宰后能量代谢是影响肉嫩度的关键生化途径,其中糖酵解是宰后能量代谢的主导过程,其进程受到众多因素的调控。本文综述了影响宰后糖酵解进程的因素及具体影响机制。一磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)和沉默信...宰后能量代谢是影响肉嫩度的关键生化途径,其中糖酵解是宰后能量代谢的主导过程,其进程受到众多因素的调控。本文综述了影响宰后糖酵解进程的因素及具体影响机制。一磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)和沉默信息调节因子1(sirtuin 1,SIRT1)是宰后糖酵解的重要上游调控因子,本文重点概括了AMPK/SIRT1信号通路对糖酵解及宰后内源酶系的影响,并解析其作用机制,以期为AMPK/SIRT1信号通路调控肉的嫩度提供新思路。展开更多
目的探讨力生长因子(MGF)对软骨终板干细胞(CESCs)增殖、迁移和分化的影响及其作用机制。方法招募因退行性椎间盘疾病于广西壮族自治区人民医院进行椎间盘融合手术患者,术中采集其椎间盘软骨终板组织约2 cm 3,取CESCs并进行培养。通过CC...目的探讨力生长因子(MGF)对软骨终板干细胞(CESCs)增殖、迁移和分化的影响及其作用机制。方法招募因退行性椎间盘疾病于广西壮族自治区人民医院进行椎间盘融合手术患者,术中采集其椎间盘软骨终板组织约2 cm 3,取CESCs并进行培养。通过CCK-8实验评估MGF对CESCs增殖的影响;通过Transwell实验评估MGF对CESCs迁移和侵袭能力的影响;通过逆转录聚合酶链式反应(RT-PCR)和Western blot实验检测成骨、成软骨及成脂分化相关因子的表达水平,并分析细胞外信号调节激酶(ERK)磷酸化对MGF作用效果的影响。结果CCK-8实验结果显示,MGF可促进CESCs增殖,且呈剂量依赖性。Transwell实验结果显示,MGF可促进CESCs迁移。经ERK抑制剂PD98059干预后,MGF的促增殖作用显著降低(P<0.05)。经胰岛素样生长因子-1受体(IGF-1R)抑制剂PQ401干预后,MGF的促迁移作用也显著降低(P<0.05)。RT-PCR检测结果显示,MGF组碱性磷酸酶(ALP)、Runt相关转录因子2(Runx2)和骨钙素(OC)的mRNA表达水平显著低于对照组(P<0.05),聚集蛋白聚糖(AGG)、性别决定区相关转录因子-9(SOX-9)和Ⅱ型胶原(CⅡ)的mRNA表达水平显著高于对照组(P<0.05)。Western blot实验结果也显示,MGF组ALP、Runx2和OC的蛋白表达水平显著低于对照组(P<0.05),AGG、SOX-9和CⅡ的蛋白表达水平显著高于对照组(P<0.05)。MGF组磷酸化细胞外信号调节激酶(p-ERK)/总细胞外信号调节激酶(t-ERK)比值显著高于对照组(P<0.05),MGF+PQ401组p-ERK/t-ERK比值低于MGF组,但仍高于对照组,差异有统计学意义(P<0.05)。结论MGF通过诱导ERK磷酸化促进CESCs的增殖和迁移。展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of ch...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.展开更多
BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contribut...BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.展开更多
Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury ...Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury was established by administration of acetaminophen(APAP)(300 mg/kg,i.p.) on C57BL/6 mice.Forty-eight male C57BL/6 mice were randomly divided into four groups,consisting of control group,GS group(GS-459679,30 mg/kg,i.p.),APAPinduced group,and GS combined with APAP-induced group.For GS combined with APAPinduced group,mice were treated with GS 30 min prior to administration of APAP.After mice were euthanized at 6 h or 12 h.respectively,serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were analyzed,and mRNA levels of TNF- α,IL-6 and IL-1βwere tested.The activity of glutathione(GSH),oxidized GSH(GSSG) and malondialdehyde were quantified.In addition,ASK1,P-ASK1,JNK and P-JNK protein levels were tested in all groups.Results:The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group.Compared to the control group,serum levels of ALT and AST.and mRNA levels of TNF- a,IL-6 and IL-1(3were increased in APAP-induced group.Meanwhile,the levels of MAD and GSSG.and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group.However,compared to APAP-induced group,GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK 1,P-ASKI and P-JNK,a reduction of serum levels of ALT and AST,a decrease in TNF- a.IL-6 and IL-1(3 mRNA levels,and a low ration of GSSG/GSH.Conclusions:GS-459679 treatment effectively down-regulates ASK1 and P-ASK 1 expression.Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors,reduces oxidative stress reaction,inhibits JNK activation,and then protects the responsiveness to APAP-induced liver injury.展开更多
