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To determine the association of peroxisome proliferator activated receptor gamma coactivator 1 Gly482Ser variant with components of metabolic syndrome. A systematic search was carried out using Web of Science, PubMed, EMBASE and the Cochrane library using the key words: Peroxisome proliferator activator receptor gamma coactivator 1, PPARGC1A, PGC-1, PGC-1alpha, and PGC1alpha alone or with polymorphism, Gly482Ser and rs8192678. Data from 19 articles generated 28 separate data sets. Under the recessive model fasting plasma glucose was significantly lower in AA genotypes when compared to GG + GA in the total sample group and in non-Asian group (p <.001). The AA genotype showed significantly lower levels of total cholesterol compared to GG + GA genotype using the recessive model with the non-Asian group (p <.05). Under the dominant model, body mass index of the GG genotype was significantly higher in Asian subgroups (p <.05). PPARGC1A Gly482Ser variant impacts differently in Asian population groups. • This is the first meta-analysis where cholesterol has been used as an indicative element in the data search strategy for this variant; • The work demonstrates a genetic distinction at the level of the BMI between the Asian and non-Asian population groups; • AA genotype showed significantly lower levels of total cholesterol compared to GG + GA genotype in the non-Asian population. [ABSTRACT FROM AUTHOR]

Abstract: Selenium (Se)-containing proteins have important roles in protecting cells from oxidative damage. This work investigated the effects of Se-depletion on the expression of the genes encoding selenoproteins in colonic mucosa from rats fed diets of different Se content and in human intestinal Caco-2 cells grown in Se-adequate or Se-depleted culture medium. Se-depletion produced statistically significant (P<0.05) falls in glutathione peroxidase (GPX) 1 mRNA (60–83%) and selenoprotein W mRNA (73%) levels, a small but significant fall in GPX4 mRNA (17–25%) but no significant change in GPX2. The data show that SelW expression in the colon is highly sensitive to Se-depletion. [Copyright &y& Elsevier]

Aim: The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione peroxidase 4 (GPX4) and has been found to have functional consequences. This systematic review aimed to conduct a meta-analysis to determine whether there is an association between GPX4 (rs713041) SNP and the risk of diseases in humans and its correlation with selenium status. Material and methods: A systematic search for English-language manuscripts published between January 1990 and November 2022 was carried out using six databases: CINAHL, Cochrane, Medline, PubMed, Scopus and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between GPX4 (rs713041) SNP and the risk of different diseases based on three genetic models. Review Manager 5.4 and Comprehensive Meta-Analysis 4 software were used to perform the meta-analysis and carry out Egger's test for publication bias. Results: Data from 21 articles were included in the systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs173041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension in the additive, dominant and recessive models (p = 0.002, p = 0.004 and p = 0.01, respectively). On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia in the additive, dominant and recessive models (p < 0.0001, p = 0.002 and p = 0.0005, respectively). Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I2 = 85%). Conclusion: GPX4 (rs713041) T allele may influence colorectal cancer risk, stroke, hypertension and pre-eclampsia. In addition, low selenium levels may play a role in the increased risk of cancer. [ABSTRACT FROM AUTHOR]

Bisnaphthalimidopropyl diaminodicyclohexylmethane (BNIPDaCHM) bisintercalates to DNA and is a potential anti-cancer therapeutic. In an attempt to elucidate the mechanism(s) underlying the potential of BNIPDaCHM; earlier work was extended to investigate its effect on DNA damage and repair as well as cell cycle modulation, in a triple negative breast cancer (TNBC) cell line in vitro . BNIPDaCHM significantly decreased cell viability in a concentration (≥5 μM) and time (≥24 h) dependent manner. The mechanism of this growth inhibition involved alterations to cell cycle progression, an increase in the sub-G1 population and changes to plasma membrane integrity/permeability observed by flow cytometry and fluorescence microscopy with acridine orange/ethidium bromide staining. Using single cell gel electrophoresis (Comet assay) and fluorescence microscopy to detect γ-H2AX-foci expression; it was found that after 4 h, ≥ 0.1 μM BNIPDaCHM treatment-induced significant DNA double strand breaks (DSBs). Moreover, exposure to a non-genotoxic concentration of BNIPDaCHM induced a significant decrease in the repair of oxidative DNA strand breaks induced by hydrogen peroxide. Also, BNIPDaCHM-treatment induced a significant time dependent increase in p21 Waf/Cip1 mRNA expression but, did not alter p53 mRNA expression. In conclusion, BNIPDaCHM treatment in MDA-MB-231 cells was associated with a significant induction of DNA DSBs and inhibition of DNA repair at non-genotoxic concentrations via p53-independent expression of p21 Waf1/Cip1 . The latter may be a consequence of novel interactions between BNIPDaCHM and MDA-MB-231 cells which adds to the spectrum of therapeutically relevant activities that may be exploited in the future design and development of naphthalimide-based therapeutics. [ABSTRACT FROM AUTHOR]

