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Olive oil and table olives are considered staples of the Mediterranean diet and have been associated with various health benefits. Literature reports that the final composition of the olive drupe is greatly affected by varietal and agronomic factors, each contributing to a different degree. To that end, the objective of the study was the evaluation of the contribution of different agronomic conditions applied to two Greek olive varieties (Koroneiki, Mastoidis) using a holistic approach of in vitro methods. The findings highlight the importance of the application of a combination of agronomic techniques for each variety, as marked by the differences found in the antioxidant radical-scavenging and reducing power assays. Furthermore, the results obtained from the measurement of redox biomarkers (GSH, ROS, TBARS) in cell lines (EA.hy926, HepG2, MKN45) treated with olive samples demonstrate the capacity of the samples to induce redox imbalance, either by protecting normal cells from damage, or by inducing oxidative damage in cancer cell lines, with the Athinolia samples exhibiting greater antioxidant potential at lower concentrations. This particular finding could have further applications in possible chemo-preventive approaches facilitated by antioxidant compounds of natural origins. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: The Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxidative status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritional and sartorial habits, comprise a population thatstrictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediterranean diet, often accompanied by profound hypovitaminosis D. Time-restricted eating (TRE) is also adopted bya large part of the general lay Greek population for health-promoting reasons, without restrictions on animal product consumption, as imposed by Orthodox religious fasting. However, the comparative effects of these nutritional patterns on oxidative stress markers remain scarce. Methods: The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D-deficient and overweight Orthodox nuns from Central and Northern Greece compared to the implementation of TRE, a 16:8 dietary regimen (16 h of food abstinence and 8 h of feeding) in a cohort of adult women from the general population from the same region with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During the enrollment, a detailed recording of their dietary habits was performed, along with a scientific registry of their demographic and anthropometric characteristics (via bioimpedance). The Orthodox nuns followed a typical Orthodox fasting regimen [daily feeding window (8 a.m.–4 p.m.)], whereas the lay women followed a TRE 16:8 regimen with the same feeding time-window with a recommendation to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [calcium—Ca, albumin, parathyroid hormone—PTH, and 25-hydroxyvitamin D—25(OH)D] and markers of TAC (total antioxidant capacity), GSH (glutathione),and thiobarbituric acid reactive substances (TBARSs) concentrations as markers of oxidative status. Results: All the groups were compared at the baseline regarding their calcium, PTH, and 25(OH)D concentrations, with no statistically significant differences between the groups apart from higher PTH levels in the nuns due to lower 25(OH)D levels. The Orthodox nuns manifested a lower median GSH compared to the controls (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p < 0.001). The TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH, and the markers of glucose homeostasis were evident. Conclusions: The results of this small pilot study indicate that both dietary regimens have advantages over the oxidative markers compared to each other, with increased TAC in the group of Orthodox nuns after a 16-week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate the superiority or non-inferiority between these dietary patterns in the daily clinical setting. [ABSTRACT FROM AUTHOR]

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics. [ABSTRACT FROM AUTHOR]

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date. [ABSTRACT FROM AUTHOR]