Tissue Barriers最新文献

{"title":"Advanced glycation endproducts induce cytokine dysregulation and weaken lung epithelial and endothelial barrier integrity.","authors":"Abdulaziz H Alanazi, Mohamed S Selim, Yin Zhu, Duo Zhang, S Priya Narayanan, Payaningal R Somanath","doi":"10.1080/21688370.2025.2521136","DOIUrl":"10.1080/21688370.2025.2521136","url":null,"abstract":"<p><p>Diabetes mellitus is a systemic disease characterized by chronic hyperglycemia, persistent inflammation, and oxidative stress. While the vascular complications of diabetes are well-documented, their impact on lung barrier integrity remains underexplored. In this study, we investigated the molecular mechanisms by which advanced glycation end-products (AGE) compromise the integrity of lung endothelial and epithelial barriers. Using human lung microvascular endothelial cells and epithelial (A549) cells, we assessed the impact of AGE on the tight junction protein claudin-5, adherens junction protein VE-cadherin, and key signaling molecules including the receptor for AGE (RAGE), phosphorylated Akt, and p38 MAPK as well as a panel of pro-inflammatory cytokines. Our findings demonstrated that AGE exposure (50 μg/mL) significantly activated Akt and p38 MAPK, upregulated Claudin-5 and RAGE, and downregulated VE-cadherin, correlating with reduced transendothelial electrical resistance <i>in vitro</i>. Notably, we observed similar effects on lung epithelial cells. Moreover, AGE-treated conditioned media from THP-1 macrophages induced a pronounced increase in inflammatory cytokines, amplifying the disruption of lung barrier integrity. These findings reveal a potential mechanism linking diabetes-induced vascular dysfunction and immune activation to compromised lung barrier function, emphasizing the need for further research into diabetes-associated lung complications.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2521136"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using mathematical approaches to answer complex biological questions: can exosomal miRnas predict cancer prognosis?","authors":"Olka Missaghi, Leman Nur Nehri, Sepehr Bakhshi, Oğuzhan Karaosmanoğlu, Hülya Sivas, Aybar Can Acar, Sreeparna Banerjee","doi":"10.1080/21688370.2025.2611205","DOIUrl":"10.1080/21688370.2025.2611205","url":null,"abstract":"<p><p>Epithelial to mesenchymal transition (EMT) has been widely implicated in diverse cellular processes such as development, would healing, as well as in cancer metastasis and therapy resistance. Exosomes are nanosized vesicles that carry cellular products and are known to mediate cell-cell communication. We describe here how a systems biology approach relying on simple experimental data in combination with <i>in silico</i> tools and mathematical modeling can be used to understand complex biological phenomenon such as EMT.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2611205"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational signatures in blood-brain barrier: mechanisms, computational insights, and clinical applications in precision oncology.","authors":"Hare Krishna, Vinod Kumar Singh, Seema Awasthi, Ajay Kumar","doi":"10.1080/21688370.2026.2664236","DOIUrl":"10.1080/21688370.2026.2664236","url":null,"abstract":"<p><p>The blood - brain barrier (BBB) plays a central role in maintaining central nervous system (CNS) homeostasis, and its disruption is a defining feature of malignant brain tumors such as glioblastoma. Emerging evidence indicates that BBB dysfunction not only alters the tumor microenvironment but also shapes the mutational processes that drive genomic instability in CNS malignancies. This review synthesizes current understanding of the biological mechanisms linking BBB breakdown with distinct mutational signatures, including those arising from oxidative stress, hypoxia-induced replication stress, lipid peroxidation, inflammation, and metabolic reprogramming. Advances in next-generation sequencing, coupled with computational tools such as non-negative matrix factorization, Bayesian modeling, and deep learning, have enabled precise extraction of these signatures and their integration with multi-omics data. Clinically, BBB-associated mutational signatures offer significant promise for therapeutic stratification, prediction of treatment response, and noninvasive monitoring through cerebrospinal fluid - derived circulating tumor DNA. Despite these advances, challenges persist due to limited tissue accessibility, low-yield CSF samples, incomplete mechanistic models, and the lack of CNS-specific analytical frameworks. A deeper understanding of BBB-driven mutational processes, supported by improved computational approaches and integrative datasets, holds potential to advance precision oncology in neuro-oncology.