BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis...BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.展开更多
The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secret-ing inlfammatory cytokines, and is an important target in the treatment of nerve inlfammation and neurodegenerative di...The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secret-ing inlfammatory cytokines, and is an important target in the treatment of nerve inlfammation and neurodegenerative diseases. In the present study, we observed the effects of transfecting three amyloid precursor-like protein 2 （APLP2） C-terminal fragments （CTFs; C57, C50 and C31） in the pEGFP-N1 vector on S100A9 expression in BV2 cells. Reverse transcription-PCR, western blot assay and immunocytochemistry revealed that S100A9 protein and mRNA expression was greater in BV2 cells after CTF transfection than after mock transfection with an empty vector. Furthermore, transfection of full-length APLP2-751 resulted in low levels of S100A9 protein ex-pression. Our results show that APLP2-CTFs upregulate S100A9 protein and mRNA expression in BV2 cells, and identify a novel pathway involved in neuronal injury and apoptosis, and repair and protection in Alzheimer’s disease.展开更多
Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin r...Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.展开更多
目的观察甲磺酸多沙唑嗪联合翁沥治疗前列腺增生(BPH)的临床效果,并探讨其对患者基质金属蛋白酶-9 (MMP-9)及S100钙结合蛋白P (S100P)水平的影响。方法选取2016年4月至2018年3月于上海市浦东新区光明中医院就诊的240例BPH患者,根据随机...目的观察甲磺酸多沙唑嗪联合翁沥治疗前列腺增生(BPH)的临床效果,并探讨其对患者基质金属蛋白酶-9 (MMP-9)及S100钙结合蛋白P (S100P)水平的影响。方法选取2016年4月至2018年3月于上海市浦东新区光明中医院就诊的240例BPH患者,根据随机数表法将其分为对照组和观察组,每组120例。两组患者均限制酒精、咖啡因等摄入,控制睡前的饮水量。对照组给予甲磺酸多沙唑嗪控释片,观察组在对照组治疗的基础上给予翁沥通胶囊,疗程均为4周。比较两组患者的临床疗效、不良反应发生率、治疗前后国际前列腺症状评分(IPSS)、受困扰评分(QOL)及前列腺体积,同时比较两组患者的S100P、MMP-9阳性率。结果观察组患者的临床总有效率为91.7%,明显高于对照组的82.5%,差异具有统计学意义(P<0.05);观察组与对照组不良反应发生率分别为2.5%、3.3%,差异无统计学意义(P>0.05);治疗后,观察组患者的MPP-9和S100P阳性率分别为85.0%、7.5%,明显低于对照组的93.3%、15.8%,差异均具有统计学意义(P<0.05);治疗前,观察组患者的IPSS评分、QOL评分及前列腺体积分别为(21.95±3.91)分、(3.94±1.15)分、(73.41±29.45) m L,对照组分别为(22.46±3.89)分、(3.89±1.21)分及(74.03±30.92) mL,两组比较差异均无统计学意义(P>0.05);治疗后,观察组患者的IPSS评分及QOL评分分别为(13.49±6.84)分、(2.03±0.94)分,明显低于对照组的(16.56±7.42)分、(2.52±1.18)分,差异均有统计学意义(P<0.05);但前列腺体积无明显变化[(72.19±11.43) m L vs (73.51±33.06) m L],差异无统计学意义(P>0.05)。结论甲磺酸多沙唑嗪联合翁沥通治疗前列腺增生具有良好的临床疗效,其不仅能缓解患者尿路梗阻症状,明显降低MMP-9、S100P水平,而且还改善患者的生活质量。展开更多
Activated nucleotide binding to the oligonucleotide receptor protein 3（NLRP3） inflammasome is possibly involved in the pathogenesis of Alzheimer＇s disease through oxidative stress and neurogenic inflammation. Low e...Activated nucleotide binding to the oligonucleotide receptor protein 3（NLRP3） inflammasome is possibly involved in the pathogenesis of Alzheimer＇s disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3（STAT3） gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress,（1） SHSY5 Y cells were incubated with 1 mM H2 O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2＋ chelator BAPATA-AM（0.1 mM） for 30 minutes as a control.（2） Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2 O2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2 O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5 Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2^＋ signaling pathway.展开更多
