肿瘤相关成纤维细胞外泌体miRNA-656-3p调控喉癌生长侵袭及丹参酮ⅡA对其调控研究

目的研究喉癌肿瘤相关成纤维细胞(CAFs)外泌体表达下调的miRNA-656-3p对喉癌细胞生长和侵袭能力的影响以及丹参酮ⅡA对其调控作用。方法将CAFs外泌体miRNA-656-3p表达上调,制备外泌体上清,检测其对喉癌细胞体外增殖、侵袭能力及细胞周期的影响。检测中药提取物丹参酮ⅡA是否具有类似的上调CAFs外泌体miRNA-656-3p表达的作用,其作用后的CAFs外泌体上清是否具有类似的抑制喉癌增殖和侵袭能力的功效。结果过表达miR-656-3p的CAFs外泌体上清能抑制喉癌细胞的体外增殖和侵袭能力,抑制CCND2的表达,并将喉癌细胞阻滞在G0/G1期。而丹参酮ⅡA也可以上调CAFs外泌体中miR-656-3p的表达水平,其作用后的CAFs外泌体能发挥类似的抑制喉癌细胞体外增殖和侵袭的功效。结论喉癌CAFs外泌体miRNA-656-3p的表达下调促进喉癌细胞的生长和侵袭能力,丹参酮ⅡA可上调CAFs外泌体miR-656-3p的表达,通过后者抑制喉癌细胞的生长和侵袭能力。     

CircRNA在胃癌液体活检中的研究进展

胃癌因其高流行状态已成为我国一大公共卫生问题。环状RNA（circRNA）由于可稳定存在于人类的多种体液中,具备液态活检的先天优势,成为近年来精准治疗领域的研究热点。本文通过检索PubMed、Web of Science、中国知网等数据库文献,基于circRNA的生物学特征,归纳circRNA在胃癌早期筛查诊断、疗效监测、预后评估等方面的研究进展,论述circRNA作为新兴液体活检标志物的可能性及可靠性,为今后circRNA作为胃癌临床诊疗、评估、预后分子标志物的开发和转化提供思路。     

外泌体在缺血性脑卒中的研究进展

正1外泌体概述外泌体是直径在30~100 nm的胞外囊泡,通过细胞被释放到细胞外液中~([1])。它们存在于生物体液中,诸如血液和脑脊液。外泌体携带有DNA、RNA、蛋白质和脂质等。由于外泌体的微泡结构为其内在的小分子提供了一个安全稳定的环境,同时这些信号小分子利用循环系统在胞间信号交换发挥重要作用,这让外泌体表现出一个成熟、稳定的信号传输系统~([2])。研究发现,外泌体中的m RNA和micro RNA     

miR-122-5p调节创伤性脑外伤后小胶质细胞极化减弱炎症反应北大核心CSCD

目的探讨miR-122-5p对创伤性脑外伤后小胶质细胞凋亡、极化和炎症反应的影响。方法建立创伤性脑外伤(traumatic brain injury,TBI)小鼠模型和细胞模型。使用TBI小鼠脑匀浆刺激星型胶质细胞产生外泌体,microRNA微阵列分析外泌体中显著改变的microRNA。实时荧光定量PCR检测TBI小鼠模型和TBI细胞模型中miR-122-5p表达。使用TUNEL凋亡染色、免疫荧光共聚焦、蛋白质印迹研究miR-122-5p抑制剂在TBI神经炎症中对小胶质细胞凋亡、小胶质细胞M1/M2表型转化、NLRP3通路及NFκB磷酸化的作用。结果通过microRNA微阵列分析发现有83个下调miRNA(改变2倍以上,P<0.05),其中miR-122-5p显著下调(P<0.01),miR-122-5p在TBI小鼠及细胞模型中表达显著下降[(1.0±0.00)vs.(0.41±0.15),P<0.001];[(1.0±0.00)vs.(0.34±0.07),P<0.001]。TUNEL凋亡检测、免疫荧光染色结果表明抑制miR-122-5p表达,可以显著减轻LPS诱导的小胶质细胞凋亡[(8.03±1.30)vs.(3.17±0.34),P<0.001],促进小胶质细胞M1向M2表型转化,即M1表型极化减少[(56.96±13.70)vs.(34.70±3.47),P=0.002],M2表型极化增加[(30.46±3.67)vs.(40.74±2.49),P=0.005]。蛋白质印迹结果表明miR-122-5p抑制剂降低NLRP3炎症小体活化[(0.77±0.10)vs.(0.51±0.11),P=0.02],降低NFκB的磷酸化[(0.73±0.08)vs.(0.50±0.07),P=0.003]。结论miR-122-5p在TBI星形胶质细胞分泌的外泌体及小胶质细胞中表达下调,miR-122-5p抑制剂可以通过抑制TBI后NLRP3炎症小体通路的活化及NFκB的磷酸化,促进小胶质细胞M1向M2表型转化,减少小胶质细胞凋亡,从而减轻TBI后小胶质细胞炎症损伤。     