文摘宰后能量代谢是影响肉嫩度的关键生化途径,其中糖酵解是宰后能量代谢的主导过程,其进程受到众多因素的调控。本文综述了影响宰后糖酵解进程的因素及具体影响机制。一磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)和沉默信息调节因子1(sirtuin 1,SIRT1)是宰后糖酵解的重要上游调控因子,本文重点概括了AMPK/SIRT1信号通路对糖酵解及宰后内源酶系的影响,并解析其作用机制,以期为AMPK/SIRT1信号通路调控肉的嫩度提供新思路。
文摘目的探讨力生长因子(MGF)对软骨终板干细胞(CESCs)增殖、迁移和分化的影响及其作用机制。方法招募因退行性椎间盘疾病于广西壮族自治区人民医院进行椎间盘融合手术患者,术中采集其椎间盘软骨终板组织约2 cm 3,取CESCs并进行培养。通过CCK-8实验评估MGF对CESCs增殖的影响;通过Transwell实验评估MGF对CESCs迁移和侵袭能力的影响;通过逆转录聚合酶链式反应(RT-PCR)和Western blot实验检测成骨、成软骨及成脂分化相关因子的表达水平,并分析细胞外信号调节激酶(ERK)磷酸化对MGF作用效果的影响。结果CCK-8实验结果显示,MGF可促进CESCs增殖,且呈剂量依赖性。Transwell实验结果显示,MGF可促进CESCs迁移。经ERK抑制剂PD98059干预后,MGF的促增殖作用显著降低(P<0.05)。经胰岛素样生长因子-1受体(IGF-1R)抑制剂PQ401干预后,MGF的促迁移作用也显著降低(P<0.05)。RT-PCR检测结果显示,MGF组碱性磷酸酶(ALP)、Runt相关转录因子2(Runx2)和骨钙素(OC)的mRNA表达水平显著低于对照组(P<0.05),聚集蛋白聚糖(AGG)、性别决定区相关转录因子-9(SOX-9)和Ⅱ型胶原(CⅡ)的mRNA表达水平显著高于对照组(P<0.05)。Western blot实验结果也显示,MGF组ALP、Runx2和OC的蛋白表达水平显著低于对照组(P<0.05),AGG、SOX-9和CⅡ的蛋白表达水平显著高于对照组(P<0.05)。MGF组磷酸化细胞外信号调节激酶(p-ERK)/总细胞外信号调节激酶(t-ERK)比值显著高于对照组(P<0.05),MGF+PQ401组p-ERK/t-ERK比值低于MGF组,但仍高于对照组,差异有统计学意义(P<0.05)。结论MGF通过诱导ERK磷酸化促进CESCs的增殖和迁移。
基金Supported by Innovation Project of Guangxi Graduate Education,No.YCBZ2023096Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442+1 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598185Future Academic Star of Guangxi Medical University,No.WLXSZX24101.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.
文摘BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.
基金supported by Soft Science Foundation of Yongchuan District of Chongqing City(Grant No.YCSTC.2011BE5015)
文摘Objective:To explore the protective effect and its molecular mechanism of apoptosis signalregulating kinase 1(ASK1) inhibitor(GS-459679) on acetaminophen-induced liver injury in mice.Methods:The model of liver injury was established by administration of acetaminophen(APAP)(300 mg/kg,i.p.) on C57BL/6 mice.Forty-eight male C57BL/6 mice were randomly divided into four groups,consisting of control group,GS group(GS-459679,30 mg/kg,i.p.),APAPinduced group,and GS combined with APAP-induced group.For GS combined with APAPinduced group,mice were treated with GS 30 min prior to administration of APAP.After mice were euthanized at 6 h or 12 h.respectively,serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were analyzed,and mRNA levels of TNF- α,IL-6 and IL-1βwere tested.The activity of glutathione(GSH),oxidized GSH(GSSG) and malondialdehyde were quantified.In addition,ASK1,P-ASK1,JNK and P-JNK protein levels were tested in all groups.Results:The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group.Compared to the control group,serum levels of ALT and AST.and mRNA levels of TNF- a,IL-6 and IL-1(3were increased in APAP-induced group.Meanwhile,the levels of MAD and GSSG.and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group.However,compared to APAP-induced group,GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK 1,P-ASKI and P-JNK,a reduction of serum levels of ALT and AST,a decrease in TNF- a.IL-6 and IL-1(3 mRNA levels,and a low ration of GSSG/GSH.Conclusions:GS-459679 treatment effectively down-regulates ASK1 and P-ASK 1 expression.Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors,reduces oxidative stress reaction,inhibits JNK activation,and then protects the responsiveness to APAP-induced liver injury.
