JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Therapeutic Potential of Gene-Modified MSC-Exos in Insulin Resistance: Mitochondrial Crosstalk and miRNA Regulation","authors":"Qinghua Jia,&nbsp;Bing Li,&nbsp;Yuan Xing,&nbsp;Yuanyuan Zhang,&nbsp;Baodong Gao,&nbsp;Xiangying Li,&nbsp;Xiaoqin Ha","doi":"10.1111/jcmm.71342","DOIUrl":"10.1111/jcmm.71342","url":null,"abstract":"<p>Insulin resistance (IR) is the key driver of type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and cardiometabolic disorders. Mesenchymal stem cell-derived exosomes (MSC-Exos) as a potent cell-free alternative can deliver miRNAs, proteins, and mitochondrial regulators to reactivate the IRS1/PI3K/Akt/GLUT4 axis. Beyond restoring insulin signalling, these vesicles can protect β-cells, alleviate endoplasmic reticulum stress, rescue mitochondrial mitophagy and respiration. The genetic engineering strategies including improving the expression of miR-21, miR-3075, or Sirtuin-3, and silencing miR-29b-3p amplify the therapeutic efficacy. However, scalable good manufacturing practice production, long-term safety of modified products, and advanced therapy medicinal product regulation are still needed to overcome. This review will introduce the potential of gene-modified MSC-Exos and miRNAs targeting insulin signalling and mitochondrial rescue, which have shown a shift from symptomatic relief to precision disease-modifying therapy for IR.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891537","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":"Graphene Oxide–Hydroxyapatite Nanocomposite Coatings and Extracellular Matrix Protein Interactions for Enhanced Osseointegration in Dental Implants","authors":"Ravinder S. Saini,&nbsp;Rayan Ibrahim H. Binduhayyim,&nbsp;Doni Dermawan,&nbsp;Masroor Ahmed Kanji,&nbsp;Syed Altafuddin Quadri,&nbsp;Artak Heboyan","doi":"10.1111/jcmm.71352","DOIUrl":"10.1111/jcmm.71352","url":null,"abstract":"<p>Graphene oxide (GO) has been recognised to have a strong protein-binding ability attributed to its high surface area and oxygen functional groups (OFGs) but is plagued with dose-dependent cytotoxicity. In contrast, hydroxyapatite (HA) is highly biocompatible but has shown relatively weak protein–protein interactions on the molecular scale. The strategic merging of GO and HA into the GO–HA nanocomposite has the potential to synergistically and precisely facilitate bioactivity and biocompatibility across the implant–tissue interface. Molecular docking, pharmacophore modelling, and molecular dynamics simulations were used to explore the molecular interactions of GO, HA, and GO–HA nanocomposites with ECM proteins, including fibronectin (FN), collagen (COL), laminin (LAM), periostin (POSTN), vitronectin (VN), and osseointegration-related integrin receptors under physiological conditions. The GO–HA nanocomposites exhibited an enhanced number of hydrogen bonds and decreased residue-level fluctuations relative to GO or HA individually, indicating improved interfacial interaction stability at the protein–surface interface. Molecular dynamics simulation results indicated that ECM proteins in the presence of GO–HA showed better conformational stability, which might lead to favourable integrin-mediated adhesion. Preliminary in silico toxicity-related screening of the individual GO and HA model structures suggested differential safety alert patterns, with GO showing more cautionary alerts than HA. These outputs were interpreted qualitatively because the predictive tools used were primarily designed for small molecules rather than nanomaterials. Overall, these in silico results at the molecular scale revealed insights into the surface–biomolecule interactions of GO–HA, which may pertain to early events in osseointegration and can be used to create awareness for downstream in vitro and in vivo validation of dental implant