Journal of Biomedical Science最新文献

{"title":"TRKB-based signature identifies high-risk squamous cell carcinoma cases and TRKB blockade reprograms tumor and stromal cells toward suppressive phenotypes.","authors":"Valeria Bartolocci, Alessio Capone, Rosanna Monetta, Erika Di Meo, Silvia Arcano, Carola Valente, Denise Campagna, Massimo Teson, Mara Mancini, Giovanni Di Lella, Damiano Abeni, Luca Fania, Francesca Ricci, Vito Gomes, Giovanni Luca Scaglione, Simona Mastroeni, Eleonora Candi, Elena Dellambra","doi":"10.1186/s12929-026-01227-0","DOIUrl":"10.1186/s12929-026-01227-0","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous squamous cell carcinoma (cSCC) is a common age-related cancer, with a subset prone to recurrence and metastasis. Currently, no useful diagnostic biomarkers for high-risk cSCC are available. Based on our previous findings, indicating that age-related changes in the neurotrophin receptor tyrosine kinase-2 (TrkB) axis may promote skin tumorigenesis, this study aims to identify novel cSCC biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on specimens from patients with in situ or invasive cSCCs using immunohistochemistry to assess the expression of TrkB and specific downstream proteins (i.e., E-cadherin, Yap1, and Notch1). Statistical and machine learning analyses were applied to identify biomarkers that distinguish cSCC subtypes and patient risk groups. In vitro studies involved treating SCC cells, cancer-associated fibroblasts (CAFs), and three-dimensional (3D) SCC models with the TrkB inhibitor ANA-12. Gene and protein expression were analyzed via RTqPCR, immunoblotting, and immunoassays. Functional assays evaluated cell proliferation, migration, and invasion. Secretomes were profiled using cytokine arrays.</p><p><strong>Results: </strong>Protein expression levels mainly correlated with cSCC types. Our findings indicated that the 'TrkB, E-cadherin, Yap1, Notch1' signature can be a relevant biomarker for both cSCC subtype classification and identification of high-risk cases. Despite the limited sample size, machine learning models demonstrated promising accuracy in differentiating between cSCC classes. Our analysis also highlighted the added value of including stromal markers for classifying high-risk patients. Furthermore, TrkB blockade suppressed tumorigenic traits in TP53-mutant SCC cells, including proliferation, EMT, migration, invasiveness, and disruption of the IL-6/STAT3 signaling loop, while promoting differentiation and senescence through modulation of key players such as p63, Yap1, Notch1, and p21. Data are consistent with a tumor-suppressive effect, thereby promoting tissue homeostasis, especially in physiologically relevant 3D models. Inhibiting TrkB reprogrammed primary CAFs into a less proliferative, migratory, inflammatory, and fibrotic phenotype by simultaneously suppressing key activating pathways, such as β-catenin, Yap1, and Notch1. This aligns with a reduction in their tumor-supportive functions.</p><p><strong>Conclusions: </strong>Our findings provide a basis for improved high-risk patient stratification by highlighting a TrkB-based signature and generating prototype predictive models. Furthermore, they offer promising therapeutic avenues for developing combined targeted interventions to overcome resistance in high-risk patients.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β signaling mediates crosstalk between CD8⁺ T cells and CD39⁺ induced Treg cells in autoimmune inflammation.","authors":"Ye Chen, Jun Long Dang, Qi Long, Nianke Zang, Ling Liu, Yang Lu, Wei Zhao, Rong Zhen Liang, Yi Yang, Jun Zhao, Jing Rong Chen, Yi Ding Xiong, Julie Wang, Yun Feng Pan, Nancy Olsen, Song Guo Zheng","doi":"10.1186/s12929-026-01228-z","DOIUrl":"10.1186/s12929-026-01228-z","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune inflammation results from dysregulated immune responses, with dysfunction of regulatory T cells (Tregs) being a key contributor due to their critical role in maintaining immune tolerance. The stability and function of Tregs are strongly influenced by the inflammatory microenvironment, yet the regulatory interactions between CD8⁺ T cells and CD4⁺Foxp3⁺ Tregs remain poorly understood.</p><p><strong>Methods: </strong>We investigated the role of CD8⁺ T cells in regulating induced Tregs (iTregs) using in vitro T cell co-culture assays and two in vivo models of autoimmune disease. A naïve CD4⁺ T cell transfer colitis model was used to evaluate the suppressive function of iTregs in the presence or absence of CD8⁺ T cells, while an autoimmune arthritis model was employed to assess therapeutic efficacy. Flow cytometry, functional suppression assays, and mechanistic analyses were performed to define signaling pathways.