Frontiers in Molecular Biosciences最新文献

{"title":"Lipid droplet-mitochondria crosstalk in osteoarthritis: linking lipid routing to metabolic mismatch.","authors":"Gang Meng, Ruijie Hou, Ping Dong, Qiannan Chen, Xueyuan Li, Kai Hu, Zixuan Du, Rong Wang, Zhaoxin Zhong","doi":"10.3389/fmolb.2026.1973436","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1973436","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a whole-joint disease characterized by metabolic reprogramming beyond structural degeneration. Increasing evidence indicates that lipid droplets (LDs) regulate lipid storage, mobilization and intracellular lipid routing, while alterations in mitochondrial metabolism determine the capacity of chondrocytes to adapt to metabolic stress. However, LD accumulation alone is insufficient to define metabolic dysfunction, as it may represent either adaptive buffering or maladaptive retention. This review proposes a lipid flux-mitochondrial capacity matching framework to integrate lipid handling with mitochondrial oxidative capacity, redox regulation and quality control. We discuss how excessive lipid flux relative to mitochondrial capacity may promote oxidative stress, lipid peroxidation, ferroptosis, senescence and extracellular matrix disruption, whereas balanced lipid utilization supports chondrocyte homeostasis. Current evidence on LD biology, fatty acid oxidation, mitophagy and whole-joint metabolic communication is summarized, with clear distinction between direct OA evidence and findings from other cellular systems. Although organelle contact sites such as PLIN5-FATP4, PLIN3-VDAC3 and ESYT1/2-VAPB represent potential regulators of lipid routing, their functional relevance in OA chondrocytes remains to be established. Future studies integrating isotope tracing, metabolic flux analysis and dynamic organelle imaging are required to clarify how lipid routing and mitochondrial capacity jointly regulate OA progression.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1973436"},"PeriodicalIF":4.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223701","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":"Instillation timing as the main determinant of aqueous humor nepafenac exposure.","authors":"Angelo Macri, Annalisa Salis, Margherita Tarallo, Michele Iester, Gianluca Damonte, Francesca Mattioli","doi":"10.3389/fmolb.2026.1913752","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1913752","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate aqueous humor concentrations of nepafenac following topical administration of 0.3% and 0.1% formulations, to assess the influence of timing of instillation on intraocular exposure.</p><p><strong>Methods: </strong>Aqueous humor samples collected during anterior segment surgery were analyzed. Nepafenac concentrations were quantified in 151 samples (0.3% instilled once daily: n = 73; 0.1% instilled three times daily: n = 78). Amfenac was quantified only in the nepafenac 0.3% group (n = 73), owing to the stepwise validation of the analytical method (see Limitations). Due to right-skewed distributions, concentrations were summarized as median (IQR) and geometric mean with 95% confidence intervals Mann-Whitney U test and Spearman's rank correlation coefficient were applied. Postoperative optical coherence tomography was performed at 1, 2, and 3 months to assess the occurrence of Irvine-Gass syndrome.</p><p><strong>Results: </strong>Geometric mean nepafenac concentrations were 22.13 nM (95% CI 15.85-30.91) for 0.3% and 21.73 nM (95% CI 13.29-35.53) for 0.1% (p = 0.319). Within the 0.1% group, instillation timing significantly influenced concentrations (p < 0.001), with markedly higher levels approximately 30-60 min after instillation compared with the 10-12 h subgroup. Amfenac correlated with nepafenac (ρ = 0.56, p < 0.001). No cases of clinically evident Irvine-Gass syndrome were observed.</p><p><strong>Conclusion: </strong>No cases of clinically evident Irvine-Gass syndrome were observed; however, the study was not powered or designed to assess clinical efficacy. Timing of instillation is a major determinant of aqueous humor nepafenac concentrations. Preoperative instillation shortly before surgery may optimize intraoperative drug availability and support maintenance of mydriasis. Standardized sampling is essential for robust pharmacokinetic comparisons.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1913752"},"PeriodicalIF":4.