Therapeutic applications of exosomes from adipose-derived stem cells in antifibrosis

Fibrosis is a condition in which connective tissue replaces normal parenchymal tissue, resulting in significant tissue remodeling. Fibrosis can affect several organs and pose a serious threat to human health and life. Adipose-derived stem cells (ASCs) have been suggested as promising candidates for antifibrotic therapies. Paracrine secretion is one of the key processes in stem cell therapy due to its critical function in cellular communication. ASC-derived exosomes (ASC-exos) are used as tools for restoring and regenerating damaged tissue, and they are now thought to orchestrate antifibrosis-related events. In this review, we summarize the recent findings and present an extensive view of the therapeutic applications of ASC-exos in fibrotic diseases.     

间充质干细胞治疗缺血性胆道损伤的研究进展

目前,缺血性胆道损伤（ITBL）的临床治疗仍以外科手术、内镜治疗等方法为主,具有治疗策略单一、治疗方法难度大和医疗费用高的缺点,亟需寻找一种新的治疗策略。间充质干细胞（MSC）具有高度的自我更新能力、多向分化潜能、低免疫原性及免疫调节作用等特性,已然成为再生医学中组织和器官修复的潜在种子细胞。近年来众多研究发现,MSC移植到ITBL动物模型后,不但可归巢到损伤区域,而且可通过抗凋亡、促血管新生等作用促进损伤胆道组织的修复,这表明MSC移植有望成为治疗ITBL的新策略。本文对MSC的生物学特性、MSC移植治疗ITBL的机制及其临床应用做一综述。     

Quantitative changes in the protein and miRNA cargo of plasma exosome-like vesicles after exposure to ionizing radiation

Purpose: Multiple cell types secrete exosome-like extracellular vesicles (ELVs) to the extracellular environment. Pathological conditions can produce characteristic changes to the vesicle cargo. We investigated if ionizing radiation is capable of inducing changes in the protein and microRNA (miRNA) cargo of ELVs.

Materials and methods: Whole blood samples from healthy donors were irradiated with 2?Gy gamma rays and then peripheral blood mononuclear cells and plasma were separated from residual blood and co-cultivated for 24?h. The released ELVs were collected by differential ultracentrifugation from irradiated and non-irradiated samples. microRNAs and proteins were quantified by qPCR and label-free proteomics.

Results: Here we report a first characterization of radiation-induced changes in the protein and miRNA cargo of ELVs isolated from plasma. Proteome analysis of ELVs identified 214 proteins, of which nine significantly changed their abundance after irradiation. The radiation-induced down-regulation of afamin and serpine peptidase F1 was confirmed by immunoblotting. miRNA expression profiling identified 58 different exosomal miRNAs, the expression of miR-204-5p, miR-92a-3p and miR-31-5p was significantly increased in ELVs from irradiated samples.

Conclusions: This study provides evidence that radiation-induced changes occur in the protein and miRNA cargo of plasma ELVs. These data imply a novel systemic communication pathway between irradiated and non-irradiated cells and tissues.     

外泌体在肿瘤转移调控中的研究进展

恶性肿瘤是当今时代威胁人类健康的头号杀手。肿瘤转移是恶性肿瘤的主要特征,是癌症治疗失败和癌症患者死亡的首要原因,其分子机制复杂,涉及多步骤、多阶段、多基因的变化。外泌体是由活细胞分泌的纳米级囊泡小体,其内含有丰富的蛋白质、miRNA、lncRNA等成分,可在细胞间转运从而调节细胞的生物学功能。研究显示外泌体与肿瘤的转移密切相关,可通过促进肿瘤血管生成,影响肿瘤转移前微环境形成,调节机体免疫功能等方式调控肿瘤转移。本文将从外泌体主要成分入手对外泌体在肿瘤转移调控中的最新研究进展进行综述。     

Effect of 5-Aza-2’-deoxycytidine on immune-associated proteins in exosomes from hepatoma

AIM: To study the effect of 5-Aza-2’-deoxycytidine (5-Aza-CdR) on heat shock protein 70 (HSP70), human leucocyte antigen-Ⅰ (HLA-Ⅰ) and NY-ESO-1 proteins in exosomes produced by hepatoma cells, HepG2 and Hep3B. METHODS: Exosomes derived from HepG2 and Hep3B cells treated with or without 5-aza-CdR were isolated and purified by ultrafiltration centrifugation and sucrose gradient ultracentrifugation. The number of exosomes was counted under electron microscope. Concentration of proteins in exosomes was measured...     

