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Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression.
Gao Ling;Wang Furong;Wang Bo;Gong Bendi;Zhang Jie;Zhang Xiumei;Zhao Jiaju
J Pharmacol Exp Ther 2006年 318卷1期 页码:53-8
Animals|Diabetes Mellitus, Experimental/drug therapy/metabolism|Down-Regulation/drug effects/physiology|Endothelium, Vascular/drug effects/metabolism|Gene Expression Regulation/drug effects/physiology|Male|NF-kappa B/antagonists & inhibitors/metabolism|Rats|Rats, Sprague-Dawley|Tetrazoles/pharmacology/therapeutic use|Vascular Cell Adhesion Molecule-1/biosynthesis|Vascular Diseases/metabolism/prevention & contro
Vascular cell adhesion molecule (VCAM)-1 plays a critical role in the initiation and development of vascular inflammation and selective inhibition of adhesion molecules expressed by endothelial cells may present a new therapeutic strategy for the treatment of vascular complications associated with diabetes mellitus. Increasing evidence indicates that cilostazol, a cAMP phosphodiesterase inhibitor, reduces VCAM-1 expression on endothelial cells. In this study, we have tested the effect of cilostazol on the development of vascular inflammation in rats with streptozotocin-induced diabetes and determined the mechanism by which cilostazol prevents diabetes-induced vascular inflammation in the aorta. Diabetic rats were treated with different dose of cilostazol (27 or 9 mg/kg/day) for 8 weeks, and aortae were removed for the evaluation of vascular inflammation. The VCAM-1 protein expression and VCAM-1 mRNA transcripts were analyzed by immunohistochemical staining and in situ hybridization assay, respectively. Our results demonstrated that cilostazol treatment prevents the overexpression of VCAM-1 and protects diabetic rats from vascular inflammation. More importantly, our mechanistic studies suggested that cilostazol controls the VCAM-1 overexpression via inhibiting the activation of nuclear factor-kappaB.
Chronic palmitate exposure inhibits AMPKalpha and decreases glucose-stimulated insulin secretion from beta-cells: modulation by fenofibrate.
Sun Ying;Ren Meng;Gao Guan-qi;Gong Bendi;Xin Wei;Guo Hua;Zhang Xiu-juan;Gao Ling;Zhao Jia-ju
Acta Pharmacol Sin 2008年 29卷4期 页码:443-50
AMP-Activated Protein Kinases/antagonists & inhibitors|Animals|Cell Culture Techniques|Cell Line, Tumor|Cells, Cultured|Dose-Response Relationship, Drug|Fenofibrate/pharmacology|Glucose/pharmacology|Insulin/secretion|Insulin-Secreting Cells/drug effects/metabolism|Insulinoma/metabolism|Islets of Langerhans/cytology/drug effects/physiology|Luminescence|Luminescent Measurements|Male|PPAR alpha/metabolism|Palmitates/pharmacology|Rats|Rats, Wista
Adenosine monophosphate-activated protein kinase (AMPK), a vital regulator of glucose metabolism, may affect insulin secretion in beta-cells. However, the role of AMPK in beta-cell lipotoxicity remains unclear. Fenofibrate has been reported to regulate lipid homeostasis and is involved in insulin secretion in pancreatic beta-cells. In the present study, we aimed to investigate the effect of palmitate on AMPK expression and glucose-stimulated insulin secretion (GSIS) in rat islets and INS-1 beta-cell, as well as the effect of fenofibrate on AMPK and GSIS in INS-1 cells treated with palmitate.
Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients
Zhang, H;Yang, QW;Liao, K;Ni, YX;Yu, YS;Hu, BJ;Sun, ZY;Huang, WX;Wang, Y;Wu, AH;Feng, XJ;Luo, YP;Chu, YZ;Chen, SL;Cao, B;Su, JR;Duan, Q;Zhang, SF;Shao, HF;Kong, HS;Gui, BD;Hu, ZD;Badal, R;Xu, YC
BMC INFECTIOUS DISEASES 2017年 17卷
RESISTANCE; CONSEQUENCES; SURVEILLANCE; CARBAPENEM; HOSPITALS; THERAPY; ADULTS
Background: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014.;-;Methods: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards.;-;Results: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non-Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63. 53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively.;-;Conclusions: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.
