Search Results (28,039)

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory dermatosis increasingly recognized as a distinct disease entity rather than a variant of plaque psoriasis. Emerging evidence indicates that GPP is primarily driven by dysregulation of the interleukin-36 (IL-36) signaling axis, leading to amplification of proinflammatory cascades in keratinocytes and a predominantly innate, neutrophil-driven immune response. This promotes rapid neutrophil recruitment, sterile pustule formation, and abrupt cutaneous and systemic inflammation. Consistent with this, GPP demonstrates a greater predominance of innate immune and neutrophil-driven inflammation, whereas plaque psoriasis is more strongly associated with IL-23/Th17-mediated adaptive immune responses. Transcriptomic and genetic studies further support this distinction, demonstrating enrichment of IL-36-associated and neutrophil-related signatures, activation of MyD88-dependent pathways, and mutations in genes regulating the IL-36 axis, including IL36RN, AP1S3, and CARD14. Consequently, conventional systemic therapies and biologics targeting TNF-α, IL-17, and IL-23 pathways show variable efficacy and may act more slowly in GPP. In contrast, IL-36 receptor inhibitors represent a more mechanism-aligned approach and have demonstrated rapid and clinically meaningful responses in acute flares. However, important gaps remain, including the lack of validated biomarkers and limited data on long-term treatment outcomes. This review provides an integrated perspective on IL-36-driven inflammation in GPP, including comparison with plaque psoriasis, and outlines its implications for mechanism-based therapeutic approaches. Full article

Capsaicin has been investigated as a phytogenic feed additive in animal production due to reported growth-promoting and immunomodulatory properties; however, its pungency limits practical application. Capsiate, a naturally occurring non-pungent capsaicin analog present in specific Capsicum annuum accessions, conserves many of its bioactive properties without inducing sensory irritation and has not been studied as a potential growth-promoting alternative. The present study evaluated whether dietary exposure to a capsiate-producing chili pepper influences growth and assessed associated intestinal responses using a murine model. A capsiate-producing Capsicum annuum accession (509-45-1) was characterized and incorporated into experimental diets providing 30 or 50 mg/kg capsiate to male C57BL/6J mice for 12 weeks. The dietary intervention was associated with dose-dependent increases in body weight and longitudinal femoral growth without altering body composition. Femoral elongation was accompanied by increased growth plate area and higher osteocyte number and area. At the intestinal level, the intervention was associated with downregulation of colonic transient receptor potential vanilloid 1 (TRPV1) gene expression, modulation of redox-associated responses, including catalase (CAT) and superoxide dismutase (SOD) expression, and differential modulation of innate immune signaling, including upregulation of Toll-like receptor 2 (TLR2) and downregulation of Toll-like receptor 4 (TLR4), together with reduced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) expression. Collectively, these findings indicate that dietary supplementation with a capsiate-producing chili is associated with increased somatic growth and enhanced femoral development in mice, accompanied by intestinal transcriptional changes consistent with immunometabolic responses, while preserving body composition. Full article

Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a comprehensive analysis of transcriptomic data from lesional psoriasis skin and healthy controls, comparing male and female cohorts. Our findings reveal 2760 overlapping differentially expressed genes (DEGs) between sexes, highlighting shared pathways like IL-17 signaling and Th17 differentiation. However, sex-specific pathways emerged, including male-enriched PI3K-Akt signaling and chemokine receptor activity, and female-enriched glycolysis and AHR-NRF2 pathways. Upstream regulator analysis identified sex-specific drivers, including VEGFA activation and CFTR inhibition in males, and AHR activation and FGF21 inhibition in females. Notably, Regulatory T cells (Tregs) and neutrophil abundance differed by sex, aligning with disease severity trends. These results highlight sex-associated molecular and cellular disparities that may be relevant to understanding differences in disease manifestation and treatment response. As an exploratory, hypothesis-generating transcriptomic analysis, this study lays the groundwork for future experimental and clinical validation of sex-specific mechanisms in psoriasis. Full article

