Sodium thiosulfate ameliorates atopic dermatitis via inhibiting the activation of NLRP3 inflammasome.

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1ß expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.

The Role of VD/VDR Signaling Pathway in Autoimmune Skin Diseases.

BACKGROUND: Immune-related cutaneous diseases are a series of disorders, such as alopecia areata, psoriasis, atopic dermatitis, systemic lupus erythematosus and autoimmune bullous dermatoses. Vitamin D is a fat-soluble vitamin, which is known for its classical pleiotropic effect. Recent studies have found that vitamin D, after catalyzed into its biologically active form [1,25(OH) 2D], correlated with its receptor, vitamin D receptor, plays a vital role in multiple pathophysiological processes, including immune-related dermatoses. This review mainly summarizes evidence on the role of vitamin D/vitamin D receptor in immune-related cutaneous diseases and the potential therapeutic targets for skin disorders. METHODS: We have carried out a comprehensive literature search in PubMed and Google Scholar databases using keywords like "vitamin D", "vitamin D receptor", "immune", "psoriasis", "atopic dermatitis", "skin", "systemic lupus erythematosus", "alopecia areata" and "autoimmune bullous dermatoses". Only articles related to the topic were included in this review. Conference, patent, graduation thesis and articles without available full text were excluded. RESULTS: Vitamin D/vitamin D receptor is critical for skin in regulating the proliferation and differentiation of keratinocytes, keeping the integrity of the skin barrier as well as maintaining the homeostasis of the "skin's immune system". Vitamin D deficiency/vitamin D receptor mutations are potential risk factors for some immune-related cutaneous diseases. CONCLUSION: Vitamin D is a pleiotropic hormone, which is important in the homeostasis of human body. Many studies have revealed vitamin D deficiency in several skin diseases. Thus, vitamin D supplementation may be a useful therapeutic option for immune-related skin diseases.

Effect of electroacupuncture on the expression of agrin and acetylcholine receptor subtypes in rats with tibialis anterior muscular atrophy induced by sciatic nerve injection injury.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on mRNA and protein expression of agrin, acetylcholine receptor (AChR)-ε and AChR-γ in a rat model of tibialis anterior muscle atrophy induced by sciatic nerve injection injury, and to examine the underlying mechanism of action. METHODS: Fifty-four adult Sprague-Dawley rats were divided into four groups: healthy control group (CON, n=6); sciatic nerve injury group (SNI, n=24), comprising rats euthanased at 1, 2, 4 and 6 weeks, respectively, after penicillin injection-induced SNI (n=6 each); CON+EA group (n=12), comprising healthy rats euthanased at 4 and 6 weeks (after 2 and 4 weeks, respectively, of EA at GB30 and ST36); and SNI+EA group, comprising rats euthanased at 4 and 6 weeks (after 2 and 4 weeks, respectively, of EA). The sciatic nerve functional index (SFI), tibialis anterior muscle weight, muscle fibre cross-sectional area (CSA), and changes in agrin, AChR-ε, and AChR-γ expression levels were analysed. RESULTS: Compared with the control group (CON), SNI rats showed decreased SFI. The weight of the tibialis anterior muscle and muscle fibre CSA decreased initially and recovered slightly over time. mRNA/protein expression of agrin and AChR-ε were downregulated and AChR-γ expression was detectable (vs zero expression in the CON/CON+EA groups). There were no significant differences in CON+EA versus CON groups. However, the SNI+EA group exhibited significant improvements compared with the untreated SNI group (p<0.05). CONCLUSIONS: EA may alleviate tibialis anterior muscle atrophy induced by sciatic nerve injection injury by upregulating agrin and AChR-ε and downregulating AChR-γ.

[Triptolide evaluates DNA methylation level of matrix metalloproteinase 9 gene in human fibrosarcoma HT-1080 cells].

OBJECTIVE: The effect of triptolide on the DNA methylation level of MMP-9 gene and the mRNA expression of tissue inhibitors of met-alloproteinases (TIMPs) were examined in human fibrosarcoma HT-1080 cells to explore the molecular mechanisms involved in the anticancer activity of triptolide. METHOD: HT-1080 cells were cultured in MEM containing 10% newborn calf serum and 1% penicillin-streptomycin. Triptolide was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 1 goL-1 and stored at -20 degrees C. Triptolide was freshly diluted with culture medium perior to use and directly added to cell cultures at the indicated concentration, and incubated for 72 hours at 37 degrees C in a humidified atmosphere with 5% CO2, with changes of reagents every 24 hours. Methylation specific PCR (MSP)was applied to assess the methylation status of MMP-9 gene promoter, and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was employed to measure the mRNA expression of tissue inhibitors of metalloproteinases (TIMPs) in human fibrosarcoma HT-1080 cells after 72 hours of treatment with 6 nmol x L(-1), 12 nmol x L(-1) or 18 nmol x L(-1) triptolide, respectively. RESULTS: The methylation index of MMP-9 gene promoter was statistically elevated in HT-1080 cells after 72 hours of treatment with 18 nmol L(-1) triptolide, compared with those in controls (0.61 +/- 0.10 vs 0.39 +/- 0.10, P < 0.05), while no significant difference was noted between 6 nmol x L(-1) or 12 nmol x L(-1) triptolide treated HT-1080 cells and controls (0.40 +/- 0.15 vs 0.39 +/- 0.10, 0.46 +/- 0.20 vs 0.39 +/- 0.10, respectively, both P > 0.05). The mRNA expression of TIMP-1, -2, -3 or -4 was not significantly changed in HT-1080 cells after 72 hours of treatment with the indicated concentrations of triptolide, respectively compared with those in controls (all P > 0.05). CONCLUSION: The results demonstrated that triptolide upregulates the methylation level of MMP-9 gene in HT-1080 cells in vitro.