Frontiers in Molecular Biosciences最新文献

{"title":"The diagnostic and prognostic significance of HOXC13-AS and its molecular regulatory mechanism in human cancer.","authors":"Xiaosi Gu, Xin Hu, Sijia Zhang, Xiaoyu Zhang, Yong Wang, Lianlian Li","doi":"10.3389/fmolb.2025.1540048","DOIUrl":"10.3389/fmolb.2025.1540048","url":null,"abstract":"<p><p>HOXC13 antisense RNA (HOXC13-AS, also known as HOXC-AS5) is a long non-coding RNA that is expressed abnormally in various types of tumors and is closely related to clinical staging, clinical pathological features, and patient survival. HOXC13-AS is involved in the occurrence and development of tumors, affecting cell proliferation, migration, invasion, epithelial-mesenchymal transition, and tumor growth. This review summarizes the clinical significance of HOXC13-AS as a biomarker for human tumor diagnosis and prognosis and outlines the function and molecular regulation mechanism of HOXC13-AS in various types of cancer, including nasopharyngeal carcinoma, breast cancer, oral squamous cell carcinoma, glioma, and cervical cancer. Overall, this review emphasizes the potential of HOXC13-AS as a human tumor predictive biomarker and therapeutic target, paving the way for its clinical application.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1540048"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467641","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":"The role of potential oxidative biomarkers in the prognosis of intracerebral hemorrhage and the exploration antioxidants as possible preventive and treatment options.","authors":"Jiayong Yao, Xiaohong Dai, Xueping Yv, Lei Zheng, Jia Zheng, Binglin Kuang, Wei Teng, Weiwei Yu, Mingyue Li, Hongtao Cao, Wei Zou","doi":"10.3389/fmolb.2025.1541230","DOIUrl":"10.3389/fmolb.2025.1541230","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a non traumatic hemorrhage that occurs in a certain part of the brain. It usually leads to brain cell damage. According to a large number of experimental research, oxidative stress is an important pathophysiological processes of cerebral hemorrhage. In this paper, we aim to determine how changes in oxidative stress biomarkers indicate the damage degree of cerebral hemorrhage, and to explore and summarize potential treatments or interventions. We found that patients with cerebral hemorrhage are characterized by increased levels of oxidative stress markers, such as total malondialdehyde (MDA), F2 isoprostaglandin, hydroxynonenal, myeloperoxidase and protein hydroxyl. Therefore, the changes of oxidative stress caused by ICH on these markers can be used to evaluate and diagnose ICH, predict its prognosis, and guide preventive treatment to turn to antioxidant based treatment as a new treatment alternative.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1541230"},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448766","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":"Synergistic effects of mutation and glycosylation on disease progression.","authors":"Shodai Suzuki, Motoyuki Itoh","doi":"10.3389/fmolb.2025.1550815","DOIUrl":"10.3389/fmolb.2025.1550815","url":null,"abstract":"<p><p>Glycosylation, a post-translational modification, plays a crucial role in proper localization and function of proteins. It is regulated by multiple glycosyltransferases and can be influenced by various factors. Inherited missense mutations in glycosylated proteins such as NOTCH3, Low-density lipoprotein receptor (LDLR), and Amyloid precursor protein (APP) could affect their glycosylation states, leading to cerebral small vessel disease, hypercholesterolemia, and Alzheimer's disease, respectively. Additionally, physiological states and aging-related conditions can affect the expression levels of glycosyltransferases. However, the interplay between mutations in glycosylated proteins and changes in their glycosylation levels remains poorly understood. This mini-review summarizes the effects of glycosylation on transmembrane proteins with pathogenic mutations, including NOTCH3, LDLR, and APP. We highlight the synergistic contributions of missense amino acids in the mutant proteins and alterations in their glycosylation states to their molecular pathogenesis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1550815"},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448743","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":"Potential biomarkers and immune infiltration linking endometriosis with recurrent pregnancy loss based on bioinformatics and machine learning.","authors":"Jianhui Chen, Qun Li, Xiaofang Liu, Fang Lin, Yaling Jing, Jiayan Yang, Lianfang Zhao","doi":"10.3389/fmolb.2025.1529507","DOIUrl":"10.3389/fmolb.2025.1529507","url":null,"abstract":"<p><strong>Objective: </strong>Endometriosis (EMs) is a chronic inflammatory disease characterized by the presence of endometrial tissue in the non-uterine cavity, resulting in dysmenorrhea, pelvic pain, and infertility. Epidemiologic data have suggested the correlation between EMs and recurrent pregnancy loss (RPL), but the pathological mechanism is unclear. This study aims to investigate the potential biomarkers and immune infiltration in EMs and RPL, providing a basis for early detection and treatment of the two diseases.