Biomedicine & Pharmacotherapy最新文献

{"title":"Effect of recombinant CYP3A4 variants and interaction on imatinib metabolism in vitro","authors":"Jie Chen ,&nbsp;Yingying Hu ,&nbsp;Jinyu Hu ,&nbsp;Zhize Ye ,&nbsp;Qianmeng Lin ,&nbsp;Jian-ping Cai ,&nbsp;Guo-xin Hu ,&nbsp;Ren-ai Xu","doi":"10.1016/j.biopha.2024.117511","DOIUrl":"10.1016/j.biopha.2024.117511","url":null,"abstract":"<div><div>The aim of this study was to investigate the catalytic activity of 26 Cytochrome P450 3A4 (CYP3A4) variants and drug interactions on imatinib metabolism in recombinant insect microsomes. This study was designed with an appropriate incubation system and carried out in the constant temperature water. By using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to measure the quantities of its metabolite <em>N</em>-desmethyl imatinib, to elucidate the impacts of the CYP3A4 genetic polymorphism and drug interactions on the metabolism of imatinib. Consequently, as compared to CYP3A4.1, the intrinsic clearance (CL_int) values of the variations were dramatically changed, rising from 2.34 % to 120.57 %. CYP3A4.14 showed an increase in CL_int in comparison to CYP3A4.1, and the remaining 24 variants demonstrated decreases in catalytic activity for the metabolism of imatinib. In addition, the metabolism of imatinib was decreased to varied degrees by ketoconazole, itraconazole, and fluconazole in CYP3A4.1 and CYP3A4.18. Moreover, most of CYP3A4 variants showed similar trend of enzyme activity under different substrates of imatinib and cabozantinib, except 6 variants (CYP3A4.3,.4,.10,.15,.29 and.31). The first study of the effects of 26 CYP3A4 variants on imatinib metabolism will contribute to the clinical evaluation of imatinib and help personalize therapy in clinical settings.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117511"},"PeriodicalIF":6.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway","authors":"Xingyue He ,&nbsp;Mingdian Wu ,&nbsp;Likun Chen ,&nbsp;Meijun Liu ,&nbsp;Xuan Hu ,&nbsp;Ying Meng ,&nbsp;Hao Yue ,&nbsp;Xiaoshan Yang ,&nbsp;Peng Zheng ,&nbsp;Yulin Dai","doi":"10.1016/j.biopha.2024.117506","DOIUrl":"10.1016/j.biopha.2024.117506","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a major cause of mortality and morbidity worldwide. Beyond thrombolysis, strategies targeting anti-oxidative apoptosis and angiogenesis are considered prospective therapeutic strategies. Nevertheless, existing natural and clinical remedies have limited efficacy in the management of IS. Moreover, despite their millennial legacy of IS remediation, natural remedies such as ginseng incur high production costs. The novel glycopeptide APMCG-1, extracted from mountain-cultivated ginseng dregs in our previous study, is a potent therapeutic candidate for IS. This study investigated APMCG-1's remedial mechanisms against IS injury using an H₂O₂-induced oxidative stress paradigm in human umbilical vein endothelial cells (HUVECs) emulating ischemic endothelial cells, in a ponatinib-induced zebrafish IS model, and in rat middle cerebral artery occlusion (MCAO) prototypes. Cellular assays confirmed the proficiency of APMCG-1 in preventing oxidative stress and cell death, fostering regeneration, and facilitating neovascularization within the H₂O₂-stressed HUVECs framework. Moreover, APMCG-1 augmented hemodynamic velocity, oxidative stress mitigation, apoptosis reduction, and motor enhancement in a zebrafish model of IS. In MCAO rats, APMCG-1 ameliorated neurological deficits and cerebral injury, as evidenced by increased neurological scores and diminished infarct dimensions. In cells and animal models, APMCG-1 activated the PI3K/AKT signaling pathway, modulating factors such as Nrf2, Bcl-2, Caspase 3, eNOS, and VEGFA, thereby ameliorating cellular oxidative distress and catalyzing angiogenesis. Collectively, these results demonstrate the potential protective effects of APMCG-1 in IS pharmacotherapy and its prospective utility as an herbal-derived IS treatment modality.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117506"},"PeriodicalIF":6.