Psoriasis is linked to an increased risk of cardiovascular disease, but the impact of psoriasis on cardiac structure and function has been less clear. To assess cardiac structure, function and cardiometabolic risk factors in individuals with psoriasis compared with matched controls and across psoriasis severity. Cross-sectional analysis of 1010 adults with psoriasis from the prospective PSOCADIA cohort and 1010 age- and sex-matched controls without inflammatory skin disease. Participants underwent clinical assessment and transthoracic echocardiography. Cardiac abnormalities assessed included hypertrophy, valvular disease, systolic and diastolic dysfunction, and myocardial dysfunction defined by global longitudinal strain (GLS) <16%. Despite well-managed skin disease, individuals with psoriasis had more prevalent myocardial dysfunction by abnormal GLS (16.7% vs. 6.0%, p < 0.001) compared with controls. This association persisted after adjustment for cardiometabolic risk factors and atherosclerotic cardiovascular disease. Cardiac structure and function were largely similar across psoriasis severity. Higher body mass index and diabetes were independently associated with myocardial dysfunction in psoriasis. Individuals with psoriasis, even with well-managed skin disease, exhibit a higher burden of myocardial dysfunction compared with controls, independent of cardiometabolic comorbidity. The prevalence was similar across psoriasis severity, highlighting the importance of cardiovascular assessment in all patients with psoriasis. GOV: NCT04950218 (Prevalence and risk factors asSOciated with CArdiac comorbiDIty in psoriAsis, registered on 6 July 2021). WHAT IS THE DISEASE?: Psoriasis is a common chronic inflammatory skin condition that affects about 2–3% of adults. It causes red, scaly patches on the skin and is linked to a higher risk of heart and blood vessel diseases due to ongoing inflammation and shared risk factors. The study was conducted in the greater Copenhagen area, Denmark. We investigated whether people with psoriasis have differences in heart structure and function compared with people without psoriasis, and whether these changes are related to psoriasis severity. This study included 1010 adults with psoriasis and 1010 matched individuals without skin disease from the general population. Participants underwent detailed heart ultrasound examinations, including advanced imaging to detect subtle heart muscle changes. Clinical information on health, lifestyle and blood tests was also collected. People with psoriasis had more common risk factors such as higher body weight, high blood pressure and diabetes. Overall, heart‐pumping function was similar between groups. However, subtle signs of heart muscle dysfunction were more common in psoriasis, even when skin disease was well controlled. These changes were not related to psoriasis severity. Higher body weight and diabetes were linked to worse heart function in psoriasis. Psoriasis is associated with early, subtle changes in heart function that may not be detected by routine tests. This suggests that people with psoriasis may benefit from careful monitoring of cardiovascular risk factors, even when their skin disease is mild or well‐controlled.
Psoriasis is a chronic, inflammatory disease affecting up to 5% of the population. It significantly impacts patients' quality of life. In Africa, data on disease severity remain limited. The aim of this study was to evaluate the prevalence of severe psoriasis among Tunisian patients and to identify factors associated with disease severity and impairment of quality of life. A cross-sectional study was conducted using data from the Tunisian National Psoriasis registry (PsoTreg) (ClinicalTrials.gov ID: NCT05258838). A total of 1100 patients with psoriasis were included between July 12, 2022, and November 15, 2024. Disease severity and quality-of-life impairment were assessed using the Simplified Psoriasis Index (SPI). Demographic, clinical, and lifestyle data were analyzed to identify factors associated with disease severity and quality-of-life impairment. Moderate-to-severe psoriasis affected 31.9% of patients, with 38.3% experiencing quality-of-life impairment. Multivariate analysis confirmed male gender (odds ratio [OR]: 2.057), psoriatic arthritis (OR: 1.693), and substance use (alcohol OR: 2.759; smoking OR: 1.609) as independent severity predictors. There were gender-specific patterns, with smoking significantly associated with severity in men and obesity with quality-of-life impairment in women. This study, the first multicenter psoriasis registry in North Africa, highlighted the prevalence of moderate-to-severe psoriasis (31.9%). It emphasized a high proportion of patients with quality-of-life impairment (38.3%). Psoriasis severity was associated with smoking in men and obesity in women. These findings suggest a need for gender-tailored lifestyle interventions prioritizing mental health screening in the management of psoriasis patients.