</p><p><strong>Methods: </strong>Two RPL and six EMs transcriptomic datasets from the Gene Expression Omnibus (GEO) database were used for differential analysis via limma package, followed by weighted gene co-expression network analysis (WGCNA) for key modules screening. Protein-protein interaction (PPI) network and two machine learning algorithms were applied to identify the common core genes in both diseases. The diagnostic capabilities of the core genes were assessed by receiver operating characteristic (ROC) curves. Moreover, immune cell infiltration was estimated using CIBERSORTx, and the Cancer Genome Atlas (TCGA) database was employed to elucidate the role of key genes in endometrial carcinoma (EC).</p><p><strong>Results: </strong>26 common differentially expressed genes (DEGs) were screened in both diseases, three of which were identified as common core genes (MAN2A1, PAPSS1, RIBC2) through the combination of WGCNA, PPI network, and machine learning-based feature selection. The area under the curve (AUC) values generated by the ROC indicates excellent diagnostic powers in both EMs and RPL. The key genes were found to be significantly associated with the infiltration of several immune cells. Interestingly, MAN2A1 and RIBC2 may play a predominant role in the development and prognostic stratification of EC.</p><p><strong>Conclusion: </strong>We identified three key genes linking EMs and RPL, emphasizing the heterogeneity of immune infiltration in the occurrence of both diseases. These findings may provide new mechanistic insights or therapeutic targets for further research of EMs and RPL.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1529507"},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440440","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":"Dual targeting carbonic anhydrase inhibitors as promising therapeutic approach: a structural overview.","authors":"Katia D'Ambrosio, Anna Di Fiore, Emma Langella","doi":"10.3389/fmolb.2025.1511281","DOIUrl":"10.3389/fmolb.2025.1511281","url":null,"abstract":"<p><p>The dual-target inhibitor strategy is an evolving approach that holds great potential for treating complex diseases by addressing their multifactorial nature. It can enhance therapeutic outcomes, reduce side effects and avoid the emergence of drug resistance, particularly in conditions like cancer, inflammation and neurological disorders, where multiple pathways contribute to disease progression. Identifying suitable targets for a dual inhibitor approach requires a deep understanding of disease biology, knowledge of critical pathways, and selection of complementary or synergistic targets. Human carbonic anhydrases (hCAs) have been recognized as suitable drug targets for this therapeutic approach. These enzymes play a key role in maintaining pH balance, ion transport, and fluid regulation across various tissues and organs and their dysregulation has been associated to a variety of human pathologies. Consequently, the inhibition of hCAs combined to the possibility to modulate the activity of a second molecular target represents a promising way for developing more effective drugs. In this mini-review, we aim to present an overview of the most significant structural results related to the development of novel therapeutics employing hCA inhibitors as dual-targeting compounds for the treatment of complex diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1511281"},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440437","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":"Epigenetic regulation in coronary artery disease: from mechanisms to emerging therapies.","authors":"Rui Gao, Meilin Liu, Haoyi Yang, Yuhan Shen, Ni Xia","doi":"10.3389/fmolb.2025.1548355","DOIUrl":"10.3389/fmolb.2025.1548355","url":null,"abstract":"<p><p>Atherosclerosis, the primary cause of coronary artery disease (CAD), remains a leading global cause of