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New peripherally-restricted CB1 receptor antagonists, PMG-505–010 and −013 ameliorate obesity-associated NAFLD and fibrosis","authors":"Hyekyung Yang ,&nbsp;Miey Park ,&nbsp;Ji Hye Lee ,&nbsp;Bokyoung Kim ,&nbsp;Chang Sang Moon ,&nbsp;Suyeal Bae ,&nbsp;Younghoon Kim ,&nbsp;Hae-Jeung Lee ,&nbsp;Cheol-Young Park","doi":"10.1016/j.biopha.2024.117501","DOIUrl":"10.1016/j.biopha.2024.117501","url":null,"abstract":"<div><div>The endocannabinoid system plays a crucial role in metabolic regulation, prompting the investigation of cannabinoid type 1 receptor (CB1R) antagonists for obesity and its complications like non-alcoholic fatty liver disease (NAFLD). Concerns over psychiatric side effects led to the development of peripheral CB1R antagonists that circumvent the blood-brain barrier (BBB). In this study, we synthesized PMG-505–010 and PMG-505–013 as peripherally restricted CB1 receptor antagonists by modifying rimonabant to minimize BBB penetration. Physicochemical analysis confirmed their reduced lipophilicity and increased polarity compared to rimonabant, indicating limited brain exposure. Molecular docking studies revealed similar binding modes to rimonabant at CB1R, characterized by robust hydrophobic interactions. Functionally, they acted as CB1R antagonists and inverse agonists, effectively reversing CP55,940-induced cAMP inhibition. In a murine model of obesity-related NAFLD, PMG-505–010 and −013 improved metabolic profiles, including fasting blood glucose levels and dyslipidemia. They also ameliorated hepatic injury, steatosis, and inflammation, evidenced by reduced liver enzymes, lipid peroxidation, hepatic lipid levels, and inflammatory cytokine levels. Notably, these compounds inhibited hepatic fibrosis by reducing extracellular matrix (ECM) deposition and altering fibrosis-related gene and protein expressions. In conclusion, PMG-505–010 and PMG-505–013 hold promise for treating obesity-related liver diseases, including NAFLD and fibrosis, through selective peripheral CB1R targeting, potentially avoiding CNS-related side effects seen with earlier CB1R antagonists.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117501"},"PeriodicalIF":6.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands","authors":"Anna Drzazga ,&nbsp;Przemysław Bernat ,&nbsp;Adriana Nowak ,&nbsp;Marcin Szustak ,&nbsp;Eliza Korkus ,&nbsp;Edyta Gendaszewska-Darmach ,&nbsp;Maria Koziołkiewicz","doi":"10.1016/j.biopha.2024.117467","DOIUrl":"10.1016/j.biopha.2024.117467","url":null,"abstract":"<div><div>Commensal microbiota is crucial for nutrient digestion and production of biologically active molecules, many of which mimic endogenous ligands of human GPCRs. <em>Bacteroides</em> spp. are among the most abundant bacteria residing in the human gut and their absence has been positively correlated with metabolic disorders. In the present study, we focused on <em>N-</em>acylated glycines (NAGlys) as products of <em>Bacteroides</em> spp. and potential GPCR ligands modulating GLP-1 secretion. Representative strains of the most abundant commensal <em>Bacteroides</em> were cultured in either yeast- or animal-based nutrient broths. The broths post-culture were investigated in terms of the contents of NAGlys and stimulatory effects towards GLP-1 production in GLUTag and NCI-H716 cell lines. Pure preparations of the detected NAGlys were further studied to evaluate stimulation of GLP-1 production and related cellular signalling evoked. The most potent NAGlys were also tested as ligands of key lipid GPCRs involved in the regulation of carbohydrate metabolism: GPR40/FFAR1, GPR55, GPR119, and GPR120/FFAR4. We found that <em>Bacteroides</em> potentiate GLP-1 production, depending on the strain and provided nutrient mix<em>.</em> Long-chain unsaturated oleoyl and arachidonoyl glycines, produced by <em>B. thetaiotaomicron</em> and <em>B. intestinalis</em> in the animal-based broth<em>,</em> were particularly effective in stimulation of GLP-1 secretion<em>.</em> They served as agonists of all the receptors under study expressed in GLP-1-producing cells. The obtained results broaden the knowledge of microbial signalling molecules and their role in regulation of carbohydrate homeostasis. They also emphasise the importance of balanced diet as a source of building blocks for commensal bacteria to produce efficient agonists of lipid GPCRs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117467"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species","authors":"Jacqueline S. Womersley ,&nbsp;Clémence Obellianne ,&nbsp;Audrey E. Padula ,&nbsp;Marcelo F. Lopez ,&nbsp;William C. Griffin ,&nbsp;Lauren E. Ball ,&nbsp;Stefano Berto ,&nbsp;Kathleen A. Grant ,&nbsp;Danyelle M. Townsend ,&nbsp;Joachim D. Uys ,&nbsp;Patrick J. Mulholland","doi":"10.1016/j.biopha.2024.117514","DOIUrl":"10.1016/j.biopha.2024.117514","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is the most prevalent substance use disorder but there is incomplete knowledge of the underlying molecular etiology. Here, we examined the cytosolic proteome from the nucleus accumbens core (NAcC) of ethanol drinking rhesus macaques to identify ethanol-sensitive signaling proteins. The