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223674","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":"AIPFusion-Net: an interaction-fusion framework for anti-inflammatory peptide prediction using protein language model embeddings, local sequence patterns, and handcrafted descriptors.","authors":"Wentao Wang, Weidong Yang, Hongmei Li, Zhenyu Cui, Dan Shen","doi":"10.3389/fmolb.2026.1952395","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1952395","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-inflammatory peptides (AIPs) are promising candidates for treating inflammatory diseases. However, experimental identification is time-consuming and costly, creating a need for accurate computational prediction methods.</p><p><strong>Methods: </strong>We developed AIPFusion-Net, an interaction-fusion framework that integrates three complementary sources of peptide information: global contextual embeddings generated by the ESM2 protein language model, local sequence patterns extracted from biologically relevant subsequences, and handcrafted physicochemical and sequence descriptors. These representations were integrated through an interaction-fusion module and evaluated on two independent test datasets, Ind-1049 and Ind-426.</p><p><strong>Results: </strong>On the Ind-1049 dataset, AIPFusion-Net achieved an accuracy of 84.6%, sensitivity of 71.7%, specificity of 89.3%, MCC of 0.654, and AUC of 0.884. On the Ind-426 dataset, it achieved an accuracy of 82.3%, sensitivity of 84.4%, specificity of 76.9%, MCC of 0.673, and AUC of 0.882. The model outperformed the comparative predictors in overall classification performance and discriminative ability.</p><p><strong>Discussion: </strong>The results indicate that combining global contextual information, local sequence patterns, and handcrafted descriptors through interaction fusion improves the representation and identification of AIPs. AIPFusion-Net provides a useful computational framework for AIP screening and may support the discovery and design of novel anti-inflammatory peptides.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1952395"},"PeriodicalIF":4.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223667","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":"Full-protein release assay in a reconstituted yeast translation system using GGQ-methylated eRF1.","authors":"Shuai Huang, Yichen Xu, Wenting Chen, Ziang Miao, Chang Liu, Riku Nagai, Muhoon Lee, Hitomi Seike, Shinji Nagata, Nono Takeuchi-Tomita","doi":"10.3389/fmolb.2026.1933983","DOIUrl":"10.3389/fmolb.2026.1933983","url":null,"abstract":"<p><p>Translation termination in eukaryotes requires the concerted action of release factors eRF1 and eRF3, together with accessory factors including eIF5A and Rli1, to achieve efficient peptide release from the ribosome. Here, we establish a yPURE system-based Termi-nLuc assay, in which pre-termination complexes (PreTCs), carrying full-length nanoluciferase (nLuc) peptidyl-tRNA, are formed by simply omitting release factors from the reconstituted yeast translation system, enabling rapid and sensitive analysis without the need for sucrose density gradient purification. To enable direct biochemical analysis of GGQ methylation-a physiologically important modification of eRF1 whose effects on peptide release activity had not previously been examined <i>in vitro</i>-we also established an <i>Escherichia coli</i> co-expression system of eRF1 and its GGQ-methylating enzyme, yielding fully GGQ-methylated eRF1. Using this platform, we characterized the individual and combined contributions of eRF1, eRF3, eIF5A, and Rli1 to peptide release, and demonstrated that the full complement of these factors is sufficient for efficient release. Under the current assay conditions, neither GGQ methylation of eRF1 nor the identity of the penultimate amino acid of the protein detectably affected peptide release activity, consistent with the possibility that eRF1•eRF3 recruitment to the ribosome, rather than the chemical hydrolysis step, is rate-limiting under these conditions. The yPURE-based Termi-nLuc assay is readily amenable to manipulation of the composition of translation factors, tRNAs, and mRNA sequences, making it a versatile and high-throughput-compatible platform for future studies of context-dependent regulation of translation termination, with potential applications in the screening of small molecules that modulate termination efficiency or promote readthrough of premature stop codons for the treatment of genetic diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1933983"},"PeriodicalIF":4.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215473","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":"Integrated transcriptome and single-cell RNA sequencing identifies transient receptor potential channel-related biomarkers in ulcerative colitis.","authors":"Tiantian Bao, Tianru Xie, Jiang Chen, Yibo Cao, Jian Zhu, Pingliang Sun, Tao Yang","doi":"10.3389/fmolb.2026.1902447","DOIUrl":"10.3389/fmolb.2026.1902447","url":null,"abstract":"<p><strong>Background: </strong>The precise cause of ulcerative colitis (UC) is still unclear. While transient receptor potential (TRP) ion channels are increasingly linked to UC pathophysiology, the comprehensive roles of TRP channel-related genes are not well understood. This study aimed to systematically identify TRP channel-related biomarkers and develop novel diagnostic and therapeutic targets for UC.