Dysregulation of the gut-brain-skin axis and key overlapping inflammatory and immune mechanisms of psoriasis and depression.

The occurrence, progression and recurrence of psoriasis are thought to be related to mood and psychological disorders such as depression. Psoriasis can lead to depression, and depression, in turn, exacerbates psoriasis. No specific mechanism can explain the association between psoriasis and depression. The gut-brain-skin axis has been used to explain correlations among the gut microbiota, emotional states and systemic and skin inflammation, and this axis may be associated with overlapping mechanisms between psoriasis and depression. Therefore, in the context of the gut-brain-skin axis, we systematically summarized and comparatively analysed the inflammatory and immune mechanisms of psoriasis and depression and illustrated the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the gut microbiota. This review provides a theoretical basis and new targets for the treatment of psoriasis and depression.

Yangxue Jiedu Fang Ameliorates Psoriasis by Regulating Vascular Regression via Survivin/PI3K/Akt Pathway.

BACKGROUND: Psoriasis (PA) is a chronic autoimmune disease of the skin that adversely affects patients' quality of life. Yangxue Jiedu Fang (YXJD) has been used for decades to treat psoriasis in China. However, its antipsoriatic mechanisms are still poorly understood. In this study, we explored the effects of YXJD on angiogenesis and apoptosis of microvessels in PA, the underlying mechanisms in HUVEC cells transfected by Survivin overexpression plasmid and in a mouse model of imiquimod-induced psoriasis and the relationship between VEGF (vascular endothelial growth factor) and Survivin. METHODS: A BALB/c mouse model of imiquimod- (IMQ-) induced PA was established, and the mice were treated with YXJD. Cell viability was assessed by CCK8 assay. Apoptosis was detected by annexin V-FITC/PI double-staining and caspase-3 assays. The PI3K/Akt/ß-catenin pathway was analyzed by western blotting, ELISA, and immunochemical analysis. RESULTS: YXJD ameliorated symptoms and psoriasis area and severity index (PASI) scores and also reduced the number of microvessels, as determined by the microvessel density (MVD). The expression of apoptotic protein Survivin in endothelial cells, autophagy-related proteins p62, and angiogenic proteins VEGF was inhibited by YXJD, and the repressed expression of LC3II/I increased by YXJD. The proteins related to the PI3K/Akt pathway and ß-catenin expression and the nuclear entry of ß-catenin were reduced in IMQ-induced PA mice treated with YXJD. In HUVEC cells transfected by Survivin overexpression plasmid, we observed YXJD regulated the expression of Survivin, LC3II/I, and p62, VEGF, and PI3K/Akt pathway-relative proteins and the nuclear entry of ß-catenin. CONCLUSIONS: YXJD inhibited the expression of Survivin via PI3K/Akt pathway to adjust apoptosis, autophagy, and angiogenesis of microvessels and thus improve the vascular sustainability in psoriasis. YXJD may represent a new direction of drug research and development for immunomodulatory therapy for psoriasis.

Plasma MicroRNA Expression Profiles in Psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis. METHODS: A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples. RESULTS: We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis. CONCLUSIONS: This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.

Efficacy and Safety of Jueyin Granules for Patients with Mild-to-Moderate Psoriasis Vulgaris: Protocol for a Multicenter Randomized Placebo-Controlled Trial.

Introduction. The etiology and pathogenesis of psoriasis are complex. Blood-heat syndrome is the core pathogenesis of psoriasis. Based on theories of Chinese medicine (CM), heat-clearing and blood-cooling (HCBC) are the primary treatment. Very few studies have investigated the pharmacological mechanism of the CM HCBC method for treating psoriasis. This multicenter randomized controlled trial will focus on treating psoriasis blood-heat syndrome with the HCBC method using Jueyin granules (JYKL). This will be an objective and standardized evaluation of the efficacy, safety, and reproducibility of the HCBC method to obtain objective evidence meeting international standards that aim to establish a clinical standard suitable for the popular application of CM for treating psoriasis. Methods and Analysis. A five-center randomized double-blind placebo-controlled clinical design will be used in this study. At least 196 participants will be randomly assigned to receive either JYKL or placebo treatment approximately 30 minutes after meals in the morning and evening (one sachet per time, twice daily for 8 consecutive weeks). The study duration will be 17 weeks, including 1 week of screening, 8 weeks of intervention, and 8 weeks of follow-up. The patients will be evaluated every 2 weeks, and the measures will be compared with baseline values. The primary outcome measure will be the psoriasis lesion area severity index. We will also observe the recurrence rate, body surface area, physician global assessment, dermatology life quality index, quality of life index, visual analogue scale score, CM symptom score, combined drug use, and adverse events. This trial is registered with NCT03961230.