Frontiers in Molecular Biosciences最新文献

{"title":"Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.","authors":"Chandra Kanta Bhusal, Shweta Sinha, Davinder Kaur, Rakesh Sehgal","doi":"10.3389/fmolb.2025.1573618","DOIUrl":"10.3389/fmolb.2025.1573618","url":null,"abstract":"<p><p>Leishmaniasis remains a significant global health challenge, with over a billion people at risk of infection and limited effective treatment options due to escalating drug resistance. This review explores the underlying mechanisms of drug resistance in <i>Leishmania</i> species, focusing on genomic plasticity as a driving factor for survival and adaptation. Key mechanisms, including genetic mutations, gene amplification, chromosomal rearrangements, and efflux transporters, contribute to the parasite's ability to evade existing therapies. Advances in genomic and proteomic studies have provided deeper insights into these resistance pathways, enabling the development of novel therapeutic strategies. Additionally, this review highlights current therapeutic approaches, including combination therapies and potential new drug candidates, that address multidrug resistance and explore the vulnerabilities of <i>Leishmania</i>. Understanding these mechanisms and their clinical implications is essential for developing targeted interventions that improve treatment outcomes and combat resistance in leishmaniasis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1573618"},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking oxidative stress biomarkers to disease progression and antioxidant therapy in hypertension and diabetes mellitus.","authors":"Alberto J Nuñez-Selles, Rodolfo A Nuñez-Musa, Rafael A Guillen-Marmolejos","doi":"10.3389/fmolb.2025.1611842","DOIUrl":"10.3389/fmolb.2025.1611842","url":null,"abstract":"<p><p>Oxidative stress (OS) is increasingly recognized as a key factor linking hypertension (HTN) and diabetes mellitus (DM). This review summarizes recent evidence regarding the dual role of OS as both an instigator and an amplifier of cardiometabolic dysfunction. In HTN, reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) and mitochondrial dysfunction contribute to endothelial impairment and vascular remodeling. In DM, hyperglycemia-induced ROS production worsens beta-cell failure and insulin resistance through pathways such as the AGE-RAGE signaling, protein kinase C (PKC) activation, and the polyol pathway. Clinically validated biomarkers of OS, such as F2-isoprostanes (which indicate lipid peroxidation), 8-OHdG (which indicates DNA damage), and the activities of redox enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx), show strong correlations with disease progression and end-organ complications. Despite promising preclinical results, the application of antioxidant therapies in clinical settings has faced challenges due to inconsistent outcomes, highlighting the need for targeted approaches. Emerging strategies include: 1. Mitochondria-targeted antioxidants to enhance vascular function in resistant HTN; 2. Nrf2 activators to restore redox balance in early diabetes; and 3. Specific inhibitors of NOX isoforms. We emphasize three transformative areas of research: (i) the interaction between the microbiome and ROS, where modifying gut microbiota can reduce systemic OS; (ii) the use of nanotechnology to deliver antioxidants directly to pancreatic islets or atherosclerotic plaques; and (iii) phenotype-specific diagnosis and therapy guided by redox biomarkers and genetic profiling (for example, KEAP1/NRF2 polymorphisms). Integrating these advances with lifestyle modifications, such as following a Mediterranean diet and exercising regularly, may provide additional benefits. This review outlines a mechanistic framework for targeting OS in the comorbidity of HTN and DM while identifying critical knowledge gaps, particularly regarding the timing of antioxidant signaling and the development of personalized redox medicine, which may serve as a reference for researchers and clinicians working in this area.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1611842"},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from veterinary models for advancing oncolytic virotherapy through comparative oncology.","authors":"Almohanad A Alkayyal","doi":"10.3389/fmolb.2025.1615393","DOIUrl":"10.3389/fmolb.2025.1615393","url":null,"abstract":"<p><p>Cancer is a complex disease affecting both humans and animals. Comparative immuno-oncology explores immune responses across species to develop effective cancer therapies. Oncolytic viruses (OVs) serve as both direct tumor-lysing agents and immune stimulants, making them an attractive therapeutic option. This review highlights the role of naturally occurring tumors in animal models for OV-based cancer immunotherapy. We examine immune responses in different species, the latest advancements in OV therapy, and the role of precision medicine in veterinary oncology. Understanding these comparative aspects enhances OV translation from preclinical to clinical applications in both veterinary and human oncology.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1615393"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Emerging advancements in the carbonic anhydrase field.","authors":"Simona Maria Monti, Vincenzo Alterio, Seppo Parkkila, Claudiu T Supuran, Giuseppina De Simone","doi":"10.3389/fmolb.2025.1624394","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1624394","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1624394"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Bridging discovery and translation in novel biomarkers and big data-based biomedical studies for cancer management.","authors":"Lin Zhang, Weiye Qian, Qingyu Luo","doi":"10.3389/fmolb.2025.1620512","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1620512","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1620512"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of diagnostic approaches for hepatitis D.","authors":"Wen-Hui Liu, Jia-Yue Cui, Miao Yu, Xiao-Dong Shi, Yi-Lin Che, Chu-Yan Wang, Xiu-Mei Chi","doi":"10.3389/fmolb.2025.1598784","DOIUrl":"10.3389/fmolb.2025.1598784","url":null,"abstract":"<p><p>Current estimates suggest 9 million to 19 million people worldwide are affected by Hepatitis D virus (HDV) infection, though significant discrepancies in diagnostic guideline implementation across regions and countries indicate these figures may not fully capture the true disease burden. HDV coinfection and superinfection with hepatitis B hasten disease progression, increasing cirrhosis and liver cancer risks, highlighting