Molecular Biology Reports最新文献

{"title":"Binding analysis of the response regulator NarL protein to the promoter of the O⁶-methylguanine-DNA methyltransferase (ogt) gene in Salmonella Typhimurium.","authors":"Pravas Ranjan Sahoo, Ajay Kumar, M Pashupathi, Jyochhna Rani Sahoo","doi":"10.1007/s11033-026-12687-w","DOIUrl":"https://doi.org/10.1007/s11033-026-12687-w","url":null,"abstract":"<p><strong>Background: </strong>Salmonella Typhimurium (STM) is a gram-negative bacterium that causes severe gastrointestinal disorders in both animals and humans. The regulation of DNA repair genes is critical for maintaining genomic stability of the bacteria. O⁶-methylguanine DNA methyltransferase (Ogt), plays a vital role in repairing alkylated DNA in STM; however, the transcriptional regulation of ogt gene remains poorly characterized. Furthermore, NarL is a transcriptional regulator, involved in the pathogenesis of STM under anaerobic condition. Therefore, this study investigated the interaction between NarL protein and the promoter region of the ogt gene.</p><p><strong>Methods: </strong>In this study, narl gene was cloned in pET32a vector and NarL protein was expressed in Escherichia coli BL21 (DE3). Subsequently, the ogt gene promoter (pogt) was selected, amplified, cloned and its activity was evaluated. Electrophoretic mobility shift assay (EMSA), isothermal titration calorimetry (ITC), molecular docking were employed to elucidate the interaction between NarL protein and ogt promoter. Furthermore, the regulatory role of NarL in ogt gene expression was validated in vivo using RT-qPCR and β-galactosidase assay.</p><p><strong>Results: </strong>This study resulted that NarL protein interacts specifically with the ogt promoter, as confirmed by EMSA and ITC, with ΔG of - 9.42 kcal mol⁻¹. Furthermore, RT-qPCR and β-galactosidase assays demonstrated that deletion of narl significantly (P ≤ 0.01) decreased ogt transcript levels and promoter activity than wild Salmonella Typhimurium, whereas exogenous supplementation of recombinant NarL protein restored the expression. These findings suggest that NarL plays a potential regulatory role in ogt gene expression in response to environmental signals.</p><p><strong>Conclusion: </strong>These findings highlight an interaction between NarL protein and the promoter region of ogt gene in Salmonella Typhimurium, linking nitrogen metabolism with the DNA repair pathway in STM, which may contribute to the bacterial survival under nitrosative stress.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic diversity and resistance determinants of staphylococci from cow and buffalo milk.","authors":"Jaydeep Banerjee, Sk Masud Karim, Deepjyoti Sharma, Barnan Choudhury, Suman Biswas, Indranil Samanta, Pramod K Nanda, Tapas K Biswas, M Suman Kumar, Premanshu Dandapat, Arnab Sen, Samiran Bandyopadhyay","doi":"10.1007/s11033-026-12729-3","DOIUrl":"https://doi.org/10.1007/s11033-026-12729-3","url":null,"abstract":"<p><strong>Background: </strong>Staphylococci are important mastitis pathogens in dairy animals and serve as reservoirs of antimicrobial resistance genes (ARGs) having zoonotic potential. Genomic characterization of resistant isolates is essential to understand their diversity, resistance mechanisms, and One Health implications.</p><p><strong>Methods and results: </strong>A total of 363 cow and buffalo milk samples-including 108 from animals with mastitis-were screened, yielding 98 staphylococcal isolates, comprising 20 Staphylococcus aureus and 78 coagulase-negative staphylococci (CoNS). Antimicrobial susceptibility testing revealed resistance to cefoxitin (CoNS: 21.7%; S. aureus: 10%), tetracycline (CoNS: 19.2%; S. aureus: 10%), erythromycin (CoNS:16.7%; S. aureus: 10%), gentamicin (CoNS: 10.2%; S. aureus: 10%) and fluoroquinolone (CoNS: 10.2%), while the majority were sensitive to chloramphenicol, cotrimoxazole (~ 95%, each), linezolid (~ 97%), and vancomycin (100%). Nineteen isolates, including two S. aureus, were cefoxitin-resistant, and eight carried the mecA gene. Whole genome sequencing of these eight isolates revealed genome sizes ranging from 2.27 to 2.78 MB, with the methicillin resistant S. aureus (MRSA, ERSST98) isolate possessing the largest genome and the highest rRNA copy number. Comparative genomic analysis revealed various SCCmec types along with an extensive array of resistance determinants, encompassing aminoglycosides, macrolides, tetracyclines, efflux systems, and heavy metals, underscoring the multifaceted resistance repertoire of these strains. Virulence profiling of ERSST98 demonstrated a broad arsenal of adhesins, toxins, and biofilm‑associated genes, highlighting its pathogenic capacity. Mobile genetic elements with diverse plasmid replicons and insertion sequence families further contributed to genomic plasticity.