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Psoriasis is a frequent chronic, recurrent and immune‐mediated inflammatory skin disease, whose pathogenesis remains unclear at present. The role of antiviral protein in the pathogenesis of psoriasis is the focus of current research. Interferon stimulated gene 15 (ISG15) is an important antiviral protein. In this study, the expression of ISG15 saw a significant increase through the immunohistochemical detection of imiquimod (IMQ)‐induced mice. In the psoriasis cell model, a remarkable increase also occurred in the expression of ISG15. In this study, it was found that the cell cycle was blocked in G1/S conversion, and a reduction took place in the proliferation of keratinocytes and the expression of a cell cycle‐related protein—cyclin D1 after the knockout of ISG15 in the psoriasis cell model. After that, messenger ribonucleic acid (mRNA) sequencing and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) analysis indicated its close association with the hypoxia inducible factor‐1α (HIF‐1α) signalling pathway. Western blot showed a decrease in the expression of HIF‐1α and vascular endothelial growth factor C (VEGFC) after the knockout of the ISG15 gene. The rescue experiment verified that ISG15 promotes the proliferation of keratinocytes by regulating the HIF‐1α signalling pathway. It was concluded that psoriasis cells and mouse models witnessed the increased expression of ISG15. In psoriasis, knocking out ISG15 inhibits the proliferation of keratinocytes and blocks the cell cycle. Besides, ISG15 promotes the proliferation of keratinocytes through the HIF‐1α signalling pathway. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease that affects approximately 125 million people worldwide. It has significant impacts on both physical and emotional health-related quality of life comparable to other major illnesses. Accurately prediction of psoriasis using biomarkers from routine laboratory tests has important practical values. Our goal is to derive a powerful predictive model for psoriasis disease based on only routine hospital tests. We collected a data set including 466 psoriasis patients and 520 healthy controls with 81 variables from only laboratory routine tests, such as age, total cholesterol, HDL cholesterol, blood pressure, albumin, and platelet distribution width. In this study, Boruta feature selection method was applied to select the most relevant features, with which a Random Forest model was constructed. The model was tested with 30 repetitions of 10-fold cross-validation. Our classification model yielded an average accuracy of 86.9%. 26 notable features were selected by Boruta, among which 15 features are confirmed from previous studies, and the rest are worth further investigations. The experimental results demonstrate that the machine learning approach has good potential in predictive modeling for the psoriasis disease given the information only from routine hospital tests. [ABSTRACT FROM AUTHOR]

Caspase recruitment domain family member 8 (CARD8) is an adaptor molecule that negatively regulates nuclear factor-κB (NF-κB) activation, interleukin (IL)-1β secretion, and apoptosis. These play important roles in the pathogenesis of psoriasis. Genetic variants of CARD8 have been associated with an increased risk of several inflammatory diseases and psoriasis in Europe. However, nothing is known about the association of the polymorphisms of CARD8 and psoriasis vulgaris (PsV) in the Han population of northeastern China. To investigate the potential association between them, we designed a case-control study to genotype four selected single nucleotide polymorphisms (SNPs) using the improved multiplex ligation reaction (iMLDR) method. Model-based single SNP frequentist-test and haplotype association studies were performed to assess the association between SNPs and PsV. The results showed that the intron SNP rs10403848 was significantly associated with PsV (additive model p = 0.0418 , p ′ = 0.0411 , and statistical power 0.1902; heterozygous model p = 0.0418 , p ′ = 0.0164 , and statistical power 0.9406). A potential risk locus of nonsynonymous SNP rs2043211 found in the European population did not show a significant association in our study. We found that the polymorphism rs10403848 in CARD8 is significantly associated with PsV risk in the Han population of northeastern China. CARD8 may be involved in PsV in this population, as in the European population, but a different genetic process should be considered for the heterogeneity of risk loci. [ABSTRACT FROM AUTHOR]

