The Southern Hemisphere (SH) zonal-mean circulation change in response to Antarctic ozone depletion is re-visited by examining a set of the latest model simulations archived for the Chemistry-Climate Model Initiative (CCMI) project. All models reasonably well reproduce Antarctic ozone depletion in the late 20th century. The related SH-summer circulation changes, such as a poleward intensification of westerly jet and a poleward expansion of the Hadley cell, are also well captured. All experiments exhibit quantitatively the same multi-model mean trend, irrespective of whether the ocean is coupled or prescribed. Results are also quantitatively similar to those derived from the Coupled Model Intercomparison Project phase 5 (CMIP5) high-top model simulations in which the stratospheric ozone is mostly prescribed with monthly-and zonally-averaged values. These results suggest that the ozone-hole-induced SH-summer circulation changes are robust across the models irrespective of the specific chemistry-atmosphere-ocean coupling.
Many studies have explored the relationship between coffee—one of the most commonly consumed beverages today—and obesity. Despite inconsistent results, the relationship has not been systematically summarized. Thus, we conducted a meta-analysis by compiling data from 12 epidemiologic studies identified from PubMed and Embase through February 2019. The included studies assessed obesity by body mass index (BMI, a measure of overall adiposity) or waist circumference (WC, a measure of central adiposity); analyzed the measure as a continuous outcome or binary outcome. Using random effects model, weighted mean difference (WMD) and 95% confidence interval (CI) were obtained for continuous outcomes; summary relative risk (RR) and 95% CI for the highest vs. lowest categories of coffee intake were estimated for binary outcome. For BMI, WMD was −0.08 (95% CI −0.14, −0.02); RR was 1.49 (95% CI 0.97, 2.29). For WC, WMD was −0.27 (95% CI −0.51, −0.02) and RR was 1.07 (95% CI 0.84, 1.36). In subgroup analysis by sex, evidence for an inverse association was more evident in men, specifically for continuous outcome, with WMD −0.05 (95% CI −0.09, −0.02) for BMI and −0.21 (95% CI −0.35, −0.08) for WC. Our meta-analysis suggests that higher coffee intake might be modestly associated with reduced adiposity, particularly in men.
Transmembrane 4 L six family member 4 (TM4SF4) is a member of the tetraspanin L6 domain family. Other members of this family, TM4SF1 (also known as L6-Ag) and TM4SF5, have been shown to be upregulated in multiple tumors and involved in epithelial-to-mesenchymal transition and cell migration. However, unlike its homologs, little is known about TM4SF4. Here, we show that TM4SF4 was highly expressed in radiation-resistant lung adenocarcinoma cells, such as A549 and Calu-3 cells, and its expression activated cell growth, migration, and invasion. Overexpression of TM4SF4 in A549 cells increased the activation of PI3K, AKT, and NF-kappaB and the expression of PTEN. IGF1R was clearly activated by overexpression of TM4SF4, although EGFR was also slightly activated. TM4SF4 expression was correlated with the increased expression of IGF1, consequently resulting in IGF1R activation. Tumorigenic activity of TM4SF4 in lung adenocarcinoma cells was also demonstrated by xenograft assay; however, this activity was almost completely suppressed by treatment with anti-TM4SF4 antibody. Our results suggest that TM4SF4 overexpression in lung carcinoma cells results in resistance to radiotherapy via IGF1-induced IGF1R activation and blocking the activity of TM4SF4 using specific antibody can be a promising therapeutics against TM4SF4-overexpressing lung adenocarcinoma.
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifolium pratense. In this study, we investigated the effects of pratol on melanogenesis. We also studied the mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were treated with various concentrations (6.25, 12.5, 25, and 50 μM) of pratol to observe its effects. The results showed that pratol significantly increased melanin content and tyrosinase activity in the cells without being cytotoxic. In addition, pratol strongly increased the expression of tyrosinase and tyrosinase-related protein-1 and 2 by enhancing the expression of microphthalmia-associated transcription factor. Furthermore, pratol stimulated melanogenesis via the phosphorylation of p38, c-Jun N-terminal kinases (JNK), and extracellular signal–regulated kinase (ERK). The findings from an assay searching for the inhibitor revealed that SB203580 (a specific p38 inhibitor) or SP600125 (a p-JNK inhibitor) attenuated pratol-induced cellular tyrosinase activity whereas PD98059 (an ERK inhibitor) did not. Additionally, pratol interfered with the phosphorylation of p-AKT. We also found that pratol-induced melanogenesis was reversed by H89, which is a specific protein kinase A inhibitor. The results suggest that, owing to its multi-functional properties, pratol may be a potential tanning agent or a therapeutic agent for hair depigmentation in the cosmetic industry.
This study was carried out to investigate the antimelanogenic effects of a Polygonum tinctorium flower extract obtained using red nuruk, a traditional Jeju barley-based fermentation starter. We also studied the mechanism of action of the P. tinctorium fermented flower extract (PTFFE) in mouse melanoma cells (B16F10). Cells were treated with various concentrations (62.5, 125 and 250 μg/mL) of PTFFE and the results showed that PTFFE significantly decreased the melanin content and tyrosinase activity without being cytotoxic. In addition, PTFFE strongly inhibited the expression of tyrosinase and tyrosinase-related protein 2 by decreasing the expression of the microphthalmia-associated transcription factor, as shown by a western blot assay. Furthermore, PTFFE inhibited melanogenesis via upregulation of the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B, also known as AKT. We also used inhibitors such as PD98059 (a specific ERK inhibitor) or LY294002 (an AKT inhibitor) to determine whether the signaling pathways are involved. High-performance liquid chromatography fingerprinting showed the presence of a quercetin glucoside (isoquercitrin) and quercetin in PTFFE. To test the potential for PTFFE application as a cosmetic material, we also performed a primary skin irritation test on human skin. In this assay, PTFFE did not induce any adverse reactions at the treatment dose. Based on these results, we suggest that PTFFE may be considered a potential antimelanogenesis candidate for topical applications.
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