Publications by authors named "Xue-Rong Wang"

19 Publications

  • Page 1 of 1

Predictors of coronary artery calcification and its association with cardiovascular events in patients with chronic kidney disease.

Ren Fail 2021 Dec;43(1):1172-1179

Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China.

Objective: To investigate the predictors of coronary artery calcification (CAC) and its association with cardiovascular events (CVE) in patients with stage 3-5 chronic kidney disease (CKD).

Method: Two hundred ninety CKD patients in our nephrology department were enrolled from 2018 to May 2019. The levels of matrix Gla protein (MGP) and interleukin 6 (IL-6) were measured enzyme-linked immunosorbent assay (ELISA) method in 131 CKD patients of all. CAC was evaluated computed tomography (CT). The covariate factors were analyzed by binary logistic regression analysis. We conducted the visits to explore the prevalence of CVE in 276 CKD patients, and covariate factors were analyzed by Cox proportional hazard model.

Results: The prevalence of CAC was up to 57.93%. We found that age, diabetes mellitus, hyperphosphatemia, dialysis duration, and the neutrophil-lymphocyte ratio (NLR) were positively associated with CAC in all patients. In 131 patients, we demonstrated that higher IL-6 and lower MGP levels were associated with CAC. A Cox proportional hazard model demonstrated that moderate to severe CAC was correlated with an increased risk for CVE [Hazard Ratio (HR): 7.250; 95% confidence interval (CI): 3.192-16.470], and a higher MGP level was associated with a reduced risk for CVE (HR: 0.340; 95% CI: 0.124-0.933).

Conclusions: The prevalence of CAC in patients with CKD is a significant issue. Older age, hyperphosphatemia, dialysis duration, diabetes mellitus, IL-6, and the NLR are associated with CAC. In addition, higher MGP levels represent protective factor for CAC. Moderate to severe CAC, and lower MGP levels are associated with an increased risk for CVE. : AGEs: Advanced glycosylation end products; CAC: Coronary artery calcification; CACS: Coronary artery calcification score; Ca: Calcium; CI: confidence interval; CKD: Chronic kidney disease; CVE: Cardiovascular events; CT: Computed tomography; ELISA: Enzyme-linked immunosorbent assay; Hb: hemoglobin; HR: Hazard ratio; hs-CRP: high-sensitivity C-reactive protein; IL-6: Interleukin 6; iPTH: Intact parathyroid hormone; Mg: Magnesium; MGP: Matrix Gla protein; NF-κB: nuclear factor-kappa gene binding; NRL: Neutrophil-lymphocyte ratio; Runx2: Runt-related transcription factor 2; RRT: Renal replacement therapy; P: Phosphorus; Scr: Serum creatinine; TNF--alpha: Tumor necrosis factor--alpha; TC: Total cholesterol; TG: Triglyceride; VSMC: vascular smooth muscle cel.
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http://dx.doi.org/10.1080/0886022X.2021.1953529DOI Listing
December 2021

Circadian clock genes as promising therapeutic targets for autoimmune diseases.

Autoimmun Rev 2021 Aug 10;20(8):102866. Epub 2021 Jun 10.

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address:

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.
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http://dx.doi.org/10.1016/j.autrev.2021.102866DOI Listing
August 2021

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study.

Rheumatology (Oxford) 2021 02;60(2):940-946

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

Objectives: Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE.

Methods: We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P < 5 × 10-8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects.

Results: The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels.

Conclusion: Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.
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http://dx.doi.org/10.1093/rheumatology/keaa506DOI Listing
February 2021

Relationship between Short-term Exposure to PM and Daily Lung Cancer Mortality in Nanjing.

Biomed Environ Sci 2020 07;33(7):547-551

Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.

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http://dx.doi.org/10.3967/bes2020.072DOI Listing
July 2020

Prevalence of coronary artery calcification and its association with mortality, cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis.

Ren Fail 2019 Nov;41(1):244-256

a Department of Nephrology , The First Affiliated Hospital of Anhui Medical University , Hefei , China.

Purpose: To date, the prevalence and prognostic role of coronary artery calcification (CAC) in patients with chronic kidney disease (CKD) have been investigated in several studies, but have yielded conflicting results. The aim of this meta-analysis is to derive a more precise estimation of CAC prevalence in CKD patients and its association with cardiovascular events and mortality.

