BMC Molecular and Cell Biology最新文献

{"title":"Anti-Inflammatory effects of Lactobacillus helveticus and Arthrospira platensis on colonic cells inflamed by Crohn's disease-associated Escherichia coli.","authors":"Samira Alipour, Hossein Halimi, Nastaran Asri, Mohammad Rostami-Nejad, Leila Pishkar, Hamidreza Houri","doi":"10.1186/s12860-025-00545-9","DOIUrl":"10.1186/s12860-025-00545-9","url":null,"abstract":"<p><strong>Background: </strong>Adherent-invasive Escherichia coli (AIEC) is linked to intestinal inflammation in inflammatory bowel disease (IBD). Arthrospira platensis and Lactobacillus helveticus exhibit anti-inflammatory properties individually, yet their effects remain underexplored in IBD-associated inflammation. We aimed to investigate the anti-inflammatory potential of L. helveticus and the hydroalcoholic extract of A. platensis (HA-A. platensis) in Caco-2 cells inflamed by IBD-associated E. coli.</p><p><strong>Methods: </strong>Caco-2 cells inflamed by a Crohn's disease (CD)-associated E. coli strain (MOI 10) were treated with HA-A. platensis (2 mg/mL) and/or L. helveticus (MOI 50) in live (LBC), heat-killed (HKC), or cell-free supernatant (CFS) forms. The anti-invasion/adhesion properties of L. helveticus and/or HA-A. platensis were investigated by assessing the CD-associated E. coli invasion/adhesion rate (%). Signaling molecules (NF-κB, STAT3, NOD2) were analyzed via qPCR to capture pathway activation dynamics, while cytokines (TNF-α, IL-1β, IL-8, IL-10) were quantified by ELISA to assess secreted functional proteins.</p><p><strong>Results: </strong>HA-A. platensis reduced E. coli adhesion by 68% (P < 0.001) and completely inhibited invasion. L. helveticus (live form) decreased adhesion by 88% and invasion by 90%. Combined treatment showed synergistic effects, reducing adhesion by 89% and fully blocking invasion. HA-A. platensis downregulated STAT3 expression by 0.4-fold (P < 0.01), while L. helveticus (heat-killed form) reduced NF-κB by 0.51-fold (P < 0.05) and increased NOD2 by 1.8-fold (P < 0.01). Cytokine analysis revealed that HA-A. platensis decreased IL-1β by 0.61-fold (P < 0.001), and L. helveticus (heat-killed) reduced TNF-α (0.51-fold) and IL-8 (0.23-fold) while elevating anti-inflammatory IL-10 (4.39-fold; P < 0.001).</p><p><strong>Conclusions: </strong>L. helveticus and HA-A. platensis synergistically inhibit CD-associated E. coli pathogenicity and modulate inflammatory responses in vitro. These findings highlight their potential as adjunctive therapies for CD, warranting further preclinical validation.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"20"},"PeriodicalIF":2.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274212","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":"Sex alters thyroid hormone's effect on protein O-GlcNAcylation in the aged mouse heart.","authors":"Aaron K Olson, Wei Zhong Zhu, Dolena Ledee","doi":"10.1186/s12860-025-00543-x","DOIUrl":"10.1186/s12860-025-00543-x","url":null,"abstract":"<p><strong>Background: </strong>The aging heart undergoes physiological changes, many of which are sex dependent and encompass differential responses to cardiac stress. However, much about the molecular changes that occur within the aging heart is still unknown. Thyroid hormone (TH) and the posttranslational modification O-GlcNAcylation (O-GlcNAc) are independently known to regulate cardiac function; therefore, we tested the hypothesis that TH disorders affect cardiac protein O-GlcNAcylation in aged hearts.</p><p><strong>Results: </strong>We treated male and female 18-22 month-old aged C57BL/6 mice to create euthyroid, hypothyroid, or hyperthyroid states. Western blots and RT-qPCR from cardiac tissue were used to determine changes in global O-GlcNAc levels along with key regulatory proteins in the O-GlcNAcylation process. Immunoprecipitation and western blotting compared global O-GlcNAc changes to differences on an individual protein. We found increased total O-GlcNAc levels for female hypo- and hyperthyroid mice and male hyperthyroid mice compared to sex-matched euthyroid hearts, with no change for male hypothyroid mice. TH's O-GlcNAc effect on female mice appears heart specific as liver O-GlcNAc levels were unchanged. The proteins regulating O-GlcNAcylation also demonstrated sex differences. Female hyperthyroid mice had increased protein expression of