coatings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887614","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":"Salvianolic Acid B Inhibits Ferroptosis in Acute Lung Injury: Network Analysis and Experimental Validation","authors":"Hejun Gao,&nbsp;Renhui Xiong,&nbsp;Na Yue,&nbsp;Jiaxin Wang,&nbsp;Shouyuan Tian","doi":"10.1111/jcmm.71344","DOIUrl":"10.1111/jcmm.71344","url":null,"abstract":"<p>This current study aimed to decipher the anti-inflammatory, anti-ferroptosis and pronounced lung-protective activities of Salvianolic acid B (Sal B) by integrating network pharmacology and experimental confirmation across multiple aspects. The optimal target protein and the relevant molecular mechanisms for Sal B in the context of ALI were analysed using network pharmacology. Molecular dynamics simulations and BLI were performed on the core protein ALB–compound Sal B identified through molecular docking. The pharmacological efficacy of Sal B and its underlying mechanisms were further substantiated through both in vitro and in vivo experiments, utilizing the LY294002 inhibitor and si-ALB to confirm the involvement of ALB as a target. Additionally, RNA sequencing of murine lung tissues was conducted to further elucidate the molecular mechanism of Sal B. The results of network pharmacology indicated that a total of 155 potential target genes through which Sal B may exert its protective effects against ALI were identified, with essential pathways including PI3K-AKT, TNF and IL-17 signalling pathways. Molecular docking, MD, and BLI demonstrated stable binding between Sal B and the core target ALB. In vitro and in vivo evidence confirmed that Sal B attenuates LPS-induced ALI by inhibiting ferroptosis via the PI3K/AKT axis, as corroborated by LY294002 and si-ALB intervention. RNA sequencing and network pharmacological analysis synergistically revealed the PI3K/AKT pathway as a potential signalling pathway for Sal B. Sal B ameliorates sepsis-induced ALI via a defined mechanism that involves the activation of the PI3K-AKT pathway, thereby inhibiting ferroptosis both in vivo and in vitro.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887589","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":"RETRACTION: Kruppel-Like Factor 4 Improves Obesity-related Nephropathy Through Increasing Mitochondrial Biogenesis and Activities","authors":"","doi":"10.1111/jcmm.71314","DOIUrl":"10.1111/jcmm.71314","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>L. Jin</span>, <span>H. Ye</span>, <span>M. Pan</span>, <span>Y. Chen</span>, <span>B. Ye</span>, <span>Y. Zheng</span>, <span>W. Huang</span>, <span>S. Pan</span>, <span>Z. Shi</span>, and <span>J. Zhang</span>, “ <span>Kruppel-Like Factor 4 Improves Obesity-related Nephropathy Through Increasing Mitochondrial Biogenesis and Activities</span>,” <i>Journal of Cellular and Molecular Medicine</i> <span>24</span>, no. <span>2</span> (<span>2019</span>): <span>1200</span>-<span>1207</span>, https://doi.org/10.1111/jcmm.14628.\u0000 </p><p>The above article, published online on 4 December 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Specifically, image elements in Figure 3C were found to have been previously published by a different author group in a different scientific context. Further investigation by the publisher identified undeclared splicing sites in the IκB blot in Figure 2F and in the α-porin blot in Figure 4c. Finally, the tubulin blot in Figure 4c was also found to have been previously published by a different author group in a different scientific context.</p><p>The first author stated that the overlap of data with a previous publication lacking shared authorship was due to data theft from their laboratory. However, no further clarification or supporting raw data was provided for the remaining concerns. As a result, the article has been retracted as the editors have lost confidence in the integrity and reliability of the whole body of data and consider the article's conclusions invalid.