Study of dietary­induced progression of psoriasis­like mice based on gut macrophage polarization.

The aim of the present study was to investigate the influence of stimulating food (SF), a Traditional Chinese Medicine term for a high protein, high fat diet, on psoriasis exacerbation. It was hypothesized that SF disposed psoriasis-like aggravation might be related to inflammatory pathways induction via gut dysbiosis. In the present study, mice were fed either an SF or normal diet for 4 weeks. In the last week, their back hair was removed to establish psoriasis-like dermatitis by imiquimod. After sacrifice, blood samples, alimentary tissues and skin lesions were collected and tested by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Compared with normal diet groups, body weight and blood glucose of SF diet mice were not increased, but they exhibited higher modified Psoriasis Area and Severity Index scores and corresponding epithelial hyperproliferation. Unexpectedly, skin lesions showed abnormal lower protein expressions of Notch and TLR-2/NF-κB p65 signaling pathway, which was attributable to severe skin damage. No difference was observed in the structure and inflammatory cell infiltration of the gut between groups. Instead, macrophage polarization (M1/M2) in the gut of the SF diet group marked by high expression of CD11b (a marker of macrophage, M1) and mild low expression of MRC1 (a marker of macrophage, M2), which resulted in increased TNF-α, decreased IL-10, IL-35, and unchanged IL-17 in serum. Furthermore, serum derived from SF diet mice promoted translocation of NF-κB p65 in HaCaT cells, which indirectly suggested a systemic inflammation. These results suggested that mice fed a continuous SF diet for a time could change gut macrophage polarization, which secretes proinflammatory cytokines into blood circulation. Once transported to skin lesions, these cytokines activate psoriasis tissue resident immune cells and present as psoriasis exacerbation.

Case Report: A Novel MVK Missense Mutation in the Sporadic Porokeratosis Ptychotropica in China.

Porokeratosis ptychotropica (PPt) is a rare type of porokeratosis (PK) characterized by pruritic, reddish-brownish verrucous papules, and plaques usually around genital area or buttocks. Here, a case of a 70-year-old woman who was diagnosed as PPt was reported. The patient suffered from severe pruritic papules and plaques in the buttock region and pubis for 4 years. The skin lesions were giant, well-defined brown plaques with many satellite papules scattered around. Both clinical manifestations and histopathological features supported the diagnosis of PPt. In review of the identified mutation was found in patients with disseminated superficial actinic porokeratosis (DSAP) combined with PPt, while its unclear in PPt. To investigate the hypothesis that the variant reported in the present case report may played as an independent "likely pathogenic factor" of PPt. Consequently, a de novo missense pathogenic mutation in the MVK gene was identified in this case. Unexpectedly, it is a first report of a novel MVK mutation in sporadic PPt. This rare case suggested an isogenetic background between PPt and DSAP, which may help to explore the underlying pathogenesis of PPt.

Relationship Between Vitamin D Level and Mortality in Adults With Psoriasis: A Retrospective Cohort Study of NHANES Data.

PURPOSE: Studies have shown an increased risk for mortality in patients with psoriasis. Furthermore, research has demonstrated an inverse relationship between 25-hydroxyvitamin D (25[OH]D) level and all-cause mortality. This study investigated the association between 25(OH)D level and all-cause mortality in US adults with psoriasis. METHODS: Data from NHANES (1999-2014 and mortality data through December 31, 2015) were analyzed. Quartiles of 25(OH)D level were created based on 25(OH)D levels among patients. Cox proportional hazards models were used for estimating hazard ratios (95% CI) for all-cause mortality. FINDINGS: A total of 82,091 participants were enrolled in the NHANES study from 1999 to 2014. Overall, 610 patients with psoriasis were identified in NHANES. The mean (SD) duration of follow-up was 5.61 (3.38) years (3427.92 person-years). The hazard ratio for mortality in the fully adjusted model was 0.12 (95% CI, 0.02-0.60; Ptrend = 0.01) in patients with a high 25(OH)D concentration compared to those with 25(OH)D deficiency. IMPLICATIONS: The 25(OH)D concentration was significantly inversely associated with all-cause mortality among these patients with psoriasis. Studies have shown an increased risk for mortality in patients with psoriasis compared to the general population. Vitamin D is not regularly metabolized in patients with psoriasis due to their skin abnormality. Vitamin D supplementation has been associated with a reduced mortality in patients with psoriasis. In practice, attention to vitamin D level is crucial, as is the use of vitamin D supplementation, for improving the health of these patients.

Potential Role of Gene Regulator NFAT5 in the Pathogenesis of Diabetes Mellitus.

Nuclear factor of activated T cells 5 (NFAT5), a Rel/nuclear factor- (NF-) κB family member, is the only known gene regulator of the mammalian adaptive response to osmotic stress. Exposure to elevated glucose increases the expression and nuclear translocation of NFAT5, as well as NFAT5-driven transcriptional activity in vivo and in vitro. Increased expression of NFAT5 is closely correlated with the progression of diabetes in patients. The distinct structure of NFAT5 governs its physiological and pathogenic roles, indicating its opposing functions. The ability of NFAT5 to maintain cell homeostasis and proliferation is impaired in patients with diabetes. NFAT5 promotes the formation of aldose reductase, pathogenesis of diabetic vascular complications, and insulin resistance. Additionally, NFAT5 activates inflammation at a very early stage of diabetes and induces persistent inflammation. Recent studies revealed that NFAT5 is an effective therapeutic target for diabetes. Here, we describe the current knowledge about NFAT5 and its relationship with diabetes, focusing on its diverse regulatory functions, and highlight the importance of this protein as a potential therapeutic target in patients with diabetes.

A Preliminary Study of the Effect of Semaphorin 3A and Acitretin on the Proliferation, Migration, and Apoptosis of HaCaT Cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) is significantly elevated in psoriatic patients and is associated with the severity of the psoriasis. Due to the effect of inhibiting production of VEGF, acitretin can effectively treat psoriasis. Semaphorin 3A (Sema3A) restrain tumor growth and angiogenesis by partially reversing VEGF effects on tumor. However, the role of Sema3A in the pathogenesis of psoriasis is unclear. AIMS AND OBJECTIVES: This study aimed to investigate the effect of VEGF, Sema3A, and acitretin on HaCaT cells, to see whether Sema3A could be a beneficial factor in psoriasis, as well as acitretin. MATERIALS AND METHODS: Functional analysis of VEGF, Sema3A, and acitretin was carried out using HaCaT cells cultured under different treatments. Cell counting kit-8 method, colony formation assay, flow cytometry, transwell migration, reverse transcription-polymerase chain reaction, and Western blot test were performed to measure proliferation, colony formation, migration, apoptosis, and the expression of Bcl2, Bax, Caspase 3, and Caspase 9 of HaCaT cells. RESULTS: Sema3A and acitretin inhibited the proliferation, colony formation, and migration of HaCaT cells, while induced the apoptosis of HaCaT cells by inhibiting the expression of Bcl2, and promoting the expression of Bax, Caspase 3, and Caspase 9, which were opposite to VEGF. Sema3A and acitretin partially reversed the function of VEGF. CONCLUSIONS: Like acitretin, exogenous supplement of Sema3A may correct the abnormal proliferation and apoptosis procedure of HaCaT cells, and partially reverse the function of VEGF.

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro.

BACKGROUND: Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. METHODS: Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and ß-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, ß-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/ß-catenin signals. RESULTS: CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, ß-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 µM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and ß-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/ß-catenin signaling. CONCLUSION: Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/ß-catenin signaling.