the importance of early and precise diagnosis. We present a thorough analysis of current and emerging hepatitis D diagnostic methods. Initial diagnosis involves detecting serum anti-HDV antibodies using radioisotope- or enzyme-linked immunosorbent assays. Established techniques like chemiluminescence immunoassay, quantitative microarray antibody capture, and lateral flow assays are being improved. Additional diagnostic markers include HDV antigens and RNA in the serum or liver, detectable through methods like northern and slot blots, fluorescence <i>in situ</i> hybridization, and quantitative real-time PCR. Droplet digital PCR allows quantifying unedited and edited HDV genomes in one sample. Next-generation sequencing offers deeper insights into HDV quasispecies for precise genotyping. Challenges persist, including qualitative diagnostic methods and need for international standards due to lab variability. This review emphasizes the urgency of establishing standardized protocols and international standards for early interventions and reducing the medical burden of chronic HDV infection.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1598784"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulating the expression of exercise-induced micro-RNAs and long non-coding RNAs: implications for controlling cardiovascular diseases and heart failure.","authors":"Guobiao Yang, Wanying Yang","doi":"10.3389/fmolb.2025.1587124","DOIUrl":"10.3389/fmolb.2025.1587124","url":null,"abstract":"<p><p>The intricate interplay between physical training and non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), has attracted considerable attention in understanding physiological adaptations and pathological conditions. Both miRNAs and lncRNAs are essential modulators of gene expression, influencing various cellular processes, including those related to muscle metabolism, inflammation, and recovery from injury. This review investigates the bifunctional role of miRNAs and lncRNAs in response to physical training, highlighting their involvement in muscle hypertrophy, endurance adaptations, and the modulation of inflammatory pathways. Additionally, we examine how pathological conditions, such as cardiovascular disease, heart failure, can alter the expression profiles of miRNAs and lncRNAs, potentially disrupting the beneficial effects of physical training. The crosstalk between these non-coding RNAs under physiological and pathological states underscores their potential as biomarkers for assessing training responses and therapeutic targets for enhancing recovery and performance. Understanding these interactions may pave the way for novel interventions to optimize health outcomes through tailored physical training programs.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1587124"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Computational analysis of the structural-functional dynamics of a Co-receptor proteoglycan.","authors":"Francesco Tavanti, Giorgia Brancolini, Roberto Perris","doi":"10.3389/fmolb.2025.1612818","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1612818","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2025.1549177.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1612818"},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.","authors":"Etianne Martini Sasso, Natalie Eaton-Fitch, Peter Smith, Katsuhiko Muraki, Sonya Marshall-Gradisnik","doi":"10.3389/fmolb.2025.1582967","DOIUrl":"10.3389/fmolb.2025.1582967","url":null,"abstract":"<p><strong>Introduction: </strong>Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca²⁺) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.</p><p><strong>Methods: </strong>NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3-4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.</p><p><strong>Results: </strong>The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).</p><p><strong>Discussion: </strong>Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca²⁺ influx necessary for homeostatic cellular processes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1582967"},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology and experimental validation to reveal the anti-growth mechanism of panaxadiol against glioblastoma via calcium signaling.","authors":"Guobin Qiu, Zhiyong Wu, Dunhui Yang, Luqiu Zhou","doi":"10.3389/fmolb.2025.1598413","DOIUrl":"10.3389/fmolb.2025.1598413","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly aggressive brain tumor and is relatively common among malignant brain tumors in adults. Its rapid proliferation and significant invasiveness make its treatment one of the major challenges in brain tumor research. Panaxadiol, a compound extracted from ginseng roots, has been found to have significant therapeutic effects on various types of tumors. Nonetheless, the precise function and underlying mechanisms of this factor in GBM have yet to be thoroughly investigated. In the current study, we employed network pharmacology to explore the potential therapeutic interactions of Panaxadiol within the framework of GBM. Subsequently, we confirmed its efficacy via biological experiments aimed at elucidating the mechanisms through which it exerts its anti-GBM effects. We collected relevant targets of Panaxadiol and differential genes of GBM from multiple databases. The network pharmacology analysis revealed 66 potential targets of Panaxadiol in the context of GBM. Enrichment analysis indicated that these targets might function through several key signaling pathways, including the calcium, cAMP, and cGMP-PKG signaling pathways. Therefore, Panaxadiol may exert its effects by regulating calcium ions. Further, In our study, we employed the MOCDE and CytoHubba plugins within the Cytoscape framework to identify seven hub genes, including GRIA2, GRIN1, GRIN2B, GRM1, GRM5, HTR1A, and HTR2A, and validated their binding capabilities with Panaxadiol through molecular docking. Furthermore, we conducted experiments <i>in vitro</i> and <i>in vivo</i> experiments, which encompassed CCK-8, colony formation, flow cytometry apoptosis, intracellular calcium ion measurement, and xenograft tumor experiments utilizing nude mice, to validate the function of Panaxadiol in suppressing the growth of GBM via the modulation of calcium ion levels. This study not only revealed the anti-GBM mechanisms of Panaxadiol through network pharmacology but also validated its inhibitory effects on GBM via calcium ion release through <i>in vitro</i> and <i>in vivo</i> experiments.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1598413"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}