Frontiers in bioscience (Landmark edition)最新文献

{"title":"Molecular Advances in Intra-Articular Injections for Knee Osteoarthritis.","authors":"Juan M Roman-Belmonte, Hortensia De la Corte-Rodriguez, E Carlos Rodriguez-Merchan","doi":"10.31083/FBL51917","DOIUrl":"https://doi.org/10.31083/FBL51917","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a common musculoskeletal condition characterized by progressive cartilage loss, subchondral bone alterations, and persistent, low-grade synovial inflammation. There is growing evidence indicates that KOA should be viewed not only as a degenerative disorder but also as a multifaceted inflammatory process driven by complex interactions among immune cells, cytokines, and cartilage-related molecular pathways. This review outlines recent molecular advances related to intra-articular injection therapies and their proposed mechanisms of action. Corticosteroid (CS) injections provide short-term pain relief by suppressing inflammatory activity; however, repeated administration raises concerns about cartilage integrity. Hyaluronic acid (HA) injections improve joint lubrication and restore viscoelasticity and modulate inflammatory signals, particularly in the early stages of the disease. Platelet-rich plasma (PRP) has gained attention as a biologically active therapy that modulates inflammatory cascades and support tissue repair by releasing diverse growth factors. Combined administration of PRP and HA may produce complementary biological effects; however, current clinical evidence is inconclusive. Regenerative modalities, such as fat-derived orthobiologics (FDO) and mesenchymal stem cell (MSC) therapies, show promise due to their paracrine actions on macrophage behavior and extracellular matrix regulation. Emerging evidence supports the investigation of exosomes, hyperosmolar dextrose, and botulinum toxin as novel intra-articular therapies, with exosomes representing a promising cell-free regenerative approach. Overall, intra-articular interventions play an important role in KOA management, though further studies are required to determine their long-term structural impact.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51917"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-Binding Protein RBMS3 Inhibits Cervical Cancer Progression by Enhancing HSPA6 mRNA Stability.","authors":"Huaping Huang, Ping Li, Lixia Zhu, Yawei Wu, Qin Liu, Hong Zhang","doi":"10.31083/FBL51761","DOIUrl":"https://doi.org/10.31083/FBL51761","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is a prevalent malignancy in women. RNA-binding motif single-stranded interacting protein 3 (RBMS3) acts as a tumor suppressor in many cancer types, but its role and underlying regulatory mechanisms in CC remain unclear.</p><p><strong>Methods: </strong>The expression levels of RBMS3 and heat shock protein family A member 6 (HSPA6) were evaluated in clinical CC tissues. Gain- and loss-of-function assays, transcriptome sequencing, and rescue experiments were performed in CC cell lines and nude mouse xenograft models.</p><p><strong>Results: </strong>RBMS3 expression was notably lower in CC tissues (n = 306) than in normal cervical tissues (n = 22), with reduced levels linked to shorter overall patient survival (<i>p</i> < 0.05). Overexpression of RBMS3 reduced cell proliferation, migration, and invasion in vitro, as well as tumor growth <i>in vivo</i> (<i>p</i> < 0.001). HSPA6 was identified as a key target of RBMS3 and was also downregulated in CC tissues. RBMS3 potentially binds to HSPA6 mRNA and enhances its stability. Knockdown of HSPA6 reversed the tumor-suppressive effects of RBMS3 (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>RBMS3 inhibits CC progression by stabilizing HSPA6 mRNA. The RBMS3-HSPA6 axis may represent a prognostic biomarker and therapeutic target in CC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51761"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes Released by Periodontal Ligament Stem Cells in Low-Inflammatory Microenvironment Promote Bone Tissue Regeneration.","authors":"Mingzhen Tan, Jianran Guo, Chengshi Wei, Qi Zhang, Nan Zhang, Wenzhao Jin, Hualong Gao, Jiqing Zhao, Xue Wang, Yujie Han, Bo Fu, Kun Liu","doi":"10.31083/FBL50928","DOIUrl":"https://doi.org/10.31083/FBL50928","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the effects of periodontal ligament stem cells preconditioned with low-inflammatory stimuli and their derived exosomes on jaw bone regeneration.</p><p><strong>Methods: </strong>Periodontal ligament stem cells (PDLSCs) were treated with varying concentrations of inflammatory induction medium to establish low-inflammatory PDLSCs, from which exosomes were subsequently extracted. The osteogenic effects of the exosomes derived from i-PDLSCs (i-PDLSCs-exo) on osteoblasts were evaluated <i>in vitro</i>.