目的:构建中草药来源的目标微小RNA(microRNA,miR)在小鼠肺组织中的靶基因谱检测方法,利用该方法检测清肺排毒汤所含miR-320—靶基因谱及其生物学功能,为清肺排毒汤治疗病毒性肺炎的分子机制补充miR维度的数据支撑。方法:采用二代高通...目的:构建中草药来源的目标微小RNA(microRNA,miR)在小鼠肺组织中的靶基因谱检测方法,利用该方法检测清肺排毒汤所含miR-320—靶基因谱及其生物学功能,为清肺排毒汤治疗病毒性肺炎的分子机制补充miR维度的数据支撑。方法:采用二代高通量测序测定目标miR(miR-320)在清肺排毒汤中的表达情况,利用“结合态miR—靶基因抓取测序技术(capturing and sequencing of miRNA-target complex technology,CSCT)”初步检测其在小鼠肺组织中的靶基因谱,并采用Alphafold3验证检测结果,取其交集作为目标miR的靶基因谱;进而分析靶基因谱的功能,阐释清肺排毒汤通过miR-320在小鼠肺组织中的调控功能;此外,将检测结果与TargetScan的预测结果进行比对,验证本检测方法(CSCT+Alphafold3序贯检测法)的优势。结果:高通量测序结果表明清肺排毒汤中富含miR-320,其表达含量居前50位。miR-320在小鼠肺组织中可作用于26类靶基因,其中19类为已知基因(18类为mRNA以及1类为转录增强子),其主要通过miR经典作用模式识别靶基因,与26类靶基因具有良好的碱基互补性,最小自由能在-35.8~-21.8 kcal·mol^(-1)之间;Alphafold3预测的靶基因的iPTM和PTM之和最小值为1.1,位于高置信度区域,100%验证了CSCT的检测结果,据此确证26类靶基因为miR-320作用谱;与TargetScan相比,本研究构建的“CSCT+Alphafold3序贯检测法”对于靶基因谱的检测准确率更高。这些靶基因具有多种功能,主要富集于白介素介导的免疫信号通路,在抗原处理与提呈、免疫因子或细胞介导的细胞凋亡、淋巴细胞增殖与活化等生物学过程中发挥作用。结论:清肺排毒汤所含miR-320在小鼠肺组织内主要富集于免疫调节相关通路,这可能是清肺排毒汤治疗病毒性肺炎的miR分子机制之一;本研究构建的“CSCT+Alphafold3”法对于miR靶基因谱的检测具有较高的可靠性和准确性,可作为中药汤剂中miR—靶基因互作谱检测技术。展开更多
背景:激素诱导股骨头坏死的发病机制复杂,涉及血管内皮损伤、骨细胞凋亡、炎症反应和骨代谢紊乱。微小RNA(microRNAs,miRNA)作为基因表达的关键调控因子在激素诱导股骨头坏死中扮演着重要角色。目的:综合分析miRNA在激素诱导股骨头坏死...背景:激素诱导股骨头坏死的发病机制复杂,涉及血管内皮损伤、骨细胞凋亡、炎症反应和骨代谢紊乱。微小RNA(microRNAs,miRNA)作为基因表达的关键调控因子在激素诱导股骨头坏死中扮演着重要角色。目的:综合分析miRNA在激素诱导股骨头坏死病理过程中的作用,评估miRNA作为激素诱导股骨头坏死生物标志物的潜力与治疗策略的最新进展。方法:通过计算机检索PubMed、Web of Science、CNKI和万方数据库中的相关文献,使用特定的关键词进行筛选,并根据纳入和排除标准选择相关文章。通过阅读标题和摘要或全文,排除与主题相关性差或内容重复的文献,最终筛选出76篇文献进行分析。结果与结论:miRNA通过与目标mRNA的3’非翻译区结合调控基因表达,影响细胞增殖、分化、凋亡和应激反应。特定的miRNA如miR-33-5p、miR-99a、miR-106b-5p、miR-155、miR-146a和miR-21在激素诱导股骨头坏死的血管损伤、炎症反应、骨细胞分化和凋亡中起着核心调控作用;此外,miRNA的表达模式与激素诱导股骨头坏死的发病机制密切相关,显示出作为生物标志物的潜力。尽管miRNA作为生物标志物展现出巨大潜力,但样本量有限和缺乏多人群验证限制了其普适性;此外,miRNA治疗策略的有效性和安全性(包括脱靶效应和递送问题)仍是实现临床应用的主要挑战。展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