非酒精性脂肪性肝病患者血浆外泌体差异蛋白分析*

目的 筛选非酒精性脂肪性肝病(NAFLD)患者血浆外泌体差异蛋白,分析其功能及其生物学过程,为NAFLD患者临床诊断提供参考依据。方法 2020年7月～10月我院诊治的NAFLD患者3例和健康体检者3例,采用串联质谱标签(TMT)标记定量蛋白质组学技术对血浆外泌体蛋白进行鉴定和定量分析,筛选差异蛋白并进行功能富集分析,了解其参与的生物学过程。结果 经外泌体蛋白质组学分析,共鉴定出蛋白质387种,以倍数上调＞1.2倍或下调＞1.2倍,且P＜0.05为标准筛选出差异表达蛋白34种;健康人比,NAFLD患者上调蛋白25种,下调蛋白9种;生物信息学分析结果显示,这些蛋白主要参与了脂质的储存和代谢、免疫反应、纤维素形成等生物学过程,并与胰岛素抵抗、炎症反应、细胞损伤等信号通路密切相关。结论 采用TMT标记定量蛋白质组学技术筛选NAFLD患者差异蛋白可能为其诊治提供指引。     

血浆外泌体HSP90α对预测结直肠癌肝转移的价值探索

目的 探讨结直肠癌患者血浆外泌体HSP90α与结直肠癌肝转移的关系.方法 应用超速离心法提取27例I～III期原发性结直肠癌患者和27例结直肠癌肝转移患者的血浆外泌体,并应用ELISA法检测其HSP90α 表达,并与相同患者血浆游离HSP90α 比较.结果 应用超速离心法能有效提取血浆外泌体,经验证符合外泌体相关特征....     

慢性丙型肝炎患者血清和外泌体LncRNA HEIH水平及其临床意义探讨*

目的 探讨慢性丙型肝炎(CHC)患者血清和外泌体肝细胞癌中高表达的中长链非编码RNA(long non-coding RNA HEIH,LncRNA-HEIH)水平变化及其临床意义。方法 2017年9月～2020年7月我院诊治的77例CHC患者和同期40例肝细胞癌(HCC)患者,采用定量RT-PCR法检测血清和外泌体LncRNA HEIH水平。CHC患者接受标准抗病毒治疗和肝活检。采用多元Logistic回归分析,应用ROC曲线分析血清和外泌体LncRNA HEIH水平预测肝组织病变的价值。结果 CHC患者血清和外泌体LncRNA HEIH水平分别为(2.3±0.2)和(3.6±0.6),均显著低于HCC患者【分别为(13.4±2.5)和(8.6±1.5),P<0.05】;53例肝组织炎症G0～G1患者血清和外泌体LncRNA HEIH水平分别为(2.5±0.3)和(3.9±0.6),显著高于24例肝组织炎症>G2者【分别为(1.9±0.4)和(2.9±0.5),P<0.05】,62例肝纤维化S0～S1患者血清和外泌体LncRNA HEIH水平分别为(2.6±0.4)和(4.1±0.7),均显著高于15例肝纤维化>S2者【分别为(1.6±0.4)和(2.5±0.5),P<0.05】;59例对抗病毒治疗应答组血清和外泌体LncRNA HEIH水平分别为(2.8±0.4)和(4.1±0.6),均显著高于18例不应答组【分别为(2.1±0.5)和(3.4±0.6),P<0.05】;CHC患者血清和外泌体LncRNA HEIH水平预测肝组织显著炎症或纤维化的AUC分别为0.764～0.778和0.723～0.736之间,具有一定的临床意义。结论 CHC患者血清和外泌体LncRNA HEIH水平异常,监测它们的变化可能对预测肝组织炎症分级和肝纤维化分期有帮助。     

Recent advances in blood-based and artificial intelligence-enhanced approaches for gastrointestinal cancer diagnosis

Gastrointestinal (GI) cancers are among the most common cancer types and leading causes of cancer-related deaths worldwide. There is a tremendous clinical need for effective early diagnosis for better healthcare of GI cancer patients. In this article, we provide a short overview of the recent advances in GI cancer diagnosis. In the first part, we discuss the applications of blood-based biomarkers, such as plasma circulating cell-free DNA, circulating tumor cells, extracellular vesicles, and circulating cell-free RNA, for cancer liquid biopsies. In the second part, we review the current trends of artificial intelligence (AI) for pathology image and tissue biopsy analysis for GI cancer, as well as deep learning-based approaches for purity assessment of tissue biopsies. We further provide our opinions on the future directions in blood-based and AI-enhanced approaches for GI cancer diagnosis, and we think that these fields will have more intensive integrations with clinical needs in the near future.     

Exosome in intestinal mucosal immunity

Intercellular communication of immune cells is critical to elicit efficient inflammatory responses. In intestinal mucosa, imbalance in pro‐inflammatory and anti‐inflammatory mediators, especially cytokines and chemokines, characterizes the underlying immune mechanisms of inflammatory bowel disease. Exosomes, small membrane vesicles secreted into the extracellular environment, are emerging as another important intercellular messenger in immune responses. A major recent breakthrough in this field unveils the capacity of exosomes to mediate the functional transfer of genetic materials (mRNAs and miRNAs) between immune cells. RAB27A and RAB27B are two small GTPases involved in exosome secretion. With respect to intestinal mucosal immunity, increased number of RAB27A‐positive immune cells and RAB27B‐positive immune cells are demonstrated in the colonic mucosa of patients with active ulcerative colitis as compared with that of healthy controls. This indicates the important role of exosome‐mediated immune responses in the pathogenesis of inflammatory bowel disease. Here, we will discuss the immune properties of exosomes and recent advances in their function with a special focus on intestinal mucosal immunity.