IMPORTANCE:Available evidence reveals markedly divergent metabolic signatures across biologics and small-molecule inhibitors, highlighting the need for further investigations. OBJECTIVE:To address this knowledge gap, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in patients with psoriasis or psoriatic arthritis (PsA) to quantify the short- and long-term effects of targeted therapies on lipid profiles. EVIDENCE REVIEW:PubMed, Embase, and Cochrane databases were searched for RCTs and observational studies published through July 25, 2025. Eligible randomized RCTs were evaluated using the Cochrane Risk of Bias tool, while nonrandomized studies were assessed using the Methodological Index for Non-Randomized Studies. All lipid effect estimates were derived from within-group pre-to-post changes in patients with psoriasis or PsA. FINDINGS:Thirty-six articles involving 21,477 patients with psoriasis and 3098 patients with PsA (total 24,575) across seven targets were analyzed. The long-term use of Janus kinase inhibitors (JAKi) significantly increases total cholesterol (TC; weighted mean difference [WMD] = 7.03; 95% confidence interval [CI] = 1.22, 12.84), triglyceride (TG; WMD = 19.98; 95% CI = 13.82, 26.14), high-density lipoprotein cholesterol (HDL-c; WMD = 6.87; 95% CI = 4.38, 9.36), and low-density lipoprotein cholesterol (LDL-c; WMD = 12.37; 95% CI = 7.24, 17.50) levels. Long-term tumor necrosis factor alpha inhibitors (TNFi) significantly lowers TC (WMD = -8.40; 95% CI = -15.21, -1.60), TG (WMD = -15.22; 95% CI = -21.92, -8.51), and LDL-c (WMD = -10.61; 95% CI = -16.77, -4.45) levels while raising HDL-c (WMD = 4.13; 95% CI = 1.23; 7.03) levels. Long-term interleukin-17 A inhibitors significantly increases TG (WMD = 7.31; 95% CI = 3.17, 11.46) levels, whereas IL-23p19 inhibitors yield the opposite effect (WMD = -32.08; 95% CI = -51.87, -12.30). CONCLUSIONS AND RELEVANCE:Our data underscore the need for routine lipid monitoring during TNF-α- and JAK-targeted therapy in patients with psoriasis or PsA. Due to the limitations of our analysis, well-designed prospective trials with extended follow-up periods are warranted to validate and refine these observations.

BACKGROUND/AIM:Melanoma is an aggressive malignancy with rising global incidence. While early surgical intervention improves survival in localized cases, treatment resistance and recurrence remain a challenge. This underscores the critical need to identify prognostic biomarkers for early diagnosis, personalized treatment, and novel therapeutic development. MATERIALS AND METHODS:The GSE126076 and melanoma dataset (Skin Cutaneous Melanoma, TCGA, PanCancer Atlas) were analyzed using an information-theoretical method to identify prognostic factors. Survival analysis was performed via Kaplan-Meier curves and log-rank tests to compare high- and low-mRNA expression groups. In vitro, A375 cells and A2058 cells were treated with the GGT inhibitor 6-diazo-5-oxo-L-norleucin (DON). Cell viability was assessed using the CCK-8 assay and intracellular GSH levels were measured following treatment. RESULTS:Through information-theoretic analysis and survival analysis, we identified GGT6 as a prognostic gene in melanoma. Survival analysis revealed that high GGT6 expression was significantly associated with shorter disease-specific survival across all disease stages. In vitro, 10 μM DON for 72 h reduced A375 cell proliferation by 90.72% versus control (p<0.0001), with an IC50 of 5.14 μM; and reduced A2058 cell proliferation by 60.93% (p<0.0001), with an IC50 of 7.93 μM. Measurement of GSH levels of A375 and A2058 cells revealed that melanoma cells treated with 10 μM DON exhibited lower GSH levels compared with the respective control groups (p<0.0001 and p=0.0042, respectively). CONCLUSION:Our study is the first to demonstrate the association between GGT6 expression levels and melanoma prognosis, and reveals that GGT inhibition suppresses melanoma cell viability. These findings provide new insights into the mechanisms of melanoma development and progression, and suggest GGT as a potential therapeutic target for clinical treatment.

