BMC Molecular and Cell Biology最新文献

{"title":"L-NAME promotes foam cell formation and synthetic phenotype marker changes in vascular smooth muscle cells independent of hemodynamic effects.","authors":"Huanhua Du, Jia Ling, Zheng Lu, Yutong Liu, Jinsong Yan, Junli Ma, Li Li, Gang Chen","doi":"10.1186/s12860-026-00600-z","DOIUrl":"10.1186/s12860-026-00600-z","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated whether L-NAME, a nitric oxide synthase (NOS) inhibitor commonly used to model hypertension-associated endothelial dysfunction, can exert direct pro-atherogenic effects on vascular smooth muscle cells (VSMCs) independent of systemic hemodynamic influences.</p><p><strong>Methods: </strong>Mouse aortic VSMCs (MOVAS) were treated with non-cytotoxic concentrations of L-NAME (50 µM) or oxidized low-density lipoprotein (ox-LDL, 100 µg/mL), which served as a positive atherogenic control. Lipid accumulation was assessed by Oil Red O staining. The expression of contractile phenotype markers (ACTA2, MYH11, and α-SMA), the synthetic phenotype marker SPP1, and matrix metalloproteinases (MMP-2 and MMP-9) was quantified by qRT-PCR and immunofluorescence.</p><p><strong>Results: </strong>Both L-NAME and ox-LDL treatments caused marked intracellular lipid accumulation in MOVAS cells, consistent with VSMC-derived foam cell formation. L-NAME and ox-LDL reduced the mRNA expression of contractile phenotype markers (ACTA2 and MYH11, p < 0.05) and decreased α-SMA protein expression (p < 0.001). Conversely, both treatments increased the mRNA expression of the synthetic phenotype marker SPP1 (p < 0.05) and matrix-remodeling genes MMP-2 and MMP-9 (p < 0.05). These effects were directionally similar to those induced by ox-LDL.</p><p><strong>Conclusion: </strong>L-NAME directly promotes lipid accumulation and synthetic phenotype-associated marker changes in MOVAS cells under the present in vitro conditions. Because eNOS/NOS activity, intracellular NO levels, rescue pathways, and primary VSMC validation were not assessed, these data should be interpreted as phenotypic evidence that NOS/NO pathway disruption may contribute to VSMC dysfunction rather than definitive proof of a single eNOS-dependent mechanism.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435138","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":"Assessment of the role of inflammation-linked signaling pathways in ventilator-induced diaphragmatic dysfunction in rats by transcriptome RNA-seq.","authors":"Yang Chen, Rongrong Xu, Zhicheng Huang, Longhuan Zeng, Kai Qiu, Nanyuan Gu, Fu Tian, Qiangqiang Shi, Hui Chen","doi":"10.1186/s12860-026-00599-3","DOIUrl":"10.1186/s12860-026-00599-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the key genes and inflammatory signaling pathways involved in the pathogenesis of ventilator-induced diaphragmatic dysfunction (VIDD) in rats, with the aim of identifying potential therapeutic targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adult male Wistar rats were randomly assigned to a control (0 h) group, a 6-hour controlled mechanical ventilation (CMV 6 h) group, and a 12-hour controlled mechanical ventilation (CMV 12 h) group, with 3 rats in each group. After model establishment, diaphragmatic tissues were collected for hematoxylin-eosin (HE) staining, immunohistochemical staining, and RNA extraction. HE staining was used to assess pathological changes and quantify myofiber cross-sectional area (CSA); immunohistochemistry was employed to detect the expression of slow (MHCslow) and fast (MHCfast) myosin heavy chain isoforms and quantify the percentage of positive area per field of view; and transcriptome sequencing (RNA-Seq) was utilized to analyze mRNA expression changes across groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to determine the biological functions and pathways associated with significant differentially expressed genes (DEGs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HE staining revealed diaphragmatic muscle fiber atrophy in both the CMV 6 h and 12 h groups, accompanied by varying degrees of inflammatory cell infiltration. Quantitative analysis showed that myofiber CSA was significantly reduced in the CMV 6 h group (P &lt; 0.05) and further reduced in the CMV 12 h group (P &lt; 0.01) compared with the control group.Immunohistochemical analysis showed no statistically significant difference in MHCslow and MHCfast expression in the CMV 6 h group compared to the control group (P &gt; 0.05), whereas the percentage of positive area for both MHCslow and MHCfast was significantly reduced in the CMV 12 h group (P &lt; 0.05). RNA-Seq identified 2,048 DEGs