Journal of Biomedical Science最新文献

{"title":"NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.","authors":"Tanqing Long, Qi Wang, Yinpeng Le, Mi Zhang, Yan Sun, Juan Iovanna, Lei Li, Chuanrui Xu, Juan Liu","doi":"10.1186/s12929-026-01254-x","DOIUrl":"https://doi.org/10.1186/s12929-026-01254-x","url":null,"abstract":"<p><p>Nuclear protein 1 (NUPR1) is an intrinsically disordered, stress-adaptive regulator that sits at the intersection of transcriptional plasticity and proteostatic control, broadly upregulated across malignancies and tightly associated with poor prognosis. Here, we synthesize evidence positioning NUPR1 as a central node of tumor adaptation that integrates metabolic rewiring, proteostatic balance, and cell-death checkpoints into a unified stress-response framework. NUPR1 orchestrates lipogenic and glycolytic programs, sustains lysosomal biogenesis and autophagic flux, and governs cell-fate decisions by restraining apoptosis and ferroptosis through iron and redox control. Beyond tumor-intrinsic roles, NUPR1 remodels the tumor microenvironment by driving immunosuppressive macrophage polarization and amplifying inflammatory signaling, collectively sustaining a pro-survival niche. These circuits underpin broad therapeutic resistance across modalities, spanning chemotherapy, targeted agents, endocrine therapy, and immune checkpoint blockade. We further discuss the development of small-molecule NUPR1 antagonists-including ZZW-115 and emerging chemotypes-that disrupt nuclear trafficking and stress tolerance, alongside formulation strategies to optimize pharmacodynamic potency and safety. Together, these insights establish NUPR1 as a druggable stress-response node and provide a mechanistic framework to overcome resistance and refine adaptive cancer therapy paradigms.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.","authors":"Chia-Wen Wang, Huai-Chia Chuang, Tse-Hua Tan","doi":"10.1186/s12929-026-01251-0","DOIUrl":"https://doi.org/10.1186/s12929-026-01251-0","url":null,"abstract":"<p><p>Multiple members (DUSP1-29) of dual-specificity phosphatase (DSP) family are key regulators of mitogen-activated protein kinases (MAPKs), which regulate numerous physiological responses. Eight DUSPs are also named MAPK phosphatases (MKPs). DUSP dysregulation contributes to the pathogenesis of various human inflammatory and chronic diseases. Downregulation of DUSP1, DUSP3, DUSP11, and DUSP22, as well as upregulation of DUSP4, DUSP6, and DUSP23 are involved in human autoimmune diseases. Besides autoimmune diseases, reduction of DUSP1, DUSP2, and DUSP14, as well as induction of DUSP8 contribute to the pathogenesis of allergic diseases. Additionally, decreased levels of DUSP2, DUSP11, DUSP22, and DUSP28 are associated with human inflammatory bowel diseases. Moreover, deficiency of 10 DUSPs, as well as induction of DUSP4 are associated with metabolic diseases. Downregulation of 5 DUSPs are involved in cardiovascular disease pathogenesis; in contrast, upregulation of other 5 DUSPs are correlated with cardiovascular diseases. Collectively, dysregulated DUSPs could be diagnostic biomarkers and therapeutic targets for inflammatory diseases. Due to complex expression patterns of DUSPs, it is crucial to study the regulatory mechanisms of individual DUSPs in various inflammatory and chronic diseases. In this review, we summarize the roles and regulatory mechanisms of DUSPs in human inflammatory and chronic diseases. We also discuss the potential therapeutic applications of DUSP agonists/inhibitors in human inflammatory and chronic diseases.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838496","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":"β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset.","authors":"Francesca Terrin, Sofia Faggin, Edoardo Bizzotto, Davide Santinello, Silvia Cerantola, Giuseppe Borsato, Fabrizio Fabris, Alessandro Scarso, Rosario Licitra, Graziano Guella, Gabriele Sales, Stefano Cagnin, Laura Treu, Luigi Bubacco, Maria Cecilia Giron, Nicoletta Plotegher, Luisa Dalla Valle","doi":"10.1186/s12929-026-01249-8","DOIUrl":"https://doi.org/10.1186/s12929-026-01249-8","url":null,"abstract":"<p><strong>Background: </strong>Glucosylated-sterols can be synthetized endogenously, absorbed through the diet or derive from bacterial infection. Their clinical relevance is currently underestimated, even though their imbalance has been associated with an increased risk of neurodegeneration over the lifespan. We studied the detrimental effects elicited by dietary consumption of the plant-derived β-sitosterol β-D-glucoside (BSSG), known to be associated with the occurrence of ALS-PDC, to elucidate its potential mechanism of action.