Myricetin treatment has ameliorative effects in DNFB-induced atopic dermatitis mice under high-fat conditions.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder. Obesity is associated with increased prevalence and severity of AD for reasons that remain poorly understood. Myricetin, a dietary flavonoid found in fruits and vegetables, is known to have anti-inflammatory effects, but its role in AD is unclear. Thus, we investigated the effects of obesity on exacerbation AD lesions and evaluated the effects of myricetin on obese AD. Mice were fed normal diet (ND) or high-fat diet, and then 2,4-dinitrofluorobenzene was used to induce AD-like lesions. We found that obesity exacerbated AD lesions, and myricetin topical administration ameliorated symptoms and skin lesions of obsess AD mice, such as dermatitis scores, scratching behavior, epidermal thickness, and mast cell infiltration. In addition, myricetin reduced the levels of immunoglobulin E and histamine, inhibited the infiltration of CD4+T cells, and modulated the expression of Th1, Th2, Th17, and Th22 cytokines and pro-inflammatory factors (CCL17, CCL22, IL-1ß, and TGF-ß). Moreover, myricetin restored impaired barrier function by reducing transepidermal water loss, increasing lamellar body secretion, as well as upregulating the mRNA and protein expression of filaggrin. Western blot results showed that significantly increased levels of phosphorylated IκB and NF-κB p65 was observed in the obese AD mice compared with the AD mice fed ND, whereas the myricetin could downregulated the phosphorylations of IκB and NF-κB, and inhibited mRNA expression of iNOS and COX2. Taken together, our results suggest that myricetin treatment exhibits potentially protective effects against the obeseassociated AD by inhibiting inflammatory response and restoring skin barrier function.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. METHODS: KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. RESULTS: NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. CONCLUSION: NMN may have a positive effect on relieving symptoms of AD.

Effects of the long and short isoforms of TIPE3 on the growth and metastasis of gastric cancer.

Tumor necrosis factor alpha-induced protein 8-like 3 (TIPE3, also known as TNFAIP8L3) plays a vital role in tumorigenesis and development. However, it is unclear whether the two transcript variants of TIPE3 (long TIPE3 and short TIPE3) have an effect on the proliferation and metastasis of gastric cancer (GC). In this study, we demonstrated that the expression of TIPE3 decreased in GC, but patient prognosis worsened as TIPE3 expression increased. Then, overexpression models were constructed to study the role of long TIPE3 and short TIPE3. Upregulation of long TIPE3 and short TIPE3 promoted GC cell proliferation and metastasis both in vitro and in vivo, and the effect of short TIPE3 was more obvious. Further studies demonstrated that long TIPE3 and short TIPE3 promoted proliferation and metastasis of GC cells vis PI3K/Akt pathway. In conclusion, the two TIPE3 isoforms play an important role in the tumorigenesis of GC and depend on the activation of the PI3K/Akt pathway.

Associations of the IL-17A rs2275913 and IL-17F rs763780 polymorphisms with the risk of digestive system neoplasms: A meta-analysis.

OBJECTIVE: To clarify the associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and the risk of digestive system neoplasms. METHODS: An internet search was used to identify relevant articles from CNKI, Wanfang, VIP, PubMed, EMBASE and Elsevier up to December 2017. The meta-analysis was performed using Stata 11.0 software. RESULTS: Twenty-three studies were included. Among these, 21 studies with 6978 cases and 8000 controls were related to IL-17A rs2275913, while 18 studies that included 5073 cases and 6040 controls were related to IL-17F rs763780. The meta-analysis results demonstrated that the overall effects of the two polymorphisms were significantly different (P < 0.05) in the allele model, dominant model, recessive model and codominant model. Subgroup analysis showed that both polymorphisms were significantly associated with susceptibility to gastric cancer but not with hepatocellular carcinoma or colorectal cancer. In the ethnicity analysis, these two polymorphisms were associated with Asian populations but not with Caucasians. Similar results were observed in the hospital-based and population-based control subgroups. CONCLUSIONS: The IL-17A rs2275913 and IL-17F rs763780 polymorphisms were associated with susceptibility to digestive system neoplasms.