BMC Molecular and Cell Biology最新文献

{"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":"https://doi.org/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":2.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":2.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1186/s12860-026-00589-5","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemoradiotherapy-induced Th17/IL-17 signaling correlates with therapeutic tolerance and early recurrence in cervical carcinoma.","authors":"Fanglei Cao, Na Li","doi":"10.1186/s12860-026-00586-8","DOIUrl":"https://doi.org/10.1186/s12860-026-00586-8","url":null,"abstract":"<p><p>This study investigates the role of Th17 cells and IL-17 signaling in mediating therapeutic resistance and early recurrence in cervical carcinoma. Th17 cells were generated in vitro, and cervical carcinoma cells were subsequently exposed to cisplatin in the presence of Th17-conditioned media or recombinant IL-17. To elucidate the underlying molecular mechanisms, synthetic siRNAs targeting Akt1 (si-Akt1) and Akt2 (si-Akt2) were employed. Gene expression levels were quantified using ABIVII7 qRT-PCR, and phosphorylation of AKT at Thr308 and Ser473 was assessed. Cervical carcinoma cell lines (HeLa and SW756) were cultured and subjected to siRNA-mediated knockdown of AKT1 and AKT2. Cytotoxicity assays were conducted to evaluate cell viability under various treatment conditions. Cells were stimulated with either standard medium or conditioned medium from in vitro-differentiated Th17 cells. Th17 cell-induced resistance to cisplatin and radiation co-treatment was found to be mediated via the AKT signaling pathway. Moreover, Th17 cells promoted chemoradiotherapy tolerance in cervical cancer cells, with a potential contribution from IL-17 signaling. Although chemoradiotherapy significantly decreased cell viability across all cell lines, preconditioning with recombinant IL-17 notably mitigated this effect, resulting in increased cellular survival. These findings suggest a critical role for Th17 cells in modulating the therapeutic response and recurrence risk in cervical carcinoma through AKT pathway activation.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomere-to-telomere characterization of rDNA chromosome in the myxomycete Didymium iridis.","authors":"Arif Khan, Tor Erik Jørgensen, Lars Martin Jakt, Bård Ove Karlsen, Annica Hedberg, Steinar Daae Johansen","doi":"10.1186/s12860-026-00587-7","DOIUrl":"https://doi.org/10.1186/s12860-026-00587-7","url":null,"abstract":"<p><strong>Background: </strong>The ribosomal DNA (rDNA) of the myxomycete Didymium iridis is located on a linear, multi-copy, non-Mendelian chromosome. Efforts to determine the complete sequence by short-read sequencing technologies have been prevented by the presence of highly repetitive regions. Here we use high coverage (~10,000 x) long-read Oxford Nanopore Technology to determine the rDNA chromosome sequence in haploid amoebae from telomere-to-telomere.</p><p><strong>Results: </strong>The 20 kb rDNA chromosome, which is present at ~ 132 copies per haploid genome, is capped by regular TTAGGG telomeric repeats at both ends and carries an 11.3 kb pre-rRNA transcription unit coding for the small and large subunit rRNAs. The rRNA genes are further interrupted by autocatalytic group I introns, one of which encodes a homing endonuclease and two catalytic RNA domains with different functions in RNA processing. RNA mapping analyses from amoeba, microcyst, flagellate, and plasmodium stages, based on Illumina short-read sequencing, support the presence of a mature intron homing endonuclease mRNA both in haploid and diploid life stages in D. iridis. The non-transcribed sequence region upstream of the transcription unit contains several direct repeat arrays, including a highly complex upstream promoter region likely to be involved in pre-rRNA transcription regulation. Adjacent to the upstream telomere, a 4.2 kb palindromic region with potential for cruciform structure formation is found. Here, two putative replication origin candidates are located.</p><p><strong>Conclusions: </strong>High coverage Oxford Nanopore Technology sequencing results in excellent resolution of complex sequence repeat feature in the D. iridis rDNA chromosome. The rRNA genes are interrupted by complex group I introns and RNA sequencing supports intron autocatalytic processing in haploid and diploid life stages. This study provides new insights into structural arrangements of nuclear rDNA in eukaryotic microorganisms.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult canine pancreatic organoids enable functional analysis of pancreatic epithelial barrier and inflammatory responses.","authors":"Meg Nakazawa, Harry Cridge, Yoko M Ambrosini","doi":"10.1186/s12860-026-00588-6","DOIUrl":"10.1186/s12860-026-00588-6","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A role for PaxB in regulating blebbing: experimental insights and theoretical perspectives from Dictyostelium discoideum.","authors":"Zully Santiago, Brian Wey, Sobana Handi Dinuka Sewwandi de Silva, Jessica Reznik, Lamina Siby, Emmanuel Asante-Asamani, Derrick Brazil","doi":"10.1186/s12860-026-00584-w","DOIUrl":"10.1186/s12860-026-00584-w","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotactic motion of coronin-null cells with impaired actin turnover.","authors":"Mary Ecke, Jana Prassler, Annette Müller-Taubenberger, Günther Gerisch","doi":"10.1186/s12860-026-00585-9","DOIUrl":"10.1186/s12860-026-00585-9","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520025","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":"Investigating the roles of macrophage age and circulating extracellular vesicles in cytoprotection of hypoxic renal tubular cell stress.","authors":"Dora Livkisa, David J Lundy, Tsung-Lin Lee, Barbara Szomolay, Chia-Te Liao","doi":"10.1186/s12860-026-00583-x","DOIUrl":"10.1186/s12860-026-00583-x","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509361","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":"Ciliary p75 neurotrophin receptor (p75NTR) facilitates the enrichment of exogenous amyloid beta (Aβ 1-42) peptide and promotes oxidative stress in human hippocampal astrocytes.","authors":"Ankan Gupta, Karthikeyan Thirugnanam, Zachary Bice, Allison K Lowman, Kevin R Rarick, Peter S LaViolette, Amy Pan, Malgorzata Franczak, Ramani Ramchandran","doi":"10.1186/s12860-026-00581-z","DOIUrl":"10.1186/s12860-026-00581-z","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479721","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}