Search Results (2,485)

Background and Objectives: Sjögren’s disease (SjD) is a chronic autoimmune disorder in which the immune system attacks the glands that produce tears and saliva, leading to symptoms such as dry eyes and dry mouth. If left untreated, SjD can also cause inflammation and damage to other parts of the body, including the skin, lungs, kidneys, and nervous system, and increase the risk of developing lymphoma. The human leukocyte antigen (HLA) class II molecule HLA-DR3 is strongly associated with SjD. Materials and Methods: To investigate how post-translational modifications (PTMs) influence the presentation of SjD-associated autoantigens by HLA-DR3, we employed a computational framework to determine the binding of PTM-mimic peptides to HLA-DR3. We further supported the in-silico results with in-vitro experiments. Results: Our analysis revealed that PTM-mimic substitutions at canonical anchor positions rarely improved predicted binding affinity using the Stabilized Matrix Method, with most modifications resulting in reduced affinity. However, a comprehensive analysis of full-length SjD-associated autoantigen sequences (Ro60, Ro52, La) identified discrete regions with high densities of PTM-eligible anchor sites, specifically, the Ro60 HEAT solenoid, Ro52 RING/B-box/PRY-SPRY modules, and the La motif-RRM1 region, suggesting that PTMs may alter epitope presentation in a sequence-dependent manner. Experimental validation of selected PTM-mimic peptides showed enhanced T cell responses, which were associated with increased binding affinity to HLA-DR3. Structural modeling of a representative complex revealed that PTM-mimic peptides adopt a slightly shifted backbone orientation and altered side-chain positioning, leading to a larger peptide–DR3 interaction interface. Conclusions: These findings provide new insights into the role of PTMs in shaping the immunogenicity of SjD-associated autoantigens and highlight the potential for PTM-mimic peptides to modulate T cell responses in SjD. Full article

Subcutaneous thrombotic vasculopathy (STV) is a rare, non-inflammatory occlusive disorder of the cutaneous microvasculature that predominantly involves the subcutaneous tissue and may closely mimic inflammatory vasculitis. We describe a case of STV with overlapping features of leukocytoclastic vasculitis (LCV) in a 23-year-old woman presenting with rapidly progressive, painful purpuric skin lesions. The patient had a history of polysubstance use disorder and reported intravenous injection of crushed oral oxycodone and methylphenidate tablets. Histopathological examination of a deep skin biopsy revealed fibrin-rich thrombi occluding small vessels of the dermis and subcutaneous tissue. Fine granular IgA deposits in the walls of numerous superficial dermal blood vessels shown using direct immunofluorescence suggested LCV. Overall, the findings supported a mixed thrombotic-inflammatory vasculopathy with predominant features of STV. This case highlights the diagnostic complexity of STV and may suggest intravenous injection of crushed oral medications as a potential trigger through particle-induced microvascular obstruction and secondary thrombosis. In addition, we conducted a literature review indicating that STV remains a rare and likely underrecognized entity, with only a limited number of reported cases. Full article

Vitiligo is a chronic, acquired autoimmune disorder characterized by white skin patches resulting from the loss of epidermal melanocytes. Vitiligo may arise through multiple mechanisms, including genetic susceptibility, oxidative stress, autoimmune dysfunction, and environmental factors. Treatment strategies have focused on inhibiting melanocyte loss and stimulating repigmentation. Mitogen-activated protein kinase (MAPK) pathways regulate various cellular processes, including differentiation, survival, and inflammatory responses. The dysregulated MAPK pathways play distinct roles in the development of vitiligo through a complex interplay of melanogenesis, oxidative stress, and autoimmune responses within different cells, thereby leading to melanocyte damage. Thus, therapeutic targeting of MAPK pathways has the potential to mitigate oxidative stress-induced damage and inhibit the exaggerated autoimmunity, thereby controlling disease progression and supporting repigmentation. This review provides an overview of MAPK signaling across the multicellular network in vitiligo pathogenesis and summarizes agents that may provide new perspectives for therapeutic intervention. Full article

The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila, has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments. Full article

