our experience indicates that CVS is a feasible and effective technique for prenatal diagnosis of thalassemia.

The Antibacterial Peptide ABP-CM4: the Current State of Its Production and Applications

Amino Acids. Jul, 2011  |  Pubmed ID: 21805135

The increasing resistance of bacteria and fungi to currently available antibiotics is a major concern worldwide, leading to enormous efforts to develop new antibiotics with new modes of actions. Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as a promising candidate for a new antibiotic. For pharmaceutical applications, a large quantity of antimicrobial peptides needs to be produced economically. In this communication, the progress in the structural characteristics, heterologous production, and biological evaluation of ABP-CM4 are reviewed.

Effects of Borneol on the Intestinal Transport and Absorption of Two P-glycoprotein Substrates in Rats

Archives of Pharmacal Research. Jul, 2011  |  Pubmed ID: 21811923

As the most prevalent route of delivery, oral administration has the challenge of potentially low bioavailability in part because P-glycoprotein (P-gp) in the intestinal tract affects absorption. Therefore, absorption enhancers or P-gp inhibitors are strategies to solve this problem. The aim of the present study was to investigate the effects of borneol on transportation of colchicine and rhodamine123, two P-gp substrates, in rats. In vitro transportation was assessed with a diffusion chamber system with isolated rat intestines. Different concentrations of borneol (10, 40 and 80 μg/mL) were prepared in solutions with two P-gp substrates compared with blank solutions. The in vivo effects on colchicine were assessed by a pharmacokinetic study. Borneol enhanced the absorptive transport of two P-gp substrates, which was relevant to the concentration. A pharmacokinetic study showed that in the presence of borneol, a significant increase in C(max) and AUC(0→8) of colchicine occurred when compared to colchicine alone. The study showed that borneol affected two P-gp substrates in the intestine, possibly by inhibiting the effects of P-gp and enhancing intestinal absorption of drugs. Therefore, borneol could be developed as a P-gp inhibitor and absorptive enhancer.

The in Vivo Contribution of Motor Neuron TrkB Receptors to Mutant SOD1 Motor Neuron Disease

Human Molecular Genetics. Nov, 2011  |  Pubmed ID: 21816949

Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) are widely expressed in the vertebrate nervous system and play a central role in mature neuronal function. In vitro BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults. Paradoxically, BDNF/TrkB signaling has also been shown, under certain in vitro circumstances, to render neurons vulnerable to insults. We show here that in vivo conditional deletion of TrkB from mature motor neurons attenuates mutant superoxide dismutase 1 (SOD1) toxicity. Mutant SOD1 mice lacking motor neuron TrkB live a month longer than controls and retain motor function for a longer period, particularly in the early phase of the disease. These effects are subserved by slowed motor neuron loss, persistence of neuromuscular junction integrity and reduced astrocytic and microglial reactivity within the spinal cord. These results suggest that manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases.

Effect of ω-3 Polyunsaturated Fatty Acid on Toll-like Receptors in Patients with Severe Multiple Trauma

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Aug, 2011  |  Pubmed ID: 21823012

This study examined the effects of ω-3 polyunsaturated fatty acid (ω-3PUFA) on the expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and some related inflammatory factors in peripheral blood mononuclear cells (PBMCs) of patients with early-stage severe multiple trauma. Thirty-two patients who were admitted to the Department of Traumatic Surgery, Tongji Hospital (Wuhan, China) between May 2010 and November 2010, and diagnosed as having severe multiple trauma with a injury severity score (ISS) no less than 16, were enrolled in the study and divided into two groups at random (n=16 in each): ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days. Peripheral blood from these patients was collected within 2 h of admission (day 0), and 1, 3, 5 and 7 days after the nutritional support. PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively, the levels of NF-κB by quantum dots-based immunofluorescence assay, the levels of TNF-α, IL-2, IL-6 and COX-2 by ELISA, respectively. The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support (both P<0.05). The levels of TNF-α, IL-2, IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day (P<0.05 for all). It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2, TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma, which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.

Copy Number Variation in CNP267 Region May Be Associated with Hip Bone Size

PloS One. , 2011  |  Pubmed ID: 21789208

Osteoporotic hip fracture (HF) is a serious global public health problem associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of key measurable risk factors for HF, independent of bone mineral density (BMD). Hip BS is highly genetically determined, but genetic factors underlying BS variation are still poorly defined. Here, we performed an initial genome-wide copy number variation (CNV) association analysis for hip BS in 1,627 Chinese Han subjects using Affymetrix GeneChip Human Mapping SNP 6.0 Array and a follow-up replicate study in 2,286 unrelated US Caucasians sample. We found that a copy number polymorphism (CNP267) located at chromosome 2q12.2 was significantly associated with hip BS in both initial Chinese and replicate Caucasian samples with p values of 4.73E-03 and 5.66E-03, respectively. An important candidate gene, four and a half LIM domains 2 (FHL2), was detected at the downstream of CNP267, which plays important roles in bone metabolism by binding to several bone formation regulator, such as insulin-like growth factor-binding protein 5 (IGFBP-5) and androgen receptor (AR). Our findings suggest that CNP267 region may be associated with hip BS which might influence the FHL2 gene downstream.

ENOS-G894T Polymorphism is a Risk Factor for Essential Hypertension in China

Indian Journal of Biochemistry & Biophysics. Jun, 2011  |  Pubmed ID: 21793305

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with coronary artery disease; however, associations between polymorphism (G894T) of the eNOS gene and essential hypertension remain unclear. This study was designed to investigate the association between a eNOS-G894T polymorphism and essential hypertension (EH). A total of 190 Chinese EH patients (EH group) and 94 healthy participants (control group) were included in the study. eNOS-G894T was determined using multi-polymerase chain reaction and polymorphisms in eNOS-G894T were genotyped using gene chip technology. Patients carrying eNOS GT + TT genotypes had a higher risk of EH than those carrying the GG genotype (OR = 2.82, 95% CI: 1.05-7.60, P = 0.033). The EH group showed a significantly higher frequency of the T-allele compared with controls (OR = 3.48, 95% CI: 1.34-9.07; P = 0.007). eNOS-894T was found to be significantly associated with EH in the dominant genetic model. Thus, the study demonstrated a significant and independent association between a eNOS-G894T polymorphism and EH in the Chinese patients. The study also showed that eNOS-G894T polymorphism is a risk factor for EH in Chinese patients.

Inhibition of Matrix Metalloproteinase 14 (MMP-14)-mediated Cancer Cell Migration

The Journal of Biological Chemistry. Sep, 2011  |  Pubmed ID: 21795678

Matrix metalloproteinases (MMPs) have been shown to be key players in both extracellular matrix remodeling and cell migration during cancer metastasis. MMP-14, a membrane-anchored MMP, in particular, is closely associated with these processes. The hemopexin (PEX) domain of MMP-14 has been proposed as the modulating region involved in the molecular cross-talk that initiates cell migration through homodimerization of MMP-14 as well as heterodimerization with the cell surface adhesion molecule CD44. In this study, minimal regions required for function within the PEX domain were investigated through a series of substitution mutations. Blades I and IV were found to be involved in cell migration. We found that blade IV is necessary for MMP-14 homodimerization and that blade I is required for CD44 MMP-14 heterodimerization. Cross-talk between MMP-14 and CD44 results in phosphorylation of EGF receptor and downstream activation of the MAPK and PI3K signaling pathways involved in cell migration. Based on these mutagenesis analyses, peptides mimicking the essential outermost strand motifs within the PEX domain of MMP-14 were designed. These synthetic peptides inhibit MMP-14-enhanced cell migration in a dose-dependent manner but have no effect on the function of other MMPs. Furthermore, these peptides interfere with cancer metastasis without affecting primary tumor growth. Thus, targeting the MMP-14 hemopexin domain represents a novel approach to inhibit MMP-14-mediated cancer dissemination.

Phenotypic Variability in a Chinese Family with Nondeletional Hb H-Hb Quong Sze Disease

Hemoglobin. , 2011  |  Pubmed ID: 21797711

Hb H (β4) disease is the most common form of thalassemia intermedia. Two main types of Hb H disease, deletional and nondeletional, are characterized. Patients with nondeletional Hb H disease are usually more anemic with organomegaly; some may require regular blood transfusions and even be as severely affected as Hb H hydrops fetalis. However, there is no clear genotype-phenotype correlation associated with this severe clinical syndrome as patients with identical genotypes do not necessarily show the same severity. In this report, we described two nondeletional Hb H-Hb Quong Sze [α125(H8)Leu→Pro, CTG>CCG (α2)] disease individuals in a family who presented with phenotypic variability.

Generation of Protective Immune Responses Against Coxsackievirus B3 Challenge by DNA Prime-protein Boost Vaccination

Vaccine. Sep, 2011  |  Pubmed ID: 21803097

Coxsackievirus B3 (CVB3) causes viral myocarditis and can ultimately result in dilated cardiomyopathy. However, there is no vaccine available for clinical use. In this study, we assessed the protection provided by three immunization strategies against CVB3 infection. Vaccination was performed with a DNA vaccine expressing the cloned capsid gene VP1 or a vaccine developed from purified VP1 protein. Third, a strategy of vaccination was attempted with the DNA vaccine followed by two boosts with the recombinant protein vaccine (DNA prime-protein boost vaccine). Followed immunization, mice were challenged with CVB3 infection. Improved induction of CVB3-specific antibodies and neutralizing antibodies were found in mice immunized by the DNA prime-protein boost regimen. Furthermore, virus-specific cytotoxic activity of spleen cells derived from DNA prime-protein boost vaccinated mice was elicited. In addition, the DNA prime-protein boost vaccine resulted in protection of 75% of mice from lethal CVB3 challenge and a significant reduction of viral load in sera of immunized mice after acute CVB3 infection. There was a significant reduction in myonecrosis and infiltrating myocardial immune cells indicating reduced severity of myocarditis in surviving mice. These findings demonstrated that a DNA prime-protein boost immunization strategy, but not a DNA vaccine or protein vaccine alone, was effective in eliciting both humoral and cell-mediated immune responses against CVB3 infection in mice and might be a promising vaccine candidate.

