Search Results (1,960)

Chronic inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, are systemic immune-mediated disorders driven by dysregulated immune responses. The gut–skin axis is a bidirectional network linking intestinal microorganisms, their metabolites, and host immunity. It connects microbiome composition and function with systemic inflammation and cutaneous pathology, shaping disease-specific mechanisms such as Th2/IL-4/IL-13-mediated barrier dysfunction in AD and Th17/IL-23/IL-17-driven hyperproliferation in psoriasis. Microbiota-derived metabolites, including short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, and bile acid-dependent FXR/TGR5 signaling, modulate immune homeostasis and epithelial integrity. Gut dysbiosis, impaired metabolite production, and barrier dysfunction disrupt regulatory networks, amplifying inflammation. Microbiota-targeted interventions, including probiotics, synbiotics, postbiotics, and precision nutrition, may serve as adjunctive therapies, although further well-controlled clinical studies are needed. Integrating multi-omics, metabolomics, and functional microbial profiling, alongside investigations of the gut mycobiome and virome, will be critical to identify predictive biomarkers and optimize therapeutic strategies. These concepts remain mechanistically compelling but largely theoretical, requiring validation in longitudinal and interventional studies. Full article

Psoriasis patients face a significantly elevated risk of cardiovascular diseases (CVD), necessitating early and accurate risk prediction tools. This study developed and validated a machine learning model to predict CVD risk in psoriasis patients using clinical and biochemical data from 2685 individuals. After preprocessing and addressing class imbalance with SMOTE-NC, six machine learning models (Logistic Regression as baseline, XGBoost, LightGBM, CatBoost, GradientBoosting, AdaBoost) were evaluated using a completely leak-free nested cross-validation framework (outer k = 10, inner k = 3) with randomized hyperparameter search (n_iter = 50). Feature selection via the Boruta algorithm was performed separately within each training fold to prevent data leakage. The Boruta algorithm identified 21 key predictors, including age, systolic blood pressure (SBP), apolipoprotein B (apoB), fasting blood glucose (FBG), and complement C1q. CatBoost emerged as the top-performing model (OOF ROC-AUC = 0.908, 95% CI [0.892–0.924]; PR-AUC = 0.509, 95% CI [0.448–0.578]; F1 = 0.540; MCC = 0.498; Brier = 0.078), while the Logistic Regression baseline achieved ROC-AUC = 0.909 but was eliminated due to poor calibration (Brier = 0.114 > 0.10). All metrics were evaluated with 95% bootstrap confidence intervals (n = 1000 iterations). Explainable AI techniques (SHAP, LIME, Anchors) revealed that older age, elevated SBP, and metabolic dysregulation (e.g., high apoB, FBG) were the strongest CVD predictors. Local explanations were provided for five representative patients (high-risk, low-risk, and randomly selected), rather than a single instance, to better characterize model stability. Limitations include the single-center, retrospective design and lack of external validation. Future work should incorporate multi-ethnic cohorts and advanced biomarkers (e.g., genetic, imaging data) to enhance generalizability. This study demonstrates the potential of explainable AI to improve CVD risk stratification in psoriasis patients, offering a scalable tool for preventive cardiology. Full article

