Biology Direct最新文献

{"title":"Sigma-1 receptor activation attenuates DOX-induced cardiotoxicity by alleviating endoplasmic reticulum stress and mitochondrial calcium overload via PERK and IP3R-VDAC1-MCU signaling pathways.","authors":"Zixuan Li, Qian Ran, Chuan Qu, Shan Hu, Shengyu Cui, You Zhou, Bo Shen, Bo Yang","doi":"10.1186/s13062-025-00617-y","DOIUrl":"10.1186/s13062-025-00617-y","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is an anthracycline with potent antitumor properties and rare yet serious cardiotoxic side effects that limit its clinical application. The sigma-1 receptor is a stress-triggered chaperone often dysregulated in diseases and has known cardioprotective effects. Although its anti-oxidative stress and anti-apoptotic effects have been demonstrated, its effectiveness in DOX-induced cardiotoxicity has never been explored. This study investigated the potential role of the activated sigma-1 receptor in a DOX-induced murine cardiotoxicity model to elucidate the receptor's mechanism of action.</p><p><strong>Methods: </strong>We established the model in C57BL/6 mice by daily intraperitoneal injections of fluvoxamine (Flv) for 4 consecutive weeks to activate the receptor and by weekly intraperitoneal injections of DOX at 5 mg/kg for 3 weeks. We performed in vitro experiments using cardiomyocytes of neonatal Sprague-Dawley rats to verify the protective effect of the sigma-1 receptor.</p><p><strong>Results: </strong>We found that sigma-1 expression in the heart decreased in the DOX-treated mice, and activating the receptor with Flv improved cardiac function. Moreover, Flv pretreatment inhibited cardiomyocyte apoptosis and endoplasmic reticulum stress and increased the expression of the Bcl2 apoptosis regulator (Bcl2), effectively alleviating the pathophysiological manifestations in mice. In addition, activating the receptor exerted cardioprotective effects by modulating endoplasmic reticulum stress through the PRKR-like endoplasmic reticulum kinase (PERK) signaling pathway. It also reduced mitochondrial and endoplasmic reticulum contact and alleviated mitochondrial calcium overload through the IP3R-VDAC1-MCU signaling pathway.</p><p><strong>Conclusion: </strong>In conclusion, our study emphasizes the therapeutic potential of activating sigma-1 receptors against DOX-induced cardiotoxicity, suggesting sigma-1 receptors as potential therapeutic targets for this disease.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"23"},"PeriodicalIF":5.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499099","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":"Functional improvement of natural Saccharomyces cerevisiae yeast strains by cell surface molecular engineering.","authors":"Sara Granuzzo, Monica Rossetto, Lucio Zennaro, Francesca Righetto, Paolo Antoniali, Raffaele Lopreiato","doi":"10.1186/s13062-025-00614-1","DOIUrl":"10.1186/s13062-025-00614-1","url":null,"abstract":"<p><strong>Background: </strong>Cellular boundaries of microorganisms can be modified by the expression in the cell wall of specific proteins endowed with relevant properties, improving their functional performance. So far, the surface display (SD) technique had been widely employed in the yeast Saccharomyces cerevisiae, but it was limited to few laboratory strains and never explored in sauvage strains, i.e., isolated from natural environment, which are featured by higher levels of genetic variability, leading to peculiar phenotypic traits of possible advantage in biotechnology.</p><p><strong>Results: </strong>In this work, a series of plasmids performing SD in natural yeast strains have been generated and further characterized by multiple functional and biochemical assays, providing the first experimental evidence that natural strains of S.cerevisiae can be genetically modified to express on their cell wall a protein-of-interest, which retains its biological competence. Interestingly, data further demonstrated that engineered strains expressing (transiently or stably) metal-binding proteins or peptides on cell surface exhibit significantly enhanced metal adsorption properties.</p><p><strong>Conclusions: </strong>The molecular tools presented here can be very useful for yeast research community, as the plasmids efficiently support the surface engineering in virtually all S.cerevisiae strains, independently from either genetic background, source, or applications (wine, beer, bread). Overall, data strongly suggest that, upon genetic modification, S. cerevisiae strains isolated from natural environments could serve as promising platforms for biotechnological applications, as heavy metals removal or enzymes immobilization. Importantly, the strains investigated here represent only a small fraction of the multitude of S. cerevisiae strains present in nature yet to be isolated.