1.Association between HBV infection and HLA-DPB1 gene in population of Guangzhou Chinese
Zehuan LIU ; Xinlan FAN ; Jianghai LIN ; Zhiyan FU ; Dejing PAN ; Yonggui FU ; Zongjian JIA ; Anlong XU
Chinese Journal of Pathophysiology 2000;0(08):-
AIM: To investigate the association between HBV infection and HLA-DPB1 gene in population of Guangzhou Chinese. METHODS: 58 unrelated patients (test positive of HbsAg,HBeAg,HbcAb) and 75 unrelated healthy control individuals were typed by sequencing based typing (SBT) method in their HLA-DPB1 gene. RESULTS: The phenotype frequencies of HLA-DPB1 alleles of patients and control have no significant difference. CONCLUSION: These results indicate that there is no association between HLA-DPB1 gene and HBV infection.
2.Relationship of polymorphisms of AhR - 1661G/A with GSTP1 - 313A/G and susceptibility to endometriosis
Yufeng WANG ; Lili ZONG ; Ting MAO ; Yifeng WANG ; Yonggui FU ; Jun ZENG ; Xingqiang RAO
Chinese Journal of Obstetrics and Gynecology 2012;47(7):522-525
Objective To investigate the association of polymorphisms of arylhydrocarbon receptor (AhR) - 1661G/A with glutathione S-transferase pi ( GSTP1 ) - 313A/G and the susceptibility to endometriosis in southern Han Chinese.Methods Total of 432 endometriosis patients undergoing laparoscopic or laparotomy surgery matched with 493 patients with fallopian tube ligation,tubal recanalization,laparoscopic hydrotubation,benign ovarian tumor and teratoma surgeries without endometriosis as control group were enrolled in this study.The single nucleotide polymorphism (SNP) of AhR -1661G/A and GSTP1 -313A/G were detected by using a fluorescent quantitative PCR-based high resolution melting (HRM).Results The numbers of combined genotypes AhR - 1661G/A and GSTP1 -313A/G were 120 patients with AG + AA,64 patients with AG + AG,8 patients with AG + GG,109 patients with GG +AA,84 patients with GG + AG,4 patients with GG + GG,31 patients with AA + AA,10 patients with AA + AG,1 patient with AA + GG at endometriosis group and 131 patients with AG + AA,68 patients with AG + AG,6 patients with AG + GG,157 patients with GG + AA,66 patients with GG + AG,4 patients with GG + GG,35 patients with AA + AA,20 patients with AA + AG,3 patients with AA + GG at endometriosis group.There was no statistically different frequencies of genotypes between endometriosis group and control group (x2 = 12.558,P = 0.128 ).Compared with genotype GG + AA,the risk of endometriosis with genotype GG + AG was increased 1.833 time (95%CI:1.233-2.274).Conclusion The combined genotype GG + AG [ from AhR - 1661G/A (GG) and GSTP1 - 313A/G (AG) ] might be related with susceptibility to endometriosis.
