Biology Direct最新文献

{"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}

{"title":"BRCA1 is involved in sustaining rapid antler growth possibly via balancing of the p53/endoplasmic reticulum stress signaling pathway.","authors":"Qianqian Guo, Zhen Wang, Jiping Li, Chao Ma, Junjun Zheng, Hengxing Ba, Guokun Zhang, Chunyi Li","doi":"10.1186/s13062-025-00606-1","DOIUrl":"10.1186/s13062-025-00606-1","url":null,"abstract":"<p><strong>Background: </strong>Regeneration is the preferred approach to restore the structure and function after tissue damage. Rapid proliferation of cells over the site of damage is integral to the process of regeneration. However, even subtle mutations in proliferating cells may cause detrimental effects by eliciting abnormal differentiation. Interestingly deer antlers, arguably the fastest regenerating mammalian tissue, have not been reported, thus far, to grow malignant tumors. They provide a mammalian model to understand the possible mechanism by which rapid regeneration is achieved while avoiding the development of malignancies. Antler regeneration is based on the proliferation and differentiation of antler stem cells (AnSCs).</p><p><strong>Results: </strong>We identified 39 hub genes which may function in regulating the balance between rapid proliferation and genomic stability in the AnSCs during antler regeneration. Among these 39 genes, the tumor suppressor gene, BRCA1, was found to be more sensitive to DNA damage in the AnSCs compared to that in the deer somatic cells, and BRCA1 deletion in the AnSCs via CRISPR/Cas9 resulted in significantly higher levels of DNA damage. Lack of BRCA1 promoted cell apoptosis and cell senescence and inhibited cell proliferation and cell self-renewal. RNA-seq results showed that in the absence of BRCA1, the p53 signaling pathway was significantly up-regulated. Associated with this change, the cell apoptosis and cell senescence-relevant-genes, CDKN1A, CDKN2A and Fas were over expressed, but the expression of cell-cycle-progression-related genes was inhibited. In addition, BRCA1 expression levels were found to be more sensitive to endoplasmic reticulum stress (ERS) in the AnSCs compared to the somatic cells. Deletion of BRCA1 gene aggravated ERS and ERS-induced cell apoptosis.</p><p><strong>Conclusions: </strong>Our results revealed that BRCA1 is involved in sustaining rapid antler growth possibly via promotion of DNA damage repair that acts to maintain genome stability while protecting cells from p53/ERS-induced cell death. Understanding the mechanisms underlying the role played by BRCA1 in the process of antler regeneration is of great significance not only for regenerative medicine, but also for the understanding of cancer development.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"13"},"PeriodicalIF":5.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027908","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: Integrated Mendelian randomization and single-cell RNA-sequencing analyses identified OAS1 as a novel therapeutic target for erectile dysfunction via targeting fibroblasts.","authors":"Yi Wang, Guihua Chen, Deng Li","doi":"10.1186/s13062-025-00607-0","DOIUrl":"10.1186/s13062-025-00607-0","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"12"},"PeriodicalIF":5.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027913","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":"Uncovering glycolysis-driven molecular subtypes in diabetic nephropathy: a WGCNA and machine learning approach for diagnostic precision.","authors":"Chenglong Fan, Guanglin Yang, Cheng Li, Jiwen Cheng, Shaohua Chen, Hua Mi","doi":"10.1186/s13062-025-00601-6","DOIUrl":"10.1186/s13062-025-00601-6","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy (DN) is a common diabetes-related complication with unclear underlying pathological mechanisms. Although recent studies have linked glycolysis to various pathological states, its role in DN remains largely underexplored.</p><p><strong>Methods: </strong>In this study, the expression patterns of glycolysis-related genes (GRGs) were first analyzed using the GSE30122, GSE30528, and GSE96804  datasets, followed by an evaluation of the immune landscape in DN. An unsupervised consensus clustering of DN samples from the same dataset was conducted based on differentially expressed GRGs. The hub genes associated with DN and glycolysis-related clusters were identified via weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. Finally, the expression patterns of these hub genes were validated using single-cell sequencing data and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Eleven GRGs showed abnormal expression in DN samples, leading to the identification of two distinct glycolysis clusters, each with its own immune profile and functional pathways. The analysis of the GSE142153 dataset showed that these clusters had specific immune characteristics. Furthermore, the Extreme Gradient Boosting (XGB) model was the most effective in diagnosing DN. The five most significant variables, including GATM, PCBD1, F11, HRSP12, and G6PC, were identified as hub genes for further investigation. Single-cell sequencing data showed that the hub genes were predominantly expressed in proximal tubular epithelial cells. In vitro experiments confirmed the expression pattern in NC.