</p><p><strong>Results: </strong>CD8⁺ T cells promoted the differentiation of a CD39⁺ iTreg subset characterized by increased frequencies of CD103, CTLA-4, and Helios, leading to enhanced immunosuppressive capacity. In the colitis model, co-transfer of CD8⁺ naïve T cells alleviated disease by reinforcing iTreg-mediated suppression of Th1 and Th17 responses. Mechanistic studies revealed that CD8⁺ T cells regulated iTreg phenotype through a ROS/TGF-β signaling axis, with IRF4 in CD8⁺ T cells acting as a key mediator. Importantly, CD8⁺ T cell-primed iTregs showed superior therapeutic efficacy in the autoimmune arthritis model by suppressing pathogenic Th1/Th17 responses and supporting endogenous Treg homeostasis.</p><p><strong>Conclusions: </strong>This study identifies a previously unrecognized role of CD8⁺ T cells in enhancing iTreg differentiation, stability, and suppressive function through the ROS/TGF-β-IRF4 pathway. These findings reveal a novel mechanism of immune regulation and suggest that harnessing CD8⁺ T cell-primed iTregs could represent a promising strategy to strengthen Treg-based therapies for autoimmune diseases.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variation and mutational determinants of azole resistance in Candida albicans strains of oropharyngeal colonization in HIV patients and bloodstream infections.","authors":"Ming-Horng Tsai, Chih-Hung Hsieh, I-An Tsai, Ching-Min Chang, Ting-Wen Chen, Jen-Fu Hsu, Shih-Ming Chu, Hsuan-Rong Huang, Shao-Hung Wang, Jang-Jih Lu","doi":"10.1186/s12929-026-01231-4","DOIUrl":"10.1186/s12929-026-01231-4","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to analyze the genomic variations associated with high azole resistance in the C. albicans isolates of intensive care unit (ICU) patients with Candida bloodstream infections (BSIs) and those from oropharyngeal colonization in HIV patients.</p><p><strong>Methods: </strong>The genomic DNA of azole-resistant C. albicans isolates was analyzed using the Oxford Nanopore platform. Subsequent analyses included ERG11 alignment to determine the extent and distribution of missense substitutions, Ka/Ks calculations to test for positive selection on ERG11, and detailed CDR1 and CDR2 mutational analysis across the coding sequence. Efflux function was assessed by measuring the fold reduction in the minimum inhibitory concentration (MIC) of azole drugs in the presence of milbemycin.</p><p><strong>Results: </strong>A total of 27 azole-resistant C. albicans isolates from ICU patients with Candida BSIs in Linkou Chang Gung Memorial Hospital in Taiwan and HIV patients' oropharyngeal colonization were identified and analyzed. The in-depth, core analyses were performed on seven representative C. albicans isolates. The C. albicans isolates of HIV-infected patients had notably higher azole resistance (fluconazole MICs > 256 mg/L) when compared with those of the ICU patients (fluconazole MICs 16-64 mg/L), suggesting the involvement of additional mechanisms. The central role of ERG11 mutations was supported by the presence of ERG11 missense mutations in all azole-resistant C. albicans isolates. The ERG11 coding regions analyses showed no evidence of positive selection (Ka/Ks < 1.0) and no specific mutation unique to the C. albicans isolates of the HIV patients, but unique missense mutations only in CDR1/CDR2 were noted. Milbemycin substantially decreased the azole MICs in all C. albicans isolates and confirmed the efflux pump involvement. The effects of milbemycin were much lower in C. albicans of the HIV patients than those from the ICU patients. Furthermore, unique ERG11 promoter variants, including changes at the Hap43p/Hap5p sites, were noted in the C. albicans isolates of the HIV patients.</p><p><strong>Conclusions: </strong>While ERG11 structural mutations are foundational, the elevated azole resistance in the C. albicans isolates of HIV-infected patients is associated with specific CDR1/CDR2 mutations and distinct ERG11 promoter variants, highlighting genomic features that warrant further functional validation.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging pathogen Candida auris: host interactions and disease drivers.","authors":"Daniel Ruben Akiola Sanya, Ashley Valle Arevalo, Djamila Onésime, Clarissa J Nobile","doi":"10.1186/s12929-026-01230-5","DOIUrl":"10.1186/s12929-026-01230-5","url":null,"abstract":"<p><p>Candida auris has emerged over the past fifteen years as a multidrug-resistant human fungal pathogen responsible for hospital-acquired infections associated with high mortality rates. Clinical isolates frequently exhibit resistance to one or more first-line antifungal drugs, and management is further complicated by persistent colonization, biofilm formation, and historical misidentification in diagnostic laboratories. Rapid species-level identification and accurate antifungal susceptibility testing are critical for effective patient care and infection control. In this article, we summarize the clinical spectrum of C. auris infections, highlight key pathogenic traits and clade-specific biological differences, and discuss emerging diagnostic, therapeutic, and preventative strategies-including novel antifungal agents, host-directed therapies, and vaccine development-that may improve detection and expand treatment options for C. auris infections.