Frontiers in Molecular Biosciences最新文献

{"title":"Gut microbiota-metabolome remodeling associated with low bone mass: an integrated multi-omics study in fracture patients.","authors":"Xian Zhao, Bin Wu, Pengli Han, Zhongyu Wang, Renwei Cao, Shuo Chen, Cheng Cheng, Hongkai Lian, Yejun Zha, Minjuan Li","doi":"10.3389/fmolb.2025.1646361","DOIUrl":"10.3389/fmolb.2025.1646361","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota is increasingly implicated in the pathogenesis of osteoporosis, but its role in the specific context of fracture patients remains poorly defined. High-resolution multi-omics studies are needed to elucidate the complex interplay between microbes, their metabolites, and bone health. This study aimed to characterize the gut microbial and fecal metabolic signatures associated with low bone mass in fracture patients.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 51 fracture patients, stratified by bone mineral density into Normal, Osteopenia, and Osteoporosis groups. For key analyses, the latter two groups were combined into a Low Bone Mass (LBM) group. We performed shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry metabolomics on fecal samples. An integrated bioinformatics and statistical analysis were used to identify differential taxa and metabolites, construct correlation networks, and build diagnostic biomarker models.</p><p><strong>Results: </strong>Patients with LBM exhibited a distinct gut microbial and metabolic profile compared to controls. A notable finding was the unexpected enrichment of <i>Lachnospira eligens</i> in the LBM group, despite its previous association with gut health. In contrast, traditionally beneficial taxa such as <i>Bifidobacterium</i> species and <i>Bacteroides stercoris</i> were markedly depleted. Metabolomic analysis identified 127 differential metabolites, and integrated analysis revealed a strong correlation between <i>L. eligens</i> and inflammation-associated metabolites, including N-acetylneuraminate. A diagnostic model incorporating four key bacterial species accurately discriminated LBM patients from controls with an area under the curve (AUC) exceeding 0.9.</p><p><strong>Conclusion: </strong>Our findings reveal a significant remodeling of the gut microbiota-metabolome axis in fracture patients with low bone mass, highlighting a context-dependent, potentially pathological role for the typically beneficial species <i>L. eligens</i>. These distinct microbial and metabolic signatures suggest potential mechanistic insights into the gut-bone axis and represent promising, non-invasive biomarkers for assessing skeletal health.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1646361"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074339","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 emerging role of exosomal LncRNAs in chronic fatigue syndrome: from intercellular communication to disease biomarkers.","authors":"Lei Wang, Yujia Xu, Xiang Zhong, Guiping Wang, Zijun Shi, Can Mei, Linwanyue Chen, Jianbo Zhan, Jing Cheng","doi":"10.3389/fmolb.2025.1653627","DOIUrl":"10.3389/fmolb.2025.1653627","url":null,"abstract":"<p><p>Chronic fatigue syndrome (CFS) is a complex disease involving multiple systems throughout the body with unknown pathogenesis and is characterized by chronic fatigue. To date, no effective treatment for CFS has been found, as well as biomarkers for early identification of diagnosis. However, exosomes, a subpopulation of extracellular vesicles (EVs), are membranous vesicles secreted by cells into the surrounding environment, and long noncoding RNAs (LncRNAs) in EVs can mediate inter-organ and inter-cellular communication, which maybe associate with CFS. Therefore, this study aims to review the association between EV-LncRNAs and CFS, and to explore whether LncRNAs can be used as potential biomarkers for early identification and diagnosis of CFS, which put forward new ideas and a theoretical basis for the pathogenesis of CFS, as well as the identification of novel targeted therapies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1653627"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063916","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":"LC-HRMS fingerprinting and chemometrics for the characterization and classification of <i>Lotus</i> cultivars from Uruguay: a study on phenolic composition.","authors":"Cristina Olivaro, Nerea Núñez, Patricia Basile, América Mederos, Rafael Reyno, Javier Saurina, Oscar Núñez","doi":"10.3389/fmolb.2025.1646758","DOIUrl":"10.3389/fmolb.2025.1646758","url":null,"abstract":"<p><strong>Introduction: </strong>The <i>Lotus</i> genus, part of the legume family, comprises over 180 species distributed across diverse ecosystems worldwide. Its broad genetic diversity enables adaptation to various environmental conditions and represents a valuable resource for breeding programs targeting key agronomic traits. One of the most attractive features of <i>Lotus</i> species is the presence of condensed tannins in the forage, which, in ruminants, help prevent bloat, exhibit antiparasitic properties, enhance the absorption of non-ammonia nitrogen compounds, and reduce greenhouse gas emissions.