Search Results (2,274)

Psoriasis is a chronic inflammatory autoimmune skin disease for which no standardised and reliable molecular biomarkers of disease course or activity are currently available. Here, we aimed to identify serum biomarkers of psoriasis. Serum samples from 40 patients with psoriasis and 40 healthy volunteers were analysed using ELISA and Proximity Extension Assay proteomics. ELISA revealed significantly increased serum levels of AGO2 and APOA1 in psoriatic patients versus controls, with a strong association between APOA1 and psoriasis (OR = 20.72, 95% CI of 4.57–93.87, p = 0.000137). Targeted serum proteomics additionally identified 35 differentially expressed proteins, including well-known psoriasis drivers (e.g., top upregulated IL17A and SERPINB4). The most downregulated was adrenomedullin (ADM, FC = −10.12). For 14 altered proteins, no previous direct associations with psoriasis were reported. Among them, DEFB103A_DEFB103B and DSG3 showed the best discrimination between psoriasis and control samples, while SERPINB4 correlated with psoriasis severity. APOA1, DEFB103A_DEFB103B, and DSG3 emerge as novel candidate circulating psoriasis biomarkers, and SERPINB4 as a biomarker of psoriasis severity. The functional role of DSG3 and other newly identified proteins (ACRV1, HAO1, ADH4, GPD1, GFER, PTGES2, DSG3, AFAP1L1, GALNT3, RASGRP2, MAP2K6, LXN, NBEAL2, and VPS54) in psoriasis requires further studies. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric burden, but longitudinal data on incident psychiatric outcomes remain limited. This study aimed to evaluate incident psychiatric disorders in adults with HS compared with matched non-HS controls and to assess sex-specific risk. Methods: We conducted a retrospective propensity score–matched cohort study using the TriNetX Global Collaborative Network. Adults with at least two HS diagnoses and no prior psychiatric diagnosis were compared with non-HS controls with repeated general health examination encounters and no psychiatric history. Time-to-event analyses estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses used a 30-day lag and restriction to the most recent 5-year period. Results: After matching, 37,964 pairs were retained for the primary individual-outcome analysis. Median follow-up was shorter in the HS cohort than in matched controls (844 vs. 1505 days). HS was associated with increased risk of any psychiatric disorder (12.3% vs. 5.8%; HR 3.17, 95% CI 3.01–3.34) and severe psychiatric illness (0.6% vs. 0.1%; HR 6.70, 95% CI 4.77–9.41). Elevated risks were observed for bipolar/manic disorders, personality disorders, substance use disorders, psychotic disorders, suicidal ideation, depression, eating disorders, anxiety, and insomnia/parasomnia. Women had higher hazards of depression and anxiety, whereas men had higher hazards of substance use disorders; insomnia/parasomnia showed a nominal association with higher hazard in men. Conclusions: In this observational EHR-based study, HS was associated with broad incident psychiatric morbidity. These findings support consideration of proactive mental health assessment and integrated dermatologic–psychiatric care in patients with HS. Full article

Bisphenol A (BPA) is a common industrial chemical primarily used in the manufacture of plastics, and it has been found in more than 90% of people worldwide. As an endocrine disruptor, BPA can impair reproduction, development, immunity, metabolism, and cognition; it also disturbs immune balance and thus fosters chronic inflammation. A number of population-based studies have indicated a link between environmental BPA exposure and atopic dermatitis (AD). Nevertheless, the detailed molecular pathways connecting BPA to AD remain poorly understood. AD is the leading chronic recurrent inflammatory skin disorder, characterized by severe itching and repeated eczema-like lesions. Its prevalence is roughly 13% among children and 5% among adults, and its global incidence continues to rise, imposing heavy health and economic burdens on societies. To clarify whether and how BPA may promote or worsen AD, we carried out a comprehensive computational study that integrated network toxicology, transcriptomic data, machine learning, molecular docking, and molecular dynamics simulations. From the CTD, ChEMBL, and SwissTargetPrediction databases, we collected 5701 potential BPA targets; from GeneCards and OMIM, we obtained 3270 genes linked to AD. The overlap between these two gene sets gave a group of common candidate genes. Enrichment analyses using GO and KEGG showed that these common genes were significantly overrepresented in the PI3K-Akt signaling pathway, Th17 cell differentiation, and the JAK-STAT signaling pathway—all central to immune and inflammatory regulation. We then built a protein–protein interaction (PPI) network by submitting the common genes to the STRING database and employed Cytoscape to extract hub genes from that network. By integrating human AD transcriptomic profiles with the hub genes and applying two machine learning techniques (LASSO and SVM), we identified six core toxic targets of BPA in AD: TIGIT, JAK3, IL22, S100A8, CCL2, and FCER1G. These six targets fall into two main functional categories: immune dysregulation and inflammatory cell infiltration. Subsequent molecular docking and molecular dynamics simulation experiments confirmed that BPA binds well to all six targets and can form stable complexes with them. Collectively, our findings offer a preliminary experimental foundation for future investigations into the pathogenesis of BPA-induced AD and provide important molecular evidence for understanding how environment–gene interactions contribute to complex inflammatory skin diseases such as AD. Full article