</p><p><strong>Conclusions: </strong>Collectively, this study underscores the genomic diversity of methicillin-resistant staphylococci from dairy animals with extensive resistance determinants and highlights their zoonotic relevance within One Health framework.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization and co-occurrence of ESBL, carbapenemase and mcr-1 genes in Klebsiella pneumoniae from poultry production systems in Pakistan.","authors":"Rameen Parvez, Mohsin Khurshid, Muhammad Hidayat Rasool, Bilal Aslam, James Jacob Sasanya","doi":"10.1007/s11033-026-12718-6","DOIUrl":"https://doi.org/10.1007/s11033-026-12718-6","url":null,"abstract":"<p><strong>Background and aims: </strong>Klebsiella pneumoniae is an important opportunistic pathogen with a high capacity to acquire antimicrobial resistance determinants. However, data on the distribution and co-occurrence of extended-spectrum β-lactamase (ESBL), carbapenemase and plasmid-mediated colistin resistance genes in poultry-associated K. pneumoniae in Pakistan remain limited. This study investigated the prevalence, antimicrobial resistance profiles and molecular characteristics of K. pneumoniae recovered from commercial broiler farms, backyard poultry flocks and retail poultry markets.</p><p><strong>Methods: </strong>A total of 900 samples were collected from commercial broiler farms, backyard poultry flocks and retail poultry markets in Faisalabad Division, Pakistan, between September 2024 and April 2025. K. pneumoniae isolates were identified using conventional biochemical testing, API 20E, MALDI-TOF MS and rpoB gene amplification. Antimicrobial susceptibility testing was performed according to CLSI 2024 recommendations, and PCR was used to detect ESBL, carbapenemase, plasmid-mediated quinolone, aminoglycoside, sulfonamide, tetracycline, chloramphenicol and colistin resistance genes.</p><p><strong>Results: </strong>K. pneumoniae was recovered from 303/900 samples (33.7%). Among the isolates, 199 (65.7%) were multidrug-resistant (MDR) and 48 (15.8%) were extensively drug-resistant (XDR). Commercial farm isolates showed a greater resistance burden than isolates from backyard flocks and retail markets. The most frequently detected ESBL genes were bla_CTXM-15 and bla_TEM, while bla_NDM, bla_KPC and bla_OXA-48 were detected among carbapenem-resistant isolates. Colistin resistance was detected in 5.9% of isolates, with mcr-1 identified among the resistant isolates. Twenty-one distinct resistance gene combinations were identified, including combinations involving ESBL, carbapenemase and colistin resistance determinants.</p><p><strong>Conclusions: </strong>Poultry-associated K. pneumoniae showed a substantial burden of multidrug resistance and diverse combinations of clinically important resistance determinants, particularly among isolates from commercial farms. The findings support strengthened antimicrobial stewardship, farm-level biosecurity and integrated molecular surveillance within poultry production systems as components of a One Health approach to AMR control.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical profiling of Egregia menziesii and anti-inflammatory potential in LPS-activated RAW 264.7 macrophages.","authors":"Omar Arroyo-Xochihua, Alberto Sánchez-Medina, Óscar López-Franco, Tatiana N Olivares-Bañuelos, Rossana C Zepeda","doi":"10.1007/s11033-026-12685-y","DOIUrl":"https://doi.org/10.1007/s11033-026-12685-y","url":null,"abstract":"<p><strong>Background: </strong>Egregia menziesii (E. menziesii) is recognized for its anticancer and hypoglycemic properties. Chemically, it contains compounds with potential anti-inflammatory activity. Within the immune system, macrophages play an essential role in containing and eradicating pathogens through phenotypic polarization.</p><p><strong>Methods and results: </strong>The ethanol and water (1:1 v/v) (EtOH: H₂O), extract of E. menziesii was obtained and fractionated. The chemical profiles of the extracts featured signals linked to sulfated polysaccharides and mannitol. Cell viability was evaluated at various concentrations with MTT assay and confirmed the safety (≥ 90% of cell viability) of the extract and fractions for cellular experimentation. The scratching assay demonstrates the impact of the EtOH: H₂O and aqueous fraction (FR_Aq) treatments, evidenced by a reduction of up to 40% and 10% in the free scratched area at 24 and 48 h, respectively. The phagocytosis assay, determined by the neutral red assay, shows that EtOH: H₂O treatment decreases the process to levels below those of the LPS- control group (< 120%). Proton signals of the extract and fractions were correlated with the scratched area value via Multivariate Data Analysis (MVDA) of the ¹H-NMR data of the extract and fractions and the results from scratching assay showed the signals at δ 0.6-3 ppm as the main contributors to the activity. Additionally, interleukin-1β (IL-1β) and interleukin-6 (IL-6) expression levels were determined by RT-qPCR and ELISA, showing that the EtOH: H₂O extract could influence their mRNA expression (Fold change < 0.5 and < 3, respectively) and protein levels.