Dihydroartemisinin targets fibroblast growth factor receptor 1 (FGFR1) to inhibit interleukin 17A (IL-17A)-induced hyperproliferation and inflammation of keratinocytes.

Psoriasis is a common chronic immune-mediated disease that often has a serious negative impact on the physical and mental health of patients. Dihydroartemisinin (DHA) is a drug with anti-fibrotic and anti-inflammatory effects that may be involved in the autoimmune regulation of immune diseases. However, the effects of DHA on psoriasis have not been reported comprehensively. Therefore, the aim of this study was to investigate the effect of DHA on abnormal proliferation and inflammation of epidermal keratinocyte cells in psoriasis and its mechanism of action. IL-17A-induced human epidermal keratin-forming cells (HaCaT) were used as a model. And after induction exposure to different concentrations of DHA, CCK-8, EDU staining, wound healing and Western blotting were performed to assess cell viability, proliferation, migration, differentiation and inflammatory factors, respectively. Subsequently, agonists of fibroblast growth factor receptor 1 (FGFR1) were added and the above experiments were repeated. The results showed that DHA obviously inhibited IL-17A-induced hyperproliferation, migration and expression of inflammatory factors in HaCaT cells. Furthermore, FGFR1 was highly expressed in IL-17A-induced HaCaT cells, and DHA inhibited its expression. However, the inhibitory effect of DHA on IL-17A-induced HaCaT cells was reversed after the addition of FGFR1 agonist. In conclusion, DHA could inhibit IL-17A-induced hyperproliferation and inflammation of keratinocytes by targeting FGFR1, which also provided a new target for the treatment of psoriasis.

The prevention effect of probiotics against eczema in children: an update systematic review and meta-analysis.

Accumulated evidences support the fetus's intestinal flora unbalance is associated with the development of allergic diseases. Probiotic supplements in pregnancy and childhood might prevent atopic diseases. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing eczema, atopic eczema, and other allergic diseases. We also explored whether different probiotic strains or intervention objects affected the antiallergic effect of probiotics and the prevention atopy effect of the long-term period. Fixed-effect models were used, and random-effects models where significant heterogeneity was present. Results were expressed as odds ratios (ORs) with a 95% confidence interval (CI). Twenty-one studies were included in the meta-analysis. The probiotics group had a significantly lower risk of eczema and atopic eczema compared to controls, especially those treated with probiotic combinations. Mothers' probiotics intake significantly contributed to reducing the risk of eczema as well as atopic eczema. What's more, probiotics seemed effective on eczema prevention ≤2 years of age, but against atopic eczema after 1 of age year. No significant difference in terms of prevention of asthma, rhinitis, wheeze, allergic diseases and sensation. In brief, a probiotic supplement is expected to become a novel potential strategy for infant eczema and atopic eczema.

Efficacy of GLP-1rA, liraglutide, in plaque psoriasis treatment with type 2 diabetes: a systematic review and meta-analysis of prospective cohort and before-after studies.

BACKGROUND: Psoriasis usually accompanies comorbidities such as type 2 diabetes, obesity, and cardiovascular disease. It has been proposed that glucagon-like peptide-1 receptor (GLP-1R) agonists used in the treatment of patients with type 2 diabetes may also improve psoriasis. However, the number of patients in every single study is relatively small. OBJECTIVES: We carried out a meta-analysis to evaluate whether GLP-1R is effective for the treatment of plaque psoriasis with type 2 diabetes. METHODS: A search of PubMed, Ovid Embase, the Cochrane Library for controlled trials was done from inception to June 20th, 2020. Published trials that included psoriasis patients with type 2 diabetes, the Psoriasis Area and Severity Index (PASI) of treated by GLP-1R before and after. All statistical analyses were conducted using the Stata 15.0 (Stata Corporation, College Station, TX, USA). RESULTS: There were 4 trials involving 32 patients. Patients treated by GLP-1R after showed significantly lower PASI (SMD: -4.332, 95% CI: -7.611 to -1.053, p = .01), lower fasting plasma glucose than treated before (SMD: -0.341, 95% CI: -0.679 to -0.004, p = .048). There was no significant difference in Body Mass Index (BMI), Dermatology Life Quality Index (DLQI), and glycated hemoglobin (HbA1c) between treated by GLP-1R after and before. CONCLUSIONS: GLP-1rA, liraglutide, therapy can reduce psoriasis who had concomitant type 2 diabetes severity, but may independently of changes in weight and glycaemic control.

Efficacy and safety of pioglitazone for treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials.

Background: A growing number of studies have shown that thiazolidinediones (TZD) can be antipsoriatic. Pioglitazone is a representative of the class of antidiabetic drugs known as TZD. TZD can activate nuclear peroxisome proliferator-activated receptors (PPAR)-c. PPARs are expressed on epidermal keratinocytes and exert their effects by promoting the terminal differentiation of keratinocytes, inhibiting epidermal growth, and reducing inflammatory responses. These observations suggest that TZD have potential benefits in the treatment of cutaneous and metabolic pathologies associated with psoriasis.Objective: A systematic review and meta-analysis was carried out to evaluate the efficacy of combined pioglitazone treatment. We point out three controversial side effects from administration of pioglitazone in psoriasis: elevated liver enzymes, weight gain, and nausea.Study selection: Randomized, single blind, or double blind, published studies of pioglitazone compared with placebo given to patients with plaque psoriasis for 10 weeks or 12 weeks were considered for inclusion in this review. The primary outcomes were 75% or greater improvement in the Psoriasis Area and Severity Index score from baseline (PASI 75) with pioglitazone.Data collection and analysis: The systematic literature search was conducted in the PubMed, Embase, Google Scholar, and Cochrane databases from inception up to December 20 2018. Data analysis was done using Revman 5.3 Haymarket, London, United Kingdom.Main results: We included six studies (three publications of pioglitazone only; three publications of pioglitazone combination therapy) comprising a total of 294 patients (n = 149 with pioglitazone only and n = 145 with pioglitazone combination therapy) in the analysis. There was a significant PASI 75 response, in the pioglitazone only subgroup as compared to placebo (OR = 8.74, 95% CI 3.76-20.31, p < .00001), and the pioglitazone combination subgroup as compared to placebo (OR = 4.64, 95% CI 2.03-10.60, p < .00001), others, the total of pioglitazone as compared to placebo (OR = 6.37, 95% CI 3.55-11.43, p < .00001), and tests of subgroup differences show: p = .29, I2 = 9.5%. The incidence rate of elevated liver enzymes (OR = 3.70, 95% CI 0.56-24.31, p = .99), weight gain (OR = 1.44, 95% CI 0.60-3.47, p = .41), and nausea (OR = 0.76, 95% CI 0.23-2.49, p = .65) were not significantly different compared with the control group.Conclusion: Pioglitazone has efficacy for the treatment of plaque psoriasis. There is no significant difference between patients treated with pioglitazone only or in combination with other therapies. The incidence rate of side effects associated with pioglitazone treatment such as elevated liver enzymes, weight gain, and nausea were not significantly different compared with the control group.