JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Unique Genetic and Epigenetic Alterations in Glioblastoma Long-Term Survivors: Insights From Two Clinical Cases","authors":"Elena Anghileri,&nbsp;Evelina Miele,&nbsp;Sara Patrizi,&nbsp;Sabina Barresi,&nbsp;Elisabetta Lazzarini,&nbsp;Luisa Maddaloni,&nbsp;Monica Patanè,&nbsp;Lucia Pedace,&nbsp;Rosina Paterra,&nbsp;Antonio Silvani,&nbsp;Franco Locatelli,&nbsp;Stefano Indraccolo,&nbsp;Bianca Pollo","doi":"10.1111/jcmm.70771","DOIUrl":"https://doi.org/10.1111/jcmm.70771","url":null,"abstract":"<p>The biological mechanisms driving the long survival in glioblastoma (GBM). Five-year long-term survival (LTS) and 10-year survival very long-term survival (VLTS) remain significantly understudied. Here we molecularly detailed two cases. AR10-046 (VLTS) was affected by a giant cell-GBM, classified as the pedHGG_RTK1a subtype according to the v12.5 Heidelberg brain tumor methylation classifier. Somatic and germline MSH6 mutations, typically in Lynch syndrome, and high tumour mutational burden were detected. The copy number variation plots showed chromosome 1q gain and chromosome 13 loss with no other typical GBM alterations. AR10-037 (LTS) suffered from a classical GBM, identified as pedHGG_MYCN subclass. Apart from the canonical chromosome 7 gain and chromosome 10q loss, we observed MDM2 gene amplification and possible rearrangements on chromosome 12 and 18 with the typical aspect of chromothripsis, harbouring two putative new gene fusions: CPSF6::CPM and PTPRR::RAB3IP. We described two patients with peculiar tumour molecular profile, widening the scenario of clinical and molecular variability in such patients.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 20","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding: In Vivo Evaluation of Decellularised Skeletal Muscle Matrices for Skeletal Muscle Repair: A Systematic Review","authors":"DuJiang Yang,&nbsp;Lin Yang,&nbsp;Shuang Wang,&nbsp;GuoYou Wang","doi":"10.1111/jcmm.70888","DOIUrl":"10.1111/jcmm.70888","url":null,"abstract":"&lt;p&gt;We read with great interest the systematic review by Hennion et al. [&lt;span&gt;1&lt;/span&gt;] which comprehensively evaluates the in vivo performance of decellularised skeletal muscle matrices (DSMMs) for muscle repair. Their work provides a valuable synthesis of current evidence regarding the regenerative potential of DSMMs in volumetric muscle loss treatment. While the authors thoroughly address key parameters influencing DSMM efficacy, several aspects warrant further discussion to advance this promising field.&lt;/p&gt;&lt;p&gt;The review appropriately highlights the critical importance of preserving native extracellular matrix (ECM) architecture to facilitate cellular infiltration and vascularisation [&lt;span&gt;1&lt;/span&gt;]. However, the substantial heterogeneity in decellularisation protocols across studies—ranging from detergent-based to enzymatic methods—deserves more emphasis regarding its impact on residual DNA content, glycosaminoglycan preservation and ultimate biocompatibility [&lt;span&gt;2&lt;/span&gt;]. Recent advances suggest that establishing standardised metrics for decellularisation efficiency (e.g., ≤ 50 ng DNA/mg tissue) and mechanical integrity (e.g., Young's modulus matching native tissue) is crucial for meaningful cross-study comparisons [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While the review discusses immune responses to DSMMs, the role of macrophage polarisation in long-term outcomes requires deeper exploration. Emerging evidence indicates that ECM-bound cytokines (e.g., TGF-β, IL-10) can be strategically leveraged to steer immune responses toward pro-regenerative phenotypes [&lt;span&gt;4&lt;/span&gt;]. Furthermore, the potential of DSMMs to modulate neuroimmunological pathways, particularly those involving aryl hydrocarbon receptor (AhR) signalling—a key regulator of inflammation and tissue repair—merits investigation given its emerging role in mitigating fibrosis in other regeneration models [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The comprehensive cataloguing of functional outcomes appropriately highlights the variability in assessment methods across studies. Integration of multimodal evaluation frameworks, including gait analysis for large animals and advanced ultrasonography for angiogenesis monitoring, could significantly enhance translational predictability [&lt;span&gt;6&lt;/span&gt;]. The limited discussion of