Tissue Barriers最新文献

{"title":"Involvement of vimentin intermediate filaments in overcoming tissue barriers during cancer cell dissemination.","authors":"Anna O Zholudeva, Ekaterina A Kozlova, Natalya A Gloushankova, Antonina Alexandrova","doi":"10.1080/21688370.2026.2689473","DOIUrl":"https://doi.org/10.1080/21688370.2026.2689473","url":null,"abstract":"<p><p>The ability to overcome numerous tissue barriers during metastasis is a characteristic feature of tumor cells. This ability is acquired during tumor progression and represents a significant challenge for the development of therapeutic strategies. The intermediate filament protein vimentin is an important regulator of the cellular mechanisms that enable overcoming of tissue barriers. While vimentin was previously considered an activator of cell migration, raising hopes of halting metastasis by suppressing its expression, recent data indicate that vimentin's role in regulating tumor cell spreading is far more complex, and in some cases, vimentin suppression can stimulate migration. In this review, we analyze the latest data regarding the involvement of vimentin intermediate filaments in regulation of tumor cell migratory plasticity and examine the key cellular mechanisms involved in this regulation. Knowledge of these mechanisms is important for understanding the regulation of metastasis processes.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2689473"},"PeriodicalIF":3.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/21688370.2026.2634592","DOIUrl":"https://doi.org/10.1080/21688370.2026.2634592","url":null,"abstract":"","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2634592"},"PeriodicalIF":4.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonists of the N-cadherin/Fibroblast growth factor receptor tyrosine kinase complex.","authors":"Orest W Blaschuk","doi":"10.1080/21688370.2025.2532160","DOIUrl":"10.1080/21688370.2025.2532160","url":null,"abstract":"<p><p>This review describes similarities between the biological actions of cell adhesion molecule antagonists and pan-growth factor receptor tyrosine kinase (GF-RTK) antagonists. In particular, the biological consequences of the interaction between the cell adhesion molecule, neural (N)-cadherin (CDH2) and the fibroblast GF-RTK (FGF-RTK) are discussed. Intercellular adhesion mediated by N-cadherin stimulates FGF-RTK activity triggering intracellular signaling pathways (<i>e.g</i>. PI3/Akt/mTOR pathway) that regulate various morphogenetic processes (<i>e.g</i>. apoptosis). Antagonists of either N-cadherin or GF-RTKs modulate these processes. N-cadherin antagonists can be regarded as a previously unappreciated class of FGF-RTK inhibitors. These antagonists, similar to GF-RTK antagonists should be capable of serving as therapeutics for treating a variety of fibrotic diseases and cancers.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2532160"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609712","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":"Nanoparticle-based strategies for overcoming the blood-brain barrier in CNS disorders and brain cancer: precision diagnostics and therapeutics for Alzheimer's, Parkinson's, multiple sclerosis, and glioblastoma.","authors":"Hossein Feyzbakhsh","doi":"10.1080/21688370.2025.2599564","DOIUrl":"10.1080/21688370.2025.2599564","url":null,"abstract":"<p><p>Nanoparticle (NP)-based technologies are transforming the management of central nervous system (CNS) disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and brain cancer (BC), glioblastoma, by surpassing the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). This review integrates NP approaches, comprising organic (e.g. liposomes, polymeric NPs), inorganic (e.g. gold, iron oxide), carbon-based, and hybrid systems, to overcome disease-specific barriers. In AD, superparamagnetic iron oxide NPs (SPIONs) and gold NPs (AuNPs) improve amyloid-beta plaque and tau protein detection, while liposomes precisely deliver anti-amyloid drugs. For PD, dopamine-loaded liposomes and cerium oxide NPs reinstate dopaminergic function and decrease oxidative stress, with improved motor outcomes. In MS, PEGylated liposomes and PLGA NPs regulate autoimmune responses, inducing remyelination and attenuating neuroinflammation. For BC, dendrimers and magnetic NPs facilitate targeted chemotherapy delivery across the BBB/BBTB, improving glioblastoma treatment outcomes. We compare NP types critically based on physicochemical characteristics, efficacy, toxicity, and clinical translation potential, highlighting gaps in long-term safety and scalability. Challenges like NP toxicity and regulatory complexities are discussed, suggesting biocompatible designs and standardized FDA/EMA pathways. By consolidating diagnostic and therapeutic innovations, this review outlines a roadmap for NP-based precision medicine, paving the way for clinical translation and better patient outcomes in CNS disorders and brain cancer.