Propan-1-aminium 3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate N,N-dimethyl-formamide Monosolvate

Acta Crystallographica. Section E, Structure Reports Online. Jun, 2011  |  Pubmed ID: 21754750

In the anion of the title solvated molecular salt, C(3)H(10)N(+)·C(9)H(3)Br(4)O(4) (-)·C(3)H(7)NO, the dihedral angles formed by the aromatic ring and the mean planes of the carboxyl-ate and meth-oxy-carbonyl groups are 64.3 (3) and 75.2 (3)°, respectively. The C atoms of the propan-1-aminium cation are disordered over two sets of sites in a 0.65 (3):0.35 (3) ratio. The crystal structure is stabilized by N-H⋯O hydrogen bonds.

Interleukin 17A Promotes Hepatocellular Carcinoma Metastasis Via NF-kB Induced Matrix Metalloproteinases 2 and 9 Expression

PloS One. , 2011  |  Pubmed ID: 21760911

BACKGROUND:  IL-17A is a pro-inflammatory cytokine that plays important role in inflammatory disease pathology and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the progression of hepatocellular carcinoma (HCC). METHODOLOGY AND PRINCIPAL FINDING: Expression pattern of IL-17A in clinical HCC samples (n = 43) was determined by immunohistochemistry staining. Transcript levels of MMP2, MMP9 and IL-17A were measured in another 50 pairs (including tumor and related non-tumor tissues) HCC samples. Cell growth, focus formation, cell migration, invasion and western blot assays were used to characterize the functional and signaling mechanisms in IL-17A-treated HCC. Association study was used to identify clinical significance of IL-17A in HCC. Compared with paired non-tumor tissue, higher frequency of IL-17A-positive cells was detected in tumor tissues in HCCs with metastasis, and the frequency of IL-17A-positive cells was also significantly associated with poor prognosis of HCC (P = 0.01). Functional study found that IL-17A could promote HCC cell migration and invasion. Further molecular analysis also showed that IL-17A could upregulate MMP2 and MMP9 expression via NF-κB signaling activation. CONCLUSIONS:  IL-17A could promote HCC metastasis by the upregulation of MMP2 and MMP9 expression via activating NF-κB signaling pathway.

Anti-inflammatory Amino Acid Derivatives from the Ascidian Herdmania Momus

Journal of Natural Products. Aug, 2011  |  Pubmed ID: 21770369

Four new amino acid derivatives, herdmanines A-D (1-4), were isolated from the marine ascidian Herdmania momus. Herdmanines A-C contain the unusual D-form of arginine. Compounds 3 and 4 had a moderate suppressive effect on the production of NO, with IC₅₀ values of 96 and 9 μM, respectively. These compounds were found to inhibit the mRNA expression of iNOS. The inhibitory activities on the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were evaluated.

Aortic Aneurysm Generation in Mice with Targeted Deletion of Integrin-linked Kinase in Vascular Smooth Muscle Cells

Circulation Research. Sep, 2011  |  Pubmed ID: 21778429

Integrin-linked kinase (ILK) is located at focal adhesions and links the extracellular matrix (ECM) to the actin cytoskeleton via β1- and β3-integrins. ILK plays a role in the activation of kinases including protein kinase B/Akt and glycogen synthase kinase 3β and regulates cell proliferation, motility, and survival.

[Investigation on Bookstore Block-printed Editions of Zheng He Ben Cao in Ming Dynasty]

Zhonghua Yi Shi Za Zhi (Beijing, China : 1980). May, 2011  |  Pubmed ID: 21781550

Many editions of Zheng He Ben Cao was published in Ming Dynasty. The bookstore block-printed editions recorded are Liu's Rixintang Edition in Zhengde year 14 (1519 AD), Yangxianchun Gui Renzai Edition and Jinling Tang's Fuchuntang Edition in Wanli year 6 (1578 AD). Rixintang Edition took Chenghua year 4 (1478 AD) Edition as source text and inherited the mistakes too. Guirenzai Version took Rixintang Version as source text, thereafter, Fuchuntang version took Guirenzai Version. Errors, missing, rough collation handed down from one version to another, thus in Fuchuntang Version, mistakes jumped out on each page. In order to attract more buyers, the bookstores erase the name Chong Xiu Zheng He Jing Shi Zheng Lei Bei Yong Ben Cao and change the name to Da Guan Ben Cao Gang Mu Quan Shu or Da Guan Ben Cao.

Hypoglycemic Effects and Constituents of the Barks of Cyclocarya Paliurus and Their Inhibiting Activities to Glucosidase and Glycogen Phosphorylase

Fitoterapia. Oct, 2011  |  Pubmed ID: 21784137

The various fractions of the barks of Cyclocarya paliurus were systematically tested for hypoglycemic effects in alloxan-induced diabetic rats. The results showed that the chloroform fraction of the 75% EtOH extract of the barks of this plant exhibited significant blood sugar reducing activity, most of which were significantly higher than that of positive-drug metformin hydrochloride. A new compound, together with nine known compounds, was isolated from the most active fraction. The structure elucidation was based on spectroscopic methods, including two-dimensional NMR experiments (¹H-¹H COSY, HMQC, and HMBC). All of the isolates were evaluated for their α-glycosidase and glycogen phosphorylase inhibitory activities.

Multi-input Multi-output Underwater Communications over Sparse and Frequency Modulated Acoustic Channels

The Journal of the Acoustical Society of America. Jul, 2011  |  Pubmed ID: 21786895

This paper addresses multi-input multi-output (MIMO) communications over sparse acoustic channels suffering from frequency modulations. An extension of the recently introduced SLIM algorithm, which stands for sparse learning via iterative minimization, is presented to estimate the sparse and frequency modulated acoustic channels. The extended algorithm is referred to as generalization of SLIM (GoSLIM). The sparseness is exploited through a hierarchical Bayesian model, and because GoSLIM is user parameter free, it is easy to use in practical applications. Moreover this paper considers channel equalization and symbol detection for various MIMO transmission schemes, including both space-time block coding and spatial multiplexing, under the challenging channel conditions. The effectiveness of the proposed approaches is demonstrated using in-water experimental measurements recently acquired during WHOI09 and ACOMM10 experiments.

Correction of Rabbit Model With Mandibular Ramus Shortening by Distraction Osteogenesis at Condylar Neck

Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. Jul, 2011  |  Pubmed ID: 21764198

PURPOSE: The rabbit model has been established to mimic the effect of temporomandibular joint (TMJ) arthroplasty of ankylosis, and distraction at the level of the condylar neck is used to elongate the ascending ramus. The histomorphologic changes of TMJ and distraction gap were investigated. MATERIALS AND METHODS: The unilateral condyles and articular discs were extirpated, and the experimental mandibular rami were shortened by 5 mm. An embedded distracter was used to restore the height of the mandibular ramus by unilateral condylar neck distraction (0.8 mm daily for 7 days). A total of 12 adult white rabbits were used, 8 in the experimental group and 4 in the control group. Of the 8 rabbits in the experimental group, 4 each were killed at 4 and 8 weeks after completion of distraction. The TMJ and distracted calluses were harvested and processed for radiographic and histologic examination. RESULTS: An open bite was seen in all rabbits postoperatively that had diminished at the end of distraction. The newly formed condyles radiologically showed remodeling, flattening, and sclerosis. The bony transport disc had gradually remodeled to a new condyle that was similar to the original condyle in appearance and structure. The surface of the transport disc was covered with a fibrous tissue. Moreover, the bony regeneration was perfect in the distraction gap. CONCLUSION: These results suggest that distraction osteogenesis at the condylar neck using the traditional preauricular approach of TMJ surgery, without the additional incision, can be performed concurrently with arthroplasty of TMJ ankylosis at the same region.

2-Methyl-propan-2-aminium 3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate Methanol Monosolvate

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754148

In the crystal structure of the title compound, C(4)H(12)N(+)·C(9)H(3)Br(4)O(4) (-)·CH(4)O, inter-molecular O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds link the components into columns stacked along the b axis. Between the columns, short Br⋯O contacts [3.122 (4) Å] and C-H⋯O hydrogen bonds are observed.

(E)-3-(1-Methyl-1H-pyrrol-2-yl)-1-phenyl-prop-2-en-1-one

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754169

The crystal structure of the title compound, C(14)H(13)NO, exhibits an E configuration. The conjugated compound is slightly twisted with a dihedral angle of 29.3° between the benzene and pyrrole rings. Two inter-molecular C-H⋯O inter-actions lead to a dimer. In the crystal, intermolecular C-H⋯O interactions generate an inversion dimer.

2-Methyl-anilinium 3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate Methanol Monosolvate

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754174

In the anion of the title compound, C(7)H(10)N(+)·C(9)H(3)Br(4)O(4) (-)·CH(3)O, the dihedral angles formed by the benzene ring and the mean planes of the carboxyl-ate and meth-oxy-carbonyl groups are 74.8 (5) and 75.0 (5)°, respectively. In the crystal, inter-molecular N-H⋯O and O-H⋯O hydrogen bonds link the components into chains along [100]. Additional stabilization is provided by weak inter-molecular C-H⋯O hydrogen bonds.

Hexane-1,6-diaminium Bis-[3,4,5,6-tetra-chloro-2-(meth-oxy-carbon-yl)benzoate]

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754175

In the anion of the title salt, C(6)H(18)N(2) (2+)·2C(9)H(3)Cl(4)O(4) (-), the meth-oxy-carbonyl and carboxyl groups are aligned at dihedral angles of 71.0 (3) and 100.9 (3)°, respectively, with the aromatic ring. The asymmetric unit contains half a cation and one anion. In the crystal, inter-molecular N-H⋯O, C-H⋯Cl and C-H⋯O hydrogen bonds link the components into a three-dimensional network.

