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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li Department of Infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.liver tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP production.Overproduction of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver function.Mitochondrial DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus.We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver disease.This review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

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World Journal of Gastroenterology 2024年第11期30卷 1494-1496页

作者： Sara Massironi Division of Gastroenterology and center for Autoimmune liver diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

关键词： Barrett's esophagus Artificial intelligence Endoscopic images Artificial intelligence model Early cancer detection Endoscopy

Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections

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World Journal of Hepatology 2024年第2期16卷 177-185页

作者： Feng Chen Shan-Shan Wu Chao Chen Cheng Zhou State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

关键词： Lipocalin 2 Microbial infection Immunity liver diseases

Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

liver disease,a major health concern worldwide,is a serious and progressive disorder.Herein,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome.As liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse models.The metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC group.The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC.Based on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were depleted.The increased abundance of C.albicans and depletion of S.cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC.Moreover,the administration of C.albicans and S.cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC.Therefore,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma

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中华医学杂志(英文版) 2024年第11期137卷 2024 May 13页

作者： Zhang Jiaqian Zhang Zhicheng Wu Zhangfan Wang Yufei Zhang Zerui Xia Limin Department of Gastroenterology Institute of Liver and Gastrointestinal Diseases Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical research center for Digestive diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University Xi’an Shaanxi China

In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.

关键词： Hepatocellular carcinoma Invasion Metastasis Lipid metabolism Tumor microenvironment

Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia

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贫困所致传染病(英文) 2024年第2期13卷 1-13页

作者： Zheng Jin-Xin Zhu Hui-Hui Xia Shang Qian Men-Bao Nguyen Hung Manh Sripa Banchob Sayasone Somphou Khieu Virak Bergquist Robert Zhou Xiao-Nong School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai China One Health center Shanghai Jiao Tong University The University of Edinburgh Shanghai China National Institute of Parasitic diseases at Chinese center for Disease Control and Prevention (Chinese center for Tropical diseases research) NHC Key Laboratory of Parasites and Vectors Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases Shanghai China Institute of Ecology and Biological Resources Graduate University of Science and Technology Vietnam Academy of Science and Technology Hoang Quoc Viet Street Hanoi Vietnam WHO Collaborating Centre for research and Control of Opisthorchiasis (Southeast Asian liver Fluke Disease) Tropical Disease Research Laboratory Department of Tropical Medicine Faculty of Medicine Khon Kaen University Mittraparb Road Khon Kaen Thailand Lao Tropical and Public Health Institute Ministry of Health Vientiane Lao PDR National Centre for Parasitology Entomology and Malaria Control Ministry of Health Phnom Penh Cambodia Ingerod Brastad Sweden (formerly at the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases) World Health Organization Geneva Switzerland

Background Clonorchiasis and opisthorchiasis, caused by the liver flukesClonorchis sinensis andOpisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.Methods We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes.Results Our analysis revealed that the endemic range ofC. sinensis andO. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identifiedC. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast,O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries ofC. sinensis andO. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap.Conclusions Our findings

关键词： liver fluke Clonorchiasis Opisthorchiasis Clonorchis sinensis Opisthorchis viverrine Southeast Asia Machine learning Ecological study

Astragaloside IV Alleviates Acute liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

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Infectious Microbes & diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses rapidly.The following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation regulation.Mice were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV group.Biochemical analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS ex-posure.Astragaloside IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating au-tophagy.Furthermore,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two groups.These data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 119-134页

作者： Wenyi Chen Feiyan Lin Xudong Feng Qigu Yao Yingduo Yu Feiqiong Gao Jiahang Zhou Qiaoling Pan Jian Wu Jinfeng Yang Jiong Yu Hongcui Cao Lanjuan Li State Key Laboratory for the Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury diseases of Zhejiang Province Hangzhou 310003China

Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.

关键词： Mesenchymal stem cell Exosomes Primary sclerosing cholangitis Fibrosis Organoids Th17

Epidemiological survey of cystic echinococcosis in southwest China:From the Qinghai-Tibet plateau to the area of Yunnan

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World Journal of Hepatology 2024年第2期16卷 229-240页

作者： Jin-Rong Zi Dan Xiao Jia Peng Fang-Wei Wu Jian-Xiong Li Xin-Liu Yan Zheng-Qing Wang Xuan Cai Qian Xu Ben-Fu Li Ya-Ming Yang Yunnan Provincial center of Malaria research Yunnan Institute of Parasitic DiseasesPuer 665000Yunnan ProvinceChina Yunnan Institute of Parasitic diseases Yunnan Institute of Parasitic DiseasesPuer 665000Yunnan ProvinceChina Tibet center for Disease Control and Prevention Tibet Center for Disease Control and PreventionLhasa 85000Tibet Autonomous RegionChina Yunnan Provincial center of Malaria research Yunnan Institute of Parasitic DiseasesPuer 655000Yunnan ProvinceChina

BACKGROUND Echinococcosis is prevalent in 9 provinces in Western and Northern China.An epidemiological survey of echinococcosis in 2012 and 2016 showed cases of echinococcosis in Yunnan Province.AIM To understand the spatial distribution and epidemiological characteristics of echinococcosis in Yunnan for the prevention and control of echinococcosis and to reduce the risk of infection in Yunnan Province.METHODS Based on the China Information System for Disease Control and Prevention(CISDCP),echinococcosis cases reported from 36 hospitals and 34 centers for Disease Control were investigated and epidemiologically analyzed from 2021 to 2022.The exclusion criteria included suspected cases,same case only counted once and cases not from Yunnan.A total of 705 cases were investigated,of which 397 cases were suitable for statistical analysis.In these 397 cases,epidemiological investigation was tracked in 187 cases.All data were inputted using double entry in the Excel database,with error correction by double-entry comparison.The data on echinococcosis cases in Yunnan Province were analyzed by ArcGIS 10.1 software to generate a density map of echinococcosis distribution.All statistical analyses were conducted using SPSS 17.0,including the chi-square test,linear regression test and logistic univariate and multivariate regression analyses.RESULTS A total of 397 cases were found in 89 counties in Yunnan Province.The number of cases in the top three prefectures were Dali(38.1%),Diqing(10.1%),and Kunming(8.3%),and the top five counties were Jianchuan(9.1%),Shangri La(8.3%),Eryuan(7.6%),Heqing(6.9%),and Dali Districts(5.0%).There were significant differences between the different areas.The case reporting rate by CISDCP(33.8%)was low;the first case was reported by CISDCP in 2002,and the highest number of cases was 50(2017).Confirmed and clinical cases accounted for 62.5%and 37.5%,respectively.However,90.9%of the cases of hydatid disease were reported by the hospital system,and only 9.1%of the cases of hydatid disease were found in

关键词： Echinococcosis Cases Epidemiological analysis Yunnan province