3.Renoprotective effect of transforming growth factor beta activator kinase 1 inhibitor in diabetic db/db mice and its mechanism
Yuanyuan LI ; Xingxin XU ; Yunxia SHAO ; Xin FU ; Shiyao FENG ; Yonggui WU
Chinese Journal of Nephrology 2015;31(11):848-854
Objective To investigate the renoprotective effect of transforming growth factor beta activator kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (OZ) in diabetic db/db mice and the mechanism.Methods Twenty-four male db/db mice were randomly divided into two groups:db/db mice (db/db,n=12) and db/db mice with 5Z-7-oxozeaenol treatment (db/db+OZ,n=12).Another group of wild type mice (n=12) was held as the control group.OZ 2 mg/kg was administrated by intraperitoneal injection every other day.At week 8 and 12 after 5Z-7-oxozeaenol treatment,blood glucose (BG),body weight (BW),kidney weight (KW) and urinary albumin excretion rate (UAER) were evaluated.Kidney pathological lesions were detected by light and electron microscopy.NF-κB p65,monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-ot (TNF-o) were detected by immunohistochemistry.Western blotting was used to detect p-TAK1,TAB1,p-p38MAPK and IL-1β expression,while ICAM-1 and MCP-1 mRNA levels were evaluated by real-time PCR.Results Compared with control group,the levels of BG,BW,KW and UAER were higher (P < 0.01) in db/db mice group,while BW,KW and UAER levels were significantly decreased in db/db + OZ group compared with that in db/db mice group (P < 0.05).In week 8 and 12 db/db mice,glomerular volume and extracellular matrix were increased,while pathological lesions in kidney tissue were positively improved by TAK1 inhibitor.Immunohistochemistry showed that NF-κB p65,MCP-1 and TNF-α expression levels were apparently increased in db/db mice group compared with that in control group (P < 0.05) and were significantly inhibited by TAK1 inhibitor (P < 0.05).Western blotting showed that p-TAK1,TAB1,p-p38MAPK and IL-1β expression levels were higher in db/db mice group than that in control group (P < 0.05) and lower in db/db+ OZ group than that in db/db mice group (P < 0.05).Moreover,real-time PCR showed that the expressions of ICAM-1 and MCP-1 mRNA were higher in db/db mice group than that in control group and lower in db/db+OZ group than that in db/db mice group (P <0.05).Conclusions TAK1 Inhibitor can down-regulate MAPK and NF-κB pathway to restrain the reaction of inflammation and alleviate kidney injury in diabetic db/db mice.
4.Role of TAK1 signaling pathways in bone marrow derived macrophage activation induced by high glucose
Shiyao FENG ; Xingxin XU ; Yunxia SHAO ; Yuanyuan LI ; Xin FU ; Yonggui WU
Chinese Journal of Nephrology 2016;32(1):37-42
Objective To investigate the role of transforming growth factor-β activated kinase-1 (TAK1) signaling pathway in the activation of bone marrow derived macrophages (BMDM) induced by high glucose.Methods Purity of mouse BMDM was detected by flow cytometry.The mice macrophages cultured in vitro were stimulated by high glucose and treated with TAK1 specific inhibitor 5Z-7-oxozeaenol.Cells were divided into normal control group (RPMI 1640),osmolality control group (25 mmol/L mannitol),high glucose group (33 mmol/L D-glucose) and inhibitor group (33 mmol/L D-glucose+300 nmol/L 5Z-7-oxozeaenol).Immunocytochemistry and flow cytometry were used to detect macrophage subtype.The expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis Factor-α (TNF-α) mRNA were determined by real time PCR.Expressions of p-TAK1,TAK1 binding protein (TAB1),p-JNK,p-p38 MAPK and NF-κB p65 proteins were analyzed by Western blotting.Results The purity of BMDM was about 99.36%.Compared with normal control group,high glucose group had increased percentage of M1 macrophages,increased expression of MCP-1 and TNF-α mRNA (all P < 0.05).Moreover,p-TAK1,TAB1,p-JNK,p-p38 MAPK and NF-κB p65 proteins expression also increased significantly in high glucose group (all P < 0.05).After treatment with inhibitor 5Z-7-oxozeaenol,the effects induced by high glucose were inhibited (P < 0.05).Conclusions High glucose can induce M1 macrophage activation and expression of inflammatory cytokine of BMDM,which can be inhibited 5Z-7-oxozeaenol through inhibiting TAK1/MAPK and TAK1/NF-κB pathway.
