Journal of Biomedical Science最新文献

{"title":"Doublecortin-like kinase 1 promotes fibroblast activation and fibrotic progression through Smad3 binding in idiopathic pulmonary fibrosis.","authors":"Lee-Yuan Lin, Wun-Hao Cheng, Yu-Chih Wu, Heng-Ching Wen, Hsao-Hsun Hsu, Chia-Hao Liu, Jing-Yun Chen, Wen-Shan Chang, Ying-Jung Wu, Jie-Syuan Wu, Fara Silvia Yuliani, Chueh-Yi Wang, Chien-Huang Lin, Bing-Chang Chen","doi":"10.1186/s12929-026-01258-7","DOIUrl":"10.1186/s12929-026-01258-7","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with limited treatment options. Although the results of a gene expression analysis revealed that lung tissues in individuals with IPF contain high levels of doublecortin-like kinase 1 (DCLK1), the role of DCLK1 in fibroblast activation remains unclear. The present study examined the function of DCLK1 in IPF and bleomycin-induced pulmonary fibrosis, exploring its potential as a therapeutic target warranting further investigation.</p><p><strong>Methods: </strong>We investigated the role of DCLK1 in fibroblast activation and pulmonary fibrosis in lung tissues from patients with IPF, a bleomycin-induced pulmonary fibrosis mouse model, and cultured normal human lung fibroblasts. DCLK1 knockout mice and mice treated with the selective DCLK1 inhibitor DCLK1-IN-1 were used to evaluate the effects of genetic DCLK1 deficiency and pharmacological DCLK1 inhibition on fibrotic progression and lung function.</p><p><strong>Results: </strong>DCLK1 was markedly upregulated in the IPF lung tissues and in bleomycin-induced fibrotic lung tissues. Global deletion of Dclk1 considerably attenuated fibrotic remodeling and preserved lung function in mice. In addition, transforming growth factor β (TGF-β) induced DCLK1 expression in normal human lung fibroblasts through Smad3 and NF-κB signaling, while Akt/DCLK1/Smad3 signaling was associated with fibroblast activation and profibrotic marker expression. Moreover, DCLK1 was associated with Smad3, and these findings were consistent with DCLK1-Smad3-associated signaling linked to connective tissue growth factor expression. Finally, oral administration of DCLK1-IN-1 slowed fibrotic progression and preserved lung function in bleomycin-treated mice.</p><p><strong>Conclusions: </strong>DCLK1 is associated with fibroblast activation and pulmonary fibrosis, with findings consistent with DCLK1-Smad3-associated signaling linked to profibrotic marker expression. Genetic deletion or pharmacological inhibition of DCLK1 attenuated fibrotic progression and preserved lung function, suggesting that DCLK1 warrants further investigation as a potential therapeutic target in pulmonary fibrosis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005358","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":"SARS-CoV-2 membrane protein recruits PP2A to dephosphorylate the nucleocapsid and promote virion production.","authors":"Sheng-Han Wang, Tai-Ling Chao, Chi-Ling Hsieh, Pei-Jer Chen, Sui-Yuan Chang, Shiou-Hwei Yeh","doi":"10.1186/s12929-026-01255-w","DOIUrl":"10.1186/s12929-026-01255-w","url":null,"abstract":"<p><strong>Background: </strong>The nucleocapsid (N) protein of coronavirus harbors a conserved serine/arginine (SR)-rich motif whose phosphorylation by GSK-3 is essential for viral transcription and replication. Our previous studies in Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the JHM strain of mouse hepatitis virus revealed a phosphorylation-to-dephosphorylation transition during the viral life cycle, with newly synthesized N highly phosphorylated and virion-associated N hypophosphorylated. Here, we characterize this transition in SARS-CoV-2 and define its functional significance.</p><p><strong>Methods: </strong>Utilizing high-resolution gel analysis and the phospho-specific antibody, the phosphorylation levels of SARS-CoV-2 N proteins in the virus-infected Calu-3 cells and secreted virions from culture supernatants were compared between different viral strains. This phosphorylation-to-dephosphorylation transition was also verified in the SARS-CoV-2 virus-like particle (SC2-VLP) platform expressing N, membrane (M), envelope, and spike proteins. In this VLP system, the substantial contribution of N dephosphorylation status to particle secretion, either by blocking GSK-3 activity or phospho-related mutants, was assessed. With different viral structural protein-expressing clones and phosphatase inhibitors, we characterized the key viral factor and host phosphatase to mediate the N dephosphorylation process. Furthermore, we evaluated the antiviral efficacy of phosphatase inhibitors using the virus-infected Calu-3 culture.