Pathophysiology : the official journal of the International Society for Pathophysiology最新文献

{"title":"Does Heat-Induced Activation of Mast Cells Contribute to Elevated Temperature-Induced Male Infertility?","authors":"Ali Sadek, Yulia Khramtsova, Boris Yushkov","doi":"10.3390/pathophysiology33030049","DOIUrl":"10.3390/pathophysiology33030049","url":null,"abstract":"<p><strong>Background: </strong>The microenvironment of spermatogonial stem cells plays a crucial role in determining their developmental trajectory. Mast cells (MCs) are an important component of this microenvironment and are present along the pathway of sperm production and maturation. Elevated temperature is associated with various disorders of male fertility and its effect on MCs has not been previously studied.</p><p><strong>Methods: </strong>The experiment was conducted on male Wistar rats, which were divided into four groups: intact, control, single, and repeated heat exposure. Morphofunctional and morphometric parameters of MCs were investigated in testes, epididymides, and seminal vesicles. Correlation analysis was performed between MC parameters, ejaculated and epididymal spermatozoa, and testosterone levels.</p><p><strong>Results: </strong>MCs become activated even after a single heat exposure, manifested by increased degranulation. Repeated exposures lead to an increase in MC numbers in the reproductive organs and an enhancement of their functional activity. Testicular MCs exhibit the highest sensitivity to elevated temperature, followed by epididymal MCs. These findings reveal organ-specific differences in MCs responses, which may be explained by the anatomical location of these organs. Correlation analysis revealed a negative relationship between MC morphofunctional parameters and sperm functional characteristics in epididymis and ejaculate, as well as testosterone levels.</p><p><strong>Conclusions: </strong>Heat exposure activates MCs in male reproductive organs, and the changes in their morphofunctional parameters support a potential role in heat-related male reproductive impairment that requires further evidence.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582030","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":"Reply to Amaç, B. Comment on \"Sklifasovskaya et al. Hypertension and Diabetes Cooperatively Drive HSP90 Activation, HSP70 Suppression, and Left Ventricular Interstitial Expansion: Relevance to Maladaptive Myocardial Remodeling. <i>Pathophysiology</i> 2026, <i>33</i>, 19\".","authors":"Anastasia P Sklifasovskaya, Mikhail L Blagonravov, Madina M Azova, Sergey V Kurevlev, Vyacheslav A Goryachev, Sergey P Syatkin, Tatyana Yu Zotova, Daniil Yu Prokofiev","doi":"10.3390/pathophysiology33030047","DOIUrl":"10.3390/pathophysiology33030047","url":null,"abstract":"<p><p>We thank the commentators for their thoughtful and constructive review of our work [...].</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581996","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":"Comment on Sklifasovskaya et al. Hypertension and Diabetes Cooperatively Drive HSP90 Activation, HSP70 Suppression, and Left Ventricular Interstitial Expansion: Relevance to Maladaptive Myocardial Remodeling. <i>Pathophysiology</i> 2026, <i>33</i>, 19.","authors":"Bişar Amaç","doi":"10.3390/pathophysiology33030046","DOIUrl":"10.3390/pathophysiology33030046","url":null,"abstract":"<p><p>We read with great interest the article by Sklifasovskaya et al [...].</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581681","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":"Crinophagy in Pancreatic Beta Cells: From Insulin Granule Turnover to Diabetes Pathogenesis.","authors":"Muralidharan Mani, Thomas F J Martin","doi":"10.3390/pathophysiology33030045","DOIUrl":"10.3390/pathophysiology33030045","url":null,"abstract":"<p><p>Pancreatic β-cells maintain glucose homeostasis through tightly regulated insulin biosynthesis, storage, and secretion. To prevent pathological accumulation of excess or aging secretory granules (SGs), β-cells use crinophagy, a selective lysosomal degradation pathway in which mature insulin-containing granules fuse directly with lysosomes to form hybrid organelles termed crinosomes. Crinophagy was historically considered a simple mechanism for discarding obsolete, aged SGs. The acidic, protease-rich environment of crinosomes is proposed to generate unconventional insulin-derived epitopes through cathepsin-mediated proteolysis and transpeptidation reactions. These cryptic epitopes, which include hybrid insulin peptides (HIPs) resulting from the covalent fusion of insulin fragments with peptides from co-resident granule proteins, are largely absent from the thymic epitope repertoire. This creates a \"peripheral-thymic mismatch\" that allows autoreactive CD4+ T cells to escape central tolerance, ultimately driving β-cell destruction in type 1 diabetes (T1D). Recent studies demonstrate that