</p><p><strong>Methods: </strong>Zebrafish larvae and adults, as well as mice, were treated with BSSG administered directly in the water or via customized food pellet, respectively. Since the intestine was identified as the primary target tissue, its morphological and functional characteristics were assessed, together with transcriptional profiling and gut microbiota sequencing. Ex vivo analysis of zebrafish gut contractility was applied to evaluate intestinal neuromuscular responses. Mutant and transgenic zebrafish lines were used to explore a potential BSSG mechanism of action.</p><p><strong>Results: </strong>BSSG induced intestinal inflammation in both zebrafish and mouse models. This previously unknown effect was evidenced by gut dysmotility and inflammatory response. Transcriptomic analyses revealed increased expression of inflammation-related genes in the intestine of both zebrafish and mice, while preliminary gut microbiota analyses suggested the onset of dysbiosis. Transgenic and mutant zebrafish lines, depleted of genes involved in glucocorticoids synthesis and activity, evidenced that BSSG likely interacts with the glucocorticoid receptor, potentially impairing its canonical anti-inflammatory activity.</p><p><strong>Conclusions: </strong>We identified novel pathways altered by dietary BSSG exposure. This molecule appears to initially induce gut inflammation, leading to changes in intestinal morphology and function, and may contribute to neurodegeneration through disruption of the well-known gut-brain axis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838467","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":"Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.","authors":"Maria Carolina Cordeiro, Andrea Barbero, Ivan Martin, Martin J Stoddart","doi":"10.1186/s12929-026-01247-w","DOIUrl":"https://doi.org/10.1186/s12929-026-01247-w","url":null,"abstract":"<p><p>Articular cartilage, as a mechanosensitive tissue, supports and distributes various mechanical forces-including compression, shear, hydrostatic pressure, and tensile strain-during joint loading and motion. These external forces deform not only the chondrocytes but also their pericellular matrix and the surrounding extracellular matrix (ECM). Those mechanical cues are detected by mechanosensors on the plasma membrane (e.g., integrins) and transmitted through the cytoskeleton, ultimately being converted into biochemical signals. These signals activate key mechanoresponsive intracellular pathways-including TGF-β-induced SMAD, Rho-GTPase, MAPKs (ERK, JNK, p38), PI3K/AKT/mTOR, MRTF-SRF, and YAP/TAZ-that regulate chondrogenic differentiation and cartilage-specific matrix synthesis. This field of study is known as mechanobiology. Over the past decades, it has gained increasing recognition, particularly with the emergence of tissue-engineering constructs as a novel strategy for cartilage repair. However, progress in chondrogenic mechanobiology has primarily centred on intrinsic substrate- or matrix-derived cues, while overlooking the role of extrinsic mechanical forces. This review therefore provides an updated perspective on chondrogenic mechanobiology, with a particular focus on the cellular responses to external mechanical stimuli. It also emphasizes the therapeutic potential of incorporating mechanical stimulation into tissue-engineering strategies for cartilage repair, an emerging filed referred to as Regenerative Rehabilitation (RR). Since this concept has so far been investigated mainly in vitro, we highlight only those studies and refer to it as In vitro Regenerative Rehabilitation. Moreover, this review also addresses post-traumatic osteoarthritis (PTOA), a common joint disorder that frequently results from traumatic cartilage damage. It explores the mechanobiological mechanisms underlying OA and discusses in vitro regenerative rehabilitation studies, highlighting how external forces could serve as an alternative to conventional biochemical treatments for preventing OA progression.