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2664236"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium nanoparticles ameliorate methotrexate-induced gastric fundus injury in adult male albino rats via TLR4/NF-κB signaling, apoptosis, and intercellular junctions modulation: biochemical and histological study.","authors":"Sahar A Mokhemer, Esraa Mohammed Khairy, Rehab Ahmed Rifaai, Nashwa Fathy Gamal El-Tahawy, Randa Ahmed Ibrahim","doi":"10.1080/21688370.2025.2559427","DOIUrl":"10.1080/21688370.2025.2559427","url":null,"abstract":"<p><p>Despite its widespread application in the treatment of cancer and autoimmune diseases, methotrexate (MTX) is associated with several adverse effects. Selenium nanoparticles (SeNPs) have antioxidant and anti-inflammatory effects. This study aimed to investigate the ameliorating effects of SeNPs against MTX-induced gastric fundus damage and the possible underlying mechanisms. Rats were randomly allocated into five groups: control group, SeNPs group, MTX group, and two SeNPs administered groups either prophylactic or concomitant. Physical and macroscopic evaluations were performed. Gastric fundus specimens were collected for biochemical and histological changes. The Methotrexate group showed a significant decrease in weight gain, food intake, and gastric total antioxidant capacity (TAC). Also, there was a disruption of the gastric epithelial barrier indicated by the significant decrease in occludin, E-cadherin gastric levels, and zonula occludens-1 (ZO-1) immune-expression, together with mucous barrier alteration indicated by a significant decrease in Periodic acid-Schiff (PAS) stain mean area fraction. While gastric malondialdehyde (MDA), toll-like receptors 4 (TLR4), and Myeloid differentiation primary response 88 (MYD88) levels, the nuclear factor kappa B (NF-κB) and cleaved caspase 3 immune-expression were significantly increased. Furthermore, histological assessment revealed mucosal ulceration, vascular congestion, and inflammatory cellular infiltration with a significant increase in mast cells. Surprisingly, SeNPs administration attenuated oxidative stress, apoptosis, and TLR4/NF-κB signaling. Moreover, a significant increase in occludin, E-cadherin, and ZO-1 and a significant decrease in mast cell number were noticed with SeNPs administration together with histological structure preservation. Notably, the prophylactic treatment with SeNPs caused more improvement than its concomitant administration.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2559427"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinating enzymes at the crossroads of blood-brain barrier integrity and neurodegeneration: mechanistic insights, therapeutic targeting and future directions.","authors":"Fahima Munavar-K, Nibedita Lenka","doi":"10.1080/21688370.2025.2504738","DOIUrl":"10.1080/21688370.2025.2504738","url":null,"abstract":"<p><p>The ubiquitin-proteasome system (UPS) carries immense significance concerning cellular homeostasis that encompasses both ubiquitination and deubiquitination as key facets for maintaining protein stability. The deubiquitinating enzymes (DUBs) have emerged as critical regulators of proteostasis, neuroinflammation and blood-brain barrier (BBB) integrity by controlling the fate of crucial proteins associated with barrier architectures in CNS and neurodegenerative disorders (NDs) alike. However, a concrete understanding of their specific neurodevelopmental and neuroprotective functions is yet to be discerned. This article discusses the multifaceted roles of DUBs in the maintenance of BBB integrity, neuroprotection and various NDs and also underscores the therapeutic prospects targeting the same. While DUBs like USP7, USP9X, USP27X, UCHL1, etc. participate in neural stem cell maintenance and neurogenesis, including BBB function, USP13, USP14, USP25, BRCC3 and CYLD, among others, are associated with BBB dysfunction and NDs. The mechanistic underpinning concerning their hitherto unexplored mode of action, DUB-substrate interactions and specificity would facilitate developing the therapeutic agonists and small-molecule inhibitors to prevent or reverse neuroinflammation, BBB impairment and developmental disorders. Recent innovations concerning DUB-targeting chimaeras (DUBTACs) and proteolysis-targeting chimaeras (PROTACs) can be explored further for their plausible administration via nanoparticle-based delivery approaches to alleviate the progressive neurodegeneration.