Hypoxia regulates allele-specific histone modification of the imprinted H19 gene.

H19 is a maternally-expressed imprinted gene that encodes long non-coding RNA. Chromatin immunoprecipitation (ChIP)-sequencing analyses of human adipose-derived stem cells (hADSCs) showed that hypoxia induced trimethylation of 4th lysine residue of histone 3 (H3K4me3) in the H19 gene, among the 40 known human imprinted genes, to the greatest extent. We investigated whether hypoxia changed the DNA and histone methylation levels of the imprinted H19 gene in an allele-specific (AS) manner. Using AS primer sets for the human H19 gene, we conducted ChIP-quantitative polymerase chain reaction, which revealed that hypoxia increased the active histone marks, H3K4me3 and H3K9/14Ac, in one allele (named B allele) but not in the other allele (named A allele). In contrast, hypoxia did not change the H3K9me3 levels in either allele. Hypoxia-inducible factor 1 (HIF-1) directly bound to the H19 promoter only in the B allele. HIF-1α knock-down prevented the increase in the active histone modification and mRNA expression of the B allele under hypoxia, indicating that HIF-1α caused AS changes in the histone modification of the H19 gene. Long-term hypoxia did not change the AS DNA methylation throughout the cell cycle. Thus, hypoxia changed the histone modification of the active allele in an HIF-1α-dependent manner, without changing the imprinted status of the H19 gene.

Spatio-temporal patterns of the minimum rest time for outdoor workers exposed to summer heat stress in South Korea.

In this study, the spatio-temporal characteristics of the minimum rest time for the safety of South Korean outdoor workers during hot summer months (June to August) are examined based on the hourly wet-bulb globe temperature (WBGT) across 27 weather stations in South Korea. The WBGT thresholds in the work-rest recommendation of the Korea Occupational Safety and Health Agency (KOSHA 2017) for the quantification of the minimum rest time are evaluated through a comparison of the given thresholds with the occurrences of occupational heat-related illness patients due to outdoor work during hot summer months in South Korea. The long-term (2009-2018) average of the hourly WBGT values during summer months shows that outdoor workers with a moderate workload are exposed to heat stress during approximately 30% of the entire daytime working hours (06:00-18:00). According to the WBGT thresholds modified from the KOSHA (2017) guidelines, the daily minimum rest time for a moderate workload noticeably increases up to 18% (11 min/h) in mid-summer (late July and early August). During mid-summer, the minimum rest time for a continuous moderate outdoor workload even increases up to 31% (18 min/h) between 12:00 and 13:00 and is regionally higher in the southwestern than in the southeastern regions of the Korean Peninsula. These results suggest that in summertime high-heat environments, a mandatory rest time must be provided according to appropriate heat management programs for the safety of workers.

New ethanol extraction improves the anti-obesity effects of black tea.

Black tea has been reported to have anti-obesity effects in both rodents and humans. Gallic acid, an active component of black tea, decomposes quickly into pyrogallol in high-temperature solutions. This study introduced a new, aqueous ethanol extraction of black tea, which resulted in extracts with higher concentrations of gallic acid than conventional black tea extracts prepared by hot-water extraction or hot-ethanol extraction. We confirmed that, compared with the hot-water extract of black tea, the cold-ethanol extract of black tea (CE-BTE) had greater effects on reducing body weight and body fat, improving fatty liver, regulating blood glucose, and reducing blood cholesterol in the high-fat diet-induced obese mouse model. Nonetheless, although CE-BTE significantly reduced fat content, it did not reduce peroxisome proliferator-activated receptor (PPARγ) protein in epididymal fat tissue of HFD mice. We also showed that CE-BTE did not inhibit the function of PPARγ protein to drive adipogenesis of mouse 3T3-L1 preadipocytes. Considering that PPARγ is a master transcription factor not only for adipocyte differentiation, but also for adipose tissue function, such as glucose and lipid metabolism and insulin sensitivity, these results suggest that CE-BTE reduced fat mass and body weight without dampening fat cell homeostasis and insulin sensitivity.