以青鳉为模式生物,通过表型观测和miRNAs测序,探究三氯生对青鳉胚胎发育的毒性机制.结果表明:5μg/L三氯生暴露15d后,青鳉胚胎(仔鱼)出现孵化率降低、体长变短、卵黄囊肿大、心包囊肿、生殖嵴缩短、眼直径减小、眼轴延长和眼间距异常.mi...以青鳉为模式生物,通过表型观测和miRNAs测序,探究三氯生对青鳉胚胎发育的毒性机制.结果表明:5μg/L三氯生暴露15d后,青鳉胚胎(仔鱼)出现孵化率降低、体长变短、卵黄囊肿大、心包囊肿、生殖嵴缩短、眼直径减小、眼轴延长和眼间距异常.miRNAs测序共鉴定出6个差异表达miRNAs,其中2个显著上调,4个显著下调,这些miRNAs共靶向3166个基因.GO(Gene Ontology)功能分析表明,显著富集的条目涉及神经肌肉接头突触的特异性形成、肌节组装、肌肉牵张感知等过程.KEGG(Kyoto Encyclopedia of Genes and Genomes)通路分析发现19条显著富集通路,包括轴突导向、PI3K-Akt信号通路和PPAR信号通路等,这些通路与代谢调控、神经系统功能、运动能力、致癌风险和发育毒性密切相关.展开更多
Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesi...Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways.Chronic alcohol consumption leads to neuroinflammation,brain damage,and impaired cognition.Evidence indicates that females are more vulnerable to alcohol-induced damage than males.While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions,their potential to counteract alcohol-induced brain damage remains unclear.In this study,we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice.Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer(^(18)F-FDG)when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice.Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation,cognitive dysfunction,and the conditioned rewarding effects of cocaine.MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration.In addition,mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes(e.g.,Socs3,Tnf,Mtor,and Atf6)in the brains of ethanol-treated female mice.These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation,cognitive dysfunction,and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.展开更多
Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role i...Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.展开更多
间充质干细胞(MSC),也称为多能基质细胞,是一种首次在骨髓中发现的非造血干细胞群,目前已从各种成体组织来源中分离出来,是能够分化为多种间充质组织(如脂肪和骨骼)的成熟细胞的多能细胞。MicroRNAs (miRNA)是一种高度保守的内源性非蛋...间充质干细胞(MSC),也称为多能基质细胞,是一种首次在骨髓中发现的非造血干细胞群,目前已从各种成体组织来源中分离出来,是能够分化为多种间充质组织(如脂肪和骨骼)的成熟细胞的多能细胞。MicroRNAs (miRNA)是一种高度保守的内源性非蛋白质编码RNA,通过翻译抑制或降解其靶标来调节基因表达,在调节BMSC分化中起主要作用。本文探讨了miRNAs骨髓间充质干细胞成骨分化中的作用。Mesenchymal stem cells (MSCs), also known as pluripotent stromal cells, are a population of non-hematopoietic stem cells first discovered in the bone marrow that have been isolated from various adult tissue sources and are pluripotent cells capable of differentiating into mature cells of a variety of mesenchymal tissues, such as fat and bone. MicroRNAs (miRNAs) are highly conserved endogenous non-protein-coding RNAs that play a major role in regulating BMSC differentiation by translating inhibition or degradation of their targets to regulate gene expression. This article explores the role of miRNAs in osteogenic differentiation of bone marrow mesenchymal stem cells.展开更多
文摘以青鳉为模式生物,通过表型观测和miRNAs测序,探究三氯生对青鳉胚胎发育的毒性机制.结果表明:5μg/L三氯生暴露15d后,青鳉胚胎(仔鱼)出现孵化率降低、体长变短、卵黄囊肿大、心包囊肿、生殖嵴缩短、眼直径减小、眼轴延长和眼间距异常.miRNAs测序共鉴定出6个差异表达miRNAs,其中2个显著上调,4个显著下调,这些miRNAs共靶向3166个基因.GO(Gene Ontology)功能分析表明,显著富集的条目涉及神经肌肉接头突触的特异性形成、肌节组装、肌肉牵张感知等过程.KEGG(Kyoto Encyclopedia of Genes and Genomes)通路分析发现19条显著富集通路,包括轴突导向、PI3K-Akt信号通路和PPAR信号通路等,这些通路与代谢调控、神经系统功能、运动能力、致癌风险和发育毒性密切相关.