Leptin is a hormone secreted by white fat tissue and signals the amount of overall body fat to the hypothalamus. The circulating concentration of leptin correlates with the level of obesity. Breast cancer risk is higher in obese postmenopausal women compared with postmenopausal women of a normal weight, and high leptin concentrations may contribute to this risk. In the present study, SK-BR-3 and MDA-MB-231 breast cancer cell lines were treated with various concentrations (6.25-1,600 ng?ml) of recombinant leptin and changes in cell proliferation were assessed. The SK-BR-3 breast cancer cells exhibited a concentration-dependent increase in proliferation with physiological leptin concentrations (<100 ng?ml), but no further increase in proliferation at high leptin concentrations (>100 ng?ml) was observed. Cell proliferation was not affected at supraphysiological leptin concentrations (>800 ng?ml) in SK-BR-3 cells, whereas it decreased in MDA-MB-231 cells. Therefore, cell signaling and cell cycle changes were assessed at supraphysiological concentrations (1,600 ng?ml). In the two cell lines, leptin treatment decreased the mitogen-activated protein kinase (MAPK) cell signaling pathway activation. Leptin treatment did not increase Akt phosphorylation or significantly alter the cell population distribution across cell cycle stages. To the best of our knowledge, leptin-induced growth inhibition of breast cancer cells at supraphysiological concentrations has not been reported in the literature to date, and the findings of this study suggest that reduced MAPK activity may be the underlying cause. Thus, the effect of leptin on breast cancer growth warrants further investigation since leptin is considered to be one of the main mediators in the obesity-breast cancer connection. [ABSTRACT FROM AUTHOR]

Lipids excess from an uterine environment can increase free radicals production of and thus induce oxidative status imbalance, a key factor for progression of non-alcoholic fatty liver disease (NAFLD) in offspring. Food antioxidant components in maternal diet may play an important role in preventing offspring metabolic disorders. The objective of the study was to evaluate the effects of açaí pulp supplementation on maternal high-fat diet, by assessing activity and expression of antioxidant enzymes and biomarkers of oxidative stress in the liver. Female Fisher rats were divided into four groups and fed a control diet (C), a high-fat diet (HF), a control diet supplemented with açaí (CA) and a high-fat diet supplemented with açaí (HFA) before mating, during gestation and lactation. The effects of açaí supplementation on oxidative stress biomarkers and antioxidant enzymes expression were evaluated in dams and male offspring after weaning. HFA diet increased body weight in dams, however reduced absolute and relative liver weight. There was a reduction in liver biomarkers of oxidative stress, malondialdehyde and carbonyl protein, as well as in catalase, glutathione peroxidase and superoxide dismutase activity. In offspring, HFA diet reduced liver weight and increased Gpx1, Gpx4 and Sod1 mRNA expression. These results suggest that açaí is able to restore redox status, preventing oxidative damage in dams by a direct mechanism and to promote beneficial effects on expression of antioxidant defences related genes in offspring. In this work, we demonstrated for the first time that açaí pulp supplementation to maternal high-fat diet may protect offspring from oxidative stress. These results showed a reduction in biomarkers of oxidative stress and antioxidants enzymes in dams. There was an increase in Gpx1, Gpx4 and Sod1 mRNA expression in offspring. Açaí pulp supplementation to maternal diet induced protection through modulation of oxidative stress by a direct mechanism in dams and may promote beneficial effects on antioxidant defences in offspring. [Display omitted] • Supplementation of açaí pulp to a maternal high fat diet prevents oxidative damage in dams and improves offspring antioxidant defences. • Supplementation of high fat diet with açaí reduces liver oxidative stress biomarkers. • Açaí supplementation to high fat diet reduces liver CAT, GPX, SOD activity in dams. • Açaí supplementation to maternal high fat diet reduces liver weight in offspring. • Maternal açaí supplemented high fat diet increases offspring liver Gpx1 , Gpx4, Sod1. [ABSTRACT FROM AUTHOR]

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans. [ABSTRACT FROM AUTHOR]