T Cell Immunoglobulin-and Mucin-Domain-Containing Molecule 3 Gene Polymorphisms and Susceptibility to Invasive Breast Cancer
Cheng, SQ;Ju, Y;Han, FY;Wang, Y;Xu, YQ;Qu, T;Lu, ZM
ANNALS OF CLINICAL AND LABORATORY SCIENCE 2017年 47卷6期 页码:668-675
LIGAND GALECTIN-9; KOREAN POPULATION; STEM-CELLS; TIM-3; EXPRESSION; DISEASE; ASSOCIATION; AUTOIMMUNE; TOLERANCE; PROGNOSIS
The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3) gene is an important immune regulatory molecule. In fact, studies have shown that polymorphisms in the (TIM-3) gene may be associated with various cancers. The goal of this study was to investigate whether the -1516G/T, -574G/T, or +4259T/G single-nucleotide polymorphisms (SNPs) in the TIM-3 gene contribute to a genetic susceptibility to invasive breast cancer in the Han ethnicity of northern China. Genotyping of the TIM-3 -1516G/T, -574G/T and +4259T/G were performed in 301 patients with invasive breast cancer and in 151 healthy individuals via a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The results showed that the prevalence of the +4259T/G genotype and the +4259G allele were significantly increased in the breast cancer patients compared to the controls [odds ratio (OR)=7.641, 95% confidence interval (CI), 1.795-32.522, P=0.001; OR=7.317, 95% CI, 1.731-30.925, P=0.001, respectively]. The GGG haplotype had a significantly different distribution between patients and controls (OR=5.421, 95% CI, 1.263-23.275, P=0.011). In addition, the prevalence of the +4259T/G polymorphism was higher in patients with metastasis than those without metastasis (13.6% vs. 4.8%, respectively, OR=3.158, 95% CI, 1.300-7.672, P=0.011). Furthermore, results showed that the prevalence of the +4259T/G genotype was correlated with the intensity of Ki-67 by immunohistochemical staining (P=0.022). Overall, these results suggested that the +4259T/G SNP in the TIM-3 gene may play an important role as a genetic risk factor for the progression and prognosis of invasive breast cancer in these patients. in Han ethnicity of northern China.
In vitro analysis of activities of antimicrobial agents against clinical common organisms causing bloodstream infections, hospital-acquired pneumonia and intra-abdominal infections from twelve teaching hospitals in China: results from the Chinese antimicrobial resistance surveillance of nosocomial infections (CARES) program
Li, HN;Zhao, CJ;Wang, Q;Zeng, J;Jin, Y;Hu, ZD;Liao, K;Luo, YP;Zhuo, C;Zhang, R;Xu, XL;Liu, WN;Liu, YM;Chu, YZ;Wang, H
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 2017年 50卷 页码:S275-S276
Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro
Cao, ZX;Yang, QQ;Yin, HY;Qi, Q;Li, HR;Sun, GY;Wang, HL;Liu, WW;Li, JF
APOPTOSIS 2017年 22卷11期 页码:1419-1430 影响因子:3.592
CISPLATIN-INDUCED OTOTOXICITY; ORGANOTYPIC CULTURES; HEARING-LOSS; RAT; GENES; DEATH; MICE; AIF; AGE
Peroxynitrite (ONOO-) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO- on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO-, then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO- could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO- led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO- treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO- can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO--induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.
Prevalence of Mutations in Deafness-Causing Genes in Cochlear Implanted Patients with Profound Nonsyndromic Sensorineural Hearing Loss in Shandong Province, China
Luo, JF;Bai, XH;Zhang, FG;Xiao, Y;Gu, LT;Han, YC;Fan, ZM;Li, JF;Xu, L;Wang, HB
ANNALS OF HUMAN GENETICS 2017年 81卷6期 页码:258-266
ENLARGED VESTIBULAR AQUEDUCT; PENDRED-SYNDROME; GJB2 MUTATIONS; CONNEXIN-26 MUTATIONS; SLC26A4 MUTATIONS; JAPANESE; IDENTIFICATION; FREQUENCIES; POPULATION; IMPAIRMENT
The mutations of GJB2, SLC26A4, and mtDNA12SrRNA are the most common inherited causes of nonsyndromic sensorineural hearing loss (NSHL) in China, yet previous genetic screenings were mainly carried on patients with moderate-to-profound impairment. We aimed to detect the mutation frequencies in NSHL population within a more specified range of severity. Patients with profound NSHL who had undergone cochlear implantation in the Shandong Provincial Hospital (Shandong, China) were recruited. The majority (n = 472) were between 0.7 and 6 years old, and the remaining (n = 63) were between 6 and 70 years old. In total, 115 mutation alleles of the three genes were screened with SNP scan assay. Of the patients, 19.44% (104/535) were found to have GJB2 mutations, and the most common allele was c.235delC, followed by c.299_300delAT and c.109G>A. SLC26A4 mutations were detected in 13.46% patients (72/535), and the most common allele was c.919-2A>G (IVS7-2A>G), followed by c.1174A>T and c.2168A>G. Seven patients (1.31%) carried mutations in mtDNA12SrRNA, with the alleles of m.1555A>G and m.1494C>T. We found the allele frequency of c.109G>A (GJB2) was relatively lower in the profound NSHL population in comparison to the moderate-to-profound ones, and the c.1174A>T (SLC26A4) relatively higher. It suggests those mutations may be connected with the degree of deafness, which needs more observations and analyses to support.
