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Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible effects of chronic nitrate supplementation on the metabolites of energy metabolism during high-intensity, high-volume intermittent training (HIHVT). In this placebo-controlled double-blind study, 17 participants exercised 3 times a week on a cycle ergometer. Sodium nitrate or sodium chloride as the placebo was supplemented daily at 8.5 mg/kg body weight for 10 days. The training exercise consisted of a warm-up, a 45-min interval period, and a post-exercise period. Oxygen uptake, respiratory exchange ratio, and various parameters were measured in the venous blood and plasma. During training, the oxygen uptake and respiratory exchange ratio did not differ between the nitrate and the placebo group. Venous plasma concentrations of nitrate and nitrite were significantly increased in the nitrate group (p < 0.001 and p = 0.007, respectively). Triglyceride concentrations were significantly lower in the nitrate group than in the placebo group (p = 0.010). The concentration of free fatty acids in the plasma did not change upon nitrate supplementation and no significant differences were observed in the contribution of fat to energy metabolism during exercise. An increase in plasma ammonia concentration was observed in the nitrate group during and after exercise (p = 0.048). Metabolites of energy-rich phosphates did not differ between the nitrate and chloride groups, suggesting no improvement in efficiency through the supplemented nitrate. It was concluded that nitrate supplementation did not reduce oxygen uptake and adenosine triphosphate resynthesis by hydrolysis or through creatine kinase activity during high-intensity, high-volume intermittent exercise. Although, lipid metabolism as well as amino acid metabolism might be affected by nitrate supplementation during HIHVT. [ABSTRACT FROM AUTHOR]

Many short-term studies with dietary nitrate supplementation in humans and animal models reported positive effects on the cardiovascular system, exercise efficiency, and immune function. However, there has been long-standing concern related to cancer and adverse hormonal effects. We studied the long-term effects of different potassium nitrate (KNO3) concentrations on laboratory mice longevity and structural changes in their organs. Four groups of male mice were treated with 0 mg (0%), 45 mg (1%), 90 mg (2%), and 140 mg (3%) KNO3 in the drinking water. The groups were monitored for agility and health status daily. The lifespan of mice and organ pathological changes were analyzed. We found no detrimental effects of life-long supplementation of KNO3 on the survival of mice in treatment groups. Nitrate supplementation was associated with a lower level of pathological changes (p = 0.002). We conclude that KNO3 supplementation had no carcinogenic effect on mice and possibly prevented the organs from aging. [ABSTRACT FROM AUTHOR]

Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASCCTRL) and from horses suffering from metabolic syndrome (ASCEMS). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASCEMS. We also showed that MβCD treatment affected GLUT4 upregulation in an insulin-independent manner via an NO-dependent signaling pathway. Furthermore, the analysis of superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels showed that MβCD treatment was associated with an increased antioxidant capacity in ASCEMS. Moreover, we indicated that methyl-β-cyclodextrin treatment did not cause a dysfunction of the endoplasmic reticulum and lysosomes. Thereby, we propose the possibility of improving the functionality of ASCEMS by increasing their metabolic stability. [ABSTRACT FROM AUTHOR]

In this study, a potentiometric sensor composed of palm shell activated carbon modified with trioctylmethylammonium thiosalicylate (TOMATS) was used for the potentiometric determination of mercury ions in water samples. The proposed potentiometric sensor has good operating characteristics towards Hg (II), including a relatively high selectivity; a Nernstian response to Hg (II) ions in a concentration range of 1.0 x 10-9 to 1.0 x 10-2 M, with a detection limit of 1 x 10-10 M and a slope of 44.08 ± 1.0 mV/decade; and a fast response time (~5 s). No significant changes in electrode potential were observed when the pH was varied over the range of 3-9. Additionally, the proposed electrode was characterized by good selectivity towards Hg (II) and no significant interferences from other cationic or anionic species. [ABSTRACT FROM AUTHOR]

