Frontiers in Molecular Biosciences最新文献

{"title":"Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people.","authors":"Tianya Liu, Siqi Zhou, Rui Wang, Xiaomei Xu, Fang Gao, Jie Zu, Zhiping Wang","doi":"10.3389/fmolb.2025.1652083","DOIUrl":"10.3389/fmolb.2025.1652083","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH), a serious disease, is characterized by various degrees of pulmonary vascular remodeling, inflammation, and increased vascular resistance, leading to fatalities in patients with severe conditions. However, the molecular mechanisms underlying the pathogenesis of PAH remain incompletely understood.</p><p><strong>Methods: </strong>RNA sequencing (RNA-seq), 4D label-free proteomics, and phosphoproteomics were employed to detect the levels of mRNA, proteins, and phosphorylation modification in the lung tissues of PAH patients, compared to those in the control group. Parallel reaction monitoring (PRM) was subsequently performed to verify the differentially expressed proteins (DEPs) identified by proteomic profiling.</p><p><strong>Results: </strong>After data filtering (|log2FoldChange| > 1 and p < 0.05), the PAH group exhibited 967 differentially expressed genes (DEGs), 764 DEPs, and 411 phosphorylated DEPs compared with those of the control group. By integrating transcriptomic and proteomic analyses, 54 proteins were identified with consistent changes at both levels. We analyzed several proteins using PRM, including known candidates such as enolase 1 (ENO1) and chloride intracellular channel 1 (CLIC1), as well as novel proteins such as caveolin-2 (CAV2) and eukaryotic translation initiation factor (EIF2A). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEPs showed significant enrichment of biological processes associated with inflammatory response, oxidative stress, and tissue remodeling. Phosphorylated DEPs showed significant enrichment in key pathways, including autophagy, apoptosis, and hypoxia inducible factor (HIF) signaling, all of which were closely associated with PAH.</p><p><strong>Conclusion: </strong>Dysregulated pathways such as autophagy, apoptosis, and HIF-1 signaling, along with altered genes or proteins, contribute to PAH by inducing pulmonary vascular remodeling and chronic vasoconstriction. These findings may facilitate the discovery of novel therapeutic targets and effective treatment strategies for PAH.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1652083"},"PeriodicalIF":3.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949029","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":"Modelling the melting of DNA oligomers with non-inert dangling ends.","authors":"Alejandro Soto, Francesco Mambretti, Emanuele Locatelli, Iliya D Stoev","doi":"10.3389/fmolb.2025.1646428","DOIUrl":"10.3389/fmolb.2025.1646428","url":null,"abstract":"<p><p>In this work, we investigate the dependence of the melting temperature of low-valency DNA constructs on the length of non-inert dangling ends, controlling their sequence composition. We compare two computational models to evaluate their effectiveness and limitations in predicting the melting behavior of DNA oligomers (bivalent linkers) and more complex structures (trivalent nanostars), benchmarking the results against experimental spectroscopic data. Our results suggest that the length of non-inert dangling ends has minimal impact on the melting point of the DNA duplex for the duplexes we studied, informing the future design of DNA supramolecular constructs.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1646428"},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949002","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":"Astrocytes from lamina cribrosa are involved in the autoregulatory function of optic nerve head vessels <i>in vitro</i>.","authors":"Xiaoxiao Feng, Wenjia Zhang, Tingting Wan, Kangwei Jiao, Liwei Zhang, Changhui Li, Libo Xiao","doi":"10.3389/fmolb.2025.1636882","DOIUrl":"10.3389/fmolb.2025.1636882","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the role of the lamina cribrosa (LC) astrocytes in the autoregulatory capacity of optic nerve head (ONH) vessels and to explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The Oxygen-glucose deprivation/reperfusion model (OGD/R) <i>in vitro</i> was constructed to examine the changes in cell morphology and protein expression in LC astrocytes. LC astrocytes were co-cultured with vascular smooth muscle cells (VSMCs) to detect the role of LC astrocytes in the autoregulatory function of vessels.</p><p><strong>Results: </strong>The partial pressure of oxygen (PO₂) in the supernatant of LC astrocytes was significantly lower following OGD, and this reduction was more pronounced with longer OGD durations. OGD inhibited proliferation and promoted apoptosis in LC astrocytes, with longer OGD durations correlating with decreased proliferation and increased apoptosis. Reoxygenation following 1 h of OGD led to upregulation of GFAP, mTOR, cPLA₂ protein expression and supernatant PGE2 concentration in LC astrocytes, an effect that can be attenuated by the mTOR inhibitor. Co-culturing with LC astrocyte resulted in increased expression of MYPT1 protein in VSMCs, and the VSMCs exhibited a relaxed morphology.</p><p><strong>Conclusion: </strong>Under <i>in vitro</i> OGD/R conditions, LC astrocyte were activated through the mTOR pathway, leading to increased secretion of PGE₂, which locally regulates the dilation of VSMCs. In conclusion, LC astrocytes may regulate local blood flow in the ONH.