in the CMV 6 h group (321 upregulated and 1,727 downregulated) (P &lt; 0.05) and 1,495 DEGs in the CMV 12 h group (534 upregulated and 961 downregulated) (P &lt; 0.05). GO analysis revealed that the CMV 6 h group comprised 1,310 DEGs related to molecular functions (n = 262), cellular components (n = 179), and biological processes (n = 869) (P &lt; 0.05). The CMV 12 h group comprised 1,017 DEGs related to molecular functions (n = 185), cellular components (n = 149), and biological processes (n = 683) (P &lt; 0.05). KEGG pathway analysis showed that the top 20 significantly enriched pathways in the CMV 6 h and 12 h groups included inflammatory responses, aldosterone synthesis and secretion, oxytocin signaling pathways, ECM-receptor interaction, and insulin signaling pathways (P &lt; 0.05). The most significantly enriched pathways known to play important roles in inflammatory responses included MAPK, PI3K-Akt, and Calcium signaling pathways, with key genes in these pathways screened and validated using RT-qPCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conc","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410421","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":"RBM39 upregulation promotes ostium re-obstruction after endoscopic endonasal dacryocystorhinostomy (En-DCR).","authors":"Jinjie Liu, Jinzhi Zhao, Xiaoyu Zhu, Xun Liu, Limin Zhu, Tingting Lin","doi":"10.1186/s12860-026-00596-6","DOIUrl":"10.1186/s12860-026-00596-6","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic dacryocystitis, characterized by epiphora, is primarily treated with dacryocystorhinostomy (DCR), yet postoperative anastomotic re-obstruction remains a significant cause of failure. This study aimed to identify the key molecular mechanisms driving this recurrence.</p><p><strong>Methods: </strong>Nasal mucosal tissues were collected from 30 post-DCR patients: 15 with re-obstruction (proliferation group) and 15 with successful outcomes (non-proliferation group). Proteomic analysis based on LC-MS/MS was conducted, with differentially expressed proteins (DEPs) defined by a fold change ≥ 1.5 and p < 0.05. Western blot and immunohistochemistry were used for validation and localization. The role of RBM39 in vascular endothelial cell proliferation was assessed via functional experiments, and its associated pathway was analyzed.</p><p><strong>Results: </strong>Proteomics identified RBM39 as significantly upregulated in re-obstruction tissues, confirmed to be expressed in the vascular endothelium. In vitro, RBM39 overexpression enhanced HMEC-1 proliferation, while its knockdown suppressed it. KEGG pathway analysis suggested the Focal Adhesion pathway may be involved as a potential downstream mechanism.</p><p><strong>Conclusion: </strong>This study observes that RBM39 is upregulated at the anastomotic site and correlates with enhanced vascular endothelial cell proliferation. The Focal Adhesion pathway may be implicated in this process, suggesting RBM39 as a candidate target for mitigating postoperative ostium re-obstruction after En-DCR. However, further mechanistic studies are needed to establish a direct causal relationship and evaluate its therapeutic potential.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209620","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":"From microscope to model: rotating signaling dynamics and cluster size in Dictyostelium discoideum aggregates.","authors":"Sanchi Saitia, Yi-Chieh Lai, Man-Ho Tang, Jasper Jain, Michael Reiss, Wouter-Jan Rappel","doi":"10.1186/s12860-026-00593-9","DOIUrl":"10.1186/s12860-026-00593-9","url":null,"abstract":"<p><strong>Background: </strong>When starved, Dictyostelium discoideum cells form clusters that, when constrained in height, exhibit clear collective rotational motion. During this collective rotation, cells secrete and relay the chemoattractant cAMP, resulting in signal propagation in the form of spiral waves, which rotate in the opposite direction of the collective rotation. The quantification of this collective rotation with reference to cAMP signaling and the dependence on cluster size is currently unclear.