Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Unequal relevance between different subtypes of fingernail psoriasis and psoriatic arthritis.

Nail disease in psoriasis has been found to be associated with psoriatic arthritis (PsA); however, which subtype of nail disease holds greater relevance to PsA remains unclear. This study was performed to explore the associations between three subtypes of fingernail disease (pitting, onycholysis, and hyperkeratosis) and PsA among patients with psoriasis. Patients with psoriasis attending five dermatology clinics in Shanghai between January 2020 and May 2021 were examined for skin, joint, and fingernail changes. Multivariate logistic regression analyses were utilized to test the strength of associations between subtypes of fingernail disease and PsA. The receiver operator characteristic (ROC) curve with area under curve (AUC) was used to evaluate their accuracies in diagnosing PsA. Sensitivity and specificity were also calculated. Of 1985 patients with psoriasis included, 228 (11.5%) patients were diagnosed with PsA, and the remaining patients were cutaneous-only psoriasis (PsC). One-hundred and fifty-seven (68.9%) patients with PsA and 748 (42.6%) patients with PsC had fingernail disease. Adjusted models showed that onycholysis and hyperkeratosis were the only type of fingernail disease independently associated with PsA. This association was further confirmed by the forward conditional stepwise regression model (OR, 95% CI for onycholysis: 2.34, 1.79 to 4.27, p < 0.01; for hyperkeratosis: 1.62, 1.12 to 2.66, p = 0.037). ROC analysis showed that, compared to pitting and hyperkeratosis, onycholysis had higher AUC (0.630) and sensitivity (52.6%). The psoriatic fingernail onycholysis and hyperkeratosis hold greater relevance to PsA than pitting. Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis. Key Points • Psoriatic fingernail onycholysis and hyperkeratosis, rather than pitting, are significantly associated with PsA • Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis.

Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris.

BACKGROUND: Methotrexate is the first systemic therapeutics of psoriasis. It is reported that 40% of the patients achieved a PASI75 after 12 weeks with a small dose of methotrexate (15mg / w) treatment. So far there is not any large-scale exome sequencing been used to predict the efficacy of methotrexate in the treatment of psoriasis vulgaris. OBJECTIVE: To analyze the genetic polymorphism to predict methotrexate efficacy in Chinese patients with psoriasis vulgaris. METHODS: In this study, we used the whole exon high-throughput sequencing technology to detect the DNA sequence of 22 psoriasis vulgaris patients (11 responders, 11 non-responders) treated with methotrexate and captured approximately 236 variants with statistically significant in the whole exon sequencing, then in accordance with statistical differences and clinical relevance, we further selected 36 SNPs and 14 SNPs that have been reported in articles associated with the response of methotrexate. We used MassARRAY method to verify the 50 SNPs in 100 psoriatic patients treated with methotrexate. RESULTS: We found 3 SNPs, rs216195T>C in SMG6, rs1050301G>A in IMMT, rs2285421T>C in UPK1A which might associate with the drug response of methotrexate. CONCLUSION: We have searched 3 new SNPs that could predict the efficacy of methotrexate in psoriasis vulgaris to some extent, providing a theoretical basis for precision medicine of methotrexate in future.

Synthesis, crystal structures, and urease inhibition of an acetohydroxamate-coordinated oxovanadium(V) complex derived from N'-(3-bromo-2-hydroxybenzylidene)-4-methoxybenzohydrazide.

A new benzohydrazone compound N'-(3-bromo-2-hydroxybenzylidene)-4-methoxybenzohydrazide (H2L) was prepared. Reaction of H2L and acetohydroxamic acid (HAHA) with VO(acac)2 in methanol gave the complex [VOL(AHA)]. Both H2L and the oxovanadium complex were characterized by elemental analysis, IR, UV-vis and (1)H NMR spectra, and single crystal X-ray diffraction. H2L was also characterized by high-resolution mass spectrum. Thermal analysis of the oxovanadium complex was carried out. The benzohydrazone ligand, in its dianionic form, coordinates to V atom through the phenolate oxygen, imino nitrogen and enolate oxygen. The acetohydroxamic acid coordinates to V atom through the carbonyl oxygen and deprotonated hydroxyl oxygen. The V atom is in octahedral coordination. H2L, HAHA and the oxovanadium complex were tested for their urease inhibitory activities. The percent inhibition at concentration of 100 µmol·L(-1) on Helicobacter pylori urease is 78% for the oxovanadium complex. The IC50 value for the complex is 36.5 µmol·L(-1). Molecular docking study was performed to study the inhibition.

Dysregulation of miRNA146a versus IRAK1 induces IL-17 persistence in the psoriatic skin lesions.

Psoriasis is a common chronic inflammatory skin disorder with dysregulation of miRNAs. The expression pattern of miR-146a and target gene IRAK1 in lesions and PBMCs of plaque psoriasis remains unclear. In our study, we found the expression of miR-146a was up-regulated both in lesions and PBMCs of psoriatic patients, and positively correlated with IL-17 expression, whereas the target gene IRAK1 expression was expressed differentially in lesions and peripheral blood. Inability of miR-146a inhibiting target gene IRAK1 may contribute to the persistent inflammation in lesions of psoriasis.