Methods: The relevant literature was identified and evaluated from inception until July 2018 through multiple search strategies on PubMed, Embase, and Web of Science. Cross-sectional or cohort (baseline data) studies reporting CAC prevalence were included. Data extracted from eligible studies were used to calculate effect estimates (ESs) and 95% confidence intervals (95%CI). We searched databases for observational studies that explored baseline CAC and subsequent cardiovascular or all-cause mortality risk in CKD patients.

Results: The meta-analysis included 47 studies; 38 of these were included in the final analysis of CAC prevalence. The pooled prevalence of CAC in random effect model was 60% (95%CI 53-68%). CAC was positively associated with an increased risk of all-cause mortality (hazard ratio [HR] 3.44; 95%CI 2.40-4.94), cardiovascular mortality (HR 3.87; 95%CI 2.06-7.26), and cardiovascular events (HR 2.09; 95%CI 1.19-3.67), when comparing individuals in the top CAC score group to those in the bottom CAC score group.

Conclusions: The pooled prevalence of CAC is highly prevalent. CAC is independently associated with all-cause and cardiovascular mortality risk as well as cardiovascular events among CKD patients. In view of the high heterogeneity, larger clinical trials are still needed.
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http://dx.doi.org/10.1080/0886022X.2019.1595646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493287PMC
November 2019

Increased Serum Levels of Soluble B7-H4 in Patients with Systemic Lupus Erythematosus.

Iran J Immunol 2019 Mar;16(1):43-52

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Background: Members of B7 family are reported to regulate lymphocytes activation, transmit both costimulatory and co-inhibitory signals, control T cell-mediated immune responses and tolerance. Among which B7-H4 is reported to regulate the immune response negatively.

Objective: To investigate the plasma concentration of soluble B7-H4 (sB7-H4) and its clinical significance in systemic lupus erythematosus (SLE).

Methods: Fifty-six SLE patients with or without active SLE (ASLE) and 29 age- and gender-matched healthy volunteers were recruited. Plasma concentration of sB7-H4 was measured using sandwich ELISA kits.

Results: Compared with healthy subjects, the concentration of sB7-H4 was significantly higher in patients with SLE (p=0.006). Plasma sB7-H4 concentration in patients with lupus nephritis (LN) were also significantly higher than healthy subjects (p=0.008), but no difference was found between LN and SLE patients without LN (non-LN). Additionally, the sB7-H4 concentration in patients was negatively correlated with the SLE disease activity index score (SLEDAI) (r=-0.3055, p=0.022). Compared with inactive disease, the concentration of sB7-H4 in ASLE patients was significantly lower (p=0.002). There were statistical significances between the positive and negative groups with decreased leukocytes or thrombocytes (p=0.012; p=0.033; respectively), but no statistically significant difference was found in other positive and negative serum laboratory indicators.

Conclusions: The increased level of sB7-H4 in patients suggests that this pathway might be involved in the pathogenesis of SLE. However, the exact mechanism or physiological role of sB7-H4 in SLE pathogenesis remains to be investigated.
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http://dx.doi.org/10.22034/IJI.2019.39405DOI Listing
March 2019

Decreased Serum/Plasma Vitamin D levels in SLE Patients: A Meta-Analysis.

Curr Pharm Des 2018 ;24(37):4466-4473

Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, China.

Background And Objective: The evidence regarding the association between serum/plasma vitamin D (VitD) concentrations and systemic lupus erythematosus (SLE) is inconsistent. The study was based on relevant results from literatures that were identified and evaluated. The aim of this meta-analysis is to determine circulating VitD in SLE patients and explore influencing factors.

Methods: Studies examining VitD levels in SLE patients were identified through targeted searches in the PubMed and EMBASE databases (up to December 2017). Data extracted from eligible studies was synthesized to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI). A fixed or a random effects model was applied to calculate the pooled SMDs and ORs depending on heterogeneity across studies.

Results: A total of 24 studies, including 6017 patients and 18,417 controls were included. The pooled analysis suggested that VitD levels were significantly lower in SLE patients compared with those in controls [SMD= -0.09, 95%CI= -0.12 to -0.06, P < 0.001]. When the studies were stratified by ethnicity, VitD concentrations were also significantly lower in Asian, Caucasian and African patients. When the studies were stratified by age, gender, VitD level was lower in patients than that in controls. Subgroup analyses stratified by measurement type (expect for radioimmunoassay) also demonstrated consistent results. Moreover, VitD insufficiency was more prevalent in SLE patients than healthy controls [OR=6.57, 95%CI=4.64-9.29].