Abstract Psoriasis is a chronic immune-mediated disease with a complex etiology involving various genetic and immunological factors as well as environmental factors. Psoriasis is thought to be mediated by T-cells polarized to a Th17 fate. PTPN2 encodes the T-cell protein tyrosine phosphatase, which acts as a negative regulator of the JAK/STAT signaling pathways downstream of cytokines and plays a prominent role in T-cell activation, signaling and/or effector function. To evaluate the association between PTPN2 gene polymorphisms and psoriasis in the Northeastern Chinese population. A case-control study was conducted, and 398 patients with psoriasis and 397 healthy controls were genotyped for thirteen genetic polymorphisms in PTPN2. Allele analysis revealed that rs2847297, rs657555 and rs482160 polymorphisms were significantly associated with psoriasis (p = 0.0018, p = 0.0017 and p = 0.0086, respectively). Genotype analysis also revealed that these polymorphisms were significantly associated with psoriasis under different models (codominant, dominant and recessive models) (p < 0.05). In this study, three haplotypes (H1, H7 and H11) were also found to be associated with psoriasis (p = 0.0015, p = 0.0094, and p = 0.0124, respectively). These results indicate that PTPN2 genetic polymorphisms are associated with psoriasis in the Northeastern Chinese population. [ABSTRACT FROM AUTHOR]

Psoriasis is an autoimmune disease characterized by abnormal differentiation and hyper-proliferation of epidermal keratinocytes. The object of the study is to investigate the role of miRNA-876-5p in psoriasis. It reported that MicroRNAs (miRNAs) played roles in the malignant progression in psoriasis development. The expression of miR-876-5p was found to be down-regulated in psoriasic tissue and blood of patients. The luciferase assay verified the targeting role of miR-876-5p to 3′UTR of Angiopoietin-1 (Ang-1). Proliferation of psoriasic cells were inhibited by miR-876-5p and hold on G0/G1 phase. Further studies showed that miR-876-5p suppressed proliferation by restraining the expression of Ang-1, which would regulate the phosphorylation level of PI3K, AKT, mTOR and ERK in psoriasic cells. Invasion and adhesion, serving as important behavioral traits of epidermal keratinocytes cells, were suppressed by excessive miR-876-5p in psoriasic cells also. MiR-876-5p would be expected to be biomarker and potential therapeutic targets for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Aim. To clarify the association between the single nucleotide polymorphisms (SNPs) in the NLRP1 and NLRP3 and Psoriasis Vulgaris (PsV) in the Chinese Han population. Methods. We genotyped eight SNPs, four from NLRP1 (rs8079034, rs11651270, rs11657747, and rs878329) and NLRP3 (rs7512998, rs3806265, rs10754557, and rs10733113) each in 540 patients with PsV and 612 healthy controls in the Chinese Han population using an improved multiplexed ligation detection reaction (iMLDR) method. The genotype and haplotype frequencies were analyzed using a case-control study design. Results. We identified two SNPs, rs3806265 and rs10754557, in NLRP3 that were significantly associated with PsV. The genotype distribution of the rs3806265 SNP was significantly different between cases and controls (p=0.0451; OR = 0.791; 95% CI = 0.627–0.998). In the recessive model, the genotype distribution of the rs10754557 SNP was significantly different between cases and controls (p=0.0344; OR = 1.277; 95% CI = 0.987–1.652). The haplotype analysis of rs3806265 and rs10754557 also presented a significant association of TA haplotype with PsV (χ2=4.529; p=0.033). Conclusion. NLRP3 may play a role in PsV susceptibility in the Chinese Han population. [ABSTRACT FROM AUTHOR]

• Phase III study was conducted in moderate-to-severity plaque psoriasis patients. • SCT630 and adalimumab showed equivalences in efficacy and similar safety. • Switching from adalimumab to SCT630 did not impact safety or efficacy. This phase III study aimed to compare the efficacy, safety, and immunogenicity of SCT630 with the reference adalimumab. A total of 367 Chinese patients with moderate-to-severe plaque psoriasis were randomly assigned to receive 80 mg of SCT630 or adalimumab subcutaneously at week 1, 40 mg at week 2, then 40 mg biweekly. At week 16, those with 50 % or more improvement in psoriasis area and severity index (PASI) were eligible to enter an extension period up to week 52. Patients on SCT630 continued the same treatment, whereas patients receiving adalimumab were re-randomized at a ratio of 1:1 to adalimumab or SCT630 group. The primary endpoint was percentage improvement in PASI at week 16. Other endpoints included PASI 50/75/90/100, Physician's Global Assessment, Dermatology Life Quality Index, safety, and immunogenicity. PASI improvement at week 16 was 85.07 % for SCT630 and 84.82 % for adalimumab. The mean difference (3.10 %, 95 % CI: −1.875 %, 8.066 %) was within the equivalence interval. Other efficacy endpoints, safety and immunogenicity profiles were similar across the two groups. There were no safety or immunogenicity difference between switched/continued groups. This phase III study demonstrated the equivalences in efficacy, safety and