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2599564"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701871","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":"The oral mucosal barrier: a dynamic gateway in oral and systemic health.","authors":"Yuan Xin, Hu Lei","doi":"10.1080/21688370.2025.2610035","DOIUrl":"10.1080/21688370.2025.2610035","url":null,"abstract":"<p><p>The oral mucosal barrier, the primary entry point for essential substances (water, food, air), is crucial for oral and systemic health. Comprising a salivary gel layer, commensal microbiota, stratified epithelia, underlying connective tissues, and immunocompetent cells, this complex interface orchestrates selective defense against pathogens and physical and chemical factors while facilitating the absorption of nutrient and bioactive compound. Disruption of this barrier is associated with oral pathologies (e.g. periodontitis) and systemic dysfunction, including cardiovascular, neurodegenerative, and metabolic diseases, underscoring its significance as a key determinant of systemic health. Although the etiology is multifactorial, the precise mechanisms linking oral mucosal barrier disruption to distant organ dysfunction remain incompletely characterized. Consequently, elucidating the underlying molecular networks and cross-organ communication pathways is imperative for oral and systemic health maintenance, as well as development of novel therapeutic strategies target oral and systemic diseases. This review synthesizes recent advances in understanding the molecular architecture of the oral mucosal barrier, explores its local and systemic regulatory networks, and evaluates emerging innovations in barrier-targeted precision medicine approaches.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2610035"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906882","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":"Placental infection by SARS-CoV-2: exploring alternative entry pathways.","authors":"Carolina Lumi Tanaka Dino, Barbara Maria Cavalli, Carolline Konzen Klein, Felipe Paes Gomes da Silva, Nicolas Henrique Borges, Ana Catharina Joaquim, Thiago Rodrigues Dos Santos, Natan de Araújo, Lucas Baena Cartens, Ana Clara Simões Flórido Almeida, Seigo Nagashima, Caroline Busatta Vaz de Paula, Cleber Machado-Souza, Lucia de Noronha, Meri Bordignon Nogueira","doi":"10.1080/21688370.2025.2585246","DOIUrl":"10.1080/21688370.2025.2585246","url":null,"abstract":"<p><p>The placenta possesses several structural and immunological barriers against viral infections, the SARS-CoV-2 detection in placental tissues has raised concerns regarding possible alternative viral entry mechanisms beyond the canonical ACE2/TMPRSS2-mediated pathway. In this context, the present study evaluated the immunohistochemical expression patterns of ADAM17, Cathepsin L, Clathrin, ACE-2, Furin, NRP-1, and TMPRSS2-molecules involved in SARS-CoV-2 placental entry pathways - as well as the detection of viral RNA by RT-qPCR in paraffin-embedded samples. The study included 75 paraffin-embedded placental samples (decidua and villi) collected after spontaneous placental delivery at birth from patients who tested positive for COVID-19 (COVID-19 Group), and 19 paraffin-embedded control placental samples collected prior to the COVID-19 pandemic (NON-COVID-19 Group). A statistically significant reduction in NRP-1 expression was observed in the COVID-19 group decidua (<i>p</i> < 0.001), including in RT-qPCR - positive samples (<i>p</i> = 0.001), regardless of comorbidities or underlying conditions. A statistically significant reduction in Clathrin expression was also found in the decidual samples of the COVID-19 group and in RT-qPCR - positive samples (<i>p</i> = 0.05and 0.013, respectively), while Cathepsin L expression was significantly increased in the placental villi of the COVID-19 group (<i>p</i> < 0.001) and in RT-qPCR - positive samples (<i>p</i> = 0.005). These findings may contribute to a better understanding of the mechanisms underlying SARS-CoV-2 interaction with the placenta, possibly through auxiliary and/or endocytic entry pathways, and may support future investigations into the impact of these alterations in the context of maternal SARS-CoV-2 infection.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2585246"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640178","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":"Structural and functional insights of the podocyte slit diaphragm complex.","authors":"Abrar H Qadri, Jyotsana Prajapati, Dagumati Praghna, Aditi Sinha, Anil K Pasupulati","doi":"10.1080/21688370.2025.2575198","DOIUrl":"10.1080/21688370.2025.2575198","url":null,"abstract":"<p><p>Glomerular podocytes, specialized epithelial cells, are central to the filtration function of vertebrate kidneys. Through their interdigitating foot processes, podocytes provide epithelial coverage to capillaries. They maintain selective filtration by allowing water, ions, and small solutes to filter while retaining proteins and larger molecules in the blood. The slit diaphragm (SD), a specialized junction between podocyte foot processes, along with glomerular basement membrane (GBM) and fenestrated endothelium, serves as a glomerular filtration barrier (GFB). Injury to GFB, such as loss of SD integrity and foot process effacement, compromises permselectivity and results in proteinuria. The SD consists of junctional proteins (nephrin, Neph1), adaptors (podocin, CD2AP), and channels (e.g. TRPC6), which assemble into a molecular sieve and a dynamic signaling hub. Monogenic mutations and resultant structural defects in SD components perturb podocyte filtration function, leading to proteinuria, nephrotic syndrome, and focal segmental glomerulosclerosis. This review summarizes structural and functional insights into SD architecture and emphasizes advances from biochemical, biophysical, and high-resolution imaging approaches. We particularly discuss the role of intrinsically disordered regions in mediating oligomerization and protein - protein networks within the SD. Emerging Cryo-EM studies further provide new perspectives on the stoichiometry of Nephrin - Neph1 complexes and their implications for SD ultrastructure. Finally, we outline unresolved questions regarding SD composition, assembly, and signaling, proposing how integrative structural biology may illuminate mechanisms underlying proteinuric kidney diseases.