Search

Current researchis focused on the influence of β-aminobutyric acid (BABA) on the metabolism of nitric oxide (NO), hydrogen sulfide (H2S), ascorbic acid, and abscisic acid (ABA) in strawberry fruit. The increases in ion leakage and malondialdehyde (MDA) concentration in strawberry fruit and the degradation of chlorophyll in the sepals of the fruit were markedly inhibited by BABA at 20 mM. BABA-immersed fruit exhibited lower activities and expressions of polygalacturonase (PG), pectinmethylesterase (PME), and ethylene biosynthetic enzymes compared to the control. Furthermore, BABA immersion evidently upgraded the metabolic levels of NO and H2S, including the enzymatic activities and intermediary contents of metabolites, which collectively enhanced the levels of endogenous NO and H2S contents in strawberry fruit. The high enzymatic activities and gene expressions of the AsA biosynthesis pathway jointly maintained AsA accumulation in the BABA-treated sample. The application of BABA led to a decrease in ABA concentration, which was associated with reduced activities and gene expression levels of key enzymes participating in ABA metabolism. Our experimental observations showed that immersion with BABA may be a highly promising means to delay senescence and reduce natural decay in strawberry fruit, and the alleviation in senescence using BABA may be attributed to the modulation of NO, H2S, AsA, and ABA metabolism. [ABSTRACT FROM AUTHOR]

Current researchis focused on the influence of β-aminobutyric acid (BABA) on the metabolism of nitric oxide (NO), hydrogen sulfide (H2S), ascorbic acid, and abscisic acid (ABA) in strawberry fruit. The increases in ion leakage and malondialdehyde (MDA) concentration in strawberry fruit and the degradation of chlorophyll in the sepals of the fruit were markedly inhibited by BABA at 20 mM. BABA-immersed fruit exhibited lower activities and expressions of polygalacturonase (PG), pectinmethylesterase (PME), and ethylene biosynthetic enzymes compared to the control. Furthermore, BABA immersion evidently upgraded the metabolic levels of NO and H2S, including the enzymatic activities and intermediary contents of metabolites, which collectively enhanced the levels of endogenous NO and H2S contents in strawberry fruit. The high enzymatic activities and gene expressions of the AsA biosynthesis pathway jointly maintained AsA accumulation in the BABA-treated sample. The application of BABA led to a decrease in ABA concentration, which was associated with reduced activities and gene expression levels of key enzymes participating in ABA metabolism. Our experimental observations showed that immersion with BABA may be a highly promising means to delay senescence and reduce natural decay in strawberry fruit, and the alleviation in senescence using BABA may be attributed to the modulation of NO, H2S, AsA, and ABA metabolism.

