Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detec...Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases,since many clinically relevant decisions,such as starting treatment and/or monitoring for complications including hepatocellular carcinoma,may depend on it.The gold standard for fibrosis staging is liver biopsy,the role of which,however,is questioned nowadays because of cost,hazards and poor acceptance by patients.On the other hand,imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy.Making progress in this field is nowmore crucial than ever,since treatments for established fibrosis appear on the horizon.Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis,such as growth arrest-specific6,Mac-2-binding protein,osteopontin,placental growth factor,growth/differentiation factor 15 and hepatocyte growth factor.All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases.Here,we review the pros and cons for their use in this setting.展开更多
目的研究生长停滞特异性蛋白6（Gas6）对脓毒症急性肺损伤小鼠的保护作用，并探讨其作用机制。方法取90只BALB／c雄性小鼠，按随机数字表法分为假手术组、脓毒症组、脓毒症＋生理盐水组、脓毒症＋Gas6干预（1μg）组、脓毒症＋Gas6干预...目的研究生长停滞特异性蛋白6（Gas6）对脓毒症急性肺损伤小鼠的保护作用，并探讨其作用机制。方法取90只BALB／c雄性小鼠，按随机数字表法分为假手术组、脓毒症组、脓毒症＋生理盐水组、脓毒症＋Gas6干预（1μg）组、脓毒症＋Gas6干预（5μg）组、脓毒症＋Gas6干预（10μg）组，每组15只。脓毒症和脓毒症＋Gas6干预组行盲肠结扎穿孔术（cecal ligation and puncture，CLP），Gas6干预组术后立即尾静脉注射Gas6。假手术组仅行开腹，不予以结扎穿孔。术后24h收集血液，酶联免疫吸附法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）水平；处死小鼠，留取肺组织，测定肺组织湿／干质量比值（W／D）；观察肺组织病理学改变，计算肺组织病理评分；蛋白免疫印迹法（Westernblotting）检测肺组织胞核NF-κB p65及胞浆IκB-α蛋白表达。统计学方法采用SPSS23．0统计软件，两组样本比较采用独立样本t检验，多组间比较采用单因素方差分析检验。结果与假手术组相比较，脓毒症组小鼠血清TNF-α（P=0．000）、IL-1β（P=0．000）、肺组织湿／干重比值（W／D）（P=0．000）、肺组织病理评分（P=0．000）、肺组织胞核NF-κBp65蛋白含量（P=0．006）的表达均增加，而肺组织胞浆IκB-α（P=0．001）表达明显下降。与脓毒症＋生理盐水组相比，脓毒症＋Gas6（1、5、10μg）组小鼠24h后血清中TNF-α（P=0．000）、IL-1β（P=0．000）、肺W／D（P=0．000）、肺组织病理评分（P=0．000）、肺组织胞核NF-κBp65蛋白含量（P=0．000）的表达水平降低，而胞浆IκB-α（P=0．009）表达水平明显上升并呈一定的剂量依赖关系。结论Gas6能够有效减轻脓毒症所致的肺损伤，其分子作用机制可能与抑制炎性反应以及下调NF-κBp65胞核内转位有关。展开更多
目的:探讨系统性红斑狼疮患者血清β2-微球蛋白(β2-MG)、颗粒蛋白前体(PGRN)、生长停滞基因6(Gas6)水平与疾病严重程度和肾脏损害的关系。方法:选择2017年1月至2020年12月河北医科大学第二医院风湿免疫科收治的系统性红斑狼疮患者105例...目的:探讨系统性红斑狼疮患者血清β2-微球蛋白(β2-MG)、颗粒蛋白前体(PGRN)、生长停滞基因6(Gas6)水平与疾病严重程度和肾脏损害的关系。方法:选择2017年1月至2020年12月河北医科大学第二医院风湿免疫科收治的系统性红斑狼疮患者105例,根据系统性红斑狼疮疾病活动度指数(SLEDAI)将患者分为活动期组(SLEDAI≥5分)62例,缓解期组(SLEDAI≤4分)43例。另取同期于河北医科大学第二医院接受体检的健康志愿者60例作为对照组。比较各组血清β2-MG、PGRN、Gas6、红细胞沉降率(ESR)、C反应蛋白(CRP)、血清补体、抗dsDNA抗体、血尿素氮(BUN)、血肌酐(Scr),24 h尿蛋白(24h UTP),并分析其相关性。结果:活动期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平高于缓解期组、对照组,Gas6、血清补体C3、C4水平低于缓解期组、对照组;缓解期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平均高于对照组,Gas6、血清补体C3、C4水平低于对照组,活动期组SLEDAI评分高于缓解期组(P<0.05)。Pearson相关性分析可得:系统性红斑狼疮患者血清β2-MG、PGRN与SLEDAI、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈正相关,与血清补体C3、补体C4呈负相关(均P<0.05),Gas6水平与SLEDAI、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈负相关,与血清补体C3、补体C4呈正相关(均P<0.05)。结论:系统性红斑狼疮患者血清β2-MG、PGRN水平异常升高,Gas6水平异常降低,且和患者疾病活动程度及肾脏损害密切相关,检测其水平可能为系统性红斑狼疮疾病的评估提供参考。展开更多
