Physiological research最新文献

Hemolysis and eryptosis contribute to anemia encountered in patients undergoing chemotherapy. Eicosapentaenoic acid (EPA) is an omega-3 dietary fatty acid that has anticancer potential by inducing apoptosis in cancer cells, but its effect on the physiology and lifespan of red blood cells (RBCs) is understudied. Human RBCs were exposed to anticancer concentrations of EPA (10-100 ?M) for 24 h at 37 °C. Acetylcholinesterase (AChE) activity and hemolysis were measured by colorimetric assays whereas annexin-V-FITC and forward scatter (FSC) were employed to identify eryptotic cells. Oxidative stress was assessed by H2DCFDA and intracellular Ca2+ was measured by Fluo4/AM. EPA significantly increased hemolysis and K+ leakage, and LDH and AST activities in the supernatants in a concentration-dependent manner. EPA also significantly increased annexin-V-FITC-positive cells and Fluo4 fluorescence and decreased FSC and AChE activity. A significant reduction in the hemolytic activity of EPA was noted in the presence extracellular isosmotic urea, 125 mM KCl, and polyethylene glycol 8000 (PEG 8000), but not sucrose. In conclusion, EPA stimulates hemolysis and eryptosis through Ca2+ buildup and AChE inhibition. Urea, blocking KCl efflux, and PEG 8000 alleviate the hemolytic activity of EPA. The anticancer potential of EPA may be optimized using Ca2+ channel blockers and chelators to minimize its toxicity to off-target tissue. Keywords: EPA, Eryptosis, Hemolysis, Calcium, Anticancer.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Therefore, understanding the molecular regulatory mechanisms underlying the pathogenesis of DKD is imperative. In this study, we aimed to explore the molecular mechanisms of tubule region endothelial dysfunction in early DKD. Early-stage DKD model was established in 16-week-old female db/db mice for 16 weeks. Body weight, glucose level, and urine albumin-to-creatinine ratio (UACR) were measured. Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were performed to evaluate pathological lesions. RNA sequencing data of the kidneys and integrated publicly available single-cell and spatial transcriptome datasets were used to investigate the mechanism of endothelial dysfunction. There was a significant increase in body weight (p = 0.001), glucose levels (p=0.0008), and UACR (p=0.006) in db/db mice compared with db/m mice. H&E and PAS staining showed that vacuolar lesions and protein casts of tubules were the major histopathological changes observed in early-stage DKD mice. The apoptotic pathway in endothelial cells was notably activated in DKD, and Thbs1 was identified as the central gene involved in this apoptotic process. Deconvolution of the cell composition in the RNA sequencing data showed a decrease in the proportion of endothelial cells in the DKD mice. Further analysis of the activity and regulatory network of transcription factors showed that Creb1 was activated in both mouse and human early-stage DKD, suggesting that Creb1 activation may be involved in early kidney injury. The endothelial cell apoptotic pathway is activated in DKD, and the proportion of endothelial cells was reduced in the DKD mice, which is significantly associated with Thbs1. Keywords: Diabetic kidney disease, Endothelial dysfunction, RNA sequencing,Thbs1, Creb1.

Perivascular adipose tissue (PVAT) envelops the majority of systemic vessels, providing crucial mechanical support and vessel protection. In physiological conditions, PVAT releases various bioactive molecules, contributing to the anti-inflammatory environment around neighboring vessels. However, in conditions like obesity, PVAT can exacerbate cardiovascular issues such as atherosclerosis. Communication between PVAT and nearby vessels is bidirectional, with PVAT responding dynamically to signals from the vasculature. This responsiveness positions PVAT as a promising indicator of vascular inflammation. Recently, the role of PVAT in the CVD risk prediction is also greatly discussed. The objective of this review is to summarize the current state of knowledge about the PVAT function, its role in physiologic and pathophysiologic processes and its potential in CVD risk prediction. Keywords: Perivascular adipose tissue, inflammation, atherogenesis, Fat attenuation index.