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"22"},"PeriodicalIF":5.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424937","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":"Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.","authors":"Jianli Qiu, Yitong Qu, Yinli Li, Cancan Li, Junling Wang, Lu Meng, Xiaojin Jing, Jiangping Fu, Yan Xu, Yuna Chai","doi":"10.1186/s13062-025-00612-3","DOIUrl":"10.1186/s13062-025-00612-3","url":null,"abstract":"<p><strong>Background: </strong>The Rho GTPase Rac family small GTPase 1 (RAC1) is considered a promising fibrotic therapeutic target, but the role of its activator, dedicator of cytokinesis 2 (DOCK2), in liver fibrosis is largely unknown. This study aimed to investigate the expression and role of DOCK2 in cholestasis-induced liver fibrosis and to further explore the potential mechanisms.</p><p><strong>Results: </strong>Cholestasis was induced in male C57BL/6 mice by bile duct ligation (BDL). DOCK2 knockdown was achieved by tail vein injection of adenovirus containing DOCK2-targeting shRNA. The effect of DOCK2 knockdown on cholestatic liver injury was evaluated at different time points after BDL. Hepatic DOCK2 expression gradually increased after BDL. Knockdown of DOCK2 reduced the necrotic area in BDL liver and downregulated serum levels of liver injury indicators. At 3d post-BDL (acute phase), DOCK2 knockdown alleviated M1 macrophage inflammation in the liver, as evidenced by reduced infiltrating iNOS + macrophages and inflammatory cytokines and mitigated NLRP3 inflammasome activation. At 14d post-BDL (chronic phase), DOCK2 knockdown suppressed hepatic stellate cell (HSC) activation and liver fibrosis as indicated by decreased α-SMA + HSCs and extracellular matrix deposition. In vitro experiments further demonstrated that DOCK2 knockdown suppressed M1 macrophage polarisation and HSC to myofibroblast transition, accompanied by inhibition of RAC1 activation.</p><p><strong>Conclusions: </strong>In summary, this study demonstrates for the first time that the RAC1 activator DOCK2 regulates M1 macrophage polarisation and hepatic stellate cell activation to promote cholestasis-induced liver inflammation and fibrosis, suggesting that DOCK2 may be a potential therapeutic target in cholestatic liver injury.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"21"},"PeriodicalIF":5.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373739","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":"Oncogenic RIT1 mutations confer ferroptosis vulnerability in lung adenocarcinoma.","authors":"Ruilan Ma, Dian Yang, Peng Wang, Ziyi Zhang, Xuehong Zhang, Jialiang Song, Han Liu, Shuyan Liu, Yingqiu Zhang, Lijuan Zou","doi":"10.1186/s13062-025-00613-2","DOIUrl":"10.1186/s13062-025-00613-2","url":null,"abstract":"<p><p>Members from the RAS GTPase superfamily have been closely implicated in the tumorigenesis of various human cancers. Recent sequencing analysis of lung adenocarcinoma has revealed the prevalence of alterations in the RIT1 gene that is a close RAS paralog. However, relative to RAS subfamily members KRAS, NRAS, and HRAS, our characterization of RIT1 oncogenic properties remains incomplete. Therefore, further investigation on RIT1 will facilitate future development of targeted therapies. Our bioinformatic analysis revealed that RIT1 alterations in lung cancer predicted poor survivals but differed from its RAS paralogs by showing largely amplification and mutation. Through biochemical characterization of RIT1 hotspot mutations, we propose that RIT1 alterations were associated with increased protein abundance that promoted cell growth. Transcriptomic profiling indicated that oncogenic RIT1 mutant expression influenced common tumorigenic RAS/MAPK, PI3K/AKT, and E2F1 pathways, in addition to altered NFE2L2 target expression. Importantly, RIT1 mutants markedly sensitized cells to ferroptosis induction, and RIT1 knockdown suppressed ferroptotic cell death. Lung adenocarcinoma NCI-H2110 cells containing endogenous RIT1 M90I mutation were susceptible to ferroptosis induction both in vitro and in vivo within xenograft models. Hence, our study unravels a novel aspect of RIT1 mutations in lung cancer and suggests ferroptosis induction as a potential therapeutic strategy to treat lung cancer patients carrying RIT1 mutations.