BYSL gene encodes the bystin-like (BYSL) protein, a nucleolar protein involved in eukaryotic ribosome biogenesis and essential for 40S ribosomal subunit synthesis. Although BYSL upregulation has been implicated in hepatocellular carcinoma, its mechanistic contribution to tumor progression remains undefined. We observed that BYSL is consistently upregulated across multiple cancer types and is associated with adverse clinicopathological features and poor prognosis, with the strongest clinical relevance observed in hepatocellular carcinoma through the integrative transcriptomic and proteomic analyses. BYSL-knockout suppresses malignant phenotypes, including proliferation, migration, and invasion, and induced G1/S arrest and apoptosis. Mechanistically, loss of BYSL disrupts nucleolar homeostasis and reduces global protein synthesis, thereby activating the RPL5/RPL11-MDM2-p53 axis, leading to p53 stabilization and tumor suppression. Importantly, MYC directly bound to the BYSL promoter and transcriptionally activated its expression, whereas co-targeting BYSL and MYC produced more synergistic antitumor effects than either intervention alone. Collectively, our study reveals that BYSL acts as a pivotal downstream mediator of MYC-regulated ribosome biogenesis and promotes hepatocellular carcinoma progression. Our findings suggest that BYSL may represent a potential therapeutic target for hepatocellular carcinoma; nevertheless, additional in vivo preclinical studies are warranted to validate its translational prospects.

The etiology and pathogenesis of melanoma are not fully elucidated. Recent studies have shown that circadian rhythm disruption can reconstruct the immune microenvironment of melanoma, and affect DNA repair, melanin synthesis and other processes, and may be an important step in the occurrence and development of melanoma. In addition, mutations in circadian clock genes can also increase the genetic susceptibility to melanoma. This review focuses on mechanisms underlying the regulation of circadian rhythm in the occurrence and development of melanoma, and new progress in melanoma treatment, providing a completely new perspective for the prevention and treatment of melanoma.

Objectives This post-hoc analysis of CM310AD005 conductedaimed to analyze the efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis (AD) with and without prior systemic treatment.Methods In CM310AD005, eligible patients were randomized 1:1 to receive stapokibart 600 (loading dose)-300 mg and placebo Q2W for 16 weeks; all patients subsequently received stapokibart 300 mg Q2W for 36 weeks.Results At week 16, in systemic treatment-naïve patients, stapokibart led to significantly higher response rates than placebo for ≥75% improvement from baseline in the Eczema Area and Severity Index score (EASI-75, 70.3% vs. 29.1%), EASI-90 (38.1% vs. 13.3%), Investigator’s Global Assessment score of 0 or 1 (45.2% vs. 19.4%), and ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale score (34.8% vs. 13.9%) (all p < 0.0001). Among patients with prior systemic treatment, these response rates were also significantly higher in the stapokibart group, reaching 61.5% vs. 19.3%, 35.4% vs. 7.2%, 42.7% vs. 9.6%, and 37.5% vs. 7.2% (all p < 0.0001), respectively. All patients showed further improvements through week 52. The most common treatment-emergent adverse events were infections and infestations, occurring in 61.6% and 70.5% of patients with and without prior systemic treatment.Conclusions Stapokibart demonstrated significant clinical efficacy and manageable safety in AD patients irrespective of prior systemic treatment.

Vitiligo is a chronic autoimmune disorder characterized by selective melanocyte loss and progressive depigmentation. Narrowband ultraviolet B (NB-UVB) and excimer-based phototherapy are widely regarded as standard treatments in clinical practice and remain the most effective approaches for inducing repigmentation. However, excessive or uncontrolled ultraviolet radiation (UVR) exposure can impair skin barrier function, cause melanocyte dysfunction, and increase the risk of photoaging and carcinogenesis. This apparent paradox arises from the bidirectional biological effects of UVR: on the one hand, UVR activates melanocytes and promotes skin pigmentation through coordinated effects on melanocyte maturation, proliferation, and melanin synthesis, while on the other hand, UVR can induce oxidative stress, DNA damage, apoptosis, and genomic instability. Therefore, combination strategies incorporating JAK inhibitors, platelet-rich plasma, or cellular grafting techniques have been increasingly explored in clinical practice. In this review, we provide an integrated perspective on the dual effects of UVR on melanocyte biology, discuss emerging combination therapies for vitiligo, and highlight the mechanistic links between phototherapy, melanocyte homeostasis, and melanoma risk.