the O-GlcNAc regulatory proteins GFAT 1, GFAT 2, and OGT, whereas the hyperthyroid male mice showed decreased expression for the regulatory protein OGA. The hypothyroid female mice had increased protein expression for OGT and NAGK, whereas the hypothyroid male mice showed increased protein expression for NAGK alone. Interestingly, the directional changes in these protein levels did not match RNA transcription. We further found O-GlcNAc levels of the mitochondrial thiolase protein ACAA2 diverged from global O-GlcNAc changes. ACAA2 was hyper O-GlcNAcylated in the female hypothyroid group and hypo O-GlcNAcylated in the male hyperthyroid group whereas there was no change in female hyperthyroid or male hypothyroid.</p><p><strong>Conclusion: </strong>Protein O-GlcNAcylation is potentially an important mechanism whereby TH perturbations affect the aged heart. We found sex influences O-GlcNAc regulation, global O-GlcNAc levels, and O-GlcNAc protein specificity in response to thyroid hormone perturbations. Our results also suggest the changes in cardiac O-GlcNAc levels are not solely due to TH transcriptional regulation of key O-GlcNAc regulatory enzymes.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"19"},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265229","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":"Searching for protein partners of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) reveals keratin 8 as a novel candidate for interaction in pancreatic β-cells.","authors":"Kelly Velasco, Janniche Torsvik, Johanna L St-Louis, Sarah Baghestani, Jonas S G Silvander, Rohit N Kulkarni, Diana M Toivola, Anders Molven","doi":"10.1186/s12860-025-00544-w","DOIUrl":"10.1186/s12860-025-00544-w","url":null,"abstract":"<p><strong>Background: </strong>Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) is a ubiquitously expressed mitochondrial enzyme with a role in the degradation of fatty acids. Because the protein also is a negative regulator of insulin secretion in pancreatic β-cells, inactivating mutations in the SCHAD gene (HADH) cause congenital hyperinsulinism of infancy (CHI) and severe hypoglycemia. Here we sought to identify novel interaction partners of SCHAD that might be particularly relevant for the endocrine pancreas.</p><p><strong>Results: </strong>Employing the SCHAD protein as bait, we performed yeast 2-hybrid screening of a cDNA library made from human islets of Langerhans. Surprisingly, the screening revealed the intermediate filament protein keratin 8 (K8) as a putative interaction partner of SCHAD with very high confidence. Previous reports have linked K8 to glucose homeostasis, and we confirmed the SCHAD interaction by co-immunoprecipitation in HEK293 cells. SCHAD and K8 expression were then characterized in the human β-cell model EndoC-βH1. By using proximity ligation assay, we demonstrated that stimulating the cells with a high level of glucose triggered a transient increase in the interaction. However, when studying knockout mice, we found that the loss of either K8 or SCHAD did not change the expression level of the other interaction partner. Still, when K8 knockout mice were challenged with a ketogenic diet, upregulation of SCHAD expression was blunted compared to the upregulation observed in wildtype littermates.</p><p><strong>Conclusions: </strong>We propose that the SCHAD protein interacts with K8 in a way that might be relevant for proper functioning of the pancreatic β-cell. Whether the SCHAD-K8 interaction influences the phenotype of CHI remains to be demonstrated.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"18"},"PeriodicalIF":2.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233165","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":"TRAIL (DR5) receptor and the modulation of TRAIL pathway in PLWHIV: key mechanisms in the progression of HIV disease.","authors":"Sarah Ratkovich-Gonzalez, Mariana Del Rocio Ruiz-Briseño, Judith Carolina De Arcos-Jiménez, Monserrat Alvarez-Zavala, Jaime Federico Andrade-Villanueva, Pedro Martínez-Ayala, Vida V Ruíz-Herrera, Luz Alicia Gonzalez-Hernandez, Karina Sánchez-Reyes","doi":"10.1186/s12860-025-00541-z","DOIUrl":"10.1186/s12860-025-00541-z","url":null,"abstract":"<p><strong>Background: </strong>HIV infection is mainly described by depletion of CD4⁺ T-cells; however, this not only occurs in infected