Frontiers in Molecular Biosciences最新文献

{"title":"GPCR systems coordinate cellular resilience against aging-associated stress.","authors":"Tabitha Boeringer, Mia Pardo, Carter J Craig, Ainhoa Nieto Gutierrez, Derek R Duckett, Patricia McDonald, Stuart Maudsley","doi":"10.3389/fmolb.2026.1771718","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1771718","url":null,"abstract":"<p><p>Aging-related diseases arise from cumulative cellular damage driven by diverse stressors. G protein-coupled receptors (GPCRs) play a critical role in coordinating cellular resilience to these stressors. We propose that stable multiprotein GPCR complexes-termed \"receptorsomes\"-function as adaptive hubs that sense, integrate, and mitigate stress across subcellular compartments. Receptorsomes comprise a GPCR core non-covalently associated with specific adaptors (e.g., β-arrestins, GIT2, RGS proteins, ASK1, YAP/TAZ), enabling pluridimensional, G protein-independent signaling that balances stress detection, damage repair, and homeostasis. This review synthesizes evidence linking receptosome composition to responses against oxidative, proteostatic, hypoxic, and other stressors, mapping these to aging hallmarks. We hypothesize that therapeutically tuning receptorsome adaptor engagement could enhance resilience, delay pathology, and extend health span, offering predictions for future testing.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1771718"},"PeriodicalIF":3.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767057","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":"D- and L-lactate dehydrogenase reactions increase pH to lactate production and decrease pH to pyruvate production.","authors":"Robert Robergs, Marek Nalos, Petr Kelbich, Adela Jizerová, Ivana Mervartová, Michal Vostrý, Milan Štengl, Vaclav Babuška","doi":"10.3389/fmolb.2026.1715499","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1715499","url":null,"abstract":"<p><strong>Background: </strong>The traditional explanation of metabolic acidosis in extrahepatic tissues is the increased cellular production of lactic acid. We tested whether the LDH reaction produces lactate and pyruvate anions, or acids, and measured the pH changes that occur for either direction of the reaction.</p><p><strong>Methods: </strong><i>In-vitro</i> reagents (25-40 mL) of the D- and L-LDH reaction were prepared for lactate and pyruvate production at known substrate concentrations ([Substrate]), no added H⁺ buffers, at ∼25 °C. The pH of the reagent was measured using a glass polymer pH electrode. The initial reagent pH was adjusted to a target pH value by addition of HCl or KOH (0.02-0.1 N). The baseline pH was recorded for 2 min, followed by the addition of LDH. The pH response was recorded continuously at varied intervals for 20 min. Reagent samples (100-200 μL) were obtained intermittently for measurements of product.</p><p><strong>Results: </strong>The H⁺ consumption of pyruvate reduction to lactate increased pH (6.3-10.5), and the H⁺ release of lactate oxidation to pyruvate decreased pH (8.8-6.9). The [Product] was small for all [Substrate] and LDH activity conditions (∼0.3 - 0.8 mmol·L^-1), and lowest for pyruvate production. The pH and [Product] results were similar for both D- and L-LDH reactions. The pH to [Product] profiles for lactate vs. pyruvate equated to 9.215 vs. -9.074 pH units·mmol^-1·L^-1, respectively.</p><p><strong>Conclusion: </strong>Scientists and clinicians are encouraged to use these results to further understand the function of the LDH reaction during perturbations of pH in biological systems.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1715499"},"PeriodicalIF":3.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767481","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":"Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics: a molecular biosciences perspective.","authors":"Qianqian Yang, Jingping Wu, Yu Su","doi":"10.3389/fmolb.2026.1775335","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1775335","url":null,"abstract":"<p><p>Cancer claims nearly 10 million lives yearly, demanding innovative diagnostics and therapies beyond surgery and chemotherapy's limitations, such as resistance and toxicity. Next-generation sequencing has unveiled PIWI-interacting RNAs (piRNAs), 26-31 nucleotide small non-coding RNAs, as pivotal regulators in cancer pathogenesis, offering fresh biomarkers and targets from a molecular biosciences lens. Once deemed germline-exclusive for transposon silencing via PIWI