Altered skin bacteriome has been associated with keloid yet the relation of fungal community to this disease remains unclear. This study aimed to characterize the skin mycobiome in patients with keloid and its correlation to disease severity. A case-control study was designed to investigate the fungal landscape in participants with keloid and healthy controls. Disease severity was assessed using Vancouver Scar Scale. Swabs of the keloid lesion (KL) and non-lesional (KNL) skin of keloid patients and corresponding skin sites of healthy controls (C) were obtained for ITS rRNA sequencing. Our findings revealed decreased richness and evenness in the fungal community within the KL as well as KNL groups compared to C (P<0.01). Notably, fungal composition was more similar between KNL and C compared to KL (KL-C, ANOSIM: R=0.12, P=0.004; KL-KNL, ANOSIM: R=0.10, P=0.021; KNL-C, ANOSIM: R=0.03, P=0.215). Skin mycobiome in KL was more enriched with Malassezia (P<0.05), and depleted in Cladosporium, Alternaria, Aspergillus and Debaryomyces (P<0.05). Correlation analysis identified a positive association between the relative abundance of Malassezia and disease severity (rs=0.56, P=0.007). The present study shows a decreased fungal diversity and altered fungal composition structure in keloid lesions. The overabundance of Malassezia and its correlation to disease severity highlight a potential role of these fungi in the pathogenesis of keloid and offer insights into novel disease-management approaches.

Background: Impaired angiogenesis is the primary driver of refractory diabetic cutaneous wounds, a devastating complication associated with persistently high global rates of amputation and disability. Circulating extracellular vesicles (EVs) and their encapsulated microRNAs (miRNAs) serve as pivotal regulators of angiogenesis and wound healing by mediating intercellular communication. Although the classic traditional Chinese medicine herb pair Astragalus membranaceus (Fisch.) Bunge–Salvia miltiorrhiza Bunge (Huangqi-Danshen, HD) has long been used for diabetic wound repair, its pro-healing mechanisms involving circulating EV-associated miRNAs remain largely unelucidated.Methods: We employed an integrated strategy combining network pharmacology, EV-related miRNA target database analysis, and systematic in vitro and in vivo experiments to explore the underlying mechanisms of HD. Serum EVs were isolated and characterized from HD-treated rats, and their effects on high glucose-injured human umbilical vein endothelial cells (HUVECs) and L929 fibroblasts were evaluated. Furthermore, the therapeutic efficacy of HD was validated in a streptozotocin-induced diabetic wound mouse model. Key targets and pathways were predicted using network pharmacology and molecular docking. Based on published evidence that miR-20b-5p is aberrantly overexpressed in circulating EVs of diabetic patients and closely associated with impaired angiogenesis and delayed wound closure, this miRNA was selected as the candidate molecule for targeted validation in the present study.Results: In vitro, HD-derived serum EVs were efficiently internalized by target cells, significantly reversing high glucose-induced damage by promoting cell proliferation, migration, and angiogenesis while inhibiting apoptosis. In vivo, HD markedly accelerated wound closure, ameliorated dyslipidemia, enhanced dermal regeneration and collagen deposition, and downregulated the levels of pathogenic miR-20b-5p in circulating EVs. Bioinformatic analysis and preliminary in vivo validation suggested that the pro-healing effects of HD may be partially associated with EV-associated miR-20b-5p and its regulatory effect on the AGE-RAGE signaling axis, with STAT3/CCND1/VEGFA as potential downstream targets.Conclusion: The Astragalus membranaceus–Salvia miltiorrhiza herb pair exerts therapeutic effects on diabetic wound healing.The EV-associated miR-20b-5p/AGE-RAGE axis may serve as a potential mechanistic target, providing a preliminary research perspective for subsequent in-depth functional validation.