mortality. It is characterized by the accumulation of cholesterol-rich plaques and inflammation, which narrow the coronary arteries and increase the risk of rupture. To elucidate this complex biological process and improve therapeutic strategies, CAD has been extensively explored from an epigenetic perspective over the past two decades. Epigenetics is a field investigating heritable alterations in gene expression without DNA sequence changes, such as DNA methylation, histone modifications, and non-coding RNAs. Increasing evidence has indicated that the development of CAD is significantly influenced by epigenetic changes. Meanwhile, the impact of epigenetics in CAD is now transitioning from pathophysiology to therapeutics. Focusing on the key epigenetic enzymes and their target genes will help to facilitate the diagnosis and treatment of CAD. This review synthesizes novel epigenetic insights into CAD, addressing the pathological processes, key molecular mechanisms, and potential biomarkers. Furthermore, we discuss emerging therapeutic strategies targeting epigenetic pathways. By focusing on pivotal enzymes and their associated genes, this work aims to advance CAD diagnostics and interventions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1548355"},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432582","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":"Sotorasib resistance triggers epithelial-mesenchymal transition and activates AKT and P38-mediated signaling.","authors":"Raquel Arantes Megid, Guilherme Gomes Ribeiro, Izabela Natalia Faria Gomes, Ana Carolina Laus, Letícia Ferro Leal, Luciane Sussuchi da Silva, Abu-Bakr Adetayo Ariwoola, Josiane Mourão Dias, Rui Manuel Reis, Renato Jose da Silva-Oliveira","doi":"10.3389/fmolb.2025.1537523","DOIUrl":"10.3389/fmolb.2025.1537523","url":null,"abstract":"<p><strong>Background: </strong>The molecular non-genetic changes of resistance to sotorasib are currently uncertain. The aim of this study was to generate a sotorasib-resistant cell line via selective pressure and systematically examine the molecular and phenotypic alterations caused by resistance.</p><p><strong>Methods: </strong>Mutant NCI-H358 (KRAS^G12C) were exposed to incremental doses (2-512 nM) of sotorasib. Then, resistant clones were separated by single-cell sorting. Proliferation was analyzed in real-time by xCELLigence; protein profiles were quantified by protein arrays; and mRNA expression profile was measured using the PanCancer Pathways panel by NanoString. <i>In silico</i> analyses were conducted from a database comprising patient-derived xenograft (PDX) models and cell lines resistant to sotorasib. AKT and p38. The synergistic effect of combining AKT, p38, and EGFR inhibitors was assessed using the SynergyFinder platform. Additionally, AKT and p38 genes were silenced using esiRNA.</p><p><strong>Results: </strong>Sotorasib-resistant H358-R cell line displayed markers of the mesenchymal-epithelial transition and loss of cell adhesion. Were identified 30 overexpressed genes in the resistance model, implicating in signaling pathways that leads to AKT activation and heightened protein expression levels of phosphorylated AKT and p38. To identify potential therapeutic strategies for overcoming sotorasib resistance, we investigated the combination of AKT and p38 inhibitors. Notably, combined inhibition of AKT (MK2206) and p38 (adezmapimod) restored sensitivity to sotorasib in resistant cell lines, as did silencing AKT expression.</p><p><strong>Conclusion: </strong>These findings underscore the importance of adaptive mechanisms in sotorasib resistance in NSCLC cells contributing by EMT activation and demonstrates synergic combination with AKT and p38 inhibitors to restore sotorasib sensitivity in KRAS^G12C cells.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1537523"},"PeriodicalIF":3.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413738","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: Exosomal biomarkers: roles in diagnostics and therapeutics, Volume II.","authors":"Dwijendra K Gupta","doi":"10.3389/fmolb.2025.1547186","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1547186","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1547186"},"PeriodicalIF":3.