immunogenicity of SCT630 to adalimumab in patients with moderate to severe psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease, which has been linked to dyslipidemia with potential functional impairment of lipoproteins. This cross-sectional study was designed to characterize the biological activities of plasma lipoproteins in 25 patients with psoriasis and 25 age- and sex-matched healthy controls. In the present study, we found that plasma levels of high-density lipoprotein (HDL) cholesterol were decreased in the psoriasis group compared to healthy controls. The malondialdehyde (MDA) content in plasma, in HDL3 and in low-density lipoprotein (LDL) were increased. However, the activity of plasma paraoxonase-1 (PON-1) decreased in psoriasis and negatively correlated with the psoriasis area and severity index (PASI). Moreover, plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in psoriasis and positively correlated with the PASI. High-sensitivity C-reactive protein (hs-CRP) was increased in psoriasis, but did not reach significance when correlated with PASI. In vitro tests displayed that the functionalities of HDL3 isolated from psoriatic patients significantly decreased, which were assessed in four independent ways, namely (1) protection against LDL oxidation, (2) inhibition of tumor necrosis factor-α (TNF-α) induced monocyte adherence to endothelial cells, (3) prevention of oxidized low density lipoprotein (ox-LDL) induced monocyte migration, and (4) protection of endothelial cells from TNF-α induced apoptosis. Further, pro-oxidative and pro-inflammatory properties of LDL isolated from psoriatic patients were increased. In conclusion, the biological activities of psoriatic lipoproteins are impaired in both HDL and LDL, which may provide a link between psoriasis and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Recent studies suggest that psoriasis is a systemic disorder associated with cardiovascular disease (CVD) risk factors, such as obesity, hypertension and dyslipidemia. However, these risk factors have not been widely recognized across different populations. This cross-sectional study aimed to examine the association of risk factors for CVD with psoriasis by comparing patients with psoriasis and matched controls in northern China. This study identified 291 patients with diagnosed moderate or severe psoriasis as cases and 445 age- and gender-matched subjects as controls. A significant association ( P < 0.01) was observed between overall psoriasis incidence and smoking [odds ratio (OR), 2.96; 95 % confidence interval (CI) 2.09-4.09], alcohol consumption (OR, 3.77; 95 % CI 2.381-5.955), diabetes (OR, 2.79; 95 % CI 1.70-4.59), hypertension (OR, 2.19; 95 % CI 1.56-3.06) and hyperlipidemia (OR, 1.76; 95 % CI 1.29-2.40). Furthermore, hypertension correlated with the duration of psoriasis after adjustment for age and sex. Hyperlipidemia, smoking and alcohol consumption were related to the severity of the disease. Moreover, patients with psoriasis had lower levels of apolipoprotein B (ApoB) and lipoprotein (Lip) than did controls ( P < 0.05). These data suggest that multiple risk factors for CVD are associated with psoriasis. CVD risk factor screening should be performed, and appropriate measures should be taken accordingly for psoriasis patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important part in the pathogenesis of autoimmune diseases. A high level of MIF has been detected in plaques of psoriasis and the sera of patients with psoriasis. Polymorphisms associated with autoimmune and inflammatory diseases exist in the promoter region of MIF and alter its expression. Objective: The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and psoriasis in a Han population in northeastern China. Methods: Two-hundred-and-forty psoriasis patients and a control group of 269 healthy volunteers were included in this study. We genotyped MIF-173G/C using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MIF-794CATT5–8 microsatellite polymorphism was genotyped by polyacrylamide gel electrophoresis (PAGE). Results: No significant difference in the distributions of alleles, genotypes and haplotypes was observed between patients and controls. When patients were divided into subtypes according to sex, family history and age of onset, distribution of the MIF-173C allele between male and female patients was significantly different (P =0.04). MIF-173C allelic distribution between late onset psoriasis patients and controls was also different (P =0.02), as well as late onset patients and early onset subjects (P =0.04). Conclusions: These results suggested a preliminary association between the MIF-173C allele and male psoriasis and late onset psoriasis in the studied population. In addition, the distributions of the two polymorphisms in Asian populations were quite different from the other continental populations. [Copyright &y& Elsevier]