Inhibition of 2-Oxoglutarate Dehydrogenase as a Chemical Model of Acute Hypobaric Hypoxia

Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) are known to change cellular amino acid pools, but the quantitative comparison of the metabolic and physiological outcomes has not been done. We hypothesize that OGDHC inhibition models metabolic changes caused by hypoxia, as both perturb the respiratory chain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply. In the current study, we quantify the changes in the amino acid metabolism after OGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare them to the earlier characterized changes after acute hypobaric hypoxia. In addition, the associated physiological effects are characterized and compared. A specific OGDHC inhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levels of many amino acids in the cerebellum of non-pregnant rats, without affecting those in the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnant rats are observed on the levels of cerebellar amino acids, electrocardiography (ECG), and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP, although none of the stressors significantly change the levels of cerebellar amino acids. The biochemical differences underlying the different physiological actions of SP and hypoxia are revealed by correlation analysis of the studied parameters. The negative correlations of cerebellar amino acids with OGDHC and/or tryptophan, shown to arise after the action of SP and hypoxia, discriminate the overall metabolic action of the stressors. More negative correlations are induced in the non-pregnant rats by hypoxia, and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibition mimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but a better prediction of the physiological outcomes requires assessment of integral network changes, such as increases in the negative correlations among the amino acids, OGDHC, and/or tryptophan.

Flavonoids: Molecular Mechanism Behind Natural Chemoprotective Behavior-A Mini Review

The given review summarizes the various molecular mechanisms responsible for the metabolic action of flavonoids as anticancer agents. Various types of flavonoids have proven to show biological & pharmacological activities like anti-inflammatory, antimicrobial, antioxidant, anticancer, anti-allergic, and antidiarrheal activities. The chemoprotective nature of flavonoids is also discussed due to their ability to inhibit topoisomerase enzymes at various stages of cancer, such as tumor initiation, promotion, and progression. The various biomolecular activities which are responsible for their role as the chemopreventive agent may be due to their antioxidative effect, anti-angiogenic properties, induction of protective enzymes, inhibitory action on the cell-like protein kinase activity inhibition, spreading of tumor cells, apoptosis induction, tumor cell invasion to name a few. There has been much-emerging evidence based on the versatility of flavonoids, their complex mechanism of action, lesser side effects, and varied pharmacological properties that make them potential anticancer agents. Challenges associated with their use in extraction, isolation, purification, and checking bioefficacy are also discussed.

A criticism of the reductionist and holistic vision in the planning of drugs in biological, chemical and physical level

In this work, two philosophical premises of science applied in the understanding of diseases and in the planning of drugs were studied. The first premise is reductionism. This idea is present in modern science when a problem can be reduced to the sum of its individual parts. Diseases can be understood as the metabolic action of few enzymes. Drugs can be planned through the mimicry of a specific enzymatic substrate. Biological molecules can be explained by the quantum theory applied to atoms and molecules. his idea has been the predominant way in modern science. On the other hand, there is a holistic view of the phenomenon. In this holistic view, the phenomenon must be understood as the whole. Drug design should be thought from a network of proteins, not just from a single enzymatic target. There is in fact a slight advantage in the reductionist method, because this philosophical view simplifies the problem. Today, a holistic view combined with methodological reductionism is used to develop new potential drugs.

The Emerging Role of Polyphenols in the Management of Type 2 Diabetes

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

Effect of microbially induced cementation on the instability and critical state behaviours of Fraser River sand

Microbially induced calcite precipitation (MICP) is a naturally driven biological process that harnesses the natural metabolic action of bacteria to induce the precipitation of calcium carbonate and alter soil engineering properties. This paper presents the results of using MICP to improve the monotonic undrained yield and critical strengths of Fraser River sand specimens. Bacteria called “Sporosarcina ureae” are employed as a ureolytic organism to achieve MICP. The formation of calcite cementation among sand particles is confirmed using scanning electron microscopic images and X-ray compositional analysis of cemented sand clusters. The progress of MICP cementation is assessed by measuring the velocity of a shear wave (VS) traveling through the specimen. The results show that VS starts to increase just as the calcium solution is introduced into each specimen after soaking the samples with the bacterial solution. Improvement in monotonic strength of sand samples is subsequently measured in a series of direct simple shear tests. Due to the combined effects of particle cementation and densification, the sand’s undrained and drained monotonic shearing strengths are significantly enhanced.