</p><p><strong>Methods: </strong>Transcriptomic data were retrieved from the Gene Expression Omnibus (GEO). Machine learning algorithms were applied to select signature genes from the overlap between differentially expressed genes (DEGs) and a curated set of 111 transient receptor potential (TRP) channel-related genes. A diagnostic nomogram incorporating signature genes was constructed, and its performance was assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). The cellular landscape was characterized using single-cell RNA sequencing (scRNA-seq) combined with pseudotime trajectory inference and cell-cell communication analysis. Key results were further validated in a dextran sulfate sodium (DSS)-induced murine colitis model by flow cytometry, multiplex immunohistochemistry, western blotting, and quantitative real-time PCR.</p><p><strong>Results: </strong>Five TRP channel-related feature genes (IL-1β, PIK3R3, ADCY3, ADCY7, and TRPV1) were identified. In UC, IL-1β, PIK3R3, ADCY3, and ADCY7 were notably upregulated, while TRPV1 was markedly downregulated. The nomogram, utilizing these five feature genes, exhibited outstanding discriminatory capability (AUC = 0.993) and provided enhanced net clinical benefit. scRNA-seq analysis identified B and plasma cells as the most significantly expanded pathogenic population, exhibiting acquired bidirectional crosstalk with epithelial cells in UC. Pseudotime trajectory analysis revealed that IL-1β and PIK3R3 were mainly concentrated during the initial developmental phases of B and plasma cells. In the DSS-induced colitis model, there was a notable increase in B-cell infiltration, accompanied by significant upregulation of IL-1β and Pik3r3 at both protein and mRNA levels, with confirmed colocalization with Cd19⁺ B cells.</p><p><strong>Conclusion: </strong>This study identified five TRP channel-related biomarkers and created a high-performance diagnostic nomogram for UC. The study underscores the pivotal role of B and plasma cells, identifying IL-1β and PIK3R3 as early-activated genes in pathogenic B-cell responses, thus offering new diagnostic biomarkers and therapeutic targets for UC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1902447"},"PeriodicalIF":4.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215478","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":"Artificially intelligent modeling of macromolecular assemblies.","authors":"Margherita Bini, Valentina Tozzini","doi":"10.3389/fmolb.2026.1856649","DOIUrl":"10.3389/fmolb.2026.1856649","url":null,"abstract":"<p><p>The study of macromolecular assembly formation is one of the most challenging tasks in computational modeling as it requires extensive exploration of conformational and configurational space, especially when driven by conformational transitions or folding instabilities, which are typically associated with high energy barriers. Although this type of study has traditionally been addressed <i>in silico</i> by using techniques that reduce the computational cost of simulations, such as coarse-grained models, artificial intelligence (AI) has recently entered the field at multiple levels, aiding in parameter optimization or trajectory analysis and even replacing potentials or force calculations. Recently developed algorithms such as AlphaFold (AF) and RoseTTAFold enable the direct prediction of final structures with high efficiency and confidence, an achievement that earned them the 2024 Nobel Prize in Chemistry. In this study, we review and analyze the different AI-based strategies used to model protein structure and dynamics and simulate macromolecular assemblies, comparing them with traditional methods, to highlight their respective advantages and limitations. By placing these approaches along an ideal continuum in which accuracy increases as interpretability decreases, we show that hybrid solutions and combinations of methods can be devised to maximize their strengths. Finally, we perspectively outline practical strategies for implementing such integrated approaches in a coherent manner, preserving accuracy and feasibility while maintaining insight into aggregation pathways, intermediate structures, and the molecular mechanisms underlying the phenomenon.