目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测G...目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测Gas6与STAT1在多种癌症中的相关性;通过染色质免疫沉淀(chromatin immunoprecipitation,ChIP)实验检测STAT1是否可与Gas6启动子结合,应用数据库预测STAT1在Gas6启动子上的结合位点并突变其关键碱基,通过双萤光素酶报告基因实验检测结合位点突变对Gas6启动子活性的影响,同时分别检测敲低或过表达STAT1对Gas6启动子和突变的Gas6启动子活性的影响;通过实时荧光定量PCR技术和蛋白质免疫印迹技术分别检测敲低或过表达STAT1对Gas6 mRNA及蛋白表达的影响。结果:Gas6基因在乳腺癌中高表达;Gas6与STAT1在多种癌症中有正相关趋势;Gas6启动子序列包含STAT1的结合位点,并且有调控Gas6启动子活性的功能性结合位点。转录因子STAT1可在转录水平对癌症相关基因Gas6进行正向调控。结论:癌症相关基因Gas6是转录因子STAT1的直接靶基因。展开更多
目的探讨参芪降糖胶囊联合地特胰岛素注射液治疗妊娠糖尿病的临床疗效。方法选取2022年2月—2024年1月在天津北大医疗海洋石油医院就诊的83例妊娠糖尿病患者,按随机数字表法将所有患者分为对照组(41例)和治疗组(42例)。对照组每日晚间...目的探讨参芪降糖胶囊联合地特胰岛素注射液治疗妊娠糖尿病的临床疗效。方法选取2022年2月—2024年1月在天津北大医疗海洋石油医院就诊的83例妊娠糖尿病患者,按随机数字表法将所有患者分为对照组(41例)和治疗组(42例)。对照组每日晚间皮下注射地特胰岛素注射液,1次/d,初始剂量10 UI/次,根据个体需要调整剂量。治疗组在对照组基础上口服参芪降糖胶囊,3粒/次,3次/d。两组患者持续治疗3个月。比较总有效率、血糖指标达标时间、血清炎症因子。结果治疗后,治疗组的总有效率为95.24%,对照组的总有效率为80.49%,组间比较差异显著(P<0.05)。治疗后,治疗组空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)达标时间均短于对照组,差异有统计学意义(P<0.05)。治疗后,治疗组的空腹胰岛素(FINS)、胰岛β细胞功能指数(HOMA-β)明显升高,胰岛素抵抗指数(HOMA-IR)明显降低(P<0.05),且治疗组的FINS、HOMA-β明显高于对照组,HOMA-IR明显低于对照组(P<0.05)。治疗后,治疗组的血清亮氨酸丰富α2-糖蛋白1(LRG1)、含pyrin结构域NOD样受体家族3(NLRP3)、生长停滞特异性蛋白6(GAS6)水平显著降低(P<0.05),且治疗组的血清LRG1、NLRP3、GAS6水平均显著低于对照组(P<0.05)。结论参芪降糖胶囊联合地特胰岛素注射液可提高妊娠糖尿病的临床疗效,改善血糖和胰岛素功能,降低炎症反应。展开更多
Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-e...Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.展开更多
文摘Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases,since many clinically relevant decisions,such as starting treatment and/or monitoring for complications including hepatocellular carcinoma,may depend on it.The gold standard for fibrosis staging is liver biopsy,the role of which,however,is questioned nowadays because of cost,hazards and poor acceptance by patients.On the other hand,imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy.Making progress in this field is nowmore crucial than ever,since treatments for established fibrosis appear on the horizon.Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis,such as growth arrest-specific6,Mac-2-binding protein,osteopontin,placental growth factor,growth/differentiation factor 15 and hepatocyte growth factor.All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases.Here,we review the pros and cons for their use in this setting.