proteins (PIWIL1-4), piRNAs exhibit somatic dysregulation across malignancies, driving hallmarks like proliferation, metastasis, and chemoresistance. In colorectal cancer, piR-823 fosters invasion by stabilizing HIF-1α and G6PD, correlating with poor prognosis. Gastric cancers overexpress piR-651, promoting G2/M arrest evasion; lung cancers feature PMLCPIR enhancing ITGB1-PI3K-AKT signaling; multiple myeloma leverages piR-823 for proliferation; and hepatocellular carcinoma shows PIWIL1 upregulation tied to stemness. PiRNAs' tissue-specific signatures enable liquid biopsy detection, with panels predicting recurrence-free survival (e.g., piR-54265/STAT3 axis in CRC). Therapeutically, piRNA mimics/inhibitors (e.g., LNA-antisense against piR-L-138 in lung squamous cell carcinoma) sensitize tumors to cisplatin, while PIWI knockdown curbs metastasis preclinically. This review dissects piRNA biogenesis, oncogenic/suppressive duality, and translational promise. By bridging molecular mechanisms to clinical utility, encompassing diagnostics via plasma profiling and therapeutics like nanoparticle-delivered piRNA therapeutics, piRNAs herald a paradigm shift in precision oncology.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1775335"},"PeriodicalIF":3.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767477","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":"Correction: The endothelial plasma membrane lipidome and its remodeling under hyperglycemia: an exploratory study.","authors":"Ana Reis, Yahya Sohrabi, Lorena Diaz-Sanchez, Ana Rita Dias Araújo, Merle Leffers, Bruno Antonny, Alisa Rudnitskaya, Rui Vitorino, Irundika H K Dias","doi":"10.3389/fmolb.2026.1814292","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1814292","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2025.1701375.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1814292"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722221","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":"Revealing the role of a novel <i>IDS</i> gene mutation in mucpolysaccharidosis type II: insights from computational analysis.","authors":"Shanzhou Huang, Chonghan Li, Yuyuan Zhi, Zengling Su, Fei Ma, Congcong Shi, Sitao Li","doi":"10.3389/fmolb.2026.1734111","DOIUrl":"10.3389/fmolb.2026.1734111","url":null,"abstract":"<p><strong>Introduction: </strong>Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked lysosomal storage disorder caused by variants in the <i>IDS</i> gene. This study reports a male infant with a novel hemizygous frameshift mutation (<i>IDS</i> gene: NM_000202.8, c.1133delA, p.Phe378SerfsTer13). We will investigate the functional consequences and pathogenic mechanisms of this novel mutation.</p><p><strong>Methods: </strong>The mutation c.1133delA in the <i>IDS</i> gene of this patient was confirmed by Sanger sequencing. Structural modeling was performed to assess the impact of the mutation on protein architecture. Additionally, a genome-scale metabolic model was employed to simulate the metabolic consequences of IDS deficiency.</p><p><strong>Results: </strong>Structural analysis revealed deletion of the sulfatase domain 2 (SD2) and disruption of the ligand-binding pocket. Metabolic modeling demonstrated that perturbations were highly localized, affecting only a limited subset of reactions primarily confined to glycosaminoglycan degradation pathways, without detectable impact on core cellular metabolism. The model further predicted accumulation of glycosaminoglycan-related intermediates, consistent with known biochemical hallmarks and clinical manifestations of MPS II.</p><p><strong>Discussion: </strong>This study demonstrates the pathogenicity of the mutation c.1133delA, our findings highlight the value of metabolic network analysis in understanding disease mechanisms and identifying potential therapeutic targets for MPS II.