Effects of Glial Cell Line-derived Neurotrophic Factor on Cultured Murine Retinal Progenitor Cells

Molecular Vision. 2010  |  Pubmed ID: 21203407

Glial cell line-derived neurotrophic factor (GDNF) is neuroprotective of retinal neurons, and transduced retinal progenitor cells (RPCs) can deliver this cytokine for the treatment of retinal diseases, yet the potential effects of GDNF on RPCs have received little attention.

[Changes of Microarchitecture and Biomechanical Properties in Callus During Fracture Healing in Ovariectomized Rats]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Nov, 2010  |  Pubmed ID: 21265106

To study the changes of biomechanical properties and microarchitecture in callus during the healing process of osteoporotic fracture.

[Influence of Mutation of -1997G-->T of COL I A1 Gene on the Biochemical Function of Osteoblast]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2010  |  Pubmed ID: 21302452

To study the influence of mutation of -1997G-->T of COL I A1 gene on the biochemical function of osteoblast, and the pathomechanism of BMD.

[The Sedative and Hypnotic Effects and Safety of Oral Emulsified Isoflurane in Rats]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2010  |  Pubmed ID: 21302459

To investigate the sedative and hypnotic effects and safety of oral emulsified isoflurane in rats.

[Preparation of Mixed Crystal TiO2 Nanoparticles and Photocatalytic Degradation of Toxic Organic Pollutants]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Dec, 2010  |  Pubmed ID: 21360887

Mixed crystal TiO2 nanoparticles were prepared from a precursor of TiO2 by hydrothermal-steam method. The effects of the reaction temperature and the reaction time on the photocatalytic activity of the brookite TiO2 were studied. The TiO2 samples were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Photocatalytic degradation of organic dye sulforhodamine B (SRB) under UV light (lambda < or = 387 nm) was used as probe reaction to evaluate the properties of the TiO2. The result showed that TiO2 prepared under 150 degrees C for 24 h had high photocatalytic activity. The size of the mixed crystal TiO2 was 14.20 nm. Brookite and anatase phase of the mixed crystal TiO2 were 63.6% and 36.4%, respectively. The dye discoloration and degradation rates were tracked, and the intermediate products hydrogen peroxide (H2O2) and hydrogen radicals (*OH) were determined during the photocatalytic experiments. The results indicated that photocatalytic degradation of brookite TiO2 mainly referred to the *OH radical mechanism. After 5 h, the mineralization and oxidation rates of SRB and 2,4-DCP mineralization were 89% and 78%, respectively. The catalyst showed good stability with no significant changes in catalytic properties after 5 cycles of SRB photocatalytic degradation experiments.

Characterization of 13 Microsatellite Loci Developed from Meconopsis Horridula

Genetics and Molecular Biology. Jul, 2010  |  Pubmed ID: 21637429

Meconopsis horridula is one of the eight most famous flowers in Chinese province of Yunnan. In this study, a modified biotin-streptavidin capture method was used to detect 13 microsatellite markers in the genome of M. horridula. The polymorphism of each locus was assessed in 24 samples collected from four populations. The number of alleles per locus ranged from 2 to 7 (mean: 3.2). The observed and expected heterozygosities ranged from 0.0833 to 0.9167 and 0.0816 to 0.8050, respectively. Additionally, nine of the 13 microsatellite markers were successfully amplified in three other congeneric species. These polymorphic SSR markers could be useful for studying the population genetics of M. horridula and for assessing genetic variation in this and congenerc species in conservation programs.

Serum Levels of IL-1β, IL-6 and TNF-α in Rats Fed with Kashin-Beck Disease-affected Diet

International Journal of Rheumatic Diseases. Oct, 2010  |  Pubmed ID: 21199478

To investigate the serum level of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in rats which have been fed with Kashin-Beck disease (KBD) epidemic district food.

Snail2 is an Essential Mediator of Twist1-induced Epithelial Mesenchymal Transition and Metastasis

Cancer Research. Jan, 2011  |  Pubmed ID: 21199805

To metastasize, carcinoma cells must attenuate cell-cell adhesion to disseminate into distant organs. A group of transcription factors, including Twist1, Snail1, Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal transition (EMT), thus promoting tumor dissemination. However, it is unknown whether these transcription factors function independently or coordinately to activate the EMT program. Here we report that direct induction of Snail2 is essential for Twist1 to induce EMT. Snail2 knockdown completely blocks the ability of Twist1 to suppress E-cadherin transcription. Twist1 binds to an evolutionarily conserved E-box on the proximate Snail2 promoter to induce its transcription. Snail2 induction is essential for Twist1-induced cell invasion and distant metastasis in mice. In human breast tumors, the expression of Twist1 and Snail2 is highly correlated. Together, our results show that Twist1 needs to induce Snail2 to suppress the epithelial branch of the EMT program and that Twist1 and Snail2 act together to promote EMT and tumor metastasis.

Negative Association Between Free Triiodothyronine Level and International Normalized Ratio in Euthyroid Subjects with Acute Myocardial Infarction

Acta Pharmacologica Sinica. Nov, 2011  |  Pubmed ID: 21963894

To investigate the relationship between free triiodothyronine (FT3) and the international normalized ratio (the ratio of the prothrombin time of a patient to the normal sample, INR) in Chinese euthyroid subjects with acute ST-segment elevation myocardial infarction (STEMI).

Clinical Observations on Therapeutic Effects of the Modified Shengjing Zhongzi Tang (see Text) in Patients with Asthenospermia and Oligozoospermia

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: 21977861

To compare the therapeutic effects of Shengjing Zhongzi Tang ((see text) Decoction for Generating Sperms) and Wuzi Yanzong Wan ((see text) Pills for Reproduction) for asthenospermia and oligozoospermia.

The Structural Basis for Homotropic and Heterotropic Cooperativity of Midazolam Metabolism by Human Cytochrome P450 3A4

Biochemistry. Dec, 2011  |  Pubmed ID: 21992114

Human cytochrome P450 3A4 (CYP3A4) metabolizes a significant portion of clinically relevant drugs and often exhibits complex steady-state kinetics that can involve homotropic and heterotropic cooperativity between bound ligands. In previous studies, the hydroxylation of the sedative midazolam (MDZ) exhibited homotropic cooperativity via a decrease in the ratio of 1'-OH-MDZ to 4-OH-MDZ at higher drug concentrations. In this study, MDZ exhibited heterotropic cooperativity with the antiepileptic drug carbamazepine (CBZ) with characteristic decreases in the 1'-OH-MDZ to 4-OH-MDZ ratios. To unravel the structural basis of MDZ cooperativity, we probed MDZ and CBZ bound to CYP3A4 using longitudinal T(1) nuclear magnetic resonance (NMR) relaxation and molecular docking with AutoDock 4.2. The distances calculated from longitudinal T(1) NMR relaxation were used during simulated annealing to constrain the molecules to the substrate-free X-ray crystal structure of CYP3A4. These simulations revealed that either two MDZ molecules or an MDZ molecule and a CBZ molecule assume a stacked configuration within the CYP3A4 active site. In either case, the proton at position 4 of the MDZ molecule was closer to the heme than the protons of the 1'-CH(3) group. In contrast, molecular docking of a single molecule of MDZ revealed that the molecule was preferentially oriented with the 1'-CH(3) position closer to the heme than position 4. This study provides the first detailed molecular analysis of heterotropic and homotropic cooperativity of a human cytochrome P450 from an NMR-based model. Cooperativity of ligand binding through direct interaction between stacked molecules may represent a common motif for homotropic and heterotropic cooperativity.

Brain-derived Neurotrophic Factor Contributes to Abdominal Pain in Irritable Bowel Syndrome

Gut. Oct, 2011  |  Pubmed ID: 21997550

ObjectiveBrain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study.MethodsRectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF(+/-) mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF(+/+) mice following different doses of BDNF administration.ResultsBiopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF(+/-) than in BDNF(+/+) mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF(+/-) mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF(+/+) mice.ConclusionsThe increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.

IDH1 and IDH2 Mutation Analysis in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Annals of Hematology. Oct, 2011  |  Pubmed ID: 21997850

The somatic mutations of isocitrate dehydrogenase genes (IDH1 and IDH2) have been identified in a proportion of hematologic malignancies. We examined IDH1 R132 and IDH2 R140/R172 mutations by high resolution melting analysis and direct sequencing in Chinese patients with different myeloid malignancies including 198 acute myeloid leukemia (AML), 82 myelodysplastic syndrome (MDS), 85 chronic myeloid leukemia, and 57 myeloproliferative neoplasms. IDH1 and IDH2 mutations were found in four (2.0%) and ten (5.0%) AML and in two (2.4%) and three (3.6%) MDS cases, but not in other patients. IDH1 and IDH2 mutations were heterozygous and mutually exclusive. IDH1/2 mutations were significantly more frequently observed in cytogenetically normal AML or MDS compared to those without mutations. There was no difference in overall survival of both AML and MDS patients with or without IDH1/2 mutations (P = 0.177 and 0.407, respectively). In conclusion, IDH1/2 mutations are recurrent but rare molecular aberrations in Chinese AML and MDS.

Activation of STAT6 by STING is Critical for Antiviral Innate Immunity

Cell. Oct, 2011  |  Pubmed ID: 22000020

STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.

Effects of Ganoderma Lucidum Polysaccharides on IEC-6 Cell Proliferation, Migration and Morphology of Differentiation Benefiting Intestinal Epithelium Healing in Vitro

The Journal of Pharmacy and Pharmacology. Dec, 2011  |  Pubmed ID: 22060291

Restoration of epithelial continuity in the intestinal surface after extensive destruction is important since intestinal epithelial cells stand as a boundary between the body's internal and external environment. Polysaccharides from Ganoderma lucidum (Gl-PS) may benefit intestinal epithelial wound healing in different aspects, which awaits clarification. To identify potential effects, a non-transformed small-intestinal epithelial cell line, IEC-6 cells, was used.

Therapeutic Monoclonal Antibodies for Multiple Myeloma: an Update and Future Perspectives

American Journal of Blood Research. Jun, 2011  |  Pubmed ID: 22065141

Multiple myeloma (MM) still remains incurable in most of the patients. Despite of treatments with high-dose chemotherapy, stem cell transplantation and other novel therapies, most patients will become refractory to the therapies and relapse. Thus, it is urgent to develop new approaches for MM treatment. Currently, antibody-targeted therapy has been extensively utilized in hematological malignancies, including MM. Several novel monoclonal antibodies (mAbs) against MM have been generated and developed over the past several years. These mAbs aim to target not only tumor cells alone but also tumor microenvironment, including interaction of tumor-bone marrow stromal cells and the components of bone marrow milieu, such as cytokines or chemokines that support myeloma cell growth and survival. These include mAbs specific for CD38, CS1, CD40, CD74, CD70, HM1.24, interleukin-6 and β(2)-microglobulin (β(2)M). We have shown that anti-β(2)M mAbs may be a potential antitumor agent for MM therapy due to their remarkable efficacy to induce myeloma cell apoptosis in tumor cell lines and primary myeloma cells from patients in vitro and in established myeloma mouse models. In this article, we will review advances in the development and mechanisms of MM-targeted mAbs and especially, anti-β(2)M mAbs. We will also discuss the potential application of the mAbs as therapeutic agents to treat MM.

Surface-engineered Substrates for Improved Human Pluripotent Stem Cell Culture Under Fully Defined Conditions

Proceedings of the National Academy of Sciences of the United States of America. Nov, 2011  |  Pubmed ID: 22065768

The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell migration, and results in significant increases in cell growth of undifferentiated cells. These chemically defined xeno-free substrates generate more than three times the number of cells than feeder-containing substrates per surface area. Further, reprogramming and typical gene-targeting protocols can be readily performed on these engineered surfaces. These substrates provide an attractive cell culture platform for the production of clinically relevant factor-free reprogrammed cells from patient tissue samples and facilitate the definition of standardized scale-up friendly methods for disease modeling and cell therapeutic applications.

Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

PloS One. 2011  |  Pubmed ID: 22066015

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.

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.

Aβ Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons is Dependent Upon the Cellular Prion Protein PrPC

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Nov, 2011  |  Pubmed ID: 22072680

Current therapies for Alzheimer's disease (AD) address a loss of cholinergic neurons, while accumulation of neurotoxic amyloid β (Aβ) peptide assemblies is thought central to molecular pathogenesis. Overlaps may exist between prionopathies and AD wherein Aβ oligomers bind to the cellular prion protein PrP(C) and inhibit synaptic plasticity in the hippocampus (Laurén et al., 2009). Here we applied oligomeric Aβ to neurons with different PrP (Prnp) gene dosage. Whole-cell recordings were obtained from dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. In wild-type (wt) mice, Aβ₁₋₄₂ evoked a concentration-dependent reduction of whole-cell outward currents in a voltage range between -30 and +30 mV; reduction occurred through a combined modulation of a suite of potassium conductances including the delayed rectifier (I(K)), the transient outward (I(A)), and the iberiotoxin-sensitive (calcium-activated potassium, I(C)) currents. Inhibition was not seen with Aβ₄₂₋₁ peptide, while Aβ₁₋₄₂-induced responses were reduced by application of anti-PrP antibody, attenuated in cells from Prnp⁰/⁺ hemizygotes, and absent in Prnp⁰/⁰ homozygotes. Similarly, amyloidogenic amylin peptide depressed DBB whole-cell currents in DBB cells from wt mice, but not Prnp⁰/⁰ homozygotes. While prior studies give broad support for a neuroprotective function for PrP(C), our data define a latent pro-pathogenic role in the presence of amyloid assemblies.

[Cropping Patterns of Bupleurum Chinense in Semi-arid Region of Loess Plateau]

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. Mar, 2011  |  Pubmed ID: 21657044

Field experiments were conducted to investigate the suitable cropping patterns of grain crops and medical plant Bupleurum chinense in the semi-arid region of the Loess Plateau. Three cropping patterns were designed, including corn-Bupleurum chinense intercropping (corn/Bupleurum chinense), wheat followed by soybean-Bupleurum chinense intercropping (wheat-soybean/Bupleurum chinense), and sequential planting of Bupleurum chinense (wheat-Bupleurum chinense). Of the three patterns, wheat-soybean/Bupleurum chinense was the best in economic yields and ecological benefits. Among the cultivars (cv. Lingchuan, Zuoquan and Wanrong) of Bupleurum chinense tested, the cv. Wanrong originated from relatively high temperature region exhibited the highest yield, while the cv. Zuoquan originated from relatively low temperature region had the lowest one, indicating that introducing Bupleurum chinense cultivars from the areas with higher temperature to lower temperature areas could increase their yield. The cropping pattern of wheat-soybean/Bupleurum chinense was the most effective one, with the yield being 11.6% and 16.8% higher than that of corn/Bupleurum chinense and wheat-Bupleurum chinense, respectively.

Green Tea and Black Tea Consumption and Prostate Cancer Risk: an Exploratory Meta-analysis of Observational Studies

Nutrition and Cancer. 2011  |  Pubmed ID: 21667398

Observational studies on tea consumption and prostate cancer (PCa) risk are still inconsistent. The authors conducted a meta-analysis to investigate the association between green tea and black tea consumption with PCa risk. Thirteen studies providing data on green tea or black tea consumption were identified by searching PubMed and ISI Web of Science databases and secondary referencing qualified for inclusion. A random-effects model was used to calculate the summary odds ratios (OR) and their corresponding 95% confidence intervals (CIs). For green tea, the summary OR of PCa indicated a borderline significant association in Asian populations for highest green tea consumption vs. non/lowest (OR = 0.62; 95% CI: 0.38-1.01); and the pooled estimate reached statistically significant level for case-control studies (OR = 0.43; 95% CI: 0.25-0.73), but not for prospective cohort studies (OR = 1.00; 95% CI: 0.66-1.53). For black tea, no statistically significant association was observed for the highest vs. non/lowest black tea consumption (OR = 0.99; 95% CI: 0.82-1.20). In conclusion, this meta-analysis supported that green tea but not black tea may have a protective effect on PCa, especially in Asian populations. Further research regarding green tea consumption across different regions apart from Asia is needed.

Endogenous Heparinoids Induced Massive Hemorrhage Postoperatively Following THA

Orthopedics. Jun, 2011  |  Pubmed ID: 21667910

A 64-year-old woman presented with right hip pain of 6 years' duration, accompanied by limping of 1 years' duration. Preoperative pelvis radiograph showed narrowing of joint space, osteophyte formation, and cystis degeneration of the femoral head surrounded by bony sclerosis, without obvious collapse of the femoral head; the diagnosis was osteoarthrosis. The patient's blood pressure on admission was 128/76 mm Hg. The patient had no special previous history. Preoperative blood and coagulation tests were normal. Total hip arthroplasty was performed via a posterolateral approach, and intraoperative bleeding was 400 mL. In the first 10 hours postoperatively, the drainage volume decreased slowly, the initial dose of 0.3 mL Fraxiparine was administered, and the blood pressure was 84∼92/45∼56 mm Hg. The drainage volume increased gradually, and 10 hours after administration of Fraxiparine, the drainage volume increased sharply and maintained at a high level. Protamine was applied and the drainage volume decreased sharply, furthermore, a high concentration of endogenous heparinoids were detected in the blood. Although no direct evidence were detected, it was clear that the massive hemorrhage was associated with administration of low-molecular-weight heparin (LMWH). The administration of LMWH combined with continuous low blood pressure caused by surgery and massive bleeding that resulted in low perfusion and inflammation in microcirculation, induced endogenous heparinoid synthesis in endothelial cells, and elevated concentration of endogenous heparinoids in blood led to more severe bleeding. Therefore, caution should be taken with administration of anticoagulant therapy in patients with massive hemorrhage, especially in patients with continuous low blood pressure.

Increased Expression of Cellular FLICE/caspase-8 Inhibitory Protein in Condyloma Acuminatum

European Journal of Dermatology : EJD. Jul-Aug, 2011  |  Pubmed ID: 21680288

Condyloma acuminatum (CA) is a benign epithelial tumor caused by infection with human papillomaviruses (HPVs) and characterized by abnormal cell proliferation. Cellular caspase-8 (FLICE)-like inhibitory protein (c-FLIP) was originally identified as an inhibitor of death-receptor signaling through competition with caspase-8 for recruitment to FAS-associated via death domain (FADD). More recently, it has been determined that c-FLIP is associated with the survival and proliferation of T cells and keratinocytes. The aim of this work was to study the expression of c-FLIP in CA and its relationship with keratinocyte proliferation. Immunoperoxidase staining methods were applied to analyze the location and expressions of both c-FLIP and proliferating cell nuclear antigens (PCNA) in 34 CA and 16 normal foreskin tissues. Semiquantitative reverse transcriptase-polymerase chain reactions (RT-PCR) and western blotting were performed to further identify the expression of c-FLIP in CA. c-FLIP expression at both mRNA and protein level was significantly higher in CA than normal foreskin. c-FLIP expression was highly correlated with the PCNA labeling index (LI) in CA. We concluded that c-FLIP overexpression might take part in keratinocyte proliferation in CA.

Deficiency of Hepatocystin Induces Autophagy Through an MTOR-dependent Pathway

Autophagy. Jul, 2011  |  Pubmed ID: 21681021

Mutations in the gene encoding hepatocystin/80K-H (PRKCSH) cause autosomal-dominant polycystic liver disease (ADPLD). Hepatocystin functions in the processing of nascent glycoproteins as the noncatalytic beta subunit of glucosidase II (Glu II) and regulates calcium release from endoplasmic reticulum (ER) through the inositol 1,4,5-trisphosphate receptor (IP3R). Little is known, however, on how cells respond to a deficiency of hepatocystin. In this study, we demonstrate that knockdown of hepatocystin induces autophagy, the major intracellular degradation pathway essential for cellular health. Ectopic expression of wild-type hepatocystin, but not pathogenic mutants, rescues the siRNA-induced effect. Our data indicate that the induction of autophagy by hepatocystin deficiency is mediated through mammalian target of rapamycin (mTOR). Despite the resulting severe reduction in Glu II activity, the unfolded protein response (UPR) pathway is not disturbed. Furthermore, the inhibition of IP3R-mediated transient calcium flux is not required for the induction of autophagy. These results provide new insights into the function of hepatocysin and the regulation of autophagy.

Targeting the Kynurenine Pathway As a Potential Strategy to Prevent and Treat Alzheimer's Disease

Medical Hypotheses. Sep, 2011  |  Pubmed ID: 21683531

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only endogenous NMDA receptor antagonist and could modulate neurotoxic effects of QA. We hypothesize that an activated kynurenine pathway induced by inflammatory cytokines would generate more neurotoxic metabolites, which could be closely related to the pathogenesis of AD in elderly patients. Moreover, some measures, which facilitate KA synthesis and reduce the formation of QA, may emerge as a new therapeutic strategy against AD.

Efficient Recombinase-mediated Cassette Exchange at the AAVS1 Locus in Human Embryonic Stem Cells Using Baculoviral Vectors

Nucleic Acids Research. Sep, 2011  |  Pubmed ID: 21685448

Insertion of a transgene into a defined genomic locus in human embryonic stem cells (hESCs) is crucial in preventing random integration-induced insertional mutagenesis, and can possibly enable persistent transgene expression during hESC expansion and in their differentiated progenies. Here, we employed homologous recombination in hESCs to introduce heterospecific loxP sites into the AAVS1 locus, a site with an open chromatin structure that allows averting transgene silencing phenomena. We then performed Cre recombinase mediated cassette exchange using baculoviral vectors to insert a transgene into the modified AAVS1 locus. Targeting efficiency in the master hESC line with the loxP-docking sites was up to 100%. Expression of the inserted transgene lasted for at least 20 passages during hESC expansion and was retained in differentiated cells derived from the genetically modified hESCs. Thus, this study demonstrates the feasibility of genetic manipulation at the AAVS1 locus with homologous recombination and using viral transduction in hESCs to facilitate recombinase-mediated cassette exchange. The method developed will be useful for repeated gene targeting at a defined locus of the hESC genome.

[Role of LRRN3 in the Cerebellum Postnatal Development in Rats]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. May, 2011  |  Pubmed ID: 21685698

To explore the effect and possible mechanism of LRRN3 in the cerebellum postnatal development in rats.

Targeting Invadopodia to Block Breast Cancer Metastasis

Oncotarget. Jul, 2011  |  Pubmed ID: 21725138

Better understanding the mechanisms underlying the metastatic process is essential to developing novel targeted therapeutics. Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix. We recently found that the transcription factor Twist1, a central regulator of the epithelial-mesenchymal transition (EMT), promotes invadopodia formation via upregulation of platelet-derived growth factor receptor (PDGFR) expression and activity. This finding, combined with other investigations into the mechanisms of invadopodia formation, reveal several novel targets for clinical inhibition of invadopodia. Here, we provide an overview of clinically-relevant targets for intervention in invadopodia, including Src signaling, PDGFR signaling, and metalloprotease activity.

A Set of Novel Microsatellite Markers Developed for the Traditional Tibetan Medicinal Plant Halenia Elliptica (Gentianaceae)

American Journal of Botany. Jul, 2011  |  Pubmed ID: 21730330

• Premise of the study: Microsatellite primers were developed in the traditional Tibetan medicinal plant Halenia elliptica D. Don to investigate its genetic diversity and population genetic structure. • Methods and Results: Using the Fast Isolation by AFLP of Sequences Containing (FIASCO) repeats protocol, 24 primer sets were identified in two wild populations. Of these primers, 12 displayed polymorphisms and 12 were monomorphic. The number of alleles per locus ranged from 2 to 6, with a mean of 3.9. The expected (H(E)) and observed (H(O)) heterozygosities ranged from 0.191 to 0.784 and from 0.417 to 0.917, respectively. All these primers successfully amplified in two close relatives of H. elliptica, Swertia bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C. B. Clarke and S. tetraptera Maxim. • Conclusions: These markers will facilitate further studies on the population genetics of Halenia elliptica and its allied species.

Travelling Waves of a Delayed SIR Epidemic Model with Nonlinear Incidence Rate and Spatial Diffusion

PloS One. 2011  |  Pubmed ID: 21731655

This paper is concerned with the existence of travelling waves to a SIR epidemic model with nonlinear incidence rate, spatial diffusion and time delay. By analyzing the corresponding characteristic equations, the local stability of a disease-free steady state and an endemic steady state to this system under homogeneous Neumann boundary conditions is discussed. By using the cross iteration method and the Schauder's fixed point theorem, we reduce the existence of travelling waves to the existence of a pair of upper-lower solutions. By constructing a pair of upper-lower solutions, we derive the existence of a travelling wave connecting the disease-free steady state and the endemic steady state. Numerical simulations are carried out to illustrate the main results.