pharmacological or genetic inhibition of crinophagy reduces crinosome abundance, narrows the pathogenic epitope repertoire, and delays the onset of diabetes in preclinical models. In type 2 diabetes (T2D), a related pathway termed stress-induced nascent granule degradation (SINGD) diverts newly synthesized insulin granules to lysosomes under glucolipotoxic conditions, contributing to insulin depletion and progressive β-cell failure. This review summarizes the current understanding of the molecular mechanisms behind crinophagy. It discusses its two main functions: maintaining physiological quality control and generating pathological antigens. Additionally, the review explores how crinophagy interacts with other cellular stress pathways and highlights new therapeutic strategies aimed at targeting this process to protect pancreatic β-cell function and potentially prevent or delay diabetes.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581720","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":"Pancreatic Hyperenzymemia in Inflammatory Bowel Disease: Clinical Characterization and Outcomes from the European PANDORA Registry.","authors":"Salvatore Crucillà, Asia Berlato, Antonietta Gerarda Gravina, Anneline Cremer, Piotr Eder, Massimo Claudio Fantini, Stefano Festa, Daniela Pugliese, Andreas Blesl, Anna Viola, Chiara Viganò, Sophie Vieujean, Ioannis Koutroubakis, Edoardo Vincenzo Savarino, Lieven Pouillon, Mathieu Uzzan, Pierre Ellul, Marie Truyens, Federico Caldart, Rachele Ciccocioppo, Luca Frulloni, Maria Cristina Conti Bellocchi","doi":"10.3390/pathophysiology33030044","DOIUrl":"10.3390/pathophysiology33030044","url":null,"abstract":"<p><p><b>Background and Aims:</b> Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. <b>Methods</b>: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). <b>Results</b>: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn's disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. <b>Conclusions</b>: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581975","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":"Neuroprotective Potential of Synaptamide in MPTP-Induced Parkinson's Disease.","authors":"Igor Manzhulo, Yuliya Kipryushina, Ekaterina Gromova, Olga Manzhulo, Elena Milkina, Darya Ivashkevich","doi":"10.3390/pathophysiology33030042","DOIUrl":"10.3390/pathophysiology33030042","url":null,"abstract":"<p><strong>Background/objectives: </strong>Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuron loss, α-synuclein pathology, neuroinflammation, and cognitive decline. Synaptamide (N-Docosahexaenoylethanolamine (DHEA)) is an endogenous lipid mediator with documented anti-inflammatory and neurogenic properties, but its effects in PD models remain unexplored. This study aimed to evaluate the neuroprotective potential of synaptamide in a subchronic MPTP-induced mouse model of PD.</p><p><strong>Methods: </strong>Male C57BL/6 mice received MPTP (30 mg/kg/day, i.p., 5 days) with or without synaptamide (10 mg/kg/day, s.c., 13 days). Behavioral tests (open field, Y-maze, elevated plus maze, novel object recognition (NOR)) were performed, followed by immunohistochemical analysis of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra, and Western blotting for α-synuclein, p-α-synuclein, TH, and IL1β in brain homogenates and serum. In vitro Neuro-2a cells were co-treated with MPP⁺ (100 µM) and synaptamide (0.1-10 µM) for cytotoxicity assessment (MTS assay).</p><p><strong>Results: </strong>Synaptamide (10 µM) significantly attenuated MPP⁺-induced cytotoxicity in Neuro-2a cells. In vivo, MPTP caused a marked loss of TH⁺-neurons in the substantia nigra, which was prevented by synaptamide treatment. Importantly, this subchronic MPTP model recapitulates early biochemical alterations (e.g., α-synuclein phosphorylation at Ser129) rather than mature Lewy body pathology, a limitation that should be considered when interpreting these findings. Although no motor deficits or anxiety-like behavior were observed, the NOR test revealed MPTP-induced long-term memory impairment, which was fully restored by synaptamide.</p><p><strong>Conclusions: </strong>These findings suggest that synaptamide may exert effects on pathological processes associated with PD, warranting further investigation into its potential role in combination or supportive therapy for this disease.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582041","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":"A Differentiated SH-SY5Y Model of Hypoxic-Ischaemic Injury Reveals Dynamic Transcriptomic Responses During Reoxygenation.","authors":"Maryam Adenike Salaudeen, Stuart M Allan, Emmanuel Pinteaux","doi":"10.3390/pathophysiology33030043","DOIUrl":"10.3390/pathophysiology33030043","url":null,"abstract":"<p><strong>Background: </strong>Hypoxic-ischaemic brain injury (HI) is a major contributor to neurological deficits following stroke. Understanding what happens to the smallest functional and structural unit of the central nervous system in the face of oxygen and nutrient deprivation is essential to fully comprehend the pathogenesis of diseases and disorders associated with HI, such as ischaemic stroke.