Background/Objective: The emergence of the COVID-19 pandemic has raised significant concerns regarding its impact on immune-mediated diseases, particularly with respect to disease induction and exacerbation. We aimed to investigate the potential association between SARS-CoV-2 infection and COVID-19 vaccination and the development of Psoriatic Arthritis (PsA). Methods: A retrospective nested case-control study in a cohort of 3,122,602 adults without a diagnosis of PsA was conducted using a database of a large health care provider. Newly diagnosed patients with PsA aged 18 years and older were identified from the database between 1 January 2021 and 30 June 2022 and were matched by age and sex to 10 non-PsA controls. Patients were tracked to assess their exposure to SARS-CoV-2 within six months prior to diagnosis (inception date). The primary outcome of exposure to SARS-CoV-2 was compared in the cases and controls. Univariate and multivariate conditional logistic regression analyses were performed, adjusting for Body Mass Index (BMI), smoking, socioeconomic status (SES), the Charlson comorbidity index, ethnicity, psoriasis and COVID-19 vaccination status within six months. Results: Overall, 718 patients had a new diagnosis of PsA and were matched with 7180 controls. SARS-CoV-2 exposure among PsA cases was (N = 88/718, 12.3%) compared to controls (N = 755/7180, 10.5%), the difference was not statistically significant (p = 0.115). No statistically significant association was found between SARS-CoV-2 infection and PsA development after adjusting for all confounders (OR = 1.08, 95% CI [0.76–1.54], p = 0.652). COVID-19 vaccination was also not associated with PsA development (OR = 1.10, 95% CI [0.86–1.41], p = 0.45). Conclusions: This study found no statistically significant association between SARS-CoV-2 exposure or COVID-19 vaccination and PsA development within six months post-exposure; however, small differences cannot be excluded. Full article

Accurate medical diagnostics for skin affections such as skin cancer, psoriasis, vascular tumors, or exanthems have become increasingly difficult due to the growing volume and visual variability of dermatological cases, as well as limited specialist availability. To address this, the present work introduces a complete and deployable deep-learning-based system capable of detecting ten distinct skin disease categories, trained using transfer learning with EfficientNet-B5 and enhanced with explainable AI through Grad-CAM. The proposed system achieves a top-3 accuracy of 95.96%, a weighted F1-score of 0.87, and class-specific F1-scores reaching 0.96 for acne and 0.95 for nail fungus. These results demonstrate strong predictive performance for the deep learning model trained, validated, and evaluated on a ten-class subset of the Dermnet dataset. The research conducted covers the visual explainability of the AI model classification process, including integration into a fully functional web application, usable as an expert system for image uploading, data processing and visualization of results. The AI visualizing technology based on Grad-CAM provides clear, class-specific heatmaps that highlight the most influential regions in each prediction, improving transparency and supporting clinical interpretability. Full article

Background/Objectives: Psoriasis and periodontitis share inflammatory pathways. Current evidence suggests a bidirectional non-causal relation. However, the evidence on the effects of periodontal treatment on psoriasis outcomes (severity, inflammatory markers, quality of life) is limited. This study aims to synthetize the available clinical and preclinical evidence of periodontal treatment effects on psoriasis outcomes, in patients with comorbid psoriasis and periodontitis (CRD420261298145). Methods: Several databases (PubMed, WebOfScience, ScienceDirect, ProQuest and GoogleScholar) were searched for relevant articles, without language or time restrictions. We included randomised and non-randomised clinical studies on humans, and controlled animal experiments. Interventions included periodontal treatment (surgical and non-surgical). Outcomes were the Psoriasis Area and Severity Index and dermatology-specific quality of life scores; secondary outcomes included inflammatory biomarkers and periodontal parameters. Studies were screened in duplicate, data extracted independently and risk of bias was assessed using Cochrane RoB 2, ROBINS I, NOS and SYRCLE. Results: A total of five studies were included in this systematic review (four clinical studies and one preclinical studies). Three studies directly assessed post-treatment psoriasis outcomes, with two studies investigating inflammation mediators as secondary outcomes. Two studies directly assessed PASI (Psoriasis Area and Severity Index) modifications, both studies confirming PASI scores decreasing post-periodontal treatment; one study also reported DLQI (Dermatology Life Quality Index). Typical follow-up durations ranged from 8 to 10 weeks for interventional studies, to 5 years for one cohort study. Conclusions: Although momentarily limited by the small number of available studies, the results of this review suggest that periodontal treatment may be associated with improvements in psoriasis outcomes. Further studies on larger samples, with longer follow-up periods would be necessary to confirm and possibly strengthen the existing results. Full article