Abstract: A flow injection analysis (FIA) incorporating a thiosemicarbazone-based coated wire electrode (CWE) was developed method for the determination of mercury(II). A 0.1 M KNO3 carrier stream with pH between 1 and 5 and flow rate of 1 mL·min-1 were used as optimum parameters. A linear plot within the concentration range of 5 × 10-6-0.1 M Hg(II), slope of 27.8 ± 1 mV per decade and correlation coefficient (R2) of 0.984 were obtained. The system was successfully applied for the determination of mercury(II) in dental amalgam solutions and spiked environmental water samples. Highly reproducible measurements with relative standard deviation (RSD < 1% (n = 3)) were obtained, giving a typical throughput of 30 samples·h-1. [ABSTRACT FROM AUTHOR]

Kombucha, which is rich in tea polyphenols and organic acid, is a kind of acidic tea soup beverage fermented by acetic acid bacteria, yeasts, lactic acid bacteria. Kombucha has been reported to possess anti-diabetic activity, but the underlying mechanism was not well understood. In this study, a high-fat, high-sugar diet combined with streptozotocin (STZ) injection was used to induce T2DM model in mice. After four weeks of kombucha intervention, the physiological and biochemical index were measured to determine the diabetes-related indicators. High-throughput sequencing technology was used to analyze the changes in gut microbiota from the feces. The results showed that four weeks of kombucha intervention increased the abundance of SCFAs-producing bacteria and reduced the abundance of gram-negative bacteria and pathogenic bacteria. The improvement in gut microbiota reduced the damage of intestinal barrier, thereby reducing the displacement of lipopolysaccharide (LPS) and inhibiting the occurrence of inflammation and insulin resistance in vivo. In addition, the increased levels of SCFAs-producing bacteria, and thus increasing the SCFAs, improved islet β cell function by promoting the secretion of gastrointestinal hormones (GLP-1/PYY). This study methodically uncovered the hypoglycemic mechanism of kombucha through gut microbiota intervention, and the result suggested that kombucha may be introduced as a new functional drink for T2DM prevention and treatment. [ABSTRACT FROM AUTHOR]

The present paper provides a description of the design, characterization, and use of a Hg2+ selective electrode (Hg2+–SE) for the determination of Hg2+ at ultra-traces levels in a variety of real samples. The ionophore in the proposed electrode is a new Schiff base, namely 4-bromo-2-[(4-methoxyphenylimino)methyl]phenol (BMPMP). All factors affecting electrode response including polymeric membrane composition, concentration of internal solution, pH sample solution, and response time were optimized. The optimum response of our electrode was obtained with the following polymeric membrane composition (% w/w): PVC, 32; o-NPOE, 64.5; BMPMP, 2 and NaTPB, 1.5. The potentiometric response of Hg2+–SE towards Hg2+ ion was linear in the wide range of concentrations (9.33 × 10–8−3.98 × 10–3 molL–1), while, the limit of detection of the proposed electrode was 3.98 × 10–8 molL–1 (8.00 μg L–1). The Hg2+–SE responds quickly to Hg2+ ions as the response time of less than 10 s. On the other hand, the slope value obtained for the developed electrode was 29.74 ± 0.1 mV/decade in the pH range of 2.0−9.0 in good agreement with the Nernstian response (29.50 mV/decade). The Hg2+–SE has relatively less interference with other metal ions. The Hg2+–SE was used as an indicator electrode in potentiometric titrations to estimate Hg2+ ions in waters, compact fluorescent lamp, and dental amalgam alloy and the accuracy of the developed electrode was compared with ICP–OES measurement values. Moreover, the new Schiff base (BMPMP) was synthesized and characterized using ATR–FTIR, elemental analysis, 1H NMR, and 13C NMR. The PVC membranes containing BMPMP as an ionophore unloaded and loaded with Hg(II) are reported by scanning electron microscope images (SEM) along with energy-dispersive X-ray spectroscopy (EDX) spectra. [ABSTRACT FROM AUTHOR]

