Eicosapentaenoic Acid Inhibits KRAS Mutant Pancreatic Cancer Cell Growth by Suppressing Hepassocin Expression and STAT3 Phosphorylation.

BACKGROUND: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. METHODS: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. RESULTS: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. CONCLUSIONS: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

Effect Size of Dietary Supplementation and Physical Exercise Interventions for Sarcopenia in Middle-Aged Women.

The purpose of this meta-analysis was to comprehensively analyze the relationship between intervention (di-etary supplementation and physical exercise), body composition, and physical activity capacity in middle-aged women with sarcopenia. A total of 19 studies published in the last ten years were selected. The overall effect size was small (0.29; 95% confidence interval: 0.195∼0.385). The Q value was 100.214 and the Higgin's I 2 value was 82.038. Each study was found to be heterogeneous and there was no publication bias. The effect size was increased when the number of study partici-pants increased from 50 to 100 and when dietary vitamin D supplementation was combined with resistance exercise. Fur-thermore, the effect on physical activity capacity was higher than that on body composition. In conclusion, dietary vitamin D supplementation combined with resistance training had a positive impact on middle-aged women with sarcopenia.

Impacts of the COVID-19 Pandemic on Food Security and Diet-Related Lifestyle Behaviors: An Analytical Study of Google Trends-Based Query Volumes.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 disease (COVID)-19 is having profound effects on the global economy and food trade. Limited data are available on how this pandemic is affecting our dietary and lifestyle-related behaviors at the global level. Google Trends was used to obtain worldwide relative search volumes (RSVs) covering a timeframe from before the COVID-19 pandemic 1 June 2019 to 27 April 2020. Spearman's rank-order correlation coefficients were used to measure relationships between daily confirmed cases and aforementioned RSVs between 31 December 2019 and 15 April 2020. RSV curves showed increased interest in multiple keywords related to dietary and lifestyle behaviors during the COVID-19 lockdown period in March and April 2020. Spearman's correlation analysis showed that the strongest variables in each keyword category were (1) food security (food shortage: r = 0.749, food bank: r = 0.660, and free food: r = 0.555; all p < 0.001), (2) dietary behaviors (delivery: r = 0.780, restaurant: r = -0.731, take-away: r = 0.731, and food-delivery: r = 0.693; all p < 0.001), (3) outdoor-related behaviors (resort: r = -0.922, hotel: r = -0.913, cinema: r = -0.844, park: r = -0.827, fitness: r = -0.817, gym: r = -0.811; plant: r = 0.749, sunbathing: r = 0.668, and online: r = 0.670; all p < 0.001), and (4) immune-related nutrients/herbs/foods (vitamin C: r = 0.802, vitamin A: r = 0.780, zinc: r = 0.781, immune: r = 0.739, vitamin E: r = 0.707, garlic: r = 0.667, omega-3 fatty acid: r = -0.633, vitamin D: r = 0.549, and turmeric: r = 0.545; all p < 0.001). Restricted movement has affected peoples' dietary and lifestyle behaviors as people tend to search for immune-boosting nutrients/herbs and have replaced outdoor activities with sedentary indoor behaviors.

Gender, reproductive output covariation and their role on gene diversity of Pinus koraiensis seed orchard crops.

BACKGROUND: Gender and fertility variation have an impact on mating dynamics in a population because they affect the gene exchange among parental members and the genetic composition of the resultant seed crops. Fertility is the proportional gametic contribution of parents to their progeny. An effective number of parents, derivative of effective population size, is the probability that two alleles randomly chosen from the gamete gene pool originated from the same parent. The effective number of parents is directly related to the fertility variation among parents, which should be monitored for manipulating gene diversity of seed crops. We formulated a fundamental equation of estimating the effective number of parents and applied it to a seed production population. RESULTS: Effective number of parents (Np) was derived from fertility variation (Ψ) considering covariance (correlation coefficient, r) between maternal and paternal fertility. The Ψ was calculated from the coefficient of variation in reproductive outputs and divided into female (ψf) and male (ψm) fertility variation in the population under study. The Np was estimated from the parental Ψ estimated by the fertility variation of maternal (ψf) and paternal (ψm) parents. The gene diversity of seed crops was monitored by Ψ and Np. in a 1.5 generation Pinus koraiensis seed orchard as a case of monoecious species. A large variation of female and male strobili production was observed among the studied 52 parents over four consecutive years, showing statistically significant differences across all studied years. Parental balance curve showed greater distortion in paternal than maternal parents. The Ψ ranged from 1.879 to 4.035 with greater ψm than ψf, and the Np varied from 14.8 to 36.8. When pooled, the relative effective number of parents was improved as 80.0% of the census number. CONCLUSIONS: We recommend the use of fertility variation (i.e., CV, Ψ), Person's product-moment correlation (r), and effective number of parents (Np) as tools for gauging gene diversity of seed crops in production populations. For increasing Np and gene diversity, additional management options such as mixing seed-lots, equal cone harvest and application of supplemental-mass-pollination are recommended.