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2575198"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309368","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":"Concordance of claudin-18.2 expression in biopsy, resection, and recurrent specimens: implications for zolbetuximab therapy in pancreatic ductal adenocarcinoma.","authors":"Daisuke Kyuno, Kazuhiko Yanazume, Akira C Saito, Yusuke Ono, Tatsuya Ito, Masafumi Imamura, Makoto Osanai","doi":"10.1080/21688370.2025.2535047","DOIUrl":"10.1080/21688370.2025.2535047","url":null,"abstract":"<p><p>Claudin-18.2 is a promising therapeutic target for gastrointestinal cancer. However, its expression pattern in pancreatic ductal adenocarcinoma, especially the concordance between biopsy and resection specimens, is unknown. This study aimed to evaluate the consistency of claudin-18.2 positivity across different specimen types using the clinically validated antibody clone 43-14A employed in ongoing zolbetuximab trials. Immunohistochemical analysis for claudin-18 was conducted on 211 resected pancreatic cancer tissues, 133 matched preoperative biopsy samples, and 60 samples from recurrent lesions. The concordance between the biopsy and resection specimens was 92.5% using a 75% staining threshold. However, this high concordance likely reflects the large proportion of claudin-18.2-negative cases, as the biopsy sensitivity for detecting claudin-18.2-positive tumors was only 54.6%. This raises concerns about underdiagnosis and suggests that biopsy alone may miss patients eligible for zolbetuximab therapy. Receiver operating characteristic analysis showed that lowering the threshold to 20% in biopsy samples improved the sensitivity to 100%. However, patients meeting this threshold would still not qualify for therapy under the current trial criteria, highlighting a potential clinical dilemma. Claudin-18.2 expression was generally preserved in recurrent lesions (83.3% concordance with primary tumors), although reductions were noted in local recurrence and liver metastasis. These findings suggest that although biopsy-based assessments may be a practical initial tool, they should be interpreted with caution. Confirmatory studies on resection specimens using the same clinical trial protocol may be necessary to ensure the accurate identification of patients eligible for claudin-18.2-targeted therapy.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2535047"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691684","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":"Claudins in ovarian cancer: emerging biomarkers and therapeutic targets.","authors":"Lubna Therachiyil, Ajaz A Bhat, Shahab Uddin","doi":"10.1080/21688370.2025.2539026","DOIUrl":"10.1080/21688370.2025.2539026","url":null,"abstract":"<p><p>Tight junctions (TJ) comprise protein complexes that help with the movement of ions and molecules through the paracellular pathway, thus maintaining both epithelial and endothelial integrity. The TJ proteins are diverse and include claudins, occludins, tricellulins, cingulins, and junctional adhesion molecules (JAM). Claudins are transmembrane proteins that serve as critical components of TJs in epithelial and endothelial cells. The human genome comprises 23 claudin genes, with 27 transmembrane domains recognized in mammals. Ovarian cancer (OC) is the most lethal form of all gynecologic malignancies worldwide, characterized by poor prognosis and a recurrence rate of up to 75%. In OC, several claudins are overexpressed relative to normal ovarian tissue. These elevated expression observed among OC subtypes indicates their potential utility as diagnostic biomarkers. Claudins represent potential targets for innovative therapeutic strategies. Though their exact involvement in OC is still not well understood, they are believed to be crucial for cancer invasion and therapy resistance. Recent studies show that claudins are involved in the EMT pathway and ERK, enlightening the effect of claudins in drug resistance. Clostridium perfringens enterotoxin (CPE) demonstrates potential as a therapy targeting claudins, specifically claudin-3 and -4, which serve as receptors for this toxin. Despite these advancements, challenges remain in comprehensively understanding claudin functions and in the development of effective claudin-targeted therapies. This review consolidates existing knowledge regarding claudins in OC, focusing on their expression patterns, biological functions, diagnostic and prognostic significance, and therapeutic implications. A thorough understanding of claudins in OC establishes a basis for enhancing diagnostic, predictive, and therapeutic approaches, which may result in improved therapy outcomes.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2539026"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849207","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":"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}