Conclusion: Compared with healthy controls, SLE patients had lower concentration of VitD. Additionally, the prevalence of VitD insufficiency is more common in SLE patients.
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http://dx.doi.org/10.2174/1381612825666190111145848DOI Listing
November 2019

Increased ratio of Th17 cells to SIGIRRCD4 T cells in peripheral blood of patients with SLE is associated with disease activity.

Biomed Rep 2018 Oct 3;9(4):339-344. Epub 2018 Aug 3.

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.

To investigate the clinical significance of the ratio of T helper cell 17 (Th17) cells to single immunoglobulin IL-1-related receptor (SIGIRR) cluster of differentiation (CD4) T cells in patients with systemic lupus erythematosus (SLE), novel data and data from previous studies were analyzed. The frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) and their correlation with clinical data were evaluated in 48 patients with SLE and 38 healthy controls through flow cytometry. Compared with healthy controls, the percentage of Th17 cells was significantly increased in the PBMCs of patients with SLE (Z=-5.82, P<0.001). Compared with inactive SLE (ISLE), the percentage of Th17 cells in active SLE (ASLE) were significantly increased (Z=-4.26, P<0.0001). Compared with patients without lupus nephritis, the frequency of Th17 cells was significant increased (Z=-2.20, P=0.028). The frequency of Th17 cells was inversely correlated with the frequency of SIGIRRCD4 T cells (r=-0.61, P<0.001). The ratio of Th17 cells to SIGIRRCD4 T cells in ASLE was significantly increased compared with healthy controls or patients with ISLE (P<0.001) and was inversely correlated with complement component 3 and complement component 4, and positively correlated with SLE disease activity index and 24-h proteinuria (P<0.05). In summary, increased numbers of Th17 cells and decreased numbers of SIGIRRCD4 T cells in patients with SLE suggested that SIGIRRCD4 T and Th17 cells may be involved in the pathogenesis of SLE.
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http://dx.doi.org/10.3892/br.2018.1139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142031PMC
October 2018

Glycyrrhizin inhibits LPS-induced inflammatory mediator production in endometrial epithelial cells.

Microb Pathog 2017 Aug 25;109:110-113. Epub 2017 May 25.

Department of Gynaecology and Obstetrics, Daqing City People's Hospital, Daqing, 163318, Heilongjiang, China.

Endometriosis is a continuous inflammation of uterine endometrium that usually affects women of reproductive age. Glycyrrhizin, a triterpene isolated from the roots and rhizomes of licorice (Glycyrrhiza glabra), has been known to have anti-inflammatory effect. The purpose of this study was to investigate the anti-inflammatory effect of glycyrrhizin on LPS-stimulated mouse endometrial epithelial cells (MEEC). The levels of TNF-α, IL-1β, and PGE were measured by ELISA. The expression of COX-2, iNOS, TLR4, and NF-ĸB were detected by western blot analysis. The results showed that glycyrrhizin significantly suppressed LPS-induced TNF-α, IL-1β, NO, and PGE production. Also, LPS-induced iNOS and COX-2 expression were attenuated by glycyrrhizin. Furthermore, glycyrrhizin significantly attenuated TLR4 expression and NF-κB activation induced by LPS in MEEC. In conclusion, the present study demonstrated that glycyrrhizin inhibited LPS-induced inflammatory response by inhibiting TLR4 signaling pathway in MEEC. Glycyrrhizin may be used as a potential agent for the treatment of endometriosis.
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http://dx.doi.org/10.1016/j.micpath.2017.05.032DOI Listing
August 2017

Serum sclerostin values are associated with abdominal aortic calcification and predict cardiovascular events in patients with chronic kidney disease stages 3-5D.

Nephrology (Carlton) 2017 Apr;22(4):286-292

Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University.

Aim: The purpose of this study was to investigate the possible association of circulating concentrations of sclerostin with abdominal aortic calcification (AAC) and cardiovascular outcomes in patients with chronic kidney disease stage 3-5.

Methods: One hundred and sixty-one patients with CKD3-5D were enrolled. The patients were divided into two groups according to the presence of AAC: an AAC group (n = 99) and a non-AAC group (n = 62). The concentration of serum sclerostin was measured using an enzyme-linked immunosorbent assay (ELISA). AAC was evaluated using abdominal lateral X-ray examination. The follow-up intervals ranged from 7 to 29 months (median 16 months), and cardiovascular events (CVEs) were recorded.