</p><p><strong>Conclusions: </strong>E. menziesii safely regulates macrophage behavior, IL-1β and IL-6 release and promotes scratch area reduction. The immunomodulatory effect could be linked to the presence of sulfate polysaccharides and mannitol.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ellagic acid regulates astrocytic responses under inflammatory conditions in primary astrocyte cultures: effects on oxidative stress, inflammatory cytokines, and glycogen synthase kinase-3β.","authors":"Thais Marini da Rosa, Larissa Menezes da Silveira, Natália Pontes Bona, Juliane Torchelsen Saraiva, Júlia Araújo da Silva, William Borges Domingues, Lucas Petitemberte de Souza, Mariana Cavalcanti Nascimento, Vinicius Farias Campos, Francieli Moro Stefanello, Cinthia Melazzo de Andrade, Nathalia Stark Pedra, Roselia Maria Spanevello","doi":"10.1007/s11033-026-12671-4","DOIUrl":"https://doi.org/10.1007/s11033-026-12671-4","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation involves the activation of glial cells, particularly astrocytes, and microglia, in response to pathological stimuli. Astrocyte activation is characterized by increased pro-inflammatory cytokines and oxidative stress. Given their role in neuroinflammation, targeting astrocytic mechanisms presents potential therapeutic opportunities. Ellagic acid (EA), a phenolic compound, exhibits antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated the effect of EA on astrocytes from neonatal rats exposed to lipopolysaccharide (LPS), a potent proinflammatory agent widely used to induce neuroinflammation in vitro.</p><p><strong>Methods and results: </strong>Astrocytes were pretreated with EA (50, 100, and 200 µM) for 48 h and subsequently exposed to LPS (1 µg/mL) for 3h. Cell viability and proliferation, inflammatory and oxidative stress parameters were evaluated. LPS decreased astrocytic viability and increased cell proliferation and EA prevented these alterations. EA also attenuated the LPS-induced increase in reactive oxygen species and nitrite levels and the decrease in sulfhydryl content and antioxidant enzyme activities. LPS induced an increase in gene expression of interleukin 1β and tumor necrosis factor-alpha, and EA treatment attenuated these alterations. Conversely, EA increased interleukin 6 (IL-6) and glycogen synthase kinase-3 beta mRNA expression compared with LPS-only exposure. LPS increased IL-6 levels and decreased interleukin 10 (IL-10) levels in astrocytes, and EA at 100 µM prevented the reduction in IL-10 levels but did not significantly modify IL-6 levels compared with LPS group.</p><p><strong>Conclusion: </strong>EA modulates oxidative and inflammatory markers in LPS-stimulated astrocytes. Further studies are needed to clarify the underlying mechanisms and evaluate these effects in more complex models of neuroinflammation.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitogenomic and phylogenomic analyses identify a cohesive Western Atlantic lineage within the Narcine complex (Torpediniformes: Narcinidae).","authors":"Paola Palacios-Barreto, Beatriz Rochitti Boza, Vanessa Paes da Cruz, Bruno Lopes da Silva Ferrette, Claudio Oliveira, Matheus Marcos Rotundo, Nadia Sandoval-Laurrabaquio-Alvarado, Douglas H Adams, Píndaro Díaz-Jaimes","doi":"10.1007/s11033-026-12694-x","DOIUrl":"https://doi.org/10.1007/s11033-026-12694-x","url":null,"abstract":"<p><strong>Background: </strong>Accurate species delimitation within electric rays of the genus Narcine has been hindered by overlapping morphological characters and limited molecular resolution in previous single-locus studies. This study aims to evaluate phylogenetic relationships and species boundaries within the Narcine species complex across the Western Atlantic using complete mitochondrial genomes.</p><p><strong>Methods and results: </strong>Seven complete mitogenomes were newly assembled from individuals representing distinct morphotypes sampled across geographically widespread Western Atlantic localities and analyzed together with publicly available reference sequences. Mitochondrial protein-coding genes (PCGs) were examined using concatenated nucleotide and amino acid datasets under partitioned maximum-likelihood frameworks. Both approaches recovered highly congruent topologies, consistently supporting a single, well-defined western Atlantic mitochondrial lineage with low internal divergence (0.04-2.13%). Species delimitation analyses based on multiple methods yielded partially congruent results but consistently identified a dominant lineage encompassing all Atlantic samples. In contrast, two Colombian reference mitogenomes formed a separate and highly divergent lineage relative to the Atlantic group, despite showing moderate divergence between them. Comparative mitogenomic analyses revealed conserved genome organization, nucleotide composition bias, codon usage, and transfer RNA (tRNA) structures. All PCGs evolved under strong purifying selection, with Ka/Ks ratios well below unity.