long-term (&gt; 12 weeks) data represents an important gap, as understanding fibrotic progression and ectopic mineralisation risks is essential for clinical adoption [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Regarding translational challenges, the review notes scalability issues but could expand on recent biomaterial innovations addressing these limitations. For instance, 3D-bioprinted DSMM scaffolds with architecturally patterned microchannels have demonstrated enhanced myoblast alignment and neural integration in large animal models [&lt;span&gt;8&lt;/span&gt;]. Similarly, while crosslinking strategies balance degradation kinetics with mechanical stability, their long-term biocompatibility requires more thorough validation","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation Mediated by OGA Activates NEK7/NLRP3 Pathway to Promote Pyroptosis in Parkinson's Disease","authors":"Zhi Wang,&nbsp;Yue Liu,&nbsp;Lili Ma,&nbsp;Hongwei Sun,&nbsp;Ying Tang","doi":"10.1111/jcmm.70874","DOIUrl":"10.1111/jcmm.70874","url":null,"abstract":"<p>Parkinson's disease (PD) is a neurodegenerative disorder characterised by pyroptosis. O-GlcNAcylation, regulated solely by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), has been shown to mitigate PD. This study aimed to investigate whether pyroptosis and PD pathogenesis are modulated by O-GlcNAcylation. In PD model cells, O-GlcNAc protein levels were downregulated, while OGA expression was upregulated. Knockdown of OGA significantly protected BV2 cells from LPS-induced injury by inhibiting pyroptosis. Inhibition of OGA notably increased the O-GlcNAc levels of NEK7. Furthermore, O-GlcNAcylated NEK7 protein levels were significantly reduced by mutations at T170 or T172, whereas phosphorylated NEK7 protein levels were downregulated only by mutations at T172. Co-immunoprecipitation (co-IP) confirmed the endogenous interaction between NEK7 and NLRP3, which was weakened by OGA knockdown. In animal experiments, OGA deficiency significantly reduced motor dysfunctions and dopaminergic neurodegeneration in MPTP-treated mice. OGT deficiency abolished the protective effects of OGA knockdown against MPTP-induced injury. Additionally, OGT inhibition in OGA knockdown mice promoted pyroptosis. Collectively, these findings indicate that high OGA levels decrease O-GlcNAcylation in PD, thereby promoting pyroptosis via the activation of the NEK7/NLRP3 pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours","authors":"Antonio Sechi,&nbsp;Jolein Mijnes,&nbsp;Sophia Villwock,&nbsp;Michael Rose,&nbsp;Florian Steib,&nbsp;Sarah Bringezu,&nbsp;Jonas Berger,&nbsp;Carmen Schalla,&nbsp;Sonja von Serenyi,&nbsp;Jana Dietrich,&nbsp;Nadina Ortiz-Brüchle,&nbsp;Lara Heij,&nbsp;Jan Bednarsch,&nbsp;Oleg Gluz,&nbsp;Ulrike Nitz,&nbsp;Nadia Harbeck,&nbsp;Monika Graeser,&nbsp;Christine zu Eulenburg,&nbsp;Mohammad Parsa Mohammadian,&nbsp;Katarzyna Jóźwiak,&nbsp;Hans-Heinrich Kreipe,&nbsp;Matthias Christgen,&nbsp;Martin Radner,&nbsp;Danny Jonigk,&nbsp;Edgar Dahl","doi":"10.1111/jcmm.70870","DOIUrl":"10.1111/jcmm.70870","url":null,"abstract":"<p>Understanding the role and molecular regulation of genes associated with tumour cell motility may be informative for future cancer therapy development. <i>Sperm-associated antigen 6</i> (<i>SPAG6</i>) gene, encoding an evolutionarily highly conserved flagellar motility protein, is regulated by promoter hypermethylation in breast cancer. Our in silico analysis of healthy and breast cancer tissues from The Cancer Genome Atlas (TCGA) showed tumour-specific <i>SPAG6</i> promoter hypermethylation in all molecular subtypes. Immunohistochemistry on the independent WSG PlanB breast cancer cohort (<i>n</i> = 2241) confirmed comprehensive down-regulation of SPAG6 on the protein level. In vitro models demonstrated that SPAG6 overexpression in luminal cells exhibited strongly increased migration capacity (<i>p</i> &lt; 0.0001) and characteristics of epithelial-mesenchymal transition (EMT) with actin and E-cadherin displacement. We propose that SPAG6 may have an important role in triggering the EMT program in luminal breast cancer cells, driving tumour progression and metastasis.