Results: The prevalence of vascular calcification (VC) was 61.5% (99/161). Serum sclerostin was significantly higher in an AAC group than in a non-AAC group (P < 0.001), but the concentration in the moderate-to-severe AAC group was lower than in the mild AAC group (P < 0.001). Binary logistic regression analysis revealed that high serum sclerostin, high serum calcium, diabetes, and old age were independently correlated with AAC. Patients with higher sclerostin values had a reduced risk of major cardiovascular events (log-rank test, P = 0.001).

Conclusion: Serum sclerostin values are associated with the presence of AAC, but are lower when AAC is moderate to severe. Higher values are predictive of reduced short-term cardiovascular events. Taken together, these results suggest that sclerostin may have a role in the development of or the response to vascular calcification.
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http://dx.doi.org/10.1111/nep.12813DOI Listing
April 2017

Association between rs6887695 and 3'-untranslated region polymorphisms within the interleukin-12B gene and susceptibility to autoimmune diseases in Asian and European population: A meta-analysis.

Autoimmunity 2016 06 12;49(4):277-84. Epub 2016 Apr 12.

a Department of Nephrology , The Second Affiliated Hospital of Anhui Medical University , Anhui , China and.

Background: The associations between rs6887695 and 3'-untranslated region (3'-UTR) single-nucleotide polymorphisms (SNPs) within interleukin-12B (IL-12B) and autoimmune diseases (ADs) remain controversial and inconclusive. The aim of this study was to evaluate the association between IL-12B (3'-UTR A/C and rs6887695 C/G SNPs) and ADs by meta-analysis.

Methods: PubMed and EMBASE were exhaustively searched for studies on the association between IL-12B SNPs and ADs. Publication bias was examined by a funnel plot and Egger's test. The robustness of the pooled results was assessed by sensitivity analysis. A fixed- or a random-effects model was applied to calculate the pooled odds ratios (ORs).

Results: A total of 34 studies were included in this meta-analysis. The pooled results demonstrated that IL-12B rs6887695 SNPs were significantly associated with the risk of ADs. However, there was no significant association between IL-12B 3'-UTR SNPs and ADs. When the studies were stratified by ethnicity, significant association between IL-12B 3'-UTR SNPs and ADs was observed in both Asian and European population. In addition, allele A within 3'-UTR of IL-12B gene was found to be a protective factor for T1DM, but a risk factor for psoriasis.

Conclusion: The IL-12B 3'-UTR and rs6887695 SNPs are associated with susceptibility to ADs.
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http://dx.doi.org/10.3109/08916934.2016.1166215DOI Listing
June 2016

HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation.

Oncotarget 2015 Dec;6(40):42854-67

State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.

HRD1 (3-hydroxy-3-methylglutaryl reductase degradation) is an E3 ubiquitin ligase. We found that HRD1 was significantly downregulated in 170 breast cancer tissues. Low tumoral HRD1 expression was correlated with clinicopathological characteristics and a shorter survival in breast cancer patients. P65 specifically bound to the HRD1 promoter and inhibited HRD1 expression. Suppression of NF-κB activity reversed IL-6-induced downregulation of HRD1 expression. HRD1 interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome. Overexpression of HRD1 resulted in the inhibition of growth, migration and invasion of breast cancer cells in vitro and in vivo. Furthermore, HRD1 attenuated IL-6-induced epithelial-mesenchymal transition in MCF10A cells. These findings uncover a novel role for HRD1 in breast cancer.
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http://dx.doi.org/10.18632/oncotarget.5733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767476PMC
December 2015

Association between IRS-2 G1057D polymorphism and risk of gastric cancer.

World J Gastrointest Oncol 2012 Jan;4(1):9-15

Xiao-Mei Zhao, Xuan Luo, Lin-Lin Xu, Su-Lan Zhai, Ping Li, Xue-Rong Wang, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Aim: To investigate the relationship between insulin receptor substrate-2 (IRS-2) G1057D polymorphism and the risk of gastric cancer (GC) in a Chinese population.

Methods: A case-control study with 197 GC patients and 156 age- and sex- matched control subjects was conducted. The genotypes of polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism.

