Tissue BarriersPub Date : 2025-09-24DOI: 10.1080/21688370.2025.2559427
Sahar A Mokhemer, Esraa Mohammed Khairy, Rehab Ahmed Rifaai, Nashwa Fathy Gamal El-Tahawy, Randa Ahmed Ibrahim
{"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":"https://doi.org/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":4.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131972","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}
Tissue BarriersPub Date : 2025-09-03DOI: 10.1080/21688370.2025.2553927
Brittany E Watson, Mihyun L Waugh, Nolan J Foreman, Melissa A Moss
{"title":"Influence of Alzheimer's associated Aβ oligomers and oxidative stress on blood-brain barrier dysfunction.","authors":"Brittany E Watson, Mihyun L Waugh, Nolan J Foreman, Melissa A Moss","doi":"10.1080/21688370.2025.2553927","DOIUrl":"https://doi.org/10.1080/21688370.2025.2553927","url":null,"abstract":"<p><p>Blood-brain barrier (BBB) dysfunction is an early event observed in Alzheimer's disease (AD). Two characteristics of AD brain and brain vasculature contribute to BBB dysfunction: the accumulation of aggregated amyloid-β protein (Aβ) and an increase in oxidative stress. This work uses a BBB model of primary human brain microvascular endothelial cells to investigate the individual and synergistic influence of both pathogenic Aβ oligomers and oxidative stress on BBB transendothelial electrical resistance (TEER), an indicator of barrier integrity. Results indicate that nontoxic, physiological concentrations of Aβ oligomers reduce TEER, while Aβ monomer remains inert. Moreover, introducing mild oxidative stress, which alone does not influence monolayer integrity, exacerbates the effect of Aβ oligomers on TEER within this BBB model. These findings advance the understanding of BBB dysfunction in AD and point toward therapeutic strategies targeting this early event that contributes to a currently irreversible disease.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2553927"},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993252","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}
Tissue BarriersPub Date : 2025-08-30DOI: 10.1080/21688370.2025.2549020
Apoorva, Sunit K Singh
{"title":"Pathogenic breaches: how viruses compromise blood-tissue barriers.","authors":"Apoorva, Sunit K Singh","doi":"10.1080/21688370.2025.2549020","DOIUrl":"https://doi.org/10.1080/21688370.2025.2549020","url":null,"abstract":"<p><p>Blood-tissue barriers (BTBs) are highly specialized, selectively permeable surfaces that separate the circulatory system from delicate tissues and organs. Critical examples include the blood-brain barrier (BBB), blood-retinal barrier (BRB), blood-testis barrier (BTB), and other organ-specific barriers, including the alveolar-capillary interface in the lungs and the glomerular filtration barrier in the kidneys. These barriers regulate the bidirectional transport of nutrients, gases, and waste while restricting pathogens, toxins, and immune cells to maintain physiological balance. Nevertheless, viruses have evolved multiple strategies to circumvent or compromise these barriers, facilitating viral entry, evading immune surveillance, and establishing infection within protected compartments. Neurotropic viruses, including the West Nile virus and Japanese encephalitis virus, impair the blood-brain barrier by disrupting tight junction proteins and cytokine storms. In contrast, respiratory viruses such as influenza and SARS-CoV-2 affect the lung barrier, resulting in alveolar injury and systemic inflammation. Other viruses, such as the Zika virus, affect the BTB and placental barriers, presenting significant risks to fetal development and reproductive health. Such breaches facilitate viral spread, exacerbate tissue damage, and complicate therapeutic interventions. This review provides a comprehensive overview of blood-tissue barrier architecture, function, and mechanisms of viral disruption, highlighting their dual role in protection and susceptibility during viral infections. By elucidating interactions between viruses and blood-tissue barriers, this work highlights emerging research directions to mitigate viral pathogenesis and enhance treatment efficacy for barrier-associated diseases.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2549020"},"PeriodicalIF":4.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970867","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":"Patient-derived 3D nasal spheroids reveal epithelial changes following Dupilumab therapy in CRSwNP: a preliminary report.","authors":"Nadia Lobello, Giovanna Lucia Piazzetta, Corrado Pelaia, Mariaimmacolata Preianò, Nicola Lombardo, Emanuela Chiarella","doi":"10.1080/21688370.2025.2552004","DOIUrl":"https://doi.org/10.1080/21688370.2025.2552004","url":null,"abstract":"<p><p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease associated with epithelial dysfunction and impaired mucosal barrier integrity. Dupilumab, an IL-4 receptor alpha antagonist, has shown clinical efficacy, but its cellular effects on nasal epithelium remain poorly understood. Advanced in vitro models such as 3D spheroid cultures may provide insight into epithelial organization under treatment. We conducted a preliminary study using nasal epithelial cells obtained from three patient groups: CRSwNP treated with Dupilumab for 16 weeks (<i>n</i> = 3), untreated CRSwNP (<i>n</i> = 3), and turbinate hypertrophy controls (<i>n</i> = 3). Cells were isolated by enzymatic digestion and cultured in ultra-low attachment plates using sphere-promoting medium to assess spheroid formation. Observations were performed using phase-contrast microscopy. Due to the limited sample size, data were analyzed qualitatively without statistical testing. Control cells formed compact spheroids, while untreated CRSwNP cells failed to generate structured spheroids, showing only aggregates. Cells from Dupilumab-treated patients produced well-organized spheroids, suggesting improved epithelial organization. Occasional surface movement was observed but not quantitatively assessed. No molecular or ultrastructural assays were performed to confirm mechanistic hypotheses. Our preliminary findings indicate that Dupilumab treatment may be associated with improved epithelial organization in CRSwNP, as shown by spheroid formation in 3D culture. However, these observations are preliminary and based on a small cross-sectional cohort. Future studies should include longitudinal sampling, functional assays, and molecular analyses to confirm mechanisms and validate these results.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2552004"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970945","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":"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":"https://doi.org/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":4.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856505","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}