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT01049425</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Multi-Omics Insights Into Monocyte Pantothenate-Mediated Protection in Acute Respiratory Distress Syndrome","authors":"Yang Wang,&nbsp;Hongyu Sun,&nbsp;Fengying Liang,&nbsp;Yanting Qian,&nbsp;Yuanyuan Wang,&nbsp;Mingdeng Wang,&nbsp;Yuansheng Lin","doi":"10.1111/jcmm.70812","DOIUrl":"10.1111/jcmm.70812","url":null,"abstract":"<p>Acute respiratory distress syndrome (ARDS) is a severe condition with complex pathogenesis, and emerging evidence highlights the potential role of metabolic factors, though the exact mechanisms are not fully understood. In this study, we used Mendelian randomisation (MR) and multi-omics approaches to investigate the causal relationship between plasma metabolites, immune cell profiles and ARDS risk. MR analysis of 1400 metabolites identified two causal metabolites linked to increased ARDS risk, primarily involved in pantothenate and CoA biosynthesis. Single-cell RNA sequencing of ARDS samples revealed that monocytes exhibited the highest levels of pantothenate synthesis. Intercellular communication and pseudotime analysis suggested that the pantothenate synthesis pathway influenced monocyte differentiation and interactions with other cell types. Gene set enrichment analysis showed that monocytes with high pantothenate synthesis were significantly enriched in phagocytosis-related pathways. Subsequent MR analysis demonstrated that CD33dim HLA DR+ CD11b+%CD33dim HLA DR+ were a risk factor against ARDS. Notably, monocytes with high pantothenate synthesis exhibited decreased expression of antigen presentation markers HLA-DRB5, HLA-DRB1 and HLA-DRA, suggesting that the high pantothenate synthesis monocytes exhibit attenuated antigen presentation and enhanced phagocytic function. Moreover, we developed a diagnostic model using machine learning algorithms. Shapley Additive explanation (SHAP) was leveraged to evaluate the model performance, with CALM2 identified as the most influential feature across the CatBoost and XGBoost models. In summary, this study integrates genetic, multi-omics and machine learning approaches to provide novel insights into the pathogenesis of ARDS and its potential therapeutic strategies targeting monocyte metabolism and function.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding: CXCL10 Secreted by SPRY1-Deficient Epidermal Keratinocytes Fuels Joint Inflammation in Psoriatic Arthritis via CD14 Signalling","authors":"DuJiang Yang,&nbsp;Jiafeng Song,&nbsp;Junjie Chen,&nbsp;Shuang Wang,&nbsp;GuoYou Wang","doi":"10.1111/jcmm.70887","DOIUrl":"10.1111/jcmm.70887","url":null,"abstract":"&lt;p&gt;The recent work by Xu et al. (JCI 186135) provides a transformative perspective on the pathophysiology of psoriatic arthritis (PsA) by elucidating a precise mechanistic link between cutaneous inflammation and articular involvement [&lt;span&gt;1&lt;/span&gt;]. Their findings position the SPRY1/CXCL10/CD14 axis as a critical driver of disease, offering a paradigm shift from viewing PsA merely as a comorbid condition to understanding it as a systemically connected process orchestrated by specific molecular cues from the skin.&lt;/p&gt;&lt;p&gt;This study compellingly demonstrates that deficiency of SPRY1 in epidermal keratinocytes is not only a progenitor of psoriatic dermatitis but also a potent instigator of joint pathology. The authors utilise a keratinocyte-specific Spry1-knockout mouse model to recapitulate key features of PsA [&lt;span&gt;1&lt;/span&gt;]. The central revelation is that these keratinocytes secrete high levels of CXCL10, which acts as a chemotactic signal, mobilising CXCR3+ immune cells to the joints [&lt;span&gt;1&lt;/span&gt;]. The subsequent engagement of the CD14 receptor on macrophages, leading to NF-κB activation and TNF-α production, represents a significant mechanistic insight [&lt;span&gt;1&lt;/span&gt;]. This work aligns with emerging evidence that CXCL10 is among the most promising biomarkers for predicting PsA development in psoriasis patients [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The translational implications of these findings are substantial [&lt;span&gt;3&lt;/span&gt;]. The demonstration that Cd14-deficient mice are resistant to CXCL10-induced arthritis underscores the non-redundant role of CD14 signalling in this pathway [&lt;span&gt;1&lt;/span&gt;]. This is particularly relevant given recent clinical trials showing that CXCL10 levels decrease following effective Tyk2 inhibition with deucravacitinib, and that higher baseline CXCL10 levels predict better treatment response [&lt;span&gt;4&lt;/span&gt;]. These parallel findings suggest that CXCL10 might serve both as a predictive biomarker and a therapeutic target.