C. asiatica (L.) Urban is a medicinal plant widely used in traditional Asian medicine with potential geroprotective properties. Its major bioactive compounds—including asiaticoside, madecassoside, asiatic acid, and madecassic acid—exhibit antioxidant, anti-inflammatory, regenerative, neuroprotective, and cytoprotective activities. Experimental studies demonstrate modulation of signaling pathways involved in oxidative stress, inflammation, apoptosis, extracellular matrix remodeling, and cellular survival, including NF-κB, PI3K/Akt/mTOR, MAPK, Nrf2/HO-1, and TGF-β/Smad pathways. Preclinical evidence further indicates attenuation of cellular senescence, improvement of mitochondrial function, enhanced collagen synthesis, and regulation of cytokine production. In experimental models, C. asiatica has shown beneficial effects on wound healing, skin aging, neuroinflammation, β-amyloid aggregation, neuroplasticity, metabolic dysfunction, and vascular protection. Preliminary preclinical findings also suggest possible effects on telomerase activity and telomere maintenance. However, clinical translation remains limited due to insufficient randomized controlled trials, low oral bioavailability of triterpenoids, variability in extract standardization, and limited pharmacokinetic and long-term safety data. This narrative review summarizes the phytochemistry, molecular mechanisms, pharmacological activities, and potential geroprotective applications of c. asiatica, highlighting its translational relevance in healthy aging and age-related disorders while emphasizing the need for standardized clinical studies. Full article

Background and Clinical Significance: Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoproliferative disorder that can clinically resemble various non-melanoma skin cancers, making diagnosis challenging. Although histopathology remains the diagnostic gold standard, non-invasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) are increasingly used as complementary tools to support the differential diagnosis. To date, no data on RCM features of C-ALCL have been described. Case Presentation: We report the case of an 80-year-old man presenting with a rapidly enlarging nodule on the lateral aspect of his right eyelid, providing a detailed account of dermoscopic and RCM findings integrated with clinicopathological correlation. Dermoscopy revealed a red-orange homogeneous background with white streaks, and polymorphic vascular structures, while subsequent RCM (Vivascope 3000 probe) demonstrated marked architectural disarray of the epidermis and dermoepidemal junction, with prominent epidermal involvement characterized by aggregates of highly reflective cells. In the absence of alternative diagnostic patterns, these features raised suspicion for a cutaneous lymphoproliferative disorder, which was later confirmed by histopathological and immunohistochemical analyses. Conclusions: Our findings support the value of RCM as a practical tool in guiding differential diagnosis and biopsy, particularly for rapidly growing lesions located in anatomically sensitive areas. Full article

Necroptosis has been implicated in the pathogenesis of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), with prior studies demonstrating tissue-level involvement of receptor-interacting protein kinases RIPK1 and RIPK3. However, their systemic expression in the circulatory compartment remains incompletely characterized. The objective of this study is to evaluate circulating levels of RIPK1 and RIPK3 in patients with SJS/TEN and explore their potential association with diseases. Serum samples from patients with SJS/TEN and control groups were analyzed for RIPK1 and RIPK3 levels using ELISA. Group differences were assessed using non-parametric statistical methods. Circulating levels of RIPK1 and RIPK3 were elevated in patients with SJS/TEN compared with controls. These findings were consistent across analyses; however, variability within groups and overlap between cohorts were observed. These results suggest an association between increased circulating RIPK1 and RIPK3 levels and SJS/TEN. Given the limited sample size, heterogeneous control populations, and lack of functional or phosphorylation-specific assays, these findings should be considered exploratory. Further studies incorporating larger cohorts and mechanistic validation are needed to clarify the role of necroptosis-related pathways in the systemic manifestations of SJS/TEN. Full article

Acne is a prevalent chronic inflammatory skin disorder with a high recurrence rate, in which Propionibacterium acnes (P. acnes) plays a key pathogenic role by colonizing subepidermal pilosebaceous units. The stratum corneum limits drug penetration, rendering conventional topical therapies ineffective. Herein, we report a detachable sustained-release microneedle system named Bacitracin@Hyaluronic Acid–Zein Microneedle (Bac@HA-ZMN) for localized antibacterial delivery in acne therapy. This microneedle patch consists of a dissolvable HA base and zein-based indwelling microneedle tips loaded with bacitracin (Bac) against P. acnes. Mechanical testing showed an average fracture force of 1.6 N per needle tip (n = 100), sufficient for skin insertion. The needle tips enabled Bac delivery to a depth of approximately 500 μm. In vitro transdermal studies demonstrated a cumulative release of 76.1% within 96 h, significantly higher than that of the control group (14.2%). In a murine acne model, the Bac@HA-ZMN treatment group showed a significantly smaller lesion area than the control group, and the immunohistochemical positive expression areas of the inflammatory factors IL-8, MMP-2, and TNF-α were reduced to 0.79%, 4.12%, and 2.14%, respectively, which was caused by the inhibitory effect of Bac on P. acnes. These results demonstrated Bac@HA-ZMN as a promising localized, sustained antibacterial delivery platform for acne treatment. Full article