cells, also arise in uninfected immunological cells through the bystander effect. Extrinsic cell death, in particular the Fas pathway has been studied in HIV extensively, and an expression increase in both its ligand and receptor has been reported, however the TRAIL pathway has been less explored in this context, and little has been relating to the immune activation characteristic of the disease. This study aims to examine the effect of HIV infection in the activation of TRAIL and Fas death pathways in CD3⁺ CD4⁺ T-cells and CD4⁺ CD14 + monocyte derived from people living with HIV (PLWHIV) and its correlation with immune activation biomarkers in cell surface and serum.</p><p><strong>Results: </strong>Expression of TRAIL receptor DR5 in CD3⁺ CD4⁺ T-cells and CD14⁺ CD4⁺ monocytes from PLWHIV were significatively increased, almost two and five times more than CD3⁺ CD4⁺ T-cells and CD14⁺ CD4⁺ monocytes from HIV-negative controls; respectively. In PLWHIV, DR5 and CCR5 expression were positively and negatively associated with time of infection; respectively. Simultaneously, DR5 was associated positively with CXCR4 expression in CD3⁺ CD4⁺-T cells and CD4⁺ CD14⁺ monocytes as well as the significant increase of serum levels of IL-18 in PLWHIV. In CD3⁺ CD4⁺-T cells from HIV patients, the expression of CD38 was upregulated. Finally, in CD14⁺ CD4⁺ monocytes from PLWHIV, it was observed an increase in early apoptosis in response to recombinant TRAIL ligand, an effect that was not inhibited by caspase 8 blockade.</p><p><strong>Conclusions: </strong>In PLWHIV before ART, the activation and regulation of TRAIL pathway shows to be an important regulator in cell depletion. The expression of TRAIL DR5 significantly increased in CD3⁺ CD4⁺-T cells and CD4⁺ CD14⁺ monocytes from PLWHIV; in the same way DR5 was positively correlated with time of infection, with CXCR4 expression and with the significant increase in serum levels of IL-18, making it an interesting target for future treatments and as a marker for HIV disease progression.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"17"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198191","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":"Conserved structural topologies in RNase A-like and trypsin-like serine proteases: a sequence-based folding analysis.","authors":"K M Ahsanul Kabir, Takuya Takahashi, Takeshi Kikuchi","doi":"10.1186/s12860-025-00542-y","DOIUrl":"10.1186/s12860-025-00542-y","url":null,"abstract":"<p><strong>Background: </strong>Protein folding is a complex process in which amino acid sequences encode the information required for a polypeptide chain to fold into its functional three-dimensional (3D) structure. Many proteins share common substructures and recurring secondary structure elements that contribute to similar 3D folding patterns, even across different protein families. This study examines two distinct groups of proteins, the RNase A-like fold and the trypsin-like serine protease fold, classified by SCOPe. These proteins share only some substructures that contribute to their folding cores. Despite minimal sequence identity, they exhibit partial structural similarities in their 3D topologies. We used a sequence-based approach, including inter-residue average distance statistics and contact frequency prediction, to explore these folding characteristics. Structural observations guided further analyses of conserved hydrophobic residue packing, highlighting key folding units within each fold.</p><p><strong>Results: </strong>Our analysis predicted two compact regions within each protein group. Interactions between these regions form a partially shared topology. We identified conserved hydrophobic residues critical to these interactions, suggesting a common mechanism for establishing these structural features. Despite overall structural differences between the RNase A-like and trypsin-like folds, our findings emphasize the presence of a shared partial folding core.</p><p><strong>Conclusions: </strong>The partially shared structural features in the RNase A-like and trypsin-like serine protease folds reflect a convergent folding mechanism. This mechanism underscores the evolutionary adaptation of protein folding, where distinct folds can still retain critical, conserved structural motifs. These findings highlight how proteins with overall different topologies can evolve to share key folding features, demonstrating the elegance and efficiency of protein evolution.