</p><p><strong>Results: </strong>Our results showed that the phosphorylation change of SR motif in N was observed across multiple strains and recapitulated in the SC2-VLP system. GSK-3 inhibition or a phospho-deficient N mutant, but not a phospho-mimetic one, enhanced VLP release, indicating that N dephosphorylation promotes virion secretion. Mechanistically, the M protein, via its C-terminal domain, interacts with phosphorylated N to recruit protein phosphatase 2A (PP2A) to the ERGIC, facilitating N dephosphorylation. Inhibition of PP2A, either by inhibitors or siRNA, impaired the M-induced N dephosphorylation, thereby suppressing viral assembly and progeny virion production. Blockade of PP2A also indirectly reduced N phosphorylation through the Akt-mediated inhibition of GSK-3, resulting in decreased genomic RNA synthesis.</p><p><strong>Conclusions: </strong>Collectively, these findings establish N dephosphorylation as a critical regulatory step in SARS-CoV-2 assembly and virion release. In ERGIC, this M protein-mediated process recruits host PP2A to dephosphorylate N, thus supporting PP2A as a promising pan-coronavirus antiviral target.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947617","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":"Modeling CLN3 Batten disease in astrocytes reveals alterations in mitochondria homeostasis, fatty acid metabolism and oxidative stress response.","authors":"Mingyi Yang, Wei Wang, María Cámara-Quílez, Borghild Hvesser Farsund, Niklas Nonboe Andersen, Karin Garten, Animesh Sharma, Xiaolin Lin, Ingrid Åmellem, Erlend Ravlo, Jing Ye, Magnar Bjørås, Mirta Mittelstedt Leal de Sousa","doi":"10.1186/s12929-026-01253-y","DOIUrl":"10.1186/s12929-026-01253-y","url":null,"abstract":"<p><strong>Background: </strong>CLN3 Batten disease is a severe pediatric neurodegenerative disorder caused by mutations in the CLN3 gene, most commonly a 1 kb deletion encompassing exons 7 and 8. CLN3 deficiency is associated with lysosomal dysfunction, impaired cellular clearance and disrupted metabolism. While neurons are particularly vulnerable in CLN3 Batten disease and have been the primary focus of research, glial cells are increasingly recognized as active contributors to disease pathology. Among them, astrocytes-the most abundant glial cell type in the brain-play critical roles in maintaining neuronal health and homeostasis. However, astrocytes remain understudied in CLN3 patient-derived models.</p><p><strong>Methods: </strong>We present the first iPSC-derived astrocyte model from a skin biopsy of a CLN3 patient carrying the common 1 kb deletion. Cellular and molecular features of iPSC and astrocytes derived from both healthy controls and the CLN3 patient were characterized via qPCR, immunocytochemistry and targeted mass spectrometry. In addition, comprehensive omics-based profiling, through transcriptomic and label-free quantitative proteomics, was performed to uncover novel molecular mechanisms and generate hypotheses that can guide future mechanistic and functional studies.</p><p><strong>Results: </strong>Transcriptomic and proteomic analyses during astrocyte differentiation revealed an upregulation of mitochondrial respiratory chain complexes I and IV-contrasting with the downregulation typically observed in CLN3-deficient neurons. We also identified a metabolic shift favoring the elongation of very-long-chain saturated fatty acids, accompanied by reduced lipid synthesis and enhanced fatty acid oxidation. These metabolic alterations were paralleled by an upregulation of proteins involved in oxidative stress responses, likely reflecting a compensatory adaptation to mitochondrial and lipid metabolic dysregulation. Furthermore, we observed significant changes in chromatin organization during astrocyte differentiation in CLN3 cells, suggesting epigenetic remodeling as a contributing factor to disease pathology.