5.Effect of TGF-βactivated kinase-1 inhibitor on bone marrow-derived macrophages activation and its mechanism
Xin FU ; Xingxin XU ; Yunxia SHAO ; Shiyao FENG ; Yuanyuan LI ; Yonggui WU
Chinese Pharmacological Bulletin 2016;32(3):355-360,361
Aim We used bone marrow-derived macro-phages ( BMMs ) , to explore the mechanism of macro-phage activation and the effect of TGF-β activated ki-nase-1 ( TAK1 ) inhibitor 5 Z-7-oxozeaenol on it under AGEs conditions. Methods The BMMs were obtained from C57 mice, and purity of BMMs was detected by flow cytometry. Cell viability was tested after treatment with different concentrations of TAK1 inhibitors. Laser confocal microscopy was used to detect macrophage M1 subtype . Flow cytometry was used to analyse the macro-phage activated by AGEs. TNF-α and MCP-1 mRNA levels were evaluated by qRT-PCR. Western blot was used to detect the expression levels of TAK1 signal pathway protein. Results AGEs stimulation could in-crese the activity of M1 macrophages,and 5Z-7-oxoze-aenol could inhibit the differentiation of BMMs. Com-pared with control group, AGEs increased the expres-sion of MCP-1 and TNF-α mRNA(P<0. 01). p-TAK1, TAB1,p-JNK,p-p38MAPK and NF-κBp65 proteins ex-pression also increased significantly ( P <0. 05 ) . After treatment with inhibitor, transcription levels of MCP-1 and TNF-α decreased significantly ( P < 0. 05 , P <0. 01 ) . 5 Z-7-oxozeaenol treatment downregulated the expression of p-TAK1,TAB1,p-JNK,p-p38MAPK and
NF-κBp65 proteins ( P <0. 05 ) . Conclusions AGEs can induce BMMs to M1 phenotypic polarization. 5Z-7-oxozeaenol reduces the expression of inflammatory cyto-kine via inhibiting TAK1/MAPKs, MAPKs/NF-κB pathways.
6.Role of ERS in Astragaloside Ⅳ-induced cardioprotection against ischemia/reperfusion injury in rats
Yonggui HE ; Yidong ZHANG ; Guobin ZHANG ; Pei WANG ; Yu FU ; Jinkun XI ; Huan ZHENG
Chinese Pharmacological Bulletin 2016;32(9):1289-1293
Aim To explore the role of endoplasmic re-ticulum stress( ERS) in Astragaloside Ⅳ-induced car-dioprotection against ischemia/reperfusion injury in rats. Methods A model of myocardial ischemia 30 min followed by 120 min reperfusion was made by liga-ting coronary artery in male Wistar rats. Rats were di-vided randomly into 4 groups: sham group, ischemia/reperfusion group, ERS inhibitor TUDCA group, As-tragaloside Ⅳgroup. Myocardial samples were collect-ed from the risk zones during ischemia and reperfu-sion, ERS was determined by measuring levels of glu-cose regulated protein 78 ( GRP78 ) , an established marker of ERS with Western blot. Immunofluorescence study was used to test GRP78 intensity with laser scan-ning confocal microscopy, TTC method was used to measure the infarct size,hematoxylin-eosin staining was used to observe the changes of morphological changes of myocardium. Results There was no statistical difference in GRP78 expression during ischemia com-pared to the sham group, but was markedly increased upon reperfusion. Astragaloside Ⅳ could mimic TUD-CA and significantly decreased the GRP78 expression, reduced infarct size and improved the morphology of myocardial tissue with a significant statistical difference compared with the control group ( P<0. 05 ) . Conclu-sions ERS is induced upon reperfusion but not during ischemia in isolated rat hearts. Astragaloside Ⅳ pre-vents myocardial reperfusion injury presumably by the inhibition of ERS.