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"19"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370558","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":"cGAS-STING targeting offers therapy choice in lung diseases.","authors":"Yu Wang, Xuan Zhang, Weixue Wang, Yi Zhang, Joshua S Fleishman, Hongquan Wang","doi":"10.1186/s13062-025-00611-4","DOIUrl":"10.1186/s13062-025-00611-4","url":null,"abstract":"<p><p>Cyclic GMP/AMP (cGAMP) synthase (cGAS), along with the endoplasmic reticulum (ER)-associated stimulator of interferon genes (STING), are crucial elements of the type 1 interferon response. cGAS senses microbial DNA and self-DNA, labeling cGAS-STING as a crucial mechanism in autoimmunity, sterile inflammatory responses, and cellular senescence. However, chronic and aberrant activation of the cGAS-STING axis results in inflammatory and autoimmune diseases. cGAS-STING has emerged as a vital mechanism driving inflammation-related diseases, including lung diseases. Insights into the biology of the cGAS-STING pathway have enabled the discovery of small-molecule agents which have the potential to inhibit the cGAS-STING axis in lung diseases. In this review, we first outline the principal components of the cGAS-STING signaling cascade. Then, we discuss recent research that highlights general mechanisms by which cGAS-STING contributes to lung diseases. Then, we focus on summarizing a list of bioactive small-molecule compounds which inhibit the cGAS-STING pathway, reviewing their potential mechanisms.These review highlights a novel groundbreaking therapeutic possibilities through targeting cGAS-STING in lung diseases.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"20"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370555","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":"Martin Karplus (1930-2024).","authors":"Maurizio Brunori, Michele Vendruscolo","doi":"10.1186/s13062-025-00603-4","DOIUrl":"https://doi.org/10.1186/s13062-025-00603-4","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"18"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fraxinellone-mediated targeting of cathepsin B leakage from lysosomes induces ferroptosis in fibroblasts to inhibit hypertrophic scar formation.","authors":"Wei Xu, Hao Lv, Yaxin Xue, Xiaofeng Shi, Shaotian Fu, Xiaojun Li, Chuandong Wang, Danyang Zhao, Dong Han","doi":"10.1186/s13062-025-00610-5","DOIUrl":"10.1186/s13062-025-00610-5","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic scar (HS) is a common fibrotic skin disorder characterized by the excessive deposition of extracellular matrix (ECM). Fibroblasts are the most important effector cells involved in HS formation. Currently no satisfactory treatment has been developed.</p><p><strong>Methods: </strong>The impact of fraxinellone (FRA) on the proliferation and migration capacity of human hypertrophic scar-derived fibroblasts (HSFs) was assessed by EdU proliferation, wound healing and transwell assays. Quantitative real-time PCR (qRT‒PCR), Western blot (WB), immunofluorescence staining and collagen gel contraction assays were performed to evaluate the collagen production and activation capacity of HSFs. Oxford Nanopore Technologies long-read RNA sequencing (ONT long-read RNA-seq) revealed the occurrence of ferroptosis in HSF and ferroptosis executioner-cathepsin B (CTSB). The mechanisms underlying FRA-induced HSF ferroptosis were examined through fluorescence staining, qRT‒PCR, WB and molecular docking study. The therapeutic efficacy of FRA was further validated in vivo using a rabbit ear scar model.</p><p><strong>Results: </strong>FRA treatment significantly suppressed the proliferation, migration, collagen production and activation capacity of HSFs. ONT long-read RNA-seq discovered that FRA modulated the expression of transcripts related to ferroptosis and lysosomes. Mechanistically, FRA treatment reduced the protein expression level of glutathione peroxidase 4 (GPX4) and induced the release of CTSB from lysosomes into the cytoplasm. CTSB further induced ferroptosis via spermidine/spermine-N1-acetyltransferase (SAT1)-mediated lipid peroxidation, mitochondrial damage and mitogen-activated protein kinase (MAPK) signalling pathway activation, eventually affecting the function of HSFs. Moreover, FRA treatment attenuated the formation of HS in rabbit ears via CTSB-mediated ferroptosis. The antifibrotic effects of FRA were abrogated by pretreatment with a CTSB inhibitor (CA-074-me).</p><p><strong>Conclusions: </strong>This study reveals that FRA ameliorates HS by inducing CTSB leakage from lysosomes, causing SAT1-mediated lipid peroxidation, mitochondrial damage and MAPK signalling pathway activation, thus mediating HSF ferroptosis. Therefore, FRA could be a promising therapeutic agent for treating HS.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"17"},"PeriodicalIF":5.