</p><p><strong>Results: </strong>The findings demonstrated that PDLSCs subjected to low-inflammatory conditions (i-PDLSCs) exhibited a significantly increased expression of osteogenesis-related genes, such as alkaline phosphatase (ALP) and Osteocalcin (OCN), and showed enhanced mineralized nodule formation. Additionally, there was an increase in the secretion of i-PDLSCs-exo, and at an optimal concentration of 20 μg/mL, they were taken up by hFOB1.19 cells, enhancing mineralized nodule formation and osteogenic gene expression. <i>In vivo</i>, a chondroitin sulfate hydrogel loaded with i-PDLSCs-exo was implanted into periodontal bone defects in Sprague-Dawley rats. This treatment group demonstrated superior bone regeneration compared to both the chondroitin sulfate hydrogel alone and the blank control groups.</p><p><strong>Conclusion: </strong>Collectively, these findings suggest that short-term pretreatment with low concentrations of inflammatory factors enhances the osteogenic potential of PDLSCs and their exosomes, promoting the regeneration of jaw bone defects in rats. This approach offers a promising therapeutic strategy for repairing bone tissue defects.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"50928"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keratinocytes: Dynamic Gatekeepers and Immune Regulators of the Skin.","authors":"Meilang Xue, Hui Wang, Siwen Han, Lyn March","doi":"10.31083/FBL50528","DOIUrl":"https://doi.org/10.31083/FBL50528","url":null,"abstract":"<p><p>Keratinocytes (KCs) constitute more than 90% of epidermal cells and are increasingly recognized as key regulators of skin immunity. In addition to forming the stratum corneum barrier, KCs are essential for immune surveillance. They express various pattern recognition receptors, such as Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptors, which enable the rapid detection of pathogen- and damage-associated molecular patterns. This detection then stimulates the release of cytokines and chemokines that regulate both innate and adaptive immune responses. In addition, KCs produce antimicrobial peptides and support barrier stability by synthesizing lipids and proteins. Abnormal signaling in KCs has been linked to inflammatory skin conditions, including psoriasis and atopic dermatitis. These findings highlight the dual role of KCs in regulating immune tolerance and inflammation. This review examines the molecular pathways by which KCs respond to environmental stressors and microbial signals while maintaining barrier integrity, highlighting their potential as therapeutic targets for skin diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"50528"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-339-5p/ACSL4 Pathway Drives Ferroptosis in Macrophages Exposed to Silica Nanoparticles.","authors":"Wanxin Zhang, Yanbo Li, Zhongjun Du, Hua Shao","doi":"10.31083/FBL51583","DOIUrl":"https://doi.org/10.31083/FBL51583","url":null,"abstract":"<p><strong>Background: </strong>The widespread application of silica nanoparticles (SiNPs) in industrial fields has raised increasing concerns regarding their potential biological toxicity. However, the cellular mechanisms underlying SiNPs-related injury remain incompletely understood. This study was designed to investigate whether ferroptosis contributes to SiNPs-mediated cytotoxicity in macrophages and to explore the potential regulatory role of microRNAs.</p><p><strong>Methods: </strong>RAW264.7 cells were exposed to SiNPs to establish an <i>in vitro</i> toxicity model. Mitochondrial ultrastructure and cellular uptake were examined. Ferroptosis-related markers, including antioxidant capacity, lipid peroxidation, ferrous iron accumulation, and the expression of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and cyclooxygenase-2 (COX2), were assessed. The involvement of apoptosis and necroptosis was evaluated using specific pathway inhibitors. Transcriptomic sequencing was performed to identify differentially expressed miRNAs, followed by functional validation through miR-339-5p mimic transfection, and the direct interaction between miR-339-5p and ACSL4 was verified by dual luciferase reporter assay.