Noncoding RNAs in alcoholic liver disease

Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA-122 is a marker of hepatocyte damage, and miRNA-155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome-derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.     

酒精性肝病与肠道菌群关系的研究进展

肠道菌群被认为是人体的"第二大脑",肝脏被称为人体内的"生化工厂",由于肠道与肝脏均起源于内胚层,且通过门静脉紧密相连,所以肝脏的各项机能都与肠道菌群息息相关。酒精性肝病是由于摄入酒精导致的慢性肝病之一,在全球范围内普遍存在。近年来的研究结果表明,酒精性肝病(alcoholic liver disease,ALD)的发生与发展与肠道菌群密切相关。本文就肠道菌群与ALD的关系作一综述,并对靶向肠道菌群治疗ALD的方法简要总结,以期对ALD的治疗提供新策略。     

补锌对酒精性肝病的影响及其分子机制

目的:本研究是为了观察饮食补充锌减轻酒精性肝病损伤的作用及与HNF-4α的关系。方法:选用成年C57BL/6小鼠40只,按随机数字表分为4组(n=10):正常对照组、酒精中毒组、正常补锌组及酒精补锌组,用不同饮食喂养6个月处死,在正常补锌组和酒精补锌组小鼠饮用水中加入硫酸锌,使锌的含量达到75 mg/L。取各组小鼠肝组织进行病理切片及增殖细胞核抗原(PCNA)免疫组织化学染色,RT-PCR检测肝细胞核因子-4α(HNF-4α)含量,Western blot检测肝组织HNF-4α蛋白表达,检测"肝组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量"。结果:酒精中毒组小鼠HNF-4α转录及表达均明显低于正常对照组,差异具有统计学意义(P<0.05),该组小鼠MDA含量增高,SOD活性下降与正常对照组相比差异有统计学意义(P<0.05);而酒精补锌组小鼠PCNA阳性肝细胞数目及HNF-4α蛋白表达水平明显高于酒精中毒组,差异有统计学意义(P<0.05),该组小鼠SOD活性增加,MDA下降,与酒精中毒组相比差异有统计学意义(P<0.05)。结论:长期酒精喂养导致小鼠氧化还原失衡,而补锌可逆转该状态。我们推测饮食补锌可能是通过增加HNF-4α的转录及表达而增强酒精喂养小鼠的肝再生,因此,饮食补锌可能对酒精性肝病有较好的影响。     

Effect of alcohol on the interleukin 6-mediated inflammatory response in a new mouse model of acute-on-chronic liver injury

Background and Aims

ACLF is usually associated with a precipitant in the setting of a chronically damaged liver. We aim to combine a mouse model with a pre-injured liver (Abcb4/Mdr2^?/?) with a recently standardized ethanol feeding model to dissect alcohol-related inflammatory responses in this model.

MicroRNAs and breast cancer stem cells: Potential role in breast cancer therapy

MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future.     

MicroRNAs在系统性硬化症纤维化中的作用及机制

微RNA（microRNAs,miRNAs）是在基因编码中起负性调控作用的内源性短链非编码RNA（non-coding RNAs,ncRNAs）,是生理和病理过程中基因表达必不可少的转录后调控物。miRNAs占人类基因组的1%～2%,通过与各自的mRNA结合并抑制其翻译,调节大于50%的人类基因及60%的哺乳动物蛋白质编码基因。系统性硬化症（systemic sclerosis,SSc）的发病机制由复杂的miRNAs网络调控。这些miRNAs位于与SSc纤维化相关的基因组区域,通过参与调节重要的细胞信号通路,如TGF-β、Wnt/β-catenin、TLR-4、IL和PDGF-β等,在SSc纤维化过程中发挥作用。同时,还与细胞信号转导、基质修复与重塑、成纤维细胞凋亡、胶原蛋白质合成和细胞外基质（extracellular matrix,ECM）沉积等相关。充分了解miRNAs在SSc纤维化中的重要性,有助于为SSc的诊断提供新的生物标记,为治疗提供新策略。本文综述了miRNAs在SSc纤维化过程中参与调节的这些复杂细胞信号通路的作用及机制,以期为SSc诊断、严重程度判断、预后评估,以及寻求潜在治疗靶点提供新思路。     