</p><p><strong>Aims and methods: </strong>This study aimed to develop a UHPLC-HRMS method for classifying ten <i>Lotus</i> cultivars produced in Uruguay using a non-targeted metabolomic fingerprinting approach. Five cultivars belong to <i>Lotus corniculatus</i>, three to <i>Lotus uliginosus</i>, and two are interspecific hybrids. The analysis focused on phenolic compound-rich fingerprints. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used for data exploration and classification, and to identify key phenolic compounds with high discriminant potential. Finally, cultivar-specific polyphenolic compounds were tentatively identified based on chromatographic and high-resolution mass spectrometry (HRMS/MS) data obtained from all cultivars.</p><p><strong>Results: </strong>When defining four classes (<i>L. uliginosus</i>, <i>L. corniculatus</i>, and the two hybrids), the optimal PLS-DA model required six latent variables and achieved 100% classification accuracy, with both sensitivity and specificity reaching 100%. Additional PLS-DA models were developed to assess intra-species discrimination among the 3 <i>L. uliginosus</i> and 5 <i>L. corniculatus</i> cultivars, with varying degrees of separation observed. In each PLS-DA model, VIP loadings scores allowed the selection of the most discriminant phenolic compounds for each class under study. A total of 105 compounds, including phenolic acids, flavonols, flavan-3-ols, proanthocyanidins, and organic acids, were tentatively identified by analyzing all cultivars.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1646758"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063911","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":"Toxicological analysis of metabolites in ischemic stroke based on salivary metabolomics.","authors":"Yan-Song Liu, Yu-Yan Long, Jie Liu, Yu-Chen Liu, Shuang Zhang, Yi-Jia Xu, Shu-Yue Fu, Hua Li, Wang-Hua Liu","doi":"10.3389/fmolb.2025.1609227","DOIUrl":"10.3389/fmolb.2025.1609227","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the characteristic patterns of salivary metabolic network instability in IS patients, reveal the association mechanism between amino acid-lipid-nucleotide metabolic cascade imbalance and stroke progression, and provide experimental basis and translational pathway for the development of diagnostic and therapeutic strategies based on metabolic microenvironment regulation.</p><p><strong>Methods: </strong>This study focused on salivary metabolomics. A prospective cohort design (40 IS patients and 30 healthy controls) was combined with high-resolution liquid chromatography-mass spectrometry (LC-MS/MS) to systematically analyze the molecular characteristics and toxicological mechanisms of metabolic disorders in stroke. Orthogonal partial least squares discriminant analysis (OPLS-DA) and game theory feature weighting method were used to screen differential metabolites, and toxicity evaluation was performed by integrating ADMETlab and ProTox databases. Finally, molecular docking technology was used to verify the metabolite-target interaction network.</p><p><strong>Results: </strong>A total of 488 salivary metabolites were identified, of which 167 showed significant differences between groups, including 4.3-fold increase in arginine, 3.5-fold increase in xanthine, and 2.1-fold increase in lipoxin A4. Toxicity prediction showed that xanthine has potential neurotoxicity and blood-brain barrier penetration ability (BBB = 0.90). Its molecular docking with targets such as XDH and PNP showed stable binding energy, suggesting that it participates in the pathological process of stroke by regulating purine metabolism and oxidative stress.