Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows...Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.展开更多
目的探讨利用siRNA下调骨髓基质细胞系ST2细胞中Spry1的内源性表达对脂肪细胞分化的调控作用。方法设计Spry1的靶向si RNA作为实验组,以转染Control si RNA作为对照组。在ST2细胞中转染Spry1si RNA和Control si RNA并进行成脂诱导,应用q...目的探讨利用siRNA下调骨髓基质细胞系ST2细胞中Spry1的内源性表达对脂肪细胞分化的调控作用。方法设计Spry1的靶向si RNA作为实验组,以转染Control si RNA作为对照组。在ST2细胞中转染Spry1si RNA和Control si RNA并进行成脂诱导,应用q RT-PCR检测2组细胞中的Spry1和成脂特异性因子过氧化物酶体增殖物激活受体(PPAR)γ、CCAAT增强子结合蛋白(C/EBP)α、脂肪细胞表征因子FABP4、脂肪因子adipsin的m RNA表达水平。脂肪细胞分化成熟后,进行油红O染色,显微镜下观察脂肪细胞的染色情况及Spry1 si RNA对ST2细胞成脂分化的影响。运用异丙醇萃取染色的脂肪细胞中的油红O并测定波长在520 nm处的光密度(OD)值。结果转染Spry1 si RNA于ST2细胞后,与转染Control si RNA的对照组相比,Spry1基因的表达水平明显下调,Spry1 si RNA可抑制脂肪细胞的分化,油红O染色显示实验组的脂肪细胞明显减少且OD值低于对照组;转染Spry1si RNA实验组的成脂特异性因子PPARγ、C/EBPα、FABP4、adipsin的m RNA表达水平显著下调,差异有统计学意义(P<0.05)。结论 Spry1 siRNA可有效抑制前体细胞向脂肪细胞分化。展开更多
目的:研究远隔缺血预适应(RIPC)对脑缺血模型大鼠的保护作用及分子机制。方法:18只成年雄性SD大鼠随机分为3组:假手术组(sham)、缺血再灌注组(MCAO/R)组、RIPC+MCAO/R组;术前利用间断夹闭双侧股动脉的方法给予大鼠RIPC处理,利用大脑中...目的:研究远隔缺血预适应(RIPC)对脑缺血模型大鼠的保护作用及分子机制。方法:18只成年雄性SD大鼠随机分为3组:假手术组(sham)、缺血再灌注组(MCAO/R)组、RIPC+MCAO/R组;术前利用间断夹闭双侧股动脉的方法给予大鼠RIPC处理,利用大脑中动脉栓塞法(MCAO)制备大鼠缺血性脑卒中模型,利用转棒实验检测大鼠运动功能,利用TUNEL染色检测缺血区细胞凋亡,利用real time RT⁃PCR检测大脑缺血区皮质中miR⁃21⁃5p及SPRY1和程序性细胞死亡因子4(PDCD4)mRNA的表达。结果:与MCAO/R组大鼠相比,RIPC处理组大鼠运动功能有所改善,皮质细胞凋亡减少。miR⁃21⁃5p表达增加,而SPRY1和PDCD4 mRNA表达下调(P<0.05)。结论:RIPC处理对减轻缺血性脑卒中大鼠miR⁃21⁃5p表达上调,后者通过抑制靶分子SPRY1和PDCD4的表达抑制细胞凋亡。展开更多
Objective Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanis...Objective Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. Methods We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. Results Low-dose arsenic exposure（≤ 5 μmol/L） can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3（pSTAT3） expression, and decrease programmed cell death protein 4（PDCD4） and protein sprouty homolog 1（Spry1） expression. High-dose arsenic exposure（〉 5 μmol/L）, can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure（≤ 24 h） can increase miRNA-21 and pS TAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure（〉 24 h） can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. Conclusion Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.展开更多
基金supported by the National Natural Science Foundation of China(32072806,31572399)National Key Research and Development Program of China(2022YFD1302201)+3 种基金Program of Shaanxi Province Science and Technology Innovation Team(2019TD-036)Major Projects of Natural Science Foundation of Inner Mongolia Autonomous Region(2020ZD10)Key Research and Development Program of Shaanxi Province(2022NY-044)Key Technologies Demonstration of Animal Husbandry in Shaanxi Province(20221086)。
文摘Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.
文摘目的探讨利用siRNA下调骨髓基质细胞系ST2细胞中Spry1的内源性表达对脂肪细胞分化的调控作用。方法设计Spry1的靶向si RNA作为实验组,以转染Control si RNA作为对照组。在ST2细胞中转染Spry1si RNA和Control si RNA并进行成脂诱导,应用q RT-PCR检测2组细胞中的Spry1和成脂特异性因子过氧化物酶体增殖物激活受体(PPAR)γ、CCAAT增强子结合蛋白(C/EBP)α、脂肪细胞表征因子FABP4、脂肪因子adipsin的m RNA表达水平。脂肪细胞分化成熟后,进行油红O染色,显微镜下观察脂肪细胞的染色情况及Spry1 si RNA对ST2细胞成脂分化的影响。运用异丙醇萃取染色的脂肪细胞中的油红O并测定波长在520 nm处的光密度(OD)值。结果转染Spry1 si RNA于ST2细胞后,与转染Control si RNA的对照组相比,Spry1基因的表达水平明显下调,Spry1 si RNA可抑制脂肪细胞的分化,油红O染色显示实验组的脂肪细胞明显减少且OD值低于对照组;转染Spry1si RNA实验组的成脂特异性因子PPARγ、C/EBPα、FABP4、adipsin的m RNA表达水平显著下调,差异有统计学意义(P<0.05)。结论 Spry1 siRNA可有效抑制前体细胞向脂肪细胞分化。
文摘目的:研究远隔缺血预适应(RIPC)对脑缺血模型大鼠的保护作用及分子机制。方法:18只成年雄性SD大鼠随机分为3组:假手术组(sham)、缺血再灌注组(MCAO/R)组、RIPC+MCAO/R组;术前利用间断夹闭双侧股动脉的方法给予大鼠RIPC处理,利用大脑中动脉栓塞法(MCAO)制备大鼠缺血性脑卒中模型,利用转棒实验检测大鼠运动功能,利用TUNEL染色检测缺血区细胞凋亡,利用real time RT⁃PCR检测大脑缺血区皮质中miR⁃21⁃5p及SPRY1和程序性细胞死亡因子4(PDCD4)mRNA的表达。结果:与MCAO/R组大鼠相比,RIPC处理组大鼠运动功能有所改善,皮质细胞凋亡减少。miR⁃21⁃5p表达增加,而SPRY1和PDCD4 mRNA表达下调(P<0.05)。结论:RIPC处理对减轻缺血性脑卒中大鼠miR⁃21⁃5p表达上调,后者通过抑制靶分子SPRY1和PDCD4的表达抑制细胞凋亡。
基金supported by the National Natural Science Foundation of China [No.81560517,81760584]the Key Areas of Science and Technology Research Project of Xinjiang Production and Construction Corps [No.2014BA039,No.2015AG014]the International Cooperative Project of Shihezi University [No.GJHZ201602]
文摘Objective Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. Methods We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. Results Low-dose arsenic exposure（≤ 5 μmol/L） can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3（pSTAT3） expression, and decrease programmed cell death protein 4（PDCD4） and protein sprouty homolog 1（Spry1） expression. High-dose arsenic exposure（〉 5 μmol/L）, can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure（≤ 24 h） can increase miRNA-21 and pS TAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure（〉 24 h） can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. Conclusion Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.