16-Isopropyl-5,9-dimethyl-tetra-cyclo-[10.2.2.0.0]hexa-dec-15-ene-5,13,14-trimethanol Ethanol Monosolvate

Acta Crystallographica. Section E, Structure Reports Online. May, 2011  |  Pubmed ID: 21754399

The title compound, C(24)H(40)O(3)·C(2)H(6)O, is a substituted tetra-cyclo-[10.2.2.0(1,10).0(4,9)]hexa-decane derivative obtained from the reduction of maleopimaric acid which was isolated from a maleic anhydride modified rosin. In the crystal, the triol mol-ecule and the ethanol solvent mol-ecule are linked by hydroxyl O-H⋯O hydrogen bonds, giving a two-dimensional network structure.

Role of Insulin Receptors in Myocardial Ischaemia-reperfusion Injury During Cardiopulmonary Bypass

Acta Cardiologica. Jun, 2011  |  Pubmed ID: 21744702

Ischaemia-reperfusion injury after cardiac bypass causes cardiac dysfunction and tissue damage. Insulin resistance during reperfusion contributes to the dysfunction, but the role of changes in myocardial insulin receptors during this period has not been determined yet.

Antibacterial Polyketides from the Jellyfish-derived Fungus Paecilomyces Variotii

Journal of Natural Products. Aug, 2011  |  Pubmed ID: 21744790

Four new polyketides (1-4) were isolated from the fungus Paecilomyces variotii, which was derived from the jellyfish Nemopilema nomurai. The planar structures and relative configurations of these polyketides were elucidated on the basis of spectroscopic analyses, including 2D NMR experiments. The compounds showed inhibitory activity against pathogenic bacteria including methicillin-resistant Staphylococcus aureus 3089 and multi-drug-resistant Vibrio parahemolyticus 7001 with MIC values in the range 5-40 μg/mL.

Genetic Association Study of Common Mitochondrial Variants on Body Fat Mass

PloS One. , 2011  |  Pubmed ID: 21747914

Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β) was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³) and body fat mass (adjusted P = 5.67×10⁻⁴) Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.

[Triterpenoid Saponins of Alternanthera Philoxeroides (Mart.) Griseb]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Apr, 2011  |  Pubmed ID: 21751496

In order to find the anti-virus constituents of Alternanthera philoxeroides (Mart.) Griseb, the investigation was carried out. The paper reported the five triterpenoid saponins isolated from n-BuOH fraction: 3-O-beta-D-glucopyranosyl (1-->3)-O-[beta-D-glucopyranosyl-oleanolic acid]-28-O-beta-D-glucuronopyranoside (1), oleanolic acid-3-O-beta-D-glucuronopyranoside (calenduloside E, 2), oleanolic acid-3-O-beta-D-glucopyranosyl-28-Obeta-D-glucopyranosyl ester (chikusetsusaponin-IVa, 3), 3-O-(6'-O-butyl-beta-D-glucuronopyranosyl)-oleanolic acid-28-O-beta-D-glucopyranosyl ester (4) and hederagenin-3-O-beta-D-glucuronopyranoside (HN-sapoins K, 5). 1 is a new compound, saponins 4 and 5 were isolated from the plant for the first time.

Cyclo-hexa-naminium 3,4,5,6-tetra-chloro-2-(meth-oxy-carbon-yl)benzoate

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754124

In the title compound, C(6)H(14)N(+)·C(9)H(3)Cl(4)O(4) (-), the cyclo-hexane ring of the cation adopts a chair conformation. In the anion, the mean planes of the meth-oxy-carbonyl and carboxyl-ate groups form dihedral angles of 67.3 (3) and 55.7 (3)°, respectively, with the benzene ring. In the crystal, inter-molecular N-H⋯O hydrogen bonds connect the components into chains along [100].

2-Hy-droxy-ethanaminium 3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate Methanol Monosolvate

Acta Crystallographica. Section E, Structure Reports Online. Apr, 2011  |  Pubmed ID: 21754146

In the title compound, C(2)H(8)NO(+)·C(9)H(3)Br(4)O(4) (-)·CH(4)O, inter-molecular N-H⋯O and O-H⋯O hydrogen bonds link the components into chains along [001].

Cohesin Selectively Binds and Regulates Genes with Paused RNA Polymerase

Current Biology : CB. Oct, 2011  |  Pubmed ID: 21962715

The cohesin complex mediates sister chromatid cohesion and regulates gene transcription. Prior studies show that cohesin preferentially binds and regulates genes that control growth and differentiation and that even mild disruption of cohesin function alters development. Here we investigate how cohesin specifically recognizes and regulates genes that control development in Drosophila.

Long-range Massively Parallel Mate Pair Sequencing Detects Distinct Mutations and Similar Patterns of Structural Mutability in Two Breast Cancer Cell Lines

Cancer Genetics. Aug, 2011  |  Pubmed ID: 21962895

Cancer genomes frequently undergo genomic instability resulting in accumulation of chromosomal rearrangement. To date, one of the main challenges has been to confidently and accurately identify these rearrangements by using short-read massively parallel sequencing. We were able to improve cancer rearrangement detection by combining two distinct massively parallel sequencing strategies: fosmid-sized (36 kb on average) and standard 5 kb mate pair libraries. We applied this combined strategy to map rearrangements in two breast cancer cell lines, MCF7 and HCC1954. We detected and validated a total of 91 somatic rearrangements in MCF7 and 25 in HCC1954, including genomic alterations corresponding to previously reported transcript aberrations in these two cell lines. Each of the genomes contains two types of breakpoints: clustered and dispersed. In both cell lines, the dispersed breakpoints show enrichment for low copy repeats, while the clustered breakpoints associate with high copy number amplifications. Comparing the two genomes, we observed highly similar structural mutational spectra affecting different sets of genes, pointing to similar histories of genomic instability against the background of very different gene network perturbations.

Psychometric Assessment of HIV/STI Sexual Risk Scale Among MSM: a Rasch Model Approach

BMC Public Health. , 2011  |  Pubmed ID: 21970669

Little research has assessed the degree of severity and ordering of different types of sexual behaviors for HIV/STI infection in a measurement scale. The purpose of this study was to apply the Rasch model on psychometric assessment of an HIV/STI sexual risk scale among men who have sex with men (MSM).

Preliminary Study on the Mechanism of Acupoint Injection of Bone Marrow Mesenchymal Stem Cells in Improving Blood Flow in the Rat of Hind Limb Ischemia

Journal of Traditional Chinese Medicine = Chung I Tsa Chih Ying Wen Pan / Sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine. Sep, 2011  |  Pubmed ID: 21977870

To explore the mechanism of acupoint injection of bone marrow mesenchymal stem cells (BM-MSCs) in improving blood flow in the rat with hind limb ischemia.

[Method and Effectiveness of Arthroscopic Debridement for Treating Gouty Arthritis of the Knee]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Aug, 2011  |  Pubmed ID: 21923020

To investigate the method and the effectiveness of a combination of the arthroscopic debridement and joint irrigation postoperatively for treating gouty arthritis of the knee.

Complexation of 1,4-bis(pyridinium)butanes by Negatively Charged Carboxylatopillar[5]arene

The Journal of Organic Chemistry. Oct, 2011  |  Pubmed ID: 21923191

The binding behavior of substituted 1,4-bis(pyridinium)butane derivatives (X-Py(CH(2))(4)Py-X, X = H, 2-methyl, 3-methyl, 4-methyl, 2,6-dimethyl, 4-pyridyl, and 4-COOEthyl) 1(2+)-7(2+), with negatively charged carboxylatopillar[5]arene (CP5A) has been comprehensively investigated by (1)H NMR and 2D ROESY and UV absorption and fluorescence spectroscopy in aqueous phosphate buffer solution (pH 7.2). The results indicated that the position of the substituents attached on pyridinium ring dramatically affects the association constants and binding modes. 3- and 4-Substituted guests (1(2+), 3(2+), 4(2+), 6(2+), 7(2+)) form [2]pseudorotaxane geometries with CP5A host, giving very large association constants (>10(5) M(-1)), while 2,6-dimethyl-substituted 5(2+) forms external complex with relatively small K(a) values [(2.4 ± 0.3) × 10(3) M(-1)] because the 2,6-dimethylpyridinium unit is too bulky to thread the host cavity. Both of the binding geometries mentioned above are observed for 2(2+), having one methyl group in the 2-position of pyridinium. Typically, the association constant of [2]pseudorotaxane 1(2+)⊂CP5A exceeds 10(6) M(-1) in water, which is significantly higher than those of previously reported analogues in organic solvents. The remarkably improved complexation of bis(pyridinium) guests by the anionic host was due to electrostatic attraction forces and hydrophobic interactions.

Effect of Colistin Exposure and Growth Phase on the Surface Properties of Live Acinetobacter Baumannii Cells Examined by Atomic Force Microscopy

International Journal of Antimicrobial Agents. Dec, 2011  |  Pubmed ID: 21925844

The diminishing antimicrobial development pipeline has forced the revival of colistin as a last line of defence against infections caused by multidrug-resistant Gram-negative 'superbugs' such as Acinetobacter baumannii. The complete loss of lipopolysaccharide (LPS) mediates colistin resistance in some A. baumannii strains. Atomic force microscopy was used to examine the surface properties of colistin-susceptible and -resistant A. baumannii strains at mid-logarithmic and stationary growth phases in liquid and in response to colistin treatment. The contribution of LPS to surface properties was investigated using A. baumannii strains constructed with and without the lpxA gene. Bacterial spring constant measurements revealed that colistin-susceptible cells were significantly stiffer than colistin-resistant cells at both growth phases (P<0.01), whilst colistin treatment at high concentrations (32 mg/L) resulted in more rigid surfaces for both phenotypes. Multiple, large adhesive peaks frequently noted in force curves captured on colistin-susceptible cells were not evident for colistin-resistant cells. Adhesion events were markedly reduced following colistin exposure. The cell membranes of strains of both phenotypes remained intact following colistin treatment, although fine topographical details were illustrated. These studies, conducted for the first time on live A. baumannii cells in liquid, have contributed to our understanding of the action of colistin in this problematic pathogen.