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838501","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":"Tubulin glutamylation: a key regulator of flagella, cilia, centrosomes, and disease pathways.","authors":"Shiau-Chi Chen, Yi-Chien Chuang, Yu-Chun Lin","doi":"10.1186/s12929-026-01244-z","DOIUrl":"https://doi.org/10.1186/s12929-026-01244-z","url":null,"abstract":"<p><p>Tubulin glutamylation is an essential post-translational modification that expands the functional diversity of microtubules in many cellular structures, including flagella, motile cilia, primary cilia, centrosomes, and neurons. This modification adds variable lengths of glutamate side chains to the C-terminal tails of tubulin, creating a finely tuned biochemical signal that regulates microtubule stability, motor protein movement, the activity of severing enzymes, and the recruitment of key signaling molecules. Growing evidence shows that glutamylation is not uniformly distributed but instead forms distinct spatial patterns along microtubule arrays, particularly within the axonemes of flagella and cilia, centriolar triplets, and long-lived neuronal microtubules. These patterns are established by tubulin ligase-like enzymes that add glutamates and by carboxypeptidases that remove them, together shaping a dynamic \"tubulin code.\" In motile cilia and flagella, glutamylation fine-tunes dynein-driven force generation and the coordination of axonemal bending. Disruption of this modification impairs ciliary beating and sperm flagellar motility, leading to disorders such as primary ciliary dyskinesia, which manifests as chronic respiratory infections and laterality defects, and can also disrupt cerebrospinal fluid flow, causing hydrocephalus and male infertility such as asthenozoospermia. In primary cilia, reduced glutamylation perturbs intraflagellar transport and ciliary signaling and contributes to ciliopathies including Joubert syndrome and retinal degeneration. In dividing cells, altered glutamylation on centrosomes leads to errors in chromosome segregation and is associated with cancer progression. This review summarizes current knowledge of the enzymes, structural principles, and cellular mechanisms governing tubulin glutamylation, highlights its emerging roles in human diseases, and discusses new technological advances-including biochemical reconstitution, super-resolution imaging, and live-cell manipulation tools-that are beginning to reveal how this modification dynamically controls microtubule properties and the functions of flagella, cilia, and centrosomes in health and disease.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838483","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":"Nanomedicine-based theranostics in atherosclerotic cardiovascular diseases.","authors":"Chih-Fan Yeh, Laura Ianalieva, Hong-Kong Wong, Chau-Chung Wu, Kai-Chien Yang","doi":"10.1186/s12929-026-01245-y","DOIUrl":"10.1186/s12929-026-01245-y","url":null,"abstract":"<p><p>Current treatment for atherosclerotic cardiovascular diseases (ASCVD) mainly focuses on the modification of systemic risk factors, such as hyperglycemia and hyperlipidemia. Despite significant efforts and expanse, achieving early and proper diagnosis of ASCVD to improve clinical outcomes remains challenging, and vascular-targeted therapies or genetic editing, while ideal, are still limited. The development of nanomedicine-based mRNA vaccines for SARS-CoV-2 has demonstrated the potential of nanotechnology to target previously inaccessible molecules. Precision therapies by nanomedicine targeting specific tissues/molecules hold potential for new treatment paradigms by precisely modulating disease-causing molecular pathways within diseased tissues, including dysfunctional vasculature. By leveraging insights into the pathogenic contributors of atherogenesis, researchers have optimized nanoplatforms' composition, synthesis strategies, and surface design to enhance therapeutic efficacy and enable early diagnosis. Herein, we present an updated overview of therapeutic and diagnostic strategies using nanomedicine for ASCVD, and explore future research directions and innovative approaches for nanomedicine-driven theranostics in cardiovascular care.