Objective: In this study, Dehydroepiandrosterone (DHEA-induced Polycystic Ovary Syndrome (PCOS) mice were used as models to evaluate the improvement effect of Vitexin (Vit) on ovarian fibrosis and explore the mechanism of action of the NR4A1/NLRP3 signaling pathway. Method: Sixty 4-week-old female ICR mice of the same batch number were selected and their systems were divided into 6 groups (n = 10): normal (Control, Ctrl) group, model (Polycystic Ovary Syndrome, PCOS) group, treatment (Vitexin, The Vit group, normal NR4A1 gene silencing group (Ctrl NR4A1^-/-), NR4A1 gene silencing model group (PCOS NR4A1^-/-), and NR4A1 gene silencing treatment group (Vit NR4A1^-/-). Silencing gene modeling was performed by tail vein injection of adeno-associated virus (serotype AAV-8), and the mouse genotypes were detected by qRT-PCR technology 14 days after injection. After the genotype was determined, the PCOS group and the PCOS NR4A1^-/- group were administered dehydroepandrosterone (6 mg/100 g/d) by gavage for 28 consecutive days for modeling, while the Vit group and the Vit NR4A1^-/- group were treated with dehydroepandrosterone + vitexin (10 mg/kg/d) by gavage for 28 consecutive days. All mice were raised with pure water and regular maintenance food. After 4 weeks of drug intervention, the mice were euthanized and samples were collected. The pathological changes in ovarian tissue were observed by H&E staining, and the degree of ovarian tissue fibrosis was observed by Masson staining. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mouse serum were detected by biochemical kits. The levels of inflammatory factors (IL-1β, IL-6, IL-18, TNF-α) in mouse serum were determined by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect oxidative kinase (Gsta4, Prdx3, Mgst1, Gpx3, Gsr), inflammatory factors (Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tnf-α) and fibrotic pathway-related genes (Tgf-β1, Smad3, Collagen1, CTGF, α-SMA, Mmp-13, and β-catenin) in ovarian tissues. The levels of inflammatory factors (NLRP3, Caspase-1, ASC, IL-1β, IL-18, TNF-α, IκBα) and fibrosis in mice were determined by Western blot method, and statistical description and analysis were performed using SPSS software. Result: In the wild-type genotype group, compared with the PCOS group, Vit treatment could effectively regulate the metabolic abnormalities of PCOS mice, including inhibiting excessive weight gain, restoring normal glucose tolerance, and reducing body fat content. After Vit treatment, the levels of MDA, TC, TG, LDL, IL-1β, IL-6, IL-18 and TNF-α in the serum of PCOS mice were significantly reduced, while the levels of SOD and HDL in the serum of PCOS mice were increased. The staining results indicated that Vit treatment could significantly inhibit the process of ovarian fibrosis in PCOS mice. The results of WB and PCR demonstrated that after Vit gavage treatment in mice, inflammatory and fibrotic factors such as Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tgf-β1, Smad3, Collagen1, CTGF, and α-SMA in ovarian tissues could be significantly down-regulated, and the fibrotic level of ovarian tissues could be reduced. Among the same measurement indicators, the silenced NR4A1 group showed a certain degree of increase compared with the wild genotype group, but there was no significant difference. Conclusions: Vit intervention can restore the sex hormone levels and follicular development in ovarian tissues of PCOS mice, regulate reproductive endocrine disorders and abnormal lipid metabolism levels, and regulate the expression of Collagen I, a-SMA and CTGF in the ovaries by inhibiting the NR4A1/NLRP3 signaling pathway, thereby improving the ovarian fibrosis level of PCOS mice. It is suggested that it may play a key role in the treatment of PCOS and the prevention and delay of its long-term complications. Full article