&lt;/p&gt;&lt;p&gt;However, several intriguing questions emerge. First, the precise molecular nature of the CXCL10-CD14 interaction requires further elucidation. Second, while the role in macrophages is clear, does CD14 signalling in other myeloid cells contribute to the pathology? Third, the relationship between this novel pathway and established cytokine networks in PsA, particularly the IL-23/IL-17 axis, needs clarification [&lt;span&gt;5&lt;/span&gt;]. Recent research has confirmed that IL-17A remains a crucial mediator in PsA pathogenesis [&lt;span&gt;6&lt;/span&gt;], and the interplay between CXCL10 and IL-17A signalling merits investigation.&lt;/p&gt;&lt;p&gt;The clinical applications of these discoveries are promising. Targeting the CXCL10/CD14 interface could offer a strategic therapeutic advantage by intercepting the inflammatory signal en route from the skin to the joint. This approach might potentially prevent arthritis development in high-risk psoriasis patients [&lt;span&gt;2&lt;/span&gt;]. The data suggest that circulating CXCL10 levels could help strat","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Yield Extruded Nanovesicles From Adipose Stem Cells Promote High-Quality Healing of Diabetic Wound Through WNT/β-Catenin Pathway Activation","authors":"Tonghao Yao,&nbsp;Liangliang Liu,&nbsp;Yibo Miao,&nbsp;Xinxin Li,&nbsp;Ying Yu,&nbsp;Rongyao Sun,&nbsp;Yining Zhang,&nbsp;Luping Cui,&nbsp;Xu Ma","doi":"10.1111/jcmm.70877","DOIUrl":"10.1111/jcmm.70877","url":null,"abstract":"<p>Diabetes is a significant global chronic disease characterised by elevated mortality and disability rates due to persistent infections resulting from refractory wounds. Currently, effective treatment strategies are lacking. Adipose-derived stem cell extracellular vesicles (ADSC-EVs) have been shown to promote skin wound healing; however, their clinical application is impeded by low yield and heterogeneity. We successfully isolated high-yield extruded nanovesicles from adipose stem cells (ADSC-NVs), achieving yields over 30 times greater than those of ADSC-EVs while maintaining similar mor-phological characteristics. Our findings indicate that ADSC-NVs exhibit a dose-dependent en-hancement of proliferation and migration in primary human dermal fibroblasts (HDF) in vitro. Notably, the expression levels of proliferating cell nuclear antigen (PCNA), collagen type I (COL-I) and collagen type III (COL-III) were significantly upregulated in HDF following treatment with ADSC-NVs. RNA-seq analysis further revealed that the differentially expressed genes (DEGs) shared between the ADSC-NVs group and control group were predominantly enriched in the Wnt signalling pathway. Consistently, ADSC-NVs facilitate efficient diabetic wound healing while promoting proliferation and inhibiting inflammation via the Wnt/β-catenin signalling pathway. In summary, high-yield ADSC-NVs represent a promising alternative to ADSC-EVs for enhancing diabetic wound healing, providing novel insights and methodologies for improving therapeutic outcomes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoimperatorin Reduces Synovial Inflammation and Fibrosis in Knee Osteoarthritis via the cAMP Signalling Pathway","authors":"Lishi Jie,&nbsp;Junnan Liu,&nbsp;Zaishi Zhu,&nbsp;Zeling Huang,&nbsp;Yujiang Liu,&nbsp;Guanhong Liu,&nbsp;Xiaofeng Shen,&nbsp;Yuwei Li,&nbsp;Xiaoqing Shi","doi":"10.1111/jcmm.70880","DOIUrl":"10.1111/jcmm.70880","url":null,"abstract":"<p>To explore the mechanism of pharmacological action of Isoimperatorin (ISO), a small molecule compound with anti-inflammatory properties extracted from the rhizome of <i>Notopterygium incisum</i>, in attenuating synovial inflammation in knee osteoarthritis (KOA). By establishing a rat model of KOA and using histopathology and molecular biology methods, we evaluated the pharmacological effect of ISO on synovitis. Synovial fluid from the knee joint was collected for transcriptomic and metabolomic analyses. Fibroblast-like synoviocytes were cultured in vitro, and calcium fluorescence imaging and mitochondrial membrane potential assays were performed to assess the effects of ISO on the cAMP signalling pathway and KOA-related synovial inflammation. Preliminary pharmacodynamic observations showed that ISO was able to reduce synovial inflammation in KOA rats. Further transcriptomic findings in synovial tissues indicated that the mechanism of action of ISO was related to the cAMP signalling pathway and calcium ion signalling