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815803","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":"Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.","authors":"Yen-Hung Lin, Yun-Hsun Liao, Sin-Bo Liao, Tzu-Yu Lin, Muniesh Muthaiyan Shanmugam, Pei-Jia Hsu, Chang-Shi Chen, Tsiu-Ting Ching, Oliver Ingvar Wagner, Chiou-Hwa Yuh, Horng-Dar Wang","doi":"10.1186/s12929-026-01246-x","DOIUrl":"https://doi.org/10.1186/s12929-026-01246-x","url":null,"abstract":"<p><strong>Background: </strong>Phosphatidylinositol transfer protein-1 (pitp-1) is involved in the phosphoinositide (PIP) cycle. The role of pitp-1 in promoting healthy longevity remains unknown. Our previous work showed that the PIP cycle-related genes diacylglycerol lipase-1 (dagl-1) and diacylglycerol kinase-5 (dgk-5) regulate lifespan, as overexpression of dagl-1 or knockdown of dgk-5 prolongs lifespan and enhances oxidative stress resistance through target of rapamycin (TOR) signaling. As pitp-1 is a key component of this pathway, we investigated its role in lifespan regulation and the underlying mechanisms, aiming to clarify whether it represents a critical regulator of healthy longevity and how it coordinates conserved signaling pathways to regulate aging.</p><p><strong>Methods: </strong>Caenorhabditis elegans (C. elegans) mutants, RNAi-mediated knockdown, and transgenic overexpression were applied to assess lifespan, motility, and stress resistance. Temporal and tissue-specific RNAi were applied to identify critical time window and tissue for pitp-1-mediated lifespan regulation. TOR signaling was measured by phosphorylated S6 kinase (p-S6K) and puromycin incorporation, and transcriptomic analysis identified affected pathways.</p><p><strong>Results: </strong>pitp-1 negatively regulated lifespan and healthspan in C. elegans. Genetic deletion or RNAi-mediated knockdown of pitp-1 extended lifespan, attenuated age-related motility decline, and increased oxidative stress resistance. Temporal and spatial analyses revealed that suppression of pitp-1 in neurons during early adulthood was sufficient to promote healthy longevity. Mechanistically, these beneficial effects upon pitp-1 reduction were associated with suppression of TOR signaling. Conversely, pitp-1 overexpression shortened lifespan and impaired healthspan via TOR activation. Moreover, pitp-1 was transcriptionally repressed by DAF-16 downstream of insulin/IGF-1 signaling (IIS), and contributed to IIS-mediated longevity regulation. Furthermore, pitp-1 reduction also improved organismal proteostasis, as evidenced by decreased polyglutamine (polyQ) aggregation and enhanced motility in a neuronal proteotoxicity model.</p><p><strong>Conclusions: </strong>These findings identify pitp-1 as a novel regulator of healthy aging, suggesting a role in coordinating IIS and TOR signaling and providing new insights into conserved mechanisms of longevity regulation.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772803","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":"Structure, mechanism and clinical relevance of NRG1 fusions in cancer.","authors":"Clarisse Thiollier-Schmitt, Manon Barre, Marie Issenmann, Emeline Cros-Perrial, Michaël Duruisseaux, Lars Petter Jordheim","doi":"10.1186/s12929-026-01242-1","DOIUrl":"10.1186/s12929-026-01242-1","url":null,"abstract":"<p><p>NRG1 gene fusions have been identified in patients with various solid tumors. Such patients have aggressive tumors and respond poorly to currently available treatments. There are many gene partners described for NRG1 fusions, and the structures and roles of the chimeric proteins are not always correctly understood. Here, we gather information on 665 reported patients with a total of 115 different known gene partners, and discuss structural elements supposed to play important roles in the biology of NRG1 fusions in cancer. This gives a better understanding of the biology of NRG1 fusions, and will help in the development of new therapeutic approaches. Our methodology described in this review can also be used for the study of other genes with disease-related fusions.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699055","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":"Comparison of hybrid-and mono-pathotype Escherichia coli isolates from South Korea based on whole genome analysis and cytotoxicity assay.","authors":"Jong Hyun Shin, Min Seok Kim, Ji Young Choi, Sunju Kim, Kun Taek Park, Mi-Ran Seo, Seung-Hyun Jung, Yeun-Jun Chung, Hyeri Seok, Hae Suk Cheong, Ki-Tae Kwon, Bo Kyeung Jung, Cheol-In Kang, Doo-Ryeon Chung, Dongwoo Shin, Kwan Soo Ko","doi":"10.1186/s12929-026-01243-0","DOIUrl":"10.1186/s12929-026-01243-0","url":null,"abstract":"<p><strong>Background: </strong>Among intestinal pathogenic Escherichia coli, hybrid pathotypes carrying virulence determinants of multiple classical pathotypes have recently been identified.