Quercetin is a potential therapy for post-infarction NETosis formation.

The surgical intervention during myocardial infarction (MI) is associated with the risk of reperfusion injury, infiltration of tissues with polymorphonuclear neutrophils, and neutrophil extracellular trap (NET) formation. We hypothesized that inhibition of NETs with the use of quercetin might be a promising cardioprotective strategy. Wistar rats underwent LAD occlusion (MI) for 40 min followed by 90 min of reperfusion.

Downregulation of lncRNAs Gomafu, NONMMUT033604.2, and NONMMUT064397.2 in the hippocampus of mice with model of post-traumatic stress disorder.

Objectives: Molecular mechanisms of post-traumatic stress disorder (PTSD) development have been analysed by evaluati-ng changes in the expression level of long non-coding RNA (lncRNA) as a potential biomarker of the disease and as one of the molecular aspects associated with the disease development.

Methods: In our study, we used quantitative polymerase chain reaction (qPCR) to evaluate changes in the expression level of long non-coding RNA - Gomafu, NONMMUT033604.2, and NONMMUT064397.

Cardiac dysfunction in spontaneously hypertensive old rats is associated with a significant decrease of SUR2 expression.

ATP-sensitive potassium (K) channels are participants of mechanisms of pathological myocardial remodeling containment. The aim of our work was to find the association of changes in the expression of Kir6.1, Kir6.

Pure purr virtual reality technology: measuring heart rate variability and anxiety levels in healthy volunteers affected by moderate stress.

Introduction: Traditional approaches to stress management are difficult to learn and to implicate in daily life. Emerging technologies like virtual reality (VR) have become a target of extensive study for recreational and medical purposes. The autonomic nervous system (ANS) plays a crucial role in stress response, post-stress relaxation, and recovery.

Melanoma Extracellular Vesicles Generate Immunosuppressive Myeloid Cells by Upregulating PD-L1 via TLR4 Signaling.

Tumor cell-derived extracellular vesicles (EV) convert normal myeloid cells into myeloid-derived suppressor cells (MDSC), inhibiting antitumor immune responses. Here, we show that EV from Ret mouse melanoma cells upregulate the expression of programmed cell death ligand 1 (PD-L1) on mouse immature myeloid cells (IMC), leading to suppression of T-cell activation. PD-L1 expression and the immunosuppressive potential of EV-generated MDSC were dependent on the expression of Toll-like receptors (TLR).

Altered biogenesis of microRNA-1 is associated with cardiac dysfunction in aging of spontaneously hypertensive rats.

Currently we face the issues of aging-associated pathologies, particularly those leading to heart failure. With that in mind, in current research we focus on aging and hypertension combination as a widely spread threating problem. In a row with functional and morphological characterization of these aging- and hypertension-associated cardiac changes, we evaluate biogenesis of microRNA-1 being one of major microRNAs in the heart.

shRNA-Induced Knockdown of a Bioinformatically Predicted Target IL10 Influences Functional Parameters in Spontaneously Hypertensive Rats with Asthma.

One of the most common comorbid pathology is asthma and arterial hypertension. For experimental modeling of comorbidity we have used spontaneously hypertensive rats with ovalbumin (OVA)-induced asthma. Rats were randomly divided into three groups: control group, OVA-induced asthma group; OVA-induced asthma + IL10 shRNA interference group.

Changes of the echocardiographic parameters in chronic heart failure patients with Ile337val, Glu23lys, and Ser1369ala polymorphisms of genes encoding the ATP-sensitive potassium channels subunits in the Ukrainian population.

Different allelic variants of genes that encode ATP-sensitive potassium (K ) channels' subunits may contribute to the development of heart failure. The purpose of the work to investigate SNPs in genes that encode K channels in relation to echocardiographic parameters in chronic heart failure (CHF) patients. Ninety-nine people with CHF of ischemic origin with left ventricular systolic dysfunction were examined.

Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) used for cancer immunotherapy were shown to boost the existing anti-tumor immune response by preventing the inhibition of T cells by tumor cells. Antibodies targeting two negative immune checkpoint pathways, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1), have been approved first for patients with melanoma, squamous non-small cell lung cancer (NSCLC), and renal cell carcinoma. Clinical trials are ongoing to verify the efficiency of these antibodies for other cancer types and to evaluate strategies to block other checkpoint molecules.

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression.

The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits antitumor immune responses, supporting the disease progression.

Ageing related down-regulation of myocardial connexin-43 and up-regulation of MMP-2 may predict propensity to atrial fibrillation in experimental animals.

Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties.

N-3 long chain polyunsaturated fatty acids increase the expression of PPARγ-target genes and resistance of isolated heart and cultured cardiomyocytes to ischemic injury.

Background: The goal of present investigation is to check the hypothesis that cardioprotective effect of polyunsaturated fatty acids (PUFAs) is mediated by influence on mRNA expression level of the FATP, IL-1ra and GJP43 through stimulation of PPARγ.

Methods: Animals obtained n-3 PUFAs orally during 4 weeks (0.1ml/100g b.

siRNA-induced silencing of hypoxia-inducible factor 3α (HIF3α) increases endurance capacity in rats.

Molecular mechanisms of adaptation to exercise despite a large number of studies remain unclear. One of the crucial factors in this process is hypoxia inducible factor (HIF) that regulates transcription of many target genes encoding proteins that are implicated in molecular adaptation to hypoxia. Experiments were conducted on 24 adult male Fisher rats.

Proteasome Inhibition Diminishes the Formation of Neutrophil Extracellular Traps and Prevents the Death of Cardiomyocytes in Coculture with Activated Neutrophils during Anoxia-Reoxygenation.