Different contributions of lipid profiles and BMI to the natural history of type 2 diabetes: a 3-year cohort study in China
Liu, L;Guan, XL;Yuan, ZS;Zhao, M;Li, Q;Zhang, X;Zhang, HQ;Zheng, DM;Xu, J;Gao, L;Guan, QB;Zhao, JJ
DIABETES-METABOLISM RESEARCH AND REVIEWS 2017年 33卷
MAPK/p38 regulation of cytoskeleton rearrangement accelerates induction of macrophage activation by TLR4, but not TLR3
Bian, HJ;Li, FF;Wang, WW;Zhao, Q;Gao, SS;Ma, JC;Li, X;Ren, WH;Qin, CY;Qi, JN
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 2017年 40卷5期 页码:1495-1503
IFN-BETA PRODUCTION; ACTIN CYTOSKELETON; IN-VIVO; CELLS; REORGANIZATION; RECOGNITION; VINCRISTINE; INHIBITION; ENDOTOXIN; LEUKEMIA
Toll-like receptor 3 (TLR3) and TLR4 utilize adaptor proteins to activate mitogen-activated protein kinase (MAPK), resulting in the acute but transient inflammatory response aimed at the clearance of pathogens. In the present study, it was demonstrated that macrophage activation by lipopolysaccharide (LPS) or poly(I:C), leading to changes in cell morphology, differed significantly between the mouse macrophage cell line RAW264.7 and mouse primary peritoneal macrophages. Moreover, the expression of alpha- and beta-tubulin was markedly decreased following LPS stimulation. By contrast, alpha- and beta-tubulin expression were only mildly increased following poly(I:C) treatment. However, the expression of beta-actin and GAPDH was not significantly affected. Furthermore, it was verified that vincristine pretreatment abrogated the cytoskeleton rearrangement and decreased the synthesis and secretion of proinflammatory cytokines and migration of macrophages caused by LPS. Finally, it was observed that the MAPK/p38 signaling pathway regulating cytoskeleton rearrangement may participate in LPS-induced macrophage cytokine production and migration. Overall, the findings of the present study indicated that MAPK/p38 regulation of the cytoskeleton, particularly tubulin proteins, plays an important role in LPS-induced inflammatory responses via alleviating the synthesis and secretion of proinflammatory cytokines and inhibiting the migration of macrophages.
Accuracy of Xpert Clostridium difficile assay for the diagnosis of Clostridium difficile infection: A meta analysis
Bai, YY;Sun, XR;Jin, Y;Wang, YL;Li, J
PLOS ONE 2017年 12卷10期 影响因子:3.057
BD MAX CDIFF; ILLUMIGENE C. DIFFICILE; STOOL SPECIMENS; TESTING ALGORITHMS; TOXIGENIC CULTURE; ABBOTT M2000; STRAIN TYPE; IMPACT; TOXIN; AMPLIFICATION
Background;-;There is an urgent need for rapid and accurate microbiological diagnostic assay for detection of Clostridium difficile infection (CDI). We assessed the diagnostic accuracy of the Xpert Clostridium difficile assay (Xpert CD) for the diagnosis of CDI.;-;Methods;-;We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves (AUC). QUADAS- 2 was used to assess the quality of included studies with RevMan 5.2. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square.;-;Results;-;A total of 22 studies were included in the meta-analysis. The pooled sensitivity (95% confidence intervals [CI]) was 0.97 (0.95-0.99) and specificity was 0.95 (0.94-0.96). The AUC was 0.99 (0.97-0.99). Significant heterogeneity was observed when we pooled most of the accuracy measures of selected studies.;-;Conclusions;-;The Xpert CD assay is a useful diagnostic tool with high sensitivity and specificity in diagnosing toxigenic CDI, and this method has excellent usability due to its rapidity and simplicity.
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