基金supported by the Spanish Ministry of Health‐Plan Nacional sobre Drogas(2023‐I024)the the Ministry of Science,Innovation and Universities/State ResearchAgency/10.13039/501100011033(PID2023-146865OB-I00)+2 种基金Generalitat Valenciana(CIAICO/2021/203)the Primary Addiction Care Research Network(RD21/0009/0005)FEDER Funds,GVA.
文摘Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways.Chronic alcohol consumption leads to neuroinflammation,brain damage,and impaired cognition.Evidence indicates that females are more vulnerable to alcohol-induced damage than males.While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions,their potential to counteract alcohol-induced brain damage remains unclear.In this study,we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice.Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer(^(18)F-FDG)when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice.Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation,cognitive dysfunction,and the conditioned rewarding effects of cocaine.MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration.In addition,mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes(e.g.,Socs3,Tnf,Mtor,and Atf6)in the brains of ethanol-treated female mice.These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation,cognitive dysfunction,and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.
基金supported by the National Natural Science Foundation of China(no.32372838,U22A20506)the National Key Research and Development Program of China(no.2024YFD1300104)+1 种基金the scientific and technological development program of Jilin province(YDZJ202203CGZH037)the earmarked fund for JLARS-2025-070203。
文摘Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.
文摘背景与目的肺癌是全球癌症死亡的主要原因之一,约80%的肺癌属于非小细胞肺癌(non-small cell lung cancer,NSCLC),其中肺鳞癌(lung squamous cell carcinoma,LUSC)在NSCLC中占据重要比例。尽管肿瘤的综合治疗极大提升了患者的总生存期,但晚期LUSC患者的预后较差。急需一种生物标志物来预测晚期LUSC患者的预后,以便通过早期诊断,改善预后。研究发现miRNAs在肺癌组织中差异表达,并作为潜在的致癌或抑癌基因发挥作用,本研究旨在筛选出早期和晚期LUSC差异表达的miRNAs,构建用于预测晚期LUSC患者预后的一组miRNAs标志物。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中下载LUSC患者临床信息及miRNAs的相关数据。应用生物信息学方法分析数据,绘制受试者工作特征(receiver operating characteristic,ROC)曲线,利用多种在线分析工具预测靶基因,分析靶基因的潜在生物学机制。结果两组间共鉴定出58个差异表达的miRNAs。根据LASSO回归筛选出7个miRNAs拟构建miRNAs标志物,又根据每个miRNAs的ROC曲线下面积(area under the curve,AUC)值,最终选取其中的4个mRNAs(miR-377-3p、miR-4779、miR-6803-5p、miR-3960)作为预测晚期LUSC患者的生物标志物。4个miRNAs联合的AUC值为0.865。富集分析显示这些靶基因富集在癌症通路、促分裂素原活化蛋白激酶(mitogen-activated protein kinase,MAPK)通路、丝氨酸/苏氨酸激酶(serine/threonine kinase,STK)及酪氨酸激酶信号通路等多种通路。结论miR-377-3p、miR-4779、miR-6803-5p、miR-3960联合预测晚期LUSC患者预后能力良好,AUC可达0.865。
文摘间充质干细胞(MSC),也称为多能基质细胞,是一种首次在骨髓中发现的非造血干细胞群,目前已从各种成体组织来源中分离出来,是能够分化为多种间充质组织(如脂肪和骨骼)的成熟细胞的多能细胞。MicroRNAs (miRNA)是一种高度保守的内源性非蛋白质编码RNA,通过翻译抑制或降解其靶标来调节基因表达,在调节BMSC分化中起主要作用。本文探讨了miRNAs骨髓间充质干细胞成骨分化中的作用。Mesenchymal stem cells (MSCs), also known as pluripotent stromal cells, are a population of non-hematopoietic stem cells first discovered in the bone marrow that have been isolated from various adult tissue sources and are pluripotent cells capable of differentiating into mature cells of a variety of mesenchymal tissues, such as fat and bone. MicroRNAs (miRNAs) are highly conserved endogenous non-protein-coding RNAs that play a major role in regulating BMSC differentiation by translating inhibition or degradation of their targets to regulate gene expression. This article explores the role of miRNAs in osteogenic differentiation of bone marrow mesenchymal stem cells.
