Frontiers in Molecular Biosciences最新文献

{"title":"Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect.","authors":"Charlotte de Ceuninck van Capelle, Leo Luo, Alexander Leitner, Stefan A Tschanz, Philipp Latzin, Sebastian Ott, Tobias Herren, Loretta Müller, Takashi Ishikawa","doi":"10.3389/fmolb.2025.1593810","DOIUrl":"10.3389/fmolb.2025.1593810","url":null,"abstract":"<p><strong>Introduction: </strong>Primary ciliary dyskinesia (PCD) is a genetic disorder affecting motile cilia across various organs, leading to recurrent respiratory infections, subfertility, and laterality defects. While several diagnostic tools exist-such as high-speed video microscopy, immunofluorescence staining, electron microscopy, and genetic screening-the relationship between different pathogenic variants within a single PCD gene and their effects on ciliary composition, structure, and clinical phenotype remains poorly understood.</p><p><strong>Methods: </strong>To investigate this, we analyzed cilia from PCD patients with different mutations in axonemal dynein heavy chain <i>dnah5</i> using mass spectrometry and cryo-electron tomography. These methods allowed us to examine both the protein composition and ultrastructural organization of motile cilia in affected individuals.</p><p><strong>Results: </strong>Though all analyzed patients present similarly in traditional diagnostic methods, we observed differences in axonemal composition among patients carrying different <i>dnah5</i> mutations. Specific reductions in ciliary components varied between individuals, indicating a mutation-specific impact. Notably, proteins such as VWA3B, KIAA1430/CFAP97, and DTHD1-not previously identified as components of human respiratory motile cilia-were detected in wild type cilia, but not in patient cilia. Lastly, we confirmed some changes in protein abundance in the 96-nm repeated unit of the axoneme between wild-type and PCD samples.</p><p><strong>Discussion: </strong>These findings suggest that mutations in <i>dnah5</i> result in varied and specific alterations in axonemal composition, reflecting the heterogeneity of the disease at the molecular level. The discovery of novel ciliary proteins and mutation-specific differences enhances our understanding of the complexity of PCD pathogenesis and may inform future diagnostic and therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1593810"},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759633","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":"Development of a human colorectal carcinoma cell-based platform for studying inducible nitric oxide synthase expression and nitric oxide signaling dynamics.","authors":"Xi Chen, Elizabeth A Grimm, Yong Qin","doi":"10.3389/fmolb.2025.1637230","DOIUrl":"10.3389/fmolb.2025.1637230","url":null,"abstract":"<p><strong>Introduction: </strong>Inducible nitric oxide synthase (iNOS) plays a critical role in inflammatory signaling and tumor immunology, contributing to both pro- and anti-tumor effects depending on the cellular context. While iNOS induction has been linked to immune activation and tumor progression, its expression in cancer cells is highly variable and often inconsistently reported across different tumor models. To address this gap, we developed a well-defined <i>in vitro</i> platform using the human colorectal adenocarcinoma cell line DLD-1 to model stimulus-dependent iNOS expression and nitric oxide (NO) signaling.</p><p><strong>Methods: </strong>DLD-1 cells were stimulated with a pro-inflammatory cytokine cocktail (lipopolysaccharide [LPS], interleukin-1β [IL-1β], and interferon-γ [IFN-γ]), resulting in marked upregulation of iNOS at both the mRNA and protein levels. iNOS specificity was confirmed using targeted siRNA knockdown. Functional assessment of NO production was performed using the Nitrate/Nitrite Colorimetric Assay Kit and the ENO-30 NOx Analyzer. Induction of iNOS was further associated with elevated levels of reactive nitrogen species (RNS), reactive oxygen species (ROS), and protein nitration, including 3-nitrotyrosine, detected by immunohistochemistry and Western blot.</p><p><strong>Results: </strong>Upon stimulation, DLD-1 cells consistently expressed enzymatically active, full-length human iNOS and produced biologically relevant levels of NO and downstream nitrosative stress markers. Treatment with selective iNOS inhibitors significantly reduced nitrite accumulation, confirming the functional activity of iNOS and the model's applicability for pharmacologic evaluation of NO-modulatory compounds.</p><p><strong>Discussion: </strong>Our findings establish the DLD-1 cell line as a reproducible and well-controlled in vitro system for studying inducible iNOS expression and downstream NO/RNS signaling in human epithelial cancer cells. This platform provides a valuable tool for mechanistic studies, screening of iNOS-targeted agents, and resolving discrepancies in iNOS detection across experimental models in cancer biology.