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes. Full article

Background and Clinical Significance: Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum, most commonly associated with inflammatory bowel disease or haematologic disorders. Its occurrence in patients with solid malignancies is uncommon. PPG in an oncologic setting poses diagnostic and therapeutic challenges because systemic immunosuppressive therapy, wound care, and ongoing chemotherapy must be carefully balanced; Case Presentation: We report the case of a Japanese man in his 50s with stage IVB rectal adenocarcinoma who developed rapidly progressive peristomal ulceration clinically consistent with PPG around a colostomy 12 weeks after initiation of panitumumab-containing systemic chemotherapy. The diagnosis was made on clinical grounds and was strongly supported by the clinical morphology, exclusion of major mimickers, and response to systemic corticosteroid therapy, although histopathological confirmation was not obtained. Because existing diagnostic criteria for pyoderma gangrenosum are not specifically designed for peristomal disease, they were used as supportive rather than definitive diagnostic tools. Skin biopsy was avoided due to the risk of pathergy at the peristomal site. Superficial cultures were not obtained because frequent cleansing and faecal contamination were likely to compromise diagnostic accuracy. To minimise mechanical pathergy, the stoma appliance was changed from a one-piece soft convex system to a two-piece flat system. Multidisciplinary management, including systemic corticosteroids, meticulous stoma care, and selective ultrasonic debridement, resulted in complete epithelialisation by Week 26. Chemotherapy was temporarily withheld during the active inflammatory phase and later resumed. Despite successful control of the peristomal ulceration, the patient died from progressive malignancy at Week 34; Conclusions: This case highlights the clinical challenge of balancing immunosuppressive therapy for clinically suspected PPG with ongoing oncologic treatment. Mechanical pathergy related to stoma appliance use was considered a more likely precipitating factor than chemotherapy alone, although panitumumab may have contributed to impaired cutaneous repair. Close collaboration among dermatologists, oncologists, surgeons, WOC nurses, and family caregivers is essential for multidisciplinary decision-making in complex oncologic settings. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the most common chronic liver disorder worldwide. Once started with hepatic steatosis, it can progress to metabolic dysfunction–associated steaohepatitis (MASH), cirrhosis, and even hepatocellular carcinoma. Insulin resistance is a major driver of hepatic lipogenesis in this disease context. Gut barrier dysfunction also contributes to the progression to MASH by allowing bacterial lipopolysaccharide (LPS) to breach into the hepatic tissues. Amphibian skin secretion peptides (ASSPs) are therefore of particular interest, given their combined metabolic and antimicrobial activities. Some ASSPs enhance glucose-stimulated insulin secretion and GLP-1 release, whereas others attenuate LPS-driven inflammatory signaling. This review introduces these ASSPs with a focus on their insulinotropic/incretinotropic and immunomodulatory activities. Also, in the latter part, pharmaceutical strategies to improve blood circulation time and structural stability would be discussed. Full article