Metabolic syndrome is considered to be a cluster of disorders that directly contribute to the development of cardiovascular disease and are characterized by chronic systemic infl ammation. Numerous epidemiological data indicate that an adverse intrauterine environment, caused by the peculiarities of the nutritional status or placental insuffi ciency in a woman with metabolic syndrome, can “program” the susceptibility of the fetus to further development of cardiovascular and metabolic diseases, has an impact on cognitive and behavioral development. Nitric oxide (NO) plays a critical role in the pathogenesis of components of the metabolic syndrome. Children born prematurely have a high incidence of brain damage, which can lead to motor, cognitive, behavioral, social and sensory disorders. The purpose the research was the study of the effect of the eNOS gene polymorphism and indicators of nitric oxide metabolism on the neonatal consequences in prematurely born children from mothers with metabolic syndrome. Material and methods. A study was conducted in which 100 premature infants were included. Two groups were formed: the main group (n=34), which included preterm infants (birth weight 2145.29±148.19 g and gestational age 33.18±0.55 weeks) of mothers with metabolic syndrome, and the comparison group (n=66), which included preterm infants (birth weight 2295.99±101.45 and gestational age 34.03±0.45 weeks) of mothers without metabolic syndrome. The children underwent a genetic study – determination of the polymorphism of the eNOS gene, as well as the level of nitrites, nitrates and nitrosothiols in the urine. By decision of the bioethics commission No. 217 dated 12.06.2023, the materials of the scientifi c work comply with the Rules of Humane Treatment of Patients. Traditional methods of parametric and nonparametric statistics were used; nonparametric methods were used to analyze qualitative characteristics expressed mainly in percentages. The methods of parametric statistics were used to check the normality of the distribution of quantitative characteristics using the Kolmogorov- Smirnov criterion. Statistical processing of the obtained results was carried out using the package of application programs EXCEL-2003® and STATA version 11 for Windows (StataCorp, Texas, USA). The work was carried out as part of the scientifi c and experimental work of the Department of Pediatrics #1 with Neonatology of the Poltava State Medical University “To develop clinical and laboratory criteria, methods of predicting and preventing metabolic disoders in young children (state registration number 0120U102856). Results. The most common diseases in the infants of the studied groups were the consequences of intrauterine hypoxia (44.1%) and respiratory failure requiring artifi cial lung ventilation (50.0%), although no signifi cant diff erences were found in the prevalence of these conditions. We identifi ed the presence of signifi cant associations between the consequences of intrauterine hypoxia and the levels of nitrates (OR 1.19; 95% CI 1.01-1.40; p=0.042), nitrosothiols (OR 1.19; 95% CI 0.99-1.42; p=0.050) and the polymorphic genotype 4aa/ab of the eNOS gene (OR 0.28; 95% CI 0.12-0.67; p=0.004). Analysis of systemic hemodynamics revealed no signifi cant diff erences in baseline values between preterm infants with and without intrauterine hypoxia, but we did observe an association with urine output on day 3 of life. To fi nally clarify the complex infl uence of indicators of nitrate metabolism on the development of intrauterine hypoxia and to predict the development of consequences of this condition in premature infants, the following indicators are included in the regression prognostic model: the level of nitrates, nitrites, 4aa/4ab genotype and urine output on the third day of life. As the research results show, there is a direct reliable relationship with nitrates and an inverse relationship with nitrites, 4aa/4ab genotype and urine output. This prediction model has high operating characteristics – the area under the ROC curve is 0.8168. Some mechanisms of the infl uence of maternal metabolic syndrome on the development of relevant disorders in newborns are known, including disorders of nitric oxide synthesis, endothelial dysfunction, and oxidative stress. In our study, the consequences of intrauterine hypoxia were reliably associated with an increase in the concentration of urinary nitrates and a decrease in nitrites, as well as the absence of the 4aa/ab genotype, which is associated with reduced release of nitric oxide. There is evidence that nitric oxide can have both protective and deleterious eff ects, depending on factors such as nitric oxide synthase isoform and duration of exposure to hypoxia. Conclusions. In preterm infants born to mothers with metabolic syndrome, elevated urinary nitrate levels and the absence of the eNOS 4aa/ab genotype increase the likelihood of suff ering the consequences of intrauterine hypoxia.