</p><p><strong>Conclusion: </strong>A panoramic analysis framework of salivary metabolomics in ischemic stroke was constructed, and the cascade disorder of the amino acid-lipid-nucleotide metabolic network was elucidated. The screened core metabolite markers and their regulatory pathways not only provide highly specific tools for early diagnosis of stroke, but also provide research basis for the development of innovative therapies based on metabolic microenvironment regulation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1609227"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063874","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":"Bibliometrics-guided cyberpharmacology and transcriptomics for multidimensional analysis of the antihepatic fibrosis mechanism of kaempferol.","authors":"Jiali Liu, Xiaowen Song, Xinni Song, Xinyue Fu, Shufang Niu, Hong Chang, Songli Shi, Meiqing Yang, Ruiqi Zhao, Peng Wang, Jun Qi, Wanfu Bai","doi":"10.3389/fmolb.2025.1607103","DOIUrl":"10.3389/fmolb.2025.1607103","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatic Fibrosis (HF), a pathological remodeling process triggered by persistent liver damage, is marked by the excessive buildup of extracellular matrix (ECM), leading to a gradual deterioration of liver function and an increased likelihood of advancing to cirrhosis and liver failure.</p><p><strong>Methods: </strong>This study adopts a systematic pharmacology methodology, initially employing bibliometric analysis to identify traditional Chinese medicine (TCM) formulations and individual herbs with potential anti-HF properties. Subsequently, a multi-dimensional network analysis is conducted to pinpoint core active components. Experimental investigations involve the construction of a carbon tetrachloride (CCl₄)-induced rat model of liver fibrosis, complemented by transcriptomic technology to systematically elucidate the mechanisms of action of the active components in TCM.</p><p><strong>Results: </strong>In this study, kaempferol (KA), identified as the principal active compound with anti-fibrotic properties, was selected from traditional Chinese medicine (TCM) and TCM prescriptions through a combination of bibliometric analysis and network pharmacology. Pharmacodynamic evaluations, including pathological section analyses, demonstrated that KA effectively mitigated the fibrotic process and decreased collagen deposition. Further corroborated by ELISA experiments, kaempferol exhibited pronounced anti-fibrotic effects, inhibited inflammatory responses, restored liver function indices, and ameliorated the progression of liver fibrosis. Mechanistic investigations revealed that KA modulated fatty acid metabolism, retinol metabolism, and arachidonic acid metabolism by regulating the expression of key metabolic enzyme genes such as <i>SCD, SCD2, FADS2,</i> and <i>CYP4A8</i>, and significantly influenced the activity of the PPAR signaling pathway. Additionally, it impacted the dysregulation of lipid metabolism and inflammatory response pathways, significantly inhibited hepatic stellate cell (HSC) activation, and reduced ECM accumulation.</p><p><strong>Discussion: </strong>This finding elucidates the mechanism by which KA attenuates HF through multi-target regulation, and provides a theoretical basis for metabolic reprogramming-based therapeutic strategies with translational valu.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1607103"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063886","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":"Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.","authors":"Sirsendu Jana, Haley Garbus-Grant, Tigist Kassa, Abdu I Alayash","doi":"10.3389/fmolb.2025.1648209","DOIUrl":"10.3389/fmolb.2025.1648209","url":null,"abstract":"<p><strong>Background: </strong>Hemoglobin-based oxygen carriers (HBOCs) also known as blood substitutes were developed by chemical or genetic alterations of cell-free human or bovine Hbs to prolong the circulation time of Hb and to improve its ability to unload oxygen. However, toxicity and safety issues led to the termination of several clinical trials. The most persistent observation was the development of cardiac lesions after transfusion of some HBOCs in animal models. Oxidation of HBOCs in circulation, subsequent heme release and cellular uptake are thought to play an important role in the overall toxicity of HBOCs.</p><p><strong>Methods: </strong>We examined the effects of different redox states, ferrous (Fe⁺²), ferric (Fe⁺³) and ferryl (Fe⁺⁴) of four different HBOCs on cardiomyocyte integrity and mitochondrial respiration. The HBOC formulations used in this study were two-human derived and two bovine-derived molecules. We analyzed cellular and subcellular impacts of these forms including mitochondrial electron transport chain (ETC.) complexes individually by measuring the enzymatic activities of Complex I, Complex II-III, and Complex IV.