7.Association of the tumor necrosis factor-alpha - 1031T/C and its combination with interleukin-6 -634C/G gene polymorphisms with susceptihility to endometriosis
Ting MAO ; Lili ZONG ; Yufeng WANG ; Jun ZENG ; Yonggui FU ; Xin ZHAO ; Xingqiang RAO ; Yuxin HUANG ; Zhengmei XU ; Xiaonan ZHU
Chinese Journal of Obstetrics and Gynecology 2012;47(5):328-332
Objective To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region - 1031T/C and its combination with interleukin-6 (IL-6 ) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis.Methods Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation,tubal recanalization,laparoscopic hydrotubation,ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group,that all cases were confirmed by operation and pathology.A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting ( HRM ) method.Results ( 1 ) TNF-α - 1031T/C genotype:the T and C of TNF-α - 1031T/C allele frequencies in the endometriosis group and control group were 79.2% (684/864),20.8% (180/864) and 81.8% (816/998),18.2% (182/998),respectively.The TT,TC and CC of TNF-α - 1031T/C genotype frequencies in the two groups were 63.7% (275/432),31.0% ( 134/432 ),5.3% (23/432) and 66.5% (332/499),30.5% (152/499),3.0% ( 15/499),respectively.There were no statistical significances in the TNF-α - 1031T/C alleles and genotypes distributions between the two groups ( P =0.158,P =0.186 ).( 2 ) TNF-α - 1031T/C and IL-6 - 634C/G conjoint genotypes:to research on the TNF-α - 1031T/C and IL-6 -634C/G genotypes for conjoint analysis,the TT + CC,TC + CC,CC +CC,TT + CG,TC + CG,CC + CG,TT + GG,TC + GG and CC + GG combination genotype frequencies in the two groups were 39.4% ( 170/432 ),19.4% ( 84/432 ),4.6% ( 20/432 ),20.6% ( 89/432 ),8.8% (38/432),0.9% (4/432),3.5% (15/432),2.3% (10/432),0.5% (2/432) and 36.7% ( 183/499),17.4%(87/499),1.4% (7/499),26.1% (130/499),10.4% (52/499),1.2% (6/499),3.8% (19/499),2.6% ( 13/499),0.4% (2/499),respectively.There were no statistical significances in the combination genotypes distributions between the two groups ( P =0.107 ).As compared with carriers of TT + CC combination genotype,the endometriosis risk of carriers of CC + CC combination genotype enhanced 3.076 times ( 95% CI:1.268 - 7.457,P =0.009 ),and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P > 0.05 ).ConclusionsThe study demonstrates that there are no significant association between the SNP of TNF-α - 1031T/C and genetic susceptibility to endometriosis.However the results indicate that there are significant association betweengenetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6- 634C/G.
8.Association of the H770H of PR gene polymorphism with susceptibility to endometriosis
Ting MAO ; Xiping LUO ; Xiaochang TAN ; Xuefang JIANG ; Yufeng WANG ; Yuxin HUANG ; Xin ZHAO ; Yonggui FU ; Xingqiang RAO ; Lili ZONG
Chinese Journal of Obstetrics and Gynecology 2015;(3):194-197
Objective To investigate the association of PR gene exon 5 region H770H (rs1042839) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (EM) in southern Han Chinese women. Methods Totally 431 EM patients and 499 non-EM women were collected and separated into EM group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in EM and control groups to evaluate the association of these SNP with the susceptibility to EM by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. Results The C and T of PR H770H allele frequencies among the EM and control groups were 97.9%(844/862), 2.1% (18/862) and 99.4% (992/998), 0.6% (6/998), respectively. The CC, CT and TT of PR H770H genotype frequencies among the EM and control groups were 95.8%(413/431), 4.2%(18/431), 0 and 98.8%(493/499), 1.2%(6/499), 0, respectively. There were statistical significances in the PR H770H alleles and genotypes distributions between the two groups (χ2=7.386, P=0.007;χ2=8.135, P=0.004). Carrying allele C reduced the risk of EM (OR=0.986, 95%CI: 0.976-0.996), while carrying allele T enhanced the risk of EM (OR=3.319, 95%CI: 1.323-8.325); carrying genotype CC reduced the risk of EM 0.970 time (OR=0.970, 95%CI: 0.949-0.991), whereas carrying genotype CT enhanced the risk of EM 3.473 times (OR=3.473, 95%CI:1.391-8.671). Conclusion There is significant association between the polymorphism of PR H770H and genetic susceptibility to EM in southern Han Chinese women.
