Cell and Bioscience最新文献

{"title":"A review of the 661W cell line as a tool to facilitate treatment development for retinal diseases.","authors":"Alicia A Brunet, Rebekah E James, Petria Swanson, Livia S Carvalho","doi":"10.1186/s13578-025-01381-2","DOIUrl":"10.1186/s13578-025-01381-2","url":null,"abstract":"<p><p>Retinal diseases encompass a diverse group of disorders that affect the structure and function of the retina, leading to visual impairment and, in some cases, irreversible vision loss. The investigation of retinal diseases is crucial for understanding their underlying mechanisms, identifying potential therapeutic targets, and developing effective treatments. The use of in vitro cell models has become instrumental in advancing our knowledge of these disorders, but given that these conditions usually affect retinal neuronal cell types, access to appropriate cell models can be potentially challenging. Among the available in vitro cell models, the 661W cone-like cell line has emerged as a valuable tool for studying various retinal diseases, ranging from monogenic conditions, such as inherited retinal diseases, to complex conditions such as age-related macular degeneration (AMD), diabetic retinopathy, amongst others. Developed from immortalized murine photoreceptor cells, and freely available for academics from its creator, the 661W cell line has offered visual scientists and clinicians around the world a reliable and well-characterised platform for investigating disease pathogenesis, exploring disease-specific molecular signatures, and evaluating potential therapeutic interventions. This review aims to provide an overview of the 661W cell line and its applications in the study of both inherited and acquired retinal diseases. By examining the applications and limitations of this unique cell line, we may gain valuable insights into its contributions in unravelling the complexities of retinal diseases and its potential impact on the development of novel treatments for these diseases.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"41"},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of OBSCN expression promotes bladder cancer progression but enhances the efficacy of PD-L1 inhibitors.","authors":"Tao Wang, Tuanjie Guo, Juanjuan Sun, Xinyue Zang, Lei Dong, Jian Zhang, Siteng Chen, Guihua Chen, Sicong Ma, Xinyu Zhai, Chuanmin Chu, Chaofu Wang, Xiang Wang, Dongliang Xu, Mingyue Tan","doi":"10.1186/s13578-025-01379-w","DOIUrl":"10.1186/s13578-025-01379-w","url":null,"abstract":"<p><strong>Background: </strong>As the objective overall response rate to immune checkpoint inhibitors (ICIs) is less than 30% in late stage or metastatic bladder cancer (BLCA), elucidating the intrinsic mechanisms of immune evasion is of great importance for the discovery of predictive and prognostic biomarkers and the exploration of novel targets for intervention. Recent studies have shown that OBSCN and the cytoskeletal protein it encodes, obscurin, play an important role in tumour progression. However, no studies have reported the role of OBSCN in BLCA.</p><p><strong>Methods: </strong>RNA sequencing and clinical data were downloaded from multiple public databases including The Cancer Genome Atlas and the Gene Expression Omnibus. Immunohistochemistry (IHC) was performed on tissue microarrays including 80 BLCA patients from Shuguang Hospital. Kaplan-Meier curves with log-rank test, univariate and multivariate COX regression were performed to evaluate the prognostic efficacy of OBSCN expression. In vitro experiments were conducted to determine the role of OBSCN deficiency in promoting BLCA progression. Pan-cancer tumour immune microenvironment (TIME) analysis was performed to explore the potential correlation between OBSCN deficiency and immune evasion.