Objective: Atopic dermatitis (AD) is a prevalent, burdensome, and psychologically important pediatric concern. Probiotics have been suggested as a treatment for AD. Some reports have explored this topic; however, the utility of probiotics for AD remains to be firmly established.Methods: To assess the effects of probiotics on AD in children, the PubMed/Medline, Cochrane Library Scopus, and OVID databases were searched for reports published in the English language.Results: Thirteen studies were identified. Significantly higher SCORAD values favoring probiotics over controls were observed (mean difference [MD], −3.07; 95% confidence interval [CI], −6.12 to −0.03; P < 0.001). The reported efficacy of probiotics in children < 1 year old was −1.03 (95%CI, −7.05 to 4.99) and that in children 1–18 years old was −4.50 (95%CI, −7.45 to −1.54; P < 0.001). Subgroup analyses showed that in Europe, SCORAD revealed no effect of probiotics, whereas significantly lower SCORAD values were reported in Asia (MD, −5.39; 95%CI, −8.91 to −1.87). Lactobacillus rhamnosus GG (MD, 3.29; 95%CI, −0.30 to 6.88; P = 0.07) and Lactobacillus plantarum (MD, −0.70; 95%CI, −2.30 to 0.90; P = 0.39) showed no significant effect on SCORAD values in children with AD. However, Lactobacillus fermentum (MD, −11.42; 95%CI, −13.81 to −9.04), Lactobacillus salivarius (MD, −7.21; 95%CI, −9.63 to −4.78), and a mixture of different strains (MD, −3.52; 95%CI, −5.61 to −1.44) showed significant effects on SCORAD values in children with AD.Conclusions: Our meta-analysis indicated that the research to date has not robustly shown that probiotics are beneficial for children with AD. However, caution is needed when generalizing our results, as the populations evaluated were heterogeneous. Randomized controlled trials with larger samples and greater power are necessary to identify the species, dose, and treatment duration of probiotics that are most efficacious for treating AD in children.
Highlights d ADORA1 inhibition promotes immune escape by regulating tumor PD-L1 via ATF3 d ADORA1 or ATF3 screening may be used to assess PD-1 mAb therapy efficacy d Combination of an ADORA1 antagonist and a PD-1 mAb provides therapeutic benefit
TRAF6 (TNF Receptor-Associated Factor 6) is an E3 ubiquitin ligase that contains a Ring domain, induces K63-linked polyubiquitination, and plays a critical role in signaling transduction. Our previous results demonstrated that TRAF6 is overexpressed in melanoma and that TRAF6 knockdown dramatically attenuates tumor cell growth and metastasis. In this study, we found that EGCG can directly bind to TRAF6, and a computational model of the interaction between EGCG and TRAF6 revealed that EGCG probably interacts with TRAF6 at the residues of Gln54, Gly55, Asp57 ILe72, Cys73 and Lys96. Among these amino acids, mutation of Gln54, Asp57, ILe72 in TRAF6 could destroy EGCG bound to TRAF6, furthermore, our results demonstrated that EGCG significantly attenuates interaction between TRAF6 and UBC13(E2) and suppresses TRAF6 E3 ubiquitin ligase activity in vivo and in vitro. Additionally, the phosphorylation of IκBα, p-TAK1 expression are decreased and the nuclear translocation of p65 and p50 is blocked by treatment with EGCG, leading to inactivation of the NF-κB pathway. Moreover, EGCG significantly inhibits cell growth as well as the migration and invasion of melanoma cells. Taken together, these findings show that EGCG is a novel E3 ubiquitin ligase inhibitor that could be used to target TRAF6 for chemotherapy or the prevention of melanoma.
The biological activities of propolis are varied from plant sources and the prominent antioxidant effects of Chinese propolis (poplar type) have been extensively reported. Oxidative stress is associated with inflammation and induces many diseases. In the study, to evaluate antioxidant capacities and clarify the underlying molecular mechanisms of ethanol extracts of Chinese propolis (EECP) and ethanol extracts of poplar gums (EEPG), we analyzed their compositions by HPLC, evaluating their free radical scavenging activities and reducing power by chemical analysis methods. Moreover, we studied the roles of EECP and EEPG on the elimination of ROS and expressions of antioxidant genes (HO-1, TrxR1, GCLM, and GCLC) in RAW264.7 cells. We further investigated the effects of MAPKs on the antioxidant genes expression by specific inhibitors. The nucleus translocation effects of Nrf2 were also measured by confocal microscopy analysis. The results indicated that EECP had higher TPC and FDC values but regarding TFC values were not significant. EECP also possessed more contents of 11 compounds than EEPG. Both phytochemical analysis and cell experiment reflected that EECP exerted stronger antioxidant activities than EEPG. EECP and EEPG enhanced endogenous antioxidant defenses by eliminating reactive oxygen species directly and activating Erk-Nrf2-HO1, GCLM, and TrxR1 signal pathways.
Although epidemiologic studies have linked arsenic exposure to the development of human cancer, the mechanisms underlying the tumorigenic role of arsenic remain largely undefined. We report here that treatment of cells with sodium arsenite at the concentrations close to environmental exposure is associated with the up-regulation of Hdm2 and the accumulation of p53 in the cytoplasm. Through the mitogenactivated protein kinase pathway, arsenite stimulates the P2 promoter-mediated expression of Hdm2, which then promotes p53 nuclear export. As a consequence, the p53 response to genotoxic stress is compromised, as evidenced by the impaired p53 activation and apoptosis in response to UV irradiation or 5FU treatment. The ability of arsenite to impede p53 activation is further demonstrated by a significantly blunted p53-dependent tissue response to 5FU treatment when mice were fed with arsenite-containing water. Together, our data suggests that arsenic compounds predispose cells to malignant transformation by up-regulation of Hdm2 and subsequent p53 inactivation. [Cancer Res 2008;68(22):9131-6]
TRAF6, a well-known adapter molecule, plays pivotal role in TLR/IL-1R associated signaling pathway. Although TRAF6 has been shown to have oncogenic activity in various malignant tumors, the details remain unclear. In this study, we demonstrated that TRAF6 facilitates Ras (G12V) and EGF-induced cellular transformation through EGFR. Silencing of TRAF6 expression significantly downregulated AP-1 activity, as well as MMP-2,9 expression after EGF stimulation. Furthermore, we found that TRAF6 plays an essential role in cutaneous squamous cell carcinoma (cSCC) malignant phenotypes, affecting cell growth and migration. CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is over-expressed in tumors and induces tumorigenesis. Our results showed that CD147 formed complex with EGFR and TRAF6. Knockdown of TRAF6 disrupted the CD147-EGFR complex, thereby inducing EGFR endocytosis. Therefore, TRAF6 might be a novel molecular target for cSCC prevention or therapy.
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