Objectives: Oculocutaneous albinism (OCA), a group of inherited disorders characterized by deficient melanin synthesis, leads to hypopigmentation of the skin, hair, and eyes. OCA type 2 (OCA2) is caused by mutations in OCA2. This study aimed to characterize the comprehensive clinical and genetic spectrum of OCA2, and to identify the key ocular determinants of visual acuity. Methods: We enrolled 90 probands clinically diagnosed with albinism. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Results: OCA2 was confirmed in 29 probands (32.2%). Visual impairment was distributed as mild/no impairment (30.8%), moderate (53.8%), and severe/blindness (15.4%). All patients exhibited nystagmus and photophobia. Ocular phenotype grading showed distinct distributions: iris translucency (n = 25) was 68% grade 3, 20% grade 2, 8% grade 1, and 4% grade 4; fundus hypopigmentation (n = 26) was 42.3% grade 1, 30.8% grade 2, and 26.9% grade 3; and foveal hypoplasia (n = 20) was 70% grade 4, 25% grade 3, and 5% grade 1. We identified 33 OCA2 variants (26 compound heterozygous and 3 homozygous), with missense variants accounting for 62.1% of alleles. Five variants were identified to be novel. The severity of foveal hypoplasia demonstrated a strong, statistically significant negative correlation with visual acuity (r = −0.71, p < 0.001). Conclusions: OCA2 accounts for 32.2% of albinism cases, with moderate visual impairment being the most common (53.8%). Graded phenotyping demonstrated moderate-to-severe iris translucency (88%), mild fundus hypopigmentation (42.3%), and severe (grade 4) foveal hypoplasia (70%). The severity of foveal hypoplasia emerged as an important determinant of visual acuity. Full article

Medicinal plants play a crucial role in primary healthcare among indigenous communities; however, systematic ethnomedicinal documentation of the Yao people in Lingyun County, Guangxi, remains limited. This study aimed to document the diversity, traditional uses, and cultural significance of medicinal plants used by the Yao community. Ethnobotanical data were collected through semi-structured interviews with 104 informants. A total of 172 species belonging to 135 genera and 73 families were recorded, with Fabaceae, Lamiaceae, and Asteraceae being the most represented families. Herbs were the dominant growth form, and whole plants, roots, and shoots were the most frequently used parts, typically prepared in dried form and administered orally. Fidelity Level (FL) values ranged from 6.67 to 100, with several species showing high consensus in therapeutic use. Informant Consensus Factor (ICF) values (0.778–1.000) indicated strong agreement among informants, particularly for musculoskeletal, skin, gastrointestinal, and immune-related disorders. These findings highlight the richness and consistency of ethnomedicinal knowledge among the Yao people and provide a scientific basis for future pharmacological research, conservation planning, and the sustainable use of medicinal plant resources. Full article