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1637230"},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of epigenetics in pulmonary fibrosis: recent advances in mechanistic insights and therapeutic implications.","authors":"Jingru Huang, Jianfeng Qin, Yuguang Zhu, Ao Shen","doi":"10.3389/fmolb.2025.1647300","DOIUrl":"10.3389/fmolb.2025.1647300","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a fatal disease characterized by progressive fibrosis of lung tissue, with a key pathological feature of excessive accumulation of extracellular matrix. PF occurs from complicated origins, while emerging findings have suggested the involvement of the environmental factors in the risk of PF through epigenetic regulation. This article will discuss how recent advances in epigenetic alterations of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs contribute to PF development through molecular mechanisms and cellular processes, including fibroblast-to-myofibroblast transition (FMT), epithelial-to-mesenchymal transition (EMT), alveolar epithelial cell injury and immune cell interactions in the past 5 years.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1647300"},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759634","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":"An overview of current research on the modulation of NLRP3 inflammasome by traditional Chinese medicine to combat acute pancreatitis.","authors":"Xiongjie He, Jia Xia, Qi Chen, Zhaozhao Huang, Juanjuan Lu, Yisong Ren","doi":"10.3389/fmolb.2025.1634132","DOIUrl":"10.3389/fmolb.2025.1634132","url":null,"abstract":"<p><p>Acute pancreatitis (AP), a life-threatening gastrointestinal emergency, is characterized by acute onset, rapid clinical deterioration, and high mortality rates, imposing profound long-term health burdens and socioeconomic costs on patients and healthcare systems. Current therapeutic strategies focus on supportive care, as no curative therapies exist to halt AP progression. Traditional Chinese medicine (TCM), with its multi-target, multi-component, and multi-pathway pharmacological properties, has emerged as a promising therapeutic drug against inflammation-driven pathologies, including AP. This review systematically discussed the assembly, activation, and pathogenic contributions of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in AP pathogenesis. Mechanistically, NLRP3 activation exacerbated pancreatic injury through caspase-1-dependent maturation of interleukin-1β (IL-1β) and gasdermin D (GSDMD)-mediated pyroptosis, perpetuating systemic inflammation. We systematically summarized the research progress of TCM in the treatment of AP by reducing pancreatic necrosis, neutrophil infiltration, and intestinal barrier dysfunction through targeting NLRP3 inflammasome, as well as its clinical evidence. Collectively, this review highlights the translational potential of TCM as an adjunctive therapy for AP through NLRP3 inflammasome inhibition, offering mechanistic insights and evidence-based support for its integration into integrative medicine strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1634132"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752883","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 validation of integrated stress-response-related genes as biomarkers for age-related macular degeneration.","authors":"Jingyi Niu, Ling Jin, Yijun Hu, Yiting Wang, Xiaoning Hao, Wenwen Geng, Ruirui Ma","doi":"10.3389/fmolb.2025.1583237","DOIUrl":"10.3389/fmolb.2025.1583237","url":null,"abstract":"<p><strong>Background: </strong>Age-related macular degeneration (AMD) is a prevalent ocular condition associated with aging, serving as a significant contributor to vision loss among middle-aged and older individuals. Studies have shown that AMD and integrated stress response (ISR) are associated with oxidative stress, but no specific molecular mechanisms have been identified. Therefore, this study aimed to identify potential biomarkers for AMD through bioinformatics analysis based on the transcriptome database and integrated stress response related genes (ISR-RGs).</p><p><strong>Methods: </strong>Transcriptomic data GSE76237, GSE247168, and ISR-RGs were sourced from public databases and related literature. The biomarkers associated with AMD were identified by differentially expressed gene (DEG) analysis, intersection of common DEGs, and ISR-RGs machine algorithm. After that, nomograms, GSEA, and immune infiltration analysis were performed for the biomarkers. The effects of transcription factors (TFs) and miRNAs on biomarkers were then explored by constructing a TF-biomarker-miRNA regulatory network. In addition, potential effective drugs of the biomarkers were explored by constructing a biomarker-effective drug interaction network. Finally, we verified the gene expression of the biomarkers by RT-qPCR.