Goose blood has anticancer properties and was recorded in ancient China, but the specific molecular mechanisms underlying this effect still require further exploration. In this study, SW1990 cells were treated with goose serum or plasma, and transcriptome analysis was performed to explore the function of goose blood on cancer cells. Metabolomic profiling was also performed on goose serum, goose plasma, chicken serum, and chicken plasma to identify the bioactive substances responsible for the anticancer effect. The study examined the effects of goose plasma and serum on SW1990 cells and compared the metabolites between goose and chicken blood. Wound scratch, CCK-8, and Annexin V-PI assays showed that goose plasma and serum inhibited SW1990 cell proliferation at 24 and 48 h. Both treatments reduced cell viability, with serum inducing early and late apoptosis and plasma inducing late apoptosis. RNA sequencing (RNA-seq) identified 2259 (1418 upregulated, 841 downregulated) and 2731 (1844 upregulated, 887 downregulated) differentially expressed genes (DEGs) in the plasma and serum groups versus the negative control (NC), respectively, and 689 DEGs between the plasma and serum groups. Gene Ontology (GO) and KEGG pathway analyses revealed that the DEGs were enriched in processes such as lipid metabolism, JAK-STAT, and IL-17 pathways. Untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis identified distinct metabolites in goose and chicken blood, with unique metabolites and differential ones between groups. In SW1990 cells, four metabolite subclusters matched the plasma and serum effects. In summary, goose blood can suppress cancer cells by regulating gene expression to affect the key signaling pathways involved in cancer cell apoptosis and autophagy. Certain metabolites present at high concentrations in goose blood, such as cucurbitacin D and Oleoyl-L-carnitine, may also contribute to the inhibition of cancer cell proliferation and migration. These findings suggest that goose blood holds broad application prospects as a future auxiliary drug for cancer treatment, and this study provides a theoretical basis for the further application of goose products. Full article

Epimedium is a traditional Chinese tonic used to tonify the kidneys, enhance sexual function, and strengthen muscles and bones. However, the potential effects of Epimedium on the semen quality of Bama boars remain incompletely elucidated. The objective of this study was to evaluate the effects of dietary Epimedium ultrafine powder (EP) supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. The objective of this study was to evaluate the effects of dietary EP supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. Eighteen healthy, sexually mature adult male Bama boars were randomly divided into three groups (n = 6) and fed either a basal diet (CON) or the basal diet supplemented with 0.3% (EP3) or 0.5% (EP5) Epimedium ultrafine powder for five weeks. This study employed enzyme-linked immunosorbent assay (ELISA), 16S RNA gene sequencing, non-targeted metabolomics (CON and EP5), and Spearman correlation analysis, among other methods. The results indicated that dietary Epimedium (0.3% and 0.5%) increased the levels of serum TP, FSH, and SOD and decreased the abnormal sperm rate and the levels of serum TBA, TNF-α, and IL-6. Among them, adding 0.5% Epimedium in the diet increased sperm motility and the levels of serum T, LH, and IgG. 16S rRNA gene sequencing analysis revealed that both 0.3% and 0.5% Epimedium supplementation reduced the abundance of Streptococcus. Specifically, the 0.3% dose decreased Prevotella abundance, while the 0.5% dose reduced Escherichia-Shigella abundance. PICRUSt2 analysis revealed that the pathways of phenylalanine, butanoate, biotin, and arachidonic acid metabolism were significantly enriched in the Epimedium group. A non-targeted metabolomics analysis identified that indole-3-acrylic acid, DL-tryptophan, 2-hydroxyphenylalanine, and propionylcarnitine showed significant upregulation after Epimedium supplementation. Spearman correlation analysis indicated that Streptococcus was negatively correlated with sperm motility and serum-related parameters (TP, T, LH, IgM, and IgG). Streptococcus and Escherichia-Shigella were negatively correlated with indole-3-acrylic acid, DL-tryptophan, and biotin. In conclusion, Epimedium has a positive impact on the seminal quality, reproductive hormones, and immune–antioxidant levels of Bama boars by regulating the composition and metabolites of the intestinal microbiota. Full article

Vascular calcification is a strong predictor of cardiovascular mortality and lacks effective treatment. The transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes is a key driver of calcification. This study identifies a regulatory role for Hyaluronan (HA) in VSMC osteogenic differentiation and arterial calcification. Human aortic VSMCs stimulated with high phosphate and/or pro-inflammatory cytokines (IL6 and TGF-β1) exhibited increased RUNX2, alkaline phosphatase and osteopontin expression, along with reduced contractility and elevated calcium deposition. This corresponded with reduced HA deposition and downregulation of HA synthase enzymes (HAS1, HAS2), Hyaluronidase enzymes (Hyal1), and HA binding proteins (CD44, TSG-6), whilst HAS3 and versican were upregulated. Comparable alterations in HA and protein expression were observed in an in vivo model of arterial calcification using vitamin K-deficient warfarin-fed mice. Pharmacological inhibition of HA synthesis, enzyme-mediated HA degradation and siRNA/plasmid modulation of HAS isoenzymes demonstrated a possible functional link between HA regulation and VSMC osteogenic differentiation. This study establishes HA and its associated binding proteins as key regulators of arterial calcification, highlighting a novel pathway for potential therapeutic intervention. Full article

Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management. Full article

Background: Postmenopausal osteoporosis is associated with cellular senescence and the accumulation of the senescence-associated secretory phenotype (SASP). While mesenchymal stem cell (MSC)-derived exosomes show tissue repair potential, the efficacy and mechanisms of MSC-derived apoptotic vesicles (apoVs) remain unclear. This study compared MSC-apoVs and exosomes in postmenopausal osteoporosis and investigated the underlying epigenetic mechanisms. Methods: Therapeutic efficacy was evaluated in an ovariectomized (OVX) mouse model and senescent human bone marrow mesenchymal stem cells (hBMMSCs). Small RNA sequencing identified differential microRNA (miRNA) cargos between vesicle types. SASP-related cytokine expression (IL-6, TNF-α, MCP-1) and pathway activation were assessed by RT-qPCR, ELISA, and Western blot. Results: MSC-apoV treatment attenuated bone loss in OVX mice and reduced SASP expression in senescent hBMMSCs to a greater extent than exosomes. Small RNA sequencing revealed that apoVs were enriched with a specific miRNA cluster, including hsa-let-7b-5p, hsa-miR-92a-3p, and hsa-miR-98-5p. Bioinformatic analyses identified BRAF and CRKL as downstream targets of this miRNA cluster, supported by reduced protein levels after apoV treatment. Subsequent molecular assays showed that apoV treatment inhibited the phosphorylation of both the MAPK (p38 and JNK) and NF-κB (p65) signaling pathways, which correlated with reduced local inflammation in the bone marrow microenvironment and preserved osteogenic differentiation capacity. Conclusions: MSC-apoVs attenuate postmenopausal osteoporosis more effectively than exosomes. This enhanced efficacy is associated with the delivery of an enriched miRNA cluster that inhibits MAPK and NF-κB signaling, together with suppression of BRAF and CRKL protein expression. ApoVs may represent a cell-free therapeutic strategy for age-related bone loss. Full article

Objectives: An infectious trigger can initiate a systemic inflammatory response, which in turn activates immune cells and causes the release of various mediators. Local mediators, such as resolvin D1 (RvD1), actively interact with immune cells to promote the resolution of inflammation. This study aimed to determine the impact of RvD1 on the inflammatory response mediated by monocytes in response to LPS. Methods: To investigate the mechanism by which RvD1 affects the monocyte-mediated inflammatory response to LPS, human THP-1 monocytic cells were treated with LPS, RvD1, or vehicle for 24 h. Inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), were measured using enzyme-linked immunosorbent assay (ELISA). RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs). The NF-κB and MAPK p38 signaling pathways were validated using real-time quantitative PCR (RT-qPCR) and Western blotting (WB). Results: RvD1 diminished the levels of IL-1β and TNF-α in LPS-induced inflammation. RvD1 significantly enhanced the mRNA expression of CREB, NRF2, and BCL-2. In addition, RvD1 significantly decreased the mRNA expression of CASP3. RvD1 regulated the inflammatory process in human monocytic THP-1 cells via the NF-κB p65 (MyD88, p65) and p38 MAPK signaling pathways (p38, BCL-2) and further suppressed the expression of apoptotic factors (PI3K, caspase-3). Conclusions: RvD1 has been shown to exert pro-resolving effects by regulating the anti-apoptotic gene BCL-2 and activating the NF-κB p65 and MAPK p38 signaling pathways. 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: Eosinophilic chronic rhinosinusitis (ECRS) is characterized by refractory nasal polyps and severely impaired mucociliary clearance (MCC). The molecular mechanisms underlying the modulation of mucociliogenesis following IL-4/13 blockade with dupilumab remain poorly understood, notwithstanding its proven clinical efficacy. Methods: Bulk RNA Barcoding and sequencing (BRB-seq) was performed on nasal polyp tissues collected from healthy controls (n = 6), patients with non-ECRS (n = 8), and patients with ECRS both before and four weeks after dupilumab treatment (n = 9) to identify the early molecular drivers underlying ciliary regeneration. Comprehensive gene-set scoring systems were developed to evaluate multiciliogenesis master regulators, master regulators of core/ciliary planar cell polarity (PCP) and PCP components. Interaction scores for epithelial-derived cytokines—thymic stromal lymphopoietin (TSLP), IL-25, and IL-33—were calculated based on ligand and cognate receptor subunit expression. Results: The ciliary master regulatory hierarchy (e.g., FOXJ1, RFX2/3), PCP components (CELSR1 and the ciliogenesis and planar polarity effector (CPLANE) module: FUZ, INTU, WDPCP), and structural ciliogenesis pathways were robustly restored following IL-4/13 blockade. The TSLP interaction score correlated with global mucosal damage, serving as a trigger for compensatory multiciliogenesis. The pre-treatment IL-33 interaction score emerged as a significant predictor of transcriptomic ciliary recovery (p < 0.05). DNASE1L3—the primary endonuclease for degrading eosinophilic extracellular traps (EETs)—remained persistently downregulated post-treatment. Conclusions: IL-4/13 blockade successfully restores the structural and directional “hardware” of the respiratory epithelium but fails to rectify the enzymatic “software” required for mucus degradation. This “residual molecular scar” may explain the persistent mucus hyperviscosity observed in some ECRS patients even after clinical polyp resolution. Full article