</p><p><strong>Conclusions: </strong>These results support mitochondrial genetic continuity across the Western Atlantic Narcine populations and do not provide mitochondrial evidence for multiple evolutionary lineages within the Western Atlantic. The marked mitochondrial divergence of Colombian reference mitogenomes highlights potential issues in sequence attribution and underscores the importance of data curation. Overall, complete mitochondrial genomes provide a robust framework for species delimitation and future integrative taxonomic assessments within Narcine.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial hub: the integrative axis connecting ferroptosis and metabolic reprogramming in periodontitis.","authors":"Tengyi Zheng, Zicong Zhang, Fumiao Lu, Yangan Chen, Pengjun Zhou, Rongxin Zhang, Xin Li","doi":"10.1007/s11033-026-12719-5","DOIUrl":"https://doi.org/10.1007/s11033-026-12719-5","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease characterized by persistent periodontal tissue destruction and alveolar bone loss, which is closely associated with multiple systemic disorders. Emerging evidence indicates that ferroptosis and metabolic reprogramming are jointly involved in the progression of periodontitis; however, their causal linkage, hierarchical regulatory network, and unified core mechanism remain unclear. This review proposes a mitochondria-centered unifying axis that links metabolic reprogramming and ferroptosis in periodontitis. Specifically, periodontal pathogens trigger mitochondrial structural and functional collapse, which in turn drives comprehensive metabolic disturbances covering iron, lipid, amino acid, and glucose metabolism, thereby facilitating ferroptosis. Exacerbated ferroptosis further aggravates mitochondrial damage, forming a self-sustaining pathological vicious cycle that underlies refractory inflammation and sustained alveolar bone resorption. We systematically elaborate the molecular basis of this mitochondria-metabolism-ferroptosis axis and outline a translational framework encompassing mitochondria-targeted therapeutics and advanced nano-delivery systems. This review provides a novel mechanistic basis for addressing therapeutic resistance and frequent recurrence in periodontitis, with profound theoretical value and translational promise for clinical application.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal nanoparticles as next-generation therapeutics against antimicrobial resistance: mechanisms, functionalization, and translational potential.","authors":"Amir Jalali, Majid Komijani, Zainab Diaa Wahab, Ameen Mohsin Hammadi, Entethar Abd Alsalam Kalf, Parisa Maleki","doi":"10.1007/s11033-026-12730-w","DOIUrl":"https://doi.org/10.1007/s11033-026-12730-w","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) poses a major global health threat, driven by bacterial defense mechanisms such as efflux pumps, enzyme-mediated drug inactivation, target site modification, and biofilm formation. Metal nanoparticles (NPs), including silver, gold, iron oxide, and zinc oxide, offer a potential multi-target strategy to dismantle these resistance pathways. Their antimicrobial activity stems from direct membrane disruption, induction of oxidative stress, and, crucially, the modulation of bacterial gene expression, including downregulation of efflux pump and biofilm-related genes and disruption of quorum-sensing networks. The efficacy and specificity of NPs are significantly enhanced through advanced functionalization strategies, such as organic ligand conjugation, antibody coupling, and green synthesis approaches using biological resources, enabling targeted drug delivery and reduced off-target toxicity. Despite promising translational applications in antimicrobial coatings, wound dressings, and adjuvant therapies, clinical adoption faces hurdles including potential cytotoxicity, unpredictable pharmacokinetics, and the need for standardized manufacturing. Future directions involve the development of environmentally responsive \"smart\" NPs, nanoparticle-mediated delivery of siRNA to suppress resistance genes, and the integration of multi-omics approaches to decipher NP-bacteria interactions at the molecular level. Collectively, engineered metal NPs represent a promising platform for next-generation antimicrobial strategies and may help address multidrug resistance through simultaneous molecular and physical effects.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration and experimental verification of triaptosis-related prognostic genes and cells in gastric cancer.","authors":"Xirong Cui, Hongkun Qiu, Hailian Zhang, Huijing Xu, Mao Liu","doi":"10.1007/s11033-026-12704-y","DOIUrl":"https://doi.org/10.1007/s11033-026-12704-y","url":null,"abstract":"<p><strong>Background: </strong>Triaptosis is a recently characterized form of programmed cell death with unclear implications in cancer. This study aimed to investigate the prognostic significance and biological relevance of triaptosis in gastric cancer (GC).