</p><p><strong>Results: </strong>SiNPs were efficiently internalized by RAW264.7 cells and induced pronounced mitochondrial structural damage, characterized by mitochondrial shrinkage and loss of cristae. SiNPs exposure markedly impaired cellular antioxidant capacity and promoted the accumulation of lipid peroxides and intracellular Fe²⁺. This coincided with a reduction in GPX4 expression, whereas ACSL4 and COX2 levels increased. Ferroptosis was identified as the predominant mode of SiNPs-induced cytotoxicity, while apoptosis and necroptosis played minor roles. Transcriptomic analysis identified miR-339-5p as a potential regulator associated with ferroptosis-related pathways, and the dual luciferase reporter assay confirmed that miR-339-5p directly targets <i>Acsl4</i>. Overexpression of miR-339-5p significantly attenuated the ferroptosis response induced by SiNPs.</p><p><strong>Conclusions: </strong>SiNPs induce ferroptosis as the predominant mode of cell death in macrophages through mechanisms involving oxidative stress and lipid peroxidation. miR-339-5p acts as a negative regulator of this process by directly targeting ACSL4, alleviating ferroptotic injury and providing new insights into the molecular mechanisms underlying the toxicity of SiNPs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51583"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Administration of isoD7-Aβ Exacerbates Motor Deficits and Tau Pathology in P301S Mice.","authors":"Yulia Stepenko, Olesya Shcheblykina, Nikita Zhunusov, Veronika Shmigerova, Sergey Kozin, Vladimir Mitkevich, Alexandra Radchenko, Elena Kuzubova, Leonid Khalzov, Mikhail Korokin","doi":"10.31083/FBL53279","DOIUrl":"https://doi.org/10.31083/FBL53279","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to dementia, disability, and premature death. Beta-amyloid (Aβ) and tau pathology are considered key components of its pathogenesis; however, the role of peripheral amyloid load in modulating pre-existing tau pathology remains understudied. We hypothesized that peripheral amyloid load could exacerbate tau pathology through mechanisms potentially linked to the disruption of the Akt/glycogen synthase kinase-3β-associated signaling pathway, which could lead to increased behavioral deficits and progression of neurodegenerative changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate the effect of double peripheral (retro-orbital) administration of the Aβ isoform D7 on the behavioral phenotype, morphological signs of tau pathology, and the expression of genes related to Akt/GSK-3β-associated signaling, neuroinflammation, and apoptosis in the brains of P301S transgenic mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The study included 12-week-old male P301S transgenic mice (Tg(Thy1-MAPT*P301S)2541Godt) (n = 20, biological duplication) and wild-type C57Black6/J mice (n = 10). P301S mice received two retro-orbital injections of isoD7-Aβ into the venous sinus at a dose of 100 µg (n = 10) with a 1-month interval; control P301S mice received an equivalent volume of water for injection (n = 10). Behavioral testing (\"open field\", \"novel object recognition\", \"vertical pole\", \"inverted screen\") was performed at 16 and 20 weeks of age. Tau pathology was assessed immunohistochemically using AT-8 (pSer202/pThr205) antibodies in the frontal cortex and brainstem, and amyloid deposits were assessed histologically using Congo red staining in the entorhinal cortex and hippocampus. The expression of &lt;i&gt;Akt1, Gfap, Mapt, Cdk5, Casp3, Bax&lt;/i&gt;, and &lt;i&gt;Bcl2&lt;/i&gt; genes in brain tissue was analyzed by quantitative real-time PCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Two peripheral administrations of isoD7-Aβ were not associated with further deterioration of performance in the \"open field\" and \"novel object recognition\" tests compared to the control P301S group, which likely reflects the already established deficit characteristic of this transgenic line. In contrast, in motor coordination tests (\"vertical pole\", \"inverted screen\"), motor impairments in the P301S+Aβ group emerged by week 16, whereas in P301S mice without amyloid load, they appeared only by week 20. Immunohistochemical analysis revealed an increase in AT-8-positive staining in the brainstem, whereas no statistically significant differences were found between groups in the frontal cortex. Histological analysis did not reveal amyloid plaques in the entorhinal cortex and hippocampus of P301S+Aβ mice and control P301S mice. At the molecular level, the P301S+Aβ group showed decreased Akt1 expression, increased Gfap and Bax expression, and decreased Bcl2 expression, with no significant changes in Mapt, Casp3, and Cd","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"53279"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol-Mediated Regulation of Molecular and Cellular Signaling Networks in Polycystic Ovary Syndrome.","authors":"Ruirui Hou, Xinyu Hu, Dong Guo, Jian Ren, Dandan