Tissue BarriersPub Date : 2025-08-13DOI: 10.1080/21688370.2025.2539026
Lubna Therachiyil, Ajaz A Bhat, Shahab Uddin
{"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":4.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849207","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}
Tissue BarriersPub Date : 2025-07-25DOI: 10.1080/21688370.2025.2537992
Carlos de Almeida Barbosa, Luize Kremer Gamba, Rossana Baggio Simeoni, Maria Fernanda Villaça Koch, Marco Andre Cardoso, Ricardo Correa Cunha, Luiz Cesar Guarita-Souza, Julio Cesar Francisco, Beatriz Luci Fernandes
{"title":"Advanced 3D-Printed hydrogel dressings incorporating platelet-rich plasma for accelerated skin repair.","authors":"Carlos de Almeida Barbosa, Luize Kremer Gamba, Rossana Baggio Simeoni, Maria Fernanda Villaça Koch, Marco Andre Cardoso, Ricardo Correa Cunha, Luiz Cesar Guarita-Souza, Julio Cesar Francisco, Beatriz Luci Fernandes","doi":"10.1080/21688370.2025.2537992","DOIUrl":"10.1080/21688370.2025.2537992","url":null,"abstract":"<p><p>The restoration of cutaneous barrier function following deep skin injury remains a critical challenge in regenerative medicine. In this study, we developed a semi-occlusive wound dressing by combining sodium alginate hydrogel with platelet-rich plasma (PRP), using 3D bioprinting technology to ensure structural precision and consistent bioactive distribution. This hybrid system was engineered to support tissue repair by enhancing re-epithelialization, stimulating angiogenesis, and promoting organized extracellular matrix remodeling. In vivo experiments using full-thickness skin wounds in mice revealed that the PRP enriched dressings accelerated wound contraction and epithelial closure, especially during the early stages of healing. Histological analyses showed increased formation of capillary-like structures, a shift toward type I collagen dominance, and reduced inflammation in PRP treated groups. These effects point to a more mature and functional regenerative process. Importantly, the combination of PRP with a bioprinted hydrogel scaffold not only facilitated structural recovery but also contributed to restoring the physiological integrity of the skin barrier. This approach offers a low-cost and adaptable platform with strong translational potential for the treatment of complex skin wounds.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2537992"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708997","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":"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":"https://doi.org/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":3.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691684","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}
Tissue BarriersPub Date : 2025-07-21DOI: 10.1080/21688370.2025.2532195
Manar Fouli Gaber Ibrahim, Elshymaa A Abdel-Hakeem, Heba A Shawky, Soha Abdelkawy Abdelwahab, Sahar A Mokhemer
{"title":"Effect of local versus systemic exosomes administration on both testes in rat model of testicular ischemic reperfusion injury: shedding light on blood testis barrier.","authors":"Manar Fouli Gaber Ibrahim, Elshymaa A Abdel-Hakeem, Heba A Shawky, Soha Abdelkawy Abdelwahab, Sahar A Mokhemer","doi":"10.1080/21688370.2025.2532195","DOIUrl":"https://doi.org/10.1080/21688370.2025.2532195","url":null,"abstract":"<p><p>Exosomes<sup>,</sup> (EXs) competence in reproductive medicine has been proven, particularly in cases of ischemia reperfusion (IR) injury models. Testicular torsion is a major clinical concern affecting male fertility and results in ischemic reperfusion injury. To the best of our knowledge, up to date, comparative studies using different routes of EXs application have not been investigated. Thus, we aimed to investigate the effect of local versus systemic EXs administration on both testes; ipsilaterally and contralaterally and to explore the involved underlying mechanisms. Rats were allocated into four groups; the control, the ischemia reperfusion group (IR group) in which unilateral testicular IR was performed, then rats were subdivided equally into two subgroups; IR-ipsi group; in which the ipsilateral testes were investigated and the IR-contra group in which the contralateral testes were examined. Group III and group IV in which unilateral IR was performed, then injected intravenously or intratesticularly consequently with EXs and finally divided in to two subgroups IR-ipsi and IR-contra. The results revealed that testicular IR resulted in functional and structural disorders with reduction in serum testosterone and sperm indices. Interestingly, both testes showed structural histopathological changes and defects in blood testis barrier. There was also an increase in oxidative stress, inflammatory, and apoptosis markers. EXs administration improved the affected parameters probably via modulation of TLR4/MyD88/NF-κB signaling pathway. In conclusion, EXs defended against testicular IR injury. Intratesticular administration had better effects on the ipsilateral testes, whereas Intravenous route had more obvious better effects on the contralateral ones.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2532195"},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675827","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":"<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":"https://doi.org/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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>/AMPK- and mTOR-dependent ERK phosphorylation.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2532229"},"PeriodicalIF":3.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643628","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}