</p><p><strong>Results: </strong>In this study, we use experiments and modeling to investigate how cell motion and cAMP signaling dynamics depend on cluster sizes in Dictyostelium using aggregates that are confined to quasi-2D environments. For rotating clusters with a single cAMP spiral arm, we find that both cAMP wave and cell angular velocities decrease as cluster sizes increase, suggesting that larger clusters signal more slowly. We also show that the angular velocity of the cells ([Formula: see text]) is linearly correlated with the angular velocity of the cAMP wave ([Formula: see text]). For clusters with multiple spiral arms, we observe a size dependence where larger clusters have a higher probability of having more spiral arms compared to smaller clusters. The qualitative experimental results are consistent with a computational model that couples a reaction diffusion model to cell motility and chemotaxis. Our simulation results suggest that a variable degradation rate of cAMP, which depends on cluster size, is a possible mechanism to explain the cluster size-dependent wave and cell angular velocities.</p><p><strong>Conclusion: </strong>Together, these findings identify cluster size as a key regulator of both cAMP wave dynamics and collective cell motion and link slower signaling and enhanced multi-armed spiral formation to larger clusters. More broadly, our work suggests that size-dependent modulation of extracellular cAMP degradation can couple cell number to emergent spatiotemporal patterns in developing Dictyostelium aggregates.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155363","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":"A goat-derived gamma-tubulin antibody for triple-channel imaging of primary cilia.","authors":"Eliza Karapetian, Christoph Gerhardt, Natalia Lemanska, Monia Budnik, Erik Stahl, Jonas Füner, Stefan Hirschberg, Thorsten Pfirrmann","doi":"10.1186/s12860-026-00595-7","DOIUrl":"10.1186/s12860-026-00595-7","url":null,"abstract":"<p><strong>Background: </strong>Primary cilia are essential sensory organelles, and their dysfunction leads to a broad spectrum of diseases known as ciliopathies. Immunofluorescence imaging of ciliary substructures is a key tool in cilia research, but multiplex staining is often limited by the availability of antibodies from different host species.</p><p><strong>Methods: </strong>We developed a novel goat-derived gamma tubulin antibody for basal body labelling and validated its specificity through triple-label immunofluorescence in different cell lines.</p><p><strong>Results: </strong>The antibody showed strong, specific staining of basal bodies under methanol fixation, enabling clear visualization in combination with rabbit- and mouse-derived antibodies.</p><p><strong>Conclusions: </strong>This antibody expands multiplex imaging capabilities for ciliary substructures, supporting both cilia research and diagnostics of ciliopathies.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052608","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":"Hypoxia-pretreated exosomes promote enterocutaneous fistula healing via regulating inflammation and tissue repair.","authors":"Yankui Liu, Beini Zhu, Hongbin Liu, Qingmei Yuan, Cong Yuan, Yijun Meng, Hong Zhou, Luming Sun, Beiyin Liu, Zhaoxiang Wu","doi":"10.1186/s12860-026-00592-w","DOIUrl":"10.1186/s12860-026-00592-w","url":null,"abstract":"<p><strong>Background: </strong>Enterocutaneous fistula (ECF) is an abnormal pathological passage. This study aims to investigate the role and mechanism of action of gelatin sponges loaded with hypoxic exosomes (GS-Hypo-Exos) in the treatment of enterocutaneous fistulas.</p><p><strong>Methods: </strong>A rat ECF model was established and subjected to intervention therapy, with the following groups: control group, gelatin sponge loaded with PBS group (GS-PBS), gelatin sponge loaded with hypoxia-exosomes group (GS-Hypo-Exos), and gelatin sponge loaded with normoxic exosomes group (GS-Nor-Exos). After 21 days of intervention, rat serum and perifistulous tissue were collected. Inflammatory response and collagen were analyzed via ELISA and histological staining. Flow cytometry determined macrophage phenotype proportions in fistula tissue. Immunofluorescence staining assessed angiogenesis. In vitro experiments further examined the effects of GS-Hypo-Exos on epithelial cell, fibroblast, endothelial cell, and macrophage function.</p><p><strong>Results: </strong>The GS-Hypo-Exos group demonstrated the most significant fistula healing effect. This group exhibited the lowest serum IL-1β levels and the highest IL-10 levels. Histopathological analysis revealed reduced inflammatory cell infiltration and increased collagen deposition in fistula tissues following GS-Hypo-Exos treatment. Flow cytometry analysis revealed a significant increase in the proportion of M2 macrophages within the GS-Hypo-Exos group. Enhanced signaling of angiogenesis-related markers indicated increased mature vascular structures. In vitro experiments confirmed that GS-Hypo-Exos promoted HaCaT cell proliferation and migration, enhanced fibroblast collagen synthesis capacity, improved endothelial cell tube formation ability, and drove macrophage polarization toward the M2 phenotype.