Novel Neutral Guest Recognition and Interpenetrated Complex Formation from Pillar[5]arenes

Chemical Communications (Cambridge, England). Oct, 2011  |  Pubmed ID: 21927747

Simple alkyl-substituted pillar[5]arenes can form stable interpenetrated complexes with neutral bis(imidazole) guests utilizing multiple C-H···O(N) hydrogen bond and C-H···π interactions.

[Effects of Reduced Solar Radiation on Winter Wheat Flag Leaf Net Photosynthetic Rate]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jun, 2011  |  Pubmed ID: 21941745

Taking winter wheat Triticum aestivum L. (cv. Yangmai 13) as test material, a field experiment was conducted in Nanjing City to study the effects of simulated reduced solar radiation on the diurnal variation of winter wheat flag leaf photosynthetic rate and the main affecting factors. Five treatments were installed, i. e., 15% (T15), 20% (T20) , 40% (T40), 60% (T60), and 100% (CK) of total incident solar radiation. Reduced solar irradiance increased the chlorophyll and lutein contents significantly, but decreased the net photosynthetic rate (Pn). Under different solar irradiance, the diurnal variation of Pn had greater difference, and the daily maximum Pn was in the order of CK > T60 > T40 > T 20 > T15. In CK, the Pn exhibited a double peak diurnal curve; while in the other four treatments, the Pn showed a single peak curve, and the peak was lagged behind that of CK. Correlation analysis showed that reduced solar irradiance was the main factor affecting the diurnal variation of Pn, but the physiological parameters also played important roles in determining the diurnal variation of Pn. In treatments T60 and T40, the photosynthesis active radiation (PAR), leaf temperature (T1) , stomatal conductance (Gs) , and transpiration rate (Tr) were significantly positively correlated with Pn, suggesting their positive effects on Pn. The intercellular CO2 concentration (Ci) and stomatal limitation (Ls) had significant negative correlations with Pn in treatments T60 and T40 but significant positive correlations with Pn in treatments T20 and T15, implying that the Ci and Ls had negative (or positive) effects on Pn when the solar irradiance was higher (or lower) than 40% of incident solar irradiance.

[Short-term Clinical Observation of Modified Resin-bonded Fixed Partial Denture Utilizing Tooth Undercuts]

Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology. Jun, 2011  |  Pubmed ID: 21914374

To observe a short-term clinical result of modified resin-bonded fixed partial denture(MRBFPD) utilizing tooth undercuts.

A New Malaria Antigen Produces Partial Protection Against Plasmodium Yoelii Challenge

Parasitology Research. Sep, 2011  |  Pubmed ID: 21915626

Of all the parasitic diseases, malaria is the number one killer. Despite tremendous efforts in disease control and research, nearly a million people, primarily children, still die from the disease each year, partly due to drug resistance and the lack of an effective vaccine. Many parasite antigens have been identified and evaluated for vaccine development; however, none has been approved for human use. Antigenic variation, complex life cycle, and inadequate understanding of the mechanisms of parasite-host interaction and of host immune response all contribute to the lack of an effective vaccine for malaria control. In a recent search of genome-wide polymorphism in Plasmodium falciparum, several molecules were found to be recognized by sera from patients infected with the P. falciparum parasite. Here, we have expressed a 350-amino acid N terminus from one of the homologous candidate antigen genes from the rodent malaria parasite Plasmodium yoelii (Py01157, a putative dentin phosphorin) in bacteria and evaluated the immune response and protection generated after immunization with the recombinant protein. We showed that the recombinant protein was recognized by sera from both mice and humans infected with malaria parasites. Partial protection was observed after challenge with non-lethal P. yoelii 17XNL but not with the lethal P. yoelii 17XL parasite. Further tests using a full-length protein or the conserved C terminus may provide additional information on whether this protein has the potential for being a malaria vaccine.

Behavioral and Neural Properties of Social Reinforcement Learning

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2011  |  Pubmed ID: 21917787

Social learning is critical for engaging in complex interactions with other individuals. Learning from positive social exchanges, such as acceptance from peers, may be similar to basic reinforcement learning. We formally test this hypothesis by developing a novel paradigm that is based on work in nonhuman primates and human imaging studies of reinforcement learning. The probability of receiving positive social reinforcement from three distinct peers was parametrically manipulated while brain activity was recorded in healthy adults using event-related functional magnetic resonance imaging. Over the course of the experiment, participants responded more quickly to faces of peers who provided more frequent positive social reinforcement, and rated them as more likeable. Modeling trial-by-trial learning showed ventral striatum and orbital frontal cortex activity correlated positively with forming expectations about receiving social reinforcement. Rostral anterior cingulate cortex activity tracked positively with modulations of expected value of the cues (peers). Together, the findings across three levels of analysis--social preferences, response latencies, and modeling neural responses--are consistent with reinforcement learning theory and nonhuman primate electrophysiological studies of reward. This work highlights the fundamental influence of acceptance by one's peers in altering subsequent behavior.

Computational Methods for Epigenetic Analysis: the Protocol of Computational Analysis for Modified Methylation-specific Digital Karyotyping Based on Massively Parallel Sequencing

Methods in Molecular Biology (Clifton, N.J.). , 2011  |  Pubmed ID: 21913089

Massively parallel sequencing technology opens new possibilities for epigenetic research. Many methods have been developed based on the new sequencing platforms, allowing an ultra-deep mapping of epigenetic variants in a fast and cost-effective way. However, handling millions of short reads produced by these sequencing platforms is a huge challenge for many laboratories. Thus, there is a need for the development of accurate and fast computational tools for epigenetic studies in the new era of genomic sequencing.Modified methylation-specific digital karyotyping (MMSDK) is an improved method for genome-wide DNA methylation profiling based on the combination of traditional MSDK and Illumina/Solexa sequencing. Here, we introduce our computational tools used in the MMSDK analysis process from the experimental design to statistical analysis. We have developed a mapping process based on the in silico simulation of combined enzyme cutting and tag extraction of the reference genome. Subsequently, the 20-21 nucleotides (nt) long tags obtained by sequencing are mapped to the simulated library using an open source software Mapping and Assembly with Qualities. Our computational methods include trimming, annotation, normalization, and counting the reads to obtain digital DNA methylation profiles. We present the complete protocol and discuss some important issues that should be considered by readers, such as handling of repeat sequences, SNPs, and normalization. The core part of this protocol (mapping and annotation of tags) is suitable for any tag profiling-based methods, and it could also be modified to analyze results from other types of epigenetic studies based on massively parallel sequencing.

Dihydroartemisinin Induces Endoplasmic Reticulum Stress-mediated Apoptosis in HepG2 Human Hepatoma Cells

Tumori. Nov-Dec, 2011  |  Pubmed ID: 22322845

Aims and background. Previous studies showed that dihydroartemisinin (DHA) possessed antitumor activity in many human tumor cells through the induction of apoptosis. The aim of this study was to investigate the effects of DHA on apoptosis in the human hepatocellular carcinoma cell line HepG2 and the possible molecular mechanisms involved. Methods. The inhibitory effect of DHA on HepG2 cells was measured by MTT assay. The percentage of apoptotic cells was detected by flow cytometry with double staining of fluorescein isothiocyanate-annexin V/propidium iodide. The intracellular production of reactive oxygen species (ROS) and intracellular Ca2+ concentration ([Ca2+]i) were detected by fluorescence spectrophotometry. Protein expression of GADD153, Bcl-2 and Bax in HepG2 cells was examined by Western blot and immunocytochemistry. Results. DHA significantly inhibited proliferation of HepG2 cells in a dose- and time-dependent manner. The apoptosis rates in HepG2 cells treated with 0, 50, 100 and 200 μmol/L DHA for 24 hours were 2.53 ± 0.88%, 24.85 ± 3.63%, 35.27 ± 5.92% and 48.53 ± 7.76%, respectively. Compared with the control group, DHA significantly increased ROS generation and [Ca2+]i level (P <0.05), with the generation of ROS preceding the increase in [Ca2+]i. An increase in GADD153 and Bax expression and a decrease in Bcl-2 were observed in DHA-treated cells. Pretreatment with the antioxidant N-acetylcysteine could attenuate the effects of DHA in the experiments. Conclusion. DHA could inhibit proliferation and induce apoptosis in HepG2 cell lines through increasing the intracellular production of ROS and [Ca2+]i. Endoplasmic reticulum stress-induced apoptosis may contribute to this effect by regulating the expression of GADD153, proapoptotic Bax, and antiapoptotic Bcl-2.

[The Relationship Between the Intraoperative Hypothermia and the Residual Neuromuscular of Single Intubation Dose of Vecuronium]

Zhonghua Yi Xue Za Zhi. Nov, 2011  |  Pubmed ID: 22333063

To study the relationship between the intraoperative hypothermia and the residual neuromuscular of single intubation dose of vecuronium.

[Screening of Serum Marker Proteins in Osteosarcoma and Preliminary Bioinformatic Analysis on POLR3F]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Nov, 2011  |  Pubmed ID: 22335949

To screen potential serum marker proteins of osteosarcoma, and to make a preliminary bioinformatics analysis of RNA polymerase III polypeptide F (POLR3F).

[Preliminary Study on Detection of Echinococcus Granulosus DNA by Loop-mediated Isothermal Amplification]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Oct, 2011  |  Pubmed ID: 22263510

To evaluate the sensitivity of loop-mediated isothermal amplification (LAMP) on the detection of Echinococcus granulosus.

Hexane-1,6-diaminium Bis-[3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate] Methanol Disolvate

Acta Crystallographica. Section E, Structure Reports Online. Oct, 2011  |  Pubmed ID: 22058736

In the title compound, C(6)H(18)N(2) (2+)·2C(9)H(3)Br(4)O(4) (-)·2CH(4)O, the carboxyl-ate and meth-oxy-carbonyl groups in one of the anions form dihedral angles of 71.9 (3) and 60.7 (3)°, respectively, with the aromatic ring while in the other anion these angles are 68.4 (3) and 56.8 (3)°, respectively. In the crystal, the constituent units are linked into a two-dimensional network parallel to the ab plane by N-H⋯O and O-H⋯O hydrogen bonds.