The skin serves as the body’s first line of defense against environmental threats, acting as a barrier between external aggressors and internal systems. Current evidence regarding the roles of sulfur dioxide (SO₂) in biology and medicine is limited. Environmental pollutants, including SO₂, can increase the production of reactive oxygen species in the skin, leading to oxidative damage that may worsen various dermatological conditions. Endogenous SO₂, proposed as the fourth member of the gasotransmitter family, functions as a biological signaling molecule. It is generated in various human skin cells, including vascular smooth muscle cells, endothelial cells, mast cells, keratinocytes, macrophages, adipocytes, fibroblasts, dermal immune cell population, etc, where it performs multiple functions at physiologically relevant concentrations. Endogenous SO₂ plays a crucial role in regulating cell signaling and maintaining skin homeostasis through its antioxidant, anti-inflammatory, and cytoprotective effects. Abnormal generation and metabolism of SO₂ are linked to several critical processes in the skin, including vascular biology, immune response, cell proliferation, pigmentation, malignancy, protective barriers, senescence, and resistance to stress. This paper provides a narrative review of the significant roles of SO₂ in skin health and disease. A comprehensive understanding of the complex molecular effects and mechanisms mediated by SO₂ in human skin, along with the development of gas therapy, will be essential for translating fundamental research into clinical applications. Full article

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic features, characterized by painful nodules, abscesses, and sinus tracts. Pro-inflammatory cytokines may serve as biomarkers of disease severity, inflammatory burden, and therapeutic response. The aim of this article is to systematically review the current evidence on serum concentrations of pro-inflammatory cytokines in patients with HS and to evaluate their potential utility as biomarkers of disease activity and personalized treatment guidance. Materials and Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. A literature search was performed in PubMed, Embase, and Scopus, with Google Scholar used as a supplementary source. The search included English-language publications from 2015 to 2026. The following keywords were used in combination: “cytokines”, “serum”, “hidradenitis suppurativa”, and “markers”. In addition, reference lists and citations of eligible full-text articles were manually screened. Eligible studies for inclusion were peer-reviewed, original human studies reporting serum cytokine levels in patients with HS. Reviews, meta-analyses, case reports, editorials, letters, in vitro and animal studies, conference abstracts without the full text available, non-serum studies, and thematically unrelated publications were excluded. Results: Database searches identified records in PubMed, Embase, Scopus, and Google Scholar, of which three PubMed studies met the inclusion criteria. Manual screening of reference lists and citations identified three additional eligible publications. Overall, six studies were included in the final qualitative synthesis. The included studies reported elevated serum levels of key inflammatory mediators, including IL-17A, IL-6, IL-1β, IL-23, IL-18, and soluble TNF receptors, in patients with HS compared to healthy controls. Several cytokines were associated with disease severity, and selected markers showed changes during biologic treatment. Stratification into immunological endotypes based on cytokine profiles and clinical features was also proposed. Conclusions: Pro-inflammatory cytokines, especially those involved in the IL-1β–IL-17 axis, show potential as biomarkers of disease severity and treatment response in HS. Their assessment may support future personalized therapeutic strategies. However, current evidence remains limited by small study numbers and methodological heterogeneity. Further large-scale prospective and longitudinal studies are required before serum cytokine profiling can be implemented in routine clinical practice. Full article

Background: Allergic contact dermatitis (ACD) is a common inflammatory skin disease and patch testing (PT) remains the gold standard for its diagnosis; however, PT interpretation is time-consuming and prone to inter-observer variability. Growing advances in digital imaging and artificial intelligence (AI) have encouraged the development of automated PT evaluation systems. This review aimed to summarize the use of deep learning networks (DNNs) and image-preprocessing techniques for PT classification. Methods: A literature review was conducted to identify original research published between 2020 and 2025 that applied deep learning algorithms to PT image analysis. Included studies were assessed with respect to model architecture, dataset characteristics, preprocessing strategies, and diagnostic performance. Results: Six original studies employing deep learning for PT image classification met the inclusion criteria. They employed a range of architectures, including YOLOv5x, EfficientNetB0, Xception, and custom CNN models. Reported diagnostic performance varied, with accuracy values ranging from 90% to 99.5%, F1-scores from 0.37 to 0.98, and AUROC values up to 0.94. Despite promising results, models remain unreliable for ICDRG grading, especially for severe reactions, and methodological variability in dataset composition, imaging conditions, preprocessing pipelines, and classification tasks limits comparability across studies. Conclusions: Deep learning shows promise for automated PT interpretation, but further standardized and multicenter studies with detailed preprocessing protocols and comprehensive ICDRG grading are required for clinical implementation. Full article

