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miRNAs in non-alcoholic fatty liver disease

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《医学前沿（英文）》 2016年 第10卷 第4期   页码 389-396 doi: 10.1007/s11684-016-0468-5

摘要：

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver cirrhosis and hepatocellular carcinoma and is a considerable threat to public health. miRNAs are important post-transcriptional regulators of gene expression, and the dysregulation of miRNAs is involved in various biological processes in the liver, including lipid homeostasis, inflammation, apoptosis, and cell proliferation. Recently, a number of studies have described the association between miRNAs and NAFLD progression and have shown that circulating miRNAs reflect histological changes in the liver. Therefore, circulating miRNAs have potential use for the evaluation of NAFLD severity. In this review, we discuss the involvement of miRNAs in NAFLD pathogenesis and the key role of miRNAs in the screening, diagnosis, and staging of NAFLD.

关键词： nonalcoholic fatty liver disease     nonalcoholic steatohepatitis     hepatocellular carcinoma     miRNA    

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Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholicfatty liver disease: a translational approach

《医学前沿（英文）》 2022年 第16卷 第5期   页码 745-759 doi: 10.1007/s11684-021-0880-3

摘要： Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ≥ 24 kg/m2; lean, BMI < 24 kg/m 2). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (−0.19 (1.47) versus 0.08 (1.99),P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.

关键词： insulin resistance     non-alcoholic fatty liver disease     Chinese herbal medicine     randomized controlled trial     DNA N6-methyladenine modification    

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Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

《医学前沿（英文）》 2011年 第5卷 第3期   页码 288-293 doi: 10.1007/s11684-011-0127-9

摘要： Haemorheological abnormalities have been described in diabetes mellitus, as well as in non-alcoholic fatty liver disease (NAFLD). However, the relationship between the changes in liver fat content and haemorheology is unknown. The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes. The serum biochemical markers, such as fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), liver enzymes, lipid profiles, and haemorheological properties, were examined. IHLC was quantified using proton magnetic resonance spectroscopy ( H-MRS) scanning of the liver. A significant correlation was observed between IHLC and whole blood viscosity at high, middle, and low shear rates. IHLC also positively correlated with haematocrit, the reduced whole blood viscosity at low and middle shear rates, and the erythrocyte aggregation index. Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD. In summary, haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

关键词： diabetes mellitus     type 2     haemorheology     non-alcoholic fatty liver disease    

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Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

Ruiting Han, Junli Ma, Houkai Li

《医学前沿（英文）》 2018年 第12卷 第6期   页码 645-657 doi: 10.1007/s11684-018-0645-9

摘要： Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical “Two-hit” theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a “metabolic organ” that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

关键词： gut microbiota     NAFLD     obesity     insulin resistance     bile acids     probiotic    

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γδ T cells in liver diseases

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells     liver infection     non-alcoholic fatty liver disease     autoimmune hepatitis     liver fibrosis and cirrhosis     liver cancer     liver regeneration    

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New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

《医学前沿（英文）》 2022年 第16卷 第5期   页码 714-722 doi: 10.1007/s11684-021-0888-8

摘要： A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01–1.55) and 1.35 (95% CI 1.07–1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07–2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

关键词： metabolic dysfunction-associated fatty liver disease     non-alcoholic fatty liver disease     fibrosis score     brachial-ankle pulse wave velocity     albuminuria    

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益生菌对非酒精性脂肪性肝病疗效的研究进展 Article