</p><p><strong>Conclusion: </strong>Our findings prompt the hypothesis that mitochondrial dysfunction may precede lysosomal defects in CLN3-deficient astrocytes. Restoring mitochondrial health could improve brain metabolism, inflammation control, neurotransmitter regulation, and neuronal survival, highlighting mitochondria as promising therapeutic targets in CLN3 Batten disease.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930013","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":"CASK promotes non-small cell lung cancer growth through coordinated regulation of EGFR expression, trafficking, and p21 expression.","authors":"Yun-Han Lai, Duen-Yi Huang, Yen-Yu Chang, Yen-Lin Huang, Wan-Wan Lin","doi":"10.1186/s12929-026-01252-z","DOIUrl":"10.1186/s12929-026-01252-z","url":null,"abstract":"<p><strong>Background: </strong>Calcium/calmodulin-dependent serine protein kinase (CASK), a member of the membrane-associated guanylate kinase (MAGUK) family, functions as a multifunctional scaffold protein by engaging diverse binding partners. Although CASK has been implicated in tumorigenesis, its molecular role in the pathogenesis of non-small cell lung cancer (NSCLC) remains poorly characterized.</p><p><strong>Methods: </strong>CASK expression was assessed by immunohistochemistry in lung adenocarcinoma tissues and matched non-tumor samples. Bioinformatics analyses were performed using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. Functional studies were conducted in epidermal growth factor receptor (EGFR) wild-type H1299 cells and EGFR exon 19-deleted PC9 cells following CASK silencing. RNA-Seq was used to identify differentially expressed genes, and assays of cell growth, cell cycle progression, EGFR trafficking, and downstream signaling were performed.</p><p><strong>Results: </strong>CASK expression was significantly elevated in early-stage NSCLC, and higher levels correlated with reduced overall and first progression survival. Silencing CASK inhibited cell growth by blocking the G1-S transition and inducing p21waf1/Cip1, a key mediator of cell cycle arrest, at both transcript and protein levels. Growth suppression was rescued by treatment with a p21 inhibitor UC2288, confirming its central role. Elevated p21 in CASK-deficient cells was reversed by EGFR, AKT, and ERK inhibitors, suggesting that CASK is involved in downregulating p21 via suppressing EGFR/ERK-dependent transcription and EGFR/AKT-dependent protein stabilization. Although p53 is constitutively involved in upregulation of p21 gene expression, the findings from the p53 inhibitor and p21 promoter activity assay excluded the role of p53 in CASK silencing-induced p21 upregulation. Furthermore, CASK modulated the autocrine EGFR loop. CASK silencing enhanced EGFR expression through gene transcription and post-transcriptional protein stabilization and promoted EGFR activation by upregulating TGF-α in p53-, ERK-, and AKT-dependent manners. Notably, CASK loss did not affect EGFR trafficking to early endosomes but delayed its transition to late endosomes in an ERK-dependent fashion, thereby reducing receptor degradation.</p><p><strong>Conclusions: </strong>We identified CASK as a previously unrecognized driver of NSCLC growth and a potential prognostic biomarker. By regulating EGFR trafficking to late endosomes and attenuating AKT and ERK signaling, CASK suppresses p21 expression and promotes NSCLC cell proliferation, revealing a novel proliferation regulator in NSCLC.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864098","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":"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":"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":14.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156883/pdf/","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":"OA","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":"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":14.5,"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":"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":14.5,"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":"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":14.5,"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":"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":14.5,"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":14.5,"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}