文摘目的研究生长停滞特异性蛋白6（Gas6）对脓毒症急性肺损伤小鼠的保护作用，并探讨其作用机制。方法取90只BALB／c雄性小鼠，按随机数字表法分为假手术组、脓毒症组、脓毒症＋生理盐水组、脓毒症＋Gas6干预（1μg）组、脓毒症＋Gas6干预（5μg）组、脓毒症＋Gas6干预（10μg）组，每组15只。脓毒症和脓毒症＋Gas6干预组行盲肠结扎穿孔术（cecal ligation and puncture，CLP），Gas6干预组术后立即尾静脉注射Gas6。假手术组仅行开腹，不予以结扎穿孔。术后24h收集血液，酶联免疫吸附法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）水平；处死小鼠，留取肺组织，测定肺组织湿／干质量比值（W／D）；观察肺组织病理学改变，计算肺组织病理评分；蛋白免疫印迹法（Westernblotting）检测肺组织胞核NF-κB p65及胞浆IκB-α蛋白表达。统计学方法采用SPSS23．0统计软件，两组样本比较采用独立样本t检验，多组间比较采用单因素方差分析检验。结果与假手术组相比较，脓毒症组小鼠血清TNF-α（P=0．000）、IL-1β（P=0．000）、肺组织湿／干重比值（W／D）（P=0．000）、肺组织病理评分（P=0．000）、肺组织胞核NF-κBp65蛋白含量（P=0．006）的表达均增加，而肺组织胞浆IκB-α（P=0．001）表达明显下降。与脓毒症＋生理盐水组相比，脓毒症＋Gas6（1、5、10μg）组小鼠24h后血清中TNF-α（P=0．000）、IL-1β（P=0．000）、肺W／D（P=0．000）、肺组织病理评分（P=0．000）、肺组织胞核NF-κBp65蛋白含量（P=0．000）的表达水平降低，而胞浆IκB-α（P=0．009）表达水平明显上升并呈一定的剂量依赖关系。结论Gas6能够有效减轻脓毒症所致的肺损伤，其分子作用机制可能与抑制炎性反应以及下调NF-κBp65胞核内转位有关。
文摘目的:探讨系统性红斑狼疮患者血清β2-微球蛋白(β2-MG)、颗粒蛋白前体(PGRN)、生长停滞基因6(Gas6)水平与疾病严重程度和肾脏损害的关系。方法:选择2017年1月至2020年12月河北医科大学第二医院风湿免疫科收治的系统性红斑狼疮患者105例,根据系统性红斑狼疮疾病活动度指数(SLEDAI)将患者分为活动期组(SLEDAI≥5分)62例,缓解期组(SLEDAI≤4分)43例。另取同期于河北医科大学第二医院接受体检的健康志愿者60例作为对照组。比较各组血清β2-MG、PGRN、Gas6、红细胞沉降率(ESR)、C反应蛋白(CRP)、血清补体、抗dsDNA抗体、血尿素氮(BUN)、血肌酐(Scr),24 h尿蛋白(24h UTP),并分析其相关性。结果:活动期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平高于缓解期组、对照组,Gas6、血清补体C3、C4水平低于缓解期组、对照组;缓解期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平均高于对照组,Gas6、血清补体C3、C4水平低于对照组,活动期组SLEDAI评分高于缓解期组(P<0.05)。Pearson相关性分析可得:系统性红斑狼疮患者血清β2-MG、PGRN与SLEDAI、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈正相关,与血清补体C3、补体C4呈负相关(均P<0.05),Gas6水平与SLEDAI、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈负相关,与血清补体C3、补体C4呈正相关(均P<0.05)。结论:系统性红斑狼疮患者血清β2-MG、PGRN水平异常升高,Gas6水平异常降低,且和患者疾病活动程度及肾脏损害密切相关,检测其水平可能为系统性红斑狼疮疾病的评估提供参考。