Temporal Dissection of Tumorigenesis in Primary Cancers

Cancer Discovery. Jul, 2011  |  Pubmed ID: 21984974

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for two separate cancer types. We detect vast, unreported expansion of simple mutation sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCCs) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.

[Spectroscopic Study of Photocatalytic Mechanism of Methanol and CO2]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Dec, 2011  |  Pubmed ID: 22295787

Ni-Ti-O/SiO2 catalyst was prepared by impregnation method, and its photocatalytic performance for carbonylation of methanol with CO2 was investigated under UV light. The in-situ IR, XPS and MS were carried out to analyze the possible photocatalytic reaction mechanism. Results indicated that the Ni-Ti-O/SiO2 exhibited good photocatalytic performance for carbonylation of methanol with CO2, the methanol conversion reached up to 24.9%, and the selectivity for the carbonylated products was more than 60% within 180 min reaction time. The catalyst characterization results showed that the O==C .--O- and CH3OC(O)* might be important intermediate in the carbonylation of methanol with CO2.

Psychometric Properties and Differential Explanation of a Short Measure of Effort-reward Imbalance at Work: A Study of Industrial Workers in Germany

American Journal of Industrial Medicine. Feb, 2012  |  Pubmed ID: 22298287

BACKGROUND: We test the psychometric properties of a short version of the Effort-Reward Imbalance (ERI) questionnaire in addition to testing an interaction term of this model's main components on health functioning. METHODS: A self-administered survey was conducted in a sample of 2,738 industrial workers (77% men with mean age 41.6 years) from a large manufacturing company in Southern Germany. The internal consistency reliability, structural validity, and criterion validity were analyzed. RESULTS: Satisfactory internal consistencies of the three scales: "Effort", "reward", and "overcommitment", were obtained (Cronbach's alpha coefficients 0.77, 0.82, and 0.83, respectively). Confirmatory factor analysis showed a good model fit of the data with the theoretical structure (AGFI = 0.94, RMSEA = 0.060). Evidence of criterion validity was demonstrated. Importantly, a significant synergistic interaction effect of ERI and overcommitment on poor mental health functioning was observed (odds ratio 6.74 (95% CI 5.32-8.52); synergy index 1.78 (95% CI 1.25-2.55)). CONCLUSIONS: This short version of the ERI questionnaire is a reliable and valid tool for epidemiological research on occupational health. Am. J. Ind. Med. © 2012 Wiley Periodicals, Inc.

Modeling of MiRNA and Drug Action in the EGFR Signaling Pathway

PloS One. , 2012  |  Pubmed ID: 22253908

MicroRNAs have gained significant interest due to their widespread occurrence and diverse functions as regulatory molecules, which are essential for cell division, growth, development and apoptosis in eukaryotes. The epidermal growth factor receptor (EGFR) signaling pathway is one of the best investigated cellular signaling pathways regulating important cellular processes and its deregulation is associated with severe diseases, such as cancer. In this study, we introduce a systems biological model of the EGFR signaling pathway integrating validated miRNA-target information according to diverse studies, in order to demonstrate essential roles of miRNA within this pathway. The model consists of 1241 reactions and contains 241 miRNAs. We analyze the impact of 100 specific miRNA inhibitors (anit-miRNAs) on this pathway and propose that the embedded miRNA-network can help to identify new drug targets of the EGFR signaling pathway and thereby support the development of new therapeutic strategies against cancer.

Suppression of Pain and Joint Destruction by Inhibition of the Proteasome System in Experimental Osteoarthritis

Pain. Jan, 2012  |  Pubmed ID: 22018973

Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate into the rat knee. Knee joint stiffness was scored and nociception was evaluated by mechanical pressure applied to the respective hind paw. Knee joint destruction was assessed by radiological and histological analyses. Expression of matrix metalloproteinase-3 (MMP-3) was analyzed by quantitative reverse transcription polymerase chain reaction in the knee articular cartilage. Expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was studied in the dorsal root ganglia (L4-L6) by quantitative reverse transcription polymerase chain reaction and in the knee joints by immunohistochemistry. Our results indicate that daily treatment of osteoarthritic rats with MG132 significantly increases their mobility while the swelling, pain thresholds, and pathological features of the affected joints were reduced. Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.

C-reactive Protein Promotes Adhesion of Monocytes to Endothelial Cells Via NADPH Oxidase-mediated Oxidative Stress

Journal of Cellular Biochemistry. Mar, 2012  |  Pubmed ID: 22020763

Enhanced monocyte adhesion to endothelial cells is an early event in atherogenesis. It has been shown that C-reactive protein (CRP) plays a key role in atherogenesis. Here, we investigated the effects of CRP on monocyte-endothelial cell adhesion and tested the hypothesis that NADPH oxidase (NOX)-mediated oxidative stress might play a key role in CRP-induced monocyte-endothelial cell adhesion. Firstly, 36 patients with carotid intima-media thickness (IMT) incrassation and 34 controls were enrolled in this study. The levels of glucose, lipids, CRP, monocyte chemotractant protein (MCP-1), malondialdehyde (MDA), and protein carbonylation were analyzed. The results showed that carotid IMT was associated with abnormal lipid metabolism, including elevated CRP, triglycerides (TG) (P < 0.01) and decreased high density lipoprotein (HDL) level (P < 0.05). The levels of CRP and MCP-1 in patients with carotid IMT incrassation were increased compared with the controls (P < 0.01). Moreover, patients with carotid IMT incrassation displayed enhanced MDA and protein carbonylation levels (P < 0.01), accompanied by activation and up-regulation of NOX in monocytes (P < 0.05) compared with the controls. The monocytes isolated from five healthy donors were used for in vitro experiments. Reactive oxygen species (ROS) production and NOX expression in monocytes were examined. The results also indicated that CRP could promote the adhesion of monocyte-endothelial cell by up-regulation of MCP-1 expression (P < 0.05). Importantly, NFκ B and p38 MAPK signaling pathways, which were activated by NOX-derived ROS, were involved in CRP-induced monocyte-endothelial cell adhesion and up-regulation of MCP-1 expression. These data suggested that CRP could promote the adhesion of monocytes to endothelial cells via NOX-mediated oxidative stress. J. Cell. Biochem. 113: 857-867, 2012. © 2011 Wiley Periodicals, Inc.

Loading 3-deazaneplanocin A into Pegylated Unilamellar Liposomes by Forming Transient Phenylboronic Acid-drug Complex and Its Pharmacokinetic Features in Sprague-Dawley Rats

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V. Feb, 2012  |  Pubmed ID: 22061261

3-Deazaneplanocin A (DZNep) is an attractive epigenetic anticancer agent through the inhibition of the cellular enhancer of zeste homolog 2 (EZH2) protein. The purpose of this study was to improve the pharmacokinetic characteristics of DZNep in vivo through developing a unilamellar pegylated liposomal formulation encapsulating DZNep (L-DZNep). A remote-loading method in the presence of phenylboronic acid (R-w-PBA) was developed to stably encapsulating DZNep inside liposomes (encapsulation efficiency=50.7% at molar ratio of 1:10 of drug to lipids) through forming a transient PBA-DZNep complex. The pharmacokinetics of L-DZNep was investigated in Sprague-Dawley rats. In comparison with free drug, encapsulation of the DZNep in pegylated liposomes resulted in 99.3% reduction of the plasma clearance, whereas it increased the elimination half-life from 1.1h to 8.0h and the area under the plasma concentration curve by 138-fold. These findings demonstrate a novel approach (R-w-PBA method) through the development of L-DZNep, which may be extensively applied for the encapsulation of hydrophilic nucleoside analogs containing vicinal hydroxyl groups and protonable amino in the pegylated liposomes. Additionally, the pegylated liposomes could effectively prolong the retention of DZNep in the systemic circulation and therefore is highly likely to increase the DZNep's tumor localization.

Embryonic Exposure to Benzo(a)pyrene Influences Neural Development and Function in Rockfish (Sebastiscus Marmoratus)

Neurotoxicology. Jan, 2012  |  Pubmed ID: 22265711

Benzo(a)pyrene (BaP) is known to be carcinogenic and teratogenic. Several epidemiological and animal studies report that BaP causes neurological abnormalities; however, the mechanism of BaP-induced impairment of nervous system development and function, particularly in fish, remains unclear. In this study, Sebastiscus marmoratus embryos were exposed to BaP at environmental levels (0.5, 5 and 25nmol/L) for 7 days. The results show disruption of the cranial innervation pattern. The expression of calmodulin (CaM) and Ca(2+)/calmodulin dependent kinase II (CaMKII) was decreased in a dose-dependent manner. BaP exposure reduced the levels of ACh and ChAT and promoted the activity of AChE. In addition, BaP exposure decreased NO concentration in all treatments and increased the activity of NOS in the 0.5 and 5nmol/L groups. These results suggest that BaP could decrease the expression CaM and CaMKII mRNA and NO, which would perturb the cholinergic system and disrupt nervous system development.

