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| 1 | Stem cell-based therapy for human diseases显示文摘Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated.Stem cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative medicine.hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ layers.MsCs are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular conditions.Moreover,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications.The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment. | Duc M.Hoang Phuong T.Pham Trung Q.Bach Anh T.L.Ngo Quyen T.Nguyen Trang T.K.Phan Giang H.Nguyen Phuong T.T.Le Van T.Hoang Nicholas R.Forsyth Michael Heke Liem Thanh Nguyen | 2022 | Signal Transduction and Targeted Therapy2022,7,9: | 7 |
| 2 | miR-145过表达对缺氧诱导心肌细胞焦亡的抑制作用及其机制显示文摘目的观察miR-145过表达对缺氧诱导心肌细胞焦亡的抑制作用并探讨其机制。方法将大鼠心肌细胞H9C2分为正常组、缺氧组、缺氧+miR-145组、缺氧+阴性对照组,缺氧+miR-145组、缺氧+阴性对照组分别使用腺病毒包装的miR-145及腺病毒包装的阴性对照序列进行腺病毒感染,正常组、缺氧组不做腺病毒感染处理;24 h后将缺氧组、缺氧+miR-145组、缺氧+阴性对照组细胞转移至缺氧培养箱中培养24 h,正常组不做缺氧诱导。采用实时荧光定量PCR法检测细胞miR-145水平,超氧化物阴离子探针检测细胞内活性氧水平,TUNEL染色及流式细胞术观察细胞焦亡情况,免疫组织化学及实时荧光定量PCR法检测细胞焦亡相关因子NOD样受体热蛋白结构域相关蛋白3(NLRP3)、(IL-1β)、白细胞介素1β(IL-18)水平,Western blotting法检测钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)/核转录因子κB(NF-κB)信号通路相关蛋白磷酸化CaMKⅡ、磷酸化NF-κB、NLRP3、Caspase-1、IL-1β、IL-18表达。结果心肌细胞miR-145 mRNA相对表达量缺氧+miR-145组>正常组>缺氧组、缺氧+阴性对照组,心肌细胞ROS水平缺氧组、缺氧+阴性对照组>缺氧+miR-145组>正常组,心肌细胞TUNEL阳性率及焦亡率缺氧组、缺氧+阴性对照组>缺氧+miR-145组>正常组,心肌细胞NLRP3蛋白及NLRP3、IL-1β、IL-18 mRNA表达缺氧组、缺氧+阴性对照组>缺氧+miR-145组>正常组,心肌细胞CaMKⅡ、磷酸化CaMKⅡ、NF-κB、磷酸化NF-κB、NLRP3、Caspase-1、IL-1β、IL-18蛋白表达缺氧组、缺氧+阴性对照组>缺氧+miR-145组>正常组(P均<0.05)。结论miR-145过表达可减轻缺氧诱导的心肌细胞焦亡,其机制可能与抑制CaMKⅡ/NF-κB信号通路有关。 | 浦湧 崔胜宇 吴浩亮 陶波 孟祥平 夏豪 徐林 | 2022 | 山东医药2022,62,29: | 1 |
| 3 | Signaling pathways and targeted therapies for psoriasis显示文摘Psoriasis is a common,chronic,and inflammatory skin disease with a high burden on individuals,health systems,and society worldwide.With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed,the therapeutic approaches for this disease have gained revolutionary progress.Nevertheless,the mechanisms of less common forms of psoriasis remain elusive.Furthermore,severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment,which,however,has been rarely explored with the integration of preliminary findings.Therefore,it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis,which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment.In this review,we looked to briefly introduce the epidemiology,clinical subtypes,pathophysiology,and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission,as well as the cross-talk between them.In the discussion,we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities.This review also outlined current treatment for psoriasis,especially targeted therapies and novel therapeutic strategies,as well as the potential mechanism of disease recurrence. | Jia Guo Hanyi Zhang Wenrui Lin Lixia Lu Juan Su Xiang Chen | 2023 | Signal Transduction and Targeted Therapy2023,8,12: | 0 |
| 4 | Wnt/β-catenin信号通路在心肌纤维化中的作用研究进展显示文摘Wnt/β-catenin信号通路是一种在胚胎发育,细胞增殖分化、迁移,干细胞更新等中起关键作用的蛋白质家族。Wnt/β-catenin信号通路的失调常常会导致各种严重的疾病,例如肿瘤、心脏疾病、肺部疾病、肝脏疾病、骨骼疾病、神经疾病等。大量研究表明,Wnt/β-catenin信号通路在心肌纤维化发病机制中起重要作用,本文结合最新研究成果,从心肌纤维化相关疾病的角度对Wnt/β-catenin通路进行综述,为预防心肌纤维化提供新的思路,进一步达到防治心血管疾病的目的。 | 高雅婷 邱对鑫 高磊 石开虎 | 2024 | 广州医药2024,55,1: | 0 |