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1734111"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722294","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":"Detection of mutations: from Ames test to duplex sequencing.","authors":"Niketa Bhawsinghka, Roel M Schaaper","doi":"10.3389/fmolb.2026.1774439","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1774439","url":null,"abstract":"<p><p>Mutation is a biological phenomenon observed in all life forms from viruses to humans. This inescapable process has fascinated scientists for nearly a century. Mutagenicity has become a concern since the 1940s following the discovery that chemicals can cause mutations, because of which the scientific community has ventured into finding effective methods of detecting harmful mutagens. The earlier studies in this field were carried out using organisms like <i>Escherichia coli</i>, <i>Drosophila</i>, and <i>Neurospora</i>. Later, the breakthrough development of an assay using bacteria allowed researchers to detect the abilities of chemical compounds or mixtures to induce DNA mutations. This assay came to be named as the Ames test after its developer Bruce Ames; since then, it has been widely adopted for mutagenicity testing. The introduction of Sanger sequencing technology enabled researchers to explore beyond phenotypic changes and uncover detailed information on DNA sequence changes and mutational spectra. With the advent of next-generation sequencing (NGS), it has become possible to expand mutation analysis to the larger genome without the need for phenotypic selection, particularly given the development of various error-corrected NGS (ecNGS) techniques. Duplex sequencing (DS) is a relatively new ecNGS technique that can detect mutations at low frequencies in isolated DNA. In this mini review, we briefly explore the genetics of the Ames test and shed light on DS as an emerging tool for detecting mutations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1774439"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722297","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 prospective observational study of lifestyle behaviors and biomarkers to promote cardiometabolic health in healthcare workers during the COVID-19 pandemic.","authors":"Mary S McCarthy, Zachary T Colburn, Laurel H Gillette, Nancy S Hodge, Ling-Hong Hung, Bryce Fukuda, Daniel Rhee, Joshua Sakai, Ka Yee Yeung","doi":"10.3389/fmolb.2026.1714752","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1714752","url":null,"abstract":"<p><strong>Introduction: </strong>Nutrition, physical activity, and sleep deficits contribute to diminished health status in healthcare workers (HCWs). The purpose of this study was to focus attention on HCWs by incorporating precision health approaches to address lifestyle behaviors believed to influence immune health, cardiometabolic status, and wellbeing.</p><p><strong>Methods: </strong>In this 1-year prospective observational study, a digital dashboard was created to post a health promotion video, targeted health messages, and personal health data accessible to each participant. Activity-sleep trackers were provided to capture actual step and sleep activity. Lifestyle questionnaires, serum biomarkers, body composition by bioelectrical impedance analysis, and blood pressure were obtained at four timepoints; gene expression was measured at three timepoints. Genes linking host immune response to key nutrients were isolated for correlational analyses with lifestyle behaviors. Participants received a comprehensive summary of their personal results at 12 months. Primary outcome was participant engagement.</p><p><strong>Results: </strong>104 HCWs enrolled between July and October 2021. At 12 months, 60% of participants were high adopters for device-wear time and daily step threshold. Daily steps declined by 831 (±3,441) steps per day, t statistic -1.742, <i>p</i> = 0.09 after 1 year. Insomnia Severity Index results suggested persistent subclinical insomnia with a mean score of 8.1 (±6.1) at 12 months. Thirteen genes had a moderate correlation with steps, <i>r</i> (49) = 0.29-37, sleep, <i>r</i> (56) = 0.27-0.37, distance, <i>r</i> (61) = 0.28, and Insomnia Severity Index, <i>r</i> (56) = 0.30-0.38, <i>p</i> = NS, after Benjamini-Hochberg adjustment.</p><p><strong>Conclusion: </strong>Participant engagement may have contributed to favorable behavior change in the first 6 months, but this was not sustained at 12 months. Novel strategies are needed to boost engagement for longer studies, promote HCW wellness to optimize immune and cardiometabolic health, and abate chronic disease progression.