Psoriasis, a chronic immune-mediated inflammatory skin condition with systemic implications and substantial psychosocial burden, affects individuals across races and ethnicities. This study explored social drivers of health (SDOH), disease burden, and the impact of psoriasis across races and ethnicities. An online, cross-sectional survey was conducted among adult US patients with psoriasis (September-December 2023). Participants were recruited through the National Psoriasis Foundation and AmeriSpeak, a national sample panel. Descriptive data were collected using patient-reported outcome measures and questions on disease knowledge, healthcare access and utilization, quality of life (QoL), and social impact. Analyses were stratified by races and ethnicities. Among 285 participants (mean age 46.7 years; 50.9% male), 68.1% identified as white, 19.3% as Black/African American (BAA), and 20.4% as Hispanic/Latino (H/L). Overall, psoriasis severity was reported as moderate by 36.8% (white: 37.6%, BAA: 25.5%, Asian: 50.0%, and H/L: 27.6%) and severe by 10.2% (white: 8.2%, BAA: 10.9%, Asian: 20.0%, and H/L: 6.9%) of patients. Participants reported moderate QoL impact (Dermatology Life Quality Index [DLQI] mean 10.3), with high burden among H/L (16.6) and BAA (15.1) groups. During flares, 58.6% used prescription medications, with similar rates across races and ethnicities. Transportation barriers were reported by 21.4% overall, more commonly reported by H/L (44.8%) and BAA (34.5%) participants. Difficulty accessing medicine/healthcare was reported by 26.3% overall, particularly white (29.4%) participants. Overall, 29.1% delayed care owing to cultural/linguistic differences, most commonly by BAA and H/L groups. Of the healthcare services requiring partial out-of-pocket payment for treatment of psoriasis, medications were reported as the highest burden by an overall 47.0% of patients (H/L: ~55%, white and BAA ~45%). Overall, only 29.5% received financial assistance. In this descriptive survey, patients perceived psoriasis as a considerable burden across races and ethnicities. Understanding diversities in patient-reported SDOH and healthcare access issues through culturally competent integrated care may potentially optimize psoriasis outcomes.
Background: Psoriasis is a chronic inflammatory disease frequently associated with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for T2DM and obesity, have demonstrated anti-inflammatory and immunomodulatory properties that may be relevant in psoriasis. However, individual GLP-1RAs differ substantially in their pharmacological characteristics and clinical effects. Our objective was to systematically review the available evidence on the effects of individual GLP-1RAs in patients with psoriasis. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and Scopus were searched up to April 2026 for studies evaluating GLP-1RAs in psoriasis. Case reports, case series, observational studies, and randomized controlled trials were included. Preclinical, clinical and safety outcomes were extracted and narratively synthesized. Results: Twenty-six studies met the inclusion criteria. Most involved patients with concomitant obesity and/or T2DM. Overall, semaglutide, liraglutide, exenatide, and tirzepatide were associated with improvements in psoriasis severity, often accompanied by reductions in body weight, glycated haemoglobin, inflammatory markers, and cardiometabolic risk factors. Semaglutide and liraglutide showed the most consistent evidence of benefit. Experimental and clinical data also suggested direct immunomodulatory effects on pathways involved in psoriasis pathogenesis. However, paradoxical psoriasiform eruptions and psoriasis exacerbations were reported with some agents. The evidence base was limited by the predominance of case reports and small observational studies, substantial heterogeneity, and the limited availability of randomized controlled trials. Conclusions: Current evidence suggests that GLP-1RAs may improve both psoriatic disease activity and cardiometabolic outcomes, particularly in patients with obesity or T2DM. Nevertheless, potential differences among individual agents warrant further investigation in larger controlled studies.