The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammatory responses, which are primarily driven by the interleukin (IL)-23/Th17 axis. Although current therapies effectively suppress inflammation, their long-term use is often limited by adverse systemic effects, underscoring the need for safe immunomodulatory agents. This study investigated the anti-psoriatic efficacy of J2H-1802, a novel hybrid compound combining mycophenolate mofetil (MMF) and 5-aminosalicylic acid (5-ASA), in an imiquimod (IMQ)-induced psoriasis-like mouse model. Methods: J2H-1802 was orally administered at doses of 125 and 250 mg/kg during IMQ treatment, and its effects were evaluated by conducting clinical assessments, histological analyses, and inflammatory cytokine measurements in the serum and skin tissues. Results: J2H-1802 treatment reduced Psoriasis Area and Severity Index (PASI) scores, skin and ear thickness, and splenomegaly in a dose-dependent manner. Histological examination revealed IMQ-induced epidermal hyperplasia attenuation and dermal collagen organization improvement. In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. Conclusions: J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways. Full article

Background: Psoriasis is a chronic immune-mediated inflammatory disease characterized by systemic inflammation and complex immune dysregulation that extends beyond the skin and may affect the oral environment. Increasing evidence suggests that saliva may serve as a non-invasive diagnostic medium reflecting both local and systemic pathological processes. This systematic review aimed to critically evaluate current evidence on salivary biomarkers in psoriasis, focusing on inflammatory mediators, oxidative stress parameters, immune-related factors, and oral microbiota alterations, and to assess their potential clinical and diagnostic relevance. Methods: A systematic literature search was performed according to PRISMA guidelines using PubMed, Scopus, and Web of Science databases, covering studies published between 1994 and October 2024. Original human studies evaluating salivary biomarkers in patients with psoriasis were included based on predefined PECOS criteria. Studies involving confounding inflammatory oral diseases without separate analysis were excluded. Eleven eligible studies were included in a qualitative synthesis. Results: The analyzed studies consistently demonstrated multidimensional alterations in salivary composition in psoriasis patients compared with healthy controls. Increased levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2) and reduced anti-inflammatory IL-10 indicated persistent immune activation. Elevated oxidative stress markers, including total oxidant status and oxidative stress index, supported the role of redox imbalance in disease pathogenesis. Alterations in innate immune components, such as salivary α-amylase, immunoglobulin A, and lysozyme, suggested impaired oral immune regulation. Moreover, emerging microbiome data revealed shifts toward pro-inflammatory bacterial taxa, including Prevotella and Porphyromonas. Some studies indicated that biologic therapy may modulate salivary biomarker profiles. Conclusions: Salivary biomarkers reflect systemic inflammatory and immunological alterations associated with psoriasis and represent promising non-invasive tools for disease monitoring and clinical assessment. Nevertheless, substantial methodological heterogeneity and limited sample sizes highlight the need for large-scale, standardized, and longitudinal studies to validate their diagnostic applicability. Full article

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation and failure of lipid repair, as a potential link between metabolic stress and immune-mediated inflammation in psoriasis. We summarize experimental evidence showing that membrane lipids remodeling, antioxidant suppression, lipid peroxidation, and dysregulated iron handling together define ferroptosis-permissive niches within psoriatic lesions. We also discuss functional studies demonstrating that ferroptosis modulation can reshape psoriasiform inflammation and explore how ferroptotic stress may amplify inflammatory signaling at the immune-epidermal interface, reinforcing IL-17/TNF/IFN-γ pathways. Finally, we discuss ferroptosis-related transcriptomic signatures as a potential approach to stratify psoriasis, capturing metabolic features that are not reflected by cytokine profiling. The translational opportunities and constraints for ferroptosis-targeted interventions are outlined, highlighting epidermal redox homeostasis as a new therapeutic frontier in psoriasis. Full article