姚铭飞, 屈玲玲, 陆艳蒙, 王保红, Björn Berglundb, 李兰娟

《工程（英文）》 2021年 第7卷 第5期   页码 679-686 doi: 10.1016/j.eng.2020.01.017

摘要：

非酒精性脂肪性肝病（NAFLD）在全球范围内的患病率高达20%~33%，已成为严重威胁人类健康的慢性肝病之一。至今为止，除了改变生活方式，改善NAFLD尚无明确的药物治疗方法。因此，找到有效、可替代的干预策略迫在眉睫。随着人们对肠道微生态在NAFLD发病机制中的重要作用的认识，益生菌防治NAFLD的研究也随之增多。NAFLD治疗中最受关注的益生菌主要包括以双歧杆菌属（Bifidobacterium）和乳酸杆菌属（Lactobacillus）为代表的传统益生菌，以及下一代新兴益生菌（NGP），如嗜黏蛋白阿克曼菌（Akkermansia muciniphila）和普拉梭菌（Faecalibacterium prausnitzii）等。本文综述了口服传统益生菌和NGP对NAFLD发生发展的影响；基于最新的动物和临床研究，阐述了益生菌直接或间接影响疾病的机制。虽然相关研究已有很多，但要全面了解益生菌、肠道微生态、NAFLD之间的具体潜在机制，仍需要深入研究，需要更多的大规模临床试验来评估益生菌治疗NAFLD的效果以及益生菌在人体内的安全性。

关键词： 非酒精性脂肪性肝病     肠道菌群     益生菌     下一代益生菌    

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NKT cells in liver diseases

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells     hepatitis B virus and hepatitis C virus infection     autoimmune liver diseases     alcoholic liver disease     nonalcoholic fatty liver disease     hepatocellular carcinoma    

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Molecular mechanisms of fatty liver in obesity

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《医学前沿（英文）》 2015年 第9卷 第3期   页码 275-287 doi: 10.1007/s11684-015-0410-2

摘要：

Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of liver disorders ranging from simple steatosis to advanced pathologies, including nonalcoholic steatohepatitis and cirrhosis. NAFLD significantly contributes to morbidity and mortality in developed societies. Insulin resistance associated with central obesity is the major cause of hepatic steatosis, which is characterized by excessive accumulation of triglyceride-rich lipid droplets in the liver. Accumulating evidence supports that dysregulation of adipose lipolysis and liver de novo lipogenesis (DNL) plays a key role in driving hepatic steatosis. In this work, we reviewed the molecular mechanisms responsible for enhanced adipose lipolysis and increased hepatic DNL that lead to hepatic lipid accumulation in the context of obesity. Delineation of these mechanisms holds promise for developing novel avenues against NAFLD.

关键词： nonalcoholic fatty liver disease     insulin resistance     obesity    

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Pien Tze Huang Protects Against Non-Alcoholic Steatohepatitis by Modulating the Gut Microbiota and Metabolites

Xianyi Zeng,Xiang Zhang,Hao Su,Hongyan Gou,Harry Cheuk-Hay Lau,Xiaoxu Hu,Ziheng Huang,Yan Li,Jun Yu,

《工程（英文）》 doi: 10.1016/j.eng.2022.10.010

摘要： Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease without effective treatment. The traditional Chinese medicine formulation Pien Tze Huang (PTH) can suppress inflammatory diseases. Here, we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms. We found that PTH prevented the development of steatohepatitis induced by various dietary models, including a high-fat high-cholesterol (HFHC) diet, choline-deficient high-fat diet (CD-HFD), and methionine- and choline-deficient (MCD) diet, along with significant suppression of liver injury, hepatic triglyceride, and lipid peroxidation. Moreover, ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice. Through the metagenomic sequencing of stool samples, we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus (L. acidophilus), Lactobacillus plantarum, Lactococcus lactis, and Bacillus subtilis. The enriched L. acidophilus prevented MCD diet-induced steatohepatitis. In addition, PTH restored the gut barrier function in mice with steatohepatitis, as evidenced by reduced intestinal permeability, decreased serum lipopolysaccharides (LPS) level, and increased epithelial tight-junction protein E-cadherin expression. Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTH-treated mice. We further confirmed that an intact gut microbiota is necessary for PTH to exhibit anti-steatohepatitis effects. In conclusion, PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites. PTH is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang     Non-alcoholic steatohepatitis     Gut barrier function     Gut microbiota    

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Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge

《医学前沿（英文）》 2022年 第16卷 第5期   页码 667-685 doi: 10.1007/s11684-022-0960-z

摘要： Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer. Akkermansia muciniphila (A. muciniphila) is a next-generation probiotic that has been reported to improve metabolic disorders. Emerging evidence indicates the therapeutic potential of A. muciniphila for NAFLD, especially in the inflammatory stage, nonalcoholic steatohepatitis. Here, the current knowledge on the role of A. muciniphila in the progression of NAFLD was summarized. A. muciniphila abundancy is decreased in animals and humans with NAFLD. The recovery of A. muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD. The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed. The modulation mechanisms by which A. muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells (such as macrophages). This review provides insights into the roles of A. muciniphila in NAFLD, thereby providing a blueprint to facilitate clinical therapeutic applications.