The primary route of SARS-CoV-2 entry is via respiratory epithelium. However, many COVID-19 patients developed dermatological lesions, and SARS-CoV-2 RNA has been detected in the patients’ skin. Inflammatory skin diseases, psoriasis and atopic dermatitis (AD), significantly increased the risk of COVID-19. To evaluate the potential role of skin in SARS-CoV-2 host interactions, we utilized 3D human skin organoids (HSO) generated from human epidermal keratinocytes, as well as neonatal skin explants. HSO were treated with cytokines involved in acute and chronic skin inflammation and cytokine storm in severe COVID-19 disease: TNF-α, IL-6, IL-1β, and IFN-γ, individually and in combination. HSO were also treated with Th1 (TNF-α + IL-17) and Th2 (IL-4 + IL-13) cocktails inducing pro-psoriasis and pro-AD HSO changes, respectively. All individual cytokines, and especially their combinations, elevated the expression of ACE2 and TMPRSS2 at mRNA/protein levels. The Th2 cocktail induced only TMPRSS2, the Th1 cocktail predominantly induced ACE2. Topically applied Spike-pseudotyped lentiviral Tomato reporter, which binds ACE2 similarly to SARS-CoV-2, successfully transduced control and cytokine-treated HSO as well as neonatal skin explants. Cytokine treatment, especially TNF-α + IL-6 + IL-1β + IFN-γ and the Th1 cocktail, significantly increased viral entry. Transcriptomic analysis further revealed partial overlap between gene expression signatures induced by Spike-mediated entry in inflamed HSO and those observed in lung tissue from COVID-19 patients, supporting the biological relevance of skin models. Together, these findings demonstrate that inflammation may transiently alter the permissiveness of human skin to SARS-CoV-2 entry, suggesting that the skin may represent a previously underappreciated, although likely limited, interface in viral- host interactions. Full article

Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article

Background—Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disorder—and evidence regarding relative impact of treatments thereof is currently scant. Objective—We aimed to systematically review and narratively synthesize comparative interventional therapies for GPP and secondarily explore their relative effectiveness through exploratory network meta-analyses (NMAs). Methods—Comprehensive searches were performed in PubMed and EMBASE to identify comparative interventional studies that investigated the impact of biologics in GPP. Bayesian NMAs were conducted only for exploratory analyses. Results—Eleven studies met our inclusion criteria and data from 4 of the 11 were used for NMAs. Methodological heterogeneity was evident; the various biologics demonstrated effectiveness in treating GPP. Inhibitors of interleukin (IL)-36 (e.g., spesolimab) resulted in rapid pustular clearance within one week and sustained reductions in flare occurrence. Inhibitors targeting IL-17, IL-23, TNF, and IL-12/23 also demonstrated high response rates, durable disease control, and improvements in quality of life among diverse patient populations. Results from our exploratory NMAs revealed patterns of relative effectiveness with IL-17 and IL-36 inhibitors that are consistent with the existing literature. However, methodological limitations across the four studies deterred us from making conclusive inferences. Conclusions—Biologic therapies provide significant clinical benefit in patients with GPP. Our narrative syntheses highlight the need for future quantitative syntheses. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

Background: Squalene is a key sebum lipid that plays an important role in skin barrier function, suppleness, and antioxidant protection. Age-related or disease-associated reductions in squalene levels—for example, in atopic dermatitis—reduce skin resilience and increase susceptibility to environmental stressors. However, its oxidation products can have inflammatory, comedogenic, and pro-aging effects on the skin, which is why adequate stabilization is essential when used in topical formulations. Objective: Therefore, identifying sustainable sources of stable squalene with beneficial skin-care properties is of considerable interest. Methods: This review employed an application-focused literature search and comparative analysis of established and new squalene sources, evaluating chemical composition, manufacturing processes, stability, and biological effects following topical applications based on predefined analytical criteria across peer-reviewed studies. Results: Silphium oil appears to be a promising novel source of highly concentrated, sustainable, and stable squalene with potential skin-conditioning properties at concentrations typically used in cosmetic products (2.1–12.6%) while preliminary formulation tests indicate emulsifiability even at concentrations up to 15%. It contains over 3% squalene, a fatty acid profile with over 66% PUFA, and negligible levels of oxidation byproducts (hexanal < 3 ppm) even after years of storage in various types of packaging. Although independent validation and broader comparative studies are limited, these results reveal new possibilities for the use of previously underutilized plant sources in skin care applications. Full article