Ginger as a spice with diverse therapeutic and prophylactic properties: prospects of application in modern conditions (review of publications)

Actuality. The rapid growth of morbidity, age-related poly- and comorbidity complicate and increase the cost of the treatment process of such patients, leading to the search for prophylactic and therapeutic agents of multisystem and diverse metabolic action. Aim of the Research. Coverage of modern scientific advances in the studies of therapeutic and prophylactic properties of ginger as a spice and source of drugs, as well as justification for its wider use under different conditions of the human body. Materials and Methods. Information search in printed and electronic publications, search databases; methods of analysis, comparison and generalization of data. Results. The healing properties of ginger have been proven on the basis of historical and modern data. Thus, it posesses hypolipidemic, antisclerous, disaggregating, hypoglycemic, antioxidant, anti-inflammatory, analgesic, vasodilating properties, and the ability to regulate secretory and motor disorders of the digestive system. Gastro-, hepato-, cardio-, neuro-, arthroprotective features of ginger products are indisputable, as well as the effectiveness of their application for the diseases of the digestive, cardiovascular, bronchopulmonary systems, musculoskeletal system and prospects for their use for endocrine diseases, in neurology, oncology , immunology. Conclusions. Ginger as a universal spice and a source of drugs of prophylactic and therapeutic action with multisystem and diverse metabolic properties should be used more widely in patients with age related poly-and comorbidity, which can improve their rehabilitation outcomes and increase economic efficiency. Key Words: ginger, properties, poly- and comorbidity, application, prophylaxis.

Occurrence of Aspergillus niger strains on a polychrome cotton painting and their elimination by anoxic treatment

This study aimed to isolate and identify the population of filamentous fungi colonizing a cotton painting, whose conservation status was compromised and showed signs of biodeterioration due to dirt accumulation and microbial metabolism. In addition, microbiological techniques such as cultivation-dependent approach and molecular biology were used to identify microbial populations and to eliminate their metabolic action. For this, the nondestructive anoxic atmosphere technique was used, in which the microbial metabolism was affected by the absence of oxygen. Prior to exposure to an anoxic atmosphere, only one fungal species, Aspergillus niger, was identified at 12 points sampled in the obverse and reverse of the artwork; no fungal species persisted as a result of anoxic treatment. These results showed that exposure to anoxic conditions was effective for the total elimination of isolated fungal strains as well as their spores. In conclusion, this study proved the unprecedented effectiveness of a nondestructive technique for artwork on textile colonized by black fungi species. Thus, this interdisciplinary work involving conservation, microbiology, and chemistry presents a tool to eliminate microorganisms, while maintaining the integrity of artwork and safety of the restorer, that can be applied prior to artwork restoration.

Prognosis of the fetal distress in pregnant women with hypertensive disorders and hyperhomocyteinemia

In the article the reisapresentation of mathematical prediction of fetal distress in pregnant women with hypertensive disorders and hyperhomocyteinemia. In the basis of the model, the factors that significantly affect the chance of an unfavorable course of pregnancy for a given group of women. The clinical significance of the prediction is necessary for the formation of a differentiated approach to the management of pregnancy, depending on the probability of perinatal complications resulting from the application of the model. The most important role belongs to the detection of factors, which preceding development distress of fatus and are accompanied by the presence of extragenital diseases and patology of pregnancy. All of these factors should be known, when evaluated prenatal fetal condition, placental function, determination of laboratory-instrumental research methods for pregnancy with hypertensive disorders. Based on the results of the research, the algorithm of examination of the pregnant women with fetus distress symptoms was created. Parametric criteria are described for the diagnosis of fetal distress based on the determination of the level of homocysteine and oxidative modifection of protein in the blood of pregnant women. The original metod of forecasting the development of the fetal distress in pregnant women with hypertension is proposed. The use of drugs with metabolic action has led to credibly positive results, namely the reduction of the incidence of fetal distress, asphyxiation of newborns and prenatal morbidity and mortality. As a result of this we can see an improvement in reproductive health of women with hypertensive disorders.