关键词： Akkermansia muciniphila     NAFLD     NASH     steatosis     inflammation    

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Pathological study of 130 cases of nonalcoholic fatty liver disease based on NASH-CRN system

ZHOU Guangde, ZHAO Jingmin, DING Xiaohui, PAN Deng, SUN Yanling, YANG Jianfa, ZHAO Yulai

《医学前沿（英文）》 2007年 第1卷 第4期   页码 413-417 doi: 10.1007/s11684-007-0081-8

摘要： To summarize the pathological features of nonalcoholic liver disease (NAFLD) in China based on a histological scoring system for NAFLD designed by the Pathology Committee of NASH Clinical Research Network (NASH-CRN), the specimens of liver needle biopsies from 130 patients with NAFLD were histopathologically analyzed by haematoxylin eosin, reticular fiber and Masson trichrome stain. Immunohistochemistry staining was used to exclude non-NAFLD cases combined with clinical data. Hepatic steatosis, lobular inflammation, hepatocytic ballooning and fibrosis were presented widespread in NAFLD liver tissues. Furthermore, macrovesicular steatosis predominantly located in acinar zone 3 was the main histologic feature of NAFLD and lobular inflammation was usually presented mildly. Hepatocyte ballooning was observed in 94.6% of all 130 cases. Mild perisinusoidal fibrosis and periportal fibrosis were often observed in stage 1 cases. According to the statistic analysis, hepatic steatosis was positively correlated with lobular inflammation, hepatocytic ballooning and fibrosis ( = 0.587, 0.488, 0.374, respectively, all value<0.01). The number of microgranulomas, lipogranulomas and apoptotic bodies increased following severity of steatosis, lobular inflammation and fibrosis. Meanwhile, the number of megamitochondria and glycogen nuclei was paralleveled to the degree of hepatocytic ballooning ( value all<0.01). We suggest that the role of portal inflammation should be emphasized besides hepatic steatosis, lobular inflammation, hepatocyte ballooning and fibrosis in diagnosis and evaluation of NAFLD. It needs to be further verified whether microgranulomas, lipogranulomas and apoptosis bodies could be used as histopathological markers of development of AFLD. The number of megamitochondria is more frequently be found in NAFLD, while in alcoholic liver diseases was Mallory bodies.
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肠道菌群与肿瘤发生及肝病

吕桂帅, 程宁涛, 王红阳

《工程（英文）》 2017年 第3卷 第1期   页码 110-114 doi: 10.1016/J.ENG.2017.01.017

摘要：

一个多世纪以前，科学家们就首次发现了肿瘤区域中细菌的存在。但是，微生物在肿瘤发生中的作用近年来才被认识到。近几十年来，与肠道菌群失调相关的疾病代表了全世界最严重的一些公共卫生问题。大量的流行病学研究表明，肠道菌群与某些常见肿瘤密切相关。然而，肠道菌群与肿瘤相关联的具体分子机制仍不明确。研究表明，肠道菌群的改变有助于确定肝癌、酒精相关肝病、非酒精性脂肪肝和肝硬化的发生和发展。鉴于益生菌是一种可通过调节免疫系统促进人类健康的药物，其可能会为肝细胞癌(HCC) 和非酒精性脂肪肝的治疗提供新方向。本文总结了肠道菌群在肿瘤及肝病中的研究进展，综述了肠道菌群与肿瘤和肝病之间的关系。此外，考虑到细菌内稳态的重要性，我们也对益生菌进行了概述，旨在为相关疾病的治疗提供指导。