细胞因子与酒精性肝病

酒精性肝病(alcoholic liver disease,ALD)的发生发展过程与体内多种细胞因子有关,尤其是肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和转化生长因子-β(transforming growth factor-β,TGF-β)在调节肝细胞的凋亡过程中具有重要作用。TNF-α可引起肝细胞凋亡与炎症反应等,抗TNF-α治疗能明显减轻酒精引起的肝损害;TGF-β具有增加细胞外基质的合成和抑制细胞外基质降解的作用,TGF-β1升高与肝纤维化密切相关。细胞因子可能是防治酒精性肝病的有效分子靶点。     

microRNAs在高血压疾病中的作用机制

高血压作为一种多因素的慢性疾病,其引起的一系列并发症是导致心血管疾病死亡的主要原因。微RNA（microRNA,miRNAs）作为内源性单链非编码RNA,在高血压的病理生理过程中发挥重要作用。miRNAs通过调控血管内皮细胞损伤、血管平滑肌细胞功能障碍、单核/巨噬细胞介导的免疫炎症反应、氧化应激、一氧化氮合成异常、肾素 血管紧张素 醛固酮系统的激活、交感神经激活、肾水钠潴留和胰岛素抵抗等过程,进而广泛参与高血压的发病过程。本文就miRNAs在高血压发生发展中的作用机制及其研究进展进行简要综述,为高血压早期诊断及治疗提供新思路。     

MicroRNA-200a induces apoptosis by targeting ZEB2 in alcoholic liver disease

Alcoholic liver disease (ALD) and its complication continued to be a major health problem throughout the world. Increasing evidence suggests that microRNA (miRNA) that regulate apoptosis, inflammation and lipid metabolism are affected by alcohol in ALD. MiR-200a has emerged as a major regulator in several liver diseases, but its role in ALD has not been elucidated. The aim of this study is to figure out the biological function of miR-200a in ALD and to explore its underlying mechanism. The expression pattern of miR-200a were analyzed in vitro and in vivo, we showed that miR-200a was up-regulated in ALD in AML-12 and primary hepatocyte. We then examined it's effect on cell apoptosis and identified zinc finger E-box binding homeobox 2 (ZEB2; also known as SIP1) as a direct target gene of miR-200a. Furthermore, reintroduction of ZEB2 could reverse the pro-apoptosis of miR-200a on AML-12. Taken together, our study demonstrated that miR-200a regulates the apoptosis of hepatocyte in ALD by directly target ZEB2, both of which could serve as new therapeutic targets for ALD.     

Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease

Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States for which there is no FDA-approved therapy. Abnormal cytokine metabolism is a major feature of ALD. Elevated serum concentration levels of TNF-alpha and TNF-alpha-inducible cytokines/chemokines, such as IL-6, -8, and -18, have been reported in patients with alcoholic hepatitis and/or cirrhosis, and levels correlated with markers of the acute phase response, liver function, and clinical outcome. Studies in animal models support an etiologic role for cytokines in the liver injury of ALD. Cytokines, such as transforming growth factor-beta, play a critical role in the fibrosis of ALD. Multiple new strategies are under investigation to modulate cytokine metabolism as a form of therapy for ALD.     

非肥胖者发生非酒精性脂肪肝的预测指标

目的：探讨能够预测非肥胖者是否发生非酒精性脂肪肝（Nonalcohohc fatty liver disease,NAFLD）的临床指标。方法：从广州社区人群中选取体重指数〈25且年龄、性别相匹配的NAFLD和非NAFLD个体分别为38和82例,测量其身高、体重、腰围、臀围及空腹血糖、甘油三脂、胆固醇、低密度脂蛋白、高密度脂蛋白、HBsAg和空腹胰岛素,计算体重指数、腰臀比、腰围身高比和HOMA胰岛素抵抗指数。先采用t检验和x^2检验对上述临床指标进行分析,对两组间存在显著差异者进行Logisde回归以发现独立的预测指标,再针对各预测指标进行受试者工作特征（reciever operating charactefistic,ROC）曲线分析判断各指标的预测准确度,并确定最佳的预测截断值。结果：NAFLD和非NAFLD的体重、腰围、臀围、体重指数、腰臀比、腰围身高比及空腹血糖、甘油三脂、低密度脂蛋白、胰岛素、HOMA胰岛素抵抗指数均有显著差异,但仅腰围、低密度脂蛋白和HOMA胰岛素抵抗指数进入Logistic回归方程,且其ROC曲线下面积均大于0．5（分别是0．821,0．665和0、722）。以腰围的预测准确度最高,且在80．5cm处敏感性和特异性之和最大。结论：腰围是预测非肥胖者是否发生NAFLD的合适指标,80．5cm为其最佳预测截断值。     