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"16"},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172259","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":"Optimizing mesenchymal stem cell therapy: from isolation to GMP-compliant expansion for clinical application.","authors":"Michael E Williams, Federica Banche Niclot, Sara Rota, Jaesang Lim, Janaina Machado, Ricardo de Azevedo, Katia Castillo, Samuel Adebiyi, Ranga Sreenivasan, Daniel Kota, Patrick C Mcculloch, Francesca Taraballi","doi":"10.1186/s12860-025-00539-7","DOIUrl":"https://doi.org/10.1186/s12860-025-00539-7","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are promising for cell-based therapies targeting a wide range of diseases. However, challenges in translating MSC-based therapies to clinical applications necessitate standardized protocols following Good Manufacturing Practices (GMP) guidelines. This study aimed at developing GMP-complained protocols for FPMSCs isolation and manipulation, necessary for translational research, by (1) optimize culture of MSCs derived from an infrapatellar fat pad (FPMSC) condition through animal-free media comparison and (2) establish feasibility of MSC isolation, manufacturing and storage under GMP-compliance (GMP-FPMSC).</p><p><strong>Methods: </strong>FPMSCs from three different patients were isolated following established protocols and the efficacy of two animal component-free media formulations in the culturing media were evaluated. The impact of different media formulations on cell proliferation, purity, and potency of MSCs was evaluated through doubling time, colony forming unit assay, and percentage of MSCs, respectively. Furthermore, the isolation and expansion of GMP-FPMSCs from four additional donors were optimized and characterized at each stage according to GMP requirements. Viability and sterility were checked using Trypan Blue and Bact/Alert, respectively, while purity and identity were confirmed using Endotoxin, Mycoplasma assays, and Flow Cytometry. The study also included stability assessments post-thaw and viability assessment to determine the shelf-life of the final GMP-FPMSC product. Statistical analyses were conducted using one-way ANOVA with Tukey's Multiple Comparisons.</p><p><strong>Results: </strong>The study demonstrated that FPMSCs exhibited enhanced proliferation rates when cultured in MSC-Brew GMP Medium compared to standard MSC media. Cells cultured in this media showed lower doubling times across passages, indicating increased proliferation. Additionally, higher colony formation in FPMSCs cultured in MSC-Brew GMP Medium were observed, supporting enhanced potency. Data from our GMP validation, including cells from 4 different donors, showed post-thaw GMP-FPMSC maintained stem cell marker expression and all the specifications required for product release, including > 95% viability (> 70% is required) and sterility, even after extended storage (up to 180 days), demonstrating the reproducibility and potential of GMP-FPMSCs for clinical use as well as the robustness of the isolation and storage protocols.</p><p><strong>Conclusions: </strong>The study underscores the feasibility of FPMSCs for clinical uses under GMP conditions and emphasizes the importance of optimized culture protocols to improve cell proliferation and potency in MSC-based therapies.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"15"},"PeriodicalIF":2.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968592","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":"PYGO2 regulates IL10 and plays immunosuppressive role through ESCC progression.","authors":"Fereshteh Ahmadian Shalchi, Nayyerehalsadat Hosseini, Fatemeh Nourmohammadi, Mohammad Arian Ahmadian Shalchi, Mohammad Mahdi Forghanifard","doi":"10.1186/s12860-025-00540-0","DOIUrl":"https://doi.org/10.1186/s12860-025-00540-0","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC), one of the most aggressive carcinomas of the gastrointestinal tract, is the sixth most common cause of cancer-related death. Wnt pathway plays a pivotal role in cell proliferation and differentiation. PYGO2 and IL10 are involved in this pathway. Our aim in this study was to examine the correlation between PYGO2 and IL10 expression in ESCC patients and cell lines.