| 5 | 去泛素化酶对TGF-β/Smads通路调控机制研究进展显示文摘去泛素化是指在蛋白质底物与泛素分子结合的复合物中去除泛素蛋白的一种重要翻译后修饰方式(post translational modifications,PTMs),可通过蛋白功能调节多种细胞生理功能;TGF-β/Smads通路可调控细胞增殖、凋亡、细胞周期、迁移、DNA修复参与炎症、胚胎发育、组织修复、调节免疫功能。文献报道,去泛素化酶可以调控TGF-β/Smads通路,但是具体作用机制尚不清楚。本文对不同去泛素化酶调控TGF-β/Smads通路具体作用机制进行综述。 | 蒙国鑫 周涛 | 2024 | 中国心血管病研究2024,22,1: | 0 |
| 6 | Danhong Injection Up-Regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium显示文摘Objective:To investigate the involvement of endothelial cells(ECs)-derived exosomes in the antiapoptotic effect of Danhong Injection(DHI)and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.Methods:A mouse permanent myocardial infarction(MI)model was established,followed by a 14-day daily treatment with DHI,DHI plus GW4869(an exosomal inhibitor),or saline.Phosphatebuffered saline(PBS)-induced ECs-derived exosomes were isolated,analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction(ddP CR).The exosomes induced by DHI(DHI-exo),PBS(PBS-exo),or DHI+GW4869(GW-exo)were isolated and injected into the peri-infarct zone following MI.The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography,Masson's trichrome staining,and TUNEL apoptosis assay.The Western blotting and quantitative reverse transcription PCR(qR T-PCR)were used to evaluate the expression levels of miR-125b/p53-mediated pathway components,including miR-125b,p53,Bak,Bax,and caspase-3 activities.Results:DHI significantly improved cardiac function and reduced infarct size in MI mice(P<0.01),which was abolished by the GW4869 intervention.DHI promoted the exosomal secretion in ECs(P<0.01).According to the results of exosomal miRNA microarray assay,30 differentially expressed miRNAs in the DHI-exo were identified(28 up-regulated miRNAs and 2 down-regulated miRNAs).Among them,DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs,a recognized apoptotic inhibitor impeding p53 signaling(P<0.05).Remarkably,treatment with DHI and DHI-exo attenuated apoptosis,elevated miR-125b expression level,inhibited capsase-3 activity,and down-regulated the expression levels of proapoptotic effectors(p53,Bak,and Bax)in post-MI hearts,whereas these effects were blocked by GW4869(P<0.05 or P<0.01).Conclusion:DHI and DHI-induced exosomes inhibited apoptosis,promoted the miR-125b expression level,and regulated the p53 apoptotic pathway in post-infarction myocardium. | LI Si-nai LIU Zi-hao ZHOU Ming-xue LIU Wei-hong LAI Xiao-lei LI Ping ZHANG Lei SHANG Ju-ju QIU Sheng-lei LOU Yan TAN Yu-pei XING Wen-long LIU Hong-xu | 2023 | Chinese Journal of Integrative Medicine2023,29,12: | 0 |
| 7 | 芪参颗粒防治阿霉素所致心肌损伤的作用机制研究及实验验证显示文摘目的:基于网络药理学及实验研究,验证芪参颗粒(QSG)治疗阿霉素心肌损伤的作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)筛选QSG的活性成分及作用靶点,借助人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、遗传药理学与药物基因组学数据库(PharmGKB)等疾病数据库搜索阿霉素心肌损伤靶点,使用蛋白质相互作用分析数据库(STRING)数据库分析蛋白质-蛋白质相互作用(PPI)进行互作分析。利用Cytoscape构建网络,Hiplot数据库进行基因组百科全书(KEGG)富集分析。最后,通过实验对QSG的药效、靶点及通路进行验证。结果:QSG中共检索到174种化学成分,无重复靶点261个,疾病数据库共检索到1 521个无重基因,二者交集靶点为156个。PPI网络提取了排名前十的基因,大多与炎症反应相关。KEGG富集结果显示主要与促分裂原活化的蛋白激酶(MAPK)、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)、verified by experi及癌症信号通路等相关。体内实验结果表明,QSG可明显提高小鼠的心功能,改善病理组织损伤并降低炎症细胞浸润,同时能显著提高磷酸化蛋白激酶B(p-AKT)并降低磷酸化促分裂原活化的蛋白激酶(p-MAPK)及磷酸化核因子κB(p-NF-κB)的表达。体外结果表明QSG可明显降低炎症介质的含量,且联合使用阿霉素时不会影响阿霉素本身的抗肿瘤效果。结论:QSG显示出良好的抗阿霉素心肌损伤作用,其机制可能与其抗炎作用相关。 | 张敬美 薛思明 李伟利 陈欢 卢令慧 王其艳 | 2023 | 世界中医药2023,18,20: | 0 |