targets were subsequently investigated using bioinformatics, genetic, and pharmacological manipulations in mouse models of ethanol drinking. Of the 1000+ cytosolic proteins identified in our screen, 50 proteins differed significantly between control and ethanol drinking macaques. Gene Ontology analysis of the differentially expressed proteins identified enrichment in pathways regulating metabolic processes and proteasome activity. Because the family of Glutathione S-transferases (GSTs) was enriched in these pathways, validation studies targeted GSTs using bioinformatics and genetically diverse mouse models. <em>Gstp1</em> and <em>Gstm2</em> were identified in Quantitative Trait Loci and published gene sets for ethanol-related phenotypes (e.g., ethanol preference, conditioned taste aversion, differential expression), and recombinant inbred strains that inherited the C57BL/6J allele at the <em>Gstp2</em> interval consumed higher amounts of ethanol than those that inherited the DBA/2J allele. Genetic deletion of <em>Gstp1/2</em> led to increased ethanol consumption without altering ethanol metabolism or sucrose preference. Administration of the pharmacologic activator of Gstp1/2, carnosic acid, decreased voluntary ethanol drinking. Proteomic analysis of the NAcC cytosolic of heavy drinking macaques that were validated in mouse models indicate a role for glutathione-mediated redox regulation in ethanol-related neurobiology and the potential of pharmacological interventions targeting this system to modify excessive ethanol drinking.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117514"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of chemotherapy-induced peripheral neuropathy by JZL195 through glia and the endocannabinoid system","authors":"Leejeong Kim ,&nbsp;Guanghai Nan ,&nbsp;Hee Young Kim ,&nbsp;Myeounghoon Cha ,&nbsp;Bae Hwan Lee","doi":"10.1016/j.biopha.2024.117515","DOIUrl":"10.1016/j.biopha.2024.117515","url":null,"abstract":"<div><div>Chemotherapy-induced peripheral neuropathy (CIPN) used to treat cancer, is a significant side effect with a complex pathophysiology, and its mechanisms remain unclear. Recent research highlights neuroinflammation, which is modulated by the endocannabinoid system (ECS) and associated with glial activation, and the role of toll-like receptor 4 (TLR4) in CIPN. This study aimed to investigate the effects of JZL195, an inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and explore the connection between cannabinoid receptors and TLR4 in glial cells. A CIPN animal model was developed using cisplatin-injected male C57BL/6 mice. Mechanical and cold allodynia were assessed through von Frey and acetone tests. Western blot analysis was used to examine the expression of catabolic enzymes, cannabinoid receptors, glial cells, and neuroinflammatory factors in the dorsal root ganglia (DRGs) and spinal cord. Immunohistochemistry was used to investigate the colocalization of cannabinoid receptors and TLR4 in glial cells. JZL195 alleviated pain by inhibiting FAAH/MAGL, modulating the ECS and neuroinflammatory factors, and suppressing glial cell activity. Additionally, cannabinoid receptors and TLR4 colocalized with astrocytes and microglia in the spinal cord. This study highlights the therapeutic potential of JZL195 in modulating the ECS and suggests a correlation between cannabinoid receptors and TLR4 in spinal glial cells, providing insight into alleviating pain and neuroinflammation in CIPN.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117515"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stapled peptides as potential therapeutics for diabetes and other metabolic diseases","authors":"Dominika Nielipińska ,&nbsp;Dominika Rubiak ,&nbsp;Agnieszka J. Pietrzyk-Brzezińska ,&nbsp;Joanna Małolepsza ,&nbsp;Katarzyna M. Błażewska ,&nbsp;Edyta Gendaszewska-Darmach","doi":"10.1016/j.biopha.2024.117496","DOIUrl":"10.1016/j.biopha.2024.117496","url":null,"abstract":"<div><div>The field of peptide drug research has experienced notable progress, with stapled peptides featuring stabilized α-helical conformation, emerging as a promising field. These peptides offer enhanced stability, cellular permeability, and binding affinity and exhibit potential in the treatment of diabetes and metabolic disorders. Stapled peptides, through the disruption of protein-protein interactions, present varied functionalities encompassing agonism, antagonism, and dual-agonism. This comprehensive review offers insight into the technology of peptide stapling and targeting of crucial molecular pathways associated with glucose metabolism, insulin secretion, and food intake. Additionally, we address the challenges in developing stapled peptides, including concerns pertaining to structural stability, peptide helicity, isomer mixture, and potential side effects.