Background and Purpose: Hypertension has serious effects on cerebral blood vessels. Oxidative stress seems to be implicated in blood pressure elevation, through increased reactive oxygen species and/or decreased antio...Background and Purpose: Hypertension has serious effects on cerebral blood vessels. Oxidative stress seems to be implicated in blood pressure elevation, through increased reactive oxygen species and/or decreased antioxidant capacity. Recently blood markers indicating damage to the central nervous system were reported to be increased in hypertensive patients. However, it is unknown whether antioxidant capacity is related to these changes. This study was designed to explore if the concentration of blood markers for nervous tissue damage was associated to antioxidant capacity in hypertensive patients. Methods: Twenty hypertensive patients and 23 healthy controls were studied. They were paired by age, sex, ethnicity, or risk factors. Serum neuron specific enolase (NSE) and S100 calcium binding protein B (S100B) were measured as nervous tissue damage markers, as well as the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase and gamma-glutamyltransferase). Results: Serum neuronal specific enolase (NSE) and S100 calcium binding protein B (S100B) concentrations determined by immunoassay were significantly increased in patients vs. controls. The activities of antioxidant enzymes measured by spectrophotometry showed that plasmatic catalase and erythrocytic glutathione peroxidase were significantly increased in patients, but erythocytic catalase was decreased. Gamma-glutamyltransferase activity was significantly correlated with S100B in hypertensive patients, while erythrocytic catalase activity was decreased in subjects with higher NSE levels. Conclusion: This preliminary investigation suggested that antioxidant status might be modulated through changes in antioxidant enzymatic activity in hypertensive patients. The association of some of these changes with peripheral markers of damage to the central nervous system could indicate that the increased levels of these proteins in hypertension are partly related to oxidative stress.展开更多
基金National Natural Science Foundation of China,No.81871723.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.
基金supported by the Natural Science Foundation of Technology Gallery in Jilin Province of China,No.2011-15237the National Natural Science Foundation of China,No.81160159
文摘The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secret-ing inlfammatory cytokines, and is an important target in the treatment of nerve inlfammation and neurodegenerative diseases. In the present study, we observed the effects of transfecting three amyloid precursor-like protein 2 （APLP2） C-terminal fragments （CTFs; C57, C50 and C31） in the pEGFP-N1 vector on S100A9 expression in BV2 cells. Reverse transcription-PCR, western blot assay and immunocytochemistry revealed that S100A9 protein and mRNA expression was greater in BV2 cells after CTF transfection than after mock transfection with an empty vector. Furthermore, transfection of full-length APLP2-751 resulted in low levels of S100A9 protein ex-pression. Our results show that APLP2-CTFs upregulate S100A9 protein and mRNA expression in BV2 cells, and identify a novel pathway involved in neuronal injury and apoptosis, and repair and protection in Alzheimer’s disease.
基金supported by grants from the Natural Science Foundation of China(81971851 and 82172229)the Natural Science Foundation of Shaanxi Province(2022JM-600)the Foundation of Xijing Hospital Grants(XJZT21CM33).
文摘Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.