</p><p><strong>Results: </strong>Pan-cancers and single-cell sequencing analysis revealed that the expression level and proportion of OBSCN was significantly decreased in BLCA cells compared to normal urothelium. Survival curves showed that BLCA patients with low OBSCN expression had a worse prognosis, yet a better clinical response to PD-L1 ICIs. Gene set variation analysis and Gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) and immune-related processes were significantly enriched in BLCA samples with low OBSCN expression. In vitro experiments identified that OBSCN-deficient BLCA cells enhanced invasion, migration and EMT. Pan-cancer analysis of TIME revealed that neoantigen, tumor mutation burden, CD8⁺T cells and immune checkpoints were significantly negatively associated with OBSCN expression. IHC and Western blot assay identified that BLCA samples with low OBSCN expression had more CD8⁺ T-cell infiltration and higher PD-L1 expression.</p><p><strong>Conclusions: </strong>This study confirmed that BLCA patients with low OBSCN expression had a worse prognosis but a superior response to ICIs, providing a reference for individualised treatment of BLCA patients.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"40"},"PeriodicalIF":6.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.","authors":"Xuepeng Wen, Kaixue Si, Dantong Zhu, Anqi Zhang, Changyou Guo, Minghui Li, Weiming Tian","doi":"10.1186/s13578-025-01377-y","DOIUrl":"10.1186/s13578-025-01377-y","url":null,"abstract":"<p><strong>Background: </strong>ABCC4 (ATP-binding cassette sub-family C member 4) is a transporter protein that is primarily localized to the plasma membrane, and its efflux activity is associated with the progression of various cancers and the development of drug resistance. Cyclic adenosine monophosphate (cAMP) is an important biomolecule that is considered a transport substrate of ABCC4. However, there is currently no direct structural understanding of how ABCC4 binds cAMP, and the mechanisms by which it recognizes a diverse range of substrate ligands remain poorly understood. Some studies have indicated that, under physiological conditions, cAMP does not significantly stimulate the ATPase activity of ABCC4, making the commonly used ATPase activity assays for ABC proteins unsuitable for studying cAMP.</p><p><strong>Results: </strong>Here, we successfully resolved the cryo-electron microscopy (cryo-EM) structure of the human ABCC4-cAMP (hABCC4-cAMP) complex, revealing how hABCC4 binds to cAMP and identifying the key residues involved. This structure was compared with two other hABCC4 complex structures we obtained (Methotrexate and Prostaglandin E₂) and with previously published structures. We discovered some new structural insights into how hABCC4 binds ligands. On the basis of the structural information obtained, we confirmed the feasibility of using 8-[Fluo]-cAMP in a transport assay to detect cAMP translocation and found that some challenges remain to be addressed.</p><p><strong>Conclusions: </strong>These results suggest that hABCC4 can bind cAMP and exhibits varying degrees of flexibility when binding with different substrates, including cAMP. These findings expand our understanding of the structural biology of ABCC4.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"39"},"PeriodicalIF":6.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer's mouse models.","authors":"Wenjie Hu, Mengting Chen, Yuxue Lin, Hui Zhang, Li Sun, Wei Shao, Yuping Ye, Yujie Cheng, Shanshan Zhou, Panpan Hu, Xingqi Wu, Yin Xu, Kai Wang","doi":"10.1186/s13578-025-01378-x","DOIUrl":"10.1186/s13578-025-01378-x","url":null,"abstract":"<p><strong>Background: </strong>Microglia are brain-resident macrophages that play a crucial role in synapse pruning during the development and progression of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and Alzheimer's disease (AD). Mechanistically, CD47 protein acts as a potent 'do not eat me' signal, protecting synapses from phagocytosis by microglia. However, the functional role of the upregulated neuronal CD47 signal under both physiological and pathological conditions remains unclear.</p><p><strong>Results: </strong>We utilized an adeno-associated virus gene expression system to induce neuron-specific overexpression of CD47 in wild-type and 5xFAD mice, assessing its effects on microglial synaptic phagocytosis and mouse behaviors. Our results indicate that neuronal CD47 induces ASD-like behaviors and synaptic pruning defects, while promoting behavioral disinhibition and improving memory in wild-type mice. Single-nucleus RNA sequencing was employed to profile gene expression patterns in subpopulations of neurons and microglia. Notably, neuronal CD47 enhances synaptic pathways in neurons and particularly shifts microglial subpopulations from a disease-associated state to a homeostatic state. Additionally, neuronal CD47 reduces excessive microglial synaptic phagocytosis induced by Aβ pathology in 5xFAD mice.