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887638","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":"Comparative Efficacy of BTK Inhibitors in Treatment-Naïve and Relapsed/Refractory Mantle Cell Lymphoma: A Systematic Review and Meta-Analysis","authors":"Fangfei Xu,&nbsp;Xiuping Zou,&nbsp;Yulin Yang,&nbsp;Kuangguo Zhou,&nbsp;Wei Huang","doi":"10.1111/jcmm.71340","DOIUrl":"10.1111/jcmm.71340","url":null,"abstract":"<p>Bruton tyrosine kinase inhibitors (BTKis) have been employed in the treatment of mantle cell lymphoma (MCL). However, direct comparisons of ibrutinib, zanubrutinib, and acalabrutinib across treatment-naïve (TN) and relapsed/refractory (R/R) MCL remain limited. This meta-analysis was intended to evaluate their efficacy, addressing critical gaps in clinical decision-making. We systematically searched PubMed, Embase, and Cochrane up to January 2025 for studies (RCT/single-arm) assessing the efficacy of BTKis in MCL patients. Among 70 studies, the pooled CR rate in the TN group was higher than that in the R/R group (76.5% vs. 43.2%). Among TN patients, the CR rate of the regimen incorporating zanubrutinib (95.2% [95% CI 0.893, 1.000]) was significantly higher than that of the regimens containing acalabrutinib or ibrutinib (<i>p</i> = 0.0042). In the R/R group, the BTKi + anti-CD20 monoclonal antibody + small-molecular therapy group presented a better CR rate (68.3% [95% CI 0.546, 0.820]; <i>p</i> &lt; 0.0001). When comparing the monotherapy efficacy of three BTKis in R/R MCL, the results indicated that acalabrutinib exhibited a higher CR rate (43.2% [95% CI 0.339, 0.525]) than zanubrutinib or ibrutinib. In addition, zanubrutinib-based therapy exhibited a lower pooled rate of haematological toxicities compared to the other two BTKi therapies. This work resolved critical uncertainties in BTKi selection for MCL, demonstrating acalabrutinib's and zanubrutinib's first-line potential, leading to a meaningful improvement in response rate and a manageable safety profile. Chemotherapy-free regimen can partially overcome the traditionally unfavourable prognosis associated with R/R MCL. These results provide a roadmap for optimizing MCL therapy. Chemotherapy-free regimens for MCL based on BTKis warrant further validation in RCTs. These findings may advocate for updated guidelines prioritizing zanubrutinib and acalabrutinib in clinical practice.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880495","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":"Delineating the Concerted Action of Virulence Attributes in Candida albicans Systemic Infection","authors":"Olivia K. A. Paulin,&nbsp;Xiaoli Xu,&nbsp;Shu Chen Chong,&nbsp;Eve W. L. Chow,&nbsp;Li Mei Pang,&nbsp;Aaron D. Hernday,&nbsp;Jonathan P. Richardson,&nbsp;Yue Wang,&nbsp;Julian R. Naglik","doi":"10.1111/jcmm.71353","DOIUrl":"10.1111/jcmm.71353","url":null,"abstract":"&lt;p&gt;&lt;i&gt;Candida albicans&lt;/i&gt; is a World Health Organisation ‘critical priority’ pathogen [&lt;span&gt;1&lt;/span&gt;], with systemic infections exhibiting a mortality rate of ~65% [&lt;span&gt;2&lt;/span&gt;]. &lt;i&gt;C. albicans&lt;/i&gt; possesses numerous virulence attributes to establish infection including hyphal formation, adhesion, toxin secretion and hydrolytic enzyme production [&lt;span&gt;3&lt;/span&gt;]. Hyphal formation is regulated by proteins including Hgc1p, a G1-cyclin critical for hyphal maintenance [&lt;span&gt;4&lt;/span&gt;]; however, a &lt;i&gt;hgc1&lt;/i&gt;Δ/Δ strain can still express hypha-associated genes (e.g., &lt;i&gt;ALS3&lt;/i&gt;, &lt;i&gt;ECE1&lt;/i&gt;) [&lt;span&gt;4&lt;/span&gt;]. Hyphal adhesion and invasion is mediated predominantly by Als3p through its interaction with host receptors such as E-cadherin [&lt;span&gt;3&lt;/span&gt;]. Hyphae secrete candidalysin (encoded by &lt;i&gt;ECE1&lt;/i&gt;), a