文摘目的观察甲磺酸多沙唑嗪联合翁沥治疗前列腺增生(BPH)的临床效果,并探讨其对患者基质金属蛋白酶-9 (MMP-9)及S100钙结合蛋白P (S100P)水平的影响。方法选取2016年4月至2018年3月于上海市浦东新区光明中医院就诊的240例BPH患者,根据随机数表法将其分为对照组和观察组,每组120例。两组患者均限制酒精、咖啡因等摄入,控制睡前的饮水量。对照组给予甲磺酸多沙唑嗪控释片,观察组在对照组治疗的基础上给予翁沥通胶囊,疗程均为4周。比较两组患者的临床疗效、不良反应发生率、治疗前后国际前列腺症状评分(IPSS)、受困扰评分(QOL)及前列腺体积,同时比较两组患者的S100P、MMP-9阳性率。结果观察组患者的临床总有效率为91.7%,明显高于对照组的82.5%,差异具有统计学意义(P<0.05);观察组与对照组不良反应发生率分别为2.5%、3.3%,差异无统计学意义(P>0.05);治疗后,观察组患者的MPP-9和S100P阳性率分别为85.0%、7.5%,明显低于对照组的93.3%、15.8%,差异均具有统计学意义(P<0.05);治疗前,观察组患者的IPSS评分、QOL评分及前列腺体积分别为(21.95±3.91)分、(3.94±1.15)分、(73.41±29.45) m L,对照组分别为(22.46±3.89)分、(3.89±1.21)分及(74.03±30.92) mL,两组比较差异均无统计学意义(P>0.05);治疗后,观察组患者的IPSS评分及QOL评分分别为(13.49±6.84)分、(2.03±0.94)分,明显低于对照组的(16.56±7.42)分、(2.52±1.18)分,差异均有统计学意义(P<0.05);但前列腺体积无明显变化[(72.19±11.43) m L vs (73.51±33.06) m L],差异无统计学意义(P>0.05)。结论甲磺酸多沙唑嗪联合翁沥通治疗前列腺增生具有良好的临床疗效,其不仅能缓解患者尿路梗阻症状,明显降低MMP-9、S100P水平,而且还改善患者的生活质量。
基金supported by Department of Science and Technology in Guizhou Province of China,No.Basic [2016]1131(to QianKe-He to HB)+2 种基金Department of Health and Family Planning Commission in Guizhou Province of China,No.2015-326(to HB)Less Developed Regions of the National Natural Science Foundation of China,No.81560482the Research Foundation for Creative Research Groups of Education Bureau of Guizhou Province of China,No.KY[2016]033(to QFZ)
文摘Activated nucleotide binding to the oligonucleotide receptor protein 3（NLRP3） inflammasome is possibly involved in the pathogenesis of Alzheimer＇s disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3（STAT3） gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress,（1） SHSY5 Y cells were incubated with 1 mM H2 O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2＋ chelator BAPATA-AM（0.1 mM） for 30 minutes as a control.（2） Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2 O2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2 O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5 Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2^＋ signaling pathway.
文摘Background and Purpose: Hypertension has serious effects on cerebral blood vessels. Oxidative stress seems to be implicated in blood pressure elevation, through increased reactive oxygen species and/or decreased antioxidant capacity. Recently blood markers indicating damage to the central nervous system were reported to be increased in hypertensive patients. However, it is unknown whether antioxidant capacity is related to these changes. This study was designed to explore if the concentration of blood markers for nervous tissue damage was associated to antioxidant capacity in hypertensive patients. Methods: Twenty hypertensive patients and 23 healthy controls were studied. They were paired by age, sex, ethnicity, or risk factors. Serum neuron specific enolase (NSE) and S100 calcium binding protein B (S100B) were measured as nervous tissue damage markers, as well as the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase and gamma-glutamyltransferase). Results: Serum neuronal specific enolase (NSE) and S100 calcium binding protein B (S100B) concentrations determined by immunoassay were significantly increased in patients vs. controls. The activities of antioxidant enzymes measured by spectrophotometry showed that plasmatic catalase and erythrocytic glutathione peroxidase were significantly increased in patients, but erythocytic catalase was decreased. Gamma-glutamyltransferase activity was significantly correlated with S100B in hypertensive patients, while erythrocytic catalase activity was decreased in subjects with higher NSE levels. Conclusion: This preliminary investigation suggested that antioxidant status might be modulated through changes in antioxidant enzymatic activity in hypertensive patients. The association of some of these changes with peripheral markers of damage to the central nervous system could indicate that the increased levels of these proteins in hypertension are partly related to oxidative stress.