</p><p><strong>Conclusion: </strong>Our study provides evidence that neuronal CD47 overexpression results in synaptic pruning defects and is involved in the pathogenesis of ASD, while also playing a beneficial role in mitigating excessive synaptic loss in Alzheimer's disease.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"38"},"PeriodicalIF":6.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.","authors":"Chunhua Ma, Kexi Liao, Jing Wang, Tao Li, Liangming Liu","doi":"10.1186/s13578-025-01373-2","DOIUrl":"10.1186/s13578-025-01373-2","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"37"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clusterin deficiency exacerbates cholestatic liver disease through ER stress and NLRP3 inflammasome activation.","authors":"Hye-Young Seo, Ji Yeon Park, So-Hee Lee, Hye Won Lee, Eugene Han, Jae Seok Hwang, Mi Kyung Kim, Byoung Kuk Jang","doi":"10.1186/s13578-025-01376-z","DOIUrl":"10.1186/s13578-025-01376-z","url":null,"abstract":"<p><strong>Background: </strong>Cholestatic liver disease, characterized by impaired bile flow, leads to the accumulation of harmful metabolites and toxins, resulting in liver damage. Inflammatory cytokines are crucial for the progression of this condition. Clusterin is a glycoprotein with roles in cell death, lipid transport, and cellular protection. We previously demonstrated that clusterin protects against hepatic steatosis and hepatic fibrosis. This study explored the roles of clusterin in cholestatic liver injury induced by a DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) diet.</p><p><strong>Methods: </strong>The study evaluated the impact of clusterin on liver injury in C57BL/6 mice and clusterin-knockout (KO) mice fed a DDC diet for 10-20 days. Primary Kupffer cells (KCs) and hepatocytes (HCs) of these mice were analyzed. Techniques such as Sirius red staining, immunohistochemistry, real-time RT-PCR, enzyme-linked immunosorbent assays, and western blotting were performed to assess the effects of clusterin.</p><p><strong>Results: </strong>Clusterin expression was upregulated in the cholestatic liver. Clusterin-KO mice exhibited elevated levels of alanine aminotransferase, aspartate aminotransferase, collagen, and αSMA upon DDC diet-induced liver injury. They also had increased levels of markers of endoplasmic reticulum (ER) stress (CHOP, ATF6, and p-eIF2α) and inflammasome activity (NLRP3, ASC, caspase-1, and interleukin 1 beta (IL1β) protein expression, and IL1β and interleukin 18 secretion). Thapsigargin, an ER stress inducer, heightened NLRP3 inflammasome activation in primary KCs and HCs, which was mitigated by overexpression of clusterin.</p><p><strong>Conclusions: </strong>The absence of clusterin exacerbates ER stress and NLRP3 inflammasome activation in mice fed a DDC diet. Conversely, overexpression of clusterin suppresses these stress responses. Thus, clusterin deficiency is associated with an enhanced inflammasome response in the liver that is linked to upregulation of ER stress.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"36"},"PeriodicalIF":6.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of structures and inhibition activities of serine protease inhibitors of Trichinella spiralis and Trichinella pseudospiralis.","authors":"Ruixue Li, Bing Zhang, Chen Chen","doi":"10.1186/s13578-025-01375-0","DOIUrl":"10.1186/s13578-025-01375-0","url":null,"abstract":"<p><strong>Background: </strong>Trichinosis is one of the most widespread parasitic infections worldwide. Trichinella spiralis not only infects humans but can also utilize wild anddomestic animals as hosts. The serine protease inhibitors secreted by Trichinella spiralis play a critical role in its invasion and immune evasion. Serpins can effectively inhibit host proteases, although the host can mount a strongimmune response against to these inhibitors.