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1856649"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215533","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":"Exosomal microRNAs as biomarkers of multimorbidity risk in lean and obese women with polycystic ovary syndrome.","authors":"Debarati Halder, P V Varshini, Tridip Mitra, A H Sruthi Anil Kumar, Piyush Agrawal, Mrinmoy Das, A Senthil Kumar, R Sajeetha Kumari, S N Meenakshi Sundari, Rajiv Janardhanan","doi":"10.3389/fmolb.2026.1868855","DOIUrl":"10.3389/fmolb.2026.1868855","url":null,"abstract":"<p><p>Polycystic ovarian syndrome (PCOS) is a multifactorial endocrine disorder that is characterised by reproductive, metabolic and cardiometabolic abnormalities. Besides typical hormonal abnormalities, inter-organ communication has a crucial role in the development of PCOS-associated multimorbidity. PCOS causes early changes in the insulin signalling pathway, inflammatory pathways, androgen synthesis genes, and ovarian theca cell activity even before the appearance of regular symptoms such as irregular periods, polycystic ovaries, weight gain, and hyperandrogenism. Exosomes are tiny extracellular vesicles discharged into the circulation. It transports molecular cargoes such as microRNAs (miRNAs), proteins that influence gene expression and reflect the underlying pathophysiological condition of target tissues. Exosomes facilitate early disease detection by carrying stable, selectively packaged gene-regulatory molecules that reflect early cellular and molecular alterations before phenotypic manifestations occur. Although exosomal miRNAs (ExomiR) are stable, non-invasive, and easily detectable in body fluids, they serve as a potent biomarkers. These circulating ExomiR have contributed to multiple organ dysfunctions, including the ovary, adipose tissue, liver, cardiovascular system, and brain, thereby raising the risk of comorbid conditions like endometrial disorder, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. In obese PCOS, circulating ExomiR influences pathways related to steroidogenesis, insulin signalling, inflammation, oxidative stress, and lipolysis. However, its role in lean PCOS is not well studied. This review summarises the potential roles of ExomiR as novel biomarkers that bridge reproductive and non-reproductive facets of PCOS, indicating new paths for precision medicine and tailored treatment interventions in both lean and obese PCOS phenotypes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1868855"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215540","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":"Discovery of metabolite biomarkers for cerebral ischemia-reperfusion injury based on metabolomics: neurotoxic mechanism and functional validation of a flavopiridol -related metabolite.","authors":"Zhi-Guang Song, Yu-Chen Liu, Zhen-Lin Zhong, Shu-Ting Yin, Si-Si Dai, Yi-di Zeng, Cai-Xing Zheng, Si-Yuan Chen, Ji-Yong Liu, Yan-Song Liu, Si-Min Peng, Shi-Min Tan, Qian-Ru Zeng, Hua Li, Wang-Hua Liu","doi":"10.3389/fmolb.2026.1752337","DOIUrl":"10.3389/fmolb.2026.1752337","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role and potential mechanism of metabolite alterations during cerebral ischemia-reperfusion injury (CIRI) and to explore novel candidate molecular markers for the diagnosis of this disease.</p><p><strong>Methods: </strong>A rat model of middle cerebral artery occlusion was established using the modified Longa EZ intraluminal suture method. The infarct status was comprehensively evaluated by neurological deficit score (mNSS), TTC staining, HE staining, and Nissl staining. Serum metabolite changes after CIRI were detected using non-targeted metabolomics, and the potential toxic effects of significantly altered metabolites were predicted using the ProTox tool. Subsequently, bioinformatics analysis was employed to identify core targets and key pathways associated with the metabolite of interest, followed by molecular docking and molecular dynamics simulations to predict their interactions.</p><p><strong>Results: </strong>Metabolomic analysis identified 41 significantly upregulated and 232 downregulated metabolites. Among the significantly altered metabolites, a flavopiridol-related metabolite (FRM) exhibited potential neurotoxic characteristics. A total of 193 CIRI-related core targets were associated with this metabolite, from which 10 core targets and 15 key pathways were further screened. ROC analysis suggested that this metabolite possessed good discriminatory ability (AUC = 0.94). Molecular docking results showed binding energies of less than -7 kcal/mol for all core targets. A 100 ns molecular dynamics simulation indicated that the complex formed by the FRM and SRC remained structurally stable, as evidenced by balanced RMSD, Rg, SASA, and P-L-RMSD values. The calculated binding free energy was -32.48 kcal/mol, with key residues LEU-393, MET-341, and GLU-339 contributing significantly to the interaction, suggesting potential biological activity.