Antroquinonol Exerts Immunosuppressive Effect on CD8 +

Antroquinonol was investigated as antioxidant and inhibition of inflammatory responses. Our study was to evaluate its immunosuppressive effect on CD8+ T cells and protective effect on depigmentation. CD8+ T cells were treated with antroquinonol in vitro, and C57BL/6 mice were treated with antroquinonol with or without H2O2 in vivo for 50 consecutive days. We found antroquinonol could inhibit proliferation of CD8+ T cells and suppress the production of cytokines IL-2 and IFN-γ and T cell activation markers CD69 and CD137 in vitro. H2O2 treatment induced depigmentation and reduced hair follicle length, skin thickness, and tyrosinase expression in vivo. Whereas, antroquinonol obviously ameliorated depigmentation of mice skin and resisted the reduction of hair follicle length, skin thickness, and tyrosinase expression induced by H2O2. Antroquinonol decreased CD8+ T cell infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Summarily, our data shows antroquinonol inhibits CD8+ T cell proliferation in vitro. It also reduces CD8+ T cell infiltration and proinflammatory cytokine secretion and suppresses the thinning of epidermal layer in vivo. Our findings suggest that antroquinonol exerts immunosuppressive effects on CD8+ T cell proliferation and activation to resist depigmentation induced by H2O2

Pathogenic Th2 Cytokine Profile Skewing by IFN-γ-Responding Vitiligo Fibroblasts via CCL2/CCL8

Purpose: Vitiligo is a T cell-mediated skin depigmentation disease. Though treatments arresting disease progression and inducing repigmentation are available, the efficacy of these options is often limited and poorly sustained. How stromal signals contribute to the interferon-γ-dominant skin niches is unclear. This study aims to determine how fibroblasts participate in the IFN-γ-dominant vitiligo niche. Patients and methods: Mouse vitiligo models were established. Fibroblasts from control and vitiligo mice were extracted for RNA sequencing. In vitro IFN-γ stimulation was performed to verify the JAK-STAT pathway by qPCR and Western blot. T cell polarization with chemokines was measured by flow cytometry. Protein levels in tissues were also examined by IHC. Results: The vitiligo mouse model recapitulates the human CD8-IFN-γ pathway. RNA sequencing revealed elevated chemokine CCL2 and CCL8 in vitiligo fibroblast, which may be regulated by the JAK-STAT signaling. Such phenomenon is verified by JAK inhibitor peficitinib in vitro. Moreover, CCL2 addition into the naïve T polarization system promoted type 2 cytokines secretion, which represents a hallmark of vitiligo lesions. Conclusion: Dermal fibroblasts, a principal constituent of skin structure, respond to IFN-γ by skewing T cells towards a type 2 cytokine profile via CCL2 and CCL8, which can be abrogated by JAK inhibitor peficitinib

A fatal case of febrile ulceronecrotic mucha-habermann disease which presenting as toxic epidermal necrolysis

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a severe form of pityriasis lichenoides et varioliformis acuta, is an inflammatory dermatosis of unknown etiology manifested by ulcerative and necrotic lesions accompanied by systemic manifestations. The mortality rate of FUMHD is about 15%. It is reported here a case of FUMHD presenting as toxic epidermal necrolysis that resulted in multiple organ failure and death

Caffeic acid derivative WSY6 protects melanocytes from oxidative stress by reducing ROS production and MAPK activation