Results: The genotype frequencies of IRS-2 G1057D polymorphism in cases were obviously different from those in the control group (P = 0.031). Compared with GG genotype carriers, the risk for GC was significantly higher (adjusted odds ratio = 2.32, 95% CI: 1.03-5.23, P = 0.042) in the individuals with the IRS-2 DD genotype. Furthermore, stratified analysis was performed based on age, sex, smoking status and residence, but no significant difference between the two groups was found. In addition, no significant association between genotypes and clinicopathological features was observed either.

Conclusion: This study demonstrates that IRS-2 G1057D is involved in susceptibility to GC, although further large-sample studies are still needed.
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http://dx.doi.org/10.4251/wjgo.v4.i1.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277875PMC
January 2012

Association between ITGA2 C807T polymorphism and gastric cancer risk.

World J Gastroenterol 2011 Jun;17(23):2860-6

Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Aim: To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer risk.

Methods: A hospital-based case-control study was conducted, including 307 gastric cancer patients and 307 age- and gender-matched control subjects. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism assay.

Results: The frequencies of the wild and variant genotypes in cases were significantly different from those of controls (P = 0.019). Compared with individuals with the wild genotype CC, subjects with the variant genotypes (CT + TT) had a significantly higher risk of gastric cancer (adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007). In stratified analyses, the elevated gastric cancer risk was especially evident in older individuals aged > 58 years, nonsmokers and rural subjects. Further analyses revealed that the variant genotypes were associated with poor tumor differentiation and adjacent organ invasion in the sub-analysis of gastric cancer patients.

Conclusion: The ITGA2 gene C807T polymorphism may be associated with an increased risk of gastric cancer, differentiation and invasion of gastric cancer.
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http://dx.doi.org/10.3748/wjg.v17.i23.2860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120947PMC
June 2011

Ku80 gene G-1401T promoter polymorphism and risk of gastric cancer.

World J Gastroenterol 2011 Apr;17(16):2131-6

Key Laboratory of Reproductive Medicine, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Aim: To evaluate the possible relationship between the Ku80 gene polymorphism and the risk of gastric cancer in China.

Methods: In this hospital-based case-control study of gastric cancer in Jiangsu Province, China, we investigated the association of the Ku80 G-1401T (rs828907) polymorphism with gastric cancer risk. A total of 241 patients with gastric cancer and 273 age- and sex-matched control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism.

Results: The frequencies of genotypes GG, GT and TT were 65.6%, 22.8% and 11.6% in gastric cancer cases, respectively, and 75.8%, 17.6% and 6.6% in controls, respectively. There were significant differences between gastric cancer and control groups in the distribution of their genotypes (P = 0.03) and allelic frequencies (P = 0.002) in the Ku80 promoter G-1401T polymorphism.

Conclusion: The T allele of Ku80 G-1401T may be associated with the development of gastric cancer.
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http://dx.doi.org/10.3748/wjg.v17.i16.2131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084400PMC
April 2011

[Experimental study in renal protective effect of tranilast on rats with adriamycin nephropathy].

Sichuan Da Xue Xue Bao Yi Xue Ban 2008 Jan;39(1):76-9

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effect and mechanism of tranilast on the adriamycin-induced nephrotic syndrome of rats.

Methods: Twenty four rats were randomly divided into 4 groups: normal control group, model group, irbesartan treatment group and tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein. The rats in the other groups were uninephrectomized and injected with adriamycin 5 mg/kg via the tail vein one week later. Rats in model group underwent gavage to receive the sodium carboxymethylcellulose, rats in irbesartan treatment group to receive the irbesartan with 10 mg/kg x d, and rats in tranilast treatment group to receive the tranilast with 400 mg/kg. Rats were then sacrificed at the end of week 8. The body weight, 24 hours urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) of each group rats were measured for the study. Renal pathological changes were evaluated. And immunohistochemistry was used to examine the expression of transforming growth factor beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). In situ hybridization was used to measure the expression of a-smooth muscle actin (alpha-SMA) mRNA in the kidney.

Results: Compared with the untreated nephrotic syndrome rats, the proteinuria and Scr of rats treated with tranilast were significantly reduced (P < 0.05); Compared with model group, the renal pathological changes of rats in tranilast treatment group were decreased, with glomerular sclerosis to be markedly lower; Tranilast could decrease the expression of TGF-beta1, TIMP-1 and alpha-SMA mRNA in the kidney of rats with adriamycin nephropathy.