</p><p><strong>Methods: </strong>Transcriptomic and clinical data from TCGA-STAD and GSE62254, and single-cell RNA sequencing data from GSE183904 were analyzed. Triaptosis-related gene (TRG) scores were calculated using single-sample gene set enrichment analysis. Differentially expressed genes identified in TRG-score and GC-versus-normal comparisons underwent functional enrichment, Cox regression, and least absolute shrinkage and selection operator regression to develop an externally validated signature. Immune profiles, pathway activity, somatic mutations, tumor mutational burden (TMB), predicted drug sensitivity, and clinical features were compared by risk group. Single-cell analyses assessed TRG activity, prognostic gene expression, cell-cell communication, and pseudotime. Reverse transcription-quantitative PCR and Western blotting assessed mRNA expression and protein levels, respectively.</p><p><strong>Results: </strong>A TRG-based prognostic model comprising ASPN, GRB14, and VTN was developed and externally validated, effectively distinguishing patients into two distinct risk groups with notably different survival outcomes. mRNA expression of all three genes and their protein levels were significantly higher in SGC-7901 cells than in GES-1 cells. High-risk patients had higher stromal scores and distinct immune profiles; 15 immune cell types differed between groups. Single-cell analysis revealed fibroblasts and pericytes among high-TRG-active cell types. Prognostic genes were significantly overexpressed in fibroblasts, which also showed high TRG activity. Fibroblasts demonstrated enhanced communication with pericytes, whereas tumor-derived fibroblasts showed weaker communication with macrophages, indicating immune microenvironment remodeling.</p><p><strong>Conclusion: </strong>The three-gene prognostic signature predicted GC prognosis and was associated with distinct immune and genomic features, suggesting potential value for risk stratification and personalized treatment.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ellagic acid and bone health: a systematic review of preclinical studies on its protective role against osteoporosis.","authors":"Masoomeh Gholizadeh, Behnam Omidi Sarajar, Jahanbakhsh Asadi, Ali Akbar Soleimani","doi":"10.1007/s11033-026-12648-3","DOIUrl":"https://doi.org/10.1007/s11033-026-12648-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Osteoporosis is a prevalent metabolic bone disorder characterized by reduced bone mineral density and disrupted bone microarchitecture, leading to increased fracture risk. Growing interest has focused on natural bioactive compounds as potential complementary therapeutic agents. This systematic review aimed to comprehensively evaluate preclinical evidence regarding the protective effects of ellagic acid (EA), a naturally occurring polyphenolic compound, and to elucidate the molecular mechanisms underlying its role in alleviation of osteoporosis.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar databases up to November 2025, following PRISMA guidelines. Eligible studies included English-language in vivo and in vitro investigations assessing the effects of EA on osteoporosis. Data were extracted on experimental models, EA dosage and administration, evaluated signaling pathways, and bone-related outcomes.</p><p><strong>Results: </strong>13 preclinical studies met the inclusion criteria. Evidence consistently demonstrated that EA enhances osteoblast differentiation, viability, and bone-forming capacity by upregulating key osteogenic markers and activating signaling pathways such as SMAD2/3, BMP2, and SIRT1/Nrf2/HO‑1, while inhibiting negative regulators including CDK12. Concurrently, EA markedly suppressed osteoclast differentiation and bone resorption by disrupting RANKL-RANK interactions and inhibiting downstream NF‑κB, MAPK, and ERK signaling pathways. In multiple animal models, including ovariectomy- and microgravity-induced osteoporosis, EA administration improved bone mineral density, trabecular microarchitecture, and mechanical strength. These effects were accompanied by attenuation of oxidative stress and inflammatory responses within the bone microenvironment.</p><p><strong>Conclusion: </strong>Collectively, preclinical evidence indicates that EA exerts multifaceted osteoprotective effects by restoring the balance between bone formation and resorption and modulating oxidative and inflammatory pathways. Although these findings support EA as a promising natural candidate for osteoporosis prevention and treatment, large-scale and long-term clinical studies are required to confirm its efficacy, optimize dosing strategies, and address bioavailability challenges.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}