Purpose: Vitiligo is a chronic depigmentation disease caused by a loss of functioning melanocytes and melanin from the epidermis. Oxidative stress-induced damage to melanocytes is key in the pathogenesis of vitiligo. WSY6 is a caffeic acid derivative synthesized from epigallocatechin-3-gallate (EGCG). This study is to investigate whether the new chemical WSY6 protected melanocytes from H2O2-induced cell damage and to elucidate the underlying molecular mechanism. Patients and methods: The present study compared the antioxidative potential of WSY6 with EGCG in hydrogen peroxide (H2O2)-treated PIG1 cells. Western blotting was used to study the protein expression of cyto-c, cleaved-caspase3, cleaved-caspase9, and the activation of MAPK family members, including p38, ERK1/2, JNK and their phosphorylation in melanocytes. ROS assay kit to detect intracellular reactive oxygen species production; CCK8 and lactate dehydrogenase leak assay to detect cytotoxicity. Results: EGCG and WSY6 ameliorated H2O2-induced oxidative stress damage in PIG1 cells in a does-dependent manner, while WSY6 was much more effective. WSY6 reduced cellular ROS production, cytochrome c release, downregulated caspase-3 and caspase-9 activation. MAPK pathway signaling including phosphorylated p38, ERK and JNK were observed under oxidative stress and can be much protected by pre-treatment of WSY6. Conclusion: These results indicated that WSY6 could be a more powerful antioxidant than EGCG and protect melanocytes against oxidative cytotoxicity

STUDY OF CALCIPOTRIOL BETAMETHASONE OINTMENT IN THE TREATMENT OF PATIENTS WITH REFRACTORY CHRONIC ECZEMA

Chronic eczema is an inflammatory-immune disease of the skin, with the characteristics of skin thickening and varying degrees of lichenification, including severe itching, tendency of persistence and recurrence with serious impact on quality of life of patients. Objective: To assess the clinical efficacy and safety of calcipotriol betamethasone ointment in patients with chronic eczema. Methods: In this multi-center, randomized, single-blind, positive drug parallel controlled clinical study, patients were randomly divided into treatment and control groups, to receive calcipotriol betamethasone ointment or halometasone/triclosan cream, respectively, once daily in the evening over a 4-week period. The safety and efficacy of the two regimens were followed up on weeks 1, 2, 4 and at a 4-week treatment-free period. According to the degree of improvement, the total scores (0-4) before and after treatment and the efficacy index were calculated. The overall efficacy was assessed by four levels of evaluation model. Results: After 4 weeks of treatment, the cure rate was high (44.70%) in treatment group compared with control group (15.56%) (P<0.001), and the effective rate was 83.33% and 55.56% in the respective groups (P<0.001). At 2 and 4 weeks after treatment, there was significant difference (P<0.05) between two groups, with a reduction in the intensity of pruritus, inflammation, infiltration/ hypertrophy, lichenification, and area of target lesions. The incidence of adverse events was more (1.52%) in treatment than control group (0.00%) (P>0.05). Conclusion: Calcipotriol betamethasone ointment appears to be a safe and effective option for the treatment of chronic eczema

Identification of QTLs and candidate genes for rice seed germinability under low temperature using high‐density genetic mapping and RNA‐seq

Abstract Reduced temperatures during germination adversely affect rice (Oryza sativa L.) production. Little is known, however, of the genes or genetic loci involved. Here, QTLs were investigated in a recombinant inbred line (RIL) resulting from a 02428 (japonica)‐YZX (indica) cross. The phenotypes of the cultivars differ significantly when exposed to low temperatures during germination. Mapping with a high‐density bin map identified 11 loci associated with low‐temperature germination of which loci 2 and 4 were identified by multiple traits over two seasons. Locus 2 was a major genetic locus, explaining 22.36% of phenotypic variation. The haplotype results showed that the pyramiding of favorable alleles of these two loci was beneficial to improving the rice seeds' low‐temperature germinability. RNA‐seq analysis was performed on the second day of germination at low temperature for both parents. Three DGEs (Os03g0119800, Os03g0120900, and Os03g0121300) were obtained for locus 2 and were confirmed as the most likely candidates by qRT‐PCR verification, gene sequence alignment, and haplotype analysis. Collectively, these quantitative trait loci and candidate genes may be valuable for the breeding of cold‐tolerant rice lines as well as broadening our knowledge of the genetics underlying germination at low temperatures