New paradigms in the study of the cholinergic system and metabolic diseases: Acetyl-and-butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that belong to the neuromuscular cholinergic system, their main function is to hydrolyze the neurotransmitter acetylcholine (ACh), through their hydrolysis these enzymes regulate the neuronal and neuromuscular cholinergic system. They have recently attracted considerable attention due to the discovery of new enzymatic and nonenzymatic functions. These discoveries have aroused the interest of numerous scientists, consolidating the relevance of this group of enzymes.

Bone Marrow as a Therapeutic Target for Type 2 Diabetes Complications.

Type 2 diabetes mellitus (T2DM) is a world epidemic with a high prevalence and mortality. The origin of macro and microvascular complications associated with T2DM is complex and new mechanisms to explain their development are emerging. The changes induced by T2DM in the microenvironment of bone marrow (BM) alter the expansion and differentiation of stem cells and have been related to the development of micro and macrovascular diseases.

[Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19].

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store.

Epithelial Mesenchymal Transition and Progression of Breast Cancer Promoted by Diabetes Mellitus in Mice Are Associated with Increased Expression of Glycolytic and Proteolytic Enzymes.

The development of breast cancer (BC) is influenced by age, overweight, obesity, metabolic syndrome, and diabetes mellitus (DM), which are associated with hyperglycemia, glucose intolerance, insulin resistance, and oxidative stress. High glucose concentration increases a metastatic phenotype in cultured breast cancer cells, promoting cell proliferation, reactive species production (ROS), epithelial mesenchymal transition (EMT), and expression of proteolytic enzymes. Our aim was to determine whether diabetes mellitus favor BC progression in mice and its association with changes in the content of ROS and glycolytic and proteolytic enzymes.

[Molecular alterations induced by fructose and its impact on metabolic diseases].

Scientific evidence has identified that the excessive consumption of products made from high-fructose corn syrup is a trigger for obesity, whose prevalence increased in recent years. Due to the metabolic characteristics of fructose, a rapid gastric emptying is produced, altering signals of hunger-satiety and decreasing the appetite. In addition to the hepatic level during catabolism, triose phosphate is generated and adenosine triphosphate (ATP) is reduced, producing uric acid.

Nicotinamide prevents sweet beverage-induced hepatic steatosis in rats by regulating the G6PD, NADPH/NADP and GSH/GSSG ratios and reducing oxidative and inflammatory stress.

The disruption of redox state homeostasis, the overexpression of lipogenic transcription factors and enzymes, and the increase in lipogenic precursors induced by sweetened beverages are determinants of the development of nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox, oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis induced by high and chronic consumption of carbohydrates. Male rats were provided drinking water with 30% glucose or fructose ad libitum for 12 weeks.

Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system.

Obesity and type II diabetes mellitus have contributed to the increase of breast cancer incidence worldwide. High glucose concentration promotes the proliferation of metastatic cells, favoring the activation of the plasminogen/plasmin system, thus contributing to tumor progression. The efficient formation of plasmin is dependent on the binding of plasminogen to the cell surface.

High glucose and insulin enhance uPA expression, ROS formation and invasiveness in breast cancer-derived cells.

Background: Accumulating evidence indicates that type 2 diabetes is associated with an increased risk to develop breast cancer. This risk has been attributed to hyperglycemia, hyperinsulinemia and chronic inflammation. As yet, however, the mechanisms underlying this association are poorly understood.

Involvement of multiple cellular pathways in regulating resistance to tamoxifen in BIK-suppressed MCF-7 cells.

Majority of women with estrogen receptor (ER)-positive breast cancers initially respond to hormone therapies such as tamoxifen (TAM; antagonist of estrogen). However, many tumors eventually become resistant to TAM. Therefore, understanding the various cellular components involved in causing resistance to TAM is of paramount importance in designing novel entities for efficacious hormone therapy.

Nicotinamide, a glucose-6-phosphate dehydrogenase non-competitive mixed inhibitor, modifies redox balance and lipid accumulation in 3T3-L1 cells.

Aims: Excessive energy uptake of dietary carbohydrates results in their storage as fat and requires glucose-6-phosphate dehydrogenase (G6PD)-mediated NADPH production. We sought to assess whether the nicotinamide-induced reduction of G6PD activity might modulate redox balance and lipid accumulation in 3T3-L1 cells.

Main Methods: 3T3-L1 preadipocytes (days 4 and 6 of differentiation) and adipocytes were cultured in the presence of 5 or 25 mM glucose.

Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months.

Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells.

Apoptosis is controlled by the BCL-2 family of proteins, which can be divided into three different subclasses based on the conservation of BCL-2 homology domains. BIK is a founding member of the BH3-only pro-apoptotic protein family. BIK is predominantly localized in the endoplasmic reticulum (ER) and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria.

Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes.

Apoptosis of granulosa cells during follicular atresia is preceded by oxidative stress, partly due to a drop in the antioxidant glutathione (GSH). Under oxidative stress, GSH regeneration is dependent on the adequate supply of NADPH by glucose-6-phosphate dehydrogenase (G6PD). In this study, we analyzed the changes of G6PD, GSH, and oxidative stress of granulosa cells and follicular liquid and its association with apoptosis during atresia of small (4-6 mm) and large (>6 mm) sheep antral follicles.

Glucose-6-phosphate dehydrogenase activity and NADPH/NADP+ ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat.

Hyperglycemia is associated with metabolic disturbances affecting cell redox potential, particularly the NADPH/NADP+ ratio and reduced glutathione levels. Under oxidative stress, the NADPH supply for reduced glutathione regeneration is dependent on glucose-6-phosphate dehydrogenase. We assessed the effect of different hyperglycemic conditions on enzymatic activities involved in glutathione regeneration (glucose-6-phosphate dehydrogenase and glutathione reductase), NADP(H) and reduced glutathione concentrations in order to analyze the relative role of these enzymes in the control of glutathione restoration.

[Molecular aspects of chronic hyperglycemia-induced tissue damage].

The knowledge of the molecular basis of diabetes mellitus physiopathology will allow improvements in treatment or prevention of the disease. Diabetes mellitus is a complex disease in which hyperglycemia leads to complications in several organs. In this condition, there is increase in reactive oxygen species (ROS) as a result of glucose autooxidation; its metabolism produces accumulation of metabolites such as fructose, sorbitol, and triose phosphate.