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146775863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation.","authors":"Federica Laudisi, Mattia Alberto Serra, Lorenzo Tomassini, Massimo Claudio Fantini, Gustavo Monasterio, Ning He, Eduardo Maria Sommella, Angela Ortenzi, Giuseppe Sigismondo Sica, Francesca Zorzi, Teresa Pacifico, Ombretta Melaiu, Cristiano De Stefanis, Valentina D'Oria, Carmine Stolfi, Ivan Monteleone, Eduardo Javier Villablanca, Giovanni Monteleone","doi":"10.1186/s12929-026-01224-3","DOIUrl":"10.1186/s12929-026-01224-3","url":null,"abstract":"<p><strong>Background and aims: </strong>Defects of the gut epithelial barrier and counter-regulatory mechanisms are a prerequisite for the onset of intestinal inflammation in patients with inflammatory bowel diseases (IBD). Elevated levels of Smad7, an inhibitor of TGF-β1, in both epithelial and immune cells have been associated with the pathological processes observed in IBD. We aim to determine the relevance of Smad7 expression in the epithelial compartment.</p><p><strong>Methods: </strong>We generated mice overexpressing Smad7 in the gut epithelium (Smad7TgCre⁺) and monitored pathology development. Inflammatory cell infiltration was assessed using multiplex immunofluorescence and flow cytometry. To investigate the molecular mechanisms underlying ileal damage, we performed spatial transcriptomics on frozen ileal samples and metabolomics on intestinal epithelial cells (IECs) from Smad7TgCre⁺ and control mice. The impact of adenosine on Mucin-2 expression was evaluated through both in vitro and in vivo approaches. Finally, we evaluated the protein expression of CD73 and Smad7 in ileal tissue from Crohn's disease (CD) patients.</p><p><strong>Results: </strong>Smad7TgCre⁺ mice developed spontaneous terminal ileitis, which was characterized by villus shortening and widening, mucus depletion, increased intestinal permeability, and infiltration of CD8 + T cells. By integrating spatial transcriptomics and metabolomics data, we demonstrated that Smad7TgCre⁺ mice exhibited altered expression of enzymes involved in purine metabolism, particularly CD73, the key enzyme responsible for adenosine production. Consequently, these mice produced lower levels of adenosine, and oral adenosine administration restored mucus production and alleviated the ileal pathology. Lastly, we observed that in the inflamed ileum of CD patients, elevated Smad7 levels were correlated with decreased CD73 expression.</p><p><strong>Conclusion: </strong>Our data indicate that Smad7 overexpression in IECs is sufficient to promote ileal mucosal damage, which is linked to the impairment of purine metabolism.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"18"},"PeriodicalIF":14.5,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hilar mossy cell oxytocin receptor signaling regulates adult hippocampal neurogenesis and context discrimination in mice.","authors":"Yu-Chieh Hung, Yi-Yu Hsieh, Kuei-Sen Hsu","doi":"10.1186/s12929-026-01221-6","DOIUrl":"10.1186/s12929-026-01221-6","url":null,"abstract":"<p><strong>Background: </strong>Neurogenesis is a crucial form of neuroplasticity in the adult mammalian brain. Hilar mossy cells (MCs) in the dentate gyrus show a uniquely high expression of oxytocin receptors (OXTRs) and are implicated in the regulation of adult hippocampal neurogenesis (AHN). However, it remains unclear whether MCs regulate AHN through OXTR signaling. Here, we sought to investigate whether loss of MC OXTR signaling affects AHN and its associated cognitive function.</p><p><strong>Methods: </strong>We used a calcitonin receptor-like receptor (Crlr)-Cre mouse line to selectively remove Oxtr in MCs. 5-Bromo-2'-deoxyuridine labeling, immunofluorescence staining, and retrovirus-mediated strategies were used to trace newborn cells. The contextual fear discrimination task was employed to evaluate learning and memory functions mediated by AHN.</p><p><strong>Results: </strong>We found that conditional deletion of MC Oxtr impairs AHN by reducing the number, but not the rate, of proliferation, differentiation, survival, and maturation of neural stem/progenitor cells (NSPCs). MC Oxtr deletion reduces cell cycle re-entry and promotes cell cycle exit and NSPC death. Furthermore, MC Oxtr deletion reduces the populations of type 1, type 2b, and type 3 NSPCs. Using a retrovirus-mediated birthdating and cell-labeling approach, we demonstrate that deletion of MC Oxtr retards dendritic development without affecting the migration or positioning of newly generated dentate granule cells. Functionally, MC OXTR-deficient mice exhibited impaired performance in the contextual fear discrimination task, indicating a deficit in fear memory specificity.