pathway. The results of metabolomics showed that the progression of synovial fibrosis was related to the abnormal metabolism of glycerophospholipids, and the intervention of ISO could significantly promote the metabolism of glycerophospholipids in synovial tissues. Finally, the results of in vitro experiments showed that ISO improved the level of inflammation and the degree of fibrosis in synovial cells, activated the cAMP signalling pathway and promoted PPAR expression, whereas inhibition of the activation of the cAMP signalling pathway attenuated the effects of ISO. ISO promotes PPAR function by upregulating the cAMP signalling pathway to modulate glycerophospholipid metabolism, thereby alleviating synovial inflammation and slowing fibrosis progression in KOA.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zerumbone Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing the NLRP3/Caspase-1/GSDMD Signalling Pathway","authors":"Yun-Jie Xu,&nbsp;Fei-Fei Fang,&nbsp;Guo-Qiang Zhao,&nbsp;Wei-Yan Yu,&nbsp;Hong-Yan Han,&nbsp;Hong Teng,&nbsp;Jun-Ning Lyu,&nbsp;Jian-Feng Wang","doi":"10.1111/jcmm.70873","DOIUrl":"10.1111/jcmm.70873","url":null,"abstract":"<p>A cyclic sesquiterpene with 11 carbon atoms is the primary component of essential oils from the wild ginger species, <i>Zingiber zerumbet</i>. It exhibits pharmacological effects, including anti-inflammatory and antioxidant properties. However, limited information exists regarding its role in pyroptosis during acute lung injury (ALI). Herein, we investigated how zingerone affects pyroptosis in a murine lipopolysaccharide (LPS)-induced ALI model established via intraperitoneal zerumbone (Zer) administration. Bronchoalveolar lavage fluid, serum, and lung tissue samples were collected after 24 h. Haematoxylin and eosin staining was performed to assess lung tissue damage. Western blot analysis and real-time quantitative polymerase chain reaction (qRT-PCR) were used to quantify protein expression levels associated with pyroptosis. Before LPS exposure, mouse alveolar epithelial (MLE)-12 cells were pretreated with 10 μM Zer for 2 h and then incubated with 1 ng/mL LPS for an additional 24 h. Zer treatment reduced lung tissue injury, inflammation, and oxidative stress in model mice. Zer counteracted pyroptosis in the alveolar epithelial cells of these mice. In MLE-12 cells, Zer significantly inhibited oxidative stress and inflammation. Zer suppressed NLRP3/Caspase-1/GSDMD signalling, pivotal in pyroptosis, mitigating ALI progression. A potential novel therapeutic agent for ALI inhibited the NLRP3/GSDMD signalling pathway involved in pyroptosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Flavonoid Kaempferol Mitigates Periprosthetic Osteolysis by Regulating the NLRP3 Inflammasome and Balancing Bone Metabolism","authors":"Cheng Huang,&nbsp;Chenhui Zhang,&nbsp;Yongjun Luo,&nbsp;Lujun Guo,&nbsp;Yanglin Wu,&nbsp;Qingyan Shi,&nbsp;Yazhong Zhang,&nbsp;Chengyuan Yang,&nbsp;Bo Wang,&nbsp;Junjie Niu,&nbsp;Jun Lin","doi":"10.1111/jcmm.70878","DOIUrl":"10.1111/jcmm.70878","url":null,"abstract":"<p>Total joint arthroplasty (TJA) is an effective intervention for end-stage arthritis; however, its long-term success is often compromised by wear particle–induced osteolysis, leading to aseptic loosening and implant failure. This study investigates the potential of kaempferol (Ka), a natural flavonoid with anti-inflammatory properties, to alleviate osteolysis by modulating NLRP3 inflammasome activation. In a murine calvarial osteolysis model, Ka administration significantly attenuated bone loss induced by CoCrMo alloy particles. Mechanistically, Ka dose-dependently inhibited NLRP3 inflammasome activation in macrophages, as evidenced by reduced IL-1β secretion, decreased ASC oligomerisation and suppressed GSDMD cleavage, ultimately leading to decreased pyroptosis. These effects were found to be partially mediated via GPR109a. Furthermore, Ka markedly suppressed osteoclast differentiation and activity both in vivo and in vitro while promoting osteoblast differentiation, thereby contributing to the restoration of bone remodelling balance. Taken together, our findings suggest that Ka exerts a protective effect against wear particle–induced osteolysis by targeting the NLRP3 inflammasome and modulating osteoimmune responses, which may offer a novel therapeutic strategy to manage periprosthetic osteolysis and prolong implant longevity.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}