旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu ...旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu black goat, DBG)、内蒙古绒山羊(Inner Mongolia cashmere goat, IMCG)个体皮肤样本(n=3),利用组织切片染色技术观察皮肤中黑色素沉积情况;通过小RNA测序技术筛选差异miRNAs;培养B16-F10皮肤黑色素瘤细胞,利用细胞转染、qPCR、Western Blot、黑色素含量检测等技术验证miR-129-5p对黑色素生成的影响。结果显示,黑色素颗粒明显在YZDG胎羊皮肤和DBG毛囊的毛球、毛干、外根鞘等部位沉积,而在CDWG胎羊皮肤和IMCG表皮、毛囊中没有被观察到。经测序分析,在肤色差异的YZDG和CDWG中筛选到62个差异表达miRNAs,其中31个在乌皮山羊中上调,31个下调。在毛色差异的DBG和IMCG中,筛选到38个差异表达miRNAs,其中10个在黑色被毛山羊中表达上调,28个表达下调。两组测序结果均显示miR-129-5p在乌皮和黑色被毛山羊皮肤中高表达(P<0.05)。在细胞中过表达miR-129-5p后,相比于对照组,mimics组细胞黑色素沉积量提高了18.9%(P<0.05),TYR、TYRP1基因表达量分别上调57.3%和16.5%(P<0.05),蛋白表达量分别显著上调49.2%和40.2%(P<0.05);但MITF基因及其蛋白表达量无显著变化(P>0.05)。在抑制miR-129-5p后,inhibitor组TYR基因mRNA表达下调38.9%、蛋白表达水平下调21.1%(P<0.05);TYRP1、MITF蛋白表达水平分别下调25.3%及28.4%(P<0.05)。本研究发现,miR-129-5p在不同肤色及毛色的山羊皮肤中差异表达,且可通过调控TYR、TYRP1等关键基因的表达影响黑色素的生成,是山羊肤色和毛色形成过程的重要调节因子。展开更多
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie...BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.展开更多
BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patien...BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.展开更多
文摘旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu black goat, DBG)、内蒙古绒山羊(Inner Mongolia cashmere goat, IMCG)个体皮肤样本(n=3),利用组织切片染色技术观察皮肤中黑色素沉积情况;通过小RNA测序技术筛选差异miRNAs;培养B16-F10皮肤黑色素瘤细胞,利用细胞转染、qPCR、Western Blot、黑色素含量检测等技术验证miR-129-5p对黑色素生成的影响。结果显示,黑色素颗粒明显在YZDG胎羊皮肤和DBG毛囊的毛球、毛干、外根鞘等部位沉积,而在CDWG胎羊皮肤和IMCG表皮、毛囊中没有被观察到。经测序分析,在肤色差异的YZDG和CDWG中筛选到62个差异表达miRNAs,其中31个在乌皮山羊中上调,31个下调。在毛色差异的DBG和IMCG中,筛选到38个差异表达miRNAs,其中10个在黑色被毛山羊中表达上调,28个表达下调。两组测序结果均显示miR-129-5p在乌皮和黑色被毛山羊皮肤中高表达(P<0.05)。在细胞中过表达miR-129-5p后,相比于对照组,mimics组细胞黑色素沉积量提高了18.9%(P<0.05),TYR、TYRP1基因表达量分别上调57.3%和16.5%(P<0.05),蛋白表达量分别显著上调49.2%和40.2%(P<0.05);但MITF基因及其蛋白表达量无显著变化(P>0.05)。在抑制miR-129-5p后,inhibitor组TYR基因mRNA表达下调38.9%、蛋白表达水平下调21.1%(P<0.05);TYRP1、MITF蛋白表达水平分别下调25.3%及28.4%(P<0.05)。本研究发现,miR-129-5p在不同肤色及毛色的山羊皮肤中差异表达,且可通过调控TYR、TYRP1等关键基因的表达影响黑色素的生成,是山羊肤色和毛色形成过程的重要调节因子。
基金Supported by the National Natural Science Foundation of China,No.81900743Heilongjiang Province Outstanding Young Medical Talents Training Grant Project,China,No.HYD2020YQ0007.
文摘BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.
文摘BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.