Langerhans cells (LCs) play a crucial role in sensing and processing stimuli from the skin and the external environment. They are implicated in various skin disorders, acting either as pro-inflammatory agents or as regulatory elements. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear. Psoriasis is characterized by a significant Th17/Treg immune imbalance. To elucidate the independent effect of Treg dysfunction on psoriatic inflammation, we established a Treg-inhibited psoriasis group using the Foxp3 inhibitor CMD178, in conjunction with LC depletion models to investigate the LC-Th17/Treg regulatory axis METHODS: Psoriasis models were established through the topical application of IMQ. Female C57BL/6N mice were divided into three groups: control, IMQ-induced psoriasis, and Treg-depleted psoriasis. Langerhans cells (LCs) were depleted using diphtheria toxin in Langerin-DTR mice, while Tregs were inhibited by CMD178. Inflammation was assessed through measurements of ear thickness, histopathology, apoptosis, and cytokine production. Additionally, RT-qPCR was utilized to detect the expression of S100A7, S100A8, and MMP2. Flow cytometry was employed to analyze the functional status of lymphocytes and T cell phenotypes. IMQ-induced psoriasis-like lesions exhibit activated LCs, an increase in Th17 cells, a decrease in Tregs, elevated levels of IL-17A and IL-22, and reduced levels of TGF-β and PD-L1. Depletion of LCs alleviated the lesions and restored the Th17/Treg balance, whereas depletion of Tregs exacerbated the inflammation. LCs play a central regulatory role in the psoriatic skin environment by influencing the Th17/Treg.
Psoriasis is a chronic, immune-mediated inflammatory disease in which durable, treatment-free remission is rarely achieved despite highly effective biologic therapies. We report a 60-year-old woman with a 49-year history of severe, treatment-refractory plaque psoriasis who developed complete and sustained disease clearance following autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy for follicular lymphoma. Psoriasis resolved within four weeks of CD19 CAR-T-cell therapy and has remained in remission for over 4.5 years without any psoriasis-directed treatment. This observation, together with emerging reports, suggests that deep tissue depletion of B-lymphoid lineage cells in psoriasis may induce long-term disease modification. Mechanistically, CD19 CAR-T therapy targets a broader spectrum of B-cell populations than anti-CD20 approaches, potentially disrupting pathogenic B-T cell interactions and autoreactive immune circuits. These findings challenge the prevailing T cell-centric paradigm of psoriasis and support exploration of B-cell-directed, immune reset strategies as a route towards durable remission or cure.
Psoriasis is a chronic, autoimmune skin disorder that can be associated with systemic comorbidities, including psoriatic arthritis (PsA). The coexistence of psoriasis, PsA, and autoimmune hepatitis (AIH) is uncommon and may present diagnostic and therapeutic challenges. This case report highlights a patient with psoriasis who developed both PsA and AIH without prior immunosuppressive therapy. A 57-year-old Palestinian woman with longstanding plaque psoriasis presented with worsening skin lesions, progressive arthralgia involving both knees and ankles, chronic inflammatory low back pain, and persistently abnormal liver biochemistry. She had been diagnosed with psoriasis at age 49, which had been resistant to various treatments, including topical corticosteroids and phototherapy. One year before presentation, the patient developed progressive arthralgia, particularly in the knees, ankles, and lower back. Physical examination revealed swollen joints and limited range of motion. Laboratory tests indicated elevated liver enzymes, and autoimmune panel results were positive for antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), raising suspicion for autoimmune hepatitis. A liver biopsy confirmed type 1 AIH, characterized by lymphocytic infiltration and plasma cell predominance. Cyclosporine 100 mg daily was initiated, atorvastatin was discontinued, and the patient was monitored clinically and biochemically. After 6 weeks, psoriasis severity improved markedly, joint symptoms decreased, and liver enzyme levels normalized. No treatment-related adverse effects were documented during the reported follow-up period. This case highlights the importance of considering autoimmune hepatitis in patients with psoriatic disease who develop persistent liver enzyme abnormalities, even in the absence of prior systemic immunosuppressive therapy. A multidisciplinary approach is important in such complex presentations, and cyclosporine may be a useful therapeutic option in selected patients requiring concomitant control of dermatologic, rheumatologic, and hepatic disease.