</p><p><strong>Methods: </strong>Relative-comparative real time-PCR (RT-qPCR) was used to evaluate the PYGO2 and IL10 mRNA expression profile in 58 non-treated ESCC compared to their margin normal tissues. Expression of PYGO2 was induced in KYSE-30 and YM1 ESCC lines and IL10 expression was analyzed.</p><p><strong>Results: </strong>The results revealed the significant overexpression of PYGO2 and IL10 mRNA in 31.0% and 51.7% of ESCCs, respectively. The PYGO2 and IL10 overexpression was significantly correlated to each other (p = 0.007). Concomitant overexpression of the genes was significantly associated to grade of tumor differentiation (p < 0.01), and tumor depth of invasion (p < 0.05). Induced expression of PYGO2 caused a meaningful change in IL10 expression in ESCC cells.</p><p><strong>Conclusion: </strong>PYGO2 may regulate IL10 through Wnt/β-catenin signaling pathway, suggesting a possible oncogenic role for PYGO2/IL10 axis in ESCC tumorigenesis. Considering the involvement of IL10 as an anti-inflammatory cytokine and PYGO2 role in elevated tumor invasion and metastasis, possible functional interaction between these factors may promote a process which induces invasion and malignant phenotype in ESCC.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"14"},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969447","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":"The formin FMNL2 plays a role in the response of melanoma cells to substrate stiffness.","authors":"Joshua D Clugston, Sarah Fox, James L Harden, John W Copeland","doi":"10.1186/s12860-025-00538-8","DOIUrl":"https://doi.org/10.1186/s12860-025-00538-8","url":null,"abstract":"<p><strong>Background: </strong>Cells constantly sense and respond to changes in their local environment to adapt their behaviour and morphology. These external stimuli include chemical and mechanical signals, and much recent work has revealed the complexity of the cellular response to changes in substrate stiffness. We investigated the effects of substrate stiffness on the morphology and motility of A2058 human melanoma cells. FMNL2, a formin protein associated with actin cytoskeleton dynamics, regulates melanoma cell morphology and motility, but its role in stiffness sensing remains unclear. This study examines how A2058 cells respond to substrates of varying stiffness and evaluates the impact of FMNL2 depletion on these responses.</p><p><strong>Results: </strong>We found that with increasing substrate stiffness the cells transitioned from a rounded cell morphology to progressively more elongated morphologies with a concomitant increase in actin stress fiber alignment. Depletion of FMNL2 expression amplified these morphological changes, with knockdown cells showing consistently greater elongation and more pronounced stress fiber alignment compared to controls. Notably, the orientational order parameter (S) revealed higher alignment of actin filaments along the cell's long axis in knockdown cells. Substrate stiffness also affected cell motility, indicated by an apparent optimal stiffness that maximized motility followed by a notable decrease in distance travelled during migration on progressively stiffer substrates. This decrease was largely attributable to a decrease in the time the cells spent in motion as the substrate stiffness increased. FMNL2 depletion significantly exacerbated this effect, with knockdown cells traveling shorter net distances and spending less time moving across all substrates.</p><p><strong>Conclusions: </strong>This study demonstrates that substrate stiffness profoundly influences A2058 melanoma cell morphology and motility, with FMNL2 playing a pivotal regulatory role. Our observations suggest that FMNL2 is critical for maintaining motility and morphological adaptability under increased stiffness. Loss of FMNL2 enhanced stress fiber alignment and cell elongation while impairing motility, particularly on stiff substrates, revealing FMNL2 as a mechanosensitive effector. This work highlights the need to study metastatic cell behaviour on substrates with biologically relevant properties and provides the foundation for future effort to determine the mechanism by which FMNL2 participates in the melanoma cell response to substrate stiffness.