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1714752"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698159","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: Reviews in ARF, the most misunderstood G protein I ever knew: a collection of papers exploring the multifaceted functions of an ancient protein family.","authors":"Paul A Randazzo, Lorraine Santy, Pei-Wen Chen","doi":"10.3389/fmolb.2026.1831289","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1831289","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1831289"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698092","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":"Sensing succinate: SUCNR1 as a context-dependent metabolic and cellular signal integrator.","authors":"Aenne-Dorothea Liebing, Claudia Stäubert","doi":"10.3389/fmolb.2026.1815835","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1815835","url":null,"abstract":"<p><p>Succinate (SUC), a central intermediate in the mitochondrial tricarboxylic acid (TCA) cycle, functions not only as a metabolic substrate but also acts as the endogenous ligand for succinate receptor 1 (SUCNR1), a G_i- and G_q protein-coupled receptor. SUC accumulates when energy demand exceeds oxygen supply or during metabolic rewiring, including hypoxia, endurance exercise, inflammation, and tumor progression. SUC can be released into the extracellular space, reaching levels sufficient to activate SUCNR1. SUCNR1 is expressed in various tissues, including the kidney, liver, and adipose tissue, as well as in immune cells and cancer subtypes. Rather than functioning as a simple pro- or anti-inflammatory receptor, SUCNR1 acts as a metabolic signal integrator whose output is determined by G protein preferences, receptor trafficking, and the balance between intra- and extracellular SUC pools. In immune cells, particularly macrophages, SUCNR1 signaling promotes either inflammatory activation or resolution depending on the metabolic state. In metabolic tissues and cancer, SUCNR1 coordinates adaptive responses to nutrient and oxygen stress while shaping the tissue microenvironment. Here, we review recent advances in SUC-SUCNR1 signaling across immune and metabolic systems, discuss unresolved controversies regarding signaling selectivity and spatial encoding, and evaluate the therapeutic opportunities and challenges of targeting this metabolic checkpoint.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1815835"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698139","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":"Breast milk miRNAs and their potential role in the development of atopy in infants.","authors":"Adrianna Porębska, Maciej Maj, Aizhan Rakhmetullina, Piotr Zielenkiewicz, Leszek Pączek","doi":"10.3389/fmolb.2026.1768239","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1768239","url":null,"abstract":"<p><p>Human breast milk is a dynamic biological fluid enriched with bioactive components, including extracellular vesicle-derived microRNAs (miRNAs), which have emerged as potential mediators of early immune programming. Growing evidence suggests that maternal atopic status can alter the breast milk miRNA profile, potentially shaping the infant's susceptibility to atopic disorders, such as atopic dermatitis, asthma, and food allergy. This review presents current research examining the link between breast milk miRNA composition and the development of atopy in infants, with a particular focus on maternal atopic status. Four studies met eligibility criteria and collectively demonstrate that maternal conditions such as asthma or atopic dermatitis are associated with distinct breast milk miRNA signatures. Certain miRNAs, e.g., miR-375-3p and miR-1290, show altered expression in the milk of atopic mothers. Elevated levels of miR-375-3p are associated with a reduced risk of infant atopic manifestations during the first year of life, including atopic dermatitis, food allergy, and wheezing. Conversely, miR-1290 is significantly upregulated in the milk of mothers with asthma and atopy during pregnancy, even after adjusting for confounders, highlighting its potential role as a biomarker of maternal allergic status. However, current findings rely primarily on statistical associations; no human study has yet demonstrated direct transfer or functional activity of milk-derived miRNAs in infants. Overall, while breast milk miRNAs represent a promising link between maternal health and infant atopy risk, conclusive evidence is lacking. Future large-scale, standardized, longitudinal studies integrating functional validation are needed to clarify mechanistic pathways and evaluate the potential of milk miRNAs as biomarkers or targets for early atopy prevention. Understanding the functional impact of breast milk miRNAs could facilitate the development of non-invasive biomarkers for predicting atopy risk, as well as early-life preventive strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1768239"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698155","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}