Beneficial metabolic effects of inorganic nitrate (NO3−) and nitrite (NO2−) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3− to NO2− and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2− to NO following ingestion of NO3−. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3−/NO2− supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2−-to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3− in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3− therapy. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is a chronic relapsing disease. Multiple factors can cause inflammatory bowel disease (IBD), including diet, imbalance of the immune system, and impaired intestinal barrier function. Type 2 diabetes mellitus is a complex and chronic metabolic disease caused by a combination of insulin resistance and an ineffective insulin secretory response. The co-occurrence of these two diseases, demonstrating interrelated effects within the gut microbiota, has been frequently reported. This study evaluated the effects of a fermented glycated conjugate of whey protein and galactose with Lactobacillus gasseri 4M13 (FMRP) to prevent type 2 diabetes mellitus with inflammatory bowel disease. C57BLKS/J- db/db mice were orally administered FMRP for 14 consecutive days and 2% dextran sulfate sodium (DSS) in water ad libitum for 5 days to induce colitis. FMRP-fed mice showed improved insulin secretion and symptoms of colitis. Compared to the DSS group, the FMRP group showed a decreased abundance of six bacterial genera and increased abundance of Alistipes and Hungateiclostridium. In cecal contents, the levels of short-chain fatty acids increased in the FMRP group compared to those in the DSS group. Continuous administration of FMRP thus may improve the homeostasis of not only insulin secretion and inflammation, but also the intestinal environment in inflammatory bowel disease and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Type 2 diabetes (T2D) affects more than 90% of all patients diagnosed with diabetes, and among its risk factors, unhealthy eating habits are worth mentioning. With the notorious increase in the incidence of diabetic patients, there has also been an increase in surgical complications in dentistry, so this work presents a study model that mimics the T2D condition in rats, where animals receive a diet composed of foods rich in sugar and fat equivalent to the poor diet of the current population. The animals were submitted to dental extraction to perform analyzes at different stages of the alveolar bone. It is important to highlight that with the development of this experimental model it will be possible to simulate different conditions that are observed in clinics and in consequence and improve the characterization of the cellular responses involved in this complex condition of T2D. The scientific evidence presented in this study shows that T2D prolongs the local inflammatory process, which impairs the organization and maturation of collagen fibers, delaying bone formation and bone turnover. This fact implies in a series of disorders in dental practice, that would need to compensate in other ways, either with systemic medications or local therapies. The aim of this study was to analyze the stages of the alveolar bone repair in type 2 diabetic rats evaluating the mechanism of mineralization and bone remodeling processes after dental extraction. Forty-eight rats were divided into normoglycemic (NG) and type 2 diabetes (T2D) groups. The upper right incisor was extracted and after 3, 7, 14 and 42 days the animals were euthanized. The following analyses were performed: immunolabeling against antibodies TNFα, TGFβ, IL6, WNT, OCN and TRAP, collagen fibers maturation, microtomography and confocal microscopy. Data were submitted to statistical analysis. The immunolabeling analysis showed that the T2D presented a more pronounced alveolar inflammation than NG. Labeling of proteins responsible for bone formation and mineralization was higher in NG than T2D, which presented greater resorptive activity characterized by TRAP labeling. Also, T2D group showed a decrease in the amount of collagen fibers. Micro-CT analysis showed that T2D causes a decrease in bone volume percentage due to deficient trabecular parameters and higher porosity. The T2D bone dynamics show a loss in bone remodeling process. T2D prolongs the local inflammatory process, which impairs the organization and maturation of collagen fibers, delaying bone formation that generates impact on mineralization and bone turnover. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are one of the most common complications of type 2 diabetes. They are considered the leading cause of death among diabetics. One of the mechanisms underlying diabetic cardiovascular complications is oxidative stress. Many phenolic acids are regarded as antioxidants. The aim of the study was to investigate the effect of rosmarinic acid (RA) and sinapic acid (SA) on oxidative stress parameters in the cardiac tissue and serum of type 2 diabetic female rats. Additionally, the effect of these compounds on glucose homeostasis and lipid profile in the serum was evaluated. Type 2 diabetes was induced with high-fat diet and streptozotocin. RA at the doses of 10 and 50 mg/kg and SA at the doses of 5 and 25 mg/kg were administrated orally for 28 days. Untreated diabetic rats exhibited unfavorable changes in glucose metabolism and lipid profile. Changes in the enzymatic and non-enzymatic markers indicated the onset of oxidative stress in these animals. The results showed that the higher doses of the tested phenolic acids—50 mg/kg of RA and 25 mg/kg of SA—revealed beneficial effects on oxidative stress in the cardiac tissue of diabetic rats. [ABSTRACT FROM AUTHOR]