</p><p><strong>Results: </strong>We obtained 2,567 and 1,454 DEGs in GSE76237 and GSE247168, respectively. The up- and downregulated genes shared in both datasets were intersected with ISR-RGs taken to obtain eight candidate genes. SLFN11 and GRIN1 were identified as common biomarkers for AMD. An analysis of the nomogram model of biomarkers revealed good diagnostic predictive abilities (AUC > 0.7). SLFN11 and GRIN1 were mainly enriched in pathways such as proteasome, lysosome, and neuroactive ligand receptor interaction. In addition, the disease group's monocyte expression was significantly higher than that of the control group in GSE76237 (p < 0.01). We obtained thirteen relevant miRNAs and 27 TFs by prediction, with three shared TFs, and seventeen potentially effective drugs were predicted. RT-qPCR validation showed in AMD patients, and SLFN11 and GRIN1 expression was significantly higher than controls (p < 0.05). Only SLFN11 expression was consistent with the bioinformatics analysis.</p><p><strong>Conclusion: </strong>SLFN11 and GRIN1 were identified as AMD biomarkers, exhibiting robust diagnostic performance and providing new insights into the condition.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1583237"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752884","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":"Expression and clinical significance of S100A8/9 in adults with secondary phagocytic lymphohistiocytosis.","authors":"Ziwei Fang, Xin Gao, Limin Duan, Jujuan Wang, Tian Tian, Ji Xu, Yongqian Shu, Guangli Yin, Hongxia Qiu","doi":"10.3389/fmolb.2025.1607352","DOIUrl":"10.3389/fmolb.2025.1607352","url":null,"abstract":"<p><strong>Introduction: </strong>The study aimed to investigate the diagnostic and prognostic value of serum S100A8/9 levels with sHLHa, a high-mortality multiorgan inflammatory syndrome with no reliable clinical biomarkers, where calreticulin's role is unclear.</p><p><strong>Methods: </strong>This was a study of 67 newly diagnosed sHLHa patients. 48 patients met criteria and were analyzed. ELISA detected S100A8/9 levels in patients and controls. The optimal classification threshold for S100A8/9 was determined to be 2.44 µg/mL by restricted cubic spline (RCS) curve analysis. Patients were categorized. Correlations, diagnostic efficacy, survival differences, and prognosis impacts were analyzed.</p><p><strong>Results: </strong>Serum S100A8/9 levels in sHLHa patients were greater than in healthy controls. Various analyses showed its diagnostic and prognostic value. ANC<1.0 × 10⁹/L and high S100A8/9 expression group were independent risk factors for poor prognosis in patients with sHLHa. It's correlated with liver function indicators and HScore.</p><p><strong>Discussion: </strong>This study evaluates S100A8/9 in sHLHa diagnosis and prognosis. S100A8/9 levels are useful for differentiating patients, providing etiologic and survival info. They show a nonlinear positive correlation with survival and a threshold effect. Serum S100A8/9 levels offer potential biomarkers, and further studies are needed.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1607352"},"PeriodicalIF":3.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741789","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":"An integrated approach for analyzing spatially resolved multi-omics datasets from the same tissue section.","authors":"Thao Tran, Felicia Wee, Craig Ryan Joseph, Wanqiu Zhang, Jeffrey Chun Tatt Lim, Zhen Wei Neo, Li Yen Chong, Francis Hong Xin Yap, Nathan Heath Patterson, Marc Claesen, Alice Ly, Joe Yeong","doi":"10.3389/fmolb.2025.1614288","DOIUrl":"10.3389/fmolb.2025.1614288","url":null,"abstract":"<p><p>Recent advances in spatial transcriptomics (ST) and spatial proteomics (SP) technologies have enabled high-dimensional molecular profiling at single-cell resolution, providing deeper insights into the tumour-immune microenvironment. However, these modalities are typically applied to separate tissue sections, limiting direct comparisons across molecular layers. We developed a wet-lab and computational framework to perform and integrate ST and SP from the same tissue section, as demonstrated on human lung cancer samples. Applying ST, SP, and hematoxylin and eosin (H&E) staining from the same section ensured consistency in tissue morphology and spatial context. Computational registration using Weave software allowed accurate alignment and annotation transfer across modalities. This co-registered dataset enabled single-cell level comparisons of RNA and protein expression, revealed segmentation accuracy and transcript-protein correlation analyses within individual cells. Notably, we observed systematic low correlations between transcript and protein levels-consistent with prior findings-now resolved at cellular resolution. Our approach highlights the feasibility and utility of performing spatially-resolved multi-omics analysis on the same section without compromising data quality, facilitating concordance studies and region-specific analysis of immune and tumour markers, and ultimately advancing our understanding of disease heterogeneity at the molecular level.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1614288"},"PeriodicalIF":3.