文摘目的:构建中草药来源的目标微小RNA(microRNA,miR)在小鼠肺组织中的靶基因谱检测方法,利用该方法检测清肺排毒汤所含miR-320—靶基因谱及其生物学功能,为清肺排毒汤治疗病毒性肺炎的分子机制补充miR维度的数据支撑。方法:采用二代高通量测序测定目标miR(miR-320)在清肺排毒汤中的表达情况,利用“结合态miR—靶基因抓取测序技术(capturing and sequencing of miRNA-target complex technology,CSCT)”初步检测其在小鼠肺组织中的靶基因谱,并采用Alphafold3验证检测结果,取其交集作为目标miR的靶基因谱;进而分析靶基因谱的功能,阐释清肺排毒汤通过miR-320在小鼠肺组织中的调控功能;此外,将检测结果与TargetScan的预测结果进行比对,验证本检测方法(CSCT+Alphafold3序贯检测法)的优势。结果:高通量测序结果表明清肺排毒汤中富含miR-320,其表达含量居前50位。miR-320在小鼠肺组织中可作用于26类靶基因,其中19类为已知基因(18类为mRNA以及1类为转录增强子),其主要通过miR经典作用模式识别靶基因,与26类靶基因具有良好的碱基互补性,最小自由能在-35.8~-21.8 kcal·mol^(-1)之间;Alphafold3预测的靶基因的iPTM和PTM之和最小值为1.1,位于高置信度区域,100%验证了CSCT的检测结果,据此确证26类靶基因为miR-320作用谱;与TargetScan相比,本研究构建的“CSCT+Alphafold3序贯检测法”对于靶基因谱的检测准确率更高。这些靶基因具有多种功能,主要富集于白介素介导的免疫信号通路,在抗原处理与提呈、免疫因子或细胞介导的细胞凋亡、淋巴细胞增殖与活化等生物学过程中发挥作用。结论:清肺排毒汤所含miR-320在小鼠肺组织内主要富集于免疫调节相关通路,这可能是清肺排毒汤治疗病毒性肺炎的miR分子机制之一;本研究构建的“CSCT+Alphafold3”法对于miR靶基因谱的检测具有较高的可靠性和准确性,可作为中药汤剂中miR—靶基因互作谱检测技术。
文摘背景:激素诱导股骨头坏死的发病机制复杂,涉及血管内皮损伤、骨细胞凋亡、炎症反应和骨代谢紊乱。微小RNA(microRNAs,miRNA)作为基因表达的关键调控因子在激素诱导股骨头坏死中扮演着重要角色。目的:综合分析miRNA在激素诱导股骨头坏死病理过程中的作用,评估miRNA作为激素诱导股骨头坏死生物标志物的潜力与治疗策略的最新进展。方法:通过计算机检索PubMed、Web of Science、CNKI和万方数据库中的相关文献,使用特定的关键词进行筛选,并根据纳入和排除标准选择相关文章。通过阅读标题和摘要或全文,排除与主题相关性差或内容重复的文献,最终筛选出76篇文献进行分析。结果与结论:miRNA通过与目标mRNA的3’非翻译区结合调控基因表达,影响细胞增殖、分化、凋亡和应激反应。特定的miRNA如miR-33-5p、miR-99a、miR-106b-5p、miR-155、miR-146a和miR-21在激素诱导股骨头坏死的血管损伤、炎症反应、骨细胞分化和凋亡中起着核心调控作用;此外,miRNA的表达模式与激素诱导股骨头坏死的发病机制密切相关,显示出作为生物标志物的潜力。尽管miRNA作为生物标志物展现出巨大潜力,但样本量有限和缺乏多人群验证限制了其普适性;此外,miRNA治疗策略的有效性和安全性(包括脱靶效应和递送问题)仍是实现临床应用的主要挑战。
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
