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Journal of Environmental Sciences 2024年第3期137卷 604-614页

作者： Di Wu Xing Lu Li-Xue Dong Juan Tian Jin Deng Lei Wei Hua Wen Shan Zhong Ming Jiang School of Basic Medical Sciences Wuhan UniversityWuhan 430071China Key Laboratory of Freshwater Biodiversity Conservation Ministry of Agriculture and Rural AffairsYangtze River Fisheries Research InstituteChinese Academy of Fishery SciencesWuhan 430223China Hubei Province Key Laboratory of Allergy and Immunology Wuhan 430071China

Microplastics(MPs)have become a significant concern for their potential ***,the correlation between the size of plastic particles and their toxicity remains ***,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm *** U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm *** gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm *** analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm *** conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver *** the above lay the foundation for further study on the pathological damage of MPs to other organisms.

关键词： Microplastics(MPs) Intestinal toxicity liver toxicity Gut microbiome Lipid metabolism

Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing

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Journal of Environmental Sciences 2024年第11期145卷 164-179页

作者： Yunmeng Bai Yali Song Miaoran Li Jinhuan Ou Hong Hu Nan Xu Min Cao SiyuWang Lin Chen Guangqing Cheng Zhijie Li Gang Liu Jigang Wang Wei Zhang Chuanbin Yang Dongguan Maternal and Child Health Care Hospital Postdoctoral Innovation Practice Base of Southern Medical UniversityDongguan 523125China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Division of Thyroid and Breast Surgery Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Faculty of Brain Sciences University College LondonWC1E 6BTUK State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public ***-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic ***-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and ***,the underlying mechanisms of MCLR-induced liver toxicity are ***,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in *** established the first single-cell atlas ofmouse livers in response to *** results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly *** analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to ***,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory ***,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and ***,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver *** findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

关键词： MC-LR liver toxicity Single-cell RNA sequencing Immune response Inflammatory responses

Herbal and dietary supplement induced liver injury:Highlights from the recent literature

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World Journal of Hepatology 2021年第9期13卷 1019-1041页

作者： Stephanie M Woo William D Davis Soorya Aggarwal Joseph W Clinton Sara Kiparizoska James H Lewis Department of Internal Medicine MedStar Georgetown University HospitalWashingtonDC 20007United States Department of Gastroenterology MedStar Georgetown University HospitalWashingtonDC 20007United States

Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the *** extensive literature review was conducted encompassing September 2019 through March *** with clinically significant findings were analyzed and included in this *** emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method *** review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal *** described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were *** has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular *** also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug *** highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

关键词： Herbal-induced liver injury Dietary supplement-induced liver injury Druginduced liver injury Roussel Uclaf Causality Assessment Method Hepatotoxicity liver toxicity

Ethanol promotes saturated fatty acid-induced hepatoxicity through endoplasmic reticulum(ER) stress response

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Chinese Journal of Natural Medicines 2015年第4期13卷 250-256页

作者： YI Hong-Wei MA Yu-Xiang WANG Xiao-Ning WANG Cui-Fen LU Jian CAO Wei WU Xu-Dong Department of Pharmacology Medical School Southeast University State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Center for Diagnostic Nanosystems Marshall University

Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in ***(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.

关键词： Ethanol(Et OH) Palmitic acid(PA) ER stress CHOP knockout liver toxicity

Commentary:Indirect action pattern:A remote and cross-organ pharmacological mechanism for drug innovation

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3448-3450页

作者： Yuan Gao Jia-bo Wang School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China

The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.

关键词： Cross-organ Indirect action pattern Phosphatidic acid liver toxicity IL-6 Epididymal white adipose tissue

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第8期14卷 331-340页

作者： Nahid Ghaedi Iran Pouraboli Mansour Mirtadzadini Mohammad-mehdi Moeini-aghtaie Department of Biology Faculty of SciencesShahid Bahonar University of KermanKermanIran Department of Pathology Pathology and Stem Cell Research CenterAfzalipour Medical FacultyKerman University of Medical SciencesKermanIran

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced ***:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and ***,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were ***:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde *** results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale ***,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and ***:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.