</p><p><strong>Conclusions: </strong>These results uncover a previously unknown role for MC OXTR signaling in regulating the dynamic processes of AHN and context discrimination.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"17"},"PeriodicalIF":14.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometry-based human spatial omics: fundamentals, innovations, and applications.","authors":"Ching-Chia Yang, Ching-Ya Lin, Hsin-Yo Yuan, Hsuan-Cheng Huang, Hsueh-Fen Juan","doi":"10.1186/s12929-026-01219-0","DOIUrl":"10.1186/s12929-026-01219-0","url":null,"abstract":"<p><p>Mass spectrometry-based spatial omics is a powerful approach for visualizing the spatial organization of proteins, metabolites, lipids, and other biomolecules in situ, combining the molecular depth of mass spectrometry with spatially resolved imaging. This systematic review traces the rapid technological and computational evolution of this field, including innovations in mass spectrometry imaging (MSI), labeling-based approaches, and proximity labeling techniques. It also highlights recent advances that enhance spatial resolution, expand molecular coverage, and enable deep molecular characterization and review analytical pipelines that integrate deep learning, cross-modality registration, and cloud-optimized data formats. From the multimodal and practical perspective, the integration of MSI with other spatial omics platforms and its transformative applications in tumor microenvironment profiling, neurodegenerative disease, developmental biology, biomarker discovery, and precision medicine are discussed. Finally, this review outlines challenges and opportunities, emphasizing the need for standardization, clinical validation, and interpretable artificial intelligence to enable broader adoption. These advances position MS-based spatial omics as a foundational pillar for multimodal spatial biology and personalized healthcare.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"16"},"PeriodicalIF":14.5,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12879364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APP-C31 pathology as a target in neurodegenerative diseases.","authors":"King Chi Yip, Woon Fei Ho, Yang Liu, Gavin Stewart Dawe","doi":"10.1186/s12929-026-01216-3","DOIUrl":"10.1186/s12929-026-01216-3","url":null,"abstract":"<p><p>Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, etc.) are caused by the progressive loss of neurons, which affects many people worldwide. Therefore, many efforts have focused on neurodegenerative disease mechanisms and therapeutic strategies. Moreover, amyloid precursor proteins and their cleaving products, including APP-C31, may play important roles in neurodegeneration. This review provides a comprehensive introduction to the structure, neurotoxicity, regulatory mechanism, and relevance of APP-C31 to clinical diseases and its therapeutic potential as a drug target. This work will bridge the gap in our understanding of the function of APP-C31, which provides an experimental basis for neurodegenerative disease therapeutics. Meanwhile, a hypothesis is postulated that the APP-C31 functions not merely as a byproduct of caspase cleavage, but as the critical \"central executioner\" bridging upstream triggers and downstream neurodegeneration. Diverse upstream stressors, initiate the cascade to generate APP-C31. Once generated, C31 acts as a multi-functional signalling hub driving four distinct pathogenic pathways. Consequently, APP-C31 is hypothesized to be the essential mediator that amplifies these molecular damages into macroscopic failures.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"15"},"PeriodicalIF":14.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombomodulin facilitates melanoma progression via FAK- and ezrin-mediated phenotypic plasticity.","authors":"Cheng-Hsiang Kuo, Ru-Han Sie, Ya-Chu Ku, Cheng-Lin Wu, Chao-Kai Hsu, Chao-Han Lai, Hua-Lin Wu","doi":"10.1186/s12929-026-01217-2","DOIUrl":"10.1186/s12929-026-01217-2","url":null,"abstract":"<p><strong>Background: </strong>Cancer cell plasticity enables dynamic transitions between cellular states, contributing to tumor progression and the acquisition of phenotypic traits such as vascular mimicry (VM), which promotes malignancy and resistance to anti-angiogenic therapies. Thrombomodulin (TM), a type I transmembrane glycoprotein known for initiating sprouting angiogenesis, has been implicated in tumor vascularization. However, its role in melanoma progression and VM remains poorly characterized.