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467637","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":"Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping.","authors":"Shaghayegh Soleimani, Ozgur Albayrak, Kayra Somay, Hong Yang, Buket Yigit, Burge Ulukan, Dila Atak, Murat Akyildiz, Metehan Gursoy, Elif Demirtas, Adil Mardinoglu, Atay Vural, Murat Dayangac, Mujdat Zeybel","doi":"10.3389/fmolb.2024.1521811","DOIUrl":"10.3389/fmolb.2024.1521811","url":null,"abstract":"<p><strong>Background: </strong>Chronic liver disease due to alcohol-related liver disease and chronic viral hepatitis pose a substantial burden on healthcare systems. Chronic liver disease may predispose to hepatocellular carcinoma, for which therapeutic options are limited. This study aimed to explore the immune cell characteristics of the clinical conditions.</p><p><strong>Methods: </strong>Explant liver samples were collected from 25 patients for bulk RNA sequencing and flow cytometry analysis. Immune cell populations were characterized by flow cytometry from isolated hepatic and peripheral mononuclear cells.</p><p><strong>Results: </strong>Significant differences in immune cell characteristics were observed among patients with three clinical conditions. Viral hepatitis and peri-tumor samples exhibited higher hepatic B cell counts compared to alcohol-related liver disease. Additionally, chronic liver disease patients showed higher levels of CD57⁺ T cells, suggestive of T cell differentiation. Differential expression analysis identified several genes associated with immune regulation, including downregulation of <i>CD27</i> and upregulation of <i>granzyme B</i> in ARLD, consistent with a highly differentiated phenotype. <i>LAG3</i> and <i>PDCD1</i> were upregulated in peri-tumor samples. The NK cell count was lower in peri-tumor liver specimens compared to ARLD, and an upregulation of <i>TIGIT</i>, an inhibitory marker, was observed in those peri-tumor specimens.</p><p><strong>Conclusion: </strong>This study contributes to the understanding of immune dynamics in chronic liver disease among different etiologies. B lymphocytes are relatively reduced in alcohol-related liver disease compared to other groups, and T cells exhibit a more differentiated subtype. The peritumor microenvironment in HCC suggests a relatively diminished presence of NK cells and a potential tendency toward increased inhibitory characteristics.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1521811"},"PeriodicalIF":3.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406569","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":"Individual-network based predictions of microbial interaction signatures for response to biological therapies in IBD patients.","authors":"Federico Melograna, Padhmanand Sudhakar, Behnam Yousefi, Clara Caenepeel, Gwen Falony, Sara Vieira-Silva, Sreenikhitha Krishnamoorthy, David Fardo, Bram Verstockt, Jeroen Raes, Severine Vermeire, Kristel Van Steen","doi":"10.3389/fmolb.2024.1490533","DOIUrl":"10.3389/fmolb.2024.1490533","url":null,"abstract":"<p><p>Inflammatory Bowel Disease (IBD), which includes Ulcerative Colitis (UC) and Crohn's Disease (CD), is marked by dysbiosis of the gut microbiome. Despite therapeutic interventions with biological agents like Vedolizumab, Ustekinumab, and anti-TNF agents, the variability in clinical, histological, and molecular responses remains significant due to inter-individual and inter-population differences. This study introduces a novel approach using Individual Specific Networks (ISNs) derived from faecal microbial measurements of IBD patients across multiple cohorts. These ISNs, constructed from baseline and follow-up data post-treatment, successfully predict therapeutic outcomes based on endoscopic remission criteria. Our analysis revealed that ISNs characterised by core gut microbial families, including Lachnospiraceae and Ruminococcaceae, are predictive of treatment responses. We identified significant changes in abundance levels of specific bacterial genera in response to treatment, confirming the robustness of ISNs in capturing both linear and non-linear microbiota signals. Utilising network topological metrics, we further validated these findings, demonstrating that critical microbial features identified through ISNs can differentiate responders from non-responders with respect to various therapeutic outcomes. The study highlights the potential of ISNs to provide individualised insights into microbiota-driven therapeutic responses, emphasising the need for larger cohort studies to enhance the accuracy of molecular biomarkers. This innovative methodology paves the way for more personalised and effective treatment strategies in managing IBD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1490533"},"PeriodicalIF":3.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406609","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}