为研究饲粮添加氧化油脂和金荞麦对肉鸡肉品质和空肠黏膜miRNA表达谱的影响,试验选用1日龄健康、体重相近的882肉仔鸡公鸡240只,随机分为3组,每组8个重复,每个重复10只鸡。Ctr、Ox、Fag组分别在基础日粮中添加新鲜油脂、氧化油脂、新鲜...为研究饲粮添加氧化油脂和金荞麦对肉鸡肉品质和空肠黏膜miRNA表达谱的影响,试验选用1日龄健康、体重相近的882肉仔鸡公鸡240只,随机分为3组,每组8个重复,每个重复10只鸡。Ctr、Ox、Fag组分别在基础日粮中添加新鲜油脂、氧化油脂、新鲜油脂+2%金荞麦。试验期为42 d。结果显示:氧化油脂可显著增加胸肌24 h pH和腿肌滴水损失(P<0.01),显著降低胸肌肉色a^(*)值(P<0.05);金荞麦可显著增加腿肌肉色L^(*)和a^(*)值(P<0.05);Ctr vs Ox,Ctr vs Fag,Ox vs Fag三个比较组的差异表达miRNAs分别为25、27、24个;这些差异表达miRNAs的靶基因显著富集在肌动蛋白细胞骨架、紧密链接、mTOR和TGF-β等信号通路;根据表达丰度和表达差异分析,共筛选了17个差异表达miRNAs,它们可作为氧化油脂和金荞麦调控肠道屏障功能的候选基因,进一步研究氧化油脂和金荞麦通过表观遗传学对肠道屏障功能的影响。综上所述,饲粮添加氧化油脂和2%金荞麦均可改变肉鸡肉品质,影响空肠黏膜miRNAs的表达谱。展开更多
pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microsc...pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.展开更多
背景:巨噬细胞M1/M2极化方向的调节在组织工程应用中尤为关键,及时调控可最大程度地减少促炎、促进抗炎或组织愈合反应。目的:将慢病毒介导的miRNA-378a过表达巨噬细胞株复合胶原蛋白海绵回植入动物模型,据此检测免疫调节在体内环境中...背景:巨噬细胞M1/M2极化方向的调节在组织工程应用中尤为关键,及时调控可最大程度地减少促炎、促进抗炎或组织愈合反应。目的:将慢病毒介导的miRNA-378a过表达巨噬细胞株复合胶原蛋白海绵回植入动物模型,据此检测免疫调节在体内环境中的相关表达水平等组织修复相关的指标,进一步阐明在体内环境中miRNA-378a是否促进巨噬细胞M2极化及其对免疫调节和组织修复的作用。方法:将慢病毒介导的miRNA-378a过表达巨噬细胞株、阴性对照病毒巨噬细胞株扩增、筛选,复苏培养巨噬细胞株后与胶原蛋白海绵共培养以此构成复合体,具体分组如下:①阳性组:过表达miRNA-378a巨噬细胞-胶原蛋白海绵复合体;②阴性组:阴性对照病毒介导的miRNA-378a巨噬细胞-胶原蛋白海绵复合体;③对照组:巨噬细胞-胶原蛋白海绵;④空白对照组:胶原蛋白海绵。通过免疫荧光及扫描电镜观察各组细胞密度、表型、黏附情况,后回植入小鼠背部皮下模型,分别于造模后4,7 d处死小鼠,通过大体观察、苏木精-伊红染色、Masson染色、免疫组化分析慢病毒介导的miRNA-378a过表达巨噬细胞胶原蛋白海绵复合体中巨噬细胞极化的方向及其对机体免疫调控、组织修复的作用。结果与结论:①免疫荧光镜下观察各组巨噬细胞株确实与胶原蛋白海绵形成复合体;②扫描电镜下慢病毒介导的miRNA-378a巨噬细胞(阳性组)较其他分组细胞密度增加,细胞出现球形、椭圆形及多边形分化,具有更多的伪足;③大体观察下总体7 d愈合好于4 d,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)无论4,7 d愈合均好于其他分组;④苏木精-伊红染色、Masson染色下,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)具有较多量的纤维细胞、毛细血管、成纤维细胞以及胶原纤维增生;⑤免疫组化显示,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)无论4,7 d M2极化细胞阳性率均大于其他分组;对照组及阴性组巨噬细胞无论4,7 d M2极化细胞阳性率均大于空白对照组,而对照组及阴性组之间无统计学差异;阳性组、阴性组、对照组无论4,7 d染色细胞数量均大于空白对照组,且阳性组>阴性组≈对照组>空白对照组;⑥提示在体内环境中miRNA-378a过表达巨噬细胞具有较多量的纤维细胞、毛细血管、成纤维细胞以及胶原纤维增生,对组织修复起到了正向作用,并且能促进巨噬细胞向M2型极化并抑制M1型极化,从而有助于减少机体炎症反应。展开更多
Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive mol...Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