The nuclear factor erythroid 2–related factor 2 (NRF2) is a master transcription factor that orchestrates cellular defense against oxidative and electrophilic stress. Dysregulation of the KEAP1–NRF2–ARE pathway has been implicated in several dermatological disorders, including vitiligo, psoriasis, atopic dermatitis, photoaging, and radiation dermatitis. This review summarizes recent advances in the understanding of NRF2 activation mechanisms and highlights pharmacological and natural compounds with potential dermatological applications. A comprehensive analysis of natural, semisynthetic, and synthetic NRF2 modulators is provided, describing their chemical structures, synthetic approaches, mechanisms of action, preclinical and clinical evidence, and therapeutic relevance for skin disorders. Multiple classes of NRF2 activators, including isothiocyanates such as sulforaphane, triterpenoids such as omaveloxolone, flavonoids including baicalein and apigenin, alkaloids such as berberine, glycosides like afzelin and paeoniflorin, stilbenoids such as tapinarof, and α,β-unsaturated fumaric acid esters such as dimethyl fumarate, have demonstrated antioxidant, anti-inflammatory, and cytoprotective effects in keratinocytes and melanocytes. Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress–driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice. Full article

Background/Objectives: Psoriasis is a chronic, systemic, and multifactorial disease affecting approximately 1–2% of the Caucasian population. It is characterized by distinct histopathological features, including epidermal hyperplasia and infiltration of immune cells into the skin. Despite its high prevalence, the underlying mechanisms driving psoriasis remain incompletely understood. Heat shock proteins (HSPs), particularly HSP70, are known to play key roles in modulating immune responses and inflammation. Although previous studies have examined the involvement of HSPs in dermatological conditions such as psoriasis, current evidence remains inconclusive. In this study, we aimed to elucidate the role of Hsp70 deficiency in the pathogenesis of psoriasis using an in vivo model. Methods: We used male mice that were either genetically normal (Hsp70+/+) or lacked the Hsp70 gene (Hsp70−/−) at 8–12 weeks of age. Psoriasis was induced by applying imiquimod cream daily for 7 days. At the end of this period mice were sacrificed and blood and tissue collected for further analysis. The severity of the psoriasis was evaluated daily using the PASI Score. Results: Hsp70 depletion was accompanied by significantly decreased psoriatic-like skin inflammation, fewer histological abnormalities, and lower PASI scores. Flow cytometry analysis revealed a decrease in LY6C⁺ monocytes and an increase in LY6G⁺ neutrophils infiltration in Hsp70-deficient mice. In addition, HSP60 expression was lower in the absence of HSP70, while HSP90 expression was markedly elevated. Conclusions: These results point to a significant regulatory function of HSP70 in psoriatic inflammation and raise the possibility that it could be a therapeutic target. Full article

Psoriasis, a chronic inflammatory skin disease, is driven by immune dysregulation and keratinocyte hyperproliferation, with current biologics facing limitations. Emerging evidence points to mitochondrial dysfunction and a pathological shift to aerobic glycolysis as core disease drivers. Here, we report that MitoFu-O, a novel mitochondria-targeting TPP-thiazole derivative, effectively ameliorates psoriasiform inflammation in imiquimod-induced mice and cytokine-stimulated keratinocytes. Mechanistically, MitoFu-O acts by inhibiting pathological glycolysis, downregulating key glycolytic enzymes (HK1, GAPDH, LDHA), and subsequently suppressing the activation of pivotal pro-inflammatory signaling pathways (MAPK, NF-κB, and STAT3). Our findings establish targeted mitochondrial modulation as a potent therapeutic strategy, positioning MitoFu-O as a promising lead compound that acts upstream of cytokine signaling by normalizing the metabolic reprogramming fundamental to psoriatic pathogenesis. Full article

