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Hidrotic ectodermal dysplasia (HED) is a rare inherited syndrome characterised by nail dystrophy, palmoplantar hyperkeratosis and alopecia. Four mutations (p.G11R, p.A88V, p.V37E and p.D50N) in gap junction beta 6 (GJB6) gene, which codes connexin30 protein, have been found to cause HED in different populations. Here, we reported a big Chinese family in which 24 patients over five generations were suffered with HED. Sequence analysis identified all 24 patients carry a recurrent missense mutation c.263C > T (p.A88V) in GJB6. Our results reveal gene testing of GJB6 is important for diagnosis, prenatal diagnosis and future gene treatment of HED.

Loss of melanocytes induced by activated CD8+ T cells is the pathological hallmark of vitiligo. Melanocyte-specific CD8+ T cells are recruited to the skin via chemokines, thereby releasing perforin, granzyme, and other cytotoxic substances that destroy the melanocytes. However, the mechanism of CD8+ T cells to adhere to melanocytes is unknown. Previous transcriptome sequencing results published by our group showed that the occluding (OCLN) gene was significantly upregulated in CD8+ T cells from skin lesions of vitiligo. Occludin is a crucial component of the tight junction between cells; in cells without tight junction, occludin mediates the adhesion of two cells in the form of a self-ligand. This study demonstrated that OCLN gene expression was elevated in the CD8+ T cells of vitiligo patients, and occludin mediates the adherence of CD8+ T cells to melanocytes. Besides, pathological changes in vitiligo skin lesions reveal that CD8+ T cells continuously persist in the skin lesions, which is related to the persistence of the disease. In this regard, we found that fibroblasts from vitiligo patients significantly express occludin, which may participate in the continuous retention of CD8+ T cells in the skin lesions. The pathogenesis of vitiligo is closely related to oxidative stress, and our data suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) increases the expression of occludin. Besides, ChIP-qPCR of CD8+ T cells revealed that HIF-1α directly binds to the OCLN promoter. Thus, occludin upregulation promotes the adhesion of CD8+ T cells and melanocytes via the HIF-1α signaling pathway. Our study results suggested a critical role for OCLN in the occurrence, progression, and maintenance of vitiligo. Therefore, inhibiting the expression of OCLN gene may be a potential targeted treatment strategy.

Perforin (PRF), a pivotal cytotoxic effector molecule of activated CD8To investigate the contributions of DNA methylation to the abnormal expression of perforin in CD8Skin samples and CD8Increased CD8Hypomethylation of the perforin promoter contributes to its overexpression in CD8

Loss of melanocytes induced by activated CD8

Background. Vitiligo is a disfiguring skin disease with profound psychosocial impacts, such as anxiety, but the reported effect sizes of associations vary. We aimed to conduct a meta-analysis to quantify the strength of association between anxiety and vitiligo and to estimate the prevalence of anxiety among individuals with vitiligo. Methods. A systematic literature search was performed in five online databases (MEDLINE, Embase, Web of Science, Cochrane Library, and PsycINFO) from inception until March 20, 2020. All of the eligible studies were comprehensively reviewed, and all of the available data were analyzed according to our predefined criteria. Results. Twenty-one studies involving 3259 patients in 11 countries were included in this meta-analysis. Compared with the healthy control group, patients with vitiligo often had concomitant anxiety ( OR = 6.14 [95% CI: 3.35–11.24], I 2 = 30.1 % ). The pooled prevalence of anxiety in female patients was significantly higher than that in males ( OR = 2.24 [95% CI: 1.31–3.84], I 2 = 0.0 % ). Subgroup analysis showed that the pooled prevalence of clinical anxiety disorder and anxiety symptoms was 12% (95% CI: 7%–16%, I 2 = 76.3 % ) and 34% (95% CI: 21%–46%, I 2 = 94.7 % ), respectively. No publication bias has been detected by Begg’s funnel plot and Egger’s test. Conclusion. Patients with vitiligo have high anxiety comorbidity, with female predominance. Dermatologists and psychiatrists should be vigilant to the presence of anxiety, apply appropriate interventions to reduce the psychological impacts in a timely manner, and thus promote recovery in vitiligo patients. However, due to some objective limitations (poor information about the OR and diversity in assessment tools among included studies), findings should be interpreted with caution.