</p><p><strong>Results: </strong>In this study we analyzed the crystal structures of the serine protease inhibitors from Trichinella spiralis and Trichinella pseudospiralis, revealing that both serpins exhibit.structural characteristics typical of serine protease inhibitors. The similarity of both \"breach\" region and \"shutter\" region of the two serpins are very high, but the \"hinge\" region are different, the \"hinge\" of Tp-serpin is closed, while of Ts-serpin was partially inserted into sheet-A, suggesting that Tp-serpin had higher inhibition activity. Using alpha chymotrypsin as Ts-serpin and Tp-serpin protease targets, the two serpins enzyme inhibition activity were measured separately, by measuring the secondary inhibition rate constant, half inhibitory concentration IC50, inhibition of stoichiometric number parameters and confirmed both the serine protease inhibitory activity, and Tp-serpin slightly higher than that of Ts-serpin, but no inhibition activity of P1-P1' mutant.</p><p><strong>Conclusion: </strong>In this study, the mechanism of enzyme inhibition activity of serpin was studied by means of structural biology and biochemistry comprehensively. These discoveries provide a theoretical foundation for a deeper understanding of the inhibition mechanisms of serpins and for the development of new drugs and vaccines against Trichinella spiralis infection.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"35"},"PeriodicalIF":6.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.","authors":"Jing Zeng, Grayson Way, Nan Wu, Xixian Jiang, Yun-Ling Tai, Derrick Zhao, Lianyong Su, Qianhua Yan, Xuan Wang, Emily C Gurley, Phillip B Hylemon, Sayed Obaidullah Aseem, Arun J Sanyal, Jiangao Fan, Huiping Zhou","doi":"10.1186/s13578-025-01362-5","DOIUrl":"10.1186/s13578-025-01362-5","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses various conditions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MASLD is a significant risk factor for hepatocellular carcinoma (HCC) and is rapidly becoming the primary cause of liver transplantation. Dysregulated sphingolipid metabolism has been linked to the development of MASH-HCC. However, detailed insight into the sphingolipid profiles and cell type-specific changes in key genes involved in sphingolipid metabolism remains limited and forms the primary focus of this study.</p><p><strong>Approaches & results: </strong>This study used the well-characterized diet-induced MASH-HCC mouse model (DIAMOND). Total RNA sequencing data, NanoString nCounter^® Gene profiling, and single-nucleus RNA sequencing (snRNA-seq) GEO data (GSE225381) were used in characterizing gene regulation in MASH-HCC progression. Sphingolipids in the serum and liver were profiled using targeted lipidomics. RNA data analysis showed dysregulation of key genes involved in sphingolipid metabolism, including ceramide synthase 6 (Cers6), serine palmitoyltransferase long chain base subunit 2 (Sptlc2), sphingosine kinase 2 (SphK2), and sphingosine-1-phosphate receptor 1-3 (S1pr1-3) which paralleled significant changes in sphingolipid composition and levels in both serum and liver. Furthermore, TCGA-LIHC patient data were analyzed and potential prognostic genes for MASH-HCC were identified using univariate and multivariate Cox analysis. The multivariate Cox analysis underscored the prognostic significance of several genes related to sphingolipid metabolism, including CERS6, SPTLC2, and S1PR1.</p><p><strong>Conclusion: </strong>Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"34"},"PeriodicalIF":6.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA binding protein CARHSP1 facilitates tumor growth, metastasis and immune escape by enhancing IL-17RA mRNA stabilization in prostate cancer.","authors":"YiFan Jiang, Yanan Wang, KaiHua Xue, JianBin Ma, Shan Xu, Ke Wang, Peng Guo","doi":"10.1186/s13578-025-01371-4","DOIUrl":"10.1186/s13578-025-01371-4","url":null,"abstract":"<p><strong>Background: </strong>Calcium-regulated heat-stable protein 1 (CARHSP1) has been identified as a cold shock domain (CSD) protein family member, participating in the regulation of ribosomal translation, mRNA degradation, and the rate of transcription termination. However, there is an extremely limited understanding of the function of CARHSP1 as an RNA binding protein (RBP) in prostate cancer (PCa).