文摘为研究饲粮添加氧化油脂和金荞麦对肉鸡肉品质和空肠黏膜miRNA表达谱的影响,试验选用1日龄健康、体重相近的882肉仔鸡公鸡240只,随机分为3组,每组8个重复,每个重复10只鸡。Ctr、Ox、Fag组分别在基础日粮中添加新鲜油脂、氧化油脂、新鲜油脂+2%金荞麦。试验期为42 d。结果显示:氧化油脂可显著增加胸肌24 h pH和腿肌滴水损失(P<0.01),显著降低胸肌肉色a^(*)值(P<0.05);金荞麦可显著增加腿肌肉色L^(*)和a^(*)值(P<0.05);Ctr vs Ox,Ctr vs Fag,Ox vs Fag三个比较组的差异表达miRNAs分别为25、27、24个;这些差异表达miRNAs的靶基因显著富集在肌动蛋白细胞骨架、紧密链接、mTOR和TGF-β等信号通路;根据表达丰度和表达差异分析,共筛选了17个差异表达miRNAs,它们可作为氧化油脂和金荞麦调控肠道屏障功能的候选基因,进一步研究氧化油脂和金荞麦通过表观遗传学对肠道屏障功能的影响。综上所述,饲粮添加氧化油脂和2%金荞麦均可改变肉鸡肉品质,影响空肠黏膜miRNAs的表达谱。
基金Funded by the National Key R&D Program of China(No.2023YFC2412300)the Natural Science Foundation of Hubei Province(No.2022CFB386)the National Natural Science Foundation of China(No.52073222)。
文摘pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.
文摘背景:巨噬细胞M1/M2极化方向的调节在组织工程应用中尤为关键,及时调控可最大程度地减少促炎、促进抗炎或组织愈合反应。目的:将慢病毒介导的miRNA-378a过表达巨噬细胞株复合胶原蛋白海绵回植入动物模型,据此检测免疫调节在体内环境中的相关表达水平等组织修复相关的指标,进一步阐明在体内环境中miRNA-378a是否促进巨噬细胞M2极化及其对免疫调节和组织修复的作用。方法:将慢病毒介导的miRNA-378a过表达巨噬细胞株、阴性对照病毒巨噬细胞株扩增、筛选,复苏培养巨噬细胞株后与胶原蛋白海绵共培养以此构成复合体,具体分组如下:①阳性组:过表达miRNA-378a巨噬细胞-胶原蛋白海绵复合体;②阴性组:阴性对照病毒介导的miRNA-378a巨噬细胞-胶原蛋白海绵复合体;③对照组:巨噬细胞-胶原蛋白海绵;④空白对照组:胶原蛋白海绵。通过免疫荧光及扫描电镜观察各组细胞密度、表型、黏附情况,后回植入小鼠背部皮下模型,分别于造模后4,7 d处死小鼠,通过大体观察、苏木精-伊红染色、Masson染色、免疫组化分析慢病毒介导的miRNA-378a过表达巨噬细胞胶原蛋白海绵复合体中巨噬细胞极化的方向及其对机体免疫调控、组织修复的作用。结果与结论:①免疫荧光镜下观察各组巨噬细胞株确实与胶原蛋白海绵形成复合体;②扫描电镜下慢病毒介导的miRNA-378a巨噬细胞(阳性组)较其他分组细胞密度增加,细胞出现球形、椭圆形及多边形分化,具有更多的伪足;③大体观察下总体7 d愈合好于4 d,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)无论4,7 d愈合均好于其他分组;④苏木精-伊红染色、Masson染色下,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)具有较多量的纤维细胞、毛细血管、成纤维细胞以及胶原纤维增生;⑤免疫组化显示,慢病毒介导的miRNA-378a过表达巨噬细胞(阳性组)无论4,7 d M2极化细胞阳性率均大于其他分组;对照组及阴性组巨噬细胞无论4,7 d M2极化细胞阳性率均大于空白对照组,而对照组及阴性组之间无统计学差异;阳性组、阴性组、对照组无论4,7 d染色细胞数量均大于空白对照组,且阳性组>阴性组≈对照组>空白对照组;⑥提示在体内环境中miRNA-378a过表达巨噬细胞具有较多量的纤维细胞、毛细血管、成纤维细胞以及胶原纤维增生,对组织修复起到了正向作用,并且能促进巨噬细胞向M2型极化并抑制M1型极化,从而有助于减少机体炎症反应。
基金supported by the National Natural Science Foundation of China(51925304)Natural Science Foundation of Sichuan Province(2024NSFSC1023)Medical Research Program of Sichuan Province(Q23015).
文摘Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