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117496"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sea cucumber-derived extract can protect skin cells from oxidative DNA damage and mitochondrial degradation, and promote wound healing","authors":"Bismoy Mazumder ,&nbsp;Meng Lu ,&nbsp;Hassan Rahmoune ,&nbsp;Ana Fernandez-Villegas ,&nbsp;Edward Ward ,&nbsp;Min Wang ,&nbsp;Jiaoyan Ren ,&nbsp;Yi Yu ,&nbsp;Ting Zhang ,&nbsp;Ming Liang ,&nbsp;Wenzhi Li ,&nbsp;Nino F. Läubli ,&nbsp;Clemens F. Kaminski ,&nbsp;Gabriele S. Kaminski Schierle","doi":"10.1016/j.biopha.2024.117466","DOIUrl":"10.1016/j.biopha.2024.117466","url":null,"abstract":"<div><div>Our skin serves as the primary barrier against external environmental insults, the latter of which can cause oxidative stress within cells, while various bioactive peptides sourced from natural resources hold promise in protecting cells against such oxidative stress. In this study, we investigate the efficacy of a low molecular weight extract from the sea cucumber <em>Apostichopus japonicus</em>, denoted as Sample-P, in facilitating cell migration and wound healing under oxidative stress conditions in skin cells. The naturally derived compound is a highly complex mix of peptides exhibiting antioxidative properties, as highlighted through liquid chromatography-mass spectrometry peptide screening and an <em>in vitro</em> antioxidant assay. Our results demonstrate that Sample-P is capable of promoting cell migration while preventing severe stress responses such as visible through mTOR expression. To further identify the molecular pathways underpinning the overall protective mechanism of Sample-P, we have utilised a proteomics approach. Our data reveal that Sample-P regulates protein expression associated with ribosomal pathways, glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum (ER), which help in preserving DNA integrity and safeguarding cellular organelles, such as mitochondria and the ER, under oxidative stress conditions in skin cells. In summary, in the presence of H₂O₂, Sample-P exhibits antioxidative properties at both molecular and cellular levels, rendering it a promising candidate for topical skin treatment to wound healing and to address age-related skin conditions.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117466"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Wnt signaling pathway in hepatocellular carcinoma: Regulatory mechanisms and therapeutic prospects","authors":"Shihui Ma,&nbsp;Guorui Meng,&nbsp;Tong Liu,&nbsp;Junqi You,&nbsp;Risheng He,&nbsp;Xudong Zhao,&nbsp;Yunfu Cui","doi":"10.1016/j.biopha.2024.117508","DOIUrl":"10.1016/j.biopha.2024.117508","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117508"},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of hepatocyte-derived extracellular vesicles in liver and extrahepatic diseases","authors":"Shihui Li ,&nbsp;Fang Cheng ,&nbsp;Zhuan Zhang ,&nbsp;Ruizi Xu ,&nbsp;Honglei Shi ,&nbsp;Yongmin Yan","doi":"10.1016/j.biopha.2024.117502","DOIUrl":"10.1016/j.biopha.2024.117502","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are vesicle-like bodies with a double membrane structure that are released from the cell membrane or secreted by cells into the extracellular environment. These include exosomes, microvesicles, and apoptotic bodies. There is growing evidence indicating that the composition of liver cell contents changes following injury. The quantity of EVs and the biologically active substances they carry vary depending on the condition of the liver cells. Hepatocytes utilize EVs to modulate the functions of different liver cells and transfer them to distant organs via the systemic circulation, thereby playing a crucial role in intercellular communication. This review provides a concise overview of the research on the effects and potential mechanisms of hepatocyte-derived EVs (Hep-EVs) on liver diseases and extrahepatic diseases under different physiological and pathological conditions. Common liver diseases discussed include non-alcoholic fatty liver disease (NAFLD), viral hepatitis, alcoholic liver disease, drug-induced liver damage, and liver cancer. Given that NAFLD is the most prevalent chronic liver disease globally, this review particularly highlights the use of hepatocyte-derived EVs in NAFLD for disease progression, diagnosis, and treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117502"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}