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2504738"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occludin deficiency is associated with developmental impairment, locomotor dysfunction, and social deficiencies.","authors":"Silvia Torices, Nikolai Fattakhov, Oandy Naranjo, Destiny Daniels, Sierra Simon, Leah Daire, Luisa Mendoza, Marta Kopanska, Michal Toborek","doi":"10.1080/21688370.2026.2647450","DOIUrl":"10.1080/21688370.2026.2647450","url":null,"abstract":"<p><p>Neurodevelopmental and psychiatric disorders, such as attention deficit hyperactivity disorder or autism spectrum disorder, have been intricately linked to structural impairments and compromised permeability of the blood-brain barrier (BBB). Occludin (ocln) is a tight junction (TJ) protein known for its role in maintaining BBB integrity. In the present manuscript, we report unexpected connection between ocln deficiency and behavioral alterations resembling neurodevelopmental and psychiatric disorders. Adolescent, occludin-deficient (ocln^-/-) mice displayed an abnormal growth and neurological phenotype along with deterioration of motor functions as compared to wild-type controls. Moreover, adult ocln^-/- mice exhibited increased hyperactivity, social difficulties, and attention deficits compared to control mice. Among the brain structures, the hippocampus appeared to be most susceptible to ocln deficiency as it exhibited higher expression levels of ocln than both the frontal cortex and striatum. Overall, the observed behavioral alteration patterns in ocln^-/- mice indicated pronounced neurological motor dysfunction and behavioral changes that parallel those seen in attention deficit hyperactivity disorder and autism spectrum disorder. These findings are important for better understanding the role of ocln in neurodevelopmental and psychiatric disorders.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2647450"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction and oxidative stress in Parkinson's disease: mechanisms, biomarkers, and therapeutic strategies.","authors":"Pothu Usha Kiran, Jigar Haria, Reena Rani, Sudhir Singh","doi":"10.1080/21688370.2025.2537991","DOIUrl":"10.1080/21688370.2025.2537991","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by motor symptoms and progressive degeneration of dopaminergic neurons. Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress are major contributors to PD pathogenesis.</p><p><strong>Objectives: </strong>This review explores the molecular mechanisms underlying PD, emphasizing mitochondrial dysfunction and oxidative stress. It also examines genetic and environmental contributors, emerging biomarkers, and future treatment strategies.</p><p><strong>Methods: </strong>An extensive literature review was conducted, focusing on mitochondrial biology, oxidative stress, genetic mutations, and environmental toxins relevant to PD. Investigations into treatment options - including redox therapies, gene therapies, and lifestyle approaches - were also examined.</p><p><strong>Results: </strong>Mitochondrial dysfunction in PD includes disrupted oxidative phosphorylation and elevated reactive oxygen species (ROS). This also affects calcium homeostasis, especially in substantia nigra neurons. Genetic mutations (PINK1, Parkin, DJ-1, LRRK2, GBA) impair mitophagy and antioxidant defenses. Environmental toxins (e.g. MPTP, rotenone) further damage mitochondrial function and contribute to dopaminergic neuron loss. Emerging biomarkers involve measurements of lipid peroxidation and mitochondrial DNA damage. Promising therapeutic strategies include mitochondria-targeted antioxidants (e.g. MitoQ), PINK1-based gene therapy, Parkin activation, ketogenic diet, and exercise-induced mitochondrial biogenesis.</p><p><strong>Conclusions: </strong>Mitochondrial dysfunction and oxidative stress are central to PD pathophysiology. Strategies targeting these mechanisms may slow disease progression. Future research should emphasize combination therapies and early intervention trials, alongside biomarker integration, to enhance clinical outcomes.