</p><p><strong>Aim: </strong>The aim of this study was to develop a robust in vitro tool for initial screening of potential therapeutics and identification of diagnostic markers of brain hypoxic injury.</p><p><strong>Methods: </strong>This study details and validates a comprehensive protocol for modelling HI using differentiated SH-SY5Y neuroblastoma cells (Neuron-like Cells, NLCs). First, we optimized the differentiation process and confirmed the maturity and purity of NLCs via standard molecular markers. The NLCs exhibited functional excitotoxicity, demonstrating a graded cell death response to N-methyl-D-aspartate (NMDA), thus validating their functional application. To simulate HI, we initially optimized the oxygen-glucose deprivation (OGD) treatment using graded concentrations of CoCl₂ (0.125 mM to 2 mM) in glucose-free media. The validated NLCs were then subjected to the refined OGD protocol (1 mM CoCl₂ in glucose-free media) for 3 h, followed by various periods of reoxygenation (1 h, 3 h, 6 h, 12 h, 18 h, and 24 h).</p><p><strong>Result: </strong>Bulk RNA-sequencing revealed a distinct temporal transcriptional response to HI. Injury-associated genes, including heat shock proteins and stress markers, were significantly (<i>p</i> < 0.05) upregulated at 3 h of reoxygenation, peaked at 6 h, and declined thereafter, remaining above baseline at 24 h. Upstream regulator analysis identified IL-1β, TNF-α, and HIF-1α as key drivers during OGD, with additional regulators emerging during reoxygenation. TNF-α and β-oestradiol were consistently identified across time points, while TGF-β1 and NTRK1 became prominent during peak injury and later phases. Analysis of secreted factors showed increased release of inflammatory (TNF-α) and neurotrophic (β-NGF, BDNF, VEGF) mediators with reoxygenation, while maximal cell death occurred at 24 h.</p><p><strong>Conclusions: </strong>This study identifies a transient, time-dependent transcriptional cascade following hypoxic-ischaemic injury, highlighting a critical window for early neuronal response. The model provides a reproducible platform for studying neuronal injury and recovery, and identifies known (TNF-α, IL-β, and HIF-1α), context-specific (NTRK1 and TGF-β) and novel (β-oestradiol) regulators of the injury response with potential relevance for therapeutic targeting.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581729","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":"Revisiting Atopy: The IgE-Dependent Amplification Loop as a Forgotten Driver of Atopic Dermatitis.","authors":"Ryoji Tanei, Yasuko Hasegawa","doi":"10.3390/pathophysiology33020041","DOIUrl":"10.3390/pathophysiology33020041","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is increasingly interpreted through frameworks emphasizing barrier dysfunction, type 2 cytokine signaling, pruritus pathways, and microbial dysbiosis, often relegating IgE-mediated mechanisms to secondary roles. In this narrative review, we synthesize historical, clinical, immunologic, and histopathologic evidence to propose a conceptual model in which IgE-bearing antigen-presenting cells (APCs)-including Langerhans cells, inflammatory dermal dendritic cells, and inflammatory dendritic epidermal cells (IDECs)-participate in an IgE-dependent amplification loop that may contribute to the chronicity of extrinsic (IgE-associated) AD. Evidence from human studies indicates that FcεRI-expressing APCs can acquire environmental allergens through IgE, enhancing antigen uptake and T-cell activation, while mast cells and basophils further reinforce type 2 inflammation through IgE-dependent and IgE-augmented pathways. Although these mechanisms have been described across distinct experimental and clinical contexts, their integration into a unified pathogenic circuit remains hypothesis-driven. We therefore present an interpretive framework that organizes these partially validated mechanisms into a coherent model linking cutaneous sensitization, allergen capture, APC activation, Th2 polarization, and spongiosis formation. This conceptual synthesis aims to reposition IgE-mediated processes within the broader pathophysiology of extrinsic AD and to highlight potential therapeutic implications for targeting IgE-FcεRI signaling and IgE-dependent APC biology.