In late 2019, the coronavirus disease 2019 (COVID-19) broke out in Wuhan and then spread over China, which greatly impacted on the medical practices and healthcare systems With most of the hospital's outpatient services closed, the routine clinical diagnosis and treatment for dermatomyositis (DM) patients has been disturbed We conducted telephone follow-up on 52 patients to concern the changes in the condition and the continuation of drug therapy, to ensure the continuity, safety and effectiveness treatment of DM patients during COVID-19

In late 2019, the coronavirus disease 2019 (COVID-19) broke out in Wuhan and then spread over China, which greatly affected the medical practices and health care systems. With most of the hospital’s outpatient services closed, the routine clinical diagnosis and treatment for patients with dermatomyositis has been disturbed. We conducted telephone follow-up for 52 patients to know the changes in the condition and the continuation of drug therapy and to ensure the continuity, safety, and effectiveness of the treatment of patients with dermatomyositis during COVID-19.

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Systemic sclerosis (SSc) is a connective tissue disease with the involvement of complex signaling pathways, such as TGF-β/Smad2/3. SSc can lead to severe multiple organ fibrosis, but no effective therapy is currently available because of its unclear pathogenesis. Exploring new treatments is the focus of recent research on SSc. Recent studies have implied a potential antifibrotic role of esomeprazole (ESO), but with currently unidentified mechanisms. Signaling of AhR, a ligand-dependent transcription factor, has been described as a key controller of fibrosis, tumorigenesis, and immune balance. Recently, it has been reported that ESO may be an exogenous agonist of AhR signaling, while no previous study has revealed the effects of ESO on SSc and its underlying mechanisms. In this study, we demonstrate that ESO suppresses the migration of SSc dermal fibroblasts, downregulates profibrotic markers, including COLIA1, α-SMA CTGF and MMP1, and limits collagen production potentially via the activation of AhR signaling. More importantly, ESO could block Smad2/3 phosphorylation concurrently with the reduction in collagen via AhR signaling. Moreover, our results from the bleomycin (BLM)-induced SSc model in skin and lung shows that ESO ameliorates fibrosis in vivo, which in keeping with our in vitro results. We conclude that ESO is a potential therapeutic drug for SSc fibrosis.

Particulate matter with an aerodynamic equivalent diameter of 2.5 μm or less in ambient air (PM2.5) has become a global public and environmental problem, and the control of the PM2.5 concentration in air is an urgent problem. PM2.5 can easily penetrate the skin, activating the inflammatory response in skin, unbalancing the skin barrier function, and inducing skin aging. Hyperpigmentation is the main manifestation of skin aging and has a considerable impact on quality of life worldwide. To date, no research on the influence of PM2.5 on hyperpigmentation has been conducted. Here, we illustrate that PM2.5 can induce melanogenesis in vivo and in vitro by regulating TYR, TYRP1, TYRP2, and MITF expression via AhR/MAPK signaling activation. Furthermore, PM2.5 increased α-MSH paracrine levels, which in turn promote hyperpigmentation. Our results provide a deeper understanding of how PM2.5 disrupts skin homeostasis and function. Treatment with AhR antagonists may be a potential therapeutic strategy for hyperpigmentation induced by PM2.5.

Systemic sclerosis (SSc) is a systemic autoimmune disease that often leads to fibrosis of multiple organs, and there are no effective treatments. Aryl hydrocarbon receptor (AhR) is a highly evolutionarily conserved transcription factor activated by endogenous and exogenous ligands and that regulate cell proliferation, tumorigenesis and immune balance. Recently, it have reported AhR signaling may participate in fibrosis process, usually consider as a negative regulator of TGF-β. However, the detailed relationship between AhR and SSc has not been reported yet. Here we firstly found that AhR and CYP1A1 downregulated in SSc fibroblast(n = 6). The AhR ligand-Ficz negatively regulates TGF-β1, COL1A1 and α-SMA expression, also enhances the MMP-1 expression via the AhR signaling activation. Conversely the AhR antagonist CH223191 could inhibit this effect. Furthermore, the antifibrosis effect of AhR signaling activation was also confirmed in bleomycin induced scleroderma mouse model. In conclusion, AhR signaling activation balances the extracellular matrix (ECM) composition and deposition, which may provide a new sight to the pathogenesis of SSc and AhR signaling activation may be a potential therapy for SSc.