</p><p><strong>Conclusions: </strong>The GS-Hypo-Exos suppress inflammatory responses, enhance the function of key repair cells, promote collagen deposition and neovascularization, thereby creating conditions for fistula tissue repair.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970290","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":"Modelling kidney cystogenesis using human kidney tubuloid cultures.","authors":"Jana Rohe, Arsila Palliyulla Kariat Ashraf, Melina Kehl, Xenia Thielmann, Jörg Ellinger, Glen Kristiansen, Dagmar Wachten, Marieta Ioana Toma","doi":"10.1186/s12860-026-00591-x","DOIUrl":"10.1186/s12860-026-00591-x","url":null,"abstract":"<p><strong>Background: </strong>Renal cyst formation, as observed in autosomal dominant polycystic kidney disease (ADPKD), is a life-threatening condition with no effective cure yet. The molecular mechanisms underlying primary cilia dysfunction, which causes cyst formation and disease development, are not well understood. Human kidney tubuloids offer a promising model system to investigate the disease mechanisms of PKD in physiologically relevant 3D structures. However, their inherent cystic morphology poses a challenge in effectively modelling kidney cystogenesis. Therefore, our study aims to refine the culture method of tubuloids and assess the efficacy of these modified cultures in modeling cyst formation and development.</p><p><strong>Results: </strong>We developed human kidney tubuloid models derived from adult kidney tubular cells using different methods for 3D in-vitro cultures. Tubuloids cultured in suspension or an extracellular matrix scaffold manifested distinctly polarized epithelial structures. Bulk RNA sequencing and immunohistochemistry revealed differential transcriptional profiles, highlighting variations in cellular composition and cellular fate within the kidney epithelium between the two types of tubuloids. Notably, the experimental activation of chronic cAMP signalling promoted cyst formation in vitro, validating the suitability of these tubuloids for studying kidney cystogenesis. Furthermore, we demonstrate that tubuloids are amenable to genetic modification through recombinant adeno-associated virus transduction.</p><p><strong>Conclusions: </strong>Our study identifies different in-vitro tubuloid cultures as relevant model systems for examining the molecular and cellular changes involved in kidney cystogenesis in humans. These models will enhance our capability to discover novel pathogenetic mechanisms underlying ADPKD and validate candidate drugs for clinical application.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873297","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":"Differential phosphorylation of PHIP phosphopeptides with implications in insulin signaling.","authors":"Ayadathil Sujina, Amal Fahma, Suhail Subair, Athira Perunelly Gopalakrishnan, Samseera Ummar, Prathik Basthikoppa Shivamurthy, Rajesh Raju, Poornima Ramesh","doi":"10.1186/s12860-026-00590-y","DOIUrl":"10.1186/s12860-026-00590-y","url":null,"abstract":"<p><strong>Background: </strong>PHIP (PH Interacting Protein) is an Insulin Receptor Substrate 1 (IRS1) interactor protein that binds to acetylated IRS1 through its bromodomain. Due to its involvement in insulin signaling pathway, it is implicated in various malignancies and metabolic disorders. Despite this role, the phosphoregulatory network governing PHIP activity is understudied. Therefore, current study aimed to elucidate the landscape of PHIP phosphorylation and its functional significance in insulin signaling by employing a global phosphoproteomic data integration and harmonization strategy.</p><p><strong>Results: </strong>A total of 1008 human phosphoproteomics datasets were used to gather 412 differential regulation datasets exhibiting differential abundance of PHIP phosphopeptides. Seven predominant phosphorylation sites of PHIP (S879, S880, S881, S1281, S1283, S1315, and S1783) were most frequently detected in phosphoproteomics data derived from cell lines and tissue samples. Further, conserved, statistically robust inter-protein co-differential regulation analysis as compared to differential phosphorylation of PHIP showed several upstream kinases (CHEK2, CLK1 and ATM) and interactors (SMARCA4 and NCOA5), which are known to be involved in the insulin signaling pathway. IRS1 and IRS2, which definitively modulate insulin signaling, also showed significant co-differential regulation with PHIP phosphorylation. When cross-validated with CPTAC and cProSite data, PHIP, SMARCA4 and CHEK2 showed differential protein abundance and phosphorylation status in Hepatocellular Carcinoma samples, further linking insulin signaling and liver cancers in connection to PHIP phosphorylation.