The skin barrier serves as the body's primary line of defense against exogenous insults and is critical for maintaining systemic homeostasis. Emerging evidence indicates that skin barrier dysfunction is not merely a secondary manifestation of psoriasis, but rather an early and pivotal pathogenic driver of the disease. It exerts bidirectional crosstalk with immune dysregulation, genetic predisposition and environmental triggers, collectively contributing to the initiation and progression of psoriasis. This review first elaborates on the normal structural composition and physiological functions of the skin barrier, followed by a discussion of the major etiological factors of psoriasis and the underlying mechanisms by which barrier impairment promotes psoriasis pathogenesis. These mechanisms include aberrant keratinocyte hyperproliferation, abnormal expression of structural proteins, tight junction disruption, aquaporin 3 dysfunction and dysregulated cutaneous lipid metabolism. Furthermore, we highlight the clinical significance of skin barrier restoration in psoriasis management and propose directions for future research. Elucidating the intricate crosstalk between skin barrier dysfunction and psoriasis pathogenesis will facilitate the identification of novel diagnostic biomarkers and the development of targeted therapeutic strategies for this disease.
Tildrakizumab is an anti-interleukin 23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. Globally, patients aged ≥65 years are 9.8% to 12.8% of patients with psoriasis who are treated with biologics, but they are often underrepresented in clinical trials. To summarize the available evidence on the efficacy and safety of tildrakizumab in patients aged ≥65 years with psoriasis for a United States (US)-based healthcare practitioners audience. A PubMed search was conducted using the search terms "(tildrakizumab OR MK-3222 OR Ilumya) AND psoriasis AND (elderly OR 65 years)" to identify English-language clinical trials and real-world studies evaluating efficacy and safety of tildrakizumab in elderly patients with psoriasis. Two clinical trials and 5 real-world studies describing the efficacy and safety of tildrakizumab in patients aged ≥65 years were identified. The short- and long-term efficacy of tildrakizumab was comparable between patients aged <65 and ≥65 years. Adverse events were consistent with those observed among the overall clinical trial population, with some expected increases in age-related events. The number of studies with data for patients aged ≥65 years, and sample sizes within some studies, were small, limiting interpretation. Based on available data, the established efficacy and safety profiles of tildrakizumab are maintained in patients aged ≥65 years with moderate-to-severe plaque psoriasis. Practical considerations, including insurance coverage, quarterly maintenance dosing, and in-office administration, in the US may increase treatment adherence and make tildrakizumab an appropriate treatment option for elderly patients.