</p><p><strong>Methods: </strong>A total of 292 E. coli isolates were collected from human, livestock, and environmental sources in South Korea, and their whole genome sequences were determined. They were classified into pathotypes based on virulence gene profiles. We constructed a phylogenetic tree based on cgSNPs. Synteny analysis on the LEE pathogenicity island was performed, and enriched accessory gene repertoires in particular hybrid-pathotypes were identified. Bacterial virulence was measured by lactate dehydrogenase (LDH) cytotoxicity assays. Genetic factors associated with increased cytotoxicity in the LDH assay were identified using SPLASH.</p><p><strong>Results: </strong>Among 192 intestinal pathogenic E. coli isolates, 63 hybrid pathotype isolates (38 STEC/EPEC, 23 STEC/ETEC, and 2 STEC/EAEC) were identified. Two main groups of STEC/EPEC hybrid-pathotype isolates and one major STEC/ETEC group were identified. Both groups of STEC/EPEC hybrid isolates were closely associated with EPEC mono-pathotype isolates, and most STEC/ETEC hybrid groups clustered with STEC mono-pathotype isolates. Synteny analysis on the LEE pathogenicity island also showed that some STEC/EPEC hybrids might originate from EPEC genomic backbone. Based on the LDH assay, cytotoxicity was higher in STEC/ETEC, but lower in STEC/EPEC. Five gene modules (adhesion-pili, plasmid conjugation, flagella-motility, iron uptake, and T3SS) were identified to be genetic factors correlated with increased cytotoxicity in STEC/ETEC.</p><p><strong>Conclusion: </strong>High prevalence of hybrid-pathotype E coli isolates was identified. They might emerge repeatedly by independent incorporation of additional virulence factors, and genomic backbones and cytotoxicity differed according to the specific hybrid pathotype.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673693","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":"Many but not all pathogen-associated molecular patterns aggravate neurogenic heterotopic ossification after spinal cord injury.","authors":"Selwin G Samuel, Hsu-Wen Tseng, Bastien Rival, Valérie Barbier, Kavita Bisht, Marjorie Salga, Shrutika M Mate, Whitney Fleming, François Genêt, Sébastien Banzet, Jean-Pierre Lévesque, Dorothée Girard, Kylie A Alexander","doi":"10.1186/s12929-026-01237-y","DOIUrl":"10.1186/s12929-026-01237-y","url":null,"abstract":"<p><strong>Background: </strong>Neurogenic heterotopic ossifications (NHOs) are heterotopic bones that develop in periarticular muscles after traumatic brain (TBI) and spinal cord injuries (SCI). The mechanisms leading to NHO are incompletely understood and the only effective treatment to-date remains surgical resection. We previously established that several inflammatory pathways drive NHO pathogenesis in injured muscles in a mouse model of NHO and in humans. We also demonstrated a functional association between gram-negative bacterial infections and NHO development via lipopolysaccharide (LPS), a pathogen associated molecular pattern (PAMP), which exacerbated NHO in a Toll-like receptor-4 (TLR4)-dependent manner in mice.</p><p><strong>Methods: </strong>Using our mouse model of NHO induced by SCI and muscle injury in mice, we tested the effect of a large array of purified PAMPs post-surgery to mimic fungal, viral and bacterial infections and measured NHO bone volumes by micro-computerized tomography (microCT). The effect of PAMPs was also tested in vitro on human muscle progenitors and monocyte/macrophage populations.</p><p><strong>Results: </strong>Muscle progenitors and monocyte/macrophage populations from humans and mice express numerous pattern recognition receptors. In mice, numerous PAMPs produced by bacteria, viruses and fungi exacerbated NHO formation, and the majority of these PAMPs indirectly stimulated fibro-adipogenic progenitor (FAP) calcium mineralization in vitro via macrophages. Likewise, in humans, some PAMPs, particularly those binding to TLR2, directly and indirectly increased the calcium mineralization and osteogenic differentiation of human FAPs isolated from muscles surrounding human NHO. Finally, we established that the indirect stimulation of human FAP mineralization was mediated by inflammatory cytokines IL-1 and oncostatin M secreted by monocytes in response to PAMPs. Overall, our findings suggest that numerous types of infection have the potential to exacerbate NHO development and further highlight the role of oncostatin M and IL-1 signaling pathways in NHO pathophysiology.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":12.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654158","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}