Objective: Polymorphic mononuclear neutrophils (PMN) are very important cells participating in nonspecific defense of the organism. Among their well-known functions, the formation of neutrophil extracellular traps (NET) is interesting and potentially dangerous for the mechanisms of other cells. Ubiquitin-dependent proteasomal proteolysis is a very important regulator of all cellular activities, but the role of proteasomal proteolysis in NET formation has not been investigated.

Silencing of TERT decreases levels of miR-1, miR-21, miR-29a and miR-208a in cardiomyocytes.

To test the hypothesis that telomerase reverse transcriptase (TERT) as an RNA-dependent RNA polymerase could be involved in the amplification of microRNA (miRNA), we have determined the levels of immature and mature miRNA in cultured neonatal rat cardiomyocytes, during the silencing of TERT by siRNA. The silencing of the TERT gene led to the reduction of both telomerase activity and the TERT mRNA expression when compared with scrambled RNA. TERT gene silencing resulted in the decrement of three studied mature miRNAs levels: miRNA-21, miRNA-29a and miRNA-208a when compared with scrambled RNA; but miRNA-1, it was not changed significantly.

Knockdown of PSMB7 induces autophagy in cardiomyocyte cultures: possible role in endoplasmic reticulum stress.

Proteasomal and autophagic pathways of protein degradation are two essential, endoplasmic reticulum (ER)-associated proteolytic systems involved in the ER stress response. The functional interaction between them has been shown by proteasome pharmacological inhibition. However, little data have been found concerning autophagy induction using an RNA interference approach due to the multisubunit composition of proteolytic systems.

[Influence of flocalin on development of apoptosis and necrosis at anoxia-reoxygenation of culture rats neonatal cardiomyocytes].

The influence of the new cardioprotector flocalin was investigated on the culture of rat's neonatal cardiomyocytes during anoxia-reoxygenation modelling. The mechanisms of apoptosis and necrosis were investigated under influence of ATP-sensitive potassium (K(ATP)) channels activation and in conditions of blocking of the L-type calcium (VGCCs) channels. Flocalin was added in the culture medium in the dose 5 and 20 microM at 2 minutes before anoxia (30 minutes) and following reoxygenation (60 minutes).

Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes.

Quercetin, a plant-derived flavonoid, has attracted considerable attention as promising compound for heart disease prevention and therapy. It has been linked to decreased mortality from heart disease and decreased incidence of stroke. Here, we report new data showing the angioprotective properties of quercetin mediated by its effect on proteasomal proteolysis.

Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion.

It is well known that 5-lipoxygenase derivates of arachidonic acid play an important pathogenic role during myocardial infarction. Therefore, the gene encoding arachidonate 5-lipoxygenase (ALOX5) appears to be an attractive target for RNA interference (RNAi) application. In experiments on cultivated cardiomyocytes with anoxia-reoxygenation (AR) and in vivo using rat model of heart ischemia-reperfusion (IR) we determined influence of ALOX5 silencing on myocardial cell death.

Effect of a low dose of proteasome inhibitor on cell death and gene expression in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation.

Background: Recent data suggest that low concentrations of proteasome inhibitors (PIs) are cytoprotective in models of ischemia-reperfusion injury, but the underlying mechanisms of this effect still remain unclear.

Aim: To investigate the effect of 100 nM of clasto-lactacystin beta-lactone on cell death and gene expression in neonatal rat cardiomyocytes exposed to anoxia-reoxygenation.

Methods: Fluorescent microscopy and real-time polymerase chain reaction were used to detect different types of cell death and gene expression, respectively, in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation.

Effects of late postconditioning on gene expression and cell death in neonatal rat cardiomyocyte cultures.

The cell death and gene expression in neonatal cardiomyocyte cultures were investigated in a late postconditioning model. The primary cultures were subjected to a 30min of anoxia followed by 60min or 24h of reoxygenation. Postconditioning was carried out in three cycles of 1min reoxygenations followed by 1min anoxia, respectively.

Proteasome inhibitors eliminate protective effect of postconditioning in cultured neonatal cardiomyocytes.

A role of proteasomal proteolysis in the pathogenesis of ischemia-reperfusion is being actively studied. To evaluate the participation of the proteasome in postconditioning phenomenon, we used primary culture of neonatal cardiomyocytes. 30 minutes of anoxia followed by 60 minutes of reoxygenation was undergone.

Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte?

Preconditioning and postconditioning increased numbers of living cells and decreased that of necrotic, apoptotic and autophagic cells in anoxia-reoxygenation of isolated cardiomyocytes. It was established that proteasome inhibitors prevented the necrotic and apoptotic cell death of cardiomyocytes in anoxia-reoxygenation and in such a way reproduce the effect of pharmacological preconditioning and postconditioning. In this case, the population of autophagic cardiomyocytes has not changed considerably or had a tendency of increasing compared to anoxia-reoxygenation.

[Effect of N-3-methyladenine on peptidase and ribonuclease activity of proteasome].

Using a culture of cardiomyocytes it has been shown, that a well-known inhibitor of autophagy, N-3-methyladenine causes a 1.4 fold increase (p = 0.023) of the chymotrypsin-like activity, a 1.

[The influence of quercetin on the activity of purified 20S, 26S proteasome and proteasomal activity in isolated cardiomyocytes].

For the clarification of the effect of quercetin on the proteasome experiments were performed using purified 20S proteasome, 26S proteasome from the proteasomal fraction II (PF II), as well as cardiomyocyte culture which underwent anoxia-reoxygenation. In the experiments with purified 20S proteasome it was shown, that quercetin in a dose-dependent manner inhibits all three peptidase activities of the proteasome, comparable to a specific proteasome inhibitor. The highest quercetin inhibition was observed in the case of chymotrypsin-like activity of proteasome.