peptide toxin critical for host cell damage, mucosal translocation and induction of pro-inflammatory immune responses [&lt;span&gt;5&lt;/span&gt;]. &lt;i&gt;C. albicans&lt;/i&gt; also secretes hydrolases including Sap2p, which degrade host proteins for nutrient acquisition and immune evasion [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Reverse genetics has identified virulence attributes important for &lt;i&gt;C. albicans&lt;/i&gt; infection. However, while single knockout studies have provided key insights, the combined action of virulence genes during systemic infection remains poorly understood. Moreover, differing methodologies and genetic backgrounds limit cross-study comparisons. Here, we generated a panel of mutant strains with additive deletions in a single genetic background, enabling systematic evaluation of individual and combined virulence factors during systemic &lt;i&gt;C. albicans&lt;/i&gt; infection.&lt;/p&gt;&lt;p&gt;Many studies have investigated the roles of &lt;i&gt;ALS3&lt;/i&gt;, &lt;i&gt;ECE1&lt;/i&gt;, &lt;i&gt;HGC1&lt;/i&gt; and &lt;i&gt;SAP2&lt;/i&gt; in &lt;i&gt;C. albicans&lt;/i&gt; infections. However, comparisons between knockout strains are complicated by different genetic backgrounds and provide limited insight into combinatorial gene function during infection. To address this, we constructed single and combinatorial mutants in a single genetic background [&lt;span&gt;6&lt;/span&gt;] and assessed virulence in a systemic murine model.&lt;/p&gt;&lt;p&gt;Although the kidney is generally considered the major target organ in murine systemic candidiasis, no clear role for each gene was observed in early kidney fungal control (day-3). Interestingly, however, during brain infections, hyphal growth/maintenance (&lt;i&gt;HGC1&lt;/i&gt;) and candidalysin (&lt;i&gt;ECE1&lt;/i&gt;) were critical for controlling fungal burden. Complementing previously published datasets investigating single &lt;i&gt;ECE1&lt;/i&gt; and &lt;i&gt;HGC1&lt;/i&gt; deletions, deletion of &lt;i&gt;ECE1&lt;/i&gt; significantly increased fungal burden compared to WT [&lt;span&gt;8, 9&lt;/span&gt;], which was further exacerbated by concurrent &lt;i&gt;HGC1&lt;/i&gt; deletion [&lt;span&gt;8&lt;/span&gt;]. By comparison, deletion of &lt;i&gt;ALS3&lt;/i&gt; or &lt;i&gt;SAP2&lt;/i&gt; had minimal impact, suggesting limited roles for Als3p and Sap2p in brain infection. These findings likely reflect the combined effects of Hgc1p-driven hyp","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880528","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":"Evolving Trends in Autoimmune Hepatitis Research: A Bibliometric Analysis From 2004 to 2024","authors":"Yuling Kong,&nbsp;Zhifeng Lin","doi":"10.1111/jcmm.71348","DOIUrl":"10.1111/jcmm.71348","url":null,"abstract":"&lt;p&gt;Autoimmune hepatitis (AIH) is a heterogeneous, immune-mediated liver disease with diverse clinical presentations. Its diagnosis relies on combined clinical, biochemical, serological and histological findings rather than a single marker [&lt;span&gt;1, 2&lt;/span&gt;]. Corticosteroid-based immunosuppression remains the cornerstone of treatment, yet diagnostic uncertainty, relapse and treatment toxicity persist [&lt;span&gt;1, 2&lt;/span&gt;]. We therefore examined whether the recent research portfolio is shifting towards questions that could address these uncertainties, rather than merely increasing in volume.