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"13"},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966292","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":"N-actylcysteine inhibits diethyl phthalate-induced inflammation via JNK and STAT pathway in RAW264.7 macrophages.","authors":"Jin Hee Kim, Jae Hoon Lee, Yoon Jung Koo, Jong Wook Song","doi":"10.1186/s12860-025-00537-9","DOIUrl":"https://doi.org/10.1186/s12860-025-00537-9","url":null,"abstract":"<p><strong>Background: </strong>Phthalates are plasticizers that cause inflammation in several cell types and adversely affect the health of humans and animals. Nacetylcysteine (NAC) has been shown to exert antioxidant effects in various diseases. However, the effect of NAC on diethyl phthalate (DEP)-induced toxicity in macrophages has not yet been elucidated. In this study, we investigated the effect and underlying mechanisms of NAC on DEP-induced inflammation in RAW264.7 macrophages. RAW264.7 macrophages were pretreated with NAC for 2 h followed by exposure to DEP. We investigated the effect of NAC on NO, reactive oxygen species (ROS), prostaglandin E2 (PGE2), and glutathione (GSH) levels following DEP exposure. In addition, pathway-related genes including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription (STAT) were evaluated using western blot.</p><p><strong>Results: </strong>Treatment with 100 and 300 µM DEHP, DBP, and DEP significantly increased the protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) compared with those in the control group. However, NAC pretreatment downregulated the levels of NO, PGE2, and ROS, elevated GSH levels, and suppressed the mRNA levels of inflammatory cytokines such as interleukin (IL)-1β, IL-6, COX-2, and iNOS compared with those in the DEP-treated group. In addition, NAC significantly reduced the levels of p-JNK and p-STAT1/3 in RAW264.7 macrophages treated with DEP.</p><p><strong>Conclusions: </strong>NAC pretreatment inhibits DEP-induced inflammation via the MAPK/JNK and STAT1/3 pathways in macrophages.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"12"},"PeriodicalIF":2.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969321","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":"Canine intestinal organoids as a platform for studying MHC class II expression in epithelial cells.","authors":"Meg Nakazawa, Itsuma Nagao, Yoko M Ambrosini","doi":"10.1186/s12860-025-00536-w","DOIUrl":"10.1186/s12860-025-00536-w","url":null,"abstract":"<p><strong>Backgrounds: </strong>The interplay between intestinal epithelial cells (IECs), the immune system, and the gut microbiome is pivotal for maintaining gastrointestinal homeostasis and mediating responses to ingested antigens. IECs, capable of expressing Major Histocompatibility Complex (MHC) class II molecules, are essential in modulating immune responses, especially CD4 + T cells, in both physiological and pathological contexts. The expression of MHC class II on IECs, regulated by the class II transactivator (CIITA) and inducible by cytokine IFN-γ, has been traditionally associated with professional antigen-presenting cells but is now recognized in the context of inflammatory conditions such as inflammatory bowel disease (IBD). In veterinary medicine, particularly among canine populations, MHC (or Dog Leukocyte Antigen, DLA) expression on IECs underlines its significance in intestinal immune pathologies, yet remains underexplored. This study aims to leverage canine intestinal organoids as a novel in vitro model to elucidate MHC class II expression dynamics and their implications in immune-mediated gastrointestinal diseases, bridging the gap between basic research and clinical application in canine health.</p><p><strong>Results: </strong>Canine colonoids derived from healthy dogs showed significant expression of MHC class II and its promoter gene, CIITA, after IFN-γ treatment. This MHC class II induction was even more pronounced in differentiated colonoids cultured in Wnt-3a-depleted medium.</p><p><strong>Conclusions: </strong>This study provides insights into the role of IECs as antigen-presenting cells and demonstrates the use of intestinal organoids for investigating epithelial immune responses in inflammatory conditions.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"11"},"PeriodicalIF":2.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810455","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}