关键词： 肠道菌群     稳态失调     肿瘤发生     肝细胞癌     非酒精性脂肪性肝病    

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Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

《医学前沿（英文）》 2021年 第15卷 第3期   页码 460-471 doi: 10.1007/s11684-021-0861-6

摘要： Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n=22) and an exercise group (EX, n=23). The subjects either adopted LCD (carbohydrate intake<50 g/day) or performed moderate-to-vigorous exercise (≥30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX (−3.56±0.37 kg vs. −1.24±0.39 kg, P<0.001), as well as a larger reduction in fat mass (−2.10±0.18 kg vs. −1.25±0.24 kg, P=0.007) and waist circumference (−5.25±0.52 cm vs. −3.45±0.38 cm, P=0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet     obesity     nonalcoholic fatty liver disease     continuous glucose monitoring     mean sensor glucose    

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decoction on CD14 expression in lipopolysaccharide signal transduction pathway of alcohol-induced liverdisease in rats

Rui ZHU MD , Lin SHEN MD , Jianguo LIU MD , Weili ZHANG MM , Ling YANG MD ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 363-367 doi: 10.1007/s11684-009-0064-z

摘要： This paper aims to investigate the effects of (枳黄) decoction on CD14 expression in the lipopolysaccharide signal transduction pathway of alcohol-induced liver disease in rats. Seventy-five Wistar rats were randomly divided into three groups. Ethanol (56%, weight/volumn) was intragastrically administrated to 50 rats (14mL/kg body weight per day) for 10 days to establish a model of alcohol-induced liver disease, and 25 of these 50 rats were treated with decoction simultaneously. Liver injury was evaluated by biochemical examination. The plasma content of endotoxin was assayed by biochemistry. The expression of CD14 mRNA and protein in rat liver was measured by reverse transcriptional polymerase chain reaction and immunohistochemistry, respectively. decoction pretreatment significantly protected against acute alcohol-induced liver injury, which was evidenced by the decrease of elevated serum alanine aminotransferase and aspartate aminotransferase. In addition, the level of plasma endotoxin and up-regulation of CD14 was also suppressed by decoction in alcohol-intoxicated rats. decoction can significantly reduce CD14 expression in the lipopolysaccharide signal transduction pathway, which is one of the most important mechanisms of decoction to treat hepatic injury induced by alcohol in rats.

关键词： liver disease     alcohol     Zhihuang decoction     CD14     signal transduction    

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标题 作者 时间 类型 操作

miRNAs in non-alcoholic fatty liver disease

null

期刊论文

Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholicfatty liver disease: a translational approach

期刊论文

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

期刊论文

Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

Ruiting Han, Junli Ma, Houkai Li

期刊论文

γδ T cells in liver diseases

null

期刊论文

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

期刊论文

益生菌对非酒精性脂肪性肝病疗效的研究进展

姚铭飞, 屈玲玲, 陆艳蒙, 王保红, Björn Berglundb, 李兰娟

期刊论文

NKT cells in liver diseases

null

期刊论文

Molecular mechanisms of fatty liver in obesity

null

期刊论文

Pien Tze Huang Protects Against Non-Alcoholic Steatohepatitis by Modulating the Gut Microbiota and Metabolites

Xianyi Zeng,Xiang Zhang,Hao Su,Hongyan Gou,Harry Cheuk-Hay Lau,Xiaoxu Hu,Ziheng Huang,Yan Li,Jun Yu,

期刊论文

Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge

期刊论文

Pathological study of 130 cases of nonalcoholic fatty liver disease based on NASH-CRN system

ZHOU Guangde, ZHAO Jingmin, DING Xiaohui, PAN Deng, SUN Yanling, YANG Jianfa, ZHAO Yulai

期刊论文

肠道菌群与肿瘤发生及肝病

吕桂帅, 程宁涛, 王红阳

期刊论文

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

期刊论文

decoction on CD14 expression in lipopolysaccharide signal transduction pathway of alcohol-induced liverdisease in rats

Rui ZHU MD , Lin SHEN MD , Jianguo LIU MD , Weili ZHANG MM , Ling YANG MD ,

期刊论文