Extracts from a Traditional Chinese Herbal Remedy (Zhuyun Recipe) Improve Endometrial Receptivity in Mice with Embryonic Implantation Dysfunction and Ovulation Stimulation

Journal of Ethnopharmacology. Sep, 2011  |  Pubmed ID: 21740961

Although ovarian stimulation has an important role in assisted reproductive technologies (ART), it may also have detrimental effects on endometrial receptivity. Traditional Chinese herbal remedy, as a kind of traditional treatments, has been widely and increasingly applied in clinic. In this article, the impact of traditional Chinese medicines (TCM) on embryonic implantation, pregnant rate and underlying mechanisms will be investigated.

An Essential Role for Transcription Before the MBT in Xenopus Laevis

Developmental Biology. Sep, 2011  |  Pubmed ID: 21741375

Most zygotic genes remain transcriptionally silent in Drosophila, Xenopus, and zebrafish embryos through multiple mitotic divisions until the midblastula transition (MBT). Several genes have been identified in each of these organisms that are transcribed before the MBT, but whether precocious expression of specific mRNAs is important for later development has not been examined in detail. Here, we identify a class of protein coding transcripts activated before the MBT by the maternal T-box factor VegT that are components of an established transcriptional regulatory network required for mesendoderm induction in Xenopus laevis, including the Nodal related ligands xnr5, xnr6, and derrière and the transcription factors bix4, and sox17α. Accumulation of phospho-Smad2, a hallmark of active Nodal signaling, at the onset of the MBT requires preMBT transcription and activity of xnr5 and xnr6. Furthermore, preMBT activation of the Nodal pathway is essential for mesendodermal gene expression and patterning of the embryo. Finally, xnr5 and xnr6 can also activate their own expression during cleavage stages, indicating that preMBT transcription contributes to a feed-forward system that allows robust activation of Nodal signaling at the MBT.

The Antagonistic Action of B56-containing Protein Phosphatase 2As and Casein Kinase 2 Controls the Phosphorylation and Gli Turnover Function of Daz Interacting Protein 1

The Journal of Biological Chemistry. Oct, 2011  |  Pubmed ID: 21878643

The Hedgehog (Hh) pathway is evolutionarily conserved and plays critical roles during embryonic development and adult tissue homeostasis. Defective Hh signaling has been linked to a wide range of birth defects and cancers. Hh family proteins regulate the expression of their downstream target genes through the control of proteolytic processing and the transcriptional activation function of Gli transcription factors. Although Hh-dependent regulation of Gli has been studied extensively, other Gli regulatory mechanisms remain relatively unappreciated. Here we report our identification of a novel signaling cascade that controls the stability of Gli proteins. This cascade consists of Daz interacting protein 1 (Dzip1), casein kinase 2 (CK2), and B56 containing protein phosphatase 2As (PP2As). We provide evidence that Dzip1 is involved in a novel Gli turnover pathway. We show that CK2 directly phosphorylates Dzip1 at four serine residues, Ser-664/665/706/714. B56-containing PP2As, through binding to a domain located between amino acid residue 474 and 550 of Dzip1, dephosphorylate Dzip1 on these CK2 sites. Our mutagenesis analysis further demonstrates that the unphosphorylatable form of Dzip1 is more potent in promoting Gli turnover. Consistently, we found that the stability of Gli proteins was decreased upon CK2 inhibition and increased by inhibition of B56-containing PP2As. Thus, reversible phosphorylation of Dzip1, which is controlled by the antagonistic action of CK2 and B56-containing PP2As, has an important impact on the stability of Gli transcription factors and Hh signaling.

Investigation of PH-responsive Properties of Polymeric Micelles with a Core-forming Block Having Pendant Cyclic Ketal Groups

Journal of Colloid and Interface Science. Dec, 2011  |  Pubmed ID: 21889164

In this study, three kinds of amphiphilic block copolymers, termed MPEG-block-PDMMA, MPEG-block-PCPMA, and MPEG-block-PMPMA, which were composed of one hydrophilic monomethoxy poly(ethylene glycol) (MPEG) block and one hydrophobic polyacrylate block bearing pendant six-member cyclic ketal groups, were synthesized by atom transfer radical polymerization (ATRP). These polymers can disperse in aqueous media to self-assemble into micellar aggregates with a spherical core-shell structure with mean diameter below 300 nm. The stimuli-responsiveness of polymeric micelles from MPEG-block-PDMMA was detected by fluorescence-probe technique at pH 3.5 and 37 °C. The effect of chemical architecture and composition of the polymers on the pH-responsive properties of polymeric micelles was also studied. A combination of pH and temperature to trigger release behavior of these polymeric micelles was discussed by comparing the encapsulated molecule release ability under various pH and temperature conditions and analyzing chemical structural changes of the polymer before and after the triggering.

Loss of Astrocyte Polarization in the Tg-ArcSwe Mouse Model of Alzheimer's Disease

Journal of Alzheimer's Disease : JAD. 2011  |  Pubmed ID: 21891870

Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis. Here we investigate by a combination of light and electron microscopic immunocytochemistry whether amyloid deposition is associated with a loss of astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model of Alzheimer's disease, as this model displays perivascular plaques as well as plaques confined to the neuropil. 3D reconstructions were done to establish the spatial relation between plaques and astrocytic endfeet, the latter known to contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just after the appearance of the first plaques. Typically, there is a loss of AQP4 from endfoot membranes at sites of perivascular amyloid deposits, combined with an upregulation of AQP4 in the neuropil surrounding plaques. By electron microscopy it could be verified that the upregulation reflects an increased concentration of AQP4 in those delicate astrocytic processes that abound in synaptic regions. Thus, astrocytes exhibit a redistribution of AQP4 from endfoot membranes to non-endfoot membrane domains. The present data suggest that the development of amyloid deposits is associated with a loss of astrocyte polarization. The possible perturbation of water and K+ homeostasis could contribute to cognitive decline and seizure propensity in patients with Alzheimer's disease.

Noncovalent Interaction of Polyethylene Glycol with Copper Complex of Ethylenediaminetetraacetic Acid and Its Application in Constructing Inorganic Nanomaterials

Dalton Transactions (Cambridge, England : 2003). Oct, 2011  |  Pubmed ID: 21904760

In this study, we try to answer a fundamental question: what is the consequence of the noncovalent interaction between a polymer and a coordination compound? Here, polyethylene glycol (PEG-4000, PEG-b) and copper complex of ethylenediaminetetraacetic acid (H(2)CuY) were employed to solve this problem. A novel adduct (CEP) between H(2)CuY and PEG-b was prepared. Our results indicated several interesting findings. First, the introduction of H(2)CuY had no effect on the stacking structure of PEG-b but led to a large change in surface structure of the polymer. Second, there was a significant difference (117 K) in the maximum degradation temperature between the PEG and the CEP, suggesting that the noncovalent interaction can drastically improve the thermal stability of the PEG. Third, sintering experiments showed that H(2)CuY and CEP produced completely different decomposition products. The former formed Cu crystals in nitrogen and CuO in air, but the latter generated Cu and CuCl crystals with good crystallinity, respectively. Finally, three independent measurements: viscosity, conductivity and nuclear magnetic resonance in solution, provided useful information and insights from both sides of the noncovalent interaction. Probable interaction mechanisms and interaction sites were proposed. We consider that the current research could create the foundation for a new understanding of how the noncovalent adduct interaction between a metallic complex and a polymer relates to the change in physical and chemical properties of the adducted components.

Etching Growth Under Surface Confinement: an Effective Strategy to Prepare Mesocrystalline Pd Nanocorolla

Journal of the American Chemical Society. Oct, 2011  |  Pubmed ID: 21919482

An etching growth strategy was developed to prepare corolla-like Pd mesocrystals consisting of unidirectionally aligned, well-spaced, and connected ultrathin (1.8-nm-thick) Pd nanosheets. The combined use of CO and Fe(3+) is critical to the successful synthesis of the branched corolla-like Pd mesocrystals. While CO functions as the surface-confining agent to allow anisotropic growth of the 1.8-nm-thick Pd nanosheets as branches, Fe(3+) etches the Pd seeds at the early stage of the reaction to induce formation of the branched structure. Inheriting the unique properties of 1.8-nm-thick Pd nanosheets, the as-prepared Pd mesocrystals display well-defined surface plasmon resonance absorption in the near-infrared region, a high electrochemically active surface area, and a significant photothermal effect when irradiated with a near-infrared laser. Owing to the presence of internal voids and increased apparent thickness, the Pd mesocrystals also exhibit several features superior to those of single-domain Pd nanosheets, making them promising for electrocatalysis and cancer photothermal therapy applications.

Expansion of a Restricted Residual Host T Reg-cell Repertoire is Dependent on IL-2 Following Experimental Autologous Hematopoietic Stem Transplantation

European Journal of Immunology. Dec, 2011  |  Pubmed ID: 21928285

We previously identified a population of residual T(reg) cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived T(reg) cells. These CD4(+) Foxp3(+) T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL-7 and IL-15, IL-2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these three STAT-5 signaling cytokines in the expansion of residual T(reg) cells after autologous HSCT. The present study found that the residual T(reg) cell population included surviving peripheral host Foxp3(+) CD4(+) T cells whose expansion was critically dependent on IL-2, which could be solely provided by surviving host cells. IL-7 was found to contribute to T(reg) cell homeostasis, however, not as a growth factor but rather for their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host T(reg) -cell compartment differed from that present in non-conditioned healthy mice since the residual host Treg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of T(reg) and T effector (T(eff) ) cells post-HSCT utilize separate pools of cytokines which has important implications regarding the development of clinical strategies to elicit the desired immune responses in patients post-transplant.

A Randomized Trial of Somatostatin to Regulate the VEGFs/VEGFRs in Patients with Gastric Cancer

Hepato-gastroenterology. Jul-Aug, 2011  |  Pubmed ID: 21937420

Angiogenesis and lymphangiogenesis are essential for tumor growth and metastasis. Vascular endothelial growth factors and their receptors (VEGFs/VEGFRs) are important to modulate vasculogenesis. Disregulation of the VEGFs/VEGFRs are closely related to tumor progression and prognosis.

Controlling the Primary Particle Evolution Process Towards Silica Monoliths with Tunable Hierarchical Structure

Journal of Colloid and Interface Science. Dec, 2011  |  Pubmed ID: 21943511

In order to establish the hierarchical structure in multiple levels on mesoporous silica, this article reports a new strategy to prepare the monolith with the pore configuration in nanometer scale, micro-morphology in micrometer level and macroscopic shape in millimeter or larger grade. These hierarchical monoliths are synthesized in a weak acidic condition by using triblock copolymer P123, hydroxyl carboxylic acid and tetramethyl orthosilicate (TMOS), and the textural properties of the mesostructure can be facilely adjusted by simply controlling the synthesis condition without any additive. During the synthesis, the primary particles can be selectively synthesized as monodispersed sphere, noodle, prism, straight rods with different size or irregular bars, and their connection plus arrangement in 3D directions can be also regulated. Therefore, various textural properties of mesopore are able to be altered including pore size (5.5-10.6 nm), total pore volume (0.48-1.2 cm(3) g(-1)), micropore surface area (47-334 m(2) g(-1)), and pore shape (from 2D or 3D straight channel to plugged channel). Moreover, these monoliths exhibit a considerable mechanical strength; they are also applied in eliminating particulate matters and tobacco special nitrosamines (TSNA) in tobacco smoke, exhibiting various morphology-assisted functions.

Arabidopsis G-protein Interactome Reveals Connections to Cell Wall Carbohydrates and Morphogenesis

Molecular Systems Biology. 2011  |  Pubmed ID: 21952135

The heterotrimeric G-protein complex is minimally composed of Gα, Gβ, and Gγ subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, we detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G-protein interactome. Within this core, over half of the interactions comprising two-thirds of the nodes were retested and validated as genuine in planta. Co-expression analysis in combination with phenotyping of loss-of-function mutations in a set of core interactome genes revealed a novel role for G-proteins in regulating cell wall modification.

Infrared Transmission and Emission Spectroscopic Study of Selected Chinese Palygorskites

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Dec, 2011  |  Pubmed ID: 21958517

Infrared transmission and emission spectroscopy were used to analyze the difference in structure and thermal behavior of two Chinese palygorskites. The position of the main bands identified in the infrared spectra of the palygorskites studied is similar for these two Chinese samples, but there are some differences in their intensity, which is significant. This discrepancy is attributed to the existence of impurities and the geological environments in different regions. The infrared emission spectra clearly show the structural changes and dehydroxylation of the palygorskites when the temperature is raised. The dehydration of the palygorskites is followed by the loss of intensity of the OH stretching vibration bands in the region of 3600-3200 cm(-1). Dehydroxylation is followed by the decrease in intensity in the bands between 3700 and 3550 cm(-1). Dehydration of pure palygorskite was completed by 600°C. Partial loss of coordinated water was observed at 400°C. Infrared emission spectroscopy is an effective method to determine the stability of the mineral.

A Putative Flowering-time-related Dof Transcription Factor Gene, JcDof3, is Controlled by the Circadian Clock in Jatropha Curcas

Plant Science : an International Journal of Experimental Plant Biology. Dec, 2011  |  Pubmed ID: 21958709

Plant-specific DNA-binding transcription factors with one finger (Dof) perform important roles in several biological processes. A yeast one-hybrid cDNA library of Jatropha curcas was used to identify Dof-type transcription factors. JcDof3, isolated from the library as a full-length cDNA, encoded a protein of 518 amino acids and contained a highly conserved Dof domain. Yeast one-hybrid systems and subcellular localization assays confirmed that JcDof3 was a typical transcription factor. In contrast to arrhythmic expression at basal level in etiolated cotyledons under continuous dark conditions, the circadian oscillations of JcDof3 transcripts were observed under long day, short day or continuous light regimes. A phylogenetic analysis showed that JcDof3 was clustered into the same clade with CYCLING DOF FACTOR (CDF), which interacts with F-box protein to regulate photoperiodic flowering. Moreover, a yeast two-hybrid assay showed that JcDof3 also interacted with F-box proteins. Our results suggest that JcDof3 is a circadian clock regulated gene, and might be involved in the flowering time regulation of J. curcas.

CpG or IFN-α Are More Potent Adjuvants Than GM-CSF to Promote Anti-tumor Immunity Following Idiotype Vaccine in Multiple Myeloma

Cancer Immunology, Immunotherapy : CII. Oct, 2011  |  Pubmed ID: 22002243

Idiotype (Id) protein in combination with GM-CSF has been used as vaccines for immunotherapy of patients with myeloma and B-cell tumors and the results have been disappointing. To search for better immune adjuvants to improve the efficacy of Id-based immunotherapy in myeloma, we evaluated and compared the efficacy of vaccination of Id protein in combination with CpG or IFN-α, or GM-CSF as a control, in the 5TGM1 myeloma mouse model. Our results showed that Id vaccine combined with CpG or IFN-α, but not GM-CSF, not only efficiently protected mice from developing myeloma but also eradicated established myeloma. The therapeutic responses were associated with an induction of strong humoral immune responses including anti-Id antibodies, and cellular immune responses including Id- and myeloma-specific CD8(+) cytotoxic T lymphocytes (CTLs), CD4(+) type-1 T-helper (Th1) cells and memory T cells in mice receiving Id vaccine combined with CpG or IFN-α. Furthermore, Id vaccine combined with CpG or IFN-α induced Id- and tumor-specific memory immune responses that protected surviving mice from tumor rechallenge. Thus, our study clearly shows that CpG or IFN-α are better immune adjuvants than GM-CSF. This information will be important for improving the strategies of Id-based immunotherapy for patients with myeloma and other B-cell tumors.

Evaluation of Cynanchum Otophyllum Glucan Sulfate Against Human Immunodeficiency Virus and Herpes Simplex Virus As a Microbicide Agent

Indian Journal of Pharmacology. Sep, 2011  |  Pubmed ID: 22021996

The root of Cynanchum otophyllum-also known as Qing Yang Sheng-is a traditional ethnical Chinese medicine. The objective of this study was to evaluate in vitro activities and safety of C. otophyllum glucan sulfate (PS20) against Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV).

Synthesis of Rare Earth Catalysts and Their Applications for Enantioselective Synthesis of Heterocyclic β-amino Alcohols

The Journal of Organic Chemistry. Dec, 2011  |  Pubmed ID: 22022861

A new family of chiral lanthanide complexes derived from (R)-binaphthol has been synthesized by a one-pot procedure using only commercially available substrates. These complexes were evaluated for the aminolysis of meso-epoxides and proved to be efficient enantioselective catalysts. The samarium complex coordinated by two (R)-binaphthoxide ligands was the most enantioselective catalyst of this series. β-Amino alcohols including heterocycles have been isolated with enantiomeric excesses up to 84%.

Gene Expression of Helicase Antigen in Patients with Acute and Chronic Myeloid Leukemia

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Oct, 2011  |  Pubmed ID: 22040965

The aim of this study was to investigate the expression status of the helicase antigen (HAGE) transcript and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The expression of HAGE cDNA in bone marrow mononuclear cells from AML and CML patients was detected by using real-time quantitative PCR. The resuts indicated that overexpression of HAGE transcript (117.12% - 9842.70%, median 434.96%) was detected in 14.8% (11/74) AML patients. AML patients with HAGE cDNA expression were significantly older than those HAGE-negative patients (median 67 and 45 years, respectively, p = 0.001). HAGE cDNA expression was more frequently present among the patients with acute monoblastic leukemia (M(4) and M(5), 7 of 20, 35.0%), compared to the patients with acute non-monoblastic leukemia (M(1), M(2), M(3) and M(6), 4 of 54, 7.4%) (p = 0.007). 28.6% (8/28) cases with normal karyotypes showed HAGE cDNA overexpression, significantly higher than 7.5% (3 of 40) in those with chromosomal abnormalities (p = 0.041). Overexpression of HAGE transcript was found in 9 (34.6%) CML cases and more frequently observed at accelerated phase and blast crisis (4/4, 100%) than that at chronic phase (5/22, 22.7%) (p = 0.008). It is concluded that HAGE cDNA expression is relevant to specific subtypes of AML and to the progression of CML.

[Treatment of Developmental Dysplasia of Hip by Modified Sutherland Pelvic Osteotomy]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Jul, 2011  |  Pubmed ID: 22041678

To investigate the clinical results of modified Sutherland pelvic osteotomy for developmental dysplasia of hip (DDH).

Ischemic Preconditioning Protects Against Myocardial Ischemia-reperfusion Injury Through Inhibiting Toll-like Receptor 4/NF-κB Signaling Pathway in Rats

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Oct, 2011  |  Pubmed ID: 22086008

To investigate whether the protection of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion (I/R) injury is mediated by toll-like receptor 4 (TLR4)/NF-κB pathway,and whether these effects are related to the release of calcitonin gene-related peptide (CGRP).

[Clinical Analysis of 18 Cases with Acute Tumor Lysis Syndrome in Children with B-cell Lymphoma]

Zhonghua Er Ke Za Zhi. Chinese Journal of Pediatrics. Aug, 2011  |  Pubmed ID: 22093429

To investigate risk factors associated with acute tumor lysis syndrome (ATLS) in children with B-cell lymphoma and to explore feasible means for the prophylaxis and treatment.

[Effects of CPKCβII/γ Membrane Translocation Ischemic/hypoxic Tolerance Induced by Morphine Postconditioning in Hippocampal Slices]

Zhonghua Yi Xue Za Zhi. Jul, 2011  |  Pubmed ID: 22093901

To determine whether or not morphine postconditioning can induce ischemic/hypoxic tolerance in neurons subjected to reperfusion injury after oxygen-glucose deprivation (OGD).

Coexpression of Hypoxia-inducible Factor-2α, TWIST2, and SIP1 May Correlate with Invasion and Metastasis of Salivary Adenoid Cystic Carcinoma

Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. Nov, 2011  |  Pubmed ID: 22103974

J Oral Pathol Med (2011) Background:  Adenoid cystic carcinoma (ACC) of salivary gland is characterized by advanced local invasion and distant metastasis. Intratumoral hypoxia was reported to be associated with epithelial-mesenchymal transition (EMT) regulators. The purpose of this study was to evaluate the relationship between hypoxia-inducible factor (HIF)-2α, TWIST2, and SIP1 expression and the invasion and metastasis in ACC of salivary gland. Method:  In vitro we first detected the expression of HIF-2α, TWIST2, and SIP1 in two ACC cell lines by Western blot and real-time RT-PCR. Then, in vivo, a retrospective investigation of 121 patients with ACC from Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 was carried out using immunohistochemistry to analyze the association between the expression of these three factors and clinical-pathological factors of patients. Results:  The protein and mRNA levels of HIF-2α, TWIST2, and SIP1 in the high-metastasis cell line (ACC-M) were much higher than those of the low-metastasis cell line (ACC-2). The positive expression of HIF-2α, TWIST2, and SIP1 (71.07%, 42.98%, and 38.02%, respectively) was associated with the perineural invasion, the local recurrence, and distant metastasis of patients with ACC (P < 0.05). The patients with the positive coexpression of the three factors had a lower survival rate than those with the negative expression (P < 0.05). Conclusion:  It is proposed that the elevated expression of HIF-2α, TWIST2, and SIP1 can contribute to invasion and metastasis of ACC, and there might be some correlation between the hypoxia microenvironment and EMT in ACC.

Characterization of the Stress Associated MicroRNAs in Glycine Max by Deep Sequencing

BMC Plant Biology. 2011  |  Pubmed ID: 22112171

ABSTRACT:

Down-regulation of Shadoo in Prion Infections Traces a Pre-clinical Event Inversely Related to PrP(Sc) Accumulation

PLoS Pathogens. Nov, 2011  |  Pubmed ID: 22114562

During prion infections of the central nervous system (CNS) the cellular prion protein, PrP(C), is templated to a conformationally distinct form, PrP(Sc). Recent studies have demonstrated that the Sprn gene encodes a GPI-linked glycoprotein Shadoo (Sho), which localizes to a similar membrane environment as PrP(C) and is reduced in the brains of rodents with terminal prion disease. Here, analyses of prion-infected mice revealed that down-regulation of Sho protein was not related to Sprn mRNA abundance at any stage in prion infection. Down-regulation was robust upon propagation of a variety of prion strains in Prnp(a) and Prnp(b) mice, with the exception of the mouse-adapted BSE strain 301 V. In addition, Sho encoded by a TgSprn transgene was down-regulated to the same extent as endogenous Sho. Reduced Sho levels were not seen in a tauopathy, in chemically induced spongiform degeneration or in transgenic mice expressing the extracellular ADan amyloid peptide of familial Danish dementia. Insofar as prion-infected Prnp hemizygous mice exhibited accumulation of PrP(Sc) and down-regulation of Sho hundreds of days prior to onset of neurologic symptoms, Sho depletion can be excluded as an important trigger for clinical disease or as a simple consequence of neuronal damage. These studies instead define a disease-specific effect, and we hypothesize that membrane-associated Sho comprises a bystander substrate for processes degrading PrP(Sc). Thus, while protease-resistant PrP detected by in vitro digestion allows post mortem diagnosis, decreased levels of endogenous Sho may trace an early response to PrP(Sc) accumulation that operates in the CNS in vivo. This cellular response may offer new insights into the homeostatic mechanisms involved in detection and clearance of the misfolded proteins that drive prion disease pathogenesis.

Spiro[pyrrolidine-2,3'-oxindole] Derivatives Synthesized by Novel Regionselective 1,3-dipolar Cycloadditions

Molecular Diversity. Dec, 2011  |  Pubmed ID: 22134725

A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.

[Clinical Application of the Transjugular Intrahepatic Portosystemic Stent-shunt in the Emergency Treatment of Esophagogastric Varices Bleeding Due to Cirrhosis]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Jul, 2011  |  Pubmed ID: 22152237

To investigate the effects of transjugular intrahepatic portosystemic stent-shunt (TIPS) in emergency treatment of esophagogastric varices bleeding for the cirrhosis patients.

[Mutation Analysis of Keratin 5 and Keratin 14 Genes in a Family with Epidermolysis Bullosa Simplex with Mottled Pigmentation]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Dec, 2011  |  Pubmed ID: 22161089

To identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.

[Serological Investigation on Toxoplasma Gondii Infection in Dialysis Patients with Renal Insufficiency]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Apr, 2011  |  Pubmed ID: 22164611

A total of 205 dialysis patients with renal insufficiency were selected as an experiment group, and 360 healthy people were selected as a control group. The specific IgG antibodies of Toxoplasma gondii of the objects in the 2 groups were detected by ELISA. The positive rates of the experiment and control groups were 27. 3% and 3. 6% ,respectively, with a significant difference between them (P < 0.05). Among the dialysis patients with renal insufficiency, the positive rates of the patients with or without a history of blood transfusion were 31.2% and 19.2% , respectively, and there was a significant difference between them (P < 0.05). In conclusion, the infection rate of T. gondii in dialysis patients with renal insufficiency is higher than that of common people, and dialysis and/or blood transfusion may be potential risk(s) for Toxoplasma gondii infection.

[Clinical and Coronary Angiographic Features of Patients with Systemic Vasculitis and Coronary Artery Disease]

Zhonghua Xin Xue Guan Bing Za Zhi. Aug, 2011  |  Pubmed ID: 22169420

To evaluate the clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease.

[Cross-sectional Study of Dentine Hypersensitivity in Smaller Cities and Rural Area in Sichuan Province]

Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology. Sep, 2011  |  Pubmed ID: 22177356

To investigate the clinical characteristics and risk factors of dentine hypersensitivity in smaller cities and rural area in Sichuan province.

Mechanical Strength of Cortical Allografts with Gamma Radiation Versus Ethylene Oxide Sterilization

Acta Orthopaedica Belgica. Oct, 2011  |  Pubmed ID: 22187845

We investigated the effects of gamma irradiation versus ethylene oxide (ETO) sterilization on the mechanical strength of cortical bone grafts. Tibias were collected from cadavers of mature goats. Sixty test specimens were randomized into four groups: fresh (no processing), frozen (freezing at -70 degrees C), gamma-irradiated, and ETO-sterilized specimens. Torsion, three-point bending, and compression testing were separately performed with a material testing machine. Parameters studied included maximum stress, strain, deflection, extension, load, shear modulus, and E-modulus. Compared with findings for the fresh specimens, findings were as follows for gamma-irradiated specimens: maximal shear modulus, reduced by 48%; shear stress, by 55%; deflection, by 71%; bending stress, by 51%; bending strain, by 74%; extension, by 60%; and compression strain, by 50%. However, there were no reductions in those parameters for the frozen specimens or the ETO-sterilized specimens. These findings confirm that shear, bending, and compression strength of cortical allografts are weakened by gamma irradiation at room temperature. To maintain optimum mechanical properties, ETO sterilization of allografts is better than gamma sterilization, especially for cortical bone, because it is usually used in load-bearing settings.

Locally Infused Gene Containg Nanoparticles to Inhibit Rabbit Intimal Hyperplasia

Journal of Controlled Release : Official Journal of the Controlled Release Society. Nov, 2011  |  Pubmed ID: 22195893

Mechanism of Isoprenylcysteine Carboxyl Methylation from the Crystal Structure of the Integral Membrane Methyltransferase ICMT

Molecular Cell. Dec, 2011  |  Pubmed ID: 22195972

The posttranslational modification of C-terminal CAAX motifs in proteins such as Ras, most Rho GTPases, and G protein γ subunits, plays an essential role in determining their subcellular localization and correct biological function. An integral membrane methyltransferase, isoprenylcysteine carboxyl methyltransferase (ICMT), catalyzes the final step of CAAX processing after prenylation of the cysteine residue and endoproteolysis of the -AAX motif. We have determined the crystal structure of a prokaryotic ICMT ortholog, revealing a markedly different architecture from conventional methyltransferases that utilize S-adenosyl-L-methionine (SAM) as a cofactor. ICMT comprises a core of five transmembrane α helices and a cofactor-binding pocket enclosed within a highly conserved C-terminal catalytic subdomain. A tunnel linking the reactive methyl group of SAM to the inner membrane provides access for the prenyl lipid substrate. This study explains how an integral membrane methyltransferase achieves recognition of both a hydrophilic cofactor and a lipophilic prenyl group attached to a polar protein substrate.

Natural Cycle is Superior to Hormone Replacement Therapy Cycle for Vitrificated-preserved Frozen-thawed Embryo Transfer

Systems Biology in Reproductive Medicine. Dec, 2011  |  Pubmed ID: 22206474

We undertook this retrospective variables-control analysis to compare the reproductive outcomes of frozen-thawed embryo transfer using endometrial preparation with either natural cycle or hormone replacement therapy cycle. Patients were divided into three subgroups. Subgroup A (n = 32) consisted of patients having three 8-cell post-thawed embryos transferred. Subgroup B (n = 404) consisted of patients having three good quality post-thawed embryos transferred. Subgroup C (n = 578) consisted of patients having two or three all intact and mitosis resumption post-thawed embryos transferred. Implantation rate, biochemical pregnancy rate, and clinical pregnancy rate were measured. In subgroup A, significantly higher implantation rate, clinical pregnancy rate ongoing pregnancy rate, and lower biochemical pregnancy rate were observed in the natural cycle compared with hormone replacement therapy (HRT) cycle. Subgroup B, had a significantly higher rate of implantation, ongoing pregnancy, and a significantly lower rate of biochemical pregnancy in natural cycle compared with HRT cycle. The natural cycle had a higher trend of clinical pregnancy rate without reaching statistical significance. No statistical difference in reproductive outcomes between natural cycle and HRT cycle was observed in subgroup C. The results suggest the superiority of the natural cycle as compared with the HRT cycle under certain circumstances in a selected population of patients.

Novel Phosphatidylinositol 3-kinase Inhibitor NVP-BKM120 Induces Apoptosis in Myeloma Cells and Shows Synergistic Anti-myeloma Activity with Dexamethasone

Journal of Molecular Medicine (Berlin, Germany). Dec, 2011  |  Pubmed ID: 22207485

NVP-BKM120 is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor and is currently being investigated in phase I clinical trials in solid tumors. This study aimed to evaluate the therapeutic efficacy of BKM120 in multiple myeloma (MM). BKM120 induces cell growth inhibition and apoptosis in both MM cell lines and freshly isolated primary MM cells. However, BKM120 only shows limited cytotoxicity toward normal lymphocytes. The presence of MM bone marrow stromal cells, insulin-like growth factor, or interleukin-6 does not affect BKM120-induced tumor cell apoptosis. More importantly, BKM120 treatment significantly inhibits tumor growth in vivo and prolongs the survival of myeloma-bearing mice. In addition, BKM120 shows synergistic cytotoxicity with dexamethasone in dexamethasone-sensitive MM cells. Low doses of BKM120 and dexamethasone, each of which alone has limited cytotoxicity, induce significant cell apoptosis in MM.1S and ARP-1. Mechanistic study shows that BKM120 exposure causes cell cycle arrest by upregulating p27 (Kip1) and downregulating cyclin D1 and induces caspase-dependent apoptosis by downregulating antiapoptotic XIAP and upregulating expression of cytotoxic small isoform of Bim, BimS. In summary, our findings demonstrate the in vitro and in vivo anti-MM activity of BKM120 and suggest that BKM120 alone or together with other MM chemotherapeutics, particularly dexamethasone, may be a promising treatment for MM.

Forces and Torques on Rotating Spirochete Flagella

Physical Review Letters. Dec, 2011  |  Pubmed ID: 22243185

Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm.

[Anti-HIV Activity and Mechanism of Cynanchum Otophyllum Glucan Sulfate in Vitro]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Sep, 2011  |  Pubmed ID: 22256764

To study anti-HIV activity and mechanism of Cynanchum otophyllum glucan sulfate in vitro.

[Effects of Ryegrass (Lolium Perenne) Root Exudates Dose on Pyrene Degradation and Soil Microbes in Pyrene-contaminated Soil]

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. Oct, 2011  |  Pubmed ID: 22263480

By simulating a gradually decreasing concentration of root exudates with the distance away from root surface in rhizosphere, this paper studied the effects of ryegrass (Lolium perenne) root exudates dose on the pyrene degradation and microbial ecological characteristics in a pyrene-contaminated soil. It was observed that with the increasing dose of ryegrass root exudates, the residual amount of soil pyrene changed nonlinearly, i. e. , increased after an initial decrease. When the root exudates dose was 32.75 mg kg(-1) of total organic carbon, the residual pyrene was the minimum, indicating that the root exudates at this dose stimulated pyrene degradation significantly. In the meantime, soil microbial biomass carbon and microbial quotient had an opposite trend, suggesting the close relationship between pyrene degradation and soil microbes. In the test soil, microbial community was dominated by bacteria, and the bacteria had the same variation trend as the pyrene degradation, which indicated that the pyrene was degraded mainly by bacteria, and the effects of root exudates on pyrene degradation were mainly carried out through the effects on bacterial population. There was a similar variation trend between the activity of soil dehydrogenase, a microbial endoenzyme catalyzing the dehydrogenation of organic matter, and the soil microbes, which further demonstrated that the variations of soil microbes and their biochemical characteristics were the ecological mechanisms affecting the pyrene degradation in the pyrene-contaminated soil when the ryegrass root exudates dose increased.

The Carbonic Anhydrase Isoforms of Chlamydomonas Reinhardtii: Intracellular Location, Expression, and Physiological Roles

Photosynthesis Research. Sep, 2011  |  Pubmed ID: 21365258

Aquatic photosynthetic organisms, such as the green alga Chlamydomonas reinhardtii, respond to low CO(2) conditions by inducing a CO(2) concentrating mechanism (CCM). Carbonic anhydrases (CAs) are important components of the CCM. CAs are zinc-containing metalloenzymes that catalyze the reversible interconversion of CO(2) and HCO(3)(-). In C. reinhardtii, there are at least 12 genes that encode CA isoforms, including three alpha, six beta, and three gamma or gamma-like CAs. The expression of the three alpha and six beta genes has been measured from cells grown on elevated CO(2) (having no active CCM) versus cells growing on low levels of CO(2) (with an active CCM) using northern blots, differential hybridization to DNA chips and quantitative RT-PCR. Recent RNA-seq profiles add to our knowledge of the expression of all of the CA genes. In addition, protein content for some of the CA isoforms was estimated using antibodies corresponding to the specific CA isoforms: CAH1/2, CAH3, CAH4/5, CAH6, and CAH7. The intracellular location of each of the CA isoforms was elucidated using immunolocalization and cell fractionation techniques. Combining these results with previous studies using CA mutant strains, we will discuss possible physiological roles of the CA isoforms concentrating on how these CAs might contribute to the acquisition and retention of CO(2) in C. reinhardtii.

A Basic Phenylalanine-rich Oligo-peptide Causes Antibody Cross-reactivity

Electrophoresis. Mar, 2011  |  Pubmed ID: 21365653

Glycolate oxidase (GO) and ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) are the two enzymes that serve key functions in the photorespiration and photosynthesis of plants. A 2 kDa highly basic phenylalanine-rich oligo-peptide (BOP) binds to the surface of acidic GO via ionic and hydrophobic interactions, forming the GO-BOP complex (GC). Previously, RubisCO was thought to exist as a single species composed of a large (rbc L, 54 kDa) and a small subunit (rbc S, 14 kDa). Here we show for the first time, using 2-DE, SDS-PAGE, immunoassays and amino acid determination, that BOP also interacts with RubisCO and that many RubisCO-BOP complexes (RCs), differing in pI, hydrophobicity and activity, coexist in green leaves. GCs, RCs and crude extract from green leaves analyzed by SDS-PAGE Western blotting showed that BOP exists either in subunit-BOP complexes (GO subunit-BOP, rbc L-BOP and rbc S-BOP etc.), with a wide variation in the number and the position of BOPs bound to each subunit molecular, or alone without a binding partner. When rbc L-BOP and rbc S-BOP were assayed by SDS-PAGE, BOP was dissociated from the subunit and it self-assembled to form 37 different BOP polymers (basic phenylalanine-rich protein) whose molecular weights (M(r)s) ranged from 34.0 to 91.6 kDa, indicating that the M(r) of BOP is about 2 kDa. Thus, the addition of BOP changes the M(r) of the subunit-BOP complexes so minimally that the rbc L and rbc S run at their predicted M(r)s on SDS-PAGE. In summary, the results described here demonstrate that the presence of BOP in complexes (both subunit-BOP complex and protein-BOP complex) can cause cross-reactivity of antibodies against different proteins.

Identification and Characterization of Protective Epitope of Trichinella Spiralis Paramyosin

Vaccine. Apr, 2011  |  Pubmed ID: 21382481

Trichinella spiralis paramyosin (Ts-Pmy) is a protective antigen that induces partial immunity against T. spiralis infection in mice. To identify protective epitope of Ts-Pmy, a monoclonal antibody (mAb) 7E2 against the recombinant protein was generated, which partially protected against T. spiralis infection following passive transfer. The mAb was used to screen a random phage-displayed peptide library. Ten positive clones were identified, most of which matched amino acids 88-107 or 108-127 of Ts-Pmy. Expression of overlapping fragments of Ts-Pmy in E. coli confirmed that region 88-107 was specifically recognized by 7E2. A peptide based on this epitope region (YX1) was synthesized and shown to compete with native Ts-Pmy for binding to 7E2. Mice immunized with KLH-conjugated YX1 were protected against T. spiralis larval challenge. The identification of a protective epitope within Ts-Pmy highlights the possibility of developing a subunit vaccine against T. spiralis infection.

Molecular Characterization of Methicillin-resistant Staphylococcus Aureus Strains from Pet Animals and Veterinary Staff in China

Veterinary Journal (London, England : 1997). Nov, 2011  |  Pubmed ID: 21382731

The aim of this study was to determine the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolates from pet animals and veterinary staff and the characteristics of these isolates. A total of 22 MRSA isolates were isolated from nasal swabs from dogs, cats and veterinary staff in six pet hospitals in six cities, and examined for antimicrobial susceptibility, the presence of resistance genes, Panton-Valentine leukocidin gene lukF-lukS, staphylococcal chromosomal cassette (SCC) mec typing, spa tying, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Of 22 MRSA isolates, 21 were recovered from pet animals, and one was isolated from a member of sstaff. All 22 MRSA strains were resistant to penicillin, oxacillin, azithromycin, clindamycin and ceftriaxone, and harboured mecA, ermB and linA genes. The lukF-lukS gene was not detected in any of the MRSA isolates. Eighteen MRSA strains from Qingdao belonged to ST59-MRSA-IV-spa t437. Of four MRSA isolates from Beijing, one belonged to ST398-MRSA-V-spa t034, and three belonged to ST239-MRSA-III-spa t030 profiles. Two PFGE types (A and B) were identified. Two isolates originating from dogs and one isolate originating from a staff member in Beijing shared similar PFGE patterns. Our cumulative data suggested that cross-transmission of MRSA may have occurred between pet animals and veterinary staff.

CD44 Splice Isoform Switching in Human and Mouse Epithelium is Essential for Epithelial-mesenchymal Transition and Breast Cancer Progression

The Journal of Clinical Investigation. Mar, 2011  |  Pubmed ID: 21393860

Epithelial-mesenchymal transition (EMT) is a tightly regulated process that is critical for embryogenesis but is abnormally activated during cancer metastasis and recurrence. Here we show that a switch in CD44 alternative splicing is required for EMT. Using both in vitro and in vivo systems, we have demonstrated a shift in CD44 expression from variant isoforms (CD44v) to the standard isoform (CD44s) during EMT. This isoform switch to CD44s was essential for cells to undergo EMT and was required for the formation of breast tumors that display EMT characteristics in mice. Mechanistically, the splicing factor epithelial splicing regulatory protein 1 (ESRP1) controlled the CD44 isoform switch and was critical for regulating the EMT phenotype. Additionally, the CD44s isoform activated Akt signaling, providing a mechanistic link to a key pathway that drives EMT. Finally, CD44s expression was upregulated in high-grade human breast tumors and was correlated with the level of the mesenchymal marker N-cadherin in these tumors. Together, our data suggest that regulation of CD44 alternative splicing causally contributes to EMT and breast cancer progression.

Twist1-induced Invadopodia Formation Promotes Tumor Metastasis

Cancer Cell. Mar, 2011  |  Pubmed ID: 21397860

The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation. Twist1 induces PDGFRα expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFRα are central mediators of invadopodia formation in response to various EMT-inducing signals. Induction of PDGFRα and invadopodia is essential for Twist1 to promote tumor metastasis. Consistent with PDGFRα being a direct transcriptional target of Twist1, coexpression of Twist1 and PDGFRα predicts poor survival in breast tumor patients. Therefore, invadopodia-mediated matrix degradation is a key function of Twist1 in promoting tumor metastasis.

[Distribution and Emission of Methane from the Changjiang]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Jan, 2011  |  Pubmed ID: 21404659

Field surveys along the Changjiang were carried out in January 2008 and September 2008, persistently. Monthly survey at Xuliujing of the Changjiang Estuary was carried out from September 2007 to August 2008. Concentrations of methane in the Changjiang were measured by purge and trap-gas chromatography and the atmospheric methane fluxes were calculated according to the equation by Wanninkhof. The mean concentration in surface waters of the Changjiang was (330.8 +/- 186.9) nmol x L(-1) in January 2008 and (80.9 +/- 58.3) nmol x L(-1) in September 2008, persistently. Concentrations in bottom waters were consistent with those in surface waters. Supersaturated in methane with an average air-water flux of (385.1 +/- 278.0) micromol x (m2 x d)(-1). Besides, average methane concentration at Xuliujing was (167.5 +/- 91.4) nmol x L(-1) with an average air-water flux (690.9 +/- 291.6) micromol x (m2 x d)(-1), the high values appeared in February and July. Along the middle reaches of the Yangtze River, methane concentrations were increased, and the lower reaches were reduced. In the estuary, methane concentrations decreased rapidly from Xuliujing to the sea, showed negative correlation with salinity. The input of CH4-rich water form tributaries and lakes impacted the methane concentration trend of the Changjiang. The Changjiang was estimated to contribute 208 Gg CH4 to the atmosphere annually. However, the freshwater CH4 discharge to the East China Sea was 112 x 10(6) mol x a(-1) in the estuary.

[Systematic Review of Validation Phase of Breast Cancer Sentinel Lymph Node Biopsy Results in China]

Zhonghua Yi Xue Za Zhi. Feb, 2011  |  Pubmed ID: 21418905

To explore the studies and application status of sentinel lymph node biopsy (SLNB) in breast cancer in China by statistically analyzing the relevant domestic literature.

[Clinical Observation of Posterior Polymorphous Corneal Dystrophy]

[Zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology. Jan, 2011  |  Pubmed ID: 21418922

To research the clinical features and in vivo confocal microscopic findings of posterior polymorphous corneal dystrophy (PPCD).

Tetraspanin Microdomains: Fine-tuning Platelet Function

Biochemical Society Transactions. Apr, 2011  |  Pubmed ID: 21428931

Platelets are crucial for preventing excessive blood loss at sites of injury by plugging holes in damaged blood vessels through thrombus formation. Platelet thrombi can, however, cause heart attack or stroke by blocking diseased vessels upon rupture of atherosclerotic plaques. Current anti-platelet therapy is not effective in all patients and carries a risk of bleeding. As such, a major goal in platelet research is to identify new drug targets to specifically inhibit platelets in disease processes. Tetraspanins are potential candidates because of their capacity to regulate other proteins in microdomains, and their defined roles in cell adhesion and signalling. In the last 6 years, analyses of tetraspanin-deficient mice have suggested that tetraspanins are indeed important for fine-tuning platelet responses. The future characterization of novel regulatory mechanisms in tetraspanin microdomains may lead to new drug targets for the prevention and treatment of heart attack and stroke.

[Scanning of C-kit Gene Mutations in Acute Myeloid Leukemias Using High-resolution Melting Analysis]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Jan, 2011  |  Pubmed ID: 21429396

To detect the common mutations (D816V and N822K) of c-kit gene in acute myeloid leukemia (AML) using high-resolution melting analysis (HRM).

Novel Phenol Capturer Derived from the As-synthesized MCM-41

Journal of Hazardous Materials. Jun, 2011  |  Pubmed ID: 21439725

Novel phenol-capturer was prepared by modifying the as-synthesized mesoporous silica MCM-41 with tetraethylenepentamine (TEPA), not only saving the energy and time for removal of template, but also opening the way to utilize the micelles for adsorption. Once the organic modifier was distributed in the template micelle of MCM-41 to form a web within the mesoporous channel, the composite could adsorb more phenols in gas stream than activated carbon for the first time. With an unwanted high adsorption capacity, this mesoporous silica-amine composite represented potential application for trapping phenols, especially in tobacco smoke to protect environment.

Surface-enhanced Fluorescence from Fluorophore-assembled Monolayers by Using Ag@SiO2 Nanoparticles

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Apr, 2011  |  Pubmed ID: 21442706

A new and simple procedure to enhance the fluorescence of analytes on the surfaces of a solid substrate is demonstrated based on Ag@SiO(2) nanoparticles. Two kinds of silver-silica core-shell nanoparticles with shell thicknesses of around 3 and 15 nm have been prepared and used as enhancing agents, respectively. By simply pipetting drops of the enhancing agents onto substrate surfaces with Rose Bengal monolayers, an enhancement of about 27 times, compared with the control sample, is achieved by using the Ag@SiO(2) nanoparticles with shells of about 3 nm, whereas an enhancement of around 11.7 times is obtained when using those with thicker shells. The effects of shell thickness and surface density of the enhancing agents on the enhancement have been investigated experimentally. The results show that this method can be potentially helpful in fluorescence-based surface analysis.

Association Analysis of GSK3B and MAPT Polymorphisms with Alzheimer's Disease in Han Chinese

Brain Research. May, 2011  |  Pubmed ID: 21443865

Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3B) phosphorylates tau protein, and increased GSK-3B expression has been associated with neurofibrillary tangles. To determine whether polymorphisms in the GSK3B gene and microtubule associated protein tau (MAPT) gene underpin susceptibility to late-onset Alzheimer's disease (LOAD), we conducted a case-control study in a Chinese cohort of 257 LOAD cases and 326 healthy controls matched for sex and age. The minor allele (T) of the promoter rs334558 within GSK3B was associated with an increased risk of LOAD (odds ratios/OR=1.381, P=0.006), T carriers may be easier to develop AD (P=0.002, power=0.92). And the association was influenced by the presence of ApoE ε4 allele. Moreover, it showed a highly significant synergistic interaction with the ApoE ε4 allele (OR=3.782, P<0.001). All subjects in this study were identified as H1 MAPT haplotype. Haplotype analysis revealed that, the -157T/-50T haplotype significantly increased the risk of developing AD (OR=1.383, P=0.013). Our findings suggest that the functional polymorphisms in GSK3B promoter may be involved in the risk of developing sporadic LOAD in Han Chinese.

Radiographic Findings of Wistar Rats Fed with T-2 Toxin and Kashin-Beck Disease-affected Diet

International Journal of Rheumatic Diseases. Feb, 2011  |  Pubmed ID: 21303488

To characterize the features of radiographic abnormalities of the tibial bone in Wistar rats which have been fed T-2 toxin and Kashin-Beck disease (KBD) epidemic district food.

The Complete Genome Analysis of Two Enterovirus 96 Strains Isolated in China in 2005 and 2009

Virus Genes. Jun, 2011  |  Pubmed ID: 21318238

Enterovirus 96 (EV96) is a new member of species Human Enterovirus C (HEV-C). In this report, genomic characterization of two EV96 strains isolated from acute flaccid paralysis surveillance in Shandong province of China in 2005 and 2009 is described. The two strains, designated 05517 and 09228C1, had 82.7% genomic similarity with each other and 75.1-84.2% with other three strains available from GenBank in complete genome sequences. In VP1 coding region, they had 77.6-86.6% nucleotide similarity with other EV96 strains. Interestingly, deletions of 3 nucleotides in the VP3 coding region of strain 09228C1, and of 3 nucleotides in the 3A region of both Shandong strains were observed. Simplot and bootscanning analysis on HEV-C genome sequences were performed, and evidence of recombination in P3 region for Shandong EV96 strains was found. In conclusion, these strains had distant genetic relationship with each other and with other EV96 strains.

Use of Isotope Mass Probes for Metabolic Analysis of the Jasmonate Biosynthetic Pathway

The Analyst. Apr, 2011  |  Pubmed ID: 21331428

In order to quantitatively study the jasmonate biosynthetic pathway, we chemically synthesized a pair of isotope mass probes and established a labeling protocol. The pair of mass probes used in our work were ω-bromoacetonylpyridinium bromide (BPB) and d(5)-ω-bromoacetonylpyridinium bromide (d(5)-BPB), which contain carboxylic acid reactive groups, isotopically labeled groups and permanent positive charges. High performance liquid chromatography (HPLC) and electrospray ionization quadrupole-time of flight mass spectrometry (ESI-QTOF-MS) were used for the detection of labeled standard mixtures and plant samples. In comparison to negative mode electrospray ionization detection of unlabeled analytes, the ESI signal of reverse charge labeled compounds was shown to improve by 20- to 80-fold. Accurate relative quantification was achieved as no isotopic effects of the different isotope labeled phytohormones during RP/SCX mixed-mode liquid chromatographic separation were observed. A data analysis method was established for analyzing metabolic pathways using our labeling strategy. We then applied our method and examined the jasmonate biosynthetic pathway of rice under salt stress and the premature senescence mutant. Here we found that under salt stress conditions, rice showed up-regulation in (13S)-hydroperoxyoctadecatrienoic acid (HOPT), cis-(+)-12-oxophytodienoic acid (OPDA), 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid (OPC-8) and jasmonoyl-valine (JA-Val) levels, while α-linolenic acid (LA) and jasmonic acid (JA) showed down-regulation, and three components (HPOT, OPC-8 and JA-Val) were accumulated. The premature senescence mutant showed up-regulation in all major components of the jasmonate biosynthetic pathway with the exception of LA, and an accumulation of HPOT, OPC-6 and JA-Val. This study demonstrates that our chemical stable isotope labeling strategy can be used as a powerful tool for metabolic pathway analysis of phytohormones in plants.

Endogenous Axon Guiding Chemorepulsant Semaphorin-3F Inhibits the Growth and Metastasis of Colorectal Carcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. May, 2011  |  Pubmed ID: 21349996

To elucidate the role of Semaphorin-3F (SEMA3F), originally described as an axon guiding chemorepulsant implicated in nerve development, in the progression of colorectal carcinoma.

Three-dimensional GaN/AlN Nanowire Heterostructures by Separating Nucleation and Growth Processes

Nano Letters. Feb, 2011  |  Pubmed ID: 21265558

Bottom-up nanostructure assembly has been a central theme of materials synthesis over the past few decades. Semiconductor quantum dots and nanowires provide additional degrees of freedom for charge confinement, strain engineering, and surface sensitivity-properties that are useful to a wide range of solid state optical and electronic technologies. A central challenge is to understand and manipulate nanostructure assembly to reproducibly generate emergent structures with the desired properties. However, progress is hampered due to the interdependence of nucleation and growth phenomena. Here we show that by dynamically adjusting the growth kinetics, it is possible to separate the nucleation and growth processes in spontaneously formed GaN nanowires using a two-step molecular beam epitaxy technique. First, a growth phase diagram for these nanowires is systematically developed, which allows for control of nanowire density over three orders of magnitude. Next, we show that by first nucleating nanowires at a low temperature and then growing them at a higher temperature, height and density can be independently selected while maintaining the target density over long growth times. GaN nanowires prepared using this two-step procedure are overgrown with three-dimensionally layered and topologically complex heterostructures of (GaN/AlN). By adjusting the growth temperature in the second growth step either vertical or coaxial nanowire superlattices can be formed. These results indicate that a two-step method allows access to a variety of kinetics at which nanowire nucleation and adatom mobility are adjustable.

Developing a Mouse Model of Acute Bacterial Rhinosinusitis

European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. Jun, 2011  |  Pubmed ID: 21267587

The objective of this study is to establish a mouse model of acute bacterial rhinosinusitis. 179 healthy male BALB/c mice were divided into four groups in this randomized and controlled study. Sponge slivers impregnated with methicillin-resistant Staphylococcus aureus (MRSA COL) suspension were inserted into the right nasal cavities for group A; sponge slivers impregnated with sterile saline were inserted into the right nasal cavities for group B; group C mice were inoculated with MRSA COL suspension in right nasal cavities; group D was control group without any treatment. Mice were killed on days 1, 4, 7 and 14, respectively. Nasal lavage fluid was prepared for microbiological culture. Histological examinations of nasal specimens were performed to observe the severity of inflammatory reaction. Acute bacterial rhinosinusitis was induced in all group A mice. Less severe inflammation was seen in partial group B mice compared with that in group A mice (P ≤ 0.05). No inflammatory reaction was found in group C and D mice. In conclusion, a mouse model of acute bacterial rhinosinusitis has been developed successfully using an easier, less invasive and potentially more reversible technique than those used in previous studies.

Induction of Murine Neonatal Tolerance Against Graves' Disease Using Recombinant Adenovirus Expressing the TSH Receptor A-subunit

Endocrinology. Mar, 2011  |  Pubmed ID: 21285313

Graves' disease is a common organ-specific autoimmune disease. The identity of its autoantigen, the TSH receptor (TSHR), was established and used to induce a typical animal model. A-subunit, the shed portion of TSHR, either initiates or amplifies the autoimmune response of the thyroid gland, thereby causing Graves' disease in humans. In the present study, we investigate the effect of the TSHR A-subunit on the induction of murine neonatal tolerance for the development of Graves' disease. Female BALB/c mice were pretreated with different doses of adenovirus expressing the A-subunit of TSHR (Ad-TSHR289) by either ip or im injection within the first 24 h after their birth. Graves' disease was induced after the animals reached adulthood. Nearly all mice pretreated with the high dose of Ad-TSHR289 failed to develop TSHR antibodies, detected by the TSH-binding inhibition assay, hyperthyroidism, and thyroid follicular hyperplasia. The mice preimmunized im with the lower doses of Ad-TSHR289 developed a relatively low level of TSH-binding inhibition and the low incidence of hyperthyroidism. Accordingly, the percentages of splenic CD4+CD25+/CD4+ and CD25+Foxp3+/CD4+ Treg cells were increased in mice pretreated with the high dose of Ad-TSHR289. Taken together, our data strongly indicate that the immunotolerance against Graves' disease could be induced in neonatal mice using a specific TSHR antigen in a high dose either by ip or im injection, preventing the development of Graves' disease.

Small Interfering RNA Targeting IKKβ Prevents Renal Ischemia-reperfusion Injury in Rats

American Journal of Physiology. Renal Physiology. Apr, 2011  |  Pubmed ID: 21289055

The transcription factor NF-κB has been found critical to the pathogenesis of renal ischemia-reperfusion injury, which is a major cause of acute kidney injury (AKI). Activation of NF-κB is dependent upon the activation of the specific inhibitory κB kinase (IKK) subunit IKKβ. Here, we investigate whether small interfering RNA (siRNA) targeting IKKβ protects rats from renal ischemia- reperfusion injury in vivo. Renal ischemia-reperfusion injury was induced by clamping the renal artery for 45 min. Rats were treated before ischemia with IKKβ siRNA or scrambled siRNA, administered by renal artery injection. Treated animals were evaluated for renal IKKβ protein and mRNA expression, blood biochemistry, tissue histopathology, NF-κB/DNA binding activity, and expression of two downstream inflammatory cytokines, neutrophil gelatinase-associated lipocalin (NGAL) and IL-18. A local injection of IKKβ siRNA resulted in inhibition of renal IKKβ gene expression, NF-κB/DNA binding activity, and expression of NGAL and IL-18. Rats pretreated with IKKβ siRNA had significantly less blood urea nitrogen and serum creatinine levels and less renal tubular damage scores. Consequently, our data confirm that targeted silencing of IKKβ using siRNA substantially diminishes kidney injury and inflammation following ischemia-reperfusion.

Three-stage Enzymatic Hydrolysis of Steam-exploded Corn Stover at High Substrate Concentration

Bioresource Technology. Apr, 2011  |  Pubmed ID: 21300538

The feasibility of three-stage hydrolysis of steam-exploded corn stover at high-substrate concentration was investigated. When substrate concentration was 30% and enzyme loading was 15-30 FPU/g cellulose, three-stage (9+9+12 h) hydrolysis could reach a hydrolysis yield of 59.9-81.4% in 30 h. Compared with one-stage hydrolysis for 72 h, an increase of 34-37% in hydrolysis yield could be achieved. When steam-exploded corn stover was used as the substrate for enzyme synthesis and hydrolysis was conducted at a substrate concentration of 25% with an enzyme loading of 20 FPU/g cellulose, a hydrolysis yield of 85.1% was obtained, 19% higher than that the commercial cellulase could reach under the same conditions. The removal of end products was suggested to improve the adsorption of cellulase on the substrate and enhance the productivity of enzymatic hydrolysis.

Coincidence of Avascular Necrosis of the Femoral Head and Unstable Intertrochanteric Fracture: is an Extensively Coated Cementless Revision Stem a Reasonable Choice?

The Journal of Trauma. Dec, 2011  |  Pubmed ID: 21206291

Expression of P-JAK2 Predicts Clinical Outcome and is a Potential Molecular Target of Acute Myelogenous Leukemia

International Journal of Cancer. Journal International Du Cancer. Nov, 2011  |  Pubmed ID: 21207414

Our study determined if Janus kinase 2 (JAK2) was activated in acute myelogenous leukemia (AML; n = 77, excluding acute promyelocytic leukemia) by immunohistochemistry (IHC) using a phosphor-specific antibody against JAK2. p-JAK2 was detectable in all cases, although its levels varied between patient samples (high levels, n = 31; low levels, n = 46). The quantification of levels of p-JAK2 by IHC was well correlated with that assessed by Western blot analyses and fluorescence-activated cell sorting (FACS). Levels of p-JAK2 were directly correlated with high white blood cell count (52.3 × 10(3) /L in patients with high p-JAK2 vs. 28.3 × 10(3) /L in patients with low p-JAK2, p < 0.01) and were inversely correlated with complete remission rates (45% in patients with high p-JAK2 vs. 78% in patients with low p-JAK2, p < 0.003). In addition, multivariate analysis confirmed that high levels of p-JAK2 remained a significant factor for overall survival (hazard ratio = 2.213; 95% confidence interval, 1.212-4.041, p = 0.023). Moreover, we found that AZ960, a novel and specific inhibitor of the JAK2 kinase, potently inhibited the clonogenic growth and induced apoptosis of freshly isolated AML cells from patients in association with cleavage of caspase 3 and downregulation of anti-apoptotic Bcl-xL proteins. Taken together, JAK2 may be a promising molecular target for treatment of AML.

The Fission Yeast Schizosaccharomyces Pombe Has Two Distinct TRNase Z(L)s Encoded by Two Different Genes and Differentially Targeted to the Nucleus and Mitochondria

The Biochemical Journal. Apr, 2011  |  Pubmed ID: 21208191

tRNase Z is the endonuclease that is involved in tRNA 3'-end maturation by removal of the 3'-trailer sequences from tRNA precursors. Most eukaryotes examined to date, including the budding yeast Saccharomyces cerevisiae and humans, have a single long form of tRNase Z (tRNase ZL). In contrast, the fission yeast Schizosaccharomyces pombe contains two candidate tRNase ZLs encoded by the essential genes sptrz1+ and sptrz2+. In the present study, we have expressed recombinant SpTrz1p and SpTrz2p in S. pombe. Both recombinant proteins possess precursor tRNA 3'-endonucleolytic activity in vitro. SpTrz1p localizes to the nucleus and has a simian virus 40 NLS (nuclear localization signal)-like NLS at its N-terminus, which contains four consecutive arginine and lysine residues between residues 208 and 211 that are critical for the NLS function. In contrast, SpTrz2p is a mitochondrial protein with an N-terminal MTS (mitochondrial-targeting signal). High-level overexpression of sptrz1+ has no detectable phenotypes. In contrast, strong overexpression of sptrz2+ is lethal in wild-type cells and results in morphological abnormalities, including swollen and round cells, demonstrating that the correct expression level of sptrz2+ is critical. The present study provides evidence for partitioning of tRNase Z function between two different proteins in S. pombe, although we cannot rule out specialized functions for each protein.

Application of Infrared Emission Spectroscopy to the Thermal Transition of Indium Hydroxide to Indium Oxide Nanocubes

Applied Spectroscopy. Jan, 2011  |  Pubmed ID: 21211162

Cubic indium hydroxide nanomaterials were obtained by a low-temperature soft-chemical method without any surfactants. The transition of nano-cubic indium hydroxide to cubic indium oxide during dehydroxylation has been studied by infrared emission spectroscopy. The spectra are related to the structure of the materials and the changes in the structure upon thermal treatment. The infrared absorption spectrum of In(OH)(3) is characterized by an intense OH deformation band at 1150 cm(-1) and two O-H stretching bands at 3107 and 3221 cm(-1). In the infrared emission spectra, the hydroxyl-stretching and hydroxyl-bending bands diminish dramatically upon heating, and no intensity remains after 200 °C. However, new low intensity bands are found in the OH deformation region at 915 cm(-1) and in the OH stretching region at 3437 cm(-1). These bands are attributed to the vibrations of newly formed InOH bonds because of the release and transfer of protons during calcination of the nanomaterial. The use of infrared emission spectroscopy enables the low-temperature phase transition brought about through dehydration of In(OH)(3) nanocubes to be studied.

Humanized Mouse Model of Thrombosis is Predictive of the Clinical Efficacy of Antiplatelet Agents

Circulation. Jan, 2011  |  Pubmed ID: 21220740

In vivo testing of novel antiplatelet agents requires informative biomarkers. By genetically modifying mouse von Willebrand factor (VWF(R1326H)), we have developed a small animal model that supports human but not mouse platelet-mediated thrombosis. Here, we evaluate the use of this biological platform as a pharmacodynamic biomarker for antithrombotic therapies.

Actions of β-amyloid Protein on Human Neurons Are Expressed Through the Amylin Receptor

The American Journal of Pathology. Jan, 2011  |  Pubmed ID: 21224052

Disruption of neurotoxic effects of amyloid β protein (Aβ) is one of the major, but as yet elusive, goals in the treatment of Alzheimer's disease (AD). The amylin receptor, activated by a pancreatic polypeptide isolated from diabetic patients, is a putative target for the actions of Aβ in the brain. Here we show that in primary cultures of human fetal neurons (HFNs), AC253, an amylin receptor antagonist, blocks electrophysiological effects of Aβ. Pharmacological blockade of the amylin receptor or its down-regulation using siRNA in HFNs confers neuroprotection against oligomeric Aβ-induced caspase-dependent and caspase-independent apoptotic cell death. In transgenic mice (TgCRND8) that overexpress amyloid precursor protein, amylin receptor is up-regulated in specific brain regions that also demonstrate an elevated amyloid burden. The expression of Aβ actions through the amylin receptor in human neurons and temporospatial interrelationship of Aβ and the amylin receptor in an in vivo model of AD together provide a persuasive rationale for this receptor as a novel therapeutic target in the treatment of AD.

Differentiation Induction of Cardiac C-kit Positive Cells from Rat Heart into Sinus Node-like Cells by 5-azacytidine

Tissue & Cell. Apr, 2011  |  Pubmed ID: 21237473

Cardiac stem cells (CSCs) can differentiate into cardiac phenotypes representing early cardiomyocyte-like cells. However, CSCs-derived specification into sinus nodal cells is rarely known. Using the demethylating agent, 5-Aazacytidine (5-Aza), we tried to follow the process of cardiac specialization into sinus node-like cells. The c-kit+ cells were isolated from 1-month-old rat hearts and sorted by a flow cytometry cell sorting system. Then, analyses of immunofluorescence and reverse transcription polymerase chain reaction were performed on the cells. The sorted c-kit+ cell are self-renewing and clonogenic. Some of the c-kit+ cell could spontaneously express GATA-4, cardiac troponin I (cTnI), smooth muscle actin (SMA) and CD31. At week 8, the cells treated with 10 μM 5-Aza expressed GATA-4 and cTnI at rates of 31.4±2.6% and 32.6±8.5%. Correspondingly, the rates were 21.4±8.1% and 18.7±4.3% in the cells without 5-Aza. The difference of GATA-4 or cTnI expression rate between two groups was of significance respectively, P<0.05. The cultured cells could express mRNA of GATA4, hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) and HCN4. The mRNA expression was also up-regulated in cells treated with 10 μM 5-Aza and growth factors. By week 2 after cell sorting, inward currents could be recorded in a fraction of the cultured cells. In conclusion, 10 μM 5-Aza could promote the differentiation of c-kit+ cells into sinus node-like cells. 5-Aza-mediated differentiation seems to be helpful in future cell therapy for the patients suffering from loss of sinus node cells.

Blocking the Apolipoprotein E/amyloid-β Interaction Reduces Fibrillar Vascular Amyloid Deposition and Cerebral Microhemorrhages in TgSwDI Mice

Journal of Alzheimer's Disease : JAD. 2011  |  Pubmed ID: 21239853

The accumulation of amyloid-β (Aβ) peptides as toxic oligomers, amyloid plaques, and cerebral amyloid angiopathy (CAA) is critical in the pathogenesis of Alzheimer's disease (AD). The binding of Aβ peptides to apolipoprotein E (ApoE) plays an important role in modulation of amyloid deposition and clearance. We have shown that blocking the Aβ/ApoE interaction with Aβ(12-28P), a nontoxic blood-brain-barrier permeable and non-fibrillogenic synthetic peptide, constitutes a novel therapeutic approach for AD by reducing Aβ parenchymal deposition. In the present study, we investigate this therapeutic effect on CAA in the transgenic (Tg) AD mice model (TgSwDI), which expresses Swedish (K670N/M671L), Dutch (E693Q)/Iowa (D694N) AβPP mutations. These mice develop abundant CAA beginning at the age of 6 months. Behavioral results show that Aβ(12-28P) treated TgSwDI AD mice performed the same as wild-type mice, whereas vehicle treated TgSwDI were impaired in spatial memory. Furthermore, this treatment resulted in a significant reduction of total amyloid burden, especially the fibrillar vascular amyloid burden, which importantly was accompanied by a reduction in microhemorrhages and neuroinflammation. Measurement of Aβ levels in the brain homogenate revealed a significant decrease in both the total amount of Aβ and Aβ oligomer levels in Aβ(12-28P) treated TgSwDI mice. These findings suggest that blocking the Aβ/ApoE interaction is a highly effective therapeutic approach for vascular amyloid deposition, in contrast to some other therapeutic approaches.

Molecule-ion Interaction and Its Effect on Electrostatic Interaction in the System of Copper Chloride and β-cyclodextrin

Inorganic Chemistry. Mar, 2011  |  Pubmed ID: 21244034

The present work was devoted to an experimental investigation of the molecule-ion interaction between copper chloride (CuCl(2)) and β-cyclodextrin (CD) and its effect on the electrostatic interaction between Cu(2+) and Cl(-) ions. Our results gave an explicit description of the mutual effect between the interactions. First, the molecular arrangement and surface feature of β-CD experienced a fundamental structural change after interaction with Cu(2+) and Cl(-) ions, which was ascribed to a good separation of Cu(2+) from Cl(-) ions in β-CD matrix. Second, arguments based on electronic structural analysis provided a direct indication of the change in charge density distributions of Cu(2+) and Cl(-) ions in the presence of β-CD. Third, the actual occurrence of a second signal in the course of water release at a higher temperature suggested that the Cu(2+) ions were trapped in the form of hydrates in the crystal interstice of β-CD molecules. Fourth, comparison of the mass spectra indicated that the thermal decomposition of β-CD in the presence of CuCl(2) produced a series of interesting molecular ions: C(3)H(2)OH(+), C(4)H(3)OH(+), C(5)H(4)OH(+), and C(7)H(6)OH(+). We consider that this study is helpful in providing a new approach to the evaluation of the extent of the mutual effect between an inorganic salt and an organic molecule.

Unique Ability of BiOBr To Decarboxylate D-Glu and D-MeAsp in the Photocatalytic Degradation of Microcystin-LR in Water

Environmental Science & Technology. Jan, 2011  |  Pubmed ID: 21247106

Bismuth oxide bromide, BiOBr, was used to catalyze the degradation of microcystin-LR (MC-LR) in water at neutral pH under visible light. During the investigation, twelve intermediates from MC-LR decomposition were identified by LC-MS. In addition to attacking MC-LR at the typically susceptible sites (i.e., the conjugated double bond of the Adda chain and terminal unsaturated bond of the Mdha chain), the BiOBr photocatalyst has the remarkable ability to decarboxylate the free acid groups on d-glutamic acid (Glu) and methyl-d-aspartic acid (MeAsp). This reactivity has not been previously observed with TiO(2) photocatalysis or with other MC-LR treatments in which decarboxylation does not occur until the MC-LR ring has been cleaved or mineralized to CO(2). Some expected intermediate products were detected with oxygen-18 labeling by using H(2)(18)O as the solvent to confirm that the decarboxylation process is mediated by BiOBr. Results from characterizing the intermediates as well as oxygen-18 labeling studies indicates that oxidative decarboxylation of MC-LR by BiOBr photocatalysis is not always initiated by hydroxyl radical attack (and/or interaction with a hole followed by hydrolysis) proposed mechanism in TiO(2) photocatalysis, whereas likely caused by a direct interaction between photoinduced hole of BiOBr and free carboxyl groups of MC-LR. This unusual decarboxylation behavior seems to be associated with the particular valence band and conduction band state of BiOBr photocatalyst. Also under BiOBr catalysis, a very stable guanidine group of l-arginine (l-Arg) that is nonreactive with TiO(2) photocatalysis is converted to an amino group and subsequently oxidized to a nitro group during the decomposition of MC-LR. This reaction sequence is also related to decarboxylation because the guanidine conversion requires a completely or partially decarboxylated precursor. Our results indicate that BiOBr, a photocatalyst that selectively destroys sites crucial to MC-LR toxicity, shows great promise as a means of effectively treating drinking water.

Detection of Amyloid Plaques Targeted by USPIO-Aβ1-42 in Alzheimer's Disease Transgenic Mice Using Magnetic Resonance Microimaging

NeuroImage. Apr, 2011  |  Pubmed ID: 21255656

Amyloid plaques are one of the pathological hallmarks of Alzheimer's disease (AD). The visualization of amyloid plaques in the brain is important to monitor AD progression and to evaluate the efficacy of therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (μMRI) in AD transgenic mice, where we used intra-carotid mannitol to enhance blood-brain barrier (BBB) permeability. In the present study, we used ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ1-42 peptide to detect amyloid deposition along with mannitol for in vivo μMRI by femoral intravenous injection. A 3D gradient multi-echo sequence was used for imaging with a 100μm isotropic resolution. The amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. Furthermore, two different quantitative analyses were used. The region of interest-based quantitative measurement of T2* values showed contrast-injected APP/PS1 mice had significantly reduced T2* values compared to wild-type mice. In addition, the scans were examined with voxel-based morphometry (VBM) using statistical parametric mapping (SPM) for comparison of contrast-injected AD transgenic and wild-type mice. The regional differences seen in VBM comparing USPIO-Aβ1-42 injected APP/PS1 and wild-type mice correlated with the amyloid plaque distribution histologically, contrasting with no differences between the two groups of mice without contrast agent injection in regions of the brain with amyloid deposition. Our results demonstrated that both approaches were able to identify the differences between AD transgenic mice and wild-type mice, after injected with USPIO-Aβ1-42. The feasibility of using less invasive intravenous femoral injections for amyloid plaque detection in AD transgenic mice facilitates using this method for longitudinal studies in the pathogenesis of AD.

Antiglioma Effects of Combined Use of a Baculovirual Vector Expressing Wild-type P53 and Sodium Butyrate

The Journal of Gene Medicine. Jan, 2011  |  Pubmed ID: 21259406

Combination therapy is usually desirable for successful cancer treatment, especially in cancers that are resistant to single forms of therapy.

Activity Levels in the Left Hemisphere Caudate-fusiform Circuit Predict How Well a Second Language Will Be Learned

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2011  |  Pubmed ID: 21262807

How second language (L2) learning is achieved in the human brain remains one of the fundamental questions of neuroscience and linguistics. Previous neuroimaging studies with bilinguals have consistently shown overlapping cortical organization of the native language (L1) and L2, leading to a prediction that a common neurobiological marker may be responsible for the development of the two languages. Here, by using functional MRI, we show that later skills to read in L2 are predicted by the activity level of the fusiform-caudate circuit in the left hemisphere, which nonetheless is not predictive of the ability to read in the native language. We scanned 10-y-old children while they performed a lexical decision task on L2 (and L1) stimuli. The subjects' written language (reading) skills were behaviorally assessed twice, the first time just before we performed the fMRI scan (time 1 reading) and the second time 1 y later (time 2 reading). A whole-brain based analysis revealed that activity levels in left caudate and left fusiform gyrus correlated with L2 literacy skills at time 1. After controlling for the effects of time 1 reading and nonverbal IQ, or the effect of in-scanner lexical performance, the development in L2 literacy skills (time 2 reading) was also predicted by activity in left caudate and fusiform regions that are thought to mediate language control functions and resolve competition arising from L1 during L2 learning. Our findings suggest that the activity level of left caudate and fusiform regions serves as an important neurobiological marker for predicting accomplishment in reading skills in a new language.

CD-insensitive PMD Monitoring Based on RF Power Measurement

Optics Express. Jan, 2011  |  Pubmed ID: 21263676

We propose and experimentally demonstrate a chromatic dispersion (CD)-insensitive first-order polarization mode dispersion (PMD) monitoring method based on radio-frequency (RF) power measurement. In high-speed (>10-GSym/s) transmission systems, a narrowband fiber Bragg grating (FBG) notch filter filters out the optical components at 10GHz away from the carrier. After square-law detection, the 10-GHz RF tone changes with PMD and is insensitive to CD, which can be used as a PMD monitoring signal. Compared with the monitoring techniques utilizing clock tone, the PMD measurement range is increased from 26.3-ps to 50-ps while the requirement of the bandwidth of photodetector is reduced from 19GHz to 10GHz in 19-Gsym/s systems. It is experimentally shown that this technique is efficient on CD-insensitive first-order PMD monitoring for 38-Gbit/s DQPSK and 57-Gbit/s D8PSK systems.

DUX4, a Candidate Gene for Facioscapulohumeral Muscular Dystrophy, Causes P53-dependent Myopathy in Vivo

Annals of Neurology. Mar, 2011  |  Pubmed ID: 21446026

Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern. In leading FSHD pathogenesis models, D4Z4 contractions are proposed to cause epigenetic changes, which ultimately increase expression of genes with myopathic potential. Although no gene has been conclusively linked to FSHD development, recent evidence supports a role for the D4Z4-encoded DUX4 gene in FSHD. In this study, our objective was to test the in vivo myopathic potential of DUX4.

[Prevalence Rate of Hypertension and Related Risk Factors in Populations of Tianjin.]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Mar, 2011  |  Pubmed ID: 21457656

OBJECTIVE: To investigate the prevalence rates of the different subtypes of hypertension and related risk factors in adults from Tianjin. METHODS: With multi-stage randomized cluster sampling method, 20 346 people aged 18 years and over were selected from both urban and rural areas of six geographical regions in Tianjin in 2006. A cross-sectional study was conducted. The prevalence rate of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), systolic and diastolic hypertension (SDH) and associated risk factors were analyzed with SPSS 17.0 software. RESULTS: The prevalence rates of hypertension in adults of Tianjin were 7.16% for ISH (standardized rate was 5.33%), 7.09% for IDH (standardized rate was 6.50%), and 13.61% for SDH (standardized rate was 9.94%) respectively. The ISH prevalence rate was lower than that of national rate of 7.6%, but the prevalence rates of IDH and SDH were higher than that of national rates of 4.4% and 7.4% respectively. The results from logistic regression model analyses indicated that the odds ratio (ORs) for combined risk factors of ISH, IDH and SDH in Tianjin that associated with factors as: lower level of education, living in rural areas were 1.291 (95%CI: 1.114 - 1.497), 1.790 (95%CI: 1.533 - 2.091) and 2.117 (95%CI: 1.879 - 2.386) respectively; ageing were 1.080 (95%CI: 1.073 - 1.086), 1.015 (95%CI: 1.010 - 1.020) and 1.055 (95%CI: 1.050 - 1.060) respectively; alcohol assumption were 1.244 (95%CI: 1.036 - 1.492), 1.199 (95%CI: 1.024 - 1.404) and 1.532 (95%CI: 1.345 - 1.744) respectively; overweight were 1.560 (95%CI: 1.358 - 1.792), 1.634 (95%CI: 1.429 - 1.869) and 2.104 (95%CI: 1.890 - 2.342) respectively; obesity were 2.216 (95%CI: 1.861 - 2.640), 3.125 (95%CI: 2.658 - 3.674) and 3.852 (95%CI: 3.383 - 4.385) respectively; impaired fasting glucose were 1.666 (95%CI: 1.327 - 2.092), 1.440 (95%CI: 1.126 - 1.841) and 1.872 (95%CI: 1.572 - 2.230) respectively. CONCLUSION: The prevalence rate of the different subtypes of hypertension was quite high in the population of Tianjin city and different measurements on prevention and treatment should be taken according to different subtypes of hypertension.

Antisense Oligonucleotides Targeting Abhydrolase Domain Containing 2 Block Human Hepatitis B Virus Propagation

Oligonucleotides. Mar-Apr, 2011  |  Pubmed ID: 21466387

Hepatitis B virus (HBV) infection is a major health concern worldwide and only a minority of treated patients develop a sustained protective response following a short course of therapy, and most patients require prolonged treatment to suppress viral replication. However, several recent reports showed that inhibition of certain host cell proteins prevented viral infection, specifically the human abhydrolase domain containing 2 (ABHD2) has been confirmed by our previous study to be upregulated in HepG2.2.15 cells but downregulated by lamivudine. These observations suggested that ABHD2 was important for HBV propagation and could be a target of novel anti-HBV drugs. To assess the importance of ABHD2 to the HBV infection process, antisense oligonucleotides (ASODNs) were used to downregulate ABHD2 expression in HepG2.2.15 cells. From 5 ASODNS candidates tested, AB3 significantly downregulated ABHD2 mRNA and protein expression levels. Further, AB3 significantly reduced HBV DNA, hepatitis B surface antigen, and hepatitis B "e" antigen protein expression levels in cell medium without affecting cell viability. These results suggest that downregulation of ABHD2 using ASODNs blocked HBV replication and expression without affecting host cell physiology. Further, data demonstrated an essential role of ABHD2 in HBV propagation, suggesting it can serve as a novel target for anti-HBV drug development.

Spironolactone Diminishes Spontaneous Ventricular Premature Beats by Reducing HCN4 Protein Expression in Rats with Myocardial Infarction

Molecular Medicine Reports. May-Jun, 2011  |  Pubmed ID: 21468609

Hyperpolarization-activated current (If) is the major ionic current contributing to the spontaneous diastolic depolarization of cardiac sinus node pacemaker cells. It is mediated by hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. However, several observations support a potential role of HCN channels in the arrhythmogenesis of working myocardium under pathological conditions. Spironolactone, a classic aldosterone blocker, has been proved to prevent spontaneous ventricular arrhythmias after myocardial infarction (MI). Here, we examined the effect of spironolactone on the expression of HCN channels and ventricular premature beats (VPBs) using a rat MI model. Sprague-Dawley rats were divided into a sham-operated group and MI groups treated with intragastric administration of saline or spironolactone (80 µg/kg/day) for 7 days immediately after ligation of the left coronary artery. Compared to the sham group, HCN2 and HCN4 protein levels were increased in MI rats. Treatment with spironolactone prevented the MI-induced increase of HCN4 protein levels (1.47 ± 0.16 vs. 1.81 ± 0.21, P<0.05). MI rats exhibited a marked increase of VPBs compared to the sham group (104 ± 17 vs. 3 ± 1 VPBs/h, P < 0.05). This the increase was reduced by spironolactone (55 ± 14 vs. 104 ± 17 VPBs/h, P < 0.05). Moreover, If current inhibitor (ivabradine, 0.5 mg/kg) further decreased the occurrence of VPBs in the control and spironolactone groups to the same level (54 ± 13 vs. 49 ± 8 VPBs/h, P > 0.05). In conclusion, spironolactone may prevent ischemia-induced VPBs by reducing HCN4 protein expression to basal levels.

A Systematic Review Assessing the Effectiveness of Alendronate in Reducing Periprosthetic Bone Loss After Cementless Primary THA

Orthopedics. Apr, 2011  |  Pubmed ID: 21469631

Periprosthetic bone loss, especially in the proximal part of the femur, is common after cementless total hip arthroplasty (THA). To determine the short- and long-term effect of alendronate on periprosthetic bone mineral density after THA, we conducted computerized searches for randomized, controlled trials evaluating the use of alendronate in patients treated with cementless primary THA. A review of PubMed, the Cochrane Central Register of Controlled Trials, Web of Science, and Embase from their inception to May 2010 was completed, and we assessed methodological quality and abstracted relevant data. Of 310 citations that were initially identified, 5 studies assessing 146 patients were reviewed. Those studies showed that significantly less periprosthetic bone loss had occurred in the alendronate-treated group than in the placebo-treated group during the short-term period after THA. For long-term investigation, the studies reported that the periprosthetic bone density was a bit higher in the alendronate-treated group compared to the placebo-treated group, but the differences did not reach statistical significance.This systematic review suggests that alendronate has a beneficial effect with regard to preservation of periprosthetic bone short-term after cementless THA. However, the studies could not provide enough evidence that the positive effect noted in the early postoperative period is maintained long-term. A longer follow-up with a larger number of participants is needed to confirm the outcome of cementless THA patients treated with alendronate.

Laser Dispersion of Detonation Nanodiamonds

Angewandte Chemie (International Ed. in English). Apr, 2011  |  Pubmed ID: 21472833

[Study of RASSF1A Expression and Promoter Demethylation in Hep-2 Cell Line]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Jan, 2011  |  Pubmed ID: 21473137

To investigate the effect of 5-Aza-dC and TSA to tumor suppressor gene RASSF1A expression and methylation level in Hep-2 cell line.

Midterm Results of Uncemented Acetabular Reconstruction for Posttraumatic Arthritis Secondary to Acetabular Fracture

The Journal of Arthroplasty. Oct, 2011  |  Pubmed ID: 21474274

At an average of 6.3 years after surgery, we evaluated midterm results of uncemented acetabular reconstruction in 31 hips with posttraumatic arthritis that developed after acetabular fracture. Patients were categorized by previous fracture treatments (open-reduction group and conservative-treatment group) and fracture patterns (simple group and complex group). Surgery duration and blood loss were greater in the open-reduction and complex groups than in the conservative-treatment and simple groups (P < .05). The mean Harris Hip Score increased from 49 before surgery to 89 after surgery. Survival with revision or radiographic acetabular loosening as an end point was 100%. Fracture treatments and patterns were associated with increased surgery duration and increased blood loss. Open reduction and internal fixation of a fracture favor anatomical restoration of the hip's rotational center.

Ascites Ultrafiltration and Concentration-reinfusion in Severe Ovarian Hyperstimulation Syndrome

British Journal of Hospital Medicine (London, England : 2005). Mar, 2011  |  Pubmed ID: 21475099

Mild forms of ovarian hyperstimulation syndrome are common in women undergoing in-vitro fertilization, affecting up to 33% of in-vitro fertilization cycles; 3-8% of cycles are complicated by moderate or severe ovarian hyperstimulation syndrome (Royal College of Obstetricians and Gynaecologists, 2006). To treat severe ovarian hyperstimulation syndrome, albumin and other colloid solutions are used intravenously to increase the perfusion pressure (Manaka et al, 1995; Balasch et al, 1996), heparin to restore coagulation (Balasch et al, 1996) and dopamine to increase renal blood flow (Brinsden et al, 1995), but these all have limited effects.

Cocirculation of Two Transmission Lineages of Echovirus 6 in Jinan, China, As Revealed by Environmental Surveillance and Sequence Analysis

Applied and Environmental Microbiology. Jun, 2011  |  Pubmed ID: 21478313

Enterovirus environmental surveillance on sewage from the city of Jinan, Shandong Province, China, was initiated in 2008. Thirty echovirus 6 (E6) strains-1 in 2008 and 29 in 2010-were isolated and identified. Most E6 isolates (n = 21) came from the sewage collected on August 2010, revealing high local E6 activity at that time. Interestingly, the VP1 sequences of most isolates, even from the same sewage, were not identical. Phylogenetic analysis of VP1 sequences revealed two lineages for these isolates, with 78.0 to 80.0% nucleotide identities with one another, 94.8 to 100.0% identity within the major lineage, and 92.7 to 98.5% identity within the minor one. The VP1 sequences of environmental isolates, clinical isolates from 1998 to 2010, and global E6 were subjected to evolutionary analysis using Bayesian phylodynamic methods. The inferred E6 VP1 ancestral sequence dated back to 1901 (range, 1873 to 1928) and evolved with 7.047 × 10(-3) substitutions per site per year. Shandong E6 segregated into three clusters, and the two environmental lineages belonged to clusters A and C, which originated in 2003 and 1992, respectively. The antigenicity analysis via neutralization assay confirmed great antigenic differences between Shandong isolates and a prototype strain. These findings underscore the value of continuous environmental surveillance and genetic analysis to monitor circulating enteroviruses in the population and give further insight into E6 evolution.

[The Effect of Aldosterone on the Proliferation and Collagen Production of Cardiac Fibroblasts]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Apr, 2011  |  Pubmed ID: 21481312

To investigate the effect of aldosterone (ALD) on the proliferation of fetal cardiac fibroblasts (FCFS) and the production of collagen I and collagen III in FCFS.

A Novel Role for TRPM8 in Visceral Afferent Function

Pain. Jul, 2011  |  Pubmed ID: 21489690

Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n=58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 μmol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P<.0001; n=37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 μmol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions.

Protection of Chronic Intermittent Hypobaric Hypoxia Against Collagen-induced Arthritis in Rat Through Increasing Apoptosis

Sheng Li Xue Bao : [Acta Physiologica Sinica]. Apr, 2011  |  Pubmed ID: 21505725

The aim of present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on collagen-induced arthritis (CIA) in rat. Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups: CIHH pre-treatment group (Pre-T), pre-control group (Pre-C), CIHH post-treatment group (Post-T), post-control group (Post-C) and blank control group (Con). The rats in Pre-T and Post-T groups were exposed to 28 d of hypobaric hypoxia (simulated 3 000 m altitude, 5 h per day, pO2 = 108.8 mmHg, 14% O2) in a hypobaric chamber before and 12 days after CIA induction, respectively. The rats in Pre-C and Post-C groups were only experienced CIA induction, being control groups for Pre-T and Post-T groups, respectively. The rats in Con group were not given any treatment. The thickness of two-hind paw of rat was measured with spiral micrometer and the degree of arthritis was evaluated by arthritis index (AI). Morphological changes of ankle joint were observed through HE staining. The apoptotic rate in synovial tissue was measured by terminal dUTP nick end labeling (TUNEL) and the apoptotic rate of CD3(+) T lymphocyte in spleen was measured by flow cytometry technique. The protein expressions of Bcl-2 and Bax were measured using immunohistochemistry SP method. The results showed that incidence rate of CIA in Pre-T rats was lower than that in Pre-C rats (P < 0.05). AI in Pre-T and Post-T rats were smaller than those in Pre-C and Post-C, respectively (P < 0.05). In Pre-C and Post-C rats, there were hyperplasia of synovial cell, pannus forming, infiltration with inflammatory cell, and destroyed cartilage and bone in ankle joint. On the contrary, pathological changes of ankle joint were alleviated significantly in Pre-T and Post-T rats. Compared with Pre-C and Post-C rats, apoptotic rates of synovial cell and T lymphocyte in Pre-T and Post-T rats were increased (P < 0.05). As to the possible anti-apoptosis mechanism, CIHH, no matter before and after CIA induction, decreased Bcl-2 expression and increased Bax expression in joint synovial cells and spleen T lymphocytes (P < 0.05), respectively. In conclusion, CIHH possesses a protective effect against CIA in rat by enhancing apoptosis of synovial cells and T lymphocytes, which may be related to the inhibition of Bcl-2 protein expression and the promotion of Bax protein expression.

High Levels of Expression of Fibroblast Growth Factor 21 in Transgenic Tobacco (Nicotiana Benthamiana)

Applied Biochemistry and Biotechnology. Sep, 2011  |  Pubmed ID: 21505802

Fibroblast growth factor-21 (FGF21) is a hepatic hormone that plays a critical role in metabolism, stimulating fatty acid oxidation in the liver and glucose uptake in adipose tissue. In this study, we produced tobacco plants expressing human recombinant FGF21 (hFGF21) via Agrobacterium-mediated transformation using a potato virus X (PVX)-based vector (pgR107). The vector contained the sequence encoding the human FGF21 gene fused with green florescence protein and a histidine tag. The recombinant plasmid was introduced into leaf cells of Nicotiana benthamiana (a wild Australian tobacco) via Agrobacterium-mediated agroinfiltration. As determined by fluorescence and Western blot of leaf extracts, the hFGF21 gene was correctly translated in tobacco plants. Seven days after agroinfection, the recombinant hFGF21 had accumulated to levels as high as 450 μg g(-1) fresh weight in leaves of agroinfected plants. The recombinant hFGF21 was purified from plant tissues by Ni-NTA affinity chromatography, and the purified hFGF21 stimulated glucose uptake in 3T3/L1 cells. This indicated that the recombinant hFGF21 expressed via the PVX viral vector in N. benthamiana was biologically active.

Impact of Luteinized Unruptured Follicles on Endometrial Receptivity

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. Apr, 2011  |  Pubmed ID: 21505981

This study examined the impact of luteinized unruptured follicle (LUF) on endometrial receptivity. The menstrual cycle of 17 LUF patients (LUF group) and 13 ovulatory women (control group) was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E(2) and P were detected by chemiluminescence. The results exhibited that (1) The mean serum P level in LUF group (7.32±2.56 ng/mL) was significantly lower than that in control group (11.17±3.17 ng/mL) (P<0.01). But there was no significant difference in the mean serum E2 levels between LUF group (179.35±81.60 pg/mL) and the control group (198.58±75.23 pg/mL) (P>0.05); (2) The mean expression intensities of ER, PR in endometrium of LUF group (183.86±2.43, 167.94±3.04) were significantly higher than those in control group (109.35±6.31, 105.98±4.07) (P<0.01); (3) The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients (114.90±11.38) were significantly lower than those in control group (191.34±1.82) (P<0.01); (4) The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level (r=0.77, P<0.01), but bore no significant relationship with serum E(2) level (r=0.01, P>0.05). It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.

Intracellular PH Sensing Using P-aminothiophenol Functionalized Gold Nanorods with Low Cytotoxicity

Analytical Chemistry. Jun, 2011  |  Pubmed ID: 21513305

We report an intracellular pH sensor based on surface enhanced Raman scattering (SERS) using the hydrochloric acid (HCl) treated gold nanorods (GNRs) as the SERS substrates and p-aminothiophenol (pATP) as the Raman reporter. Using the HCl treated GNRs previously reported by us, the biocompatibility and the SERS performance of GNRs have been greatly improved. Meanwhile, the adsorbed reporters are allowed to be directly exposed to the surrounding environments, which is very important for biosensors. It is found that the SERS spectrum of pATP is strongly dependent on the pH value. The intensities of SERS bands at 1142 cm(-1), 1390 cm(-1), and 1432 cm(-1) increased obviously with the pH value varying from 3.0 to 8.0. This pH-dependent SERS performance of pATP-functionalized HCl treated GNRs was well retained after the incorporation of the GNRs into living HeLa cells. Our experimental results indicate that such pATP-functionalized HCl treated GNRs can be used as an effective intracellular pH sensor. Thus, we show a good example that the bioapplications of the normal CTAB-stabilized GNRs can be expanded after the simple HCl treatment.

Hypomethylation of PRAME Promoter is Associated with Poor Prognosis in Myelodysplastic Syndrome

British Journal of Haematology. Jul, 2011  |  Pubmed ID: 21517806

Superabsorbent Polysaccharide Hydrogels Based on Pullulan Derivate As Antibacterial Release Wound Dressing

Journal of Biomedical Materials Research. Part A. Jul, 2011  |  Pubmed ID: 21523902

To accomplish ideal wound dressing, hydrogels based on a natural polysaccharide, pullulan were synthesized by chemical cross-linking. The tensile strengths of the hydrogel films (1 mm thick) were determined to range from 0.663 to 1.097 MPa in proportion to cross-linking degrees and water contents. The swelling study of the hydrogels in water showed remarkable water absorption property with swelling ratio up to 4000%, which provided the hydrogel with quick hemostatic ability and prevent the wound bed from accumulation of exudates. The water vapor transmission rate and water retention of the hydrogels were found to be in the range of 2213-3498 g/m²/day and 34.74-45.81% (after 6 days), indicating that the hydrogel can maintain a moist environment over wound bed, which could prevent the dehydration of the wound bed and prevent the scab formation. Biocompatibility test revealed that the hydrogels were not cytotoxic. The hydrogel could load antimicrobial agents and effectively suppress bacterial proliferation to protect the wound from bacterial invasion. These results suggest that the pullulan hydrogels prepared in this study may have high potential as new ideal wound-dressing materials.

Near-infrared and Mid-infrared Investigations of Na-dodecylbenzenesulfate Intercalated into Hydrocalumite Chloride (CaAl-LDH-Cl)

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Aug, 2011  |  Pubmed ID: 21531615

Hydrocalumite (CaAl-LDH-Cl) belongs to layered double hydroxides (LDHs). The intercalation of Na-dodecylbenzenesulfate (SDBS) into CaAl-LDH-Cl has been investigated by X-ray diffraction (XRD), mid-infrared (MIR) spectroscopy and near-infrared (NIR) spectroscopy. The mid-infrared spectra indicated that SDBS could be intercalated into CaAl-LDH-Cl, with the same lattice structure to that of CaAl-LDH-Cl, and the interlayer distance of resultant product was expanded to 2.78 nm as confirmed by XRD. The near-infrared spectra (9200-4000 cm(-1)) showed that a special spectral range from 6200 to 5600 cm(-1) and prominent bands of CaAl-LDH-Cl intercalated with SDBS around 8300 cm(-1). This band was assigned to the second overtone of the first fundamental of C-H stretching vibrations of SDBS, and can be used to determinate the result of CaAl-LDH-Cl modified by anionic surfactants. The bands of water stretching vibrations and -OH groups shifted to higher wavenumbers when CaAl-LDH-Cl was intercalated by SDBS, and their intensity of MIR and NIR spectra became lower in intensity.

Rapid and Reliable Detection of IDH1 R132 Mutations in Acute Myeloid Leukemia Using High-resolution Melting Curve Analysis

Clinical Biochemistry. Jul, 2011  |  Pubmed ID: 21539821

The mutations of isocitrate dehydrogenase 1 (IDH1) gene have been identified in a proportion of hematologic malignancies including acute myeloid leukemia (AML). The aim of the present study was to explore the reliability of the high-resolution melting analysis (HRMA) for the identification of IDH1 R132 mutations in AML.

Facile Synthesis of Zinc Hydroxide Carbonate Flowers on Zinc Oxide Nanorods with Attractive Luminescent and Optochemical Performance

Nanotechnology. Jun, 2011  |  Pubmed ID: 21543828

A simple synthesis route was designed to fabricate a functional composite, zinc hydroxide carbonate (ZHC) flowers on zinc oxide (ZnO) nanorods. The hydrolysis of hexamethylenetetramine (HMT) can generate various species which are slowly released and gradually change reaction modes in a Zn(NO(3))(2)/HMT solution. As a result, ZnO nanorods and ZHC flowers can be sequentially synthesized and connect very well under constant experimental conditions. The obtained composite has the advantages of both components and exhibits attractive properties. For instance, ZHC flowers on ZnO nanorods exhibit strong blue emission under the excitation of ultraviolet light, and dye-sensitized solar cells with the annealed composite as photoanode achieve much higher conversion efficiency than pure nanorod arrays.

Dynamic Behavior and Spontaneous Differentiation of Mouse Embryoid Bodies on Hydrogel Substrates of Different Surface Charge and Chemical Structures

Tissue Engineering. Part A. Sep, 2011  |  Pubmed ID: 21548714

Differentiation of embryoid bodies (EBs) into particular cell lineages has been extensively studied. There is an increasing interest in the effect of soft hydrogel scaffolds on the behavior of EBs, such as the initial adhesion, dynamic morphology change, and differentiation. In this study, without adding any other bioactive factors in the serum-containing medium, dynamic behaviors of mouse EBs loaded on the surface of hydrogels with different surface charge and chemical structures are investigated. EBs adhered quickly to negatively charged poly(sodium p-styrene sulfonate) (PNaSS) hydrogels, which facilitates EBs spreading, migration, and differentiation into three germ layers with high efficiency of cardiomyocytes differentiation, similar to that on gelatin coated polystyrene (PS) culture plate. While on neutral poly(acrylamide) (PAAm) hydrogels, EBs maintained the initial spherical morphology with high expression of pluripotency-related markers in the short culture periods, and then showed the significantly greater levels of selected endoderm markers after long-time culture. EBs cultured on negatively charged poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS) gels demonstrated the analogous behaviors with that of neutral PAAm gels at early differentiation phase (day 4+1). Then, their adhesion, spreading and differentiation were quite similar to that on negatively charged PNaSS gels. The correlation between surface properties of hydrogels and EBs differentiation was discussed.

Effect of Chemokine Receptors CCR7 on Disseminated Behavior of Human T Cell Lymphoma: Clinical and Experimental Study

Journal of Experimental & Clinical Cancer Research : CR. 2011  |  Pubmed ID: 21548969

The expression of chemokine receptors CCR7 has been studied in relation to tumor dissemination and poor prognosis in a limited number of cancers. No such studies have been done on CCR7 expression in non-Hodgkin's lymphoma (T-NHL). Our aim in this paper is to investigate the association between CCR7 expression and progression and prognosis of T-NHL.

Simultaneous Inhibition of DNA Methyltransferase and Histone Deacetylase Induces P53-independent Apoptosis Via Down-regulation of Mcl-1 in Acute Myelogenous Leukemia Cells

Leukemia Research. Jul, 2011  |  Pubmed ID: 21550660

We have recently established the MV4-11 acute myelogenous leukemia (AML) subline, designated as MV4-11 TP53 R248W, which possesses a missense mutation (CGG→TGG; R248W) in the TP53 gene, leading to inactivation of this transcription factor. DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-AzadC) induced apoptosis in MV4-11, but not in MV4-11 TP53 R248W cells. Another class of anti-epigenetic agent histone deacetylase inhibitor (HDACI) inhibited the proliferation of both MV4-11 and MV4-11 TP53 R248W cells. Notably, when 5-AzadC was combined with HDACI MS-275, apoptosis in MV4-11 TP53 R248W cells was significantly enhanced in parallel with activation of the caspase cascade, up-regulation of p21waf1 and γ-H2AX, and down-regulation of Mcl-1. Interestingly, inhibition of caspase 3 by the pan-caspase inhibitor attenuated the combination of 5-AzadC and MS-275-mediated apoptosis and down-regulation of Mcl-1 in MV4-11 TP53 R248W cells. Moreover, down-regulation of p21waf1 in MV4-11 R248W cells by a small interfering RNA blunted activation of caspase 3 after exposure to the combination of 5-AzadC and MS-275, indicating the role of p21waf1 to activate caspase 3. Taken together, TP53-independent up-regulation of p21waf1 activates caspase 3 and down-regulates Mcl-1 in AML cells. Combination of 5-AzadC and MS-275 may be a promising treatment strategy for individuals with leukemia in which TP53 is inactivated.

Targeting Cell Surface β2 -microglobulin by Pentameric IgM Antibodies

British Journal of Haematology. Jul, 2011  |  Pubmed ID: 21554263

Monoclonal antibodies (mAbs) specific for human β(2) -microglobulin (β(2) M) have been shown to induce tumour cell apoptosis in haematological and solid tumours via recruiting major histocompatibility complex (MHC) class I molecules into and excluding cytokine receptors from the lipid rafts. Based on these findings, we hypothesized that IgM anti-β(2) M mAbs might have stronger apoptotic effects because of their pentameric structure. Our results showed that, compared with IgG mAbs, IgM anti-β(2) M mAbs exhibited stronger tumouricidal activity in vitro against different tumour cells, including myeloma, mantle cell lymphoma, and prostate cancer, and in vivo in a human-like xenografted myeloma mouse model without damaging normal tissues. IgM mAb-induced apoptosis is dependent on the pentameric structure of the mAbs. Disrupting pentameric IgM into monomeric IgM significantly reduced their ability to induce cell apoptosis. Monomeric IgM mAbs were less efficient at recruiting MHC class I molecules into and exclusion of cytokine receptors from lipid rafts, and at activating the intrinsic apoptosis cascade. Thus, we developed and validated the efficacy of anti-β(2) M IgM mAbs that may be utilized in the clinical setting and showed that IgM anti-β(2) M mAbs may be more potent than IgG mAbs at inducing tumour apoptosis.

[Instantaneous Expression AFGF-GFP Fusion Gene in Safflower]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Feb, 2011  |  Pubmed ID: 21585026

To study the instantaneous expression aFGF-GFP fusion gene in Carthamus tinctorius.

Aqueous Synthesis of Internally Doped Cu:ZnSe/ZnS Core-shell Nanocrystals with Good Stability

Nanotechnology. Jul, 2011  |  Pubmed ID: 21597150

To prepare biologically available Zn-based NCs in aqueous solution, we herein reported the synthesis of aqueous Cu:ZnSe/ZnS NCs with internally doped aqueous Cu:ZnSe NCs as the core template. Due to the dual protection of Cu impurities by the ZnSe core and ZnS shells, the as-prepared Cu:ZnSe/ZnS NCs show excellent stability in the open air, which overcomes the intrinsic instability of traditional aqueous Cu:ZnSe NCs. The as-prepared Cu:ZnSe/ZnS NCs possess extremely good stability, good biocompatibility and lower cytotoxicity, and thus can be used as a promising candidate for fluorescent NC-based biological applications.

Multiple Factors Confer Specific Cdc42 and Rac Protein Activation by Dedicator of Cytokinesis (DOCK) Nucleotide Exchange Factors

The Journal of Biological Chemistry. Jul, 2011  |  Pubmed ID: 21613211

DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

Simple N-sulfinyl-based Chiral Sulfur-olefin Ligands for Rhodium-catalyzed Asymmetric 1,4-additions

Organic Letters. Jul, 2011  |  Pubmed ID: 21618990

A variety of N-sulfinyl-based chiral sulfur-olefin ligands has been successfully developed for the first time for rhodium-catalyzed highly efficient and enantioselective 1,4-additions. The ease of synthesis and needless consideration of the carbon chirality makes this novel type of ligands attractive for asymmetric catalysis.

The Myocardial Protection of Polarizing Cardioplegia Combined with Delta-opioid Receptor Agonist in Swine

The Annals of Thoracic Surgery. Jun, 2011  |  Pubmed ID: 21619990

The purpose of this study was to determine whether polarized arrest using adenosine/lidocaine cold crystalloid cardioplegia in combination with the hibernation inductor δ-opioid receptor agonist pentazocine would give satisfactory myocardial protection rather than using depolarized supranormal potassium cardioplegia, supranormal potassium cardioplegia with pentazocine, or adenosine/lidocaine cardioplegia.

[DNA Methylation and Histone Modification Relate to RASSF1A Gene Deletion in Laryngeal Carcinoma Tissues]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery. Apr, 2011  |  Pubmed ID: 21624251

To investigate the relationship between RASSF1A gene expression and DNA methylation or histone modification in laryngeal carcinoma tissues.

Up-regulation of CC Chemokine Ligand 20 and Its Receptor CCR6 in the Lesional Skin of Early Systemic Sclerosis

European Journal of Dermatology : EJD. Sep-Oct, 2011  |  Pubmed ID: 21742595

Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in systemic sclerosis (SSc) skin. However, little is known about the recruitment of these cells into skin lesions. Recently, the role of chemokines has been suggested in the pathogenesis of SSc. Here we studied the expressions and distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin lesions and the difference in CCL20 expressions and ability to recruite MNCs of normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated in SSc in contrast to normal human skin. mRNA levels were significantly expressed in SSc lesional skins vs normal skin tissues. SSDF displayed increased constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines (TNF-α and IL-1β) remarkably increased the expression of CCL20 in both NDF and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed stronger chemotactic activity to PBMCs than those from NDF. Thus our findings suggest that CCL20 released from cytokine-activated SSDF plays an important role in the induction of SSc by further recruiting more MNCs to the skin.

Adsorption of Enterobactin to Metal Oxides and the Role of Siderophores in Bacterial Adhesion to Metals

Langmuir : the ACS Journal of Surfaces and Colloids. Sep, 2011  |  Pubmed ID: 21744856

The potential contribution of chemical bonds formed between bacterial cells and metal surfaces during biofilm initiation has received little attention. Previous work has suggested that bacterial siderophores may play a role in bacterial adhesion to metals. It has now been shown using in situ ATR-IR spectroscopy that enterobactin, a catecholate siderophore secreted by Escherichia coli, forms covalent bonds with particle films of titanium dioxide, boehmite (AlOOH), and chromium oxide-hydroxide which model the surfaces of metals of significance in medical and industrial settings. Adsorption of enterobactin to the metal oxides occurred through the 2,3-dihydroxybenzoyl moieties, with the trilactone macrocycle having little involvement. Vibrational modes of the 2,3-dihydroxybenzoyl moiety of enterobactin, adsorbed to TiO(2), were assigned by comparing the observed IR spectra with those calculated by the density functional method. Comparison of the observed adsorbate IR spectrum with the calculated spectra of catecholate-type [H(2)NCOC(6)H(3)O(2)Ti(OH)(4)](2-) and salicylate-type [H(2)NCOC(6)H(3)O(2)HTi(OH)(4)](2-) surface complexes indicated that the catecholate type is dominant. Analysis of the spectra for enterobactin in solution and that adsorbed to TiO(2) revealed that the amide of the 2,3-dihydroxybenzoylserine group reorientates during coordination to surface Ti(IV) ions. Investigation into the pH dependence of enterobactin adsorption to TiO(2) surfaces showed that all 2,3-dihydroxybenzoyl groups are involved. Infrared absorption bands attributed to adsorbed enterobactin were also strongly evident for E. coli cells attached to TiO(2) particle films. These studies give evidence of enterobactin-metal bond formation and further suggest the generality of siderophore involvement in bacterial biofilm initiation on metal surfaces.

Trichinella Spiralis Paramyosin Binds to C8 and C9 and Protects the Tissue-dwelling Nematode from Being Attacked by Host Complement

PLoS Neglected Tropical Diseases. Jul, 2011  |  Pubmed ID: 21750743

Paramyosin is a thick myofibrillar protein found exclusively in invertebrates. Evidence suggested that paramyosin from helminths serves not only as a structural protein but also as an immunomodulatory agent. We previously reported that recombinant Trichinella spiralis paramyosin (Ts-Pmy) elicited a partial protective immunity in mice. In this study, the ability of Ts-Pmy to bind host complement components and protect against host complement attack was investigated.

The Complete Genome Sequence of an Enterovirus 76 Isolate in China Reveals a Recombination Event

Archives of Virology. Sep, 2011  |  Pubmed ID: 21755310

Enterovirus 76 (EV76) is a new member of species Human Enterovirus A (HEV-A). So far, the only complete genome sequence of the prototype strain from France has been available. In this study, we determined the complete nucleotide sequence of strain 04360, isolated from an acute flaccid paralysis patient in Shandong province, China in 2004. Sequence analysis revealed 80.7-94.7% VP1 nucleotide identity to other EV76 strains and provided evidence of recombination with other types of HEV-A in the P2 and P3 coding regions.

Glioma Gene Therapy Using Induced Pluripotent Stem Cell Derived Neural Stem Cells

Molecular Pharmaceutics. Oct, 2011  |  Pubmed ID: 21755959

Using neural stem cells (NSCs) with tumor tropic migratory capacity to deliver therapeutic genes is an attractive strategy in eliminating metastatic or disseminated tumors. While different methods have been developed to isolate or generate NSCs, it has not been assessed whether induced pluripotent stem (iPS) cells, a type of pluripotent stem cells that hold great potential for regenerative medicine, can be used as a source for derivation of NSCs with tumor tropism. In this study, we used a conventional lentivirus transduction method to derive iPS cells from primary mouse embryonic fibroblasts and then generated NSCs from the iPS cells. To investigate whether the iPS cell derived NSCs can be used in the treatment of disseminated brain tumors, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected into the cerebral hemisphere contralateral to a tumor inoculation site in a mouse intracranial human glioma xenograft model. We observed that NSCs expressing the suicide gene were, in the presence of ganciclovir, effective in inhibiting the growth of the glioma xenografts and prolonging survival of tumor-bearing mice. Our findings provide evidence for the feasibility of using iPS cell derived NSCs as cellular vehicles for targeted anticancer gene therapy.

Seed Oil of Brucea Javanica Induces Apoptotic Death of Acute Myeloid Leukemia Cells Via Both the Death Receptors and the Mitochondrial-Related Pathways

Evidence-based Complementary and Alternative Medicine : ECAM. 2011  |  Pubmed ID: 21760826

Seed oil of Brucea javanica (BJO) is extracted from the seeds of herb medicine Brucea javanica (L.), and its emulsion formulation (BJOE) has been used clinically to treat carcinomas for many years in China. The antileukemia potential of BJO was investigated in human acute myeloid leukemia cell lines (AML) U937 and HL-60 in vitro and in a mouse U937 xenograft tumor model. BJO induced AML cell apoptosis through activation of caspase-8 and modulation of apoptosis-related proteins. Meanwhile, the inhibition of survivin and XIAP increased the cytotoxicity of BJO. Consistent with these findings, BJO also increased subG(1) phase cells and cause PARP cleavage in AML patients' leukemia cells. In contrast, only weak cytotoxicity of BJO was found in peripheral blood lymphocytes (PBLs) of healthy volunteers. Moreover, oleic acid and linoleic acid were found to be the active components of BJO. Our study provided strong evidence for the first time that BJO induced apoptosis of both cultured and primary AML cells. Furthermore, intravenous injection of BJO significantly inhibited U937 tumor growth in the xenograft mouse model. These results suggest that BJO may have a therapeutic role in the treatment of human leukemia.

Nanoparticle-delivered VEGF-silencing Cassette and Suicide Gene Expression Cassettes Inhibit Colon Carcinoma Growth in Vitro and in Vivo

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Dec, 2011  |  Pubmed ID: 21761115

The strategies for tumor-specific expression of suicide genes and target tumor angiogenesis have been tested in tumors. However, the anti-tumor efficacy of the combination of these two strategies, particularly, delivering suicide gene and anti-angiogenesis agent by nanoparticles, has not yet been evaluated in colon carcinoma. We constructed a cassette to silence VEGF-A expression and express a fused yCDglyTK gene driven by tumor-specific promoter (shVEGF-CDTK). The DNA carrying shVEGF-CDTK was delivered into colon carcinoma cells by calcium phosphate nanoparticles (CPNPs). Cell proliferation was measured by MTT assay, and apoptosis was detected by flow cytometry. The anti-tumor effect of the combined cassette was tested in xenograft animal model. With 5-fluorocytosine (5-FC), CPNP-delivered shVEGF-CDTK DNA (CPNP-shVEGF-CDTK) showed high expression of fused yCDglyTK gene and effectively silenced VEGF-A expression in vitro and in vivo, which significantly inhibited colon carcinoma cell proliferation and induced apoptosis in vitro. With 5-FC, the systemic delivery of CPNP-shVEGF-CDTK significantly inhibited tumor growth in the colon carcinoma xenograft animal model. The combined cassette is obviously effective in inhibiting tumor cell proliferation and inducing apoptosis in vitro and tumor growth in vivo than the CPNP-shVEGF or CPNP-CDTK alone. The combination of VEGF-A-silencing and tumor-specific expression of suicide gene is an effective strategy for colon carcinoma treatment.

Cloning of a Vacuolar H(+)-pyrophosphatase Gene from the Halophyte Suaeda Corniculata Whose Heterologous Overexpression Improves Salt, Saline-alkali and Drought Tolerance in Arabidopsis

Journal of Integrative Plant Biology. Sep, 2011  |  Pubmed ID: 21762382

Salt, saline-alkali conditions, and drought are major environmental factors limiting plant growth and productivity. The vacuolar H(+)-translocating inorganic pyrophosphatase (V-H(+)-PPase) is an electrogenic proton pump that translocates protons into vacuoles in plant cells. Expression of V-H(+)-PPase increases in plants under a number of abiotic stresses, and is thought to have an important role in adaptation to abiotic stress. In this work, we report the isolation and characterization of the gene, ScVP, encoding a vacuolar inorganic pyrophosphatase (V-H(+)-PPase) from the halophyte, Suaeda corniculata. Semi-quantitative reverse transcription-polymerase chain reaction analysis showed that ScVP was induced in roots, stems and leaves under treatment with salt, saline-alkali and drought. Compared with wild-type (WT) Arabidopsis, transgenic plants overexpressing ScVP accumulated more Na(+) in leaves and roots, and showed increased tolerance to high salinity, saline-alkali and drought stresses. The germination percentage of transgenic Arabidopsis seeds was higher than that of WT seeds under the abiotic stresses. The root length of transgenic plants under salt stress was longer than that of WT plants. Furthermore, the rate of water loss during drought stress was higher in WT than in transgenic plants. Collectively, these results indicate that ScVP plays an important role in plant tolerance to salt, saline-alkali and drought stress.

[Study on the Influence of Bioclogging on Permeability of Saturated Porous Media by Experiments and Models]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. May, 2011  |  Pubmed ID: 21780592

This paper studied on the influence of bioclogging on permeability of saturated porous media. Laboratory hydraulic tests were conducted in a two-dimensional C190 sand-filled cell (55 cm wide x 45 cm high x 1.28 cm thick) to investigate growth of the mixed microorganisms (KB-1) and influence of biofilm on permeability of saturated porous media under condition of rich nutrition. Biomass distributions in the water and on the sand in the cell were measured by protein analysis. The biofilm distribution on the sand was observed by confocal laser scanning microscopy. Permeability was measured by hydraulic tests. The biomass levels measured in water and on the sand increased with time, and were highest at the bottom of the cell. The biofilm on the sand at the bottom of the cell was thicker. The results of the hydraulic tests demonstrated that the permeability due to biofilm growth was estimated to be average 12% of the initial value. To investigate the spatial distribution of permeability in the two dimensional cell, three models (Taylor, Seki, and Clement) were used to calculate permeability of porous media with biofilm growth. The results of Taylor's model showed reduction in permeability of 2-5 orders magnitude. The Clement's model predicted 3%-98% of the initial value. Seki's model could not be applied in this study. Conclusively, biofilm growth could obviously decrease the permeability of two dimensional saturated porous media, however, the reduction was much less than that estimated in one dimensional condition. Additionally, under condition of two dimensional saturated porous media with rich nutrition, Seki's model could not be applied, Taylor's model predicted bigger reductions, and the results of Clement's model were closest to the result of hydraulic test.

Chiral N-tert-butanesulfinyl α,β-unsaturated Ketimine: a Simple and Highly Effective Olefin/sulfinimide Hybrid Ligand for Asymmetric 1,4-additions

Organic & Biomolecular Chemistry. Sep, 2011  |  Pubmed ID: 21785794

One novel type of chiral olefin/sulfinimide hybrid ligands has been developed through a simple one-step condensation of α,β-unsaturated ketones with tert-butanesulfinamide and utilized successfully for rhodium-catalyzed asymmetric conjugated additions to furnish the desired adducts in high yields with excellent ee's.

Detection of the JAK2 Mutation in Myeloproliferative Neoplasms by Asymmetric PCR with Unlabeled Probe and High-resolution Melt Analysis

Journal of Clinical Laboratory Analysis. 2011  |  Pubmed ID: 21786333

Several methods have been established to detect the JAK2 V617F mutation, a frequent event involved in the pathogenesis of myeloproliferative neoplasms (MPNs). High-resolution melt (HRM) analysis is a newly established technique without the requirement of any gel-based post-PCR handling.

Drosophila Adducin Regulates Dlg Phosphorylation and Targeting of Dlg to the Synapse and Epithelial Membrane

Developmental Biology. Sep, 2011  |  Pubmed ID: 21791202

Adducin is a cytoskeletal protein having regulatory roles that involve actin filaments, functions that are inhibited by phosphorylation of adducin by protein kinase C. Adducin is hyperphosphorylated in nervous system tissue in patients with the neurodegenerative disease amyotrophic lateral sclerosis, and mice lacking β-adducin have impaired synaptic plasticity and learning. We have found that Drosophila adducin, encoded by hu-li tai shao (hts), is localized to the post-synaptic larval neuromuscular junction (NMJ) in a complex with the scaffolding protein Discs large (Dlg), a regulator of synaptic plasticity during growth of the NMJ. hts mutant NMJs are underdeveloped, whereas over-expression of Hts promotes Dlg phosphorylation, delocalizes Dlg away from the NMJ, and causes NMJ overgrowth. Dlg is a component of septate junctions at the lateral membrane of epithelial cells, and we show that Hts regulates Dlg localization in the amnioserosa, an embryonic epithelium, and that embryos doubly mutant for hts and dlg exhibit defects in epithelial morphogenesis. The phosphorylation of Dlg by the kinases PAR-1 and CaMKII has been shown to disrupt Dlg targeting to the NMJ and we present evidence that Hts regulates Dlg targeting to the NMJ in muscle and the lateral membrane of epithelial cells by controlling the protein levels of PAR-1 and CaMKII, and consequently the extent of Dlg phosphorylation.

[Effects of CDH1 Gene Promoter Methylation on Expression of E-cadherin and Beta-catenin and Its Clinicopathological Significance in Colon Carcinoma]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Jul, 2011  |  Pubmed ID: 21792768

To investigate the relationship between methylation of the CDH1 gene promoter on the expression of E-cadherin and β-catenin, and to evaluate the correlation with clinicopathological characteristics of the colonic carcinoma.

[Dehydrogenation by Short Ethoxy Chain Nonylphenol Dehydrogenase from Ensifer Sp. AS08]

Wei Sheng Wu Xue Bao = Acta Microbiologica Sinica. May, 2011  |  Pubmed ID: 21800626

To study dehydrogenation by short ethoxy chain nonylphenols dehydrogenase (sNPEO-DH) from Ensifer sp. AS08.

Bromodomain-peptide Displacement Assays for Interactome Mapping and Inhibitor Discovery

Molecular BioSystems. Oct, 2011  |  Pubmed ID: 21804994

Histone lysine acetylation is a key component of epigenetic regulation of gene transcription. Bromodomains, found in histone acetyl transferases and other chromatin-associated proteins, bind selectively to acetylated lysines, acting as "readers" of the histone code, and have recently been shown to contain a druggable binding pocket. Here we report the development of high-throughput assays that quantify the binding of bromodomains to acetylated histone peptides. We have used these assays to screen for histone binding partners of as yet uncharacterized bromodomains, adding to current knowledge of the histone code and expanding the repertoire of assays for chemical probe discovery. We have also demonstrated that these assays can be used to detect small molecule binding from the very weak to the nanomolar range. This assay methodology is thereby anticipated to provide the basis both for broader interactome profiling and for small molecule inhibitor discovery.

[Signal Transduction Pathway for TNF-induced IL-6 Release from Mast Cells]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Aug, 2011  |  Pubmed ID: 21806874

To investigate the effect of TNF on release of IL-6, IL-10 and histamine from mast cells and to explore its potential signal transduction pathway.

[Purification and Identification of Pregnancy Associated Plasma Protein A]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Aug, 2011  |  Pubmed ID: 21806876

To purify pregnancy associated plasma protein A (PAPP-A) from the pregnancy serum using the methods of G200 gel filtration, reverse affinity chromatography and DEAE ion exchange.

LRRC4 Inhibits the Proliferation of Human Glioma Cells by Modulating the Expression of STMN1 and Microtubule Polymerization

Journal of Cellular Biochemistry. Dec, 2011  |  Pubmed ID: 21809374

LRRC4 is a tumor suppressor of glioma, and it is epigenetically inactivated commonly in glioma. Our previous study has shown that induction of LRRC4 expression inhibits the proliferation of glioma cells. However, little is known about the mechanisms underlying the action of LRRC4 in glioma cells. We employed two-dimensional fluorescence differential gel electrophoresis (2-D DIGE) and MALDI -TOF/TOF-MS/MS to identify 11 differentially expressed proteins, including the significantly down-regulated STMN1 expression in the LRRC4-expressing U251 glioma cells. The levels of STMN1 expression appeared to be positively associated with the pathogenic degrees of human glioma. Furthermore, induction of LRRC4 over-expression inhibited the STMN1 expression and U251 cell proliferation in vitro, and the glioma growth in vivo. In addition, induction of LRRC4 or knockdown of STMN1 expression induced cell cycle arrest in U251 cells, which was associated with modulating the p21, cyclin D1, and cyclin B expression, and the ERK phosphorylation, and inhibiting the CDK5 and cdc2 kinase activities, but increasing the microtubulin polymerization in U251 cells. LRRC4, at least partially by down-regulating the STMN1expression, acts as a major glioma suppressor, induces cell cycle arrest and modulates the dynamic process of microtubulin, leading to the inhibition of glioma cell proliferation and growth. Potentially, modulation of LRRC4 or STMN1 expression may be useful for design of new therapies for the intervention of glioma.

Fast Computing Betweenness Centrality with Virtual Nodes on Large Sparse Networks

PloS One. 2011  |  Pubmed ID: 21818337

Betweenness centrality is an essential index for analysis of complex networks. However, the calculation of betweenness centrality is quite time-consuming and the fastest known algorithm uses O(N(M + N log N)) time and O(N + M) space for weighted networks, where N and M are the number of nodes and edges in the network, respectively. By inserting virtual nodes into the weighted edges and transforming the shortest path problem into a breadth-first search (BFS) problem, we propose an algorithm that can compute the betweenness centrality in O(wDN2) time for integer-weighted networks, where w is the average weight of edges and D is the average degree in the network. Considerable time can be saved with the proposed algorithm when w < log N/D + 1, indicating that it is suitable for lightly weighted large sparse networks. A similar concept of virtual node transformation can be used to calculate other shortest path based indices such as closeness centrality, graph centrality, stress centrality, and so on. Numerical simulations on various randomly generated networks reveal that it is feasible to use the proposed algorithm in large network analysis.

Identification and Expression Analysis of a Novel Transcript of the Human PRMT2 Gene Resulted from Alternative Polyadenylation in Breast Cancer

Gene. Nov, 2011  |  Pubmed ID: 21820040

The arginine N-methyltransferase 2 protein (PRMT2, also known as HRMT1L1) is thought to act as a coactivator of ERα. The present results show the occurrence of a novel transcript by alternative polyadenylation in the human PRMT2 gene. We demonstrated that the newly identified intron-retaining PRMT2L2 transcript is functionally intact, efficiently translated into protein in vivo. PRMT2 and PRMT2L2 mRNA expression profiles overlap with the distribution of ERα, with the strongest abundance in estrogen target tissues. Transient co-transfection assays demonstrated that PRMT2L2 enhance ERα-mediated transactivation activity of ERE-Luc in a ligand-dependent manner. Confocal microscopy scanning revealed a distinct intra-cellular localization of their fusion proteins, suggesting that the C-terminal region absent in PRMT2L2 is critical for the localization. Statistical analysis further showed that both PRMT2 and PRMT2L2 mRNAexpressions were up-regulated in breast cancer tissues, and significantly associated with ERα positivity status. Thus, post-transcriptional processing mechanism as alternative polyadenylation and splicing may play a crucial role in regulating human PRMT2 gene expression.

Genome-wide Association Analysis of Thirty One Production, Health, Reproduction and Body Conformation Traits in Contemporary U.S. Holstein Cows

BMC Genomics. 2011  |  Pubmed ID: 21831322

Genome-wide association analysis is a powerful tool for annotating phenotypic effects on the genome and knowledge of genes and chromosomal regions associated with dairy phenotypes is useful for genome and gene-based selection. Here, we report results of a genome-wide analysis of predicted transmitting ability (PTA) of 31 production, health, reproduction and body conformation traits in contemporary Holstein cows.

A Logistic Regression Analysis of Factors Related to the Treatment Compliance of Infertile Patients with Polycystic Ovary Syndrome

The Journal of Reproductive Medicine. Jul-Aug, 2011  |  Pubmed ID: 21838163

To investigate factors that can affect compliance with treatment of polycystic ovary syndrome (PCOS) in infertile patients and to provide a basis for clinical treatment, specialist consultation and health education.

Novel Electropharmacological Activity of Amiodarone on Human HCN Channels Heterologously Expressed in the Xenopus Oocytes

European Journal of Pharmacology. Nov, 2011  |  Pubmed ID: 21839071

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the pacemaker currents (I(f)) in cardiac cells. The objectives of this study were to investigate the electropharmacological activity of amiodarone on human HCN channels heterologously expressed in Xenopus laevis oocytes. hHCN channels were expressed in oocytes and studied using the standard two-electrode voltage-clamp techniques. The results show that amiodarone blocks hHCN channels heterologously expressed in the Xenopus oocytes in a concentration- and use-dependent manner, but doesn't modify the voltage dependence of activation and reversal potentials. And the removal of blockage of HCN channels by amiodarone was favored by inward current flow, not by hyperpolarizing potential. Characteristics of blockage on hHCN channels were consistent with those of amiodarone as "trapped" drugs on human ether-a-go-go-related gene (HERG) channels. These results will be useful for elucidating the potentially antiarrhythmic mechanism of amiodarone.

Preclinical Pharmacokinetic Analysis of Felotaxel (SHR110008), a Novel Derivative of Docetaxel, in Rats and Its Protein Binding Ability in Vitro

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. Dec, 2011  |  Pubmed ID: 22264880

Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new taxane with potent antitumor effects. The purpose of this research was to evaluate the pharmacokinetic profiles of felotaxel in rats and the protein binding in plasma. Data were collated from several preclinical investigations, where the plasma pharmacokinetics, tissue distribution and excretion of felotaxel were assessed after a single intravenous (i.v.) injection (5mg/kg) to rats. Samples felotaxel concentration was determined by a LC-MS/MS method. The plasma concentration versus time data was analyzed non-compartmental model. Plasma protein binding was assessed using ultrafiltration. Pharmacokinetic properties of felotaxel were similar to the previous data from the rats. Felotaxel was rapidly distributed to normal tissues, drug concentrations in the tissues tested except the brain were two to eight times higher than those in plasma, but half-lives and mean residence times were similar. The kidneys manifested as the dominant organs with high exposure that might be responsible for elimination of felotaxel. Approximately 0.21% and 0.72% of felotaxel was excreted via the urine and feces within 24h; 0.25% was excreted into the bile up to 12h after a single dose. The protein binding ability of felotaxel with concentration 100-5000ng/mL in the plasma was nearly linear. This study first provided the full absorption, distribution, and excretion characteristics of felotaxel, which would be helpful for its clinical regiment design.

Effects of Amlodipine on the Oral Bioavailability of Cephalexin and Cefuroxime Axetil in Healthy Volunteers

Journal of Clinical Pharmacology. Jan, 2012  |  Pubmed ID: 22275382

In this study, the authors compared the effects of amlodipine (AML) on the bioavailability of cephalexin (LEX) and cefuroxime axetil (CXM). Twenty-four healthy men were randomized to 4 treatments according to a crossover design with a 14-day washout. After an overnight fast, they were administered orally LEX 500 mg alone, LEX 500 mg 2 hours after oral administration of AML 5 mg, CXM 500 mg alone, and CXM 500 mg 2 hours after oral administration of AML 5 mg. All participants completed the whole study without side effects being observed. Pharmacokinetic data were analyzed by noncompartmental modeling with WinNonlin software. The geometric mean (GM) ratios were 1.38 (90% confidence interval [CI], 1.32-1.45) for the area under the concentration-time curve (AUC) for LEX and 1.27 (1.18-1.36) for the maximum concentration of drug in serum (C(max)) for LEX followed by AML versus alone. In contrast, no significant differences were found in the pharmacokinetic parameters of CXM between treatments (P < .05). They authors conclude that AML possesses an enhancement effect in β-lactam antibiotic bioavailability (in this case, LEX), and this interaction may be specific to the peptidomimetic β-lactam antibiotics.

Correction to The Structural Basis for Homotropic and Heterotropic Cooperativity of Midazolam Metabolism by Human Cytochrome P450 3A4

Biochemistry. Feb, 2012  |  Pubmed ID: 22277091

Application of a Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) Method to the Pharmacokinetics, Tissue Distribution and Excretion Studies of Felotaxel (SHR110008) in Tumor-bearing Mice

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Jan, 2012  |  Pubmed ID: 22309773

Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new effective taxane with greater anticancer activity and less toxicity than docetaxel. Pharmacokinetic studies in animal models are the important components in clinical development of this agent. In this study, a rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of felotaxel in tumor-bearing mice plasma, urine, feces and tissues (brain, heart, liver, lung and kidney and tumor). For all matrices, sample preparation involved liquid-liquid extraction with ethyl acetate. Calibration curves (1/x(2) weighted) offered satisfactory linearity (r(2)≥0.995) within the test range. The lower limit of quantitation (LLOQ) for all matrices was 10ng/ml except that for mouse plasma and brain LLOQ was 1ng/ml. The accuracy and precision ranged from 86.1 to 107.2% and 1.1 to 9.2%, respectively. Recoveries (73.9-96.1%) and matrix effects (76.4-97.2%) were satisfactory in all the biological matrices examined. Stability studies (85.1-101.5%) showed that felotaxel was stable both during the assay procedure and long-term storage. The assay was successfully applied to plasma pharmacokinetics, tissue distribution and excretion study of mice. The pharmacokinetic parameters, such as half-life, mean residence time, maximum concentration were determined. The preclinical data are useful for the design of clinical trials of felotaxel.

Evaluating the Prevalence and Molecular Epidemiology of Echovirus 11 Isolated from Sewage in Shandong Province, China in 2010

Virus Genes. Feb, 2012  |  Pubmed ID: 22311429

Echovirus 11 (E11) is an important human pathogen, but its genetic information in China is in scarce. In this study, 12 sewage samples from Jinan city and 18 from Linyi city were collected in Shandong Province, China in 2010, and E11 was the predominant serotype with 54 isolates from 16 samples. Numbers of E11 isolates reached peaks in August in both Jinan and Linyi city, while another peak occurred in December in Linyi. The complete VP1 genes of all these isolates were sequenced and phylogenetically compared with clinical isolates from Shandong in 1994-2010 (n = 29) and global E11. Shandong isolates segregated into five clusters, four in genogroup A and one in genogroup C. Environmental isolates belonged to two clusters of genogroup A, with high inter-cluster genetic divergence (18.5-20.9%). No local clinical E11 was isolated in the two cities in 2010, revealing the value of environmental surveillance in investigating circulating viruses. These findings underscored the significance of environmental VP1 sequence divergences in comprehending the local enterovirus circulation, and updated the global molecular epidemiology of E11.

Tumor Tropism of Intravenously Injected Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells and Their Gene Therapy Application in a Metastatic Breast Cancer Model

Stem Cells (Dayton, Ohio). Feb, 2012  |  Pubmed ID: 22311724

Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we employed a conventional lentiviral transduction method to derive human induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole body imaging technology, we demonstrated that after tail vein injection these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help overcome problems associated with allogeneic transplantation of other types of human NSCs.

Retention of a Well-fixed Acetabular Component in the Setting of Acetabular Osteolysis

International Orthopaedics. Feb, 2012  |  Pubmed ID: 22314642

PURPOSE: The treatment strategy for pelvic osteolysis with a well-fixed acetabular component after total hip arthroplasty (THA) involves replacing the acetabular cup liner and femoral head, débriding osteolytic lesions, and grafting. METHODS: We investigated whether retention of a well-fixed acetabular component using the two-approach technique-the ilioinguinal approach combined with the posterolateral approach-was compatible with socket survival. We reviewed clinical and radiographic findings for 24 patients (24 hips) who had undergone acetabular revision arthroplasty of a well-fixed socket for progressive osteolysis. The surgical techniques used included osteolytic lesion débridement and bone grafting through the ilioinguinal approach, and replacement of the acetabular liner and femoral head through the posterolateral approach. RESULTS: The mean duration of follow-up after revision was 2.3 (range 2.1-3.9) years. At follow-up evaluation, all acetabular components were well fixed and showed no evidence of loosening, osseous integration was apparent and there was no radiographic evidence that any lesions had progressed. No new osteolytic lesions were identified, and there were no clinical or radiographic complications. CONCLUSIONS: Curettage and bone grafting under direct vision, cup liner and femoral-head replacement because of progressive retroacetabular osteolysis and retention of well-fixed components using the two-approach technique results in good osseous integration of lysis. Larger studies with longer follow-up periods are required to establish the long-term success of this technique.

CCND1 G870A Polymorphism is Associated with Increased Risk of Colorectal Cancer, Especially for Sporadic Colorectal Cancer and in Caucasians: A Meta-analysis

Clinics and Research in Hepatology and Gastroenterology. Feb, 2012  |  Pubmed ID: 22322158

AIMS: To detect the association between G870A polymorphism of cyclin D1 (CCND1) gene and colorectal cancer. METHODS: We performed a systematic literature and abstract search using PubMed, EMBase digital database. Keywords included CCND1, cyclin D1, polymorphism, SNP, colon cancer, rectal cancer and colorectal cancer. "And", "OR" and "NOT" were used as conjunction to narrow and widen the search. Data were extracted by two investigators independently, and meta-analysis was carried out by using Review Manager 4.2.8. The following pairwised combinations of genotypes for the CCND1 G870A polymorphism were evaluated: AA vs. GG, AG vs. GG, AA+AG vs. GG. Subsequently, sub-group analyses for cancer type, ethnicity, and the family history were performed. Sensitivity analysis was conducted by excluding the articles deviated from Hardy-Weinberg equilibrium. RESULTS: Using GG genotype as a reference, A carriers were associated with a significantly increased cancer risk (OR=1.15, 95%CI=1.06-1.25, P=0.001, P(heterogeneity)=0.130), especially with rectal cancer (OR=1.24, 95%CI=1.02-1.51, P=0.030, P(heterogeneity)=0.570) and sporadic colorectal cancer (OR=1.26, 95%CI=1.08-1.46, P=0.003, P(heterogeneity)=0.730). The effect of A carriers on cancer also existed in Caucasians (OR=1.19, 95%CI=1.06-1.32, P=0.002, P(heterogeneity)=0.100). CONCLUSIONS: CCND1 G870A polymorphism is associated with the increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians.

Syndrome Differentiation in Modern Research of Traditional Chinese Medicine

Journal of Ethnopharmacology. Feb, 2012  |  Pubmed ID: 22322251

Syndrome differentiation (Bian Zheng) in traditional Chinese medicine (TCM) is the comprehensive analysis of clinical information gained by the four main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, and it is used to guide the choice of treatment either by acupuncture and/or TCM herbal formulae, that is, Fufang. TCM syndrome differentiation can be used for further stratification of the patients' conditions with certain disease, identified by orthodox medical diagnosis, which could help the improvement of efficacy of the selected intervention. In modern TCM research it is possible to integrate syndrome differentiation with orthodox medical diagnosis leading to new scientific findings in overall medical diagnosis and treatment. In this review, the focus is to screen published evidence on the role of syndrome differentiation in modern TCM research with particular emphasis on basic and clinical research as well as, pharmacological evaluation of TCM herbal formulary for drug discovery.

Partition Dataset According to Amino Acid Type Improves the Prediction of Deleterious Non-synonymous SNPs

Biochemical and Biophysical Research Communications. Feb, 2012  |  Pubmed ID: 22326261

Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

Thrombomodulin Enhances the Anti-fibrinolytic and Anti-leukemic Effects of All-trans Retinoic Acid in Acute Promyelocytic Leukemia Cells

Experimental Hematology. Feb, 2012  |  Pubmed ID: 22327096

This study found that levels of thrombomodulin (TM) were down-regulated in freshly isolated leukemia cells from patients with acute promyelocytic leukemia (APL, n=7) and acute myelogenous leukemia (AML, n=14), as compared with CD34(+)/CD38(-) hematopoietic stem/progenitor cells and CD34(-)/CD33(+)/CD11b(-) promyelocytes isolated from healthy volunteers (n=3). Exposure of APL NB4 cells to recombinant human soluble TM (rTM, 1500 ng/mL) inhibited clonogenic growth of these cells by approximately 30%, and induced expression of CD11b, a marker of myeloid differentiation, on their surfaces, in association with up-regulation of nuclear levels of myeloid specific transcription factor CCAAT/enhancer binding protein ε. These anti-leukemic effects of rTM were mediated by thrombin/activated protein C (APC)-dependent mechanisms, as hirudin, an inhibitor of thrombin and a blocking antibody against endothelial receptor for protein C to which APC binds hampered the ability of rTM to induce expression of CD11b in NB4 cells. This study also found that rTM down-regulated expression of annexin II, a receptor for both plasminogen and tissue plasminogen activator, and inhibited plasmin activity in APL cells. Interestingly, rTM significantly enhanced the ability of all-trans retinoic acid (ATRA) to induce growth arrest, differentiation and apoptosis, and inhibited plasmin activity in APL cells. Taken together, these results suggest that administration of rTM should be considered for treatment of individuals with DIC associated with APL.

CD40 C/T(-1) and CTLA-4 A/G(49) SNPs Are Associated with Autoimmune Thyroid Diseases in the Chinese Population

Endocrine. Feb, 2012  |  Pubmed ID: 21866398

This study was to investigate whether the common polymorphisms of CD40 and CTLA4 genes confer susceptibility to AITD in the Chinese population. A set of unrelated subjects including 303 GD patients, 208 HT patients, and 215 matched healthy controls were recruited. SNPs were genotyped by the method of PCR-RFLP. (1) As for CD40 C/T(-1) SNP, only a significant difference was found in allele frequencies between GD and control groups (P = 0.033). (2) On the part of CTLA-4 A/G(49) SNP, significant differences were found in genotype and allele frequencies between GD and control groups (P = 7.0 × 10(-5) and P = 0.002, respectively), and similar results were found between HT and control groups (P = 0.015 and P = 0.003, respectively). (3) The logistic regression analysis showed there was no interaction between CD40 and CTLA4 genotypes (P = 0.262). These results indicate that both CTLA-4 A/G(49) and CD40 C/T(-1) SNPs are associated with genetic susceptibility of GD, and CTLA-4 A/G(49) is also associated with HT.

Long-term Exposure of Gastrointestinal Stromal Tumor Cells to Sunitinib Induces Epigenetic Silencing of the PTEN Gene

International Journal of Cancer. Journal International Du Cancer. Feb, 2012  |  Pubmed ID: 21445973

Although sunitinib possesses significant clinical effects on imatinib-resistant gastrointestinal stromal tumors (GISTs), the individuals with GIST eventually become resistant to treatment with this tyrosine kinase inhibitor. The mechanism of resistance to sunitinib is still under investigation. To address this issue, we have established sunitinib-resistant GIST-T1 sublines (designated as GIST-T1R) by culturing cells with increasing concentrations of sunitinib. GIST-T1R cells were also resistant to imatinib-mediated growth inhibition. Examination of intracellular signaling found that Akt/ mammalian target of rapamycin (mTOR) signaling remained activated in GIST-T1R but not in parental GIST-T1 cells, after exposure of these cells to sunitinib, as measured by immunoblotting. Further study found that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was silenced by methylation of the promoter region of the gene. Notably, forced-expression of PTEN in GIST-T1R cells negatively regulated the Akt/mTOR pathways and sensitized these cells to sunitinib-mediated growth arrest and apoptosis. Taken together, epigenetic silence of PTEN might be one of the mechanisms which cause drug-resistance in individuals with GIST after exposure to tyrosine kinase inhibitors. Blockade of the PI3K/Akt signaling with the specific inhibitors could be useful in such a case.

Association of Interleukin 10 and Interferon Gamma Gene Polymorphisms with Enterovirus 71 Encephalitis in Patients with Hand, Foot and Mouth Disease

Scandinavian Journal of Infectious Diseases. Jan, 2012  |  Pubmed ID: 22263663

Abstract Enterovirus 71 (EV71) is one of the common causative agents of hand, foot and mouth disease (HFMD), and is associated with several outbreaks with neurological complications including encephalitis. This study investigated the polymorphisms of interferon gamma (IFN-γ)+874 T/A and interleukin 10 (IL-10)-1082 G/A in 65 Chinese patients with EV71 encephalitis and 113 Chinese HFMD patients without complications. The polymorphisms of IFN-γ+874 T/A and IL-10-1082 G/A were determined by polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) and PCR-sequence-specific primer (SSP) analysis, respectively. The IFN-γ + 874 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (76.2%) compared with HFMD patients without complications (61.1%, p < 0.01). Similarly, the IL-10 - 1082 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (86.2%) compared with HFMD patients without complications (77.0%, p < 0.05). IFN-γ + 874 A and IL-10 - 1082 A alleles are associated with susceptibility to EV71 encephalitis in Chinese patients.

Small Adsorbate-assisted Shape Control of Pd and Pt Nanocrystals

Advanced Materials (Deerfield Beach, Fla.). Feb, 2012  |  Pubmed ID: 22252856

The shape control of noble metal nanocrystals is crucial to their optical properties and catalysis applications. In this Progress Report, the recent progress of shape-controlled synthesis of Pd and Pt nanostructures assisted by small adsorbates is summarized. The use of small strong adsorbates (e.g., I(-) , CO, amines) makes it possible to fabricate Pd and Pt nanostructures with not only well-defined surface structure but also morphologies that have not been achieved by other synthetic strategies. The roles of small adsorbates in shape control of Pd and Pt nanocrystals are discussed in the Report. Also presented in the Report are unique optical and catalytic properties of several Pd and Pt nanostructures (e.g., ultrathin Pd nanosheets, concave Pt octapod, concave Pd tetrahedra), as well as their bioapplications, to demonstrate the power of using small strong adsorbates in the shape control of Pt and Pd nanostructures.

Serum Bone Alkaline Phosphatase in Assessing Illness Severity of Infected Neonates in the Neonatal Intensive Care Unit

International Journal of Biological Sciences. 2012  |  Pubmed ID: 22211102

Infections can influence bone metabolism of neonates, which may lead to changes in some bone metabolism biomarkers. The purpose of this study was to determine whether serum bone alkaline phosphatase (BALP), osteocalcin (OC) and beta carboxy-terminal peptide of type I collagen (CTX), as specific biomarkers of bone metabolism, can be used to assess the severity of neonatal infections. METHODs: Sixty-three neonates in the NICU were enrolled in this study. The neonates were divided into infected group (n=33) and non-infected group (n=30). The scores for neonatal acute physiology-perinatal extension II (SNAPPE-II) were calculated and interleukin-6 (IL-6), procalcitonin (PCT), BALP, OC and CTX were measured among the neonates with or without infections, and among the infected neonates before and after treatment.

Photoelectrochemical Biofuel Cell Using Porphyrin-sensitized Nanocrystalline Titanium Dioxide Mesoporous Film As Photoanode

Biosensors & Bioelectronics. Feb, 2012  |  Pubmed ID: 22221794

Electrical energy generated directly from sunlight and biomass solution with a Photoelectrochemical Biofuel Cell (PEBFC) was investigated. The PEBFC consisted of a meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP)-sensitized nanocrystalline titanium dioxide (TiO(2)) mesoporous film (NTDMF) as the photoanode and platinum black as the cathode. The interaction between TCPP sensitizer and NTDMF was evaluated by X-ray photoelectron spectra and FT-IR absorption spectra, indicating that the TCPP sensitizer was adsorbed on the NTDMF by bridging or bidentate coordinate bonds. The spectroscopic properties of pure TCPP ethanol solution and TCPP-sensitized NTDMF were obtained by UV-vis absorption spectra, demonstrating that the characteristic absorption peaks of TCPP on NTDMF displayed slight red shift compared with pure TCPP ethanol solution. The performances of the PEBFC were obtained by photocurrent-photovoltage characteristic curves. The open-circuit photovoltage (V(oc)), the short-circuit photocurrent (I(sc)) and the maximum power density (P(max)) was 0.74 V, 69.96 μA and 33.94 μWcm(-2) at 0.45 V, respectively. The fill factor (FF) was 0.19 and the incident photo-to-current efficiency (IPCE) was 36.0% at 436 nm. The results demonstrated that the TCPP was an appropriate photosensitizer for PEBFC.

Methicillin-resistant Staphylococcus Pseudintermedius Isolated from Canine Pyoderma in North China

Journal of Applied Microbiology. Jan, 2012  |  Pubmed ID: 22229826

Aims:  To determine the prevalence of carriage of methicillin-resistant Staphylococcus pseudintermedius (MRSP) among dogs with pyoderma from two small animal hospitals in North China during a 21-month period, and to characterize these isolates. Methods and Results:  Swabs were taken from 260 dogs with pyoderma, the staphylococcal species isolated and methicillin resistance were confirmed phenotypically and genotypically. The identified MRSP isolates were characterized by multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome (SCC) mec typing, testing for susceptibility to nine antimicrobial agents and SmaI-digested pulsed-field gel electrophoresis. Thirty-three (12.7%) dogs were positive for MRSP. The most prevalent genotypes detected among MRSP were ST71(MLST)-t06(spa)-II-III(SCCmec) (n=22, 66.7%), followed by ST5-t19 (n=8, 24.2%), ST126-III(n= 2, 6.1%) and ST6-t02-V (3.0%). All MRSP isolates showed extended resistance to tested antimicrobial agents. Eight different SmaI patterns were observed in 21 typeable MRSP isolates. Conclusions:  Clinical isolates of MSRP isolated from dogs in North China belonged to two major clonal lineages ST71 and ST5. Significance and Impact of the Study:  This study is the first report on MRSP from canine pyoderma in China. Further surveillance study is needed to gain more detailed data concerning this major clinical challenge in veterinary medicine. © 2012The Authors Journal of Applied Microbiology© 2012 The Society for Applied Microbiology.

Rh(I)-Catalyzed Asymmetric 1,2-Addition to α-Diketones with Chiral Sulfur-Alkene Hybrid Ligands

Organic Letters. Jan, 2012  |  Pubmed ID: 22233270

This paper describes a Rh(I)-catalyzed highly efficient and enantioselective 1,2-addition of arylboronic acids to α-diketones with the use of a simple sulfur-alkene hybrid ligand. With as low as a 0.1 mol % catalyst loading, a variety of optically active α-hydroxyketones can be furnished in high yields with excellent ee's.

[Expression and Its Clinical Significance of SLC22A18 in Non-small Cell Lung Cancer]

Zhongguo Fei Ai Za Zhi = Chinese Journal of Lung Cancer. 2012  |  Pubmed ID: 22237119

It has been proven that multidrug resistance (MDR) is the main cause of chemotherapy failure in lung cancer. Research on emergence mechanisms of MDR has great clinical significance in improving the curative efficiency of lung cancer chemotherapy. Proteins encoded by the SLC22A18 gene, which is similar to the transmembrane transporter, may influence the sensitivity of chemotherapeutics as well as the metabolism and growth of cells. In addition, these proteins probably have some effect on the development of lung cancer MDR. The aim of the present study is to investigate the expression of SLC22A18 protein in non-small cell lung cancer (NSCLC) as well as in corresponding normal lung tissue. Furthermore, the relationship between SLC22A18 expression and pathological grade and TNM stage is analyzed.

A Controllable Transformation in Copper Valence States and Its Applications

Dalton Transactions (Cambridge, England : 2003). Feb, 2012  |  Pubmed ID: 22200050

The present study revealed a surprising valence transformation of copper (Cu) in the sintering process of mixtures of copper chloride dihydrate (CuCl(2)·2H(2)O) with β-cyclodextrin (β-CD) in ambient atmosphere. Such a transformation in Cu valence states can be modulated by changing the initial molar ratio (IMR) of CuCl(2)·2H(2)O to β-CD in the mixtures. Firstly, as the value of IMR decreased, the content of cuprous chloride (CuCl) decreased, while the content of cupric oxide (CuO) increased gradually. That is to say, there is an unambiguous IMR-dependence of the contents of CuCl and CuO formed. However, such a controllable valence transformation from Cu(II) to Cu(I) to Cu(II) did not happen in nitrogen atmosphere. Secondly, the in situ composite of CuCl and CuO produced a highly ordered structure of self-assembled nanowires, intertwined, with a diameter of 30 to 50 nm. Furthermore, electronic structural analysis provided direct evidence that the Cu-Cl and Cu-O bonds in this composite material were simultaneously impaired by self-assembled growth. Finally, we noticed that the photoluminescence property of CuCl was regulated through the formation of composites with CuO. In addition, this in situ composite synthesis technique was used to modify the magnetic property of CuO. Furthermore, the anomalous ferromagnetic behaviour of the CuO nanocrystal was observed and explained. In short, this work not only demonstrates a flexible and easily controllable valence transformation of Cu, but also provides a novel approach for constructing inorganic nanocomposite materials. We believe that the implications of these findings are important and make significant contributions to the development of inorganic chemistry and material science.

Resistive Switching Induced by Metallic Filaments Formation Through Poly(3,4-ethylene-dioxythiophene):Poly(styrenesulfonate)

ACS Applied Materials & Interfaces. Jan, 2012  |  Pubmed ID: 22201222

We report the design and fabrication of Al/poly(3,4-ethylene-dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/Cu resistive memory devices that utilize the Cu redox reaction and conformational features of PEDOT:PSS to achieve resistive switching. The top Cu electrode acts as the source of the redox ions that are injected through the PEDOT:PSS layer during the forming process. The Cu filament is confirmed directly using the cross-sectional images of transmission electron microscopy and energy-dispersive X-ray spectroscopy. The resultant resistive memory devices can operate over a small voltage range, i.e., the switching-on threshold voltage is less than 1.5 V and the absolute value of the switching-off threshold voltage is less than 1.0 V. The on/off current ratio is as large as 1 × 10(4) and the two different resistance states can be maintained over 10(6) s. Moreover, the devices present good thermal stability that the resistive switching can be observed even at temperature up to 160 °C, at which the oxidation of the Cu top electrode is the failure factor. Furthermore, the cause of failure for Al/PEDOT:PSS/Cu memory devices at higher temperature is confirmed to be the oxidation of Cu top electrode.

Disruption of a Glutathione Reductase Encoding Gene in Acremonium Chrysogenum Leads to Reduction of Its Growth, Cephalosporin Production and Antioxidative Ability Which is Recovered by Exogenous Methionine

Fungal Genetics and Biology : FG & B. Feb, 2012  |  Pubmed ID: 22202809

Glutathione is a ubiquitous thiol in eukaryotic cells, and its high intracellular ratio of reduced form (GSH) to oxidized form (GSSG) is largely maintained by glutathione reductase (GR) using NADPH as electron donor. glrA, a glutathione reductase encoding gene, was found and cloned from Acremonium chrysogenum by searching its genomic sequence based on similarity. Its deduced protein exhibits high similarity to GRs of other eukaryotic organisms. Disruption of glrA resulted in lack of GR activity and accumulation of a high level of GSSG in A. chrysogenum. Overexpression of glrA dramatically enhanced GR activity and the ratio of GSH/GSSG in this fungus. The spore germination and hyphal growth of glrA disruption mutant was strongly reduced in chemical defined medium. Meanwhile, the mutant was more sensitive to hydrogen peroxide than the wild-type strain. We found that the glrA mutant recovered normal germination and growth by adding exogenous methionine (Met). Exogenous Met also enhanced the antioxidative ability of both the mutant and wild-type strain. GSH determination indicated that the total GSH and ratio of GSH/GSSG in the mutant or wild-type strain were significantly increased when addition of Met into the medium. The glrA mutant grew poorly and could not produce detectable cephalosporin in the fermentation medium without Met. However, its growth and cephalosporin production was restored with addition of exogenous Met. These results indicate that glrA is required for the normal growth and protection against oxidative damage in A. chrysogenum, and its absence can be complemented by exogenous Met.

NADPH Oxidase and PKC Contribute to Increased Na Transport by the Thick Ascending Limb During Type 1 Diabetes

Hypertension. Feb, 2012  |  Pubmed ID: 22203737

-Type 1 diabetes triggers protein kinase C (PKC)-dependent NADPH oxidase activation in the renal medullary thick ascending limb (mTAL), resulting in accelerated superoxide production. As acute exposure to superoxide stimulates NaCl transport by the mTAL, we hypothesized that diabetes increases mTAL Na(+) transport through PKC-dependent and NADPH oxidase-dependent mechanisms. An O(2)-sensitive fluoroprobe was used to measure O(2) consumption by mTALs from rats with streptozotocin-induced diabetes and sham rats. In sham mTALs, total O(2) consumption was evident as a 0.34±0.03 U change in normalized relative fluorescence (ΔNRF)/min per mg protein. Ouabain (2 mmol/L) reduced O(2) consumption by 69±4% and 500 μmol/L furosemide reduced O(2) consumption by 58±8%. Total O(2) consumption was accelerated in mTAL from diabetic rats (0.74±0.07 ΔNRF/min/mg protein; P<0.05 versus sham), reflecting increases in ouabain- and furosemide-sensitive O(2) consumption. NADPH oxidase inhibition (100 μmol/L apocynin) reduced furosemide-sensitive O(2) consumption by mTAL from diabetic rats to values not different from sham. The PKC inhibitor calphostin C (1 μmol/L) or the PKCα/β inhibitor Gö6976 (1 μmol/L) decreased furosemide-sensitive O(2) consumption in both groups, achieving values that did not differ between sham and diabetic. PKCβ inhibition had no effect in either group. Similar inhibitory patterns were evident with regard to ouabain-sensitive O(2) consumption. We conclude that NADPH oxidase and PKC (primarily PKCα) contribute to an increase in O(2) consumption by the mTAL during type 1 diabetes through effects on the ouabain-sensitive Na(+)-K(+)-ATPase and furosemide-sensitive Na(+)-K(+)-2Cl(-) cotransporter that are primarily responsible for active transport Na(+) reabsorption by this nephron segment.

Effective Adsorption of Sodium Dodecylsulfate (SDS) by Hydrocalumite (CaAl-LDH-Cl) Induced by Self-dissolution and Re-precipitation Mechanism

Journal of Colloid and Interface Science. Feb, 2012  |  Pubmed ID: 22137168

Hydrocalumite (CaAl-LDH-Cl) was synthesized through a rehydration method involving a freshly prepared tricalcium aluminate (C(3)A) with CaCl(2) solution. To understand the intercalation behavior of sodium dodecylsulfate (SDS) with CaAl-LDH-Cl, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), inductively coupled plasma-atomic emission spectrometer (ICP), and elemental analysis have been undertaken. The sorption isotherms with SDS reveal that the maximum sorption amount of SDS by CaAl-LDH-Cl could reach 3.67 mmol g(-1). The results revealed that CaAl-LDH-Cl holds a self-dissolution property, about 20-30% of which is dissolved. And the dissolved Ca(2+) and Al(3+) ions are combined with SDS to form CaAl-SDS or Ca-SDS precipitation. It has been highlighted that the composition of resulting products is strongly dependent upon the SDS concentration. With increasing SDS concentrations, the main resulting product changes from CaAl-SDS to Ca-SDS, and the value of interlayer spacing increased to 3.27 nm.

Rapid Characterization of Caged Xanthones in the Resin of Garcinia Hanburyi Using Multiple Mass Spectrometric Scanning Modes: the Importance of Biosynthetic Knowledge Based Prediction

Journal of Pharmaceutical and Biomedical Analysis. Feb, 2012  |  Pubmed ID: 22142619

Although the anticancer activities of the resin of Garcinia hanburyi have been well demonstrated, the chemical composition of this medicinal plant is still not fully understood. In this study, a highly effective qualitative method was developed for rapidly profiling the target and non-target caged xanthones in the resin of G. hanburyi. This method mainly involves three steps as follows: (1) prediction of the possible unknown caged xanthones in the resin of G. hanburyi according to the structure characters of the known ones and some well established biosynthetic knowledge; (2) structure classification according to the diagnostic fragment ions (DFIs) of the known caged Garcinia xanthones; (3) detection and characterization of the target and non-target caged xanthones in the resin of G. hanburyi using multiple mass spectrometric (MS) scanning modes. By use of such procedures, mass spectrometric data can be used for confirming the rationally predicted chemical structure rather than sophisticated and time-consumed de novo structure elucidation of a completely unknown component. Finally, a total of 34 caged xanthones including 18 likely new ones from the resin of G. hanburyi were rapidly detected and characterized within one working day.

Distinguishing Breast Cancer Cells Using Surface-enhanced Raman Scattering

Analytical and Bioanalytical Chemistry. Jan, 2012  |  Pubmed ID: 22124755

The detection and identification of epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is crucial for the clinic therapy of breast cancer. For the aim of the detection, a novel surface-enhanced Raman scattering (SERS) probe for distinguishing breast cancers at different HER2 statuses is reported in this paper. In such a probe, anti-HER2 antibody-conjugated silver nanoparticles have been synthesized for specific targeting of HER2-positive breast cancer cells. More importantly, different from the previously reported SERS probe for targeting cancer cells, p-mercaptobenzoic acid is utilized as both the Raman reporter and the conjugation agent for attaching antibody molecules, which leads to a much simplified structure. For investigating the ability of such a probe to distinguish breast cancer cells, SKBR3 and MCF7 cells were chosen as two model systems, which are HER2-positive- and HER2-negative-expressing cells, respectively. The experimental results reveal that SKBR3 cells exhibit much stronger SERS signals than MCF7 cells, indicating that the probe could be utilized to distinguish breast cancer cells at different HER2 statuses. This kind of SERS probe holds a potential for a direct detection of living breast cancer cells with the advantages of easy fabrication, high SERS sensitivity, and biocompatibility.

Blocking Effects of Acehytisine on Pacemaker Currents (I(f)) in Sinoatrial Node Cells and Human HCN4 Channels Expressed in Xenopus Laevis Oocytes

Journal of Ethnopharmacology. Jan, 2012  |  Pubmed ID: 22107837

The root of Aconitum coreanum (Levl.) Raipaics has been extensively used to treat various kinds of disorders including cardiovascular disease in China for a long time. According to recent studies, its antiarrhythmic actions are attributable to the active component, acehytisine. However, the underlying mechanism remains poorly understood.

Over-expression of PcvA Involved in Vesicle-vacuolar Fusion Affects the Conidiation and Penicillin Production in Penicillium Chrysogenum

Biotechnology Letters. Mar, 2012  |  Pubmed ID: 22109934

Rab GTPase is required for vesicle-vacuolar fusion during the vacuolar biogenesis in fungi. Rab GTPase-encoding gene, pcvA, was cloned from Penicillium chrysogenum: it contained five introns and its predicted protein contained the conserved Rab GTPase domain involved in GTP-binding and hydrolysis. Over-expression of pcvA significantly stimulated the vesicle-vacuolar fusion but repressed the conidiation and decreased conidial tolerance against thermal stress. Penicillin production was decreased in the pcvA over-expressed strain suggesting that pcvA is involved in vesicle-vacuolar fusion participates in the penicillin biosynthesis in P. chrysogenum.

Identification and Characterization of Novel Spliced Variants of PRMT2 in Breast Carcinoma

The FEBS Journal. Jan, 2012  |  Pubmed ID: 22093364

Protein N-arginine methyltransferases (PRMTs) participate in a number of cellular processes, including cell growth, nuclear/cytoplasmic protein shuttling, differentiation, RNA splicing and post-transcriptional regulation. PRMT2 (also known as HRMT1L1) is clearly involved in lung function, the inflammatory response, apoptosis promotion, Wnt signaling and leptin signaling regulation through different mechanisms. In this study, we report the molecular and cell biological characterization of three novel PRMT2 splice variants isolated from breast cancer cells and referred to as PRMT2α, PRMT2β and PRMT2γ. Compared with the wild-type PRMT2, these variants lack different motifs and therefore generate distinct C-terminal domains. Confocal microscopy scanning revealed a distinct intracellular localization of PRMT2 variants, suggesting that the alternatively spliced C-terminus of PRMT2 can directly influence its subcellular localization. Our findings reveal that these variants are capable of binding to estrogen receptor alpha (ERα) both in vitro and in vivo, and the N-terminal regions of these variants contribute to ERα-PRMT2 interactions. Furthermore, these variants were proved to be able to enhance ERα-mediated transactivation activity. Luciferase reporter assays showed that PRMT2s could modulate promoter activities of the ERα-targeted genes of Snail and E-cadherin. In addition, PRMT2 silencing could enhance 17β-estradiol-induced proliferation by regulating E2F1 expression and E2F1-responsive genes in ERα-positive breast cancer cells. Real-time PCR and immunohistochemistry showed that overall PRMT2 expression was upregulated in breast cancer tissues and significantly associated with ERα positivity status both in breast cancer cell lines and breast cancer tissues. We speculate that PRMT2 and its splice variants may directly modulate ERα signaling and play a role in the progression of breast cancer.

Active Vaccination with Dickkopf-1 Induces Protective and Therapeutic Antitumor Immunity in Murine Multiple Myeloma

Blood. Jan, 2012  |  Pubmed ID: 22049519

Dickkopf-1 (DKK1), broadly expressed in myeloma cells but highly restricted in normal tissues, together with its functional roles as an osteoblast formation inhibitor, may be an ideal target for immunotherapy in myeloma. Our previous studies have shown that DKK1 (peptide)-specific CTLs can effectively lyse primary myeloma cells in vitro. The goal of this study was to examine whether DKK1 can be used as a tumor vaccine to elicit DKK1-specific immunity that can control myeloma growth or even eradicate established myeloma in vivo. We used DKK1-DNA vaccine in the murine MOPC-21 myeloma model, and the results clearly showed that active vaccination using the DKK1 vaccine not only was able to protect mice from developing myeloma, but it was also therapeutic against established myeloma. Furthermore, the addition of CpG as an adjuvant, or injection of B7H1-blocking or OX40-agonist Abs, further enhanced the therapeutic effects of the vaccine. Mechanistic studies revealed that DKK1 vaccine elicited a strong DKK1- and tumor-specific CD4+ and CD8+ immune responses, and treatment with B7H1 or OX40 Abs significantly reduced the numbers of IL-10-expressing and Foxp3+ regulatory T cells in vaccinated mice. Thus, our studies provide strong rationale for targeting DKK1 for immunotherapy of myeloma patients.

The Effect of Staggered Administration of Zinc Sulfate on the Pharmacokinetics of Oral Cephalexin

British Journal of Clinical Pharmacology. Mar, 2012  |  Pubmed ID: 22023069

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Zinc supplementation is an important intervention against mortality from infectious disease. • Many patients using zinc supplementation will also be prescribed antimicrobials at some time. • Recently, an inhibitory effect of zinc on the absorption of β-lactam antibiotics has been demonstrated in animal studies, but there has been no clinical assessment of this drug-nutrient interaction. WHAT THIS STUDY ADDS • Zinc sulfate dosing significantly impaired the bioavailability and decreased T > MIC of cephalexin in healthy volunteers, which might lead to a clinical failure. • The dosing recommendation is that zinc sulfate can be safely administered 3 h after a cephalexin dose. AIMS To investigate the effect of zinc sulfate on pharmacokinetics of cephalexin when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction in healthy volunteers. METHODS In this study, all subjects (n= 12) were randomized to receive the following four treatments, separated by a wash-out period of 7 days: cephalexin 500 mg alone, concomitantly with zinc 250 mg, 3 h after zinc 250 mg or 3 h before zinc 250 mg. RESULTS All subjects completed the study safely. Zinc supplements administered concurrently with cephalexin significantly decreased the peak serum concentration (C(max) ), area under the plasma concentration-time curve from zero to infinity (AUC(0-∞) ) and the time for which the plasma concentration of the drug remained above the minimal inhibitory concentration of the pathogenic organism (T > MIC) of cephalexin [mean percentage decrease (95% confidence intervals) of 31.05% (22.09-40.01%), 27.40% (18.33-36.47%) and 22.33% (12.51-32.16%), respectively; P < 0.05] compared with administration of cephalexin alone. Also, administration of zinc 3 h before cephalexin decreased the C(max) , AUC(0-∞) and T > MIC of the drug compared with administration of cephalexin alone [mean percentage decrease (95% confidence intervals) of 11.48% (3.40-19.55%), 18.12% (9.63-26.60%) and 23.75% (14.30-33.20%), respectively; P < 0.05]. In contrast, the pharmacokinetics of cephalexin was not notably altered by administration of zinc 3 h after cephalexin dosing (P > 0.05). CONCLUSIONS The significant interaction between zinc and cephalexin might affect the clinical outcome of cephalexin therapy. The dosing recommendation is that zinc sulfate can be safely administered 3 h after a cephalexin dose.

Mechanism of Interaction of Hydrocalumites (Ca/Al-LDH) with Methyl Orange and Acidic Scarlet GR

Journal of Colloid and Interface Science. Jan, 2012  |  Pubmed ID: 21963204

The development of new materials for water purification is of universal importance. Among these types of materials are layered double hydroxides (LDHs). Non-ionic materials pose a significant problem as pollutants. The interaction of methyl orange (MO) and acidic scarlet GR (GR) adsorption on hydrocalumite (Ca/Al-LDH-Cl) was studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), scanning electron microscope (SEM), and near-infrared spectroscopy (NIR). The XRD results revealed that the basal spacing of Ca/Al-LDH-MO was expanded to 2.45 nm, and the MO molecules were intercalated with a interpenetrating bilayer model in the gallery of LDH, with 49° tilting angle. Yet, Ca/Al-LDH-GR was kept the same d-value as Ca/Al-LDH-Cl. The NIR spectrum for Ca/Al-LDH-MO showed a prominent band around 5994 cm(-1), assigned to the combination result of the NH stretching vibrations, which was considered as a mark to assess MO(-) ion intercalation into Ca/Al-LDH-Cl interlayers. From SEM images, the particle morphology of Ca/Al-LDH-MO mainly changed to irregular platelets, with a "honey-comb" like structure. Yet, the Ca/Al-LDH-GR maintained regular hexagon platelets, which was similar to that of Ca/Al-LDH-Cl. All results indicated that MO(-) ion was intercalated into Ca/Al-LDH-Cl interlayers, and acidic scarlet GR was only adsorbed upon Ca/Al-LDH-Cl surfaces.

Are the Results of Multiple Drilling and Alendronate for Osteonecrosis of the Femoral Head Better Than Those of Multiple Drilling? A Pilot Study

Joint, Bone, Spine : Revue Du Rhumatisme. Jan, 2012  |  Pubmed ID: 21742531

The treatment of osteonecrosis of the femoral head (ONFH) remains controversial. A recently proposed treatment is multiple drilling core decompression combined with systemic alendronate as a femoral head-preserving procedure for ONFH. However, it is not known whether alendronate enhances the risk of collapse. We wondered whether the combined procedure could delay or prevent progression of ONFH compared to multiple drilling alone.

EventRiver: Visually Exploring Text Collections with Temporal References

IEEE Transactions on Visualization and Computer Graphics. Jan, 2012  |  Pubmed ID: 22076487

Many text collections with temporal references, such as news corpora and weblogs, are generated to report and discuss real life events. Thus, event-related tasks, such as detecting real life events that drive the generation of the text documents, tracking event evolutions, and investigating reports and commentaries about events of interest, are important when exploring such text collections. To incorporate and leverage human efforts in conducting such tasks, we propose a novel visual analytics approach named EventRiver. EventRiver integrates event-based automated text analysis and visualization to reveal the events motivating the text generation and the long term stories they construct. On the visualization, users can interactively conduct tasks such as event browsing, tracking, association, and investigation. A working prototype of EventRiver has been implemented for exploring news corpora. A set of case studies, experiments, and a preliminary user test have been conducted to evaluate its effectiveness and efficiency.

Quantitative Spectroscopic Analysis of Heterogeneous Mixtures: the Correction of Multiplicative Effects Caused by Variations in Physical Properties of Samples

Analytical Chemistry. Jan, 2012  |  Pubmed ID: 22084930

Spectral measurements of complex heterogeneous types of mixture samples are often affected by significant multiplicative effects resulting from light scattering, due to physical variations (e.g., particle size and shape, sample packing, and sample surface, etc.) inherent within the individual samples. Therefore, the separation of the spectral contributions due to variations in chemical compositions from those caused by physical variations is crucial to accurate quantitative spectroscopic analysis of heterogeneous samples. In this work, an improved strategy has been proposed to estimate the multiplicative parameters accounting for multiplicative effects in each measured spectrum and, hence, mitigate the detrimental influence of multiplicative effects on the quantitative spectroscopic analysis of heterogeneous samples. The basic assumption of the proposed method is that light scattering due to physical variations has the same effects on the spectral contributions of each of the spectroscopically active chemical components in the same sample mixture. On the basis of this underlying assumption, the proposed method realizes the efficient estimation of the multiplicative parameters by solving a simple quadratic programming problem. The performance of the proposed method has been tested on two publicly available benchmark data sets (i.e., near-infrared total diffuse transmittance spectra of four-component suspension samples and near-infrared spectral data of meat samples) and compared with some empirical approaches designed for the same purpose. It was found that the proposed method provided appreciable improvement in quantitative spectroscopic analysis of heterogeneous mixture samples. The study indicates that accurate quantitative spectroscopic analysis of heterogeneous mixture samples can be achieved through the combination of spectroscopic techniques with smart modeling methodology.

Combination of Atiprimod and the Proteasome Inhibitor Bortezomib Induces Apoptosis of Mantle Cell Lymphoma in Vitro and in Vivo

Leukemia Research. Mar, 2012  |  Pubmed ID: 22000823

The proteasome inhibitor bortezomib (BTZ) is known to be chemotherapeutic in relapsed or refractory mantle cell lymphoma (MCL). Atiprimod (ATI), a novel cationic amphophilic compound, has been tested in clinical trials in multiple myeloma (MM). We sought to evaluate the effect of an ATI-BTZ combination on MCL and to elucidate its therapeutic mechanisms. The ATI and BTZ combination significantly inhibited growth and induced apoptosis of both cultured MCL cell lines and freshly isolated tumor cells from patients with refractory or relapsed MCL. However, the combination yielded lower cytotoxicity in normal peripheral blood mononuclear cells (PBMC). Furthermore, ATI and BTZ induced apoptosis via two different signaling pathways. More significantly, ATI and BTZ markedly delayed tumor growth and prolonged survival in MCL-bearing NOD-SCID mice. Our results demonstrate that ATI and BTZ confer significant therapeutic effects in MCL in vitro and in vivo and should therefore be investigated in a clinical trial in patients with relapsed or refractory MCL.

Differentiation Potential of Human Mesenchymal Stem Cells Derived from Adipose Tissue and Bone Marrow to Sinus Node-like Cells

Molecular Medicine Reports. Jan, 2012  |  Pubmed ID: 21971826

Adult mesenchymal stem cells (MSCs) hold great promise for the repair of heart defects. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose tissue-derived stem cells (ASCs) are multipotent and may be induced by 5-azacytidine to differentiate into cardiomyocytes. However, the differentiation potential of human MSCs into sinus node-like cells has not been studied extensively. The aim of this study was to analyze the differences in proliferation and phenotype of ASCs and BMSCs from the same donors and to evaluate their capacity to differentiate into sinus node-like cells in vitro. Five passaged cells from bone marrow and adipose tissue were treated with 10 µM 5-azacytidine for 48 h and further cultured in complete medium for 4 weeks. A comparative study of cultured ASCs and BMSCs was carried out, and the morphological parameters, proliferative capacity, expression of surface markers and differentiation potential to sinus node-like cells were characterized. No morphologic differences were observed between ASCs and BMSCs. Flow cytometric analysis revealed that ASCs and BMSCs both expressed CD29, CD44, CD90 and CD105 and did not express CD34 and CD14, while CD49d, CD106 and CD34 were differentially expressed. Growth curves and doubling time determined with the Cell Counting Kit-8 (CCK-8) demonstrated that ASCs had a stronger proliferative ability than BMSCs. Histological immuofluorescence staining suggested that ASCs and BMSCs were capable of differentiating into sinus node-like cells and that the positive expression ratios of cTNI were higher in ASCs compared to BMSCs at 4 weeks. Expression of the HCN2 and HCN4 genes was detected by reverse transcriptase polymerase chain reaction, and the results revealed that the expression of the HCN genes appeared earlier in ASC-derived sinus node-like cells. ASCs expressed HCN2 and HCN4 shortly after induction with 5-azacytidine for 2 weeks, although BMSCs expressed these genes after 4 weeks. The expression levels of HCN2 and HCN4 mRNA in ASC-derived cells were higher compared to those of BMSCs at 4 weeks. In conclusion, ASCs may be a better candidate as a novel source of cell therapy in sinus bradycardia disorders than BMSCs.