While dietary factors are known to be associated with the development and progression of psoriasis, their effect on treatment efficacy remains unclear. Therefore, this study aimed to elucidate the influence of tea consumption, sugar drinks, and high-fat foods on the treatment response in psoriasis. We undertook a prospective cohort study comprising 559 patients with psoriasis from Shanghai Skin Disease Hospital between 2022 and 2024. Data on demographics, lifestyle (including tea, sugary drinks, and high-fat food consumption), and disease severity (PASI, BSA, PGA) were collected via structured questionnaires at baseline, week 4, and week 8. The primary endpoints were the proportions of patients achieving PASI 50 responses at week 8. Multivariable logistic regression was used to estimate odds ratios with 95% confidence intervals, adjusting for age, sex, BMI, smoking, alcohol, and treatment regimen. Data were analyzed using SAS 9.4 software. In the psoriasis cohort (mean age 48.5 years; 73.2% male), 37.1% and 68.7% of patients consumed sugar drinks and high-fat foods ≥2 times/week, respectively. Frequent sugar drinks consumption (≥4 times/week) was independently associated with significantly reduced odds of achieving PASI 50 (adjusted OR=0.24, 95% CI: 0.08-0.75) and PASI 75 (adjusted OR=0.27, 95% CI: 0.07-1.00) at week 8. Moderate intake of high-fat foods (2-3 times/week) showed an inverse, borderline significant association with PASI 50 at week 4 (adjusted OR=0.68, 95% CI: 0.45-1.00). Tea consumption showed a non-significant association with treatment response (e.g, week 8 PASI 50 adjusted OR=1.44, 95% CI: 0.88-2.35), warranting further investigation in larger cohorts. This study demonstrates that high consumption of sugar drinks and high-fat foods is associated with suboptimal treatment response in psoriasis. Tea consumption was not significantly associated with treatment outcomes, although further investigation with larger cohorts may be warranted. These findings highlight the importance of integrating dietary assessment and counseling into comprehensive psoriasis management.
Psoriasis is a prevalent inflammatory skin disorder exhibiting a rapidly increasing incidence. Curcumin (Cur) serves as an effective therapeutic agent for psoriasis and is commonly administered through the cutaneous route. Nevertheless, the poor skin permeability and retention of Cur restrict its therapeutic efficacy against psoriasis. In this study, we fabricated mussel adhesion protein (MAP)-modified Cur-loaded ethosomes (Cur-MAP-Es) aimed at enhancing both the permeation and retention of Cur within the skin for improved topical treatment of psoriasis. The average particle size of Cur-MAP-Es was 197.17 nm, and the encapsulation efficiency was 90.84%. The Cur-MAP-Es exhibited a spherical morphology, along with high elasticity, favorable stability, and a prolonged release pattern within 24 h. Additionally, the Cur-MAP-Es exhibited a 3.47-fold higher skin retention compared to the Cur-Es. Intradermal fluorescence distribution analysis indicated that most of the Cur in the Cur-MAP-Es was effectively retained in the epidermis after being delivered into the skin via vesicles. The interaction mechanisms of Cur-MAP-Es with the skin have revealed that Cur-MAP-Es can weaken the skin barrier, thereby facilitating enhanced permeability and drug retention. Furthermore, Cur-MAP-Es could significantly alleviate the inflammation in the mouse model of psoriasis. These results suggest that Cur-MAP-Es may serve as an effective strategy to enhance the topical delivery efficiency of Cur, thereby showing considerable potential in the management of psoriasis.
Psoriasis is a chronic inflammatory skin disorder driven by epidermal hyperplasia, immune infiltration, and pathological angiogenesis. PAP‑1, a selective Kv1.3 channel blocker, exhibits therapeutic potential, though its underlying mechanisms remain incompletely understood. Here, we show that both preventive and therapeutic administration of PAP‑1 markedly attenuates imiquimod (IMQ)-induced psoriasis‑like skin lesions and reduces splenomegaly in male rats. RNA sequencing revealed that PAP-1 downregulated genes associated with inflammation and angiogenesis, accompanied by decreased levels of pro-inflammatory cytokines and vascular markers. PAP-1 also inhibited VEGF-A-induced HUVEC proliferation, migration, invasion, and tube formation. Mechanistically, PAP-1 not only blocked Kv1.3 currents, but also suppressed Kv1.3 expression in the skin of IMQ-induced psoriasis-like male rats and VEGF-A-induced HUVECs. Cryo-EM structural analysis revealed that PAP-1 binds within the central cavity of Kv1.3, beneath the selectivity filter, in an inactivated state. These results establish that preventive and therapeutic PAP-1 alleviates psoriasis-like dermatitis via dual anti-inflammatory and anti-angiogenic mechanisms, supporting its further therapeutic development.