</p><p><strong>Results: </strong>The ferrous, and ferric forms of these HBOCs generally induced minimum lactate dehydrogenase (LDH) release from human cardiac myocytes (AC16). Meanwhile higher oxidation state, ferryl forms of all HBOCs generated substantial cell injury as measured by LDH levels. We examined the effects of these redox forms of HBOCs and their ability to impair bioenergetic function of cultured AC16 cells. The ferrous forms of HBOCs did not cause measurable impairment of mitochondrial ETC functions, whereas ferric non-functional versions of all the HBOCs caused a significant loss of Complex IV activity but not Complex I or II-III in those cardiac cell lines. On the other hand, complex I, II-III and IV activities were completely blunted by the ferryl forms of HBOCs.</p><p><strong>Conclusion: </strong>This study for the first time investigated the impact of different chemical modifications on the redox activities of HBOCs towards mitochondrial complexes in cardiac myocytes. Higher oxidation ferryl states once formed trigger cellular and subcellular changes in cardiac myocytes. Our findings on the impact of HBOC redox states on mitochondrial function may therefore inform future design of alternative molecular entities to ensure safety and minimize toxicity.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1648209"},"PeriodicalIF":3.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063894","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: Plasticity of the haematopoietic niche: from embryonic development to aging and disease.","authors":"Rio Sugimura, Antonella Fidanza, Emanuele Azzoni, Giovanni Canu","doi":"10.3389/fmolb.2025.1683902","DOIUrl":"10.3389/fmolb.2025.1683902","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1683902"},"PeriodicalIF":3.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063939","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":"Insights into the protein ubiquitinome in the host‒pathogen interplay during <i>Mycobacterium tuberculosis</i> infection.","authors":"Qishun Feng, Qiao Lin, Guoxin Huang, Siqi Li, Yating Xu, Taosheng Ye, Guoliang Zhang","doi":"10.3389/fmolb.2025.1613454","DOIUrl":"10.3389/fmolb.2025.1613454","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (Mtb) is the causative agent of tuberculosis capable of manipulating and circumventing the host's immune system to establish infection. Ubiquitination plays a crucial role in the host's response to pathogens; however, the global alterations in protein ubiquitination during Mtb infection remain poorly understood. To elucidate the regulatory roles of ubiquitination in the immune response to Mtb, we investigated the ubiquitome of human macrophages following Mtb infection. In our study, we identified a total of 1,618 proteins exhibiting altered ubiquitination levels, with 1,182 lysine-ubiquitination sites in 828 proteins showing increased ubiquitination and 1,077 sites in 790 proteins displaying decreased ubiquitination. Bioinformatics analyses revealed that most proteins involved in the immune response were upregulated, including those associated with autophagy, lysosome, the NF-κB signaling pathway, necroptosis, and ferroptosis. Furthermore, the ubiquitination levels of numerous proteins involved in conserved physiological processes, such as ribosome biogenesis, spliceosome function, nucleocytoplasmic transport, and mRNA surveillance, were also altered, suggesting that these pathways may be regulated by ubiquitination during Mtb infection. The extensive pool of ubiquitinated proteins and sites identified in this study will serve as a valuable resource for understanding the regulatory mechanisms of the ubiquitination system in immune responses during Mtb infection.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1613454"},"PeriodicalIF":3.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039582","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":"Tracing priming effects in palsa peat carbon dynamics using a stable isotope-assisted metabolomics approach.","authors":"Christian Ayala-Ortiz, Moira Hough, Elizabeth K Eder, David W Hoyt, Rosalie K Chu, Jason Toyoda, Steven J Blazewicz, Patrick M Crill, Ruth Varner, Scott R Saleska, Virginia I Rich, Malak M Tfaily","doi":"10.3389/fmolb.2025.1621357","DOIUrl":"10.3389/fmolb.2025.1621357","url":null,"abstract":"<p><strong>Introduction: </strong>Peatlands store up to a third of global soil carbon, and in high latitudes their litter inputs are increasing and changing in composition under climate change. Although litter significantly influences peatland carbon and nutrient dynamics by changing the overall lability of peatland organic matter, the physicochemical mechanisms of this impact-and thus its full scope-remain poorly understood.