MicroRNA-21 Promotes Tumor Proliferation and Invasion in Gastric Cancer by Targeting PTEN

Oncology Reports. Apr, 2012  |  Pubmed ID: 22267008

Gastric cancer is one of the most common carcinomas in China. microRNAs, a type of non-coding RNA, are important specific regulators and are involved in numerous bioprocesses of an organism. microRNA-21 (miR-21) has been identified as the most suitable choice for further investigation because it is overexpressed in nearly all solid tumors; furthermore, it has been demonstrated that miR-21 is involved in the genesis and progression of human cancer. It has been reported that PTEN, an important tumour suppressor, is regulated by multiple miRNAs. Thus, in this study we focused on the expression and significance of miR-21 in gastric cancer tissues, and the role of miR-21 in the biological behaviour and the expression of PTEN in gastric cancer cells. Real-time PCR was used to detect miR-21 expression in gastric cancer tissues, the adjacent normal tissues, and the gastric cell lines. The gastric cancer cell line BGC-823 was transfected with pre-miR-21/miR-21 inhibitor to overexpress/downregulate miR-21. The influence of miR-21 on the biological behaviour of gastric cancer cells was evaluated using the CCK-8 kit, FCMs, the scratch healing assay and the transwell test. Western blotting and the Luciferase Reporter Assay were used to evaluate the change of PTEN expression after lowered expression of miR-21 in gastric cancer cell lines. Real-time PCR analysis indicated that miR-21 exhibited higher expression in gastric cancer tissues compared to the adjacent non-tumor tissues. miR-21 expression was significantly associated with the degree of differentiation of the tumour tissues (P=0.004), as well as local invasion and lymph node metastasis (P<0.01). After transfection, pre-miR21 BGC-823 cells grew faster than the negative and control groups (P<0.01). The reduction in miR-21 expression demonstrated a remarkable effect on the biological behaviour of gastric cancer cells (P<0.05); the pre-miR-21-transfected cells healed more quickly compared to the control cells in the scratch healing assay, whereas the transwell test indicated that cell migration in vitro was notably inhibited with the downregulation of miR-21 (P<0.05). The western blot results and Luciferase Reporter Assay demonstrated that PTEN expression was remarkably increased after miR-21 inhibition (P<0.05). microRNA-21 expression was upregulated in gastric carcinoma tissues and was significantly associated with the degree of differentiation of tumour tissues, local invasion and lymph node metastasis. Overexpression of miR-21 promoted BGC-823 cell growth, invasion and cell migration in vitro, whereas downregulation of miR-21 exhibited a stronger inhibitory effect on the biological behaviour of gastric cancer cells; additionally, miR-21 inhibition may upregulate the PTEN expression level, which indicates that PTEN may be a target gene for gastric cancer initiation and development.

Tanshinone IIA in Acute Promyelocytic Leukemia

The American Journal of the Medical Sciences. Jan, 2012  |  Pubmed ID: 22270391

INTRODUCTION: The prognosis of acute promyelocytic leukemia (APL) has been significantly improved by the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, the utility of these drugs is limited by resistance to ATRA and the side effects of ATO. It has been reported that Tanshinone IIA (Tan IIA), a diterpene quinone isolated from Salvia Miltiorrhiza Bunge, induces apoptosis in the APL cell line, NB4. The effect of Tan IIA on the ATRA-resistant APL cell line (MR2) is unknown. METHODS: In this study, the effects of Tan IIA and ATO, alone and in combination, on MR2 cell apoptosis were investigated using transmission electron microscopy, flow cytometry and Western blot analyses. RESULTS: Nuclear changes typical of apoptosis were observed in Tan IIA-treated MR2 cells. Apoptosis was shown to be induced in a dose- and time-dependent manner with the activation of caspase-3 resulting in upregulation of tumor necrosis factor-α expression, activation of caspase-8 and alteration in mitochondrial transmembrane potential with release of cytochrome c (cyto-c). Tan IIA and ATO acted synergistically on the induction of MR2 cell apoptosis. CONCLUSIONS: These data indicate that Tan IIA may be beneficial in the treatment of ATRA-resistant APL and in combination with ATO for APL therapy in the clinic.

Disposition of Human Recombinant Lubricin in Naive Rats and in a Rat Model of Post-traumatic Arthritis After Intra-articular or Intravenous Administration

The AAPS Journal. Jan, 2012  |  Pubmed ID: 22228117

We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

Fur in Magnetospirillum Gryphiswaldense Influences Magnetosomes Formation and Directly Regulates the Genes Involved in Iron and Oxygen Metabolism

PloS One. , 2012  |  Pubmed ID: 22238623

Magnetospirillum gryphiswaldense strain MSR-1 has the unique capability of taking up large amounts of iron and synthesizing magnetosomes (intracellular magnetic particles composed of Fe(3)O(4)). The unusual high iron content of MSR-1 makes it a useful model for studying biological mechanisms of iron uptake and homeostasis. The ferric uptake regulator (Fur) protein plays a key role in maintaining iron homeostasis in many bacteria. We identified and characterized a fur-homologous gene (MGR_1314) in MSR-1. MGR_1314 was able to complement a fur mutant of E. coli in iron-responsive manner in vivo. We constructed a fur mutant strain of MSR-1. In comparison to wild-type MSR-1, the mutant strain had lower magnetosome formation, and was more sensitive to hydrogen peroxide and streptonigrin, indicating higher intracellular free iron content. Quantitative real-time RT-PCR and chromatin immunoprecipitation analyses indicated that Fur protein directly regulates expression of several key genes involved in iron transport and oxygen metabolism, in addition it also functions in magnetosome formation in M. gryphiswaldense.

Panax Notoginseng and Its Components Decreased Hypertension Via Stimulation of Endothelial-dependent Vessel Dilatation

Vascular Pharmacology. Jan, 2012  |  Pubmed ID: 22239978

Ginsenoside Rb1 and Rg1 are major components of Panax notoginseng (P.N.), an herb with known clinical efficacy in hypertension and myocardial ischemia in Eastern countries. This investigation is to elicit the mechanism of these components in hypertension via their effect on vascular reaction. To assess the ability of P.N. in hypertension, P.N. extracts were injected in spontaneously hypertensive rats (SHR) via the vena caudalis; Low dosages of P.N. extracts significantly lowered blood pressure in SHR. Examination with Rb1 and Rg1 revealed significant vasodilatation using mouse coronary arteries in a dose-dependent manner. Rb1- and Rg1-induced vasodilatation was blocked by pre-incubation with eNOS and PI3K inhibitors. Coronaries of eNOS-/- mice showed attenuated vasodilatation with Rb1 and Rg1. In addition, both Rb1 and Rg1 induce nitric oxide (NO) generation through increasing the phosphorylation of eNOS, activating Na+-independent l-arginine transport, and stimulating cationic amino acid transport (CAT)-1 mRNA expression in cultured endothelial cells. CONCLUSION: Ginsenoside Rb1 and Rg1 increased endothelial-dependent vessel dilatation through the activation of NO by modulating the PI3K/Akt/eNOS pathway and l-arginine transport in endothelial cells. These findings may have important implications for understanding the mechanisms of clinical efficacy of the herb P.N. when used in the regulation of blood pressure.

Effect of Thymosin Alpha-1 on Subpopulations of Th1, Th2, Th17, and Regulatory T Cells (Tregs) in Vitro

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [et Al.]. Jan, 2012  |  Pubmed ID: 22245858

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

High-definition Computed Tomography for Coronary Artery Stent Imaging: a Phantom Study

Korean Journal of Radiology : Official Journal of the Korean Radiological Society. Jan, 2012  |  Pubmed ID: 22247632

To assess the performance of a high-definition CT (HDCT) for imaging small caliber coronary stents (≤ 3 mm) by comparing different scan modes of a conventional 64-row standard-definition CT (SDCT).

Hypertension Prevalence, Awareness, Treatment, Control, and Associated Factors in Adults in Southern China

American Journal of Hypertension. Feb, 2012  |  Pubmed ID: 22337206

BackgroundHypertension is the most important risk factor for cardiovascular diseases. Little information exists on the status of hypertension among southern Chinese. We therefore investigated the hypertension prevalence, awareness, treatment, control, and associated factors in a southern Chinese population with 85 million residents.MethodsStratified multistage cluster sampling with probability proportional to size method was used in this survey. A representative sample of 13,889 residents aged 20 years or above with completed questionnaire and blood pressure (BP) measurement was obtained. BP was measured in accordance with the 1999 World Health Organization/International Society of Hypertension Guidelines. Information related to history of diagnosis and treatment of hypertension was collected through questionnaire.ResultsThe prevalence of hypertension in this population was 20.5% (16.5%, 24.4%), which translated to 9.8 million adults suffering from hypertension in Guangdong province. The urban population had higher prevalence of hypertension than the rural population (25.1 vs. 16.1%). The prevalence of awareness, treatment, and control of hypertension in hypertensive patients living in urban regions were 42.8, 37.9, and 13.5%, respectively, which were higher than those in rural regions (the corresponding figures were 17.6, 10.4, and 3.4%, respectively). Nearly 50% urban adults and 80% rural adults did not measure their BP in the last 12 months. Frequency of BP measurement was associated with both awareness and treatment.ConclusionsHypertension was prevalent in southern China. The prevalence of awareness, treatment, and control of hypertension is low. Urgent strategies are needed to improve prevention, detection, and treatment of hypertension in this large Chinese population.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.11.

Prehypertension in Children and Adolescents: Association with Body Weight and Neck Circumference

Internal Medicine (Tokyo, Japan). , 2012  |  Pubmed ID: 22214619

The present study was undertaken to investigate the role of neck circumference (NC) in predicting prehypertension in children and adolescents.

Normal or Non-diagnostic Neuroimaging Studies Prior to the Detection of Malignant Primary Brain Tumors

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Mar, 2012  |  Pubmed ID: 22277560

We aimed to describe a single institution experience of neuroimaging failure to demonstrate malignant primary brain tumors. We retrospectively reviewed case histories for all newly diagnosed adult patients with malignant primary brain tumors treated at a single institution between 1 July 2006 and 30 June 2008. We specifically looked at patients in whom neuroimaging was normal or non-diagnostic at initial presentation. Among 193 patients with malignant primary brain tumors, there were 102 with World Health Organization (WHO) grade IV gliomas (glioblastoma multiforme, GBM), 54 with anaplastic gliomas, 18 with low grade gliomas, and 19 with primary central nervous system lymphomas (PCNSL). Initial imaging was normal in nine patients and abnormal but non-diagnostic in an additional eight patients with primary brain cancer. Normal or non-diagnostic neuroimaging was not uncommon among patients with GBM. Dramatic, rapid tumor growth is possible. Close interval clinical and radiographic follow-up can be important especially in the management of elderly patients presenting with seizures and non-diagnostic neuroimaging studies.

