Peng Zhang

Introduction: Rosacea is a common chronic inflammatory skin disorder and dysregulation of neuroimmune functions and neurovascular loops play critical roles in the development of rosacea. Huperzine A (Hup A) has several bioactive properties, including anti-inflammatory, antioxidant, and neuroprotective effects. However, the potential roles of Hup A in treating rosacea is unknown.Methods: Network pharmacology, molecular docking, and molecular dynamics simulation techniques has been used to investigate the anti-rosacea mechanisms of Hup A in rosacea.Results: Our results predicted 21 potential anti-rosacea targets of Hup A through public databases. KEGG pathway enrichment analysis revealed that these key targets participated in the regulation of MAPK signaling, NF-kappa B signaling, and PI3KAKT signaling pathways. Further machine learning analysis identified six core targets (BCL2, RXRA, PKN2, XDH, PRKCA, and FAP). Analysis of the GSE65914 dataset showed that XDH was upregulated in rosacea lesions, while BCL2 and RXRA were downregulated, with no significant expression changes of the other genes. Molecular docking results indicated that Hup A could bind to key targets (XDH, BCL2, and RXRA), which were further confirmed by molecular dynamics simulations.Discussion: This study systematically elucidates the potential mechanisms of Hup A in the treatment of rosacea and provides a theoretical basis for its application in rosacea therapy.

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation of lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism of ferroptosis in the genesis and development of psoriasis are available. (2) Methods: Levels of lipid reactive oxygen species (ROS) and ferrous iron were measured by flow cytometry. Ultrastructure analysis was performed by transmission electron microscopy. Imiquimod-induced psoriasis-like mice were treated with a ferroptosis inducer. The expressions of mRNA of genes were measured by qRT-PCR. HaCaT cells were used to explore the function of Cyb561d2. (3) Results: In this work, we observed that levels of lipid ROS and ferrous iron in the epidermis of psoriasis vulgaris (PV) patients were increased. The existence of ferroptosis activation in the epidermis of individuals with PV was confirmed by transmission electron microscope both in patients with PV and psoriasis-like mice models. Intradermal injection of the ferroptosis inducer RSL3 in psoriasis-like mice significantly promoted and aggravated the development of psoriasis-like dermatitis, and the level of serum transferrin was also increased in PV samples. Moreover, abnormal expression of some genes related to iron metabolism was also proved in the epidermis of PV cases, among which Cyb561d2 was shown to promote ferrous iron overload and lipid peroxidation accumulation in HaCaT cells. (4) Conclusions: In summary, our study suggested that ferroptosis activation owing to iron overload may be a novel mechanism underlying the formation of skin lesions in individuals with PV.

Objective: Psoriasis is a chronic inflammatory disease with autoimmune aetiology. A possible link between psoriasis and autoimmune thyroid disease (AITD) has been suggested in some studies with inconsistent findings. This meta-analysis aims to determine the association between psoriasis and AITD. Design: A meta-analysis of observational studies. Data sources: PubMed, EMBASE, Scopus and the Cochrane Library were searched up to 1 November 2021. Eligibility criteria for selecting studies: We included non-randomised studies, each with over 50 cases in every group, focusing on the rate of comorbidity between psoriasis and AITD. Data extraction and synthesis: Two independent reviewers screened the articles and extracted data. The restricted maximum-likelihood was applied to perform the meta-analysis. OR and 95% CIs were pooled to compare the prevalence of AITD in psoriasis and control groups. Heterogeneity was assessed with I ² statistic. The Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality were applied for quality assessment. The risk of bias was assessed with Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I). Results: Eleven available studies with data on 253 313 patients with psoriasis and 1 376 533 controls were included. Meta-analysis showed that patients with psoriasis had a higher prevalence of AITD (OR 1.76, 95% CI 1.35 to 2.28, Z=4.25, p<0.01), especially loss-of-function disorder of the thyroid gland. Both thyroglobulin antibodies positive rate (OR 1.98, 95% CI 1.27 to 3.10, Z=3.00, p<0.01) and thyroid peroxidase antibodies positive rate (OR 2.15, 95% CI 1.31 to 3.52, Z=3.05, p<0.01) were also increased in the psoriasis group compared with the control group. Conclusions: Our study indicates that the rate of co-occurring AITD was significantly increased in patients with psoriasis. It suggests that the increased risk of AITD should be concerned in patients with psoriasis. PROSPERO registration number: CRD42020206005.

Psoriasis is a chronic inflammatory skin disease with multiple genetic backgrounds, whose etiology and pathogenesis are still unclear. Complex T-cell immune imbalance has been demonstrated to play an important role in pathogenesis of psoriasis. This study reported that microRNA-126 (miR-126) expression was decreased in CD4⁺ T cells of both psoriasis patients and psoriasis-like mouse models and its expression was negatively correlated with the Psoriasis Area and Severity Index (PASI) score of psoriasis patients. Conditional Mir126 knockout in mouse CD4⁺ T cells can obviously aggravate the psoriasis-like dermatitis and promote T-helper (Th)1 and Th17 cells’ infiltration in spleen of imiquimod (IMQ)-induced psoriasis-like mouse model. In addition, the mRNA expression of Il17a and Il17f were significantly increased in mouse naïve CD4⁺ T cells with Mir126 knockout after stimulating with CD3 and CD28. Compared with naïve CD4⁺ T cells, the expression of Mir126 was decreased in Th17 cells, and Mir126 knockout notably promoted the differentiation of naïve CD4⁺ T cells to Th17 cells as well as the mRNA expression of Il17a, Il17f, Rorc, and Il23R. Our results revealed that decreased miR-126 in psoriatic CD4⁺ T cells might accelerate the formation of skin lesions through promoting the differentiation of Th17 cells, thus suggesting a potential intervention target for psoriasis.

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by abnormal T cell activation and excessive proliferation of keratinocytes. In addition to skin manifestations, psoriasis has been associated with multiple metabolic comorbidities, such as obesity, insulin resistance, and diabetes. An increasing amount of evidence has highlighted the core role of adipokines in adipose tissue and the immune system. This review focus on the role of adiponectin in the pathophysiology of psoriasis and its comorbidities, highlighting the future research avenues.