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321466","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":"Pulmonary Squamous Cell Carcinoma Dissemination Through Air Spaces (STAS): Clinicopathologic Findings in Different Tumor Origins.","authors":"Bianca Herrmann, Horia Sirbu, Hayk Kikoyan, Mostafa Higaze, Abbas Agaimy, Arndt Hartmann, Ralf Rieker, Mohamed Anwar Haj Khalaf","doi":"10.3390/pathophysiology33020040","DOIUrl":"10.3390/pathophysiology33020040","url":null,"abstract":"<p><p><b>Background</b>: Spread through air spaces (STAS) is a recognized histologic pattern of invasion associated with poor prognosis in non-small-cell lung cancer (NSCLC), particularly adenocarcinoma. However, its presence in pulmonary squamous cell carcinoma (SCC), whether primary or metastatic, remains largely unexplored. Given the limited available evidence, this study was designed as an exploratory analysis to evaluate the prevalence and potential prognostic significance of STAS in pulmonary SCC. <b>Material and Methods</b>: In this exploratory retrospective study, we analyzed 57 patients who underwent surgical resection for pulmonary squamous cell carcinoma (P-SCC) at the Department of Thoracic Surgery at the University Hospital Erlangen between 2008 and 2020. The cohort included both primary lung SCC and metastatic SCC to the lung from extrapulmonary sites, primarily from ear, nose, and throat (ENT) tumors. Histological slides were reviewed to assess the presence of STAS, as defined by established morphological criteria. The Chi-square test was used to investigate the presence of STAS. Disease-free survival (DFS) and overall survival (OS) was evaluated using Kaplan-Meier analysis, and the prognostic impact of STAS along other variables were assessed using Cox proportional hazards regression. <b>Results</b>: A total of 57 patients with squamous cell carcinoma (SCC), 22 (39%) had primary lung SCC and 35 (61%) had metastatic SCC from head and neck tumours (ENT). Spread through air spaces (STAS) was detected in 20 patients (35%). Disease-free survival (DFS) differed according to primary tumour location (<i>p</i>-value of 0.009), with higher 1-, 3-, and 5-year DFS in patients with primary lung SCC (86.4%, 77.3%, 63.3%) than in those with head and neck SCC (54.3%, 31.4%, 22.2%). DFS was also significantly higher in patients undergoing solitary resections compared with multiple resections (78.6%, 64.3%, 49.5% vs. 33.3%, 6.7%, not estimable; <i>p</i>-value < 0.001). DFS was slightly longer in STAS-negative patients compared with STAS-positive patients (1-, 3-, 5-year DFS: 64.9%, 51.4%, 40.5% vs. 70%, 45%, not estimable), (median DFS 36 vs. 25 months; <i>p</i>-value of 0.776). Overall survival (OS) was significantly longer in patients with primary lung SCC (median OS 125 months) than in those with head and neck SCC (27 months; <i>p</i>-value of 0.039). STAS-negative patients had also a longer OS than STAS-positive patients (median OS 46 vs. 38 months; HR = 1.11, 95% CI 0.56-2.20; <i>p</i>-value of 0.771). <b>Conclusions:</b> STAS was identified in metastatic pulmonary SCC lesions as well as in primary lung SCC, occurring in approximately one-third of cases. However, due to the limited cohort size and the exploratory univariate design of the study, the prognostic significance of STAS could not be definitively established and requires further investigation in larger, adequately powered studies.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321509","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":"Oxidative and Nitrosative Stress in Atopic Dermatitis and Depression: Similarities in Biomarkers and Pathophysiological Mechanisms.","authors":"Dominika Jabłonka, Stefan Modzelewski, Napoleon Waszkiewicz","doi":"10.3390/pathophysiology33020039","DOIUrl":"10.3390/pathophysiology33020039","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, whereas major depressive disorder is a common psychiatric condition with a substantial impact on quality of life; increasing attention has been given to oxidative and nitrosative stress as a potential biological link between these disorders.</p><p><strong>Methods: </strong>This narrative review synthesizes current evidence on molecular biomarkers of oxidative and nitrosative stress in AD and MDD and examines shared mechanisms within the skin-brain axis.</p><p><strong>Results: </strong>Across both conditions, studies consistently report increased markers of lipid peroxidation (e.g., malondialdehyde, 4-hydroxynonenal), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and nitrosative stress, alongside impaired antioxidant defenses, particularly involving glutathione; these alterations are closely associated with chronic inflammation, cytokine signaling, mitochondrial dysfunction, and dysregulation of neuroimmune and hypothalamic-pituitary-adrenal axis pathways.</p><p><strong>Conclusions: </strong>Although the available evidence is heterogeneous and largely based on cross-sectional studies, limiting causal inference, the findings support a biologically plausible link between AD and depression mediated by shared redox pathways and highlight the need for further longitudinal and mechanistic research.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"33 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321500","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}