Prediction in the Face of Uncertainty: A Monte Carlo-based Approach for Systems Biology of Cancer Treatment

Mutation Research. Jan, 2012  |  Pubmed ID: 22285941

Cancer is known to be a complex disease and its therapy is difficult. Much information is available on molecules and pathways involved in cancer onset and progression and this data provides a valuable resource for the development of predictive computer models that can help to identify new potential drug targets or to improve therapies. Modeling cancer treatment has to take into account many cellular pathways usually leading to the construction of large mathematical models. The development of such models is complicated by the fact that relevant parameters are either completely unknown, or can at best be measured under highly artificial conditions. Here we propose an approach for constructing predictive models of such complex biological networks in the absence of accurate knowledge on parameter values, and apply this strategy to predict the effects of perturbations induced by anti-cancer drug target inhibitions on an epidermal growth factor (EGF) signaling network. The strategy is based on a Monte Carlo approach, in which the kinetic parameters are repeatedly sampled from specific probability distributions and used for multiple parallel simulations. Simulation results from different forms of the model (e.g., a model that expresses a certain mutation or mutation pattern or the treatment by a certain drug or drug combination) can be compared with the unperturbed control model and used for the prediction of the perturbation effects. This framework opens the way to experiment with complex biological networks in the computer, likely to save costs in drug development and to improve patient therapy.

Genome-Wide Association Study of Copy Number Variants Suggests LTBP1 and FGD4 Are Important for Alcohol Drinking

PloS One. , 2012  |  Pubmed ID: 22295116

Alcohol dependence (AD) is a complex disorder characterized by psychiatric and physiological dependence on alcohol. AD is reflected by regular alcohol drinking, which is highly inheritable. In this study, to identify susceptibility genes associated with alcohol drinking, we performed a genome-wide association study of copy number variants (CNVs) in 2,286 Caucasian subjects with Affymetrix SNP6.0 genotyping array. We replicated our findings in 1,627 Chinese subjects with the same genotyping array. We identified two CNVs, CNV207 (combined p-value 1.91E-03) and CNV1836 (combined p-value 3.05E-03) that were associated with alcohol drinking. CNV207 and CNV1836 are located at the downstream of genes LTBP1 (870 kb) and FGD4 (400 kb), respectively. LTBP1, by interacting TGFB1, may down-regulate enzymes directly participating in alcohol metabolism. FGD4 plays a role in clustering and trafficking GABA(A) receptor and subsequently influence alcohol drinking through activating CDC42. Our results provide suggestive evidence that the newly identified CNV regions and relevant genes may contribute to the genetic mechanism of alcohol dependence.

The High Mitotic Count Detected by Phospho-histone H3 Immunostain Does Not Alter the Benign Behavior of Angiocentric Glioma

Brain Tumor Pathology. Jan, 2012  |  Pubmed ID: 21892765

Angiocentric glioma (AG) has been formally codified in the revised 2007 WHO Classification of Tumours of the Central Nervous System. AGs characteristically exhibit mixed features of ependymal and diffuse astrocytic differentiation and low proliferation rates, with Ki-67 labeling indices ranging from less than 1 to 5%. A single case with anaplastic recurrence and a labeling index of 10% has been reported. In the present study, we report a series of three AGs (Case 1: 4-year-old girl at right frontal lobe; Case 2: 4-year-old boy at left frontal lobe; Case 3: 9-year-old boy at right temporal lobe). Case 1 with elevated proliferation index (~10%) and increased mitotic activity (six mitoses per 10 high-power fields) on phospho-histone H3 (pHH3) immunostain at presentation, nonetheless, has shown protracted recurrence-free survival after 6 years of follow-up. So far, this is the first report for evaluating the mitotic activity in AGs using pHH3 immunostain.

Anti-HBV Activities of Streblus Asper and Constituents of Its Roots

Fitoterapia. Jan, 2012  |  Pubmed ID: 22305944

The extracts from leaves, heartwood, barks and roots of the Streblus asper were investigated for anti-HBV activities, separately. The results suggested that the MeOH extracts of the heartwood, barks, and roots exhibited good anti-HBV activities. Further investigations displayed that ethyl acetate and n-butanol soluble parts of their MeOH extracts showed more significant anti-HBV activities. Moreover, a new lignan, together with 11 known compounds, was isolated from n-butanol-soluble part of MeOH extract of the roots of S. asper. The structures were elucidated by spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC) and HR-EI-MS experiments. Compounds 1-3 were evaluated for their anti-HBV activities. Honokiol showed significant anti-HBV activity with IC(50) values of 3.14μM and 4.74μM for HBsAg and HBeAg with no cytotoxicity respectively, while lamivudine (3TC, positive control) exhibited weak anti-HBV activity with IC(50) values of 11.81μM and 25.80μM for HBsAg and HBeAg respectively.

Identification of a Molecular Component of the Mitochondrial Acetyl Transferase Program; a Novel Role for GCN5L1

The Biochemical Journal. Feb, 2012  |  Pubmed ID: 22309213

SIRT3 modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondrial protein acetylation is controlled by a counter-regulatory program has remained elusive. Here we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1/Bloc1s1 counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology to a prokaryotic acetyltransferase. Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics. These data identify GCN5L1 as a critical, prokaryote-derived component of the mitochondrial acetyltransferase program.

[Dandy-Walker Syndrome and Microdeletions on Chromosome 7]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Feb, 2012  |  Pubmed ID: 22311491

To investigate genetic etiology of Dandy-Walker syndrome with array-based comparative genomic hybridization (array-CGH).

Highly Effective Binding of Neutral Dinitriles by Simple Pillar[5]arenes

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22314976

Highly effective binding of neutral dinitriles by simple alkyl-substituted pillar[5]arenes and the formation of interpenetrated geometries are reported. The resulting host-guest complexes represent one of the most efficient recognition motifs based on pillararenes.

Structure Insights into Mechanisms of ATP Hydrolysis and the Activation of Human Heat-shock Protein 90

Acta Biochimica Et Biophysica Sinica. Feb, 2012  |  Pubmed ID: 22318716

The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity.

Psychometric Assessment of Scales Measuring HIV Public Stigma, Drug-use Public Stigma and Fear of HIV Infection Among Young Adolescents and Their Parents

AIDS Care. Jan, 2012  |  Pubmed ID: 21756072

The objective of this study was to design and assess measurement instruments that accurately measure the levels of stigma among individuals with a primarily collectivist culture. A cross-sectional study was conducted among middle school students and their parents or guardians in a rural area of China. Exploratory and confirmatory factor analyses were used to examine and determine the latent factors of the sub-scales of stigma respectively, among students and their parents. Factor analyses identified three sub-scales: HIV public stigma (seven items), drug-use public stigma (nine items), and fear of HIV infection (seven items). There were no items with cross-loading onto multiple factors, supporting the distinctness of the constructs that these scales were meant to measure. Goodness of fit indices indicated that a three-factor solution fit, the data at an acceptable level in the student sample (χ(2) /degree ratio=1.98, comparative fit index [CFI]=0.92, root mean square error of approximation [RMSEA]=0.055, standardized root mean square residual [SRMR]=0.057) and in the parent sample (χ(2)/degree ratio=1.95, CFI=0.91, RMSEA=0.06, SRMR=0.059). Reliability of the three scales was excellent (Cronbach's alpha: 0.78-0.92 for students; 0.80-0.94 for parents or guardians) and stable across split samples and for the data as a whole. The scales are brief and suitable for use in developing countries where the collectivist culture prevails.

Genome-wide Association Study Identifies HMGN3 Locus for Spine Bone Size Variation in Chinese

Human Genetics. Mar, 2012  |  Pubmed ID: 21947420

Bone size (BS) is one of the major risk factors for osteoporotic fractures. BS variation is genetically determined to a substantial degree with heritability over 50%, but specific genes underlying variation of BS are still largely unknown. To identify specific genes for BS in Chinese, initial genome-wide association scan (GWAS) study and follow-up replication study were performed. In initial GWAS study, a group of 12 contiguous single-nucleotide polymorphism (SNP)s, which span a region of ~25 kb and locate at the upstream of HMGN3 gene (high-mobility group nucleosomal binding domain 3), achieved moderate association signals for spine BS, with P values ranging from 6.2E-05 to 1.8E-06. In the follow-up replication study, eight of the 12 SNPs were detected suggestive replicate associations with BS in 1,728 unrelated female Caucasians, which have well-known differences from Chinese in ethnic genetic background. The SNPs in the region of HMGN3 gene formed a tightly combined haplotype block in both Chinese and Caucasians. The results suggest that the genomic region containing HMGN3 gene may be associated with spine BS in Chinese.

Colistin-resistant, Lipopolysaccharide-deficient Acinetobacter Baumannii Responds to Lipopolysaccharide Loss Through Increased Expression of Genes Involved in the Synthesis and Transport of Lipoproteins, Phospholipids, and Poly-β-1,6-N-acetylglucosamine

Antimicrobial Agents and Chemotherapy. Jan, 2012  |  Pubmed ID: 22024825

We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971-4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface.

Synthesis of 3-substituted 1,5-aldehyde Esters Via an Organocatalytic Highly Enantioselective Conjugate Addition of New Carbonylmethyl 2-pyridinylsulfone to Enals

Chemical Communications (Cambridge, England). Jan, 2012  |  Pubmed ID: 22057586

A highly enantioselective organocatalytic protocol for conjugate addition of new nucleophilic carbonylmethyl 2-pyridinylsulfone to enals has been developed in good yields and with high enantioselectivities. The resulting Michael adducts are versatile building blocks for a variety of organic transformations.

Kashin-Beck Disease in Sichuan, China: Report of a Pilot Open Therapeutic Trial

Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases. Jan, 2012  |  Pubmed ID: 22157279

The objective of the study was to identify adults with symptomatic Kashin-Beck disease (KBD) and observe the efficacy and safety of diclofenac sodium, naproxen, and glucosamine hydrochloride in these adult patients in Rang-tang (Sichuan Province), China.

