Hamannspears1360

The additional daily contribution of 10 g of cocoa-rich chocolate in postmenopausal women could have a slight impact on their perception toward their health state, although without modifying the health-related QoL or the dimensions that compose it.Neuroblastoma are pediatric, extracranial malignancies showing alarming survival prognosis outcomes due to their resilience to current aggressive treatment regimens, including chemotherapies with cisplatin (CDDP) provided in the first line of therapy regimens. Metabolic deregulation supports tumor cell survival in drug-treated conditions. However, metabolic pathways underlying cisplatin-resistance are least studied in neuroblastoma. Our metabolomics analysis revealed that cisplatin-insensitive cells alter their metabolism; especially, the metabolism of amino acids was upregulated in cisplatin-insensitive cells compared to the cisplatin-sensitive neuroblastoma cell line. A significant increase in amino acid levels in cisplatin-insensitive cells led us to hypothesize that the mechanisms upregulating intracellular amino acid pools facilitate insensitivity in neuroblastoma. We hereby report that amino acid depletion reduces cell survival and cisplatin-insensitivity in neuroblastoma cells. Since cells regulate their amino acids levels through processes, such as autophagy, we evaluated the effects of hydroxychloroquine (HCQ), a terminal autophagy inhibitor, on the survival and amino acid metabolism of cisplatin-insensitive neuroblastoma cells. Our results demonstrate that combining HCQ with CDDP abrogated the amino acid metabolism in cisplatin-insensitive cells and sensitized neuroblastoma cells to sub-lethal doses of cisplatin. Our results suggest that targeting of amino acid replenishing mechanisms could be considered as a potential approach in developing combination therapies for treating neuroblastomas.Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease caused by Rickettsia rickettsii, which is widely distributed throughout the Americas. Over 4000 cases of RMSF are recorded annually in the United States, while only around 100 cases are reported in Brazil. Conversely, while case fatality rates in the United States oscillate around 5%, in Brazil they can surpass 70%, suggesting that differences in tick vectoring capacity, population sensitivity, and/or variability in virulence of the rickettsial strains may exist. In this study, we compared the susceptibility of C3H/HeN mice to two highly virulent strains of R. rickettsii, one from the United States (Sheila Smith) and the other from Brazil (Taiaçu). Animals inoculated with the Taiaçu strain succumbed to infection earlier and exhibited severe histological lesions in both liver and spleen sooner than mice infected with the Sheila Smith strain. These differences in survival and signs of the disease are not related to a greater proliferation of the Taiaçu strain, as there were no significant differences in the rickettsial load in mice tissues inoculated with either strain. The present study is the first step to experimentally assess differences in fatality rates of RMSF in two different regions of the American continent.Efficient catabolic metabolism of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial-mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, PFK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets.

Brown adipose tissue (BAT) provides a minor contribution to diet-induced thermogenesis (DIT)-the metabolic response to food consumption. Increased BAT activity is generally considered beneficial for mammalian metabolism and has been associated with favorable health outcomes. The aim of the current systematic review was to explore whether nutritional factors and/or diet affect human BAT activity.

We searched PubMed Central, Embase and Cochrane Library (trials) to conduct this systematic review (PROSPERO protocol CRD42018082323).

We included 24 eligible papers that studied a total of 2785 participants. We found no mean differences in standardized uptake value of BAT following a single meal or after 6 weeks of L-Arginine supplementation. Resting energy expenditure (REE), however, was increased following a single meal and after supplementation of capsinoid and catechin when compared to a control condition (Z = 2.41,

= 0.02; mean difference = 102.47 (95% CI = 19.28-185.67)).

Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.

Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.Response Surface Methodology (RSM) was used to assess the optimal conditions for a Water/Oil/Water (W/O/W) emulsion for encapsulated nisin (EN). Nano-encapsulated nisin had high encapsulation efficiencies (EE) (86.66 ± 1.59%), small particle size (320 ± 20 nm), and low polydispersity index (0.27). Biodegradable polyvinyl alcohol (PVA) and polyacrylate sodium (PAAS) were blended with EN and prepared by electrospinning. Scanning electron microscopy (SEM) revealed PVA/PAAS/EN nanofibers with good morphology, and that their EN activity and mechanical properties were enhanced. When the ultrasonication time was 15 min and 15% EN was added, the nanofibers had optimal mechanical, light transmittance, and barrier properties. Besides, the release behavior of nisin from the nanofibers fit the Korsemeyer-Peppas (KP) model, a maximum nisin release rate of 85.28 ± 2.38% was achieved over 16 days. At 4 °C, the growth of Escherichia coli and Staphylococcus aureus was inhibited for 16 days in nanofibers under different ultrasonic times. The application of the fiber in food packaging can effectively inhibit the activity of food microorganisms and prolong the shelf life of strawberries, displaying a great potential application for food preservation.Intramuscular fat (IMF) is essential for improving the palatability and flavor of meat, and it is strongly associated with human insulin resistance. RNA editing is a widespread regulating event in different tissues. Here, we investigated the global RNA editing difference of two groups of pig with different IMF contents to find the potential editing sites affecting IMF. In this research, RES-Scanner and REDItools were used to identify RNA editing sites based on the whole genome and transcriptome sequencing data of the high and low groups composed of three full-sib pairs with opposite IMF phenotypes. A total of 295 RNA editing sites were investigated in the longissimus dorsi muscle, and 90.17% of these sites caused A to G conversion. After annotation, most editing sites were located in noncoding regions (including five sites located on the 3' UTR regions). Five editing sites (including two sites that could lead to nonsynonymous amino acid changes) were located in the exons of genes. A total of 36 intergroup (high and low IMF) differential RNA editing sites were found in 33 genes. Some candidate editing sites, such as sites in acyl-coenzymeA cholesterol acyltransferase 1 (ACAT1), coatomer protein, subunit alpha (COPA), and nuclear receptor coactivator 3 (NCOA3), were selected as candidate RNA editing sites associated with IMF. One site located on the 3' UTR region of growth hormone secretagogue receptor (GHSR) may regulate GHSR expression by affecting the interaction of miRNA and mRNA. In conclusion, we identified a total of 36 nonredundant RNA editing sites in the longissimus dorsi muscle, which may reveal the potential importance of RNA editing in IMF. Four were selected as candidate sites associated with IMF. Our findings provide some new insights of RNA editing function in pig longissimus dorsi muscle which useful for pig IMF breeding or human insulin resistances research.DNA methyltransferase 3B (DNMT3B) as one member of the DNMT family functions as a de novo methyltransferase, characterized as more than 30 splice variants in humans and mice. However, the expression patterns of DNMT3B in pig as well as the biological function of porcine DNMT3B remain to be determined. In this study, we first examined the expression patterns of DNMT3B in porcine alveolar macrophages (PAM). We demonstrated that only DNMT3B2 and DNMT3B3 were the detectable isoforms in PAM. Furthermore, we revealed that DNTM3B2 was the predominant isoform in PAM. Next, in the model of LPS (lipopolysaccharide)-activated PAM, we showed that in comparison to the unstimulated PAM, (1) expression of DNTM3B is reduced; (2) the methylation level of TNF-α gene promoter is decreased. We further establish that DNMT3B2-mediated methylation of TNF-α gene promoter restricts induction of TNF-α in the LPS-stimulated PAM. In summary, these findings reveal that DNMT3B2 is the predominant isoform in PAM and its downregulation contributes to expression of TNF-α via hypomethylation of TNF-α gene promoter in the LPS-stimulated PAM.Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase activity. Using C-P4H1 tetramer purified from the eukaryotic expression system, we showed that the Succinate-GloTM Hydroxylase assay was more sensitive for measuring C-P4H1 activity compared with the hydroxyproline colorimetric assay.