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741788","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: Ironome: a still untapped frontier.","authors":"Gloria C Ferreira, Vladimir N Uversky, Zoubida Karim","doi":"10.3389/fmolb.2025.1651154","DOIUrl":"10.3389/fmolb.2025.1651154","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1651154"},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729352","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":"Untargeted plasma metabolite detection in sudden sensorineural hearing loss: identifying key metabolic signatures.","authors":"Rongyue Ma, Huangruici Zhang, Weijie Wang, Changping Yu, Guohang Xiong, Qing Li, Yan Wang, Li Zhou, Yu Zhang, Min Li, Min Guo","doi":"10.3389/fmolb.2025.1567064","DOIUrl":"10.3389/fmolb.2025.1567064","url":null,"abstract":"<p><strong>Background: </strong>Sudden sensorineural hearing loss (SSNHL) is a common otological disorder with complex etiologies and unclear pathophysiology. This study aimed to detect and analyze plasma metabolites in SSNHL, identify potential biomarkers, and uncover underlying metabolic mechanisms.</p><p><strong>Methods: </strong>A cohort of 64 SSNHL, classified into four subtypes (low-frequency, high-frequency, flat and total deafness type), and 53 normal controls (NC) were recruited. Plasma samples were collected and analyzed by high-performance liquid chromatography-mass spectrometry (LC-MS). Metabolite profiling was performed, followed by multivariate statistical analyses, including orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and partial least-squares discriminant analysis (PLS-DA) to find differentially expressed metabolites between the groups.</p><p><strong>Results: </strong>The results showed significant differences in the plasma metabolome when comparing each of the four SSNHL types with NC. A total of 130 differentially expressed metabolites were identified, with sphingosine, anthranilic acid, and 6-hydroxyflavanone (6-HF) being prominent examples. Were prominent. Pathway enrichment analysis indicated that these metabolites were mainly involved in central carbon metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, mineral absorption, etc.</p><p><strong>Conclusion: </strong>These findings imply that plasma metabolite profiling holds promise as a non-invasive approach for screening biomarkers in SSNHL. The identified differential metabolites and associated metabolic pathways may offer novel perspectives on the pathophysiology of SSNHL, presenting potential targets for future therapeutic interventions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1567064"},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729343","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":"Neuroprotective effect of silymarin-loaded nanoliposomes against monosodium glutamate-induced cerebellar motor deficit and Purkinje cell damage in experimental rats via PI3K/AKT pathway activation.","authors":"Medhat Taha, Ahmed Alzahrani, Omer Abdelbagi, Rehab M Bagadood, Naeem F Qusty, Rami Obaid, Mohammad El-Nablaway, Tourki A S Baokbah","doi":"10.3389/fmolb.2025.1621240","DOIUrl":"10.3389/fmolb.2025.1621240","url":null,"abstract":"<p><strong>Background and aim: </strong>This study investigated the ameliorative effect of Silymarin-nanoliposome (SLNPs) against monosodium glutamate (MSG)-induced cerebellar toxicity, illuminating its impact on motor coordination.</p><p><strong>Methods: </strong>Forty male Wistar albino rats were divided into four groups. Group I (control group): rats received 2 mL of 0.9% NaCl solution; Group II (SLNPs group): rats received SLNPs with a dose of 500 μg/kg bw orally; Group III (MSG group): rats received 3.5 mg/kg bw of MSG intraperitoneally; and Group IV: rats received combined treatment of MSG + SLNPs for ten consecutive days.</p><p><strong>Results: </strong>MSG-induced cerebellar motor incoordination is represented by increased falls in rats and decreased tow latency spent on the rotarod test. Moreover, MSG altered cerebellar histological structure and significantly (p < 0.05) decreased antioxidant system activity and protein levels of phosphorylated phosphoinositide 3-kinases (p-PI3K), phosphorylated protein kinase B (p-AKT), and brain-derived neurotrophic factor (BDNF). Additionally, there is a decrease in the immunoexpression of nuclear factor erythroid 2-related factor 2 (Nrf2) and gene expression of heme oxygenase-1 (HO-1), tropomyosin receptor kinase B (TrkB), and anti-apoptotic B-cell lymphoma-2 (Bcl-2), alongside an increase in the sera and protein levels of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), immunoexpression of glial fibrillary acidic protein (GFAP), nuclear factor kabba beta (NF-κB), caspase-3, and gene expression of proapoptotic Bax. However, SLNPs prevented MSG-induced cerebellar toxicity, improving motor coordination and morphological structure by enhancing antioxidant, anti-inflammatory, and anti-apoptotic activity by stimulating the PI3K/AKT pathway.</p><p><strong>Conclusion: </strong>The current study indicated that SLNP administration protects against MSG-induced cerebellar damage, preventing cerebellar oxidative stress, inflammation, and apoptosis, opening the door to examining its clinical use in preventing MSG-induced cerebellar motor incoordination.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1621240"},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729339","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}