</p><p><strong>Methods: </strong>TM expression was evaluated in human cutaneous melanoma biopsies and an endothelial-melanoma co-culture system. Functional assays were conducted to assess the impact of TM knockdown and overexpression on cell adhesion and VM formation. Domain-specific contributions of TM were investigated using constructs targeting its lectin-like domain and ezrin-binding motif. Mechanistic studies involved pharmacological inhibition of focal adhesion kinase (FAK) and siRNA-mediated silencing of ezrin. Therapeutic potential was assessed using a soluble TM lectin domain in both in vitro and in vivo melanoma models.</p><p><strong>Results: </strong>TM was expressed in both angiogenic and non-angiogenic vessels within melanoma tissues and co-culture systems. TM knockdown impaired cell adhesion and suppressed VM formation, while TM overexpression in TM-null melanoma cells enhanced cellular plasticity via its lectin-like domain and ezrin-binding motif. Inhibition of FAK or silencing of ezrin reversed the TM-induced phenotypic switch. Treatment with a soluble TM lectin domain reduced cancer cell plasticity in vitro and significantly inhibited melanoma tumor growth and metastasis in vivo.</p><p><strong>Conclusions: </strong>TM promotes melanoma cell plasticity and VM through FAK- and ezrin-dependent pathways. These findings position TM as a key regulator of tumor progression and suggest that targeting TM may offer a novel therapeutic strategy to disrupt cancer cell plasticity and suppress melanoma growth.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"14"},"PeriodicalIF":14.5,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osmotin-derived 9-amino-acid peptide alleviates α-synuclein and MPTP-induced glial cell activation mediated neuroinflammation, protecting dopaminergic neurons in Parkinson's disease mice brain.","authors":"Kyonghwan Choe, Muhammad Tahir, Min Hwa Kang, Hyun Young Park, Riaz Ahmad, Tae Ju Park, Myeong Ok Kim","doi":"10.1186/s12929-026-01215-4","DOIUrl":"10.1186/s12929-026-01215-4","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is the second most common neurodegenerative disorder, categorized by the loss of dopaminergic neurons in the brain's Substantia Nigra pars compacta (SNpc) due to α-synuclein (α-syn) aggregation, leading to reduced dopamine levels in the striatum. This research study evaluates the neuroprotective potential of the novel peptide osmotin-derived 9-amino-acid (Os_9aa, C-T-Q-G-P-C-G-P-T) against α-syn (neuron-specific enolase promoter human alpha-synuclein (NSE-hαSyn)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models.</p><p><strong>Methods: </strong>Human neuroblastoma SH-SY5Y cells were employed as an in vitro model, while NSE-hαSyn (α-synuclein) transgenic mice and MPTP-treated mice were used as in vivo models of PD. MPTP was administered intraperitoneally (30 mg/kg) once daily for five consecutive days. Mice were immunized with Os_9aa (15 mg/kg, i.p., twice weekly for five weeks), followed by behavioral assessments including open field test, wire hang test, pole test, and rotarod test, and biochemical analysis using the Triplex Assay, western blotting, and confocal microscopy.</p><p><strong>Results: </strong>Our study demonstrated that the novel peptide Os_9aa enhanced cell viability, reduced cytotoxicity, and apoptosis in SH-SY5Y neuroblastoma cells. Os_9aa attenuated synucleinopathy-related pathology in NSE-hαSyn transgenic mice and MPTP-induced PD mouse models. Current findings also highlighted the therapeutic potential of Os_9aa in mitigating behavioral deficits observed in NSE-hαSyn and MPTP mouse models of PD. Furthermore, Os_9aa administration effectively restored key dopaminergic markers, including tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). Additionally, it reduced neuroinflammation by decreasing the activation of glial cells-ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), as well as pro-inflammatory cytokines, such as phosphorylated nuclear factor-κB (p-NF-кB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), in the striatum and SNpc regions. Furthermore, Os_9aa mitigated oxidative stress (OS) by upregulating the expression of nuclear factor erythroid-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), and improved cognitive performance.</p><p><strong>Conclusion: </strong>Collectively, these findings highlight the neuroprotective potential of the Os_9aa, which counteracts α-synuclein- and MPTP-induced neurotoxicity by reducing oxidative stress, glial activation, and neuroinflammation. This multifaceted protection preserves neuronal integrity in both the NSE-hαSyn transgenic and MPTP-induced PD mouse models, underscoring Os_9aa as a promising therapeutic candidate for modifying PD pathogenesis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"13"},"PeriodicalIF":14.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}