</p><p><strong>Conclusions: </strong>This phosphorylation-centric study suggests the role of phosphorylated PHIP in insulin signaling pathway through modulation and co-differential phosphorylation of key proteins, paving the way for a robust and replicable approach in elucidating putative targets.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762233","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":"Immunomodulatory effects of TAK-242 on osteogenesis of mesenchymal stem cells in acute inflammatory conditions.","authors":"Mahsa Ghiasvand, Maryam Talebi Jouybari, Mahmood Talkhabi, Leila Taghiyar","doi":"10.1186/s12860-026-00576-w","DOIUrl":"10.1186/s12860-026-00576-w","url":null,"abstract":"<p><strong>Background: </strong>Bone regeneration involves a complex series of stages that need proper regulation of the acute inflammatory response. Toll-like receptor 4 (TLR4) is expressed in cells necessary for bone metabolism and modulates inflammatory conditions. However, excessive TLR4 activation can lead to immune dysregulation and decreased bone mineral deposition. This study investigates the effects of inhibiting TLR4 using TAK-242 on the osteogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) under an acute inflammatory condition induced by lipopolysaccharide (LPS).</p><p><strong>Methods: </strong>BM-MSCs were obtained from rats, cultured, and evaluated to validate their characteristics. Subsequently, the cells were stimulated with LPS to induce an acute inflammatory model, followed by treatment with TAK-242 to assess its immunomodulatory effects on inflammatory responses, and osteogenic differentiation.</p><p><strong>Results: </strong>TAK-242 exhibited significant anti-inflammatory effects on LPS-stimulated cells, with decreased expressions of IL-6 (p < 0.01), TNF-α (p < 0.0001), and MMP-13 (p < 0.0001) and increased expression of TGF-β (p < 0.0001) compared to LPS-only treatment cells. Notably, the TAK-242 treatment group exhibited a decrease in osteogenic differentiation compared to the LPS-only treatment group in the early stage. This was evidenced by reduced formation of mineralized nodules and decreased expression of CoL1A1 (p < 0.0001). However, RUNX-2, ALP, and OCN expression levels did not significantly reduce, indicating that TAK-242 did not impede the process of osteogenesis.</p><p><strong>Conclusions: </strong>These findings emphasize the possible therapeutic use of TAK-242 in the field of osteoimmunology, particularly for treating inflammatory bone conditions.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762235","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":"Alcohol exposure induces ferroptosis-dominated programmed cell death in esophageal epithelial cells.","authors":"Dongxue Wang, Zhenyu Jiang, Zhiyi Meng, Wei Hou, Tong Dang, Xianmei Meng, Jianyuan Chai","doi":"10.1186/s12860-026-00589-5","DOIUrl":"10.1186/s12860-026-00589-5","url":null,"abstract":"<p><p>BACKGROUND: Alcohol consumption has been a risk factor for nearly 200 diseases. Although swallowing an alcoholic beverage takes only a few seconds, the substance can stick to the esophageal lining longer after drinking. What alcohol does to the esophageal cells is not fully understood. This study explored the issue through in vitro experimentation. RESULTS: It was found that < 0.5% alcohol or a < 30-minute exposure benefited cell growth primarily through autophagy, while > 0.5% alcohol or a > 30-minute exposure caused cell death, including apoptosis, necroptosis, and ferroptosis, but not pyroptosis. Autophagy took place within the first 30 min of alcohol exposure, followed by apoptosis, which peaked at 2 h, and then was gradually replaced by necroptosis as the alcohol exposure continued. Ferroptosis initiated immediately after contact with alcohol and became dominant progressively. However, as alcohol exposure continued, cells developed tolerance through anastasis, reviving and reforming the epithelial monolayer. CONCLUSIONS: Low concentrations of alcohol or a short exposure promote esophageal cell growth owing to autophagy, while higher concentrations or a longer exposure cause multiple forms of cell death, including apoptosis, necroptosis, and ferroptosis. Yet, cells can recover from alcohol insult through anastasis as the exposure extends. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643906","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}