Exercise-induced Galanin Release Facilitated GLUT4 Translocation in Adipocytes of Type 2 Diabetic Rats

Pharmacology, Biochemistry, and Behavior. Jan, 2012  |  Pubmed ID: 22079346

Although galanin has been shown to increase insulin sensitivity in skeletal muscle of rats, there is no literature available about the effect of galanin on Glucose Transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of type 2 diabetic rats. In the present study M35, a galanin antagonist was used to elucidate whether exercise-induced galanin release increased GLUT4 translocation in adipocytes of streptozotocin-induced diabetic rats. The present findings showed that plasma galanin levels after swimming training in all four trained groups were higher compared with each sedentary control. M35 treatment had an inhibitory effect on glucose infusion rates in the euglycemic-hyperinsulinemic clamp test and GLUT4 mRNA expression levels in adipocytes. Moreover, M35 treatment reduced GLUT4 concentration in both plasma membranes and total cell membranes. The ratios of GLUT4 contents in plasma membranes to total cell membranes in four drug groups were lower compared with each control. These data demonstrate a beneficial role of endogenous galanin to transfer GLUT4 from internal stores to plasma membranes in adipocytes of type 2 diabetic rats. Galanin plays a significant role in regulation of glucose metabolic homeostasis and is an important hormone relative to diabetes.

Ascorbic Acid Protects Against the Nephrotoxicity and Apoptosis Caused by Colistin and Affects Its Pharmacokinetics

The Journal of Antimicrobial Chemotherapy. Feb, 2012  |  Pubmed ID: 22127588

The use of colistin in the treatment of life-threatening Gram-negative infections is associated with a high rate of nephrotoxicity that is dose limiting. This study aimed to examine the nephroprotective effect of ascorbic acid against colistin-induced nephrotoxicity.

IFN-γ and Indoleamine 2,3-dioxygenase Signaling Between Donor Dendritic Cells and T Cells Regulates Graft Versus Host and Graft Versus Leukemia Activity

Blood. Jan, 2012  |  Pubmed ID: 22130799

Allogeneic hematopoietic stem cell transplantation (HSCT) can eradicate chemorefractory leukemia through the graft-versus-leukemia (GVL) activity of donor T cells. However, the clinical success of allo-HSCT is limited by the graft-versus-host disease (GVHD) activity of donor T cells. We have reported previously that donor bone marrow precursors of plasmacytoid dendritic cells (pre-pDCs) can activate donor T cells toward T-helper 1 immune polarization in murine allogeneic HSCT. To optimize the GVL activity of these activated donor T cells and limit their graft versus host activity, we engineered the cellular constituents of an allogeneic hematopoietic stem cell graft with highly purified hematopoietic stem cells, T cells, and pre-pDCs and studied their GVL and GVHD activities in a murine model of allogeneic HSCT. Transplanted donor pre-pDCs expanded in vivo for 2 weeks after transplant, and they markedly augmented the activation and GVL activity of donor T cells while attenuating their GVHD activity, leading to an improved therapeutic index. Bidirectional signaling between donor T cells and donor pDCs with IFN-γ synthesis by donor T cells inducing indoleamine 2,3-dioxygenase synthesis by donor pDCs limited GVHD by altering the balance between donor T-reg and inflammatory T cells. Manipulating the content of donor DC precursors in allogeneic HSCT is a novel method to optimize the balance between GVL and GVHD.

Synthesis of Pillar[5]arene Dimers and Their Cooperative Binding Toward Some Neutral Guests

Organic Letters. Jan, 2012  |  Pubmed ID: 22142518

Three pillar[5]arene dimers, bridged by a flexible aliphatic chain (H1) or a relatively rigid phenylene unit (H2 and H3), were synthesized, with the possible synthetic strategies being discussed. The dimers could significantly enhance the binding affinities toward neutral model substrates in comparison with monomeric 1,4-dimethoxypillar[5]arene (H4) through the cooperative binding of two pillar[5]arene moieties. The molecular binding ability and selectivity are discussed from the viewpoints of the size/shape-fit concept and multiple recognition mechanism.

Pulmonary Embolism Detection and Characterization Through Quantitative Iodine-based Material Decomposition Images with Spectral Computed Tomography Imaging

Investigative Radiology. Jan, 2012  |  Pubmed ID: 22107805

To assess the diagnostic value of pulmonary embolism (PE) detection and characterization through quantitative iodine-based material decomposition images with spectral computed tomography (CT) imaging.

Synthesis of Highly Functionalized Chiral 3,3'-disubstituted Oxindoles Via an Organocatalytic Enantioselective Michael Addition of Nitroalkanes to Indolylidenecyanoacetates

Organic Letters. Jan, 2012  |  Pubmed ID: 22149210

An efficient bifunctional cinchona alkaloid derived thiourea-promoted enantioselective conjugate addition of nitroalkanes to indolylidenecyanoacetates has been developed under neat conditions. The process leads to synthetically interesting densely functionalized 3,3'-disubstituted oxindoles with creation of up to three stereogenic centers.

Osteogenic Effects of a Potent Src-over-Abl-Selective Kinase Inhibitor in the Mouse

The Journal of Pharmacology and Experimental Therapeutics. Mar, 2012  |  Pubmed ID: 22171089

Src-null mice have higher bone mass because of decreased bone resorption and increased bone formation, whereas Abl-null mice are osteopenic, because of decreased bone formation. Compound I, a potent inhibitor of Src in an isolated enzyme assay (IC(50) 0.55 nM) and a Src-dependent cell growth assay, with lower activity on equivalent Abl-based assays, potently, but biphasically, accelerated differentiation of human mesenchymal stem cells to an osteoblast phenotype (1-10 nM). Compound I (≥0.1 nM) also activated osteoblasts and induced bone formation in isolated neonatal mouse calvariae. Compound I required higher concentrations (100 nM) to inhibit differentiation and activity of osteoclasts. Transcriptional profiling (TxP) of calvaria treated with 1 μM compound I revealed down-regulation of osteoclastic genes and up-regulation of matrix genes and genes associated with the osteoblast phenotype, confirming compound I's dual effects on bone resorption and formation. In addition, calvarial TxP implicated calcitonin-related polypeptide, β (β-CGRP) as a potential mediator of compound I's osteogenic effect. In vivo, compound I (1 mg/kg s.c.) increased vertebral trabecular bone volume 21% (microcomputed tomography) in intact female mice. Increased trabecular volume was also detected histologically in a separate bone, the femur, particularly in the secondary spongiosa (100% increase), which underwent a 171% increase in bone formation rate, a 73% increase in mineralizing surface, and a 59% increase in mineral apposition rate. Similar effects were observed in ovariectomized mice with established osteopenia. We conclude that the Src inhibitor compound I is osteogenic, presumably because of its potent stimulation of osteoblast differentiation and activation, possibly mediated by β-CGRP.

Organocatalytic Enantioselective Conjugate Addition of Ketones to Isatylidine Malononitriles

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22190075

An enantioselective Michael addition of ketones to alkylidenemalononitriles catalyzed by chiral primary amine I with (R)-5c as a co-catalyst in good yields (>90%) and with good enantioselectivities (85-96% ee) has been developed. The strategy has also been extended to a three-component version through a domino Knoevenagel/Michael sequence with similar or better outcomes.

Mesocavoatrial Shunt for Budd-Chiari Syndrome: a Case Report with Long-term Follow-up

Annals of Vascular Surgery. Feb, 2012  |  Pubmed ID: 22079462

A case of mesocavoatrial shunting for the treatment of Budd-Chiari syndrome (BCS) with long-term follow-up is reported.

IPSCs Are Transcriptionally and Post-transcriptionally Indistinguishable from FESCs

Frontiers in Bioscience : a Journal and Virtual Library. , 2012  |  Pubmed ID: 22201828

Induced pluripotent stem cells (iPSCs) are generated by reprogramming mouse or human somatic cells to a pluripotent state by introducing key transcription factors and have great therapeutic potential. It has been illustrated that the transcriptional and post-transcriptional profiles of nuclear-transferred embryonic stem cells (ntESCs) is identical to those of embryonic stem cells derived from fertilized blastocysts (fESCs). Although iPSCs seem to be indistinguishable from fESCs, the degree of transcriptomic and proteomic similarity among iPSCs, ntESCs, and fESCs has not yet been elucidated completely. To investigate whether iPSCs and fESCs have similar therapeutic potential, we compared mRNA and protein pro?les of mouse iPSC, ntESCs, and matching fESCs lines using microarray technology, iTRAQ method, and bioinformatic analyses. Real-time PCR, two-dimensional LC, and MS/MS analyses were further conducted to study the expression of speci?c transcripts and identify and quantitate 929 proteins. Our results demonstrate that, like ntESCs, the iPSC and matching fESCs lines have very similar transcriptional and protein expression profiles. This is consistent with their similar developmental potential.

A Role for the Melatonin-related Receptor GPR50 in Leptin Signaling, Adaptive Thermogenesis, and Torpor

Current Biology : CB. Jan, 2012  |  Pubmed ID: 22197240

The ability of mammals to maintain a constant body temperature has proven to be a profound evolutionary advantage, allowing members of this class to thrive in most environments on earth. Intriguingly, some mammals employ bouts of deep hypothermia (torpor) to cope with reduced food supply and harsh climates [1, 2]. During torpor, physiological processes such as respiration, cardiac function, and metabolic rate are severely depressed, yet the neural mechanisms that regulate torpor remain unclear [3]. Hypothalamic responses to energy signals, such as leptin, influence the expression of torpor [4-7]. We show that the orphan receptor GPR50 plays an important role in adaptive thermogenesis and torpor. Unlike wild-type mice, Gpr50(-/-) mice readily enter torpor in response to fasting and 2-deoxyglucose administration. Decreased thermogenesis in Gpr50(-/-) mice is not due to a deficit in brown adipose tissue, the principal site of nonshivering thermogenesis in mice [8]. GPR50 is highly expressed in the hypothalamus of several species, including man [9, 10]. In line with this, altered thermoregulation in Gpr50(-/-) mice is associated with attenuated responses to leptin and a suppression of thyrotropin-releasing hormone. Thus, our findings identify hypothalamic circuits involved in torpor and reveal GPR50 to be a novel component of adaptive thermogenesis in mammals.