Conclusions: Tranilast has a renoprotective effect on adriamycin-induced nephrotic syndrome in rats, of which the mechanism may be related to that tranilast can depress the expression of TGF-beta1, and TIMP-1 in the kidney, with result in decreasing the synthesis and secretion of extracellular matrix. And tranilast inhibits the transdifferentation of renal primary cells, regulates the synthesis and degradation system of extracellular matrix.
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January 2008

[Study of matrine's use on the reversion of obtained multi-drug resistance of mice S80 tumour cell].

Zhong Yao Cai 2006 Jan;29(1):40-2

ShanDong Academy of Chinese Medicine, Jinan 250014, China.

Objective: To Observe the effect caused by matrine's used on the reversion of obtained multi-drug resistance of mice S180's tumour cell induced by chemotherapy of Cisplatin + 5-FU + Cytoxan (PFC) and discuss its molecular mechanism.

Methods: Patterned the methods of PFC chemotherapy in clinic, the mice were given Cisplatim 3 mg/kg x ip once a week and Cytoxan, CTX and 5-FU 3 mg/kg x ip once everyday for 4 weeks to set up the mice models of multi-drug resistance of S180 tumor cell. At the same time, gave the mice models matrine 4 weeks, and observed the P170, LRP, TOPO II by flow cytometry.

Results: matrine could obviously reduce the express of P170, LRP and the activiation of TOPO II, correlated with mulit-drug resistance tumour cells which were induced by chemotherapy.

Conclusion: Matrine, with its adjustment of correlated biotic active matter, can intervene the ocurrence of the multidrug resistance of tumor cells induced by chemotherapy.
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January 2006

[The interference in correlated molecular mechanism obtained multi-drug resistance of mouse S180's tumour cell for different alkaloid].

Zhongguo Zhong Yao Za Zhi 2005 Dec;30(23):1844-8

Shandong Academy of Traditional Chinese Medicine, Jinan, China.

Objective: To observe the base of the interference in correlated biotic active matter obtained multi-drug resistance induced by chemotherapy for different alkaloid, and to supervise the use in clinic to restrain the multi-drug resistant of chemotherapy, and thereby to improve the curative effect.

Method: After bestowing subter-dosage unite chemotherapeutant to ascites S180 mouse to set up the mouse models of multi-drug resistance of S180 tumour cell, and giving the mouse matrine, terandrine, oxymatrine and berberine hydrooh loride for 4 weeks, the P170, LRP, TOPOII, Fas and apoposis were determined by flow cytometry.

Result: Matrine and terandrine could obviously reduce the express of P170, LRP and the activation of TOPOII, and increase the ratio of the express of Fas and the apoposis of drug resistant tumour cell. And at the same time it could obviously reduce the express of intercellular adhesion molecule(CD54).

Conclusion: Matrine and terandrine can interfere in MDR which results from chemotherapeutics by the adjustment of correlated biotic active matter, besides, the different degree of alkaloid effect with different configuration.
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December 2005

Deficiency in ClC-3 chloride channels prevents rat aortic smooth muscle cell proliferation.

Circ Res 2002 Nov;91(10):E28-32

Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Recent growing evidence suggests that chloride (Cl-) channels are critical to the cell cycle. In cultured rat aortic vascular smooth muscle cells (VSMCs), we have previously found that Cl- channel blockers inhibit endothelin-1 (ET-1)-induced cell proliferation. The present study was designed to further identify the specific Cl- channels responsible for VSMC proliferation. Due to the lack of a specific blocker or opener of any known Cl- channels, we used the antisense strategy to investigate the potential role of ClC-3, a member of the voltage-gated Cl- channel gene family, in cell proliferation of cultured rat aortic VSMCs. With [3H]-thymidine incorporation and immunoblots, we found that ET-1-induced cell proliferation was parallel to a significant increase in the endogenous expression of ClC-3 protein. Transient transfection of rat aortic VSMCs with antisense oligonucleotide specific to ClC-3 caused an inhibition in ET-1-induced expression of ClC-3 protein and cell proliferation of VSMCs in the same concentration- and time-dependent pattern, whereas sense and missense oligonucleotides resulted in no effects on ClC-3 protein expression and cell proliferation. These results strongly suggest that ClC-3 may be the Cl- channel involved in VSMC proliferation and thus provide compelling molecular evidence linking a specific Cl- channel to cell proliferation. The full text of this article is available at http://www.circresaha.org.
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http://dx.doi.org/10.1161/01.res.0000042062.69653.e4DOI Listing
November 2002
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