Background/Objectives: Chronic inflammatory skin diseases are frequently associated with pruritus, in which the neurokinin-1 receptor (NK₁R) and its ligand substance P (SP) play a central role. The development of compounds combining anti-inflammatory and antipruritic effects represents a promising therapeutic strategy. This study aims to identify fiscalin B derivatives as anti-inflammatory agents with high affinity to NK₁R using an integrated in silico and in vitro approach. Methods: A library of fiscalin B derivatives was screened through molecular docking against NK₁R to identify high-affinity ligands. Selected compounds were further evaluated using in silico ADMET and toxicity predictions. In vitro assays were conducted in HaCaT keratinocytes, RAW264.7 macrophages, and NIH/3T3 fibroblasts to assess cytotoxicity, nitric oxide production, inflammatory proteins expression, and cell migration. Results: Docking studies identified several derivatives with predicted binding affinities comparable to or exceeding those of aprepitant, a well-established NK₁R antagonist. Several compounds, particularly 2, 3, 4, 6, and 7, reduced lipopolysaccharide-induced nitric oxide production to 41–51% without relevant cytotoxicity. This effect was associated with reduced iNOS protein levels, suggesting modulation of inflammatory pathways rather than direct nitric oxide scavenging. Most compounds showed positive safety profiles, although in silico analysis indicated limited biodegradability and potential aquatic toxicity. Conclusions: The fiscalin B derivatives, 2, 3, and 4, demonstrate potential as anti-inflammatory agents, in vitro, and as NK₁R high affinity ligands, in silico. These findings support their potential as lead compounds for topical therapies for inflammatory skin disorders associated with pruritus, although further optimization and validation are required. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease traditionally viewed through a purely dermatologic lens. However, this perspective fails to explain stress-induced flares, menstrual cycle-linked exacerbations, and severe pain and itch disproportionate to visible cutaneous inflammation. This narrative review synthesizes evidence supporting a neuroendocrine–immune model of HS pathogenesis, with emphasis on mechanisms underlying pain and itch. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases (January 1990–September 2025) with terms including hidradenitis suppurativa, neuroendocrine mechanisms, HPA axis, sex hormones, neuropeptides, pain (including nociceptive and neuropathic pain, burning, and dysesthesia), and pruritus (itch). Eligible studies included peer-reviewed research examining hormonal, stress-related, or neuropeptide mechanisms in HS. Data were synthesized into thematic categories: endocrine influences, HPA axis function, neuropeptide signaling, immune crosstalk, and clinical implications. Results: Sex hormones promote follicular occlusion and modulate immune responses, explaining perimenstrual flares. Prolactin amplifies inflammation during stress through immune cell activation. Insulin resistance and adipokine imbalance create pro-inflammatory conditions. Chronic stress induces HPA axis dysfunction with cortisol resistance, exacerbating inflammation. Neuropeptides released from cutaneous nerves amplify immune activation and directly mediate pain and itch. These pathways establish self-perpetuating feedback loops wherein inflammation drives stress, and neuroendocrine dysfunction amplifies immune responses. Conclusions: HS represents a systemic disorder with a strong neuroendocrine–immune component, rather than a purely dermatologic condition. This framework supports multidisciplinary management integrating hormonal therapies, targeted immunomodulation, and stress reduction. Future research should characterize neuroendocrine biomarkers and test combination therapies targeting multiple system nodes. Full article

Chronic inflammatory skin diseases, including psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD), are increasingly recognized as systemic disorders associated with chronic immune dysregulation. Growing evidence supports their links with metabolic disorders, reflected in heightened interest in therapeutic strategies targeting the immunometabolic axis. This review summarizes current knowledge on the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the regulation of immune and metabolic processes in chronic inflammatory skin diseases, with particular emphasis on molecular mechanisms and available experimental and clinical data. GLP-1RAs, widely used in the treatment of type 2 diabetes and obesity, may also exhibit anti-inflammatory and immunomodulatory properties beyond their classical metabolic effects. GLP-1 signalling can influence keratinocyte function, immune cell activity, and wound healing. Furthermore, it modulates multiple intracellular signalling pathways, including cAMP/PKA, AMPK, PI3K/Akt, and NF-κB, as well as immune axes such as IL-23/Th17/IL-17 and inflammasome-related signalling. Available evidence suggests that GLP-1RAs may reduce inflammation and disease activity in selected inflammatory dermatoses. However, current evidence remains limited and is based primarily on experimental studies, case reports, and small-scale observational studies. Further well-designed clinical trials are needed to better define the therapeutic potential of GLP-1RAs and their role in dermatological practice. Full article

Background/Objectives: Wrist cock-up orthoses are standard for work-related musculoskeletal disorders, yet consensus is lacking on whether commercial orthoses (COs) or custom-made thermoplastic orthoses (THs) better preserve function. While COs offer availability, THs provide a superior anatomical fit. This study evaluated dexterity and satisfaction in healthy female employees to establish a functional baseline for preventive strategies. Methods: Healthy female office workers with no prior musculoskeletal or neurological conditions participated in this randomized cross-over study. Manual dexterity was assessed at baseline and after each of two consecutive workdays, during which participants wore, in a randomized order, either a CO or a TH made by an expert physiotherapist. Outcome measures included the Functional Dexterity Test (FDT), recording time and errors, and the Client Satisfaction with Device (CSD-It) scale. Results: Twenty right-handed women (mean age 45.6 ± 11 years) participated. A significant difference in FDT completion times across conditions (χ² = 12.6, p = 0.002) was found. While both orthoses slowed performance compared to baseline (p < 0.01), the CO allowed for faster dexterity than the TH (p < 0.01). No differences were found in error rates. Regarding satisfaction, the CO achieved significantly better CSD-It scores than the TH (p = 0.0047), despite 60% of users reporting increased skin temperature with the CO. Final preferences were nearly evenly split (55% CO vs. 45% TH). Conclusions: Both orthoses impact manual dexterity without compromising precision. While the CO offered better execution speed and overall satisfaction, the TH version was preferred for prolonged skin tolerability. Selection should be individualized, balancing mechanical efficiency with the superior fit of custom-fabricated solutions in office environments. Full article

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit. Full article