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188368","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":"New hope for the world cancer day.","authors":"Gerry Melino, Julia Bischof, Wen-Lian Chen, Wei Jia, Harmut Juhl, Gelina S Kopeina, Alessandro Mauriello, Flavia Novelli, Manuel Scimeca, Yufang Shi, Brunella Maria Pirozzi, Giuseppe Sica, Alexey V Zamaraev, Boris Zhivotovsky","doi":"10.1186/s13062-025-00608-z","DOIUrl":"10.1186/s13062-025-00608-z","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"14"},"PeriodicalIF":5.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122020","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":"Ultrastructural studies distinguish skin diversities among Galápagos iguanas.","authors":"Manuel Scimeca, Rita Bonfiglio, Giuliano Colosimo, Eleonora Candi, Glenn P Gerber, Gregory A Lewbart, Alessandro Mauriello, Gerry Melino, Christian Sevilla, Yufang Shi, Ying Wang, Gabriele Gentile","doi":"10.1186/s13062-025-00602-5","DOIUrl":"10.1186/s13062-025-00602-5","url":null,"abstract":"<p><p>Iguanas exhibit diverse colors and behaviors reflecting evolutionarily adaptation to various habitats; in particular, the Galápagos iguanas represent unique color morphologies with distinct ecological niches. While external coloration in iguanas has ecological implications, comprehensive studies on the histological and ultrastructural aspects of their skin can provide insight into their adaptation to extreme environments, such as high UV exposure. Starting from these considerations the present study investigates the histological, ultrastructural and immunohistochemical features to comprehensively characterize the skin in adults of three species of Galápagos iguanas (A. cristatus, C. subcristatus and C. marthae). Morphological analysis revealed significant differences among the species, with the black-colored skin of A. cristatus showing a melanin-rich but vessel-poor dermis, while C. subcristatus and C. marthae displayed varying distributions of melanosomes and melanocytes. Notably, the absence of iridophores was consistent across all samples due to the absence of birefringent material under the optical microscope. Morphometric evaluations highlighted interspecific differences in the stratum corneum thickness, particularly between black- and non-black-colored (irrespectively if yellowish or pink) skin. The ultrastructural investigation confirmed the absence of iridophores in all analyzed samples. The cytokeratin expression assessed by immunohistochemistry showed stratified epithelium in the epidermis of C. marthae non-black-colored (pink) skin. The presence of a thickened stratum corneum and the stratification of the epidermis in non-pigmented skin could help the pink iguana to cope with the extreme conditions of the Wolf volcano, especially in relation to UV exposure. These skin characteristics may reduce the penetration power of UV rays into the superficial loose dermis, thereby attenuating potential UV-related damage such as DNA breaks and ROS generation. These findings offer insights into the adaptive strategies of these iguanas.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"16"},"PeriodicalIF":5.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188372","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":"Exploring the role of oxidative stress in carotid atherosclerosis: insights from transcriptomic data and single-cell sequencing combined with machine learning.","authors":"Yiqin Yang, Mei Dong","doi":"10.1186/s13062-025-00600-7","DOIUrl":"10.1186/s13062-025-00600-7","url":null,"abstract":"<p><strong>Background: </strong>Carotid atherosclerotic plaque is the primary cause of cardiovascular and cerebrovascular diseases. It is closely related to oxidative stress and immune inflammation. This bioinformatic study was conducted to identify key oxidative stress-related genes and key immune cell infiltration involved in the formation, progression, and stabilization of plaques and investigate the relationship between them.</p><p><strong>Results: </strong>We show that the up-regulation of oxidative stress-related genes such as IDH1 and CD36 in resident-like macrophages and foam macrophages play a key role in the formation and progression of carotid atherosclerotic plaques.</p><p><strong>Conclusions: </strong>We discuss the role of oxidative stress and immune inflammation in the formation, progression, and stabilization of plaques by combining predictive models with analysis of single-cell data. It introduced novel insights into the mechanisms underlying carotid atherosclerosis formation and plaque progression and may assist in identifying potential therapeutic targets for their treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"15"},"PeriodicalIF":5.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063625","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}