</p><p><strong>Conclusion: </strong>This study reveals a complex metabolic reprogramming phenomenon during CIRI and preliminarily identifies a FRM as a potential candidate molecular marker and possible interventional target, providing a new theoretical basis and directions for future research on the diagnosis and treatment of CIRI.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1752337"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215528","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":"Bacterial actin MreB as a new antibiotic target.","authors":"Emőke Bódis, Beáta Longauer, András Lukács, Tamás Huber, Miklós Nyitrai, Géza Makkai, Tibor Jánosi, Rita Börzsei, Csaba Hetényi, Zoltán Gazdag, Szilvia Barkó","doi":"10.3389/fmolb.2026.1912759","DOIUrl":"10.3389/fmolb.2026.1912759","url":null,"abstract":"<p><p>Actin homolog MreB plays a crucial role in the synthesis of the bacterial cell wall. Disruption of the MreB filament network results in the disruption of the cell wall, which thus serves an unconventional antibacterial strategy. A22, a small inhibitor molecule, binds directly to the MreB filament, altering its structure and causing a morphological change of the cell, leading to cell death. This effective antibacterial property is shadowed by the fact that at high concentration, A22 is toxic to eukaryotic host cells, so it cannot be administered at higher doses. Vancomycin is a widely used antibiotic targeting Gram-positive bacteria at concentrations as high as 10-20 μg/mL, which can occasionally cause serious side effects. In this study, we present our recent findings that a synergistic interaction exists between A22 and vancomycin, which results in the inhibition of cell proliferation by the combined use of very low concentrations of A22 (6.25 μg/mL) and vancomycin (1.56 μg/mL). In addition, in the presence of A22, vancomycin is effective not only against Gram-positive bacteria but also against Gram-negative bacteria. Since 5 of the 7 most common antibiotic-resistant bacteria according to the WHO are Gram-negative, this synergism between A22 and vancomycin opens a new way of combating bacterial infections. Our spectroscopic results indicate that vancomycin binds directly to MreB; using a computer docking method, we determined the possible binding site of vancomycin on the MreB filament. This newly identified interaction between vancomycin and A22 highlights the potential of the combined use, providing a new strategy to tackle antibiotic resistance.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1912759"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215483","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":"Gut microbiota-cancer crosstalk: emerging molecular targets for personalized cancer treatment- a comprehensive review.","authors":"Pooja Negi, Arpita Upreti, Preeti Budhlakoti, Amit Kumar Sen, Mitali Danu, Sumit Tewari, Nirmal Joshi, Deepak Chandra Joshi","doi":"10.3389/fmolb.2026.1924197","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1924197","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, and growing evidence indicates that the gut microbiota plays an important role in cancer initiation, progression, metastasis, and response to treatment through complex interactions with host signaling, metabolism, and immunity. This comprehensive narrative review discusses the molecular mechanisms underlying gut microbiota-cancer crosstalk, with particular emphasis on dysbiosis, microbial metabolites, immune modulation, and microbiota-regulated oncogenic pathways, including TLR/NF-κB, Wnt/β-catenin, JAK/STAT, PI3K/Akt/mTOR, and Hippo-YAP signaling. The review also examines emerging molecular targets, including microbial extracellular vesicles, bacterial small RNAs, ferroptosis-related mechanisms, and microbiota-mitochondria interactions. In addition, current microbiota-targeted therapeutic strategies, such as fecal microbiota transplantation, engineered bacterial therapeutics, CRISPR-based microbiome engineering, and microbiome-informed approaches to precision oncology are discussed. Relevant peer-reviewed literature published primarily within the recent 5-year period was considered from major scientific databases and publisher platforms, including PubMed, Scopus, Web of Science, Springer, Elsevier, and MDPI. Overall, the available evidence suggests that gut microbiota represents an important component of the tumor ecosystem and may provide promising biomarkers and therapeutic targets. Integration of microbiome research with multi-omics and artificial intelligence may further support the development of personalized cancer treatment.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1924197"},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192744","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}