Induction of protective immunity against Eimeria tenella infection using antigen-loaded dendritic cells (DC) and DC-derived exosomes

Current methods for sustainable control of avian coccidiosis, whether by prophylactic medication or parasite vaccination, are suboptimal. In this study, we describe an alternative immunization strategy against Eimeria tenella infection using parasite antigen (Ag)-loaded dendritic cells (DCs), or their derived exosomes, in the absence of free Ag. CD45⁺ intestinal DCs were isolated from E. tenella-infected chickens and loaded ex vivo with an extract of sporozoites as parasite Ag. Extracellular vesicles purified from the Ag-pulsed DCs expressed surface proteins associated with DC-derived exosomes, including major histocompatibility complex proteins (MHC I and MHC II), CD80, flotillin, and heat shock protein (HSP70). Following intramuscular immunization of chickens with Ag-pulsed DCs or Ag-pulsed DC-derived exosomes, Ag-containing cells were observed diffusely localized in the lymphoid tissue and concentrated in germinal centers of caecal tonsils, and restricted to germinal centers (GC) in the spleen. Chickens immunized with pulsed DCs or exosomes exhibited (a) higher numbers of caecal tonsil and spleen cells expressing IgG and/or IgA antibodies that were reactive with E. tenella Ag, (b) greater numbers of IL-2-, IL-16-, and IFN-γ-producing cells, and (c) higher E. tenella Ag-driven cell proliferation, compared with chickens immunized with Ag in the absence of DCs or exosomes. Chickens immunized with Ag-pulsed DCs or Ag-pulsed DC-derived exosomes and subsequently given a live E. tenella challenge infection at 10 d post-immunization displayed (a) increased body weight gains, (b) decreased feed conversion ratios, (c) reduced fecal oocyst shedding, (d) diminished intestinal lesions, and (e) lower mortality, compared with animals given Ag alone. This is the first demonstration of Ag-specific protective immunity against avian coccidiosis using parasite Ag-loaded DCs or DC-derived exosomes.     

Extracellular vesicles: Their emerging roles in the pathogenesis of respiratory diseases

Alveoli are the basic structure of the lungs, consisting of various types of parenchymal and bone marrow-derived cells including alveolar macrophages. These various types of cells have several important functions; thus, communication between these cells plays an important role in homeostasis as well as in the pathophysiology of diseases in the lungs. For a better understanding of the pathophysiology of lung diseases, researchers have isolated each type of lung cell to investigate the changes in their gene expressions, including their humoral factor or adhesion molecules, to reveal the intercellular communication among these cells. In particular, investigations during the past decade have focused on extracellular vesicles, which are lipid bilayer delimited vesicles released from a cell that can move among various cells and transfer substances, including microRNAs, mRNAs and proteins, thus, functioning as intercellular messengers. Extracellular vesicles can be classified into three general groups: apoptotic bodies, exosomes, and microparticles. Extracellular vesicles, especially exosomes and microparticles, are attracting increasing attention from pulmonologists as tools for understanding pathogenesis and disease diagnosis. Here, we review studies, including our own, on exosomes and microparticles and their roles in both lung homeostasis and the pathogenesis of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive lung diseases, and acute respiratory distress syndrome. This review also addresses the roles of extracellular vesicles in COVID-19, the current global public health crisis.     

肝癌肿瘤微环境中非癌细胞成分的研究进展与介入治疗展望

肝癌肿瘤微环境中的非癌细胞成分,因其基因组的相对稳定性而受到关注。本文从肿瘤微环境的组成及其特点、肝癌肿瘤微环境的组成出发,对肝癌肿瘤微环境中非癌细胞成分的3个研究新的热点(外泌体、趋化因子及无生物活性条件的局部调节)进行综述,并对其在介入治疗方面的应用进行展望。     

间充质干细胞源性外泌体在脑损伤治疗中的研究进展

间充质干细胞(MSC)移植被认为是脑损伤修复最具潜力的治疗策略之一,其在神经修复的各个环节发挥着重要作用。最新研究表明MSC分泌的外泌体可能主导了脑损伤的修复,发挥促血管增生、免疫调节、抗凋亡及神经修复作用,其在新生儿脑损伤的治疗中具有较大潜力。该文根据当前的研究,就外泌体在脑损伤修复中的作用机制和应用前景及挑战作一概述,以期为干细胞治疗新生儿脑损伤提供新导向。     

肿瘤来源的胞外体对肿瘤进展的影响

胞外体是真核细胞在正常生理过程中分泌的一种具有多种细胞膜结构的小囊泡,作为一类重要的细胞间信号分子,胞外体具有多种生物活性成分,其异常分泌是恶性肿瘤的标志.胞外体与肿瘤细胞生长、肿瘤血管生成、免疫抑制及化疗耐药关系密切.因此,探究胞外体的形成过程、主要组成成分及肿瘤相关的胞外体在肿瘤进展、免疫调节中的作用有助于进一步了解肿瘤进展过程,具有重要意义.