Psoriasis patients were 4- 5 times more likely to have S. aureus colonize their skin. Psoriasis is caused by staphylococcal infection-induced keratinocyte death, which is maintained by elevated cytokine production of TNF-α and IFN-γ. The study sought to determine the association between the influence of gene expression of certain genes in psoriasis infections in the presence of S. aureus and their effect in Skin Cutaneous Melanoma infections. GEO with accession number (GSE207390) was used to acquire the data. The microarray test was used to perform this investigation. Six sets of keratinocytes, IL-17A, and TNF-α were cultivated together. Several kinds of bioinformatics tools were employed to fulfill the study's objective. Gene hub analysis of 34284 genes was scanned. Six genes demonstrated high expression rates were expressed during the metastatic stage: CCL27, IL19, PAPPA2, UHRF1, IFNAR2, and GLS2. IFNAR2 and UHRF1 had the highest levels of expression. The expression of the COL4A4 gene rose in response to sun exposure, but the expression of the other genes remained same. The existence of cytokine groups with S. aureus in keratinocytes influences the expression difference compared to the other groups. This work adds to our understanding of the molecular alterations that occur in the epidermis of psoriasis patients, as well as their relationship to comorbidities.
Emerging evidence suggests the involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of autoimmune dermatological diseases. In a small exploratory study, we investigated angiotensin-converting enzyme (ACE) activity in blood obtained from male probands with psoriasis vulgaris (n = 4) and atopic dermatitis (AD, n = 5). The degradation capacity of dabsylated synthetic bradykinin (DBK) with and without inhibition was determined using a thin-layer chromatography (TLC)-based neuropeptide reporter assay. We observed a significantly reduced capacity for cleavage of DBK in psoriasis patients compared with that in AD patients and controls. In patient samples, the variation in the measured values was generally greater than that in healthy controls. We could not confirm the increased ACE activity in the circulation in psoriasis patients reported by others, likely because of different study designs and detection methods. We did not include samples of female patients and focused on younger men to avoid hormonal effects and minimize age-related factors. This preliminary study of the hypothesis-generating nature lacks power, but it certainly adds a question to the current view of the role of ACE in psoriasis. Treatments targeting specific components of the RAS could ameliorate inflammatory responses; thus, research in this area is becoming increasingly important.
Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by persistent epidermal hyperplasia and relapsing inflammation. Although extensive progress has been made in elucidating individual pathogenic pathways, a unifying framework that integrates innate immune activation, adaptive immune maintenance, and keratinocyte-driven amplification remains incomplete. Accumulating evidence indicates that nuclear factor-κB (NF-κB) functions as a central convergence hub that coordinates these diverse inflammatory inputs in psoriasis. In this review, we synthesize recent advances demonstrating how innate immune sensors, including nucleic acid-sensing pathways and Toll-like receptors, converge on NF-κB to initiate inflammatory programs, and how adaptive immune circuits-particularly Th17/IL-17 signaling-exploit NF-κB to sustain disease chronicity. We further highlight the active role of keratinocytes as intrinsic amplifiers of inflammation through NF-κB-dependent programs governing hyperproliferation, oxidative stress responses, and secondary cytokine production. Beyond canonical signaling, emerging evidence reveals that non-coding RNAs and epigenetic regulators fine-tune NF-κB activity, shaping transcriptional persistence and inflammatory memory in psoriatic skin. Finally, we discuss therapeutic strategies targeting the NF-κB convergence hub, including upstream sensor antagonism, adaptor-level modulation, multi-target small molecules, natural products, and advanced skin-targeted delivery systems. By framing NF-κB as a networked regulatory hub rather than a linear pathway, this review provides an integrated perspective on psoriasis pathogenesis and highlights opportunities for precision immunomodulation with improved efficacy and safety.
Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune activation. The single nucleotide polymorphism (SNP) rs610604 within the TNFAIP3 locus is associated with increased psoriasis susceptibility and response to TNF-targeted therapies, yet its functional mechanism remained unclear. In this study, we identify, to our knowledge, previously unreported regulatory axis linking IKKα to TNFAIP3 in keratinocytes and demonstrate how genetic variation at rs610604 modulates inflammatory signaling. Genome-wide chromatin profiling revealed nuclear IKKα predominantly occupies transcriptionally inactive regions and acts as a chromatin-associated repressor. Among its targets, TNFAIP3 emerged as a key locus containing an IKKα-binding region overlapping the rs610604 variant. Functional analyses showed allele-specific recruitment of IKKα, with the psoriasis-risk G allele displaying stronger and more persistent binding compared with the protective T allele. This interaction promotes transcriptional repression of TNFAIP3, a negative regulator of NF-κB, MAPK, and IL-17 pathways, thereby sustaining pro-inflammatory signaling; consistently in psoriatic lesions nuclear IKKα is reduced. These findings identify a nuclear IKKα-TNFAIP3 axis linking genetic susceptibility to inflammatory signaling, providing a potential explanation for the paradox of chronic inflammation without frequent malignant transformation in psoriatic skin, and highlighting IKKα as a potential therapeutic target in psoriasis and related inflammatory disorders.
Psoriasis is a chronic inflammatory seronegative disease closely associated with ankylosing spondylitis and inflammatory bowel disease. This study aimed to investigate the anti-inflammatory effects of candidate metabolites, such as D-proline, L-iditol, and propionylcarnitine, identified in Clonorchis sinensis preparations, in in vitro and in vivo models. None of the 3 metabolites exhibited cytotoxicity within the tested concentration range. In LPS-stimulated RAW 264.7 cells, D-proline and L-iditol significantly reduced the expression of pro-inflammatory cytokines, and in an imiquimod-induced psoriasis-like mouse model, L-iditol significantly reduced disease severity and histopathological scores, whereas the effects of other metabolites were inconsistent. These research results suggest that L-iditol, a candidate metabolite identified in Clonorchis sinensis formulations, exhibits anti-inflammatory effects in both in vitro and in vivo environments and may have therapeutic potential for inflammatory skin diseases such as psoriasis.
Background/Objectives: Psoriasis vulgaris is a chronic inflammatory skin condition with significant psychosocial burden. While phototherapy remains one of the most widely used treatment regimens, novel modalities like blue light therapy offer UV-free alternatives with potentially more favorable safety profiles, but their systemic immunomodulatory effects remain poorly understood. We aimed to evaluate the impact of full-body blue light irradiation on clinical outcomes and selected systemic biochemical and immunological markers in patients with mild-to-moderate psoriasis vulgaris. Methods: This preliminary study involved 21 patients (13 females, 8 males) with mild-to-moderate psoriasis vulgaris. Participants received ten sessions of full-body blue light therapy (453 nm, 40 mW/cm2, 30 min per session). Clinical assessments (PASI, PGA, DLQI, VAS, Pruritus Scale) and serum analyses of inflammatory (TNF-α, IL-13, IL-17, IL-31), metabolic (adiponectin, 25(OH)D3), and neuroimmune markers (serotonin, kynurenic acid, quinolinic acid) were performed pre- and post-treatment. Results: Significant improvements were observed in PASI, PGA, DLQI, and pruritus scores (p < 0.05). 25(OH)D3, serotonin, and kynurenic acid levels increased significantly, while IL-31 and IL-17 levels decreased and IL-13 levels increased; TNF-α, adiponectin, and quinolinic acid levels showed no significant changes. Counterintuitively, correlation analysis demonstrated a moderate positive association between changes in IL-13 and PASI improvement (r = 0.51, p = 0.02), while changes in other biochemical parameters were not significantly associated with clinical outcomes. Conclusions: Full-body blue light therapy resulted in significant clinical improvement accompanied by heterogeneous systemic immunometabolic changes. These findings suggest complex, pathway-specific immunomodulation, but this requires further investigation in larger controlled studies.