BackgroundSSGJ-608 is an anti-interleukin-17A monoclonal antibody with high specificity and high affinity and has shown promising efficacy in treatment of moderate-to-severe psoriasis in preliminary trials.ObjectiveThis multicenter, randomized, open-label, phase 3 trial aimed to further evaluate SSGJ-608 at different dosing intervals (80mg every two weeks and 160mg every four weeks) in patients with moderate-to-severe plaque psoriasis.MethodsA total of 770 patients with moderate to severe plaque psoriasis were randomly assigned (1:1) to receive subcutaneous injections of 80mg of SSGJ-608 every two weeks (Q2W) after a starting dose of 160mg at week 0(608A group), or 160mg of SSGJ-608 every four weeks (Q4W) (608 B group) for 12 weeks. Efficacy was assessed by PASI75 and sPGA 0 or 1 response rates at week 12 as co-primary endpoints, and proportion of patients who achieved PASI90, PASI100 or sPGA score of 0 at week 12 as secondary endpoints. The safety profile was also evaluated.ResultsAt week12, the proportions of patients achieving PASI75 (92.7% vs. 95.1%) and sPGA 0/1 (80.3% vs. 79.0%) were comparable between the two SSGJ-608 dose regimens. The PASI90, PASI100 and sPGA 0 response rates were 81.0% vs.82.3%, 49.4% vs. 47.5%, and 49.4% vs.47.3% in the 608A group and the 608B group, respectively. In the subgroup of patients previously treated with anti-IL-17 therapy, SSGJ-608 also achieved high clinical response rates at week12. The most common TEAEs were hypertriglyceridemia, upper respiratory tract infection, hyperuricemia, increased alanine aminotransferase and hypercholesterolemia. Both treatment groups demonstrated a favorable safety profile and no new safety signals were identified.ConclusionsSSGJ-608 was highly effective for treating patients with moderate-to-severe plaque psoriasis at 80mg Q2W and 160mg Q4W in a larger population, especially in patients previously treated with anti-IL-17 therapy, and exhibited a favorable tolerability profile in Chinese patients with moderate-to-severe plaque psoriasis.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT06299982.

BACKGROUND:Eosinophils are involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE:This post-hoc analysis evaluated the effect of stapokibart on blood eosinophil counts in moderate-to-severe AD patients. METHODS:The phase II AD002 trial (n = 120) randomly assigned patients to stapokibart 300 mg every 2 weeks (Q2W), 150 mg Q2W, or placebo for 16 weeks. The phase III AD005 trial (n = 500) randomly assigned patients to stapokibart 300 mg Q2W or placebo for 16 weeks, followed by open-label stapokibart 300 mg Q2W for 36 weeks. Efficacy and safety were analyzed in subgroups stratified by baseline blood eosinophil counts (≥500 or <500 cells/µL). RESULTS:Stapokibart treatment resulted in sustained reductions in blood eosinophil counts versus placebo (baseline vs. Week 16: high-dose 420 vs. 235 cells/μL, low-dose 530 vs. 315 cells/μL in AD002; 370 vs. 210 cells/μL in AD005). Furthermore, stapokibart demonstrated superior efficacy over placebo in achieving higher Eczema Area and Severity Index (EASI)-75 response rates at Week 16 in both eosinophil subgroups. The incidence of adverse events was similar across eosinophil subgroups, with most events being mild or moderate. CONCLUSION:Stapokibart reduced blood eosinophil counts in AD patients and demonstrated favorable efficacy and safety regardless of baseline blood eosinophil counts.

The long-term efficacy of biologics in psoriasis is compromised by primary or secondary resistance, and poor treatment adherence due to frequent dosing. We assessed the efficacy and safety of switching to an interleukin-23 subunit p19 (IL23p19) inhibitor picankibart at 200 mg every 12 weeks, without a washout period, on skin clearance and quality of life (QoL) in patients with plaque psoriasis. A total of 152 patients were enrolled, comprising 83 suboptimal responders (static Physician’s Global Assessment [sPGA] ≥ 2 or body surface area [BSA] ≥ 3