De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose

Hepatic de novo lipogenesis (DNL) is the biochemical process of synthesising fatty acids from acetyl‐CoA subunits that are produced from a number of different pathways within the cell, most commonly carbohydrate catabolism. In addition to glucose which most commonly supplies carbon units for DNL, fructose is also a profoundly lipogenic substrate that can drive DNL, important when considering the increasing use of fructose in corn syrup as a sweetener. In the context of disease, DNL is thought to contribute to the pathogenesis of non‐alcoholic fatty liver disease, a common condition often associated with the metabolic syndrome and consequent insulin resistance. Whether DNL plays a significant role in the pathogenesis of insulin resistance is yet to be fully elucidated, but it may be that the prevalent products of this synthetic process induce some aspect of hepatic insulin resistance.     

茄子microRNAs与其靶基因的生物信息学预测

microRNAs(miRNAs)是一类在真核生物中发现的长度为21 nt左右、非编码、内源性的单链小分子RNA,通过与靶基因的互补发挥转录后水平的负调控作用。目前,已在许多物种中报道了miRNAs的存在,然而还未见关于茄子miRNAs的报道。根据miRNAs在植物中的高度保守性及其前体的二级结构特征,文章通过同源预测的方法,将已知植物的miRNAs与茄子EST数据库比对,经过一系列的筛选,最终预测到12个家族的16条茄子miRNAs,其中包括3个miRNA家族的正义/反义miRNAs,而miR390和miR399家族的正义/反义miRNAs属于第一次发现。文章还通过在线软件psRNATarget预测到15条茄子miRNAs的71个靶基因,这些靶基因主要编码与茄子生长发育、新陈代谢以及胁迫响应等过程相关的蛋白。     

酪酸梭菌活菌片联合多烯磷脂酰胆碱对酒精性肝病患者肠道菌群及炎症因子的影响

目的 探讨酪酸梭菌活菌片联合多烯磷脂酰胆碱对酒精性肝病（ALD）患者肠道菌群及炎症因子的影响。方法 选取2015年1月至2018年1月进行治疗的ALD患者80例,随机分为观察组和对照组。两组患者均予以严格戒酒、高蛋白高热量低脂饮食、维生素及门冬氨酸钾镁等常规治疗。观察组患者在此基础上加用酪酸梭菌活菌片（0.7 g/次,3次/d,口服）和多烯磷脂酰胆碱胶囊（456 mg/次,3次/d,口服）联合治疗8周。对照组患者在常规治疗基础上单纯加用多烯磷脂酰胆碱片治疗,其剂量、用法及疗程与观察组相同。观察并比较治疗前后患者肝功能指标、肠道菌群数量及炎症因子的变化。结果 治疗8周后,两组患者血清ALT、AST和TBiL水平均较治疗前显著下降（P<0.05）,且观察组下降幅度较对照组更大（P<0.05）。两组患者肠道双歧杆菌和乳杆菌数量较治疗前明显上升,大肠埃希菌数量较治疗前明显下降（P<0.05）,且观察组变化幅度较对照组更大（P<0.05）。两组患者血清IL-6和TNF-α水平较治疗前明显下降（P<0.05）,且观察组下降幅度较对照组更大（P<0.05）。结论 酪酸梭菌活菌片联合多烯磷脂酰胆碱能有效改善ALD患者肝功能指标,促进肝功能恢复,其作用机制可能与其能纠正肠道菌群失调,促进有益菌的繁殖,同时下调血清炎症因子水平,抑制肝内炎症反应密切相关。     

EBV编码miRNAs在病毒感染和肿瘤发生中的功能和意义

EB病毒(Epstein-Barr virus,EBV)是一种172 kb大小的线性双链DNA病毒,与鼻咽癌、淋巴瘤、胃癌等恶性肿瘤的发生密切相关. EBV编码的微小RNAs (miRNAs)可以调节病毒和宿主细胞基因的表达,并且在癌症发生发展中起着多种作用.本文综述了EBV编码的miRNAs (EBV-encoded miRNA,EBV miRNAs)在病毒感染和肿瘤发生、侵袭转移、抗凋亡、信号通路等方面的生物学功能,以及对于EBV相关肿瘤诊断标志物的潜在意义. EB病毒编码的miRNAs也可能成为进一步研究EBV相关肿瘤治疗的一个候选靶点.