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2537991"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective activity of bacopaside I encapsulated polymeric nanoparticles against kainic acid-induced excitotoxicity.","authors":"Vini C Sekhar, Sabulal Baby, Prabath Gopalakrishnan Biju, Gayathri Viswanathan","doi":"10.1080/21688370.2025.2582881","DOIUrl":"10.1080/21688370.2025.2582881","url":null,"abstract":"<p><p>Bacopaside I (BM4), a saponin found in <i>Bacopa monnieri</i>, has nootropic, neuroprotective, and anti-depressant properties. Neuroprotective entities generally are impermeable across the brain membrane, and this hassle can be resolved by using drug-encapsulated polymeric nanoparticles (NPs). Epileptic seizures are linked to the increased expression of fractalkine, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors, and mammalian target of rapamycin (mTOR) dysregulation. This study investigated the effect of BM4 encapsulated poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-nanoparticles (BM4NP) in comprehending seizure and its ability to protect brain tissues from kainic acid (KA)-induced excitotoxicity associated neuroinflammation, oxidative stress, and over-expression of seizure markers. The optimal size (87.31 ± 9.2 nm) and zeta potential (-18.8 ± 4.7 mV) of BM4NP resulted in efficient drug loading and release kinetics. Our data demonstrated that BM4NP reduced KA-induced brain tissue damage, by restoring normal nuclear outline and strengthening brain membrane integrity. BM4NP also suppressed the over-expression of fractalkine, AMPA receptors, and mTORC1 signaling and increased antioxidant levels, suggesting it as a therapeutic agent to contain seizures.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2582881"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Centella asiatica</i> phytochemical Madecassoside enhances skin wound healing and protects against UVB-induced keratinocyte damage.","authors":"Tadhi Sucharitakul, Pimngeon Chatkul, Wilasinee Satianrapapong, Apiwan Arinno, Wanapas Wachiradejkul, Suticha Kittayaruksakul, Jaturon Kwanthongdee, Saimai Chatree, Anyamanee Chatsirisupachai, Pawin Pongkorpsakol","doi":"10.1080/21688370.2025.2532229","DOIUrl":"10.1080/21688370.2025.2532229","url":null,"abstract":"<p><p>Madecassoside, one of the main bioactive compounds found in <i>Centella asiatica</i> extract, has long been used in the cosmetic regime for skin care with doubtful effects. The main objectives of this study are to investigate the effects of Madecassoside on skin wound healing, UVB-induced keratinocyte damages, and to search for its pharmacological mechanism. Here, using fully differentiated keratinocyte-like HaCaT cell monolayers as an <i>in vitro</i> model, we found that Madecassoside enhanced wound healing and protected against UVB-induced keratinocyte apoptosis and reduction of cell viability. Indeed, these pharmacological effects of Madecassoside were completely abolished by pretreatment of an intracellular Ca²⁺ chelator (BAPTA), inhibitors of AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and extracellular signal-regulated kinase (ERK). In addition, our Western blotting analyses strongly indicated that Madecassoside-induced ERK phosphorylation was suppressed by pretreatment of BAPTA, inhibitors of AMPK and mTOR signaling. Collectively, these data suggested that Madecassoside promotes wound healing and reduces keratinocyte apoptosis after being damaged by UVB radiation, at least in part, via Ca²⁺/AMPK- and mTOR-dependent ERK phosphorylation.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2532229"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of claudins 6 and 9 in epithelial-mesenchymal transition and the metastatic process.","authors":"Naresh E Diego, Luis F Montaño, Erika P Rendón-Huerta","doi":"10.1080/21688370.2025.2529091","DOIUrl":"10.1080/21688370.2025.2529091","url":null,"abstract":"<p><p>Claudins are essential components of tight junctions, and their abnormal expression is linked to cancer development. Claudin-6 (CLDN6) and Claudin-9 (CLDN9) are claudins whose expression is suppressed post-development but reinduced in various malignancies. This review highlights the distinct yet complementary roles of CLDN6 and CLDN9 during epithelial-mesenchymal transition (EMT) and their contributions to cell migration and invasion in cancer. CLDN9 primarily enhances cell migration by inducing cytoskeletal rearrangement and activating pathways, including MAPK and Tyk2/STAT3. Moreover, CLDN9 overexpression is associated with pseudopodia formation, glycolytic remodeling, and immune evasion. Conversely, CLDN6 is more strongly linked to cell invasiveness and matrix degradation, primarily through the induction of MMPs via the EGFR/mTOR and PI3K/AKT pathways. CLDN6 also plays a role in stemness and therapy resistance in specific cancers. While CLDN6 and CLDN9 can function independently, their co-expression is connected with aggressive tumor behavior and poor prognosis, suggesting a synergistic process that promotes migration and invasion.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2529091"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}