BACKGROUND:The development of interleukin-23 inhibitors that offer sustained complete skin clearance with reduced-frequency dosing addresses a significant unmet clinical need in managing moderate-to-severe plaque psoriasis. OBJECTIVE:To evaluate the efficacy and safety of picankibart, an interleukin-23p19 inhibitor, in Chinese patients. METHODS:CLEAR-1 enrolled participants aged 18-75 years to randomly receive picankibart subcutaneously 200 mg at weeks 0/4/8/20/32/44, picankibart 200 mg at weeks 0/4/8 then 100 mg at weeks 20/32/44; or placebo at weeks 0/4/8 then picankibart 200 mg at weeks 16/20/24/32/44. The co-primary endpoints were ≥90% improvement in psoriasis area and severity index and static physician's global assessment clear/almost clear status (0/1) at week 16. RESULTS:In picankibart 200 mg group, 80.3% achieved ≥90% improvement in psoriasis area and severity index and 93.5% achieved static physician's global assessment 0/1 at week 16 vs 2.0% and 13.1%, respectively with placebo. All key secondary endpoints were significantly improved (all two-sided P < .0001 vs placebo). Efficacy was maintained through week 52 for both 100 mg and 200 mg doses, with no new safety signal observed. LIMITATIONS:Chinese only; no active comparator. CONCLUSION:Picankibart provided effective skin clearance in Chinese participants by week 16. A dosing regimen of every 12 weeks with either 100 mg or 200 mg maintained these clinical improvements through week 52.

Background Vitiligo is a common depigmentation disorder that affects approximately 1–2% of the global population. Oxidative stress plays a crucial role in its pathogenesis, yet systematic identification of oxidative stress-related biomarkers remains limited. This study aimed to identify and validate oxidative stress-related biomarkers for vitiligo and to construct a risk prediction model using bioinformatics, machine learning, and Mendelian randomization approaches. Results Through integration of high-throughput sequencing data, 1,581 differentially expressed genes were identified, of which 42 intersected with known oxidative stress-related genes. Three machine learning algorithms converged on five candidate genes. Real-time polymerase chain reaction validation in paired vitiligo lesional and non-lesional skin tissues confirmed the significant upregulation of ATOX1, STAT1, and PDCD10 and downregulation of FXN (p < 0.05). A risk prediction nomogram based on these four genes achieved high accuracy in the training dataset (area under the curve = 1.00) and an independent validation dataset (area under the curve = 0.93). PDCD10 demonstrated the strongest individual discriminatory performance (area under the curve = 0.820) in external validation. Mendelian randomization analysis indicated that ATOX1, STAT1, and PDCD10 had odds ratios greater than 1, suggesting a potential trend toward increased vitiligo risk, although the associations did not reach statistical significance. Conclusions This study identified ATOX1, STAT1, FXN, and PDCD10 as oxidative stress-related biomarkers for vitiligo. The four-gene risk prediction model demonstrated promising accuracy, with potential implications for early detection and personalized treatment strategies, pending further validation in larger cohorts.How to cite: Xia Y, Liu L, Zhou H, et al. Oxidative stress gene signature associated with vitiligo: A multi-algorithm machine learning and Mendelian randomization validation. Electron J Biotechnol 2026;83. https://doi.org/10.1016/j.ejbt.2026.100724.

Atopic dermatitis (AD) and psoriasis are the two canonical chronic inflammatory skin disorders, classically differentiated by their distinct histopathological features and immune polarization—Th2-dominant in AD versus IL-23/Th17-dominant in psoriasis. However, this conventional dichotomy is increasingly contested by clinical observations, such as the mixed immunophenotypes seen in Asian AD and overlap syndromes, which complicate clear-cut classification. Growing evidence highlights substantial immunological plasticity and pathological overlap, suggesting that these diseases may represent segments of a continuous spectrum rather than discrete entities. In this Mini Review, we integrate classical morphological observations with recent advances in molecular immunology to explore the mechanisms underlying these tissue responses. We examine how immune cell plasticity—particularly of tissue-resident memory T cells—and their crosstalk with the structural microenvironment contribute to disease heterogeneity and therapy-induced phenotypic shifts. We propose that a shift from static histologic evaluation toward dynamic immunopathological profiling is crucial for narrowing the gap between conventional diagnosis and the emerging paradigm of precision medicine.