| 8 | 秋水仙碱对心肌梗死后大鼠预后的影响显示文摘目的研究秋水仙碱对心肌梗死(myocardial infarction,MI)大鼠预后的影响。方法40只雄性SD大鼠随机分为假手术(Sham)组、心肌梗死+空白溶剂(MI)组、心肌梗死+秋水仙碱灌胃治疗(MI+Col/i.g)组及心肌梗死+秋水仙碱心肌内注射(MI+Col/i.m)组,每组10只。记录大鼠体质量及死亡情况,干预28天后取材,采集大鼠超声心动图,采用酶联免疫吸附法检测血清炎性细胞因子及肝、肾功能指标。取心脏组织,行Masson染色,光镜下分析心肌纤维化程度。结果秋水仙碱治疗未能显著提升大鼠MI后28天内生存率。但与MI组比较,MI+Col/i.g组及MI+Col/i.m组均能明显降低血清炎性细胞因子(P<0.05),抑制MI后心肌纤维化,改善MI大鼠心功能(P<0.001),且均未造成与之相关的肝肾功能损伤,且MI+Col/i.m组体质量较MI+Col/i.g组显著增长(P<0.001)。结论秋水仙碱口服及心肌内注射治疗MI大鼠安全可行,能显著改善MI大鼠心功能,且心肌内注射相较于口服能大幅提升大鼠对药物的耐受性。 | 陈广 李彬 文英 蒋学俊 | 2024 | 医学研究杂志2024,53,1: | 0 |
| 9 | Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction显示文摘BACKGROUND Cardiovascular disease,particularly myocardial infarction(MI)profound impact on patients'quality of life and places a substantial burden on the healthcare and economy systems.Developments in medical technology have led to the emer-gence of coronary intervention as an essential method for treating MI.AIM To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.METHODS This study included a total of 180 patients with MI during the period from June 2022 to July 2023.Selected patients were divided into two groups:An observation group,which receiving cardiac rehabilitation care;a control group,which re-ceiving conventional care.By comparing multiple observation indicators such as cardiac function indicators,blood pressure,exercise tolerance,occurrence of adverse cardiac events,and negative emotion scores between the two groups of patients.All the data were analyzed and compared between two groups.RESULTS There were 44 males and 46 females in the observation group with an average age of 36.26±9.88 yr;there were 43 males and 47 females in the control group,with an average age of 40.87±10.5 yr.After receiving the appropriate postoperative nursing measures,the results of the observation group showed significant improvement in several indicators compared with the control group.Indicators of cardiac function,such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group(P<0.05).Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group(P<0.01).In addition,the incidence of adverse cardiac events was significantly lower in the observation group,and negative mood scores were significantly reduced(P<0.05).CONCLUSION Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery.This emphasizes the importance of cardiac rehabilitation care to improve patient recovery. | Ming Yang Yuan-Tao Huang Xi-Wen Hu Chun-Ling Wu | 2024 | World Journal of Clinical Cases2024,12,1: | 0 |
| 10 | 急性心肌梗死的研究进展显示文摘急性心肌梗死(AMI)临床发病率和死亡率日趋升高,严重危害人们的身体健康,并带来巨大的社会经济负担。综述AMI的定义、病理机制、临床表现以及常规治疗如再灌注治疗和药物治疗,并对目前新型治疗如抗炎治疗、干细胞疗法、基因疗法、抑制心肌纤维化等做了详细介绍,以期为临床治疗AMI提供思路,并进一步推动AMI的规范化管理。 | 邵祯 李军 孟超 谭雨晴 | 2024 | 中西医结合心脑血管病杂志2024,22,7: | 0 |
| 11 | 瓜蒌皮注射液治疗稳定型心绞痛作用机制的网络药理学研究显示文摘目的探讨瓜蒌皮注射液治疗稳定型心绞痛(SAP)的作用机制。方法检索相关文献,获取制剂活性成分,采用SwissTargetPre⁃diction数据库预测其靶点。利用GeneCards数据库获取SAP疾病靶点;利用Venny 2.1平台获取共有靶点;利用MetaScape软件对作用靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,利用Cytoscape 3.9.1软件构建成分-靶点-通路网络,通过String数据库构建蛋白相互作用网络;通过基因表达综合(GEO)数据库获取的差异表达基因和分子对接进行验证,采用PyMOL 2.3.0软件进行可视化分析。结果共获得制剂活性成分57个,靶点517个,其中26个作用于SAP。核心活性成分为黄酮类,如木犀草素、芦丁、木犀草苷、芹菜素-7-O-β-D-葡萄糖苷和香叶木素-7-O-β-葡萄糖苷,核心靶点为TNF,FGF2,MMP-9,ICAM1,EGFR等。基因主要富集于37个GO功能(其中生物过程20个,分子功能9个,细胞组成8个)及9条KEGG通路。验证结果表明,活性成分可特异性作用于部分疾病差异表达基因。核心活性成分与靶点的结合能均小于-10.6 kcal/mol。结论瓜蒌皮注射液可能通过多种活性成分作用于多个特异性靶点,进而通过多通路发挥抗炎、抗氧化应激、抗凋亡作用,从而治疗SAP。 | 魏龙 李文洁 洪国君 陶洋 吴连平 | 2024 | 中国药业2024,33,4: | 0 |