TRAF3 (TNF Receptor Associated Factor 3) is a regulator of NF-κB signaling, acting mainly as an inhibitor of the alternative NF-κB pathway. While TRAF3 has a well-established role in immune function, mainly via B- and T-lymphocyte regulation, its roles in cancer remain unclear. Breast cancer is the most common malignancy in women and a neoplasm displaying high levels of intratumoral heterogeneity. Identifying and understanding key molecules at the interface of breast cancer cells and the immune system is crucial for advancing therapeutic strategies for breast cancer patients. Here, by employing publicly available breast cancer datasets, breast cancer cell lines stably expressing TRAF3, mass spectrometry analysis in combination with functional assays, co-culture systems, and signal pathway characterization, we sought to assess the specific role of TRAF3 in breast cancer cells and how TRAF3-expressing breast cancer cells affect their immune microenvironment. Our results indicate that TRAF3 protein overexpression inhibits colony formation through apoptosis regulation. Proteome analysis for TRAF3 interactors and over-representation analysis identified multiple protein complexes related to cell cycle, apoptosis, and immune responses. Furthermore, TRAF3-expressing breast cancer cells displayed reduced levels of PD-L1 and when co-cultured with PBMCs induced a pro-inflammatory profile with increased CD16-NK cells and higher levels of IFN-γ and TNF-α and lower IL-10 and Tregs in the culture. These findings further expand the role of TRAF3 in breast cancer, not only as a regulator of EMT and survival of cancer cells, but also as a modulator of the tumor-immune microenvironment. Full article

Psoriasis is an immune-mediated inflammatory disease with a genetic component, characterized by dysregulation of cytokine signaling and activation of T lymphocytes. This study investigated genetic variants associated with psoriasis, psoriatic arthritis (PsA), and response to tumor necrosis factor alpha (TNF-α) inhibitors (adalimumab, infliximab, and etanercept) in a Russian cohort. A genome-wide association study (GWAS) was conducted in 1026 psoriasis patients and 9212 controls using Infinium Global Screening Array-24 v3.0 microarrays. Exploratory analyses of treatment response (n = 48) and PsA (n = 96) were performed without covariate adjustment or explicit modeling of population structure. Polygenic risk scores (PRS) were derived from internally estimated effect sizes in a split-sample design. The GWAS replicated a robust association in the major histocompatibility complex (MHC) region (rs12189871 near HLA-C, p = 3.2 × 10⁻⁵⁰, OR = 2.99 [2.59–3.45]). Additional loci included variants in ZC3H8 and PLCL2. Nominal signals were observed for IL18R1/IL18RAP in treatment response (including rs17027071) and for RCL1 and FBLIM1 in PsA; these findings remain exploratory. PRS demonstrated moderate predictive performance (AUC = 0.6355) and should be interpreted with caution given the study design. Overall, the results highlight a strong MHC signal in psoriasis, while findings for PsA and treatment response remain hypothesis-generating and require independent validation. Full article