Meng","doi":"10.31083/FBL50398","DOIUrl":"https://doi.org/10.31083/FBL50398","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder characterized by dysregulated ovarian signaling, metabolic inflammation, insulin resistance, and aberrant angiogenesis, for which effective disease-modifying therapies remain limited. Resveratrol (RES), a pleiotropic polyphenol, has attracted increasing attention for its ability to modulate multiple molecular and cellular pathways implicated in PCOS pathophysiology. In this review, we synthesize current evidence to clarify how RES regulates key pathological signaling networks in PCOS, including ovarian follicular dysfunction, impaired insulin signaling, hyperandrogenism, oxidative stress, and vascular remodeling. Rather than merely cataloguing isolated mechanisms, we integrate findings from experimental models to highlight major convergent nodes-such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR), sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and vascular endothelial growth factor (VEGF)-related pathways-through which RES may exert coordinated regulatory effects at the cellular and tissue levels. We further examine the available clinical studies to assess the translational relevance of these mechanistic insights, with particular emphasis on phenotypic heterogeneity, dose dependence, and the treatment window. Although clinical outcomes remain modest and variable, the available evidence suggests that RES may provide context-dependent benefits in selected PCOS subtypes. Collectively, this review offers a network-based framework linking the molecular actions of RES to the complex pathophysiology of PCOS and identifies key knowledge gaps that must be addressed to improve translational precision and therapeutic applicability.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"50398"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantable Microsphere-Mediated Targeted Delivery of Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuates Neuroinflammation and Promotes Recovery After Cerebral Ischemia.","authors":"Yiran Wang, Xiaorui Lei, Xiao Liang, Yiwen Huang, Xin Zhang, Tian Tian","doi":"10.31083/FBL52994","DOIUrl":"https://doi.org/10.31083/FBL52994","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a major cause of death and disability, in which neuroinflammation exacerbates injury. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer therapeutic potential but face translational hurdles in scalable production, rapid systemic clearance, and inefficient targeted delivery.</p><p><strong>Methods: </strong>We engineered an implantable alginate-microsphere system encapsulating EV-secreting MSCs and displaying the RGD-4C peptide (ACDCRGDCFC) on its surface. This platform functions as a bioreactor that sustains the release of functionalized EVs with enhanced targeting to the ischemic brain. Proteomics analyses compared EVs derived from 3D-microsphere cultures and conventional 2D cultures. Efficacy was evaluated in a mouse stroke model with intraperitoneal microsphere implantation, assessing biodistribution, neuroinflammation, microglial polarization, and recovery.</p><p><strong>Results: </strong>The system sustained the release of targeted EVs, demonstrating proteomic enrichment of anti-inflammatory cargo. <i>In vivo</i>, the platform enhanced EV accumulation in the ischemic brain, reduced neuroinflammation, shifted microglia toward a reparative phenotype, and significantly improved neuronal survival and functional recovery.</p><p><strong>Conclusion: </strong>This integrated platform represents a promising preclinical strategy for treating ischemic stroke and has potential applications in other neuroinflammatory diseases. This system circumvents the need for EV extraction and storage while eliminating the peak-and-trough kinetics of bolus injections, and suggests potential for future translation pending further validation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"52994"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Properties and Molecular Mechanisms of Action of 4H-Pyran-Based Acids.","authors":"Alexander Kravtsov, Stanislav Kozin, Rodion Kondratenko, Oksana Lyasota, Anna Dorohova, Olga Leontyeva, Jose Luis Hernandez-Caceres, Stepan Dzhimak","doi":"10.31083/FBL48552","DOIUrl":"https://doi.org/10.31083/FBL48552","url":null,"abstract":"<p><p>The development of effective neuroprotective agents remains one of the most urgent and complex challenges in modern medical and biological research, given the increasing prevalence of neurodegenerative diseases and the limited efficacy of existing therapeutic options. In recent years, compounds belonging to the 4H-pyran chemical class have attracted significant attention due