Metabolic syndrome is considered to be a cluster of disorders that directly contribute to the development of cardiovascular disease and are characterized by chronic systemic inflammation. Numerous epidemiological data indicate that an adverse intrauterine environment, caused by the peculiarities of the nutritional status or placental insufficiency in a woman with metabolic syndrome, can "program" the susceptibility of the fetus to further development of cardiovascular and metabolic diseases, has an impact on cognitive and behavioral development. Nitric oxide (NO) plays a critical role in the pathogenesis of components of the metabolic syndrome. Children born prematurely have a high incidence of brain damage, which can lead to motor, cognitive, behavioral, social and sensory disorders. The purpose the research was the study of the effect of the eNOS gene polymorphism and indicators of nitric oxide metabolism on the neonatal consequences in prematurely born children from mothers with metabolic syndrome. Material and methods. A study was conducted in which 100 premature infants were included. Two groups were formed: the main group (n=34), which included preterm infants (birth weight 2145.29±148.19 g and gestational age 33.18±0.55 weeks) of mothers with metabolic syndrome, and the comparison group (n=66), which included preterm infants (birth weight 2295.99±101.45 and gestational age 34.03±0.45 weeks) of mothers without metabolic syndrome. The children underwent a genetic study - determination of the polymorphism of the eNOS gene, as well as the level of nitrites, nitrates and nitrosothiols in the urine. By decision of the bioethics commission No. 217 dated 12.06.2023, the materials of the scientific work comply with the Rules of Humane Treatment of Patients. Traditional methods of parametric and nonparametric statistics were used; nonparametric methods were used to analyze qualitative characteristics expressed mainly in percentages. The methods of parametric statistics were used to check the normality of the distribution of quantitative characteristics using the Kolmogorov-Smirnov criterion. Statistical processing of the obtained results was carried out using the package of application programs EXCEL-2003® and STATA version 11 for Windows (StataCorp, Texas, USA). The work was carried out as part of the scientific and experimental work of the Department of Pediatrics #1 with Neonatology of the Poltava State Medical University "To develop clinical and laboratory criteria, methods of predicting and preventing metabolic disoders in young children (state registration number 0120U102856). Results. The most common diseases in the infants of the studied groups were the consequences of intrauterine hypoxia (44.1%) and respiratory failure requiring artificial lung ventilation (50.0%), although no significant differences were found in the prevalence of these conditions. We identified the presence of significant associations between the consequences of intrauterine hypoxia and the levels of nitrates (OR 1.19; 95% CI 1.01-1.40; p=0.042), nitrosothiols (OR 1.19; 95% CI 0.99-1.42; p=0.050) and the polymorphic genotype 4aa/ab of the eNOS gene (OR 0.28; 95% CI 0.12-0.67; p=0.004). Analysis of systemic hemodynamics revealed no significant differences in baseline values between preterm infants with and without intrauterine hypoxia, but we did observe an association with urine output on day 3 of life. To finally clarify the complex influence of indicators of nitrate metabolism on the development of intrauterine hypoxia and to predict the development of consequences of this condition in premature infants, the following indicators are included in the regression prognostic model: the level of nitrates, nitrites, 4aa/4ab genotype and urine output on the third day of life. As the research results show, there is a direct reliable relationship with nitrates and an inverse relationship with nitrites, 4aa/4ab genotype and urine output. This prediction model has high operating characteristics - the area under the ROC curve is 0.8168. Some mechanisms of the influence of maternal metabolic syndrome on the development of relevant disorders in newborns are known, including disorders of nitric oxide synthesis, endothelial dysfunction, and oxidative stress. In our study, the consequences of intrauterine hypoxia were reliably associated with an increase in the concentration of urinary nitrates and a decrease in nitrites, as well as the absence of the 4aa/ab genotype, which is associated with reduced release of nitric oxide. There is evidence that nitric oxide can have both protective and deleterious effects, depending on factors such as nitric oxide synthase isoform and duration of exposure to hypoxia. Conclusions. In preterm infants born to mothers with metabolic syndrome, elevated urinary nitrate levels and the absence of the eNOS 4aa/ab genotype increase the likelihood of suffering the consequences of intrauterine hypoxia. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer is a common adult malignancy in the USA. Clear cell renal cell carcinoma (ccRCC), the predominant subtype of kidney cancer, is characterized by widespread metabolic changes. Urea metabolism is one such altered pathway in ccRCC. The aim of this study was to elucidate the contributions of urea cycle enzymes, argininosuccinate synthase 1 (ASS1), and argininosuccinate lyase (ASL) towards ccRCC progression. Methods: We employed a combination of computational, genetic, and metabolomic tools along with in vivo animal models to establish a tumor-suppressive role for ASS1 and ASL in ccRCC. Results: We show that the mRNA and protein expression of urea cycle enzymes ASS1 and ASL are reduced in ccRCC tumors when compared to the normal kidney. Furthermore, the loss of ASL in HK-2 cells (immortalized renal epithelial cells) promotes growth in 2D and 3D growth assays, while combined re-expression of ASS1 and ASL in ccRCC cell lines suppresses growth in 2D, 3D, and in vivo xenograft models. We establish that this suppression is dependent on their enzymatic activity. Finally, we demonstrate that conservation of cellular aspartate, regulation of nitric oxide synthesis, and pyrimidine production play pivotal roles in ASS1+ASL-mediated growth suppression in ccRCC. Conclusions: ccRCC tumors downregulate the components of the urea cycle including the enzymes argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). These cytosolic enzymes lie at a critical metabolic hub in the cell and are involved in aspartate catabolism and arginine and nitric oxide biosynthesis. Loss of ASS1 and ASL helps cells redirect aspartate towards pyrimidine synthesis and support enhanced proliferation. Additionally, reduced levels of ASS1 and ASL might help regulate nitric oxide (NO) generation and mitigate its cytotoxic effects. Overall, our work adds to the understanding of urea cycle enzymes in a context-independent of ureagenesis, their role in ccRCC progression, and uncovers novel potential metabolic vulnerabilities in ccRCC. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a signaling molecule that plays important roles in diverse biological processes and thus its dysregulation is involved in the pathogenesis of various disorders. In cancer, NO has broad and sometimes dichotomous roles; it is involved in cancer initiation and progression, but also restricts cancer proliferation and invasion, and contributes to the anti-tumor immune response. The importance of NO in a range of cellular processes is exemplified by its tight spatial and dosage control at multiple levels, including via its transcriptional, post-translational and metabolic regulation. In this Review, we focus on the regulation of NO via the synthesis and availability of its precursor, arginine, and discuss the implications of this metabolic regulation for cancer biology and therapy. Despite the established contribution of NO to cancer pathogenesis, the implementation of NO-related cancer therapeutics remains limited, likely due to the challenge of targeting and inducing its protective functions in a cell- and dosage-specific manner. A better understanding of how arginine regulates the production of NO in cancer might thus support the development of anti-cancer drugs that target this key metabolic pathway, and other metabolic pathways involved in NO production.

Acute hypoxia increases cerebral blood flow (CBF) and ventilation (...E). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (...P; index of CBF), and ...E during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. ...P and ...E sensitivity to hypoxia was reduced in Older by ~60% (P < 0.02). COPD patients exhibited similar ...P and ...E responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic ...E response but selectively decreased the ...P sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia. [ABSTRACT FROM AUTHOR]