Thermal spring waters (TSWs) have long been used in dermatology for chronic inflammatory dermatoses and sensitive skin and are increasingly positioned as cosmeceutical active ingredients. This review summarizes studies on the use of TSW and their hydrobiome derivatives in dermocosmetics and cosmeceuticals for skin health. TSW exhibits anti-inflammatory, antioxidant, soothing, hydrating and barrier-restoring effects in vitro, ex vivo and in clinical studies, improving conditions such as atopic dermatitis, psoriasis, acne, sensitive skin, radiation dermatitis and post-procedure erythema. In parallel, the hydrobiome of TSW has enabled the development of postbiotic and paraprobiotic ingredients, which modulate skin immunity, microbiota, barrier function and clinical signs of inflammatory and sensitive skin. Despite robust preclinical and growing clinical evidence, cosmeceuticals remain regulated as cosmetics in most regions, highlighting the need for specific regulatory frameworks and standardized approaches to demonstrate the safety and efficacy of TSW-based cosmeceuticals, as well as defining acceptable claim categories and minimum evidence thresholds. Full article

Frankincense, a traditional Chinese medicinal resin with well-documented skin barrier-protective and anti-inflammatory properties, has elusive underlying mechanisms in psoriasis-like dermatitis. This study aimed to elucidate its therapeutic potential and molecular targets by investigating frankincense oil extract (FOE) and three key constituents (linalool, α-pinene and 1-octanol) in a classic imiquimod-induced murine psoriasis model, with clinical first-line topical drugs (calcipotriol, tapinarof and dithranol) used as positive controls. Phenotypically, FOE and its constituents significantly ameliorated core psoriasis symptoms (desquamation, erythema, epidermal thickening and splenomegaly) at an efficacy comparable to that of positive controls. FOE suppressed epidermal hyperproliferation and dermal inflammatory infiltration, attenuated the abnormally elevated epidermal expression of TRPV3, β-catenin and COX-2, and increased the expression of the barrier protein K10. Taken together, these findings suggest that FOE restores impaired epidermal barrier function by regulating TRPV3, β-catenin, COX-2 and K10 expression, providing a novel mechanistic basis for the clinical application of traditional frankincense in psoriasis and identifying promising targets for antipsoriatic-drug development. Full article

Human skin and hair act as multifunctional barriers but are highly sensitive to environmental pollutants originating from air, water, and cosmetic products. Epidemiological studies report that exposure to particulate matter (PM_2.5–PM₁₀), nitrogen oxides (NO_x), and volatile organic compounds increases the risk of skin and hair disorders. For instance, women in high-traffic areas (N = 211) show significantly more pigment spots and nasolabial wrinkles compared to those in rural areas (N = 189), indicating accelerated skin ageing. Children aged 9–11 exposed to PM₁₀, benzene, and NO_x exhibit increased incidence of atopic dermatitis. Systemic exposure to dioxins causes chloracne, while co-exposure to polycyclic aromatic hydrocarbons (PAHs) and UVA radiation elevates skin cancer risk. Psoriasis flares are associated with mean pollutant concentrations over the 60 days preceding flare events in 957 patients, and hyperpigmentation prevalence increases in populations exposed to traffic-related PM and ROS-inducing pollutants. Hair loss is linked to oxidative stress from PM and PAHs absorbed on hair fibers, with in vitro studies showing keratinocyte apoptosis in scalp hair follicles. This review evaluates natural adsorbents such as zeolites, clays, activated carbon, and polyphenol-rich plant extracts for anti-pollution cosmetic formulations. Adsorption capacities range from 60 to 150 mg·g⁻¹ depending on the pollutant, with removal efficiencies of 30–55% in model topical systems. Mechanisms include ion exchange, surface adsorption, hydrophobic interactions, and radical scavenging. Incorporating 2–5% w/w of these adsorbents in cosmetic formulations significantly reduces pollutant deposition on skin and hair. These findings support the development of evidence-based, sustainable anti-pollution cosmetic strategies that quantitatively mitigate environmental stressor effects. Full article