文摘目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测Gas6与STAT1在多种癌症中的相关性;通过染色质免疫沉淀(chromatin immunoprecipitation,ChIP)实验检测STAT1是否可与Gas6启动子结合,应用数据库预测STAT1在Gas6启动子上的结合位点并突变其关键碱基,通过双萤光素酶报告基因实验检测结合位点突变对Gas6启动子活性的影响,同时分别检测敲低或过表达STAT1对Gas6启动子和突变的Gas6启动子活性的影响;通过实时荧光定量PCR技术和蛋白质免疫印迹技术分别检测敲低或过表达STAT1对Gas6 mRNA及蛋白表达的影响。结果:Gas6基因在乳腺癌中高表达;Gas6与STAT1在多种癌症中有正相关趋势;Gas6启动子序列包含STAT1的结合位点,并且有调控Gas6启动子活性的功能性结合位点。转录因子STAT1可在转录水平对癌症相关基因Gas6进行正向调控。结论:癌症相关基因Gas6是转录因子STAT1的直接靶基因。
文摘目的探讨参芪降糖胶囊联合地特胰岛素注射液治疗妊娠糖尿病的临床疗效。方法选取2022年2月—2024年1月在天津北大医疗海洋石油医院就诊的83例妊娠糖尿病患者,按随机数字表法将所有患者分为对照组(41例)和治疗组(42例)。对照组每日晚间皮下注射地特胰岛素注射液,1次/d,初始剂量10 UI/次,根据个体需要调整剂量。治疗组在对照组基础上口服参芪降糖胶囊,3粒/次,3次/d。两组患者持续治疗3个月。比较总有效率、血糖指标达标时间、血清炎症因子。结果治疗后,治疗组的总有效率为95.24%,对照组的总有效率为80.49%,组间比较差异显著(P<0.05)。治疗后,治疗组空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)达标时间均短于对照组,差异有统计学意义(P<0.05)。治疗后,治疗组的空腹胰岛素(FINS)、胰岛β细胞功能指数(HOMA-β)明显升高,胰岛素抵抗指数(HOMA-IR)明显降低(P<0.05),且治疗组的FINS、HOMA-β明显高于对照组,HOMA-IR明显低于对照组(P<0.05)。治疗后,治疗组的血清亮氨酸丰富α2-糖蛋白1(LRG1)、含pyrin结构域NOD样受体家族3(NLRP3)、生长停滞特异性蛋白6(GAS6)水平显著降低(P<0.05),且治疗组的血清LRG1、NLRP3、GAS6水平均显著低于对照组(P<0.05)。结论参芪降糖胶囊联合地特胰岛素注射液可提高妊娠糖尿病的临床疗效,改善血糖和胰岛素功能,降低炎症反应。
基金supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW)the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)
文摘Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