Psoriasis is a chronic immune-mediated inflammatory skin disease driven by persistent IL-23/Th17 axis activation. While biologics have improved disease control, their clinical use is constrained by immunotoxicity risks and long-term safety concerns. Plant-derived extracellular vesicle-like nanoparticles (EVLNs) are being investigated as a potential biocompatible nanotherapeutic platform, yet systematic safety profiling and network-level elucidation of their immunomodulatory mechanisms remain lacking. This study integrates Systems Pharmacology, computational transcriptomic profiling, and experimental validationto evaluate the preliminary safety profiles and therapeutic mechanisms of Panax notoginseng-derived EVLNs (PN-EVLNs) in Th17-driven psoriatic inflammation. PN-EVLNs were isolated, characterized, and evaluated in an imiquimod-induced psoriasis-like mouse model and IL-6/TGF-β-stimulated Jurkat T cells. A systems biology framework integrating bulk RNA sequencing, public single-cell transcriptomic datasets, and pathway enrichment analysiswas employed to map treatment-responsive molecular networks and identify key regulatory modules. Computational toxicity prediction and immune pathway deconvolution were combined with histological, biochemical, and molecular validation. Systems Pharmacology and transcriptomic profiling revealed that PN-EVLNs reversed psoriasis-associated inflammatory gene signatures, with computational pathway analysis identifying suppression of chemokine, IL-17, and NF-κB signaling networks. Computational safety profiling, supplemented by histological observation, suggested a favorable preliminary safety profile with no significant immunotoxic gene signatures observed in the tested models in treated models. Experimental validation confirmed that PN-EVLNs downregulated Th17-associated markers (CCR6, Tim-3) and pro-inflammatory cytokines (IL-17A, TNF-α, CCL7, CXCL10, IL-1β). Network-based mechanistic analysis pinpointed STAT5/SOCS3 as a key negative feedback regulatory module restraining Th17-driven inflammation. Integrative Systems Pharmacology and computational safety profiling suggest that PN-EVLNs may serve as a biocompatible plant-derived nanotherapeutic with a promising preliminary safety profile. Reactivation of the STAT5/SOCS3 regulatory network underlies its immunomodulatory effects,providing a basis for the network-guided development of safer anti-psoriatic therapies using PN-EVLNs.
Interleukin (IL)-17 and IL-23 inhibitors have transformed psoriasis care, delivering high clearance rates and quality-of-life gains. Nevertheless, inadequate response or adverse events can lead to treatment discontinuation or biologic switching. Dose modifications are also commonly implemented in routine practice to optimize efficacy, safety, and cost. The objective of this study is to characterize real-world outcomes of dose adjustment and switching of IL-17 and IL-23 inhibitors in Thai patients with psoriasis. We retrospectively reviewed 173 treatment courses with IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and the IL-23 inhibitor guselkumab, documenting loading regimens, maintenance dosing, efficacy to Week 52, and switching events. At Week 12, full loading and standard maintenance dosing were associated with higher response rates in most cases. Ixekizumab was least often given with a full loading dose or standard maintenance dosing. By Weeks 24 and 52, reduced-dose regimens achieved comparable or better outcomes, suggesting careful patient selection. Thirty courses underwent biologic switching, predominantly for secondary failure. Intraclass switching among IL-17 inhibitors predominated. Switching from IL-23 to IL-17 inhibitors potentially outperformed both intraclass IL-17 switching or IL-17-to-IL-23 transitions. Erythrodermic psoriasis and higher baseline disease severity predicted switching, whereas incomplete loading doses and dose reductions did not. In conclusion, full loading and standard maintenance regimens facilitate early treatment response, while dose reduction in carefully selected patients can sustain long-term disease control without increasing the risk of switching.