to their pronounced antioxidant, anti-inflammatory, and cytoprotective properties. These molecules exhibit structural versatility, enabling modulation of multiple molecular targets involved in neuronal survival, redox homeostasis, and mitochondrial function. This review provides a comprehensive analysis of the pharmacological activity and molecular mechanisms of action of five 4H-pyran-based compounds-maltol, kojic acid, chelidonic acid, comenic acid, and meconic acid. Special attention is paid to their effects on signaling pathways that play a central role in maintaining neuronal integrity and resistance to stress factors. In particular, the review examines how these compounds regulate key intracellular cascades such as nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE), Nrf2/PTEN-induced putative kinase 1 (PINK1)/Parkin, nuclear factor-kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), which are critically involved in controlling oxidative stress, mitochondrial autophagy, inflammation, and neuronal plasticity. The integrated evaluation of these mechanisms demonstrates that 4H-pyran-based acids can act as multitarget neuroprotective agents capable of influencing both primary metabolic processes and secondary signaling responses to neurotoxic stimuli. Their pleiotropic action highlights the promise of these compounds as molecular scaffolds for the development of novel drugs aimed at preventing or delaying the progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"48552"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MGST1 Suppresses Ferroptosis in Nucleus Pulposus Cells and Attenuates Intervertebral Disc Degeneration by Regulating GPX4.","authors":"Zhenxin Huo, Ding Li, Yuxuan Kuang, Baoshan Xu","doi":"10.31083/FBL50880","DOIUrl":"https://doi.org/10.31083/FBL50880","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IDD) is a major pathological contributor to low back pain, and its progression is closely associated with oxidative stress and cell death. Ferroptosis is a form of programmed cell death characterized by iron-dependent lipid peroxidation, which has recently been confirmed to participate in IDD progression. Microsomal glutathione S-transferase 1 (MGST1) plays an important role in glutathione metabolism and cellular antioxidant defense, but its function in IDD remains unclear. This study aimed to investigate the expression profile of MGST1 in IDD and to elucidate its molecular mechanism in delaying degeneration by regulating ferroptosis.</p><p><strong>Methods: </strong>Differentially expressed ferroptosis-related genes associated with intervertebral disc degeneration were screened through bioinformatics analysis. MGST1 expression changes were validated using a needle puncture-induced rat IDD model and a degenerated nucleus pulposus (NP) cell model. MGST1 knockdown and overexpression strategies were employed to evaluate its effects on the extracellular matrix metabolism, apoptosis, and senescence of nucleus pulposus cells. Further examinations of ferroptosis-related indicators were conducted, including levels of lipid peroxidation, reactive oxygen species generation, intracellular Fe²⁺ content, and changes in mitochondrial membrane potential. For <i>in vivo</i> experiments, the therapeutic effect of MGST1 overexpression was assessed by intradiscal injection of an MGST1-overexpressing lentivirus into the rat intervertebral disc degeneration model.</p><p><strong>Results: </strong>Bioinformatics analysis indicated that MGST1 is a key candidate gene in IDD. MGST1 expression was consistently upregulated with increasing degeneration severity in rat disc tissues and degenerated NP cells. Knockdown of MGST1 significantly promoted extracellular matrix degradation and increased apoptosis and senescence levels in NP cells, while MGST1 overexpression markedly improved these changes. Mechanistic studies revealed that MGST1 deficiency significantly enhanced ferroptosis characteristics in NP cells, including accumulation of lipid peroxides and ROS, increased Fe²⁺ content, and decreased mitochondrial membrane potential. In vivo experiments demonstrated that MGST1 overexpression significantly alleviated the degree of IDD in rats.</p><p><strong>Conclusion: </strong>MGST1 exhibits compensatory upregulation during the progression of intervertebral disc degeneration and delays its progression by inhibiting ferroptosis in nucleus pulposus cells. This study reveals a novel mechanism by which MGST1 regulates ferroptosis in IDD and provides a potential molecular target for the prevention and treatment of IDD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"50880"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}