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1636882"},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949011","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: Protein regulation by lipids.","authors":"Mikhail V Bogdanov, Elena G Govorunova","doi":"10.3389/fmolb.2025.1669083","DOIUrl":"10.3389/fmolb.2025.1669083","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1669083"},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949047","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":"MicroRNAs at the crossroad of cancer therapeutics: insights from WNT signaling & flavonoids.","authors":"Akanksha Gupta, Arpit Mehrotra, Abhilasha Sood, Bunty Sharma, Vikas Yadav, Ginpreet Kaur, Katrin Sak, Shakti Ranjan Satapathy, Hardeep Singh Tuli","doi":"10.3389/fmolb.2025.1616221","DOIUrl":"10.3389/fmolb.2025.1616221","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are pivotal post-transcriptional regulators that orchestrate gene expression programs governing cancer initiation, progression, metastasis, and therapeutic resistance. Among their many targets, the WNT signaling pathway, a key driver of malignancy, is tightly controlled by miRNAs, forming intricate feedback loops that shape tumor behavior. Concurrently, flavonoids, naturally occurring plant-derived polyphenols, are emerging as promising anticancer agents that can modulate both WNT signaling and miRNA expression. This review highlights miRNAs as the central regulators of oncogenic signaling, focusing on their dualistic role in cancer biology and their modulation by flavonoids. We explore the mechanistic frameworks underpinning miRNA-WNT interactions and the therapeutic potential of flavonoid-mediated miRNA reprogramming for precision miRNA targeting. Unraveling this regulatory axis offers a promising avenue for developing multi-targeted therapies and personalized cancer treatment strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1616221"},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949034","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":"Targeted urinary metabolomics combined with machine learning to identify biomarkers related to central carbon metabolism for IBD.","authors":"Miao-Lin Lei, Guan-Wei Bi, Xiao-Lin Yin, Yue Wang, Zi-Ru Sun, Xin-Rui Guo, Hui-Peng Zhang, Xiao-Han Zhao, Feng Li, Yan-Bo Yu","doi":"10.3389/fmolb.2025.1615047","DOIUrl":"10.3389/fmolb.2025.1615047","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Current diagnostic approaches are invasive, costly, and time-consuming, underscoring the need for non-invasive, accurate diagnostic methods.</p><p><strong>Methods: </strong>We conducted a targeted metabolomic analysis of 49 metabolites related to central carbon metabolism in urinary samples from individuals with IBD and control group. Diagnostic models were constructed using six machine learning algorithms, and their performance was evaluated by cross-validated area under the receiver operating characteristic curve (AUC). The SHAP (SHapley Additive exPlanations) method was used to interpret the models and identify key discriminatory features.</p><p><strong>Results: </strong>Six metabolites-xylose, isocitric acid, fructose, L-fucose, N-acetyl-D-glucosamine (GlcNAc), and glycolic acid-differentiated UC from control group, while three metabolites-xylose, L-fucose, and citric acid-distinguished CD from control group. The optimal diagnostic model achieved a mean AUC of 0.84 for UC and 0.93 for CD. These models retained high diagnostic accuracy even after adjusting for disease activity. SHAP analysis identified L-fucose, xylose, and GlcNAc as important features for UC, and citric acid and xylose for CD.</p><p><strong>Discussion: </strong>Our findings highlight distinct metabolic signatures in central carbon metabolism associated with IBD subtypes. The identified metabolite panels, combined with machine learning models, offer promising non-invasive tools for differentiating UC and CD from healthy individuals.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1615047"},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948644","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":"Beyond the glitter: gold nanoparticles as powerful weapons against multi-drug resistant pathogens.","authors":"Hazim O Khalifa, Hind Alkhoori","doi":"10.3389/fmolb.2025.1612526","DOIUrl":"10.3389/fmolb.2025.1612526","url":null,"abstract":"<p><p>Gold nanoparticles (AuNPs) have emerged as promising antimicrobial agents in the fight against multidrug-resistant (MDR) pathogens. Their distinctive physicochemical properties allow them to target a broad spectrum of MDR microorganisms, including highly virulent strains such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i>, <i>Acinetobacter baumannii</i>, and <i>Candida albicans</i>. AuNPs exert potent antimicrobial effects through various mechanisms, including bacterial growth inhibition, biofilm disruption, reactive oxygen species (ROS) generation, and enhancement of conventional antibiotic efficacy. Compared to traditional antimicrobials, these nanoparticles offer key advantages such as low toxicity, high biocompatibility, and a reduced likelihood of promoting bacterial resistance. This review provides a comprehensive analysis of the antimicrobial mechanisms, synergistic interactions with antibiotics, and therapeutic potential of AuNPs. Additionally, it examines recent advancements in their clinical applications, formulation strategies, and safety profiles. Despite encouraging results, challenges persist in optimizing AuNP synthesis, evaluating their long-term effects, and ensuring their large-scale clinical translation. Future research should focus on improving nanoparticle formulations, assessing their <i>in vivo</i> efficacy, and conducting extensive clinical trials to confirm their therapeutic viability. Overall, AuNPs represent a promising and multifaceted approach to tackling antimicrobial resistance, offering new avenues for the development of effective treatments against MDR pathogens.