The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis

The World Health Organization has identified oncological diseases as one of the most serious health concerns of the current century. Current research on oncogenesis is focused on the molecular mechanisms of energy-biochemical reprogramming in cancer cell metabolism, including processes contributing to the Warburg effect and the pro-oncogenic and anti-oncogenic roles of sirtuins (SIRTs) and poly-(ADP-ribose) polymerases (PARPs). However, a clear understanding of the interaction between NAD+, SIRTs in cancer development, as well as their effects on carcinogenesis, has not been established, and literature data vary greatly. This work aims to provide a summary and structure of the available information on NAD+, SIRTs interactions in both stimulating and countering carcinogenesis, and to discuss potential approaches for pharmacological modulation of these interactions to achieve an anticancer effect

Molecular mechanisms of endothelial remodeling under doxorubicin treatment

Doxorubicin (DOX) is an effective antineoplastic agent used to treat various types of cancers. However, its use is limited by the development of cardiotoxicity, which may result in heart failure. The exact mechanisms underlying DOX-induced cardiotoxicity are not fully understood, but recent studies have shown that endothelial–mesenchymal transition (EndMT) and endothelial damage play a crucial role in this process. EndMT is a biological process in which endothelial cells lose their characteristics and transform into mesenchymal cells, which have a fibroblast-like phenotype. This process has been shown to contribute to tissue fibrosis and remodeling in various diseases, including cancer and cardiovascular diseases. DOX-induced cardiotoxicity has been demonstrated to increase the expression of EndMT markers, suggesting that EndMT may play a critical role in the development of this condition. Furthermore, DOX-induced cardiotoxicity has been shown to cause endothelial damage, leading to the disruption of the endothelial barrier function and increased vascular permeability. This can result in the leakage of plasma proteins, leading to tissue edema and inflammation. Moreover, DOX can impair the production of nitric oxide, endothelin-1, neuregulin, thrombomodulin, thromboxane B2 etc. by endothelial cells, leading to vasoconstriction, thrombosis and further impairing cardiac function. In this regard, this review is devoted to the generalization and structuring of information about the known molecular mechanisms of endothelial remodeling under the action of DOX

Dynamics of Skin Vessels Microcirculation Parameters in Rats at the Hypoxia

The work is devoted to the study of the effect of interval hypoxic training on the state of microcirculation of the skin in rats in the experiment. The study was conducted on white male Wistar rats weighing 70 g ±10%. In order to study the state of the dynamic characteristics of blood microcirculation, a change in blood perfusion of the tissue was considered. A non-invasive method for quantifying microvascular perfusion was used. The results showed that inhibition of microcirculation up to 50 % was observed in comparison to this value before exposure during the formation of a compensatory reaction of the body to a hypoxic effect on the 7–14th day of the experiment. It was noted that the predominant role in the regulation of the microvasculature belongs to the passive regulation factor of microcirculation which is characterized by the involvement of blood vessels in the microvasculature due to periodic changes in blood volume in the vessel together with an increase in the arithmetic mean perfusion rate. Thus, experimentally modulated hypobaric exposure, changes the volume of blood in arterioles that is determined by a pulse wave

Dynamics of Skin Vessels Microcirculation Parameters in Rats at the Hypoxia

The work is devoted to the study of the effect of interval hypoxic training on the state of microcirculation of the skin in rats in the experiment. The study was conducted on white male Wistar rats weighing 70 g ±10%. In order to study the state of the dynamic characteristics of blood microcirculation, a change in blood perfusion of the tissue was considered. A non-invasive method for quantifying microvascular perfusion was used. The results showed that inhibition of microcirculation up to 50 % was observed in comparison to this value before exposure during the formation of a compensatory reaction of the body to a hypoxic effect on the 7–14th day of the experiment. It was noted that the predominant role in the regulation of the microvasculature belongs to the passive regulation factor of microcirculation which is characterized by the involvement of blood vessels in the microvasculature due to periodic changes in blood volume in the vessel together with an increase in the arithmetic mean perfusion rate. Thus, experimentally modulated hypobaric exposure, changes the volume of blood in arterioles that is determined by a pulse wave

Influenza A Virus Causes Histopathological Changes and Impairment in Functional Activity of Blood Vessels in Different Vascular Beds

It has been established that blood vessels are a target for influenza virus; however, the mechanism by which virus affects the cardiovascular system remains unknown. The aim of the study is the identification of histological changes and changes in the functional activity of the pulmonary and mesenteric blood vessels of Wistar rats. Wistar rats were intranasally infected with the influenza A(H1N1)pdm09 virus. At 24 and 96 h post infection (hpi), histopathological changes were observed in lung tissues with the absence of histological changes in mesenteric tissues. The functional activity of pulmonary and mesenteric arteries was determined using wire myography. In pulmonary arteries, there was a tendency towards an increase in integral response to the vasodilator and a decrease in the integral response to the vasoconstrictor at 24 hpi (compared with control). At 96 hpi, a tendency towards a decrease in the integral response to the vasoconstrictor persisted, while the response to acetylcholine was slightly increased. The functional activity of the mesenteric blood vessels was inverted: a significant decrease in the integral response to the vasodilator and an increase in the response to the vasoconstrictor at 24 hpi were observed; at 96 hpi, the integral response to the vasoconstrictor persisted, while the response to the vasodilator remained significantly reduced. Obtained data indicate the development of endothelial dysfunction in non-lethal and clinically non-severe experimental influenza virus infection

Intravenous Nicotinamide Riboside Administration Has a Cardioprotective Effect in Chronic Doxorubicin-Induced Cardiomyopathy

Doxorubicin, which is widely used to treat a broad spectrum of malignancies, has pronounced dose-dependent side effects leading to chronic heart failure development. Nicotinamide riboside (NR) is one of the promising candidates for leveling the cardiotoxic effect. In the present work, we performed a comparative study of the cardioprotective and therapeutic actions of various intravenous NR administration modes in chronic doxorubicin-induced cardiomyopathy in Wistar rats. The study used 60 mature male SPF Wistar rats. The animals were randomized into four groups (a control group and three experimental groups) which determined the doxorubicin (intraperitoneally) and NR (intravenous) doses as well as the specific modes of NR administration (combined, preventive). We demonstrated the protective effect of NR on the cardiovascular system both with combined and preventive intravenous drug administration, which was reflected in a fibrous tissue formation decrease, reduced fractional-shortening decrease, and better antioxidant system performance. At the same time, it is important to note that the preventive administration of NR had a more significant protective effect on the animal organism as a whole. This was confirmed by better physical activity parameters and vascular bed conditions. Thus, the data obtained during the study can be used for further investigation into chronic doxorubicin-induced cardiomyopathy prevention and treatment approaches

Neutrophils mediate pulmonary artery thrombosis in situ

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting