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Find video protocols related to scientific articles indexed in Pubmed.
Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis.
J. Cell. Mol. Med.
PUBLISHED: 08-28-2014
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The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3(+) CD4(+) IL-17(+) Th17 cells were significantly higher, and CD4(+) CD25(+) FOXP3(+) Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro-inflammatory cytokines, including IL-17, IL-6, IL-1?, TNF-? and IL-22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR-21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up-regulated miR-21 expression from healthy controls, but down-regulated miR-21 expression from RA patients. Therefore, we speculate that miR-21 may be part of a negative feedback loop in the normal setting. However, miR-21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR-21 may thus serve as a novel regulator in T-cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.
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Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development.
Mol. Carcinog.
PUBLISHED: 08-11-2014
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Zinc ribbon domain containing 1 (ZNRD1), cloned from human leukocyte antigen (HLA) region, may play integral roles in diverse processes including immune response against HBV infection and hepatocarcinogenesis. ZNRD1-AS1 (ZNRD1 antisense RNA 1) may be an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. In this study, we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence both chronic HBV infection and hepatocellular carcinoma (HCC) development. We designed a case-control study of 1300 HBV-positive HCC patients, 1344 HBV persistent carriers and, 1344 HBV natural clearance subjects to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and, rs9261204) in ZNRD1-AS1 with the risk of both chronic HBV infection and HCC. Logistic regression analyses in additive genetic model showed that variant alleles of all the three SNPs increased host HCC risk, whereas variant allele of rs3757328 was associated with HBV clearance. Moreover, the haplotype containing variant alleles of the three SNPs was significantly associated with both HCC development (adjusted OR?=?1.18, 95% CI?=?1.01-1.38, P?=?0.035) and HBV clearance (adjusted OR?=?0.83, 95% CI?=?0.71-0.96, P?=?0.013), when compared with the most frequent haplotype. In vitro experiments showed that ZNRD1 knockdown inhibited the expression of HBV mRNA and promoted proliferation of HepG2.2.15 cells. These findings suggest that ZNRD1 regulatory SNPs may be susceptibility makers for risk of both chronic HBV infection and HCC. © 2014 Wiley Periodicals, Inc.
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Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats.
Cell. Physiol. Biochem.
PUBLISHED: 06-27-2014
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Endoplasmic reticulum (ER) stress-induced podocyte apoptosis plays a critical role in the development of diabetic nephropathy (DN). Here, we tested the hypothesis that suppression of PERK-ATF4-CHOP pathway by Astragaloside IV (AS-IV) is associated with inhibition of ER stress-induced podocyte apoptosis in streptozotocin (STZ)-induced diabetic rats.
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Cancer survival in China, 2003-2005: A population-based study.
Int. J. Cancer
PUBLISHED: 06-09-2014
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Limited population-based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population-based cancer registries, data from 17 registries (n?=?138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003-2005 and followed until the end of 2010. Age-standardized relative survival was calculated using region-specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age-standardized 5-year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%-31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban-rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health-care to the disadvantaged populations will be essential for reducing this disparity in the future.
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Cyclosporine-mediated allograft fibrosis is associated with micro-RNA-21 through AKT signaling.
Transpl. Int.
PUBLISHED: 06-03-2014
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Calcineurin inhibitors (CNIs) are potent immunosuppressants with associated long-term nephrotoxicity mediated by tubular epithelial cell injury and arterial vasoconstriction. We hypothesized that CNI-induced renal injury is regulated by specific microRNAs (miRNAs). In this study, we found that 46 miRNAs were significantly altered in human proximal tubular epithelial cells (HPTECs) following exposure to cyclosporine A (CsA), particularly miR-21 (5.47 ± 0.47-fold versus vehicle, P = 0.002). This increase was accompanied by alterations in epithelial-mesenchymal transformation (EMT) markers including vimentin (2.80 ± 0.28-fold; P = 0.03), S100A4 (2.29 ± 0.29-fold; P = 0.04), and ?-SMA (5.0 ± 0.31-fold; P = 0.03). Notably, transfection of HPTECs with miR-21 precursor also resulted in significant induction of EMT-associated genes, which were inhibited by a single-stranded nucleic acid inhibitor of miR-21. miR-21 induction resulted in a rapid increase of phosphorylated AKT and downregulation of PTEN. While CsA induces SMAD7 downregulation and TGF-?1 upregulation in HPTECs, such changes were independent of miR-21. Moreover, there was no effect on ERK phosphorylation. We confirmed these changes using a mouse model of CsA toxicity. Collectively, our results suggest that miR-21 mediates CsA nephrotoxicity via PTEN/AKT signaling pathway. Further exploration into the epigenetic response to CsA exposure may provide new therapeutic targets to ameliorate CsA nephrotoxicity.
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NFATc3 pathway participates in the process that 15-LO/15-HETE protects pulmonary artery smooth muscle cells against apoptosis during hypoxia.
J. Recept. Signal Transduct. Res.
PUBLISHED: 05-22-2014
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Hypoxia activates nuclear factor of activated T cells isoforms c3 (NFATc3), a Ca(2+)-dependent transcription factor in murine pulmonary arteries (PAs), and NFATc3 has been proved to be implicated in hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, but it remains unclear whether NFATc3 acts on the apoptosis of PASMCs, an important step in PAs remodeling. Our laboratory has demonstrated that 15-hydroxyeicosatetraenoic acid (15-HETE) is a key factor in hypoxia-induced PA remodeling and can increase PASMC intracellular Ca(2+) ([Ca(2+)](i)) in rats. It is possible that NFATc3 is related with the function of 15-HETE anti-apoptosis during hypoxia. Our results identified that NFATc3 was mainly localized in rat PASMCs and was upregulated in PAs during hypoxia-induced rat pulmonary hypertension (PH), while this effect was inhibited by administration of nordihydroguaiaretic acid (NDGA), a 15-lipoxygenase (15-LO) inhibitor. Moreover, hypoxia and exogenous 15-HETE promoted the expression and nuclear translocation of NFATc3 in PASMCs, which was inhibited by NDGA or small interfering RNA targeted to rat 15-LO1 or 15-LO2. Furthermore, endogenous 15-HETE induced by hypoxia and exogenous 15-HETE suppressed serum deprivation-induced loss of rat PASMCs survival and prevented annexin V binding, mitochondrial membrane potential depolarization, DNA nick end labeling and chromatin condensation. Although all these effects were suppressed after the cells were treated with cyclosporin A (a calcineurin/NFAT inhibitor), it aggravated the apoptosis induced by serum deprivation. Thus, all these results indicate that 15-HETE-mediated PASMCs anti-apoptosis in hypoxic PH via the Ca(2+)-NFATc3 pathway.
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Ficus carica polysaccharides promote the maturation and function of dendritic cells.
Int J Mol Sci
PUBLISHED: 02-25-2014
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Various polysaccharides purified from plants are considered to be biological response modifiers and have been shown to enhance immune responses. Ficus carica L. is a Chinese traditional plant and has been widely used in Asian countries for its anti-tumor properties. Ficus carica polysaccharides (FCPS), one of the most essential and effective components in Ficus carica L., have been considered to be a beneficial immunomodulator and may be used in immunotherapy. However, the immunologic mechanism of FCPS is still unclear. Dectin-1 is a non-toll-like pattern recognition receptor, predominately expressed on dendritic cells (DCs). Activation of DCs through dectin-1 signaling can lead to the maturation of DC, thus inducing both innate and adaptive immune responses against tumor development and microbial infection. In our study, we found that FCPS could effectively stimulate DCs, partially through the dectin-1/Syk pathway, and promote their maturation, as shown by the up-regulation of CD40, CD80, CD86, and major histocompatibility complex II (MHCII). FCPS also enhanced the production of cytokines by DCs, including IL-12, IFN-?, IL-6, and IL-23. Moreover, FCPS-treated DCs showed an enhanced capability to stimulate T cells and promote T cell proliferation. Altogether, these results demonstrate that FCPS are able to activate and maturate DCs, thereby up-regulating the immunostimulatory capacity of DCs, which leads to enhanced T cell responses.
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Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats.
Eur. J. Pharmacol.
PUBLISHED: 02-02-2014
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Podocyte loss and dysfunction play key role during the development of diabetic nephropathy (DN). The aim of this study was to observe the protective effects of astragaloside IV on podocyte in diabetic rats and explore its mechanisms preliminary. Healthy male Sprague-Dawley (SD) rats were randomized into normal control group, diabetic nephropathy group and diabetic nephropathy with AS-IV treatment group. DN was induced by intraperitoneal injection of streptozotocin (STZ). AS-IV treatment started 2 weeks before STZ injection and lasted 14 weeks. 24h Urinary proteins were measured 4, 8 and 12 weeks after STZ injection. Body weight, blood glucose, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured 12 weeks after STZ injection. Renal pathology, podocyte morphological changes, podocyte density, protein and mRNA expression of integrin ?3, integrin ?1 and integrin-linked kinase (ILK) were detected by histopathology, electron microscopy, immunohistochemistry, western blot and real-time PCR, respectively. Hyperglycemia, proteinuria, mesangial expansion and podocyte loss, increased protein expression of ILK and decreased protein expression of integrin ?3 and integrin ?1 were detected in diabetic rats. AS-IV treatment ameliorated podocyte loss, renal histopathology and podocyte foot process effacement, decreased proteinuria, partially restored protein expression of integrin ?3, integrin ?1 and ILK. These findings suggested that AS-IV may protect podocyte and ameliorate diabetic nephropathy by inhibiting the expression of ILK and restoring the expression of integrin ?3?1 in diabetic rats.
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Evaluation of electromechanical coupling parameters of piezoelectric materials by using piezoelectric cantilever with coplanar electrode structure in quasi-stasis.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 01-30-2014
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Based on Timoshenko beam theory, a principle model is proposed to establish the relationship between electric charge and excitation acceleration, and in quasi-stasis we apply the direct piezoelectric effect of multilayer cantilever with coplanar electrode structure to evaluate the piezoelectric strain coefficient d15 and electromechanical coupling coefficient k15. They are measured as 678 pC/N and 0.74 for the commercial piezoelectric ceramic lead zirconate titanate (PZT-51) bulk specimen and 656 pC/N and 0.63 for the lead magnesium niobate (PMN) bulk specimen, and they are in agreement with the calibration and simulation values. The maximum of relative errors is less than 4.2%, so the proposed method is reliable and convenient.
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Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis.
Immunol. Res.
PUBLISHED: 01-10-2014
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Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 66 patients with gastric cancer were included; the expression level of Th1- and Th17-related IFN-?, IL-17, T-bet, ROR?t in gastric cancer tissues and peripheral blood mononuclear cell (PBMC) were detected, analyzed the relationship between Th17 or Th1 infiltration and metastasis and explored the possible mechanism. Our results showed that IL-17 and ROR?t expression were significantly increased in gastric cancer tissues and PBMC, especially, in metastasis patients; plasma IL-17 also increased; furthermore, the mRNA and protein levels of IL-1?, IL-21 and TGF-? were up-regulated. All the data indicated that Th17 was infiltrated the cancer tissue; IL-1?, IL-21 and TGF-? were also involved in gastric cancer development by promoting Th17 cell generation. From the above data, we speculated that Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis.
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The expression of Toll-like receptor 8 and its relationship with VEGF and Bcl-2 in cervical cancer.
Int J Med Sci
PUBLISHED: 01-01-2014
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Cervical cancer is one of the most common cancers in women worldwide, often associated with the infection of human papillomavirus (HPV). Toll-like receptor 8 (TLR8), a pattern recognition receptor, is involved in viral nucleic acid sensing. Recently TLR8 has been shown to be expressed in cancer cells, and it has been suggested that it may help cancer cell growth and tumor development. The objective of this study is to investigate the expression of TLR8 expression and its relationship with Bcl-2 and VEGF in cervical cancer cells.
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BmCREC is an endoplasmic reticulum (ER) resident protein and required for ER/Golgi morphology.
J. Biol. Chem.
PUBLISHED: 08-06-2013
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Silkworm posterior silkgland is a model for studying intracellular trafficking. Here, using this model, we identify several potential cargo proteins of BmKinesin-1 and focus on one candidate, BmCREC. BmCREC (also known as Bombyx mori DNA supercoiling factor, BmSCF) was previously proposed to supercoil DNA in the nucleus. However, we show here that BmCREC is localized in the ER lumen. Its C-terminal tetrapeptide HDEF is recognized by the KDEL receptor, and subsequently it is retrogradely transported by coat protein I (COPI) vesicles to the ER. Lacking the HDEF tetrapeptide of BmCREC or knocking down COPI subunits results in decreased ER retention and simultaneously increased secretion of BmCREC. Furthermore, we find that BmCREC knockdown markedly disrupts the morphology of the ER and Golgi apparatus and leads to a defect of posterior silkgland tube expansion. Together, our results clarify the ER retention mechanism of BmCREC and reveal that BmCREC is indispensable for maintaining ER/Golgi morphology.
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SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface.
Hum. Mol. Genet.
PUBLISHED: 07-17-2013
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The processing of amyloid precursor protein (APP) is a key event in the pathogenesis of Alzheimers disease. As certain cleavage pathways tend to occur in particular subcellular compartments, the processing of APP is greatly influenced by factors that regulate its trafficking. Here we report that SCG10 directly interacts with the KFFEQ motif of the APP intracellular domain and promotes the non-amyloidogenic processing of the APP. Knockdown of SCG10 led to decreases in ? cleavage products, sAPP? and CTF?, while increases of both A?1-40 and A?1-42. Elevation of SCG10 induced APP accumulation in post-Golgi vesicles and on the cell surface by facilitating its secretory pathway. In addition, the APP processing was dependent on the palmitoylation-mediated membrane-anchoring of SCG10. Furthermore, elevation of SCG10 reduced A? accumulation and amyloid plaque formation in the hippocampus of APPswe/PS1dE9 mice. Taken together, these results show that SCG10 has a potential role in preventing and treating Alzheimers disease.
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Traumatic scratch injury in astrocytes triggers calcium influx to activate the JNK/c-Jun/AP-1 pathway and switch on GFAP expression.
Glia
PUBLISHED: 05-07-2013
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Astrocyte activation is a hallmark of central nervous system injuries resulting in glial scar formation (astrogliosis). The activation of astrocytes involves metabolic and morphological changes with complex underlying mechanisms, which should be defined to provide targets for astrogliosis intervention. Astrogliosis is usually accompanied by an upregulation of glial fibrillary acidic protein (GFAP). Using an in vitro scratch injury model, we scratched primary cultures of cerebral cortical astrocytes and observed an influx of calcium in the form of waves spreading away from the wound through gap junctions. Using the calcium blocker BAPTA-AM and the JNK inhibitor SP600125, we demonstrated that the calcium wave triggered the activation of JNK, which then phosphorylated the transcription factor c-Jun to facilitate the binding of AP-1 to the GFAP gene promoter to switch on GFAP upregulation. Blocking calcium mobilization with BAPTA-AM in an in vivo stab wound model reduced GFAP expression and glial scar formation, showing that the calcium signal, and the subsequent regulation of downstream signaling molecules, plays an essential role in brain injury response. Our findings demonstrated that traumatic scratch injury to astrocytes triggered a calcium influx from the extracellular compartment and activated the JNK/c-Jun/AP-1 pathway to switch on GFAP expression, identifying a previously unreported signaling cascade that is important in astrogliosis and the physiological response following brain injury.
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Cep57 protein is required for cytokinesis by facilitating central spindle microtubule organization.
J. Biol. Chem.
PUBLISHED: 04-08-2013
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Cytokinesis is the final stage of cell division in which the cytoplasm of a cell is divided into two daughter cells after the segregation of genetic material, and the central spindle and midbody are considered to be the essential structures required for the initiation and completion of cytokinesis. Here, we determined that the centrosome protein Cep57, which is localized to the central spindle and midbody, acts as a spindle organizer and is required for cytokinesis. Depletion of Cep57 disrupted microtubule assembly of the central spindle and further led to abnormal midbody localization of MKLP1, Plk1, and Aurora B, which resulted in cytokinesis failure and the formation of binuclear cells. Furthermore, we found that Cep57 directly recruited Tektin 1 to the midbody matrix to regulate microtubule organization. Thus, our data reveal that Cep57 is essential for cytokinesis via regulation of central spindle assembly and formation of the midbody.
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LRRC45 is a centrosome linker component required for centrosome cohesion.
Cell Rep
PUBLISHED: 04-07-2013
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During interphase, centrosomes are connected by a proteinaceous linker between the proximal ends of the centrioles, which is important for the centrosomes to function as a single microtubule-organizing center. However, the composition and regulation of centrosomal linker remain largely unknown. Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation. Thus, LRRC45 is a critical component of the proteinaceous linker between two centrioles and is required for centrosome cohesion.
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MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1.
Biochem. J.
PUBLISHED: 03-15-2013
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Unbalanced apoptosis is a major cause of structural remodelling of vasculatures associated with PAH (pulmonary arterial hypertension), whereas the underlying mechanisms are still elusive. miRNAs (microRNAs) regulate the expression of several proteins that are important for cell fate, including differentiation, proliferation and apoptosis. It is possible that these regulatory RNA molecules play a role in the development of PAH. To test this hypothesis, we studied the effect of several miRNAs on the apoptosis of cultured PASMCs (pulmonary artery smooth muscle cells) and identified miR-138 to be an important player. miR-138 was expressed in PASMCs, and its expression was subjected to regulation by hypoxia. Expression of exogenous miR-138 suppressed PASMC apoptosis, prevented caspase activation and disrupted Bcl-2 signalling. The serine/threonine kinase Mst1, an amplifier of cell apoptosis, seemed to be a target of miR-138, and the activation of the Akt pathway was necessary for the anti-apoptotic effect of miR-138. Therefore the results of the present study suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and plays an important role in HPVR (hypoxic pulmonary vascular remodelling).
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High-temperature actuation performance of BiScO3-PbTiO3 ceramics and their multilayer configuration.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 03-12-2013
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Electric-field-induced strains of BiScO3-PbTiO3 (BS-PT) ceramics and actuation performance in multilayer configuration were investigated in the temperature range from 25°C to 250°C. Experimental results confirmed that BS-PT ceramics showed better piezoelectric temperature stability than PZT-5H ceramics, and larger strain than PZT-4 and PZT-8 ceramics at temperatures above 50°C. The strain of a BSPT multilayer actuator prepared by the silicate-cement-glue method was comparable to that of a single-layer BS-PT ceramic. Under ±7.5 kV/cm electric field, the strain of a BS-PT multilayer actuator reached 0.115% at 200°C. Our work shows that BS-PT ceramics are suitable for high-temperature actuation applications.
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Cleavage of bleomycin hydrolase by caspase-3 during apoptosis.
Oncol. Rep.
PUBLISHED: 03-06-2013
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Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis.
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Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China.
Carcinogenesis
PUBLISHED: 01-14-2013
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Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.
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Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.
Mol. Carcinog.
PUBLISHED: 01-07-2013
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Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.
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A square-plate ultrasonic linear motor operating in two orthogonal first bending modes.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 01-05-2013
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A novel square-plate piezoelectric ultrasonic linear motor operated in two orthogonal first bending vibration modes (B?) is proposed. The piezoelectric vibrator of the linear motor is simply made of a single PZT ceramic plate (sizes: 15 x 15 x 2 mm) and poled in its thickness direction. The top surface electrode of the square ceramic plate was divided into four active areas along its two diagonal lines for exciting two orthogonal B? modes. The achieved driving force and speed from the linear motor are 1.8 N and 230 mm/s, respectively, under one pair orthogonal voltage drive of 150 V(p-p) at the resonance frequency of 92 kHz. The proposed linear motor has advantages over conventional ultrasonic linear motors, such as relatively larger driving force, very simple working mode and structure, and low fabrication cost.
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Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-?B-mediated inflammatory genes expression.
Cytokine
PUBLISHED: 01-04-2013
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Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n=8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mgkg(-1)d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n=8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-?B activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-?, MCP-1 and ICAM-1 in kidney tissues. The ?1-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-?, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-?B mediated inflammatory genes expression.
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Characterization of the mechanism of inhibin ?-subunit gene in mouse anterior pituitary cells by RNA interference.
PLoS ONE
PUBLISHED: 01-01-2013
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Inhibin, a member of the transforming growth factor-? [TGF-?] superfamily, is a suppressor of follicle-stimulating hormone [FSH] release through pituitary-gonadal negative feedback loop to regulate follicular development. In this study, Inhibin ?-subunit [Inha] gene was knocked down successfully in mice primary anterior pituitary cells at both transcriptional and translational levels by RNAi-Ready pSIREN-RetroQ-ZsGreen Vector mediated recombinant pshRNA vectors. The results indicated that inhibin silencing significantly promoted apoptosis by up-regulating Caspase-3, Bax and Bcl-2 genes without affecting p53 both at transcriptional and translational levels. Furthermore, it markedly impaired the progression of G1 phase of cell cycle and decreased the amount of cells in S phase [as detected by flow cytometry]. Inhibin silencing resulted in significant up-regulation of mRNA and protein expressions of Gondotropin releasing hormone receptors [GnRHR] and down-regulated mRNA levels of ?-glycans with parellel change in the amount of its protein expression. Silencing of inhibin-a significantly increased [P<0.05] activin-? concentration without affecting FSH and LH levels in anterior pituitary cells. These findings revealed that up regulation of GnRH receptors by silencing inhibin a-subunit gene might increase the concentration of activin-? in the culture medium. Inhibin a silencing resulted in increased mRNA and protein expressions of inhibin? which may demonstrate that both inhibin subunits co-participate in the regulation of reproductive events in anterior pituitary cells. This study concludes that inhibin is a broad regulatory marker in anterior pituitary cells by regulating apoptosis, cellular progression and simultaneously by vital fluctuations in the hormonal signaling.
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Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease.
J. Clin. Endocrinol. Metab.
PUBLISHED: 12-21-2011
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Follicular helper T (Tfh) cells exert an important role in the autoimmune diseases.
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Yin yang-1 regulates the characterized murine focal adhesion-associated protein promoter.
DNA Cell Biol.
PUBLISHED: 10-06-2011
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The focal adhesion-associated protein (FAAP), product of the murine D10Wsu52e gene, is involved in modulating cell adhesion dynamics. The ubiquitously expressed protein belongs to the highly conserved UPF0027 family, the newly identified RNA >p ligase family. To understand the mechanisms underlying FAAP expression and regulation, we first mapped its major transcription start site at the nucleotide 79? bp upstream of the ATG codon. The murine FAAP 2.1? kb 5-flanking region was cloned, analyzed, and aligned with the corresponding 1.7? kb region of its human homolog HSPC117. Despite the differences in activity, cell in vitro transfection and testis in vivo electroporation identified a 0.2 kb efficient promoter region lacking a functional TATA-box. Gel shift assays confirmed the specific interaction between Yin Yang-1 (YY1) and the potential element in the proximal region of the FAAP promoter. Site mutation, truncation, RNAi, and overexpression analyses suggested that YY1 is an important regulator of the FAAP promoter.
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Aquaporin-4 promotes memory consolidation in Morris water maze.
Brain Struct Funct
PUBLISHED: 08-10-2011
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Aquaporin-4 (AQP4), the most abundant aquaporin in the brain, is polarized at the glial end-feet facing peri-synaptic areas. AQP4 has been hypothesized to modulate water and potassium fluxes associated with neuronal activity in pathophysiological states. However, the role of AQP4 in astroglial signaling under physiological conditions is unclear. Herein, AQP4 knockout mice and wild-type littermates were tested in the Morris water maze (MWM), which allows for investigating the role of AQP4 in long-term learning and memory. Compared with wild-type mice, AQP4 knockout mice appeared actually to find the platform more easy, but to forget more quickly, in the MWM, indicating that AQP4 knockout mice exhibited impaired memory consolidation in MWM. Moreover, the deficits of memory consolidations were associated with defects in theta-burst stimulation-induced long-term potentiation both in vivo and in vitro. Furthermore, AQP4 knockout mice were accompanied by a decrease in the incorporation of adult-generated granule cells into spatial memory networks. Taken together, our findings indicate that AQP4 plays a modulatory role in memory consolidation. Targeting glial AQP4 may be a new therapeutic strategy for neurodegenerative disorders and related memory impairment.
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Glucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells.
Am. J. Pathol.
PUBLISHED: 08-01-2011
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Rheumatoid arthritis (RA), a chronic autoimmune form of inflammatory joint disease, progressively affects multiple joints with pathological changes in the synovia, cartilage, and bone. Numerous studies have suggested a critical role for glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) in the pathogenesis of autoimmune arthritis by modulating both innate and adaptive immune reactions, but the underlying mechanisms by which GITR activation promotes arthritic progression remain largely unclear. In this study, we found that collagen-induced arthritis mice treated with the ligand of GITR (GITRL) displayed an earlier onset of arthritis with a markedly increased severity of arthritic symptoms and joint damage, in which significantly increased Th17 cells in both spleen and draining lymph nodes were observed. Notably, results showed that a marked expansion of Th17 cells with increased ROR?t mRNA expression was induced from naïve CD4(+) T cells when cultured with GITRL. Consistently, normal mice that were treated with GITRL were found to display a substantial expansion of splenic Th17 cells. Furthermore, we detected elevated serum levels of GITRL in patients with RA, which were positively correlated with an increase in interleukin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells.
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[Determination of polycyclic aromatic hydrocarbons in thermoplastic elastomer by gas chromatography-mass spectrometry].
Se Pu
PUBLISHED: 05-19-2011
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A simple and accurate method for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in thermoplastic elastomer by gas chromatography-mass spectrometry (GC-MS) has been developed. The effects of various operational parameters (e. g. sample pretreatment, extraction solvent, extraction method, extraction temperature, extraction time, etc) on the extraction efficiency were carefully investigated by analyzing different kinds of positive PAHs thermoplastic elastomer samples made by the manufacturer. The samples were extracted ultrasonically with toluene, concentrated to about 1 mL and then redissolved by cyclohexane. After being purified by dimethyl sulfoxide liquid-liquid extraction, 16 PAHs in the sample were analyzed by GC-MS and quantified by internal standard method. Different kinds of thermoplastic elastomer materials and products were analyzed by this method with the recoveries ranged from 70% to 117% and the relative standard derivations between 0.2% and 10.8%. The method is acceptable for the determination of PAHs in thermoplastic elastomer materials and products.
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Enhanced HMGB1 expression may contribute to Th17 cells activation in rheumatoid arthritis.
Clin. Dev. Immunol.
PUBLISHED: 05-03-2011
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Rheumatoid arthritis(RA) is a common autoimmune disease associated with Th17 cells, but what about the effect of high-mobility group box chromosomal protein 1 (HMGB1) and the relationship between Th17-associated factors and HMGB1 in RA remains unknown. In the present study, we investigated the mRNA levels of HMGB1, ROR?t, and IL-17 in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by quantitative real-time PCR (RT-qPCR), and the concentrations of HMGB1, IL-17, and IL-23 in plasma were detected by ELISA. And then, the effect of HMGB1 on Th17 cells differentiation was analyzed in vitro. Our clinical studies showed that the mRNAs of HMGB1, ROR?t, and IL-17 in patients were higher than that in health control (P < 0.05), especially in active RA patients (P < 0.05). The plasma HMGB1, IL-17, and IL-23 in RA patients were also higher than that in health control (P < 0.05); there was a positive correlation between the expression levels of HMGB1 and the amount of CRP, ERS, and RF in plasma. In vitro, the IL-17-produced CD4(+)T cells were increased with 100 ng/mL rHMGB1 for 12h, which indicated that the increased HMGB1 might contribute to Th17 cells activation in RA patients.
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A new specialization in astrocytes: glutamate- and ammonia-induced nuclear size changes.
J. Neurosci. Res.
PUBLISHED: 02-23-2011
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We observed nuclear swelling in glutamate (Glu)-treated astrocytes that was concomitant with but independent of astrocytic cell swelling. We confirmed Glu-induced nuclear swelling with nuclei isolated from astrocytes. Ammonia is metabolically related to Glu and could induce a nuclear swelling in intact astrocytes but shrinkage in isolated nuclei. Other compounds such as glutamine, aspartate, taurine, glycine, and ATP did not cause any nuclear swelling in isolated nuclei of astrocytes. Surprisingly, Glu and ammonia did not induce nuclear swelling in microglia, C6, HEK 293, or Hep G2 cell lines in cultures and their isolated nuclei. The Glu- and ammonia-induced nuclear size changes appear to be a specific response of astrocytes to these two closely related metabolic compounds.
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Increased expression of mGITRL on D2SC/1 cells by particulate ?-glucan impairs the suppressive effect of CD4+CD25+ regulatory T cells and enhances the effector T cell proliferation.
Cell. Immunol.
PUBLISHED: 01-19-2011
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?-Glucans have been shown to enhance immune responses for centuries, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Dectin-1, the C-type lectin receptor for ?-glucan, is expressed abundantly on dendritic cells (DCs). Activation of DCs via Dectin-1 can lead to the maturation of DC, inducing both innate and adaptive immune responses against tumor development and microbial infection. In this study, we found that particulate yeast-derived ?-glucans could induce the maturation of murine dendritic cell line D2SC/1 cells and increase the expression of mGITRL on D2SC/1 cells via Dectin-1/Syk pathway in a dose dependent manner. Furthermore, we demonstrated that the increased mGITRL on D2SC/1 cells could impair the suppressive activity of CD4(+)CD25(+) regulatory T cells (Tregs) and enhance the proliferation of CD4(+)CD25(-) effector T cells (Teffs). These findings suggest that particulate ?-glucan can be used as immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate immune suppressive activity, leading to a more efficient defense mechanism against tumor development or infectious diseases.
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[Analysis on lung cancer survival from 2001 to 2007 in Qidong, China].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 01-12-2011
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Lung cancer is one of the most important malignancies in China. Survival rates of lung cancer on the population-based cancer registry for the years 2001-2007 in Qidong were analysed in order to provide the basis for the prognosis assessment and the control of this cancer.
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Astrocytes express N-methyl-D-aspartate receptor subunits in development, ischemia and post-ischemia.
Neurochem. Res.
PUBLISHED: 11-11-2010
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The expression of the N-methyl-D-aspartate receptor (NMDA-R) in astrocytes is controversial. The receptor is commonly considered neuron-specific. We showed that astrocytes in primary cultures differentially expressed mRNA of NMDA-R subunits, NR1, NR2A and NR2B, in development, ischemia and post-ischemia. One-week-old cultures expressed detectable NR1 mRNA, which fell significantly at 2 weeks and became barely detectable at 4 weeks. NR2A and NR2B mRNA were both significantly up-regulated from 1 to 2 weeks. In 4 weeks, 2 h of ischemia caused a significant up-regulation of NR1 and NR2B mRNA; while 6 h caused down-regulation of NR2A mRNA. Under 3 h of post-ischemia, only NR1 mRNA was increased. Ischemia induced the expression of major NMDA-R effecter, nitric oxide synthase 1, which was unaffected by AMPA-R antagonist CNQX, but dose-dependently inhibited by NMDA-R specific antagonist MK-801. These findings reflected that astrocyte could express inducible functional NMDA receptors without the presence of neurons.
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Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma.
Gut
PUBLISHED: 09-28-2010
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Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC.
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Single photon emission computed tomography demonstrated efficacy of 17?-estradiol therapy in male rats after trauma-hemorrhage and extended hypotension.
J Trauma
PUBLISHED: 06-24-2010
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This study evaluated the effect of 17?-estradiol (E2) administration on cardiovascular parameters in male rats after trauma-hemorrhage and for an extended period (3 hours) of severe hypotension, based on blood-pool single photon emission computed tomography imaging.
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Silkworm coatomers and their role in tube expansion of posterior silkgland.
PLoS ONE
PUBLISHED: 06-13-2010
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Coat protein complex I (COPI) vesicles, coated by seven coatomer subunits, are mainly responsible for Golgi-to-ER transport. Silkworm posterior silkgland (PSG), a highly differentiated secretory tissue, secretes fibroin for silk production, but many physiological processes in the PSG cells await further investigation.
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Effects of xylazole alone and in combination with ketamine on the metabolic and neurohumoral responses in healthy dogs.
Vet Anaesth Analg
PUBLISHED: 05-22-2010
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To evaluate the effects of xylazole (an analogue of xylazine), also known as Jingsongling, alone and in combination with ketamine, on metabolic and neurohumoral responses in healthy dogs.
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Expression and regulation of FAAP in the mouse epididymis.
Endocrine
PUBLISHED: 04-21-2010
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The focal adhesion-associated protein (FAAP), encoded by the murine D10Wsu52e gene, is named as involved in modulating cell adhesion dynamics. It is a highly conserved and ubiquitously expressed protein, and its human homologue HSPC117 has been identified in many protein complexes. However, the expression and regulation of the FAAP gene have not yet been well characterized. Herein, we demonstrate that FAAP mRNA and protein expression are highly regionalized in the mouse epididymis with predominant enrichment in the initial segment. During sexual maturation, FAAP mRNA is always expressed in the caput epididymides. Castration causes rapid and significant decrease of FAAP mRNA abundance within the initial segment, whereas testosterone replacement fails to reverse the regression. Unilateral orchidectomy and efferent duct ligation studies further validate that expression of the FAAP mRNA is highly dependent on the presence of luminal testicular factors rather than testosterone. Furthermore, FAAP expression in the initial segment is not affected by cryptorchism.
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Herbaspirillum species: a potential pathogenic bacteria isolated from acute lymphoblastic leukemia patient.
Curr. Microbiol.
PUBLISHED: 04-13-2010
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Herbaspirillum species, colonized the plant rhizosphere, also called rhizobacteria, are plant growth-promoting bacteria. Recently we isolated Herbaspirillum from blood cultures of acute lymphoblastic leukemia (ALL) and identified by PCR and gene sequencing. Herbaspirillum may be a potential pathogenic bacteria. Although the exact role that these species play in ALL patients is unknown, their differentiation from other species has serious implications for clinical care and patient well-being.
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Characterization of kinesin-like proteins in silkworm posterior silk gland cells.
Cell Res.
PUBLISHED: 04-06-2010
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Kinesins are microtubule-based motors involved in various intracellular transports. Neurons, flagellated cells, and pigment cells have been traditionally used as model systems to study the cellular functions of kinesins. Here, we report silkworm posterior silkgland (PSG), specialized cells with an extensive endomembrane system for intracellular transport and efficient secretion of fibroin, as a novel model for kinesin study. To investigate kinesin-driven intracellular transport in PSG cells, we cloned five silkworm kinesin-like proteins (KLPs), BmKinesin-1, BmKinesin-6, BmKinesin-7, BmKinesin-13, and BmKinesin-14A. We determined their expression patterns by relative real-time PCR and western blotting. Immunofluorescence microscopy verified their colocalization with microtubules. By combining pull-down assays, LC-MS/MS, and western blotting analysis, we identified many potential cargoes of BmKinesin-1 in PSG, including fibroin-containing granules and exuperantia-associated ribonucleoprotein (RNP) complexes. Moreover, BmKinesin-13 overexpression disrupted the microtubule network in BmN cells, which is consistent with a role of Kinesin-13 in regulating microtubule dynamics in other organisms. On the basis of these results, we concluded that PSG might have advantages in elucidating mechanisms of intracellular transport in secretory tissues and could serve as a potential model for kinesin studies.
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IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population.
Int. J. Cancer
PUBLISHED: 03-30-2010
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To investigate the association between the potentially functional polymorphisms in IL12A and IL12B, HBV infection and risk of hepatocellular carcinoma in a Chinese population, we genotyped three polymorphisms, rs568408 (3UTR G>A), rs2243115 (5UTR T>G) in IL12A and rs3212227 (3UTR A>C) in IL12B in a case-control study of 869 hepatocellular carcinoma (HCC) cases and 891 cancer-free controls. We found that the IL12A rs568408 GA/AA variant genotypes were associated with a significantly increased risk of HCC (adjusted odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.17-2.00), compared with the wild-type GG homozygote. In the stratified analyses, the increased risk of HCC associated with rs568408 GA/AA was more evident in patients who were negative for HBsAg (adjusted OR = 1.71, 95% CI = 1.23-2.39). However, no significant associations between IL12A rs2243115 T/G, IL12B rs3212227 A/C and risk of HCC were observed. Our findings indicate that IL12A rs568408 may contribute to the risk of HCC and modify HCC risk associated with HBV infection.
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Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch.
Mol. Syst. Biol.
PUBLISHED: 03-09-2010
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Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and memorize the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch.
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CTLA-4 gene polymorphism +49 A/G contributes to genetic susceptibility to two infection-related cancers-hepatocellular carcinoma and cervical cancer.
Hum. Immunol.
PUBLISHED: 03-07-2010
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Accumulated evidence suggested that cytotoxic T-lymphocyte antigen 4 (CTLA4) plays an important role in the negative regulation of T-cell proliferation and activation, and thus participates in antitumor immunity and cancer surveillance. Previously we reported that the CTLA4 49A/G (rs231775) single nucleotide polymorphism (SNP) was a candidate cancer susceptibility marker for breast, lung, esophageal, and gastric cancers. In the present study, we expanded our study to two infection-related cancers, namely, hepatocellular carcinoma (HCC) and cervical cancer. We genotyped rs231775 in two independent case-control studies of 864 HCC patients and 864 control subjects, and 719 cervical cancer patients and 719 control subjects. In the multivariate logistic regression models, CTLA4 +49 A/G variant genotype was associated with increased risk (AA vs GG) by 1.43-fold (95% CI = 0.94-2.17) for HCC, and 1.66-fold (95% CI = 1.13-2.44) for cervical cancer. Taken together, the results suggest that CTLA4 rs231775 may serve as a common cancer susceptibility marker.
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A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma.
Int. J. Cancer
PUBLISHED: 01-21-2010
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The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located in the CpG island and might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. In our study, we hypothesized that SNPs miR-34b/c rs4938723 and TP53 Arg72Pro may independently or jointly contribute to primary hepatocellular carcinoma (HCC) susceptibility. We then genotyped the 2 SNPs in a case-control study of 501 patients with primary HCC and 548 cancer-free controls in a Chinese population. We observed that the variant genotypes of miR-34b/c rs4938723 were associated with significantly increased HCC risks compared with the wild-type TT genotype (adjusted OR = 1.37, 95% CI =1.06-1.78 for TC; OR = 1.53, 95% CI = 1.02-2.31 for CC and OR = 1.40, 95% CI = 1.10-1.80 for TC/CC). Furthermore, we found a significant interaction between alcohol drinking and SNP rs4938723 on HCC risk (p = 0.05 for multiplicative and p = 0.01 for additive interaction). However, we did not find any main effect of TP53 Arg72Pro on HCC risk in this population. These findings indicate that the potentially functional SNP rs4938723 in the promoter region of pri-miR-34b/c may contribute to the susceptibility of HCC in this Chinese population.
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Convenient synthesis of silver nanowires with adjustable diameters via a solvothermal method.
J Colloid Interface Sci
PUBLISHED: 01-04-2010
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Silver nanowires have been successfully synthesized via a simple solvothermal method by adding sodium sulfide (Na(2)S) into the solution. The Ag(2)S colloids produced in the initial stage help reduce the concentration of free Ag(+) ions in the initial formation of silver seeds and subsequently release Ag(+) ions to the solution. Otherwise, there is no oxidative etching owing to the absence of oxygen. In these cases, silver nanowires are grown preferentially. Furthermore, silver nanowires with adjustable diameters can be obtained by adjusting the concentration of Na(2)S. Electron microscopy, X-ray diffraction, and absorption spectra have been used to investigate the products, and a mechanism is proposed to interpret the controlled synthesis of silver nanowires. Finally, our results indicate that this approach provides a versatile route to prepare silver nanowires with controllable diameters.
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Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.
J. Neurochem.
PUBLISHED: 12-26-2009
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Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway.
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Convenient, rapid synthesis of silver nanocubes and nanowires via a microwave-assisted polyol method.
Nanotechnology
PUBLISHED: 12-03-2009
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Silver nanostructures have been synthesized via a microwave-assisted polyol method by adding sodium sulfide (Na(2)S) into the solution. An interesting morphology evolution can be observed by adjusting the concentration of Na(2)S and the heating power. It is found that the ideal concentration of Na(2)S is 31.25-500 microM for the fast reduction of Ag(+) at 300 W under optimal conditions for producing monodispersed silver nanocubes. When the heating power is increased to 400 W, 62.5-250 microM is the ideal concentration of Na(2)S for the synthesis of silver nanocubes. On increasing the concentration of Na(2)S (>500 microM), a mixture of silver nanowires, nanocubes, bipyramids, and irregular/quasispherical particles is synthesized at 300 and 400 W. In particular, an increase in the concentration of Na(2)S to 750 microM at 400 W leads to the production of a quantity of silver nanowires. In addition, silver nanocubes with controllable sizes can be obtained by changing the concentration of Na(2)S and the heating power. Compared to traditional wet-chemical methods, this method has the advantage of a marked decrease in reaction time to 3.5 min. Finally, our work provides a simple strategy for fabricating silver nanostructures with controllable morphologies and sizes.
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Structures of discoidal high density lipoproteins: a combined computational-experimental approach.
J. Biol. Chem.
PUBLISHED: 11-30-2009
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Conversion of discoidal phospholipid (PL)-rich high density lipoprotein (HDL) to spheroidal cholesteryl ester-rich HDL is a central step in reverse cholesterol transport. A detailed understanding of this process and the atheroprotective role of apolipoprotein A-I (apoA-I) requires knowledge of the structure and dynamics of these various particles. This study, combining computation with experimentation, illuminates structural features of apoA-I allowing it to incorporate varying amounts of PL. Molecular dynamics simulated annealing of PL-rich HDL models containing unesterified cholesterol results in double belt structures with the same general saddle-shaped conformation of both our previous molecular dynamics simulations at 310 K and the x-ray structure of lipid-free apoA-I. Conversion from a discoidal to a saddle-shaped particle involves loss of helicity and formation of loops in opposing antiparallel parts of the double belt. During surface expansion caused by the temperature-jump step, the curved palmitoyloleoylphosphatidylcholine bilayer surfaces approach planarity. Relaxation back into saddle-shaped structures after cool down and equilibration further supports the saddle-shaped particle model. Our kinetic analyses of reconstituted particles demonstrate that PL-rich particles exist in discrete sizes corresponding to local energetic minima. Agreement of experimental and computational determinations of particle size/shape and apoA-I helicity provide additional support for the saddle-shaped particle model. Truncation experiments combined with simulations suggest that the N-terminal proline-rich domain of apoA-I influences the stability of PL-rich HDL particles. We propose that apoA-I incorporates increasing PL in the form of minimal surface bilayers through the incremental unwinding of an initially twisted saddle-shaped apoA-I double belt structure.
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Carbonyl stress: malondialdehyde induces damage on rat hippocampal neurons by disturbance of Ca(2+) homeostasis.
Cell Biol. Toxicol.
PUBLISHED: 11-10-2009
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The objective of this study was to investigate the influences of carbonyl stress induced by malondialdehyde (MDA), a typical intermediate of lipid peroxidation, on intracellular free Ca(2+) concentration ([Ca(2+)](i)) alterations in cultured hippocampal neurons of rat. The microphotographic study clearly demonstrated that the hippocampal neurons became gradually damaged following exposure to different concentrations of MDA. Further study indicated that the plasma membrane Ca(2+)-ATPase (PMCA) activity was inhibited by MDA in a concentration- and time-dependent manner. The supplementation of 100 microM MDA was found to cause a notable early phase increase of [Ca(2+)](i) in hippocampal neuron cultures followed by a more pronounced late-phase elevation of [Ca(2+)](i). Such effect of MDA was prevented by the addition of nimodipine, an inhibitor of L-type calcium channel or by an extracellular Ca(2+) chelator EGTA. The identification of the calcium signalling pathways were studied by applying U73122, an inhibitor of PL-C, and H-89, an inhibitor of protein kinase A (PKA), showing the involvement of PL-C/IP3 pathway but not the PKA/cAMP pathway. These results suggested that MDA-related carbonyl stress caused damages of rat hippocampal neurons by triggering Ca(2+) influx and influencing Ca(2+) homeostasis in cultured neurons, and also MDA may act as a signalling molecule regulating Ca(2+) release from intracellular stores.
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Effects of gallium on the structure and electrical properties of 0.65 (Bi0.94La0.06) (Ga(x)Fe(1-x))O3-0.35PbTiO3 ceramics.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 10-09-2009
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Crystalline solutions of 0.65 Bi(0.94)La(0.06)) (Ga(x)Fe(1-x))O(3)-0.35PbTiO(3) Ceramics (BLGF-PT) for x = 0 and 0.05 have been fabricated by the solid-state reaction method. X-ray diffraction (XRD) was utilized to characterize the crystal structure and examine any possible impurities existing in the ceramics. The effects of Ga substitution on dielectric properties of the samples were studied at frequencies from 10(2) to 10(6) Hz over a temperature range from 20 to 620 degrees C. The results indicate that Ga modification can reduce the room temperature dielectric loss. The conduction mechanism of the material was investigated using ac conductivity. It is concluded that electrons originating from Fe(2+) and oxygen ion vacancies are the main charge carriers, and Ga doping could decrease the electronic conduction effectively. The frequency dependence of ac conductivity was found to follow Jonschers universal power law.
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A high temperature piezoelectric ceramic: (1-x)(Bi0.9La0.1)FeO(3-x)PbTiO3 crystalline solutions.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 10-09-2009
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(1-x)(Bi(0.9)La(0.1))FeO(3-x)PbTiO(3) (BLF-PT) crystalline solutions for x = 0.35, 0.37, 0.4, 0.43 and 0.45 have been prepared by the solid-state reaction method. The X-ray diffraction analysis shows that BLF-PT has a single perovskite phase with mixed tetragonal and rhombohedral phases between x = 0.4 and 0.43. The Curie temperature of BLF-PT for x = 0.4 attains 460 degrees C, which is about 80 degrees C higher than that of hard Pb(Zr,Ti)O(3) ceramics. The remnant polarization and piezoelectric constant of BLF-PT for x = 0.4 reach 38 microC/cm(2) and 112 pC/N, respectively. The planar coupling factor k(p) of BLF-PT for x = 0.4 remains stable at temperature increases of up to 360 degrees C. The impedance spectroscopy study reveals that the high temperature conduction of BLF-PT may be attributed to the motion of oxygen vacancies within the material. Our results indicate that BLF-PT is a promising candidate for high temperature applications.
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Determination of ultra-trace amount methyl-, phenyl- and inorganic mercury in environmental and biological samples by liquid chromatography with inductively coupled plasma mass spectrometry after cloud point extraction preconcentration.
Talanta
PUBLISHED: 06-12-2009
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The cloud point extraction (CPE) preconcentration of ultra-trace amount of mercury species prior to reverse-phase high performance liquid chromatography (HPLC) with inductively coupled plasma mass spectrometry (ICP-MS) detection was studied. Mercury species including methyl-, ethyl-, phenyl- and inorganic mercury were transformed into hydrophobic chelates by reaction with sodium diethyldithiocarbamate, and the hydrophobic chelates were extracted into a surfactant-rich phase of Triton X-114 upon heating in a water bath at 40 degrees C. Ethylmercury was found partially decomposed during the CPE process, and was not included in the developed method. Various experimental conditions affecting the CPE preconcentration, HPLC separation, and ICP-MS determination were optimized. Under the optimized conditions, detection limits of 13, 8 and 6 ng l(-1) (as Hg) were achieved for MeHg(+), PhHg(+) and Hg(2+), respectively. Seven determinations of a standard solution containing the three mercury species each at 0.5 ng ml(-1) level produced relative standard deviations of 5.3, 2.3 and 4.4% for MeHg(+), PhHg(+) and Hg(2+), respectively. The developed method was successfully applied for the determination of the three mercury species in environmental water samples and biological samples of human hair and ocean fish.
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A case study of the dynamics of in vitro DNA evolution under constant selection pressure.
J. Mol. Evol.
PUBLISHED: 05-30-2009
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Although thousands of in vitro selection and evolution experiments have been performed to seek different types of targets, most of them have only inspected the terminal evolutionary pool for patterns. In addition, to rapidly obtain the most favorable target, many experiments have been carried out under increasing selection pressure. However, increasing selection pressure seldom occurs in natural evolution. We studied the dynamic features of DNA in vitro evolution in the presence of the Mnt repressor under sequential constant selection pressure. When evolving under a constant pressure from an initial random pool of DNA, our system showed a clear, sharp, and reproducible crossover from a random population to an advantageous population (higher binding affinities of DNA sequences to the Mnt repressor). This crossover occurs after a long latent period during which there are no obvious changes in the population phenotype. We demonstrated that the existence of the crossover is caused by a significant sequence-nonspecific binding in the repressor-DNA system. After the crossover, the population settled in a stationary distribution of genotypes, which responded immediately to a subsequent sudden increase in selection pressure. We also experimentally tested the linear correlation between the evolution speed and sequence diversity (Fishers theorem) in our system.
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Determination of trace mercury species by high performance liquid chromatography-inductively coupled plasma mass spectrometry after cloud point extraction.
J. Hazard. Mater.
PUBLISHED: 05-27-2009
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A sensitive method for speciation analysis of inorganic mercury (Hg(2+)) and methyl mercury (MeHg(+)) has been developed by using high performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectrometry (ICP-MS) after cloud point extraction. The analytes were complexed with sodium diethyldithiocarbamate (DDTC) and preconcentrated by a non-ionic surfactant Triton X-114. Mercury species were effectively separated by HPLC in less than 6 min. The enhancement factors for 25 mL sample solution were 42 and 21, and the limits of detection were 4 and 10 ng L(-1) for Hg(2+) and MeHg(+), respectively. The developed method was successfully applied to the determination of trace amount of mercury species in environmental and biological samples.
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Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1 alpha-mediated pathway.
Shock
PUBLISHED: 05-21-2009
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Cardiac dysfunction is a major concern after trauma-hemorrhage, and increased IL-6 is one of the underlying causes for producing the dysfunction. Studies have shown that administration of 17beta-estradiol (estrogen) after trauma-hemorrhage normalized cardiac IL-6 levels and restored cardiac functions under those conditions. Because hypoxia-inducible factor (HIF) 1 alpha is expressed during hypoxia and cellular stress and up-regulates the expression of IL-6, we hypothesized that HIF-1 alpha induces the increased cardiac IL-6 after trauma-hemorrhage and that estrogen suppresses this induction. To examine this, C3H/HeN mice were subjected to trauma-hemorrhage or sham operation. Vehicle, the HIF-alpha inhibitor YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzylindazole, a novel activator of platelet guanylate cyclase], or estrogen was administered to trauma-hemorrhage and sham groups during resuscitation. Mice were killed at 2 h after resuscitation, and cardiac IL-6, HIF-1 alpha, and nuclear factor (NF) kappaB activities were measured. IL-6, NF-kappaB, and HIF-1 alpha levels were markedly elevated after trauma-hemorrhage; all of these parameters were normalized by estrogen as well as YC-1 administration after trauma-hemorrhage. Because elevated IL-6 levels after trauma-hemorrhage were decreased with YC-1 treatment, it indicates that IL-6 expression in cardiomyocytes is induced via HIF-1 alpha. In addition, estrogen decreased the elevated HIF-1 alpha, NF-kappaB, and IL-6 levels after trauma-hemorrhage. These results indicate that the beneficial effects of estrogen on cardiac function after trauma-hemorrhage seem to be mediated by the inhibition of HIF-1 alpha expression and activity.
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Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3gamma in astrocyte.
J. Neurochem.
PUBLISHED: 04-28-2009
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Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14-3-3gamma could be up-regulated by ischemia in astrocyte to protect cells from ischemia-induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14-3-3gamma up-regulation in primary culture of astrocytes under ischemic-like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3gamma up-regulation in astrocytes. At the same time, we observed an ischemia-induced nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition of AP-1 with curcumin also inhibited 14-3-3gamma up-regulation indicating that ischemia-induced up-regulation of 14-3-3gamma in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway.
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Basic fibroblast growth factor stimulates epithelial cell growth and epithelial wound healing in canine corneas.
Vet Ophthalmol
PUBLISHED: 04-28-2009
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To evaluate the effect of basic fibroblast growth factor (bFGF) on the proliferation of canine corneal epithelial cells and epithelial wound healing.
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JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma.
Mol. Cancer
PUBLISHED: 04-19-2009
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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.
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Method for the mapping of a female partial-sterile locus on a molecular marker linkage map.
Theor. Appl. Genet.
PUBLISHED: 04-14-2009
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The female gametophyte is an absolutely essential structure for angiosperm reproduction, and female sterility has been reported in a number of crops. In this paper, a maximum-likelihood method is presented for estimating the position and effect of a female partial-sterile locus in a backcross population using the observed data of dominant or codominant markers. The ML solutions are obtained via Baileys method. The process for the estimating of the recombination fractions and the viabilities of female gametes are described, and the variances of the estimates of the parameters are also presented. Application of the method is demonstrated using a set of simulated data. This method circumvents the problems of the traditional mapping methods for female sterile genes which were based on data from seed set or embryo-sac morphology and anatomy.
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Allo-restricted CTLs generated by coculturing of PBLs and autologous monocytes loaded with allogeneic peptide/HLA/IgG1-Fc fusion protein.
J. Leukoc. Biol.
PUBLISHED: 04-07-2009
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The graft-versus-leukemia effect of allogeneic marrow transplantation suggests the dramatic effect of the allogeneic T cell to eradicate malignant disease. Preparation and adoptive transfusion of tumor-specific T cells from HLA-mismatched donors might be expected to circumvent CTL tolerance to the tumor. In this study, a soluble, divalent HLA-A2 molecule was constructed with the Fc part of human IgG1 and was pulsed with a peptide related to melanoma tyrosinase 368-376 [Tyr(368-376) (Tyr)] to form the Tyr/HLA-A2 dimer, which allowed loading onto monocytes via interaction of the Fc and FcR. The HLA-A2-negative (HLA-A2-ve) monocytes loaded with the Tyr/HLA-A2 dimer acted as allo-APC with copies of a single allogeneic epitope. After coculture of the HLA-A2-ve PBLs and autologous monocytes loaded with the dimer, CD8+ cells in the coculture show an obvious proliferation and increased frequency of Tyr/HLA-A2 tetramer-stained cells. The sorted Tyr/HLA-A2 tetramer-positive CD8+ cells display an elevated cytotoxic activity against HLA-A2-positive melanoma cells expressing tyrosinase endogenously (i.e., SK-Mel-5) but little against tyrosinase-negative melanoma cells (i.e., A375). The coculture of PBLs and autologous monocytes loaded with allogeneic peptide/HLA complexes offers a novel approach to expand allo-restricted, peptide-specific CTLs, which might be a potential arsenal for treatment of patients with malignant disease, if the tumor-related epitope were defined.
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Inhibition of intracellular Ca2+ release by a Rho-kinase inhibitor for the treatment of ischemic damage in primary cultured rat hippocampal neurons.
Eur. J. Pharmacol.
PUBLISHED: 03-31-2009
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The effects of hydroxy fasudil, a specific Rho-kinase inhibitor, on behavior and brain neuronal activity in animal studies have been described previously. However, whether a Rho-kinase inhibitor can directly protect neurons against ischemic damage and the molecular mechanisms underlying these effects are poorly understood. The present work was designed to investigate the effect of hydroxy fasudil against oxygen-glucose deprivation (OGD) induced acute neuronal injury and the underlying mechanisms in vitro. Pretreatment with hydroxy fasudil at 5 and 10 microM could concentration-dependently improve cell viability and decrease Lactate dehydrogenase (LDH) level in extracellular solution of neurons suffered from OGD either in Ca(2+)-containing or Ca(2+)-free culture medium. Moreover, we found that abnormal elevation of extracellular glutamate (Glu) level induced by OGD was markedly repressed by hydroxy fasudil as measured by high performance liquid chromatography (HPLC). Using Fura-2 based calcium imaging techniques, we further demonstrated that preincubation with hydroxy fasudil suppressed the increase of [Ca(2+)](i) induced by 50 microM Glu and 20 microM ATP, but had no effect on the increase of [Ca(2+)](i) induced by 50 mM KCl. These data demonstrated that the neuroprotective effect of hydroxy fasudil was attributed to repressing Glu excitotoxicity and ischemic induced calcium overload by inhibiting Ca(2+) release from Ca(2+) stores rather than by inhibiting Ca(2+) influx via receptor-operated or voltage-dependent calcium channel.
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Mechanism of the salutary effects of estrogen on kupffer cell phagocytic capacity following trauma-hemorrhage: pivotal role of Akt activation.
J. Immunol.
PUBLISHED: 03-21-2009
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Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-kappaB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-kappaB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-alpha, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.
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DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.
Eur. J. Pharmacol.
PUBLISHED: 03-19-2009
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Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldnt suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.
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Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer.
J. Hepatol.
PUBLISHED: 03-18-2009
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Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC.
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Four novel resistance integron gene-cassette occurrences in bacterial isolates from zhenjiang, china.
Curr. Microbiol.
PUBLISHED: 03-13-2009
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Integrons, which are widely distributed among bacteria and are strongly associated with resistance, are specialized genetic elements that are capable of capturing, integrating, and mobilizing gene cassette. In this work, we investigated classes 1, 2, and 3 integrons associated integrases genes in 365 bacteria isolates, amplified and analyzed the structure of class 1 integron, detected 8 resistant gene cassettes [dfr17, aadA5, aadA1, aadA2, dhfrI, aadB, aac(6)-II, and pse-I], and found four novel gene-cassette arrays. We also found that commensal bacteria in the common microenvironment had the same integron gene cassette, which provided direct evidence that integron was an important horizontal transmission element.
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Mechanism of hepatoprotection in proestrus female rats following trauma-hemorrhage: heme oxygenase-1-derived normalization of hepatic inflammatory responses.
J. Leukoc. Biol.
PUBLISHED: 02-24-2009
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Hepatic damage occurs in males and ovariectomized (OVX), not in proestrus (PE), females following trauma-hemorrhage (T-H). The mechanism responsible for hepatoprotection remains unknown. We hypothesized protection in PE is a result of enhanced heme oxygenase-1 (HO-1)-derived down-regulation of liver inflammatory responses. PE and OVX rats underwent T-H (midline laparotomy, 60% blood loss). PE rats received vehicle (Veh; saline), HO-1 inhibitor chromium mesoporphyrin IX chloride (CrMP; 2.5 mg/kg), zinc protoporphyrin IX (ZnPP; 25 mg/kg), or Akt/PI-3K inhibitor Wortmannin (Wort; 1 mg/kg) 30 min prior to resuscitation or sham operation i.p. OVX rats received Veh or 17beta-estradiol (E2; 1 mg/kg) 30 min before hemorrhage. Rats were killed 2 h thereafter. Following T-H, left ventricular performance was maintained in PE and E2 OVX rats but was depressed in OVX and CrMP-, ZnPP-, and Wort-treated PE rats; liver damage was not evident in PE rats, and CrMP, ZnPP, and Wort abrogated protection; liver HO-1, p38 MAPK, Akt/PI3K, and Bcl-2 expression increased in PE and E2 OVX rats, which was abrogated by CrMP, ZnPP, and Wort, and liver ICAM-1, caspase-3, phospho-IkappaB-alpha, and NF-kappaB expression increased in OVX and CrMP-, ZnPP-, and Wort-PE rats; liver myeloperoxidase, NF-kappaB DNA-binding activity, TNF-alpha, IL-6, plasma proinflammatory cytokines, and cytokine-induced neutrophil chemoattractants increased in OVX and CrMP-, ZnPP-, and Wort-PE rats; and plasma estradiol levels and hepatic estrogen receptor-alpha and -beta expression decreased in OVX but were unaltered by CrMP, ZnPP, and Wort. Thus, enhanced HO-1 in PE and E2 OVX females modulates inflammatory responses and protects liver following T-H.
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Identification and characterization of class 1 integrons among Pseudomonas aeruginosa isolates from patients in Zhenjiang, China.
Int. J. Infect. Dis.
PUBLISHED: 02-08-2009
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The role of integrons in the spread of antibiotic resistance has been well established. The aim of this study was to investigate the resistance profiles of Pseudomonas aeruginosa isolated from patients in Zhenjiang to 13 antibiotics, and to identify the structure and dissemination of class 1 integrons.
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Thermal stability of apolipoprotein A-I in high-density lipoproteins by molecular dynamics.
Biophys. J.
PUBLISHED: 01-27-2009
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Apolipoprotein (apo) A-I is an unusually flexible protein whose lipid-associated structure is poorly understood. Thermal denaturation, which is used to measure the global helix stability of high-density lipoprotein (HDL)-associated apoA-I, provides no information about local helix stability. Here we report the use of temperature jump molecular dynamics (MD) simulations to scan the per-residue helix stability of apoA-I in phospholipid-rich HDL. When three 20 ns MD simulations were performed at 500 K on each of two particles created by MD simulations at 310 K, bilayers remained intact but expanded by 40%, and total apoA-I helicity decreased from 95% to 72%. Of significance, the conformations of the overlapping N- and C-terminal domains of apoA-I in the particles were unusually mobile, exposing hydrocarbon regions of the phospholipid to solvent; a lack of buried interhelical salt bridges in the terminal domains correlated with increased mobility. Nondenaturing gradient gels show that 40% expansion of the phospholipid surface of 100:2 particles by addition of palmitoyloleoylphosphatidylcholine exceeds the threshold of particle stability. As a unifying hypothesis, we propose that the terminal domains of apoA-I are phospholipid concentration-sensitive molecular triggers for fusion/remodeling of HDL particles. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling has substantial biomedical implications.
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