</p><p><strong>Conclusion: </strong>Our study provides valuable insights into the molecular mechanisms underlying DN, highlighting the involvement of GRGs and immune cell infiltration.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"10"},"PeriodicalIF":5.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000230","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 genomic imaging (FGI), a virtual tool for visualization of functional gene expression modules in heterogeneous tumor samples.","authors":"Xinlei Chen, Youbing Guo, Xiaorong Gu, Danyi Wen","doi":"10.1186/s13062-025-00598-y","DOIUrl":"10.1186/s13062-025-00598-y","url":null,"abstract":"<p><p>Advances in sequencing technologies are reshaping clinical diagnostics, prompting the development of new software tools to decipher big data. To this end, we developed functional genomic imaging (FGI), a visualization tool designed to assist clinicians in interpreting RNA-Seq results from patient samples. FGI uses weighted gene co-expression network analysis (WGCNA), followed by a modified Phenograph clustering algorithm to identify co-expression gene clusters. These gene modules were annotated and projected onto a t-SNE map for visualization. Annotation of FGI gene clusters revealed three categories: tissue-specific, functional, and positional. These clusters may be used to build tumor subtypes with pre-annotated functions. At the multi-cancer cohort level, tissue-specific clusters are enriched, whereas at the single cancer level, such as in lung cancer or ovarian cancer, positional clusters can be more prominent. Moreover, FGI analysis could also reveal molecular tumor subtypes not documented in clinical records and generated a more detailed co-expression gene cluster map. Based on different levels of FGI modeling, each individual tumor sample can be customized to display various types of information such as tissue origin, molecular subtypes, immune activation status, stromal signaling pathways, cell cycle activity, and potential amplicon regions which can aid in diagnosis and guide treatment decisions. Our results highlight the potential of FGI as a robust visualization tool for personalized medicine in molecular diagnosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"11"},"PeriodicalIF":5.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000141","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":"Methyltransferase-like 7B participates in bladder cancer via ACSL3 m⁶A modification in a ferroptosis manner.","authors":"Jiani He, Changming Dong, Xiandong Song, Zhongkai Qiu, Hao Zhang, Yuanjun Jiang, Tao Liu, Xiaojun Man","doi":"10.1186/s13062-025-00597-z","DOIUrl":"10.1186/s13062-025-00597-z","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is a malignant tumor. Methyltransferase-like 7B (MEETL7B) is a methyltransferase and its role in BC has not yet been revealed.</p><p><strong>Method: </strong>Stable METTL7B knockdown or overexpression were achieved by lentiviral transduction in SW780 and TCCSUP cell lines. Xenografts tumors were established via subcutaneous injection of stable transfectants in BALB/c mice.</p><p><strong>Results: </strong>A database search indicated that METTL7B was elevated in BC and it was validated in BC cell lines. METTL7B silencing suppressed cell proliferation and tumorigenesis in vitro and in vivo. Besides, METTL7B knockdown induced cell cycle arrest in G1 phase with a reduction in cyclin D1(CCND1), CDK4, and CDK6 levels and an elevation in CDKN2D levels in cells. Considering that ferroptosis is emerging as a therapeutic target for cancer, and the possible relationship between METTL7B and antioxidant enzymes. We, here, examined that ectopic METTL7B expression abolished ferroptosis markers in cells raised by Erastin treatment, including the production of lipid ROS, the increased cellular iron and MDA content, the decreased gene expression of ACSL3, FANCD2, and FADS2, as well as the mitochondrial injury observed by electron microscopy. Mechanically, ectopic METTL7B expression promoted m⁶A modification on ACSL3 mRNA. Gain of functional experiment exhibited that METTL7B inhibited Erastin-induced ferroptosis via ACSL3. Overexpressed PLAGL2 is identified as a possible independent predictor in BC and bioinformatics predicted the potential binding sites between PLAGL2 and METTL7B promoter region. Dual luciferase and chromatin immunoprecipitation analysis provided evidence that PLAGL2 directly binds to METTL7B promoter region.</p><p><strong>Conclusions: </strong>METTL7B is involved in BC development and progression. METTL7B may mediate m⁶A modification on ACSL3 mRNA to negatively regulate ferroptosis in BC cells, which provides a potential therapeutic target for BC via ferroptosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"9"},"PeriodicalIF":5.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000227","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}