关键词： Levisticum officinale CCl4 Inflammation liver toxicity Antioxidant

Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy

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Gastroenterology Report 2020年第1期8卷 25-30,I0001页

作者： Eva Rajha Patrick Chaftari Mona Kamal Julian Maamari Christopher Chaftari Sai-Ching Jim Yeung Department of Emergency Medicine The University of Texas MD Anderson Cancer CenterHoustonTXUSA Schoool of Medicine Lebanese American UniversityByblosLebanon Biomedical Engineering College of EngineeringTexas A&M UniversityCollege StationTXUSA

Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer,supported by favorable outcomes and good ***,it is linked to multiple immune manifestations,referred to as immune-related adverse events(irAEs).These adverse events frequently affect the skin,colon,endocrine glands,lungs,and *** gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from ***,because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs,many health-care providers remain unfamiliar with the management of *** involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain,diarrhea,and other nonspecific symptoms that may be challenging to *** article reviews the gastrointestinal,hepatic,and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended *** also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.

关键词： immune checkpoint inhibitor immune-related adverse events colitis enterocolitis liver toxicity pancreatic toxicity

Statins in Alcoholic and Non-Alcoholic Fatty liver Disease and Chronically Elevated liver Enzymes

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International Journal of Clinical Medicine 2022年第7期13卷 229-252页

作者： Arigapudi Aishwarya Oroszi Terry Boonshoft School of Medicine Wright State University Dayton USA

The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased with arisen due to alcohol consumption and obesity. The diagnosis plays a crucial role in treating such conditions based on the stages of liver functioning. The elevated liver enzymes are the key characterizing of identifying the alcoholic liver disease (ALD) and NAFLD. Later on, there is a progression of the disease conditions by developing fibrosis and cirrhosis, leading to liver carcinoma. The other state, steatohepatitis, is associated with an increase in liver-related and can lead to mortality. Risk factors for both diseases are growing, leading to various complications in health. There is no specific treatment up to date for these conditions, but statins play a crucial role in managing several liver disease conditions. The commonly used drug is hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors. It is also known as statins, which help normalize liver enzymes in patients with elevated plasma aminotransferases. As a result, external liver damage is considered safe for the liver as the Statin medication at low to moderate dose usage. OBJECTIVES: The main scope of this review is to study the various factors like pharmacological actions, adverse events, and biochemical and liver cell imaging results in patients with ALD and NAFLD. The different types of statins used in alcoholic and non-alcoholic patients’ clinical data for the safety of the statin therapy were concluded in this review. Fatty liver changes of both liver disease conditions were studied using different drugs. The other liver enzymes like Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl Transferase (GGT), and the effectiveness of Statin therapy are considered vital concepts in this review.

关键词： Statin Therapy liver Enzymes Alcohol Steatosis Fibrosis Hepatocellular Carcinoma liver toxicity Steatohepatitis

Hepatobiliar manifestations in inflammatory bowel disease: A practical approach

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World Journal of Hepatology 2022年第2期14卷 319-337页

作者： Paulina Núñez F Fabiola Castro Gabriel Mezzano Rodrigo Quera Diego Diaz Lorena Castro Universidad de los Andes Inflammatory Bowel Disease ProgramDigestive Disease CenterSantiago 7600976RMChile Inflammatory Bowel Disease Program Hospital San Juan de DiosUniversidad de ChileSantiago 7701230RMChile Universidad de los Andes Hepatology ProgramDigestive Disease CenterSantiago 7600976RMChile Department of Gastroenterology Hospital del Salvador/Universidad de ChileSantiago 7600976RMChile Universidad de los Andes Santiago 770976RMChile

Inflammatory bowel diseases(IBD)are associated with various hepatobiliary *** can occur at any moment in the course of the disease or associated with the *** prevalence of liver dysfunction can reach up to 50%in different *** fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most *** of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with *** medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.

关键词： Extraintestinal manifestations Inflammatory bowel disease Sclerosing primary cholangitis Hepatic steatosis liver toxicity

Network pharmacology-based analysis of the mechanism of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity

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Gastroenterology & Hepatology Research 2022年第1期4卷 19-24页

作者： Heng Xu Yaqi Zhang Huan Chen Tengfei Bai School of Life Sciences Beijing University of Traditional Chinese MedicineBeijingChina100029 College of Traditional Chinese Medicine Hebei UniversityBaodingHebeiChina071000.

Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network ***:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced *** possible mechanism of action was analyzed in terms of ***:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced *** process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of *** components(CC terms)mainly involved cytosol and membrane *** function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and ***:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.

关键词： Radix Paeoniae Alba Toosendan Fructus liver toxicity network pharmacology compatibility