9.Association of P53 gene polymorphisms with susceptibility to endometriosis.
Yuxin HUANG ; Lili ZONG ; Jianghai LIN ; Yonggui FU ; Zehuan LIU ; Ting MAO ; Jun ZENG ; Yufeng WANG ; Xin ZHAO
Chinese Journal of Medical Genetics 2013;30(3):335-339
OBJECTIVETo assess the association of a single nucleotide polymorphism(SNP) in tumor suppressor gene P53 with the risk of endometriosis (EM) in Han Chinese women.
METHODSFor 460 EM patients, 113 patients with endometrial carcinoma and 530 matched unrelated controls, a rs1042522(C/G) SNP of the P53 gene was genotyped by polymerase chain reaction-single strand polymorphism (PCR-SSP) and DNA sequencing.
RESULTSA significant difference has been detected in the distribution of rs1042522 alleles and genotypes between the EM patients and controls (P< 0.01). Allele G has increased the risk of EM by 1.209 times, while allele C has reduced this risk by 0.837 times. Compared with GG genotype, GC and CC genotypes have both increased the risk for EM (OR=2.073, 95%CI: 1.521-2.820, and OR=1.930, 95%CI: 1.363-2.733, respectively). Significant differences were also detected in the distribution of rs1042522 alleles and genotypes between endometrial carcinoma patients and controls (P< 0.01). Allele G has increased the risk to endometrial carcinoma by 1.311 times, while allele C has reduced this risk by 0.757 times. Compared with GG genotypes, individuals with GC and CC genotypes are more likely to be affected with endometrial carcinoma (OR=2.778, 95%CI: 1.585-4.870, and OR=2.864, 95%CI: 1.557-5.263, respectively).
CONCLUSIONOur study has suggested a significant association between the rs1042522(G/C) polymorphism and susceptibility to EM in Han Chinese women. The mechanism of EM is similar to carcinoma from genetics point of view.
Alleles ; Asian Continental Ancestry Group ; Base Sequence ; China ; Endometrial Neoplasms ; genetics ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide ; Tumor Suppressor Protein p53 ; genetics
10.Measurement of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome and its clinical significance.
Xiaoping TANG ; Chibiao YIN ; Fuchun ZHANG ; Yonggui FU ; Weilie CHEN ; Yanqing CHEN ; Jian WANG ; Weidong JIA ; Anlong XU
Chinese Medical Journal 2003;116(6):827-830
OBJECTIVETo investigate the changes of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome (SARS) and its clinical significance.
METHODSSubgroups of blood T lymphocytes in 93 patients with SARS were detected by flow cytometer. The results detected in 64 normal subjects and 50 patients with AIDS served as controls.
RESULTSThe numbers of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes all significantly decreased in acute phase of patients with SARS [(722 +/- 533)/microliter, (438 +/- 353)/microliter, (307 +/- 217)/microliter] compared with those in normal controls [(1527 +/- 470)/microliter, (787 +/- 257)/microliter, (633 +/- 280)/microliter, all P <0.01], which was different from what we observed in patients with AIDS who had decreased CD(4)(+) [(296 +/- 298)/microliter] but increased CD(8)(+) [(818 +/- 566)/microliter] counts. The counts of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes decreased more apparently in patients with severe SARS. All the five patients who died had CD(4)(+) counts less than 200/microliter. As the patients' condition improved, CD(3)(+), CD(4)(+), and CD(8)(+) counts gradually returned to normal ranges.
CONCLUSIONThe damage of cellular immunity is probably an important mechanism of pathogenesis of SARS.
Acquired Immunodeficiency Syndrome ; immunology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Severe Acute Respiratory Syndrome ; immunology ; T-Lymphocyte Subsets ; immunology