</p><p><strong>Methods: </strong>The expression pattern of CARHSP1 and the correlation between the CARHSP1 expression and clinical prognosis in PCa patients were analyzed by using multiple public databases. In vitro and in vivo functional assays were conducted to assess the role of CARHSP1. The mechanisms of CARHSP1 function on IL-17RA were identified by RNA pull-down and RNA stability assays. A co-culture model of Jurkat cells and PCa cells was established to investigate the potential role of CARHSP1 in tumor immunity of PCa.</p><p><strong>Results: </strong>CARHSP1 was highly expressed in PCa, and correlated with advanced characteristics of PCa and unfavorable prognosis in PCa patients. Moreover, knockdown of CARHSP1 significantly dampened the capacity of proliferation, migration, invasion, and immune evasion of PCa cells in vitro and in vivo. Mechanistically, the RNA-binding protein CARHSP1 selectively bound to the mRNA of IL-17RA, resulting in the increased expression of both IL-17RA mRNA and protein. Downregulating expression of CARHSP1 shortened the half-life of IL-17RA mRNA and reduced its expression. Subsequently, the downstream pathways of IL-17RA, JAK-STAT3 signaling pathway and NF-κB signaling pathway, were activated by CARHSP1 and contributed to the malignant phenotype of PCa cells.</p><p><strong>Conclusions: </strong>In conclusion, our results demonstrated that the increased expression of CARHSP1 in PCa is correlated with advanced clinical characteristics and unfavorable prognosis, and CARHSP1 may promote the progression of PCa through enhancing the mRNA stability of IL-17RA and activating its downstream pathways. These results suggest that CARHSP1 is an important regulator of tumor microenvironment in PCa, and CARHSP1-IL-17RA axis could be potential novel therapeutic targets for PCa.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"33"},"PeriodicalIF":6.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gram-positive probiotics improves acetaminophen-induced hepatotoxicity by inhibiting leucine and Hippo-YAP pathway.","authors":"Wenkang Gao, Gang Wang, Hang Yuan, Yue Chen, Jiake Che, Zilu Cheng, Liuying Chen, Li Zhang, Yuanqing Zhu, Xin Liu, Ao Liu, Quancheng Yang, Peng Cao, Wei Qian, Weiyan Huang, Bernd Schnabl, Ling Yang, Huikuan Chu","doi":"10.1186/s13578-025-01370-5","DOIUrl":"10.1186/s13578-025-01370-5","url":null,"abstract":"<p><strong>Objectives: </strong>Drug-induced liver injury (DILI) can be improved by modulating gut microbiota. We aimed to investigate a probiotic mixture comprising Bifidobacterium Longum, Streptococcus thermophilus, and Lactobacillus delbrueckii subspecies bulgaricus (BSL) in mitigating acetaminophen induced liver injury (AILI), and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Gut bacterial communities were analyzed in fecal samples from patients with DILI and healthy controls. Mice were pretreated with BSL or PBS for 10 days, then subjected to a single dose of acetaminophen (300 mg/kg) gavage and euthanized 24 h later. Transcriptome sequencing, microbiome, and metabolome sequencing were performed on mouse samples, respectively.</p><p><strong>Results: </strong>Gut bacterial dysbiosis existed in DILI patients, with a decrease in Gram-positive bacteria and an increase in Gram-negative bacteria. A similar situation occurred in AILI mice. Pretreatment of BSL significantly improved APAP-induced disorders of gut bacteria and alleviated hepatic inflammation and necrosis. Transcriptome sequencing showed that BSL inhibited the hepatic damage pathways, such as Hippo and TGF-β signaling pathway. Metabolomic profiling revealed an obvious increase in oligopeptides containing branched-chain amino acids (BCAAs) in AILI mice, whereas these metabolites were significantly negatively correlated with the abundance of BSL, but positively with key genes of Hippo pathway. In vitro experiments showed that leucine exerted a dose-related exacerbation pattern on APAP-mediated hepatocellular injury. Mice supplemented with leucine resulted in the further overexpression of Yes-associated protein, an increase in oxidative stress, and a worsening of AILI.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"32"},"PeriodicalIF":6.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}