</p><p><strong>Methods: </strong>We applied multimodal metabolomics (UPLC-HRMS, ¹H NMR) paired with ¹³C Stable Isotope-Assisted Metabolomics (SIAM) to track litter carbon and its potential priming effects on both existing soil organic matter and carbon gas emissions. Through this approach, we achieved molecule-specific tracking of carbon transformations at unprecedented detail.</p><p><strong>Results: </strong>Our analysis revealed several key findings about carbon dynamics in palsa peat. Microbes responded rapidly to litter addition, producing a short-term increase in CO₂ emissions, fueled nearly exclusively by transformations of litter carbon. Litter inputs significantly contributed to the organic nitrogen pool through amino acids and peptide derivatives, which served as readily accessible nutrient sources for microbial communities. We traced the fate of plant-derived polyphenols including flavonoids like rutin, finding evidence of their degradation through heterocyclic C-ring fission, while accumulation of some polyphenols suggested their role in limiting overall decomposition. The SIAM approach detected subtle molecular changes indicating minimal and transient priming activity that was undetectable through conventional gas measurements alone. This transient response was characterized by brief microbial stimulation followed by rapid return to baseline metabolism. Pre-existing peat organic matter remained relatively stable; significant priming of its consumption was not observed, nor was its structural alteration.</p><p><strong>Discussion: </strong>This suggests that while litter inputs temporarily increase CO₂ emissions, they don't sustain long-term acceleration of stored carbon decomposition or substantially decrease peat's carbon store capacity. Our findings demonstrate how technological advancements in analytical tools can provide a more detailed view of carbon cycling processes in complex soil systems.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1621357"},"PeriodicalIF":3.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014516","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 protection of sulforaphane on subarachnoid hemorrhage-induced intestinal mucosa injury in rats.","authors":"Zixiang Liu, Pengpeng Li, Yuanhai Zhang, Shidi Zhao, Wei Gao","doi":"10.3389/fmolb.2025.1635795","DOIUrl":"10.3389/fmolb.2025.1635795","url":null,"abstract":"<p><strong>Introduction: </strong>Sulforaphane (SFN) is recognized for its anti-inflammatory properties; however, the underlying molecular mechanisms remain unclear. In this study, we explored the effect of SFN on subarachnoid hemorrhage (SAH) and the potential mechanisms.</p><p><strong>Methods: </strong>Sprague-Dawley (SD) rats were divided into three groups (n = 12): Sham + vehicle group (Sham + V), SAH + vehicle group (SAH + V), and SAH + SFN group (SAH + S). SFN (50 mg/kg) dissolved in 250-280 μL corn oil was intraperitoneally injected, and the same volume of corn oil was served as the control. The appetite score, gut wet/dry weight ratio, and histological changes in ileum tissues were examined to determine intestinal mucosal injury. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to examine the expression of genes. LC3 immunofluorescence and Hoechst 33258 staining were used to assess cell autophagy and apoptosis.</p><p><strong>Results: </strong>Compared to the SAH + V group, the SAH + S group demonstrated a significantly increased appetite score (1.55 ± 0.23 vs. 1.90 ± 0.35); decreased gut wet/dry weight ratio (4.02 ± 0.21 vs. 3.18 ± 0.21) and inflammatory score (2.89 ± 0.33 vs. 1.89 ± 0.60); elevated mRNA expression of Nrf-2 (1.12 ± 0.14 vs. 1.89 ± 0.12), HO-1 (0.46 ± 0.02 vs. 1.02 ± 0.10), and NQO-1 (1.35 ± 0.09 vs. 1.97 ± 0.18); and elevated protein levels of Nrf-2 (0.92 ± 0.18 vs. 1.43 ± 0.23), Keap1 (0.31 ± 0.03 vs. 0.44 ± 0.02), HO-1 (0.65 ± 0.02 vs. 0.88 ± 0.02), NQO-1 (0.58 ± 0.02 vs. 0.78 ± 0.02), LC3-II/I (0.20 ± 0.004 vs. 0.28 ± 0.01), ATG4D (0.45 ± 0.01 vs. 0.72 ± 0.04), and P62 (0.85 ± 0.01 vs. 0.99 ± 0.03). The <i>in vitro</i> experiments further revealed that 3-methyladenine (3-MA) significantly reversed the decreased apoptosis of IEC-6 cells induced by 20 μmol/L SFN (20.60 ± 1.28 vs. 11.50 ± 0.58).</p><p><strong>Conclusion: </strong>SFN exhibited the protective effect on intestinal mucosa injury after SAH via activating autophagy, which may provide an innovative approach to alleviate the intestinal mucosa injury caused by SAH.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1635795"},"PeriodicalIF":3.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014314","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}