&lt;/p&gt;&lt;p&gt;We analysed English-language articles and reviews indexed in the Web of Science Core Collection between 1 January 2004 and 31 December 2024. The search and screening were completed on 19 April 2025. We used VOSviewer 1.6.20, CiteSpace 6.4.R1 and the R package bibliometrix to analyse collaboration, co-citation, keyword co-occurrence, citation bursts and thematic evolution [&lt;span&gt;3-5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The 6310 records spanned 110 countries, 5717 institutions, 28,429 authors and 1348 journals, with annual output rising markedly after 2020 (Figure 1). The United States, China, the United Kingdom and Japan were the leading contributors. Mayo Clinic and King's College Hospital London occupied prominent positions in the collaboration network. Liver International published the most records, whereas Hepatology was the most frequently co-cited journal. Albert J. Czaja and Ansgar W. Lohse were prominent in the authorship and citation analyses. These rankings reflect research activity and network position, not methodological quality or clinical impact.&lt;/p&gt;&lt;p&gt;More important than growth alone was the shift in the questions attracting attention. Earlier research focused on diagnosis, immunosuppressive treatment and liver transplantation. Recent burst and trend analyses increasingly highlighted the gut microbiota, gut–liver axis, biomarker discovery, immune regulation, multi-omics and computational approaches (Figure 2). In a clinical cohort, Liwinski et al. identified reduced microbial diversity and a disease-specific decline in Bifidobacterium [&lt;span&gt;6&lt;/span&gt;]. Lower abundance was associated with failure to achieve remission [&lt;span&gt;6&lt;/span&gt;]. Zhang et al. reported increased intestinal permeability among patients with AIH. In murine models, barrier dysfunction and bacterial translocation intensified RIP3-associated hepatic inflammation, while antibiotic treatment attenuated liver injury [&lt;span&gt;7&lt;/span&gt;]. Together, these findings support further investigation of host–microbe interactions in AIH. However, human associations and animal interventions do not establish a causal gut mechanism in patients.&lt;/p&gt;&lt;p&gt;Biomarker research warrants similarly cautious interpretation of the available evidence. A review catalogued candidate gene-expression, protein, metabolite and immune-cell markers, while emphasising that clinically useful predictors remain inadequately established [&lt;span&gt;8&lt;","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880505","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":"Single-Cell Immune Profiling Suggests Non-Classical Monocyte Is Associated Immunodepression in Tuberculosis Treatment Non-Responders","authors":"Yiqun Xiong,&nbsp;Yahong Qu,&nbsp;Ying Wang,&nbsp;Dongliang Zhang,&nbsp;Hao Shen,&nbsp;Weixin Wang,&nbsp;Junshun Gao,&nbsp;ZhenBo Wang,&nbsp;Zhihong Shen,&nbsp;Yang Che","doi":"10.1111/jcmm.71345","DOIUrl":"10.1111/jcmm.71345","url":null,"abstract":"<p>Sputum culture conversion (SCC) at 2 months is an early indicator of tuberculosis (TB) treatment response, yet the associated immune alterations remain incompletely defined. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from eight TB patients, stratified by 2-month SCC status. Non-responders showed a relative enrichment of non-classical monocytes and higher TB progression risk scores. CellChat analysis inferred altered IL16 and TRAIL communication involving these cells. CD4+ Tregs in non-responders showed higher LGALS9 expression and inferred GALECTIN signalling towards cytotoxic lymphocyte subsets; cell-level LGALS9 co-expression correlated with HAVCR2 and TIGIT in non-responders. Mature NK subclusters showed distinct enrichment profiles. These results describe an observational, transcriptomic and computationally inferred immune network associated with early treatment non-response. They generate candidate biomarkers and hypotheses for prospective protein-level and functional validation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865168","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":"Early SOX9 Activation Primes Hippo–YAP/TAZ Rewiring During Glioblastoma Stemness Acquisition","authors":"Maimaitili Mijiti,&nbsp;Yandong Li,&nbsp;Aierpati Maimaiti,&nbsp;Gaocai Zhang,&nbsp;Minghao Lian,&nbsp;Chunyu Song,&nbsp;Yongtao