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1612526"},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949072","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":"In-silico evaluation of putative maternal semiochemicals of pigs with receptor proteins.","authors":"Devaraj Sankarganesh, Ambritha Balasundaram, Hayavadhan Sampath, Diya Manjunath, George Priya Doss C","doi":"10.3389/fmolb.2025.1600209","DOIUrl":"10.3389/fmolb.2025.1600209","url":null,"abstract":"<p><p>Piglets at weaning experience stress owing to environmental changes. Mixing unfamiliar littermates also induces fighting and biting behaviors among them, affecting their welfare. In addition, post-weaning weight gain or loss is also influenced during the first week of weaning. Many compounds have been identified in the secretions of sows to address these behavioral and welfare issues; nevertheless, the positive influence of these compounds on piglet behavior and welfare is not fully understood. Therefore, we sought to study the interaction between the compounds (myristic acid, oleic acid, lauric acid, palmitic acid, 3-methyl phenol, tiglic aldehyde, and skatole, reported as maternal pheromones/urinary metabolites) and receptor proteins using computational approaches. We used five proteins, including alpha-1-acid glycoprotein (AGP), odorant binding protein (OBP), salivary lipocalin (SAL), pheromaxein, and Von Ebner's Gland Protein (VEGP). We utilized molecular docking with AutoDock Vina and molecular dynamics simulations (MDS) using GROMACS to examine the stability of interactions between the listed compounds and proteins. The binding energies for the docked complexes ranged between -3.4 and -6.7 kcal/mol. Through analysis of the lowest root mean square deviation (RMSD) and hydrogen bond formations, we identified that at least one of the fatty acids exhibited optimal docking with four distinct proteins. The RMSD data for these complexes also indicated stability over a 100-ns MDS period. However, the post-MDS Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) binding energy data revealed that palmitic acid had the highest stabilizing energy across all five proteins compared to other complexes. Additionally, myristic acid and oleic acid also exhibited a high binding affinity with the proteins. Taken together, our findings suggest that fatty acids could be the most effective semiochemicals for managing behavioral and welfare issues in weaning piglets.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1600209"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948993","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: Multi-scale systems: ecological approaches to investigate the role of the microbiota in different niches.","authors":"Padhmanand Sudhakar, Kristel Van Steen, Amirul Islam Mallick, Kaline Arnauts","doi":"10.3389/fmolb.2025.1665390","DOIUrl":"10.3389/fmolb.2025.1665390","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1665390"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949009","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":"Identification and verification of biomarkers associated with neutrophils in acute myocardial infarction: integrated analysis of bulk RNA-seq, expression quantitative trait loci, and mendelian randomization.","authors":"Guoqing Liu, Xiangwen Lv, Jiahui Qin, Xingqing Long, Miaomiao Zhu, Chuwen Fu, Jian Xie, Peichun He","doi":"10.3389/fmolb.2025.1614350","DOIUrl":"10.3389/fmolb.2025.1614350","url":null,"abstract":"<p><strong>Background: </strong>Immune infiltration is closely related to the progression of acute myocardial infarction (AMI), among which neutrophils have received extensive attention. However, the concrete association between AMI and neutrophils remains uncertain.</p><p><strong>Methods: </strong>Bulk RNA-seq data for patients with AMI were downloaded from the Gene Expression Omnibus (GEO) database. CIBERSORT was utilized to measure 22 degrees of immune cell composition. The causal link between neutrophils and AMI was determined by Mendelian randomization (MR) analysis. Genes with correlation coefficients >0.7 with neutrophils were selected, and their representativeness was confirmed by functional enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was performed to screen for AMI-related modular genes. Robust molecular clusters linked to neutrophils were recognized via consensus clustering methodology. Hub genes were screened using the least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms. A cellular model of AMI was established using oxygen- and glucose-deprived AC16 cells. Quantitative reverse transcription‒polymerase chain reaction (RT‒qPCR) was used to validate the gene expression levels. The expression quantitative trait loci (eQTL) analysis is used to identify genetic variations in the expression of regulatory genes in AMI.</p><p><strong>Results: </strong>MR results demonstrated a significant causal relationship between neutrophils and AMI. The consensus clustering method delineated two gene subclusters, and the expression of AMI-related neutrophil coexpressed genes was consistent with innate immune cell infiltration. Three hub neutrophil coexpressed genes (<i>BCL6</i>, <i>CDA</i>, and <i>IL1R2</i>) were identified. The receiver operating characteristic (ROC) curves indicated that the three genes were valuable for diagnosing AMI in the training and validation sets, and the RT‒qPCR results verified the gene expression data. A prediction model was constructed based on three hub neutrophil coexpressed genes in AMI, and the results revealed good accuracy. The eQTL analysis further confirmed that <i>BCL6</i> plays a pivotal role as a key risk gene in neutrophil-mediated damage in AMI.</p><p><strong>Conclusion: </strong>There is a causal relationship between neutrophils and AMI. <i>BCL6</i> plays a pivotal role as a key risk gene in neutrophil-mediated damage in AMI. However, more comprehensive studies are needed to determine the molecular mechanism of AMI-related neutrophil coexpressed genes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1614350"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949017","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}