Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid...Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.展开更多
The experiment was designed to study effects of retinoic acid and ascorbic acid on differentiation of mouse embryonic stem cells to cardiomyocytes. Embryonic bodies （EB） were developed from mESC in suspension cultur...The experiment was designed to study effects of retinoic acid and ascorbic acid on differentiation of mouse embryonic stem cells to cardiomyocytes. Embryonic bodies （EB） were developed from mESC in suspension culture, different levels of concentration of retinoic acid and ascorbic acid were used to determine the optimal conditions for EB formation. The results showed that the optimal concentrations were 10.9 mol. L-1 and 0.1 mg. mL-1 for retinoic acid and ascorbic acids, respectively. 50% of EB which was significantly （p〈0.05） different from the control group developed to cardiomyocytes. In conclusion, rctinoic acid and ascorbic acid had strong ability to promote cardiomyocyte differentiation of mouse embryonic stem cells. 10-9 mol. L-1 retinoic acid and 0.10 mg. mL-1 ascorbic acids were recommended to induce differentiation of mouse ES ceUs toward cardiomyocytes.展开更多
胆汁酸受体作为关键的代谢调节因子,在维持机体稳态中扮演着重要角色。这类受体不仅参与糖脂代谢的精细调控,还广泛影响多种生理过程。近期研究揭示了胆汁酸受体与骨代谢之间存在密切关联。值得关注的是,法尼醇X受体(farnesoid X recept...胆汁酸受体作为关键的代谢调节因子,在维持机体稳态中扮演着重要角色。这类受体不仅参与糖脂代谢的精细调控,还广泛影响多种生理过程。近期研究揭示了胆汁酸受体与骨代谢之间存在密切关联。值得关注的是,法尼醇X受体(farnesoid X receptor,FXR)和武田G蛋白偶联受体5(takeda G protein⁃coupled receptor 5,TGR5)在骨组织中的广泛表达,这一现象提示它们可能在骨代谢过程中发挥重要的调控作用。然而,FXR与TGR5调控骨代谢的具体分子机制尚未完全阐明。该文通过总结FXR和TGR5在骨代谢调控作用中的研究现状,旨在为骨代谢疾病的治疗提供新的理论基础和创新思路。展开更多
基金supported by the Natural Science Foundation of Hunan Province(2021JJ31089)the Scientific Research Project of Health Commission of Hunan Province(202203104548),China。
文摘Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
基金Supported by the Scientifi c Research Foundation for Doctors of Northeast Agricultural University(2012RCB27)Open Projects of Key Laboratory of Animal Genetics,Breeding and Reproduction,College of Heilongjiang Province(GXZDSYS-2012-07)
文摘The experiment was designed to study effects of retinoic acid and ascorbic acid on differentiation of mouse embryonic stem cells to cardiomyocytes. Embryonic bodies （EB） were developed from mESC in suspension culture, different levels of concentration of retinoic acid and ascorbic acid were used to determine the optimal conditions for EB formation. The results showed that the optimal concentrations were 10.9 mol. L-1 and 0.1 mg. mL-1 for retinoic acid and ascorbic acids, respectively. 50% of EB which was significantly （p〈0.05） different from the control group developed to cardiomyocytes. In conclusion, rctinoic acid and ascorbic acid had strong ability to promote cardiomyocyte differentiation of mouse embryonic stem cells. 10-9 mol. L-1 retinoic acid and 0.10 mg. mL-1 ascorbic acids were recommended to induce differentiation of mouse ES ceUs toward cardiomyocytes.
文摘胆汁酸受体作为关键的代谢调节因子,在维持机体稳态中扮演着重要角色。这类受体不仅参与糖脂代谢的精细调控,还广泛影响多种生理过程。近期研究揭示了胆汁酸受体与骨代谢之间存在密切关联。值得关注的是,法尼醇X受体(farnesoid X receptor,FXR)和武田G蛋白偶联受体5(takeda G protein⁃coupled receptor 5,TGR5)在骨组织中的广泛表达,这一现象提示它们可能在骨代谢过程中发挥重要的调控作用。然而,FXR与TGR5调控骨代谢的具体分子机制尚未完全阐明。该文通过总结FXR和TGR5在骨代谢调控作用中的研究现状,旨在为骨代谢疾病的治疗提供新的理论基础和创新思路。