Zhang,&nbsp;Jufan Wang,&nbsp;Yunbo Wang,&nbsp;Xiaoqin Chen,&nbsp;Xiangrui Kong,&nbsp;Xiahela Xiaokaiti,&nbsp;Nuerzhati Wusiman,&nbsp;Guohua Zhu,&nbsp;Dangmurenjiafu Geng,&nbsp;Hua Shi","doi":"10.1111/jcmm.71341","DOIUrl":"10.1111/jcmm.71341","url":null,"abstract":"<p>Glioblastoma progression is driven by stemness acquisition and cellular plasticity, yet the temporal and spatial organization of these processes remains incompletely defined. In this study, single-cell RNA sequencing, pseudotime reconstruction, spatial transcriptomics, and in vitro and in vivo functional assays were integrated to delineate the role of SOX9 during glioblastoma stemness acquisition. SOX9 expression peaked during the early astrocyte-to-malignant transition and declined after malignant states became stabilized. Along pseudotime, SOX9 was inversely associated with the upstream Hippo kinase module and showed phase-dependent coupling with YAP/TAZ-associated transcriptional programmes. Spatial analyses further revealed marked regional heterogeneity, with the strongest SOX9-malignant coupling observed in the perivascular niche. Functionally, SOX9 gain and loss produced reciprocal changes in glioblastoma cell proliferation, migration, invasion, apoptosis, and xenograft growth, while pharmacological modulation of Hippo signalling partially rescued the effects induced by SOX9 loss. Consistent pathway-level changes were also observed in YAP/TAZ expression and p-YAP/YAP and p-MOB1/MOB1 ratios, and xenograft histology showed SOX9-associated morphological and CD68-positive cell changes. These findings identify SOX9 as a temporally restricted regulator of glioblastoma stemness acquisition and support an early priming-late decoupling model of Hippo-YAP/TAZ rewiring, providing a rationale for stage-specific and niche-aware therapeutic targeting in glioblastoma.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857032","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":"From Periodontal Pocket to Systemic Diseases: Mechanistic Insights Into the Role of Porphyromonas gingivalis in Host Pathology","authors":"Alaa Ahmed Basalim,&nbsp;Emily Ming-Chieh Lu","doi":"10.1111/jcmm.71327","DOIUrl":"10.1111/jcmm.71327","url":null,"abstract":"<p><i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), a keystone pathogen in periodontitis, has been increasingly recognised as a mechanistic bridge linking periodontal infection to pathological destruction in distant organs. <i>P. gingivalis</i> virulence factors, including gingipains, lipopolysaccharides (LPS), and outer membrane vesicles (OMVs), mediate complex host–pathogen interactions. In this review, we critically evaluated recent experimental studies which demonstrate the effects of <i>P. gingivalis</i> oral infection on systemic diseases, including cardiovascular disease (CVD), diabetes mellitus (DM), adverse pregnancy outcomes (APOs), colorectal cancer (CRC), and Alzheimer's disease (AD). In CVD, DM, and AD, <i>P. gingivalis</i> gingipains exert proteolytic activity that disrupts key cellular targets, including endothelial adhesion molecules, insulin receptors in insulin-responsive tissues, and neuronal proteins. In AD, <i>P. gingivalis</i> LPS contributes to neuronal damage by inducing tau hyperphosphorylation and synaptic dysfunction. In APO and AD, <i>P. gingivalis</i> OMVs play a central role in compromising barrier integrity. These processes converge on five principal pathogenic pathways: (1) barrier and structural disruption, (2) immune activation and subversion, (3) mitochondrial dysfunction and oxidative stress induction, (4) systemic inflammation, and (5) metabolism-mediated effects. Understanding these shared pathways underscores the importance of controlling periodontal disease in promoting systemic health.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828558","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}