Metabolic syndrome (MetS) represents a worldwide health problem, affecting cardiovascular and mental health. People with MetS are often suffering from depression. We used hereditary hypertriacylglycerolemic (HTG) rats as an animal model of MetS, and these were fed a high-fat-high-fructose diet (HFFD) to imitate unhealthy eating habits of people having several MetS risk factors and suffering depression. Male HTG rats were fed a standard diet (HTG-SD) or HFFD for eight weeks (HFFD8). Venlafaxine was administered for the last three weeks of the experiment (HFFD8+VE). Heart function was observed on the level of intact organisms (standard ECG in vivo), isolated hearts (perfusion according to Langendorff ex vivo), and molecular level, using the RT-PCR technique. The function of the isolated perfused heart was monitored under baseline and ischemia/reperfusion conditions. Analysis of ECG showed electrical abnormalities in vivo, such as significant QRS complex prolongation and increased heart rate. Ex vivo venlafaxine significantly reduced QT interval after ischemia/reperfusion injury. Baseline values of contractile abilities of the heart tended to be suppressed by HFFD. A significant reduction of LVDP was present in the HFFD8 group. Molecular analysis of specific genes involved in cardiac electrical (Cacna1c, Scn5a), contractile (Myh6, Myh7), metabolic function (Pgc1alpha) and calcium handling (Serca2a, Ryr2) supported some of the functional findings in vivo and ex vivo. Based on the present effect of venlafaxine on heart function, further research is needed regarding its cardiometabolic safety in the treatment of patients with MetS suffering from depression. Keywords: Metabolic syndrome, Venlafaxine, ECG, Cardiac contraction, Ischemia/Reperfusion.

Although the heart atria have a lesser functional importance than the ventricles, atria play an important role in the pathophysiology of heart failure and supraventricular arrhythmias, particularly atrial fibrillation. In addition, knowledge of atrial morphology recently became more relevant as cardiac electrophysiology and interventional procedures in the atria gained an increasingly significant role in the clinical management of patients with heart disease. The atrial chambers are thin-walled, and several vessels enter at the level of the atria. The left and right atrium have different structures and shape. In general, both atrial chambers have the venous part, the appendage, and the vestibule; different aspects of each part allow us to distinguish morphologically between the left and right atrium. The human atrial conduction system consists of the sinus node and the atrioventricular node with no histologically specialized conduction pathways in the atrial chamber and an interatrial connection. The data show that the propagation of the impulse depends mainly on the myocardial architecture in the atria and the orientation of the myocytes plays a significant role in conduction. To complete the picture, it is also important to know how the atria develop and what is the embryonic origin of its different structures, as this may play a role in the development of some pathological conditions such as atrial fibrillation or certain types of congenital heart defects. Functional impairment of the atria can in some situations severely compromise heart pumping function, and conversely, can support it if other areas are damaged, balancing the blood flow to the body for some time. Key words Morphology of atrial chambers, Pectinate muscles, Atrial function.

High-intensity interval training (HIIT) is considered an effective therapy strategy for improving chronic pain associated with osteoarthritis (OA). Perineuronal nets (PNNs) are specialized extracellular matrix structures in the cerebral cortex that play a crucial role in regulating chronic pain. However, little is unknown whether HIIT could alleviate OA pain sensitization by reducing PNN levels. This study aimed to determine whether HIIT could reduce sensitivity of the affected joint(s) to pain in a chronic pain model in rats with OA. A rat model of interest was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Thereafter, the mechanical withdrawal thresholds (MWTs) and PNN levels in the contralateral medial prefrontal cortex (mPFC) were measured in rats in the presence or absence of HIIT alone or in combination with injection of chondroitinase-ABC (ChABC) into the contralateral mPFC (inducing the degradation of PNNs), respectively. Results indicated that rats with OA exhibited significant reductions in MWTs, but a significant increase in the PNN levels; that HIIT reversed changes in MWTs and PNN levels in rats with OA, and that pretreatment of ChABC abolished effects of HIIT on MWTs, with PNN levels not changed. We concluded that pain sensitization in rats with OA may correlate with an increase in PNN levels in the mPFC, and that HIIT may increases OA pain-sensitive threshold by reduction of the PNN levels in the mPFC. Keywords: Osteoarthritis, Chronic pain, Pain sensitization, High-intensity interval training, Perineuronal nets.

The aim of the present narrative review is to summarise the existing knowledge concerning physiological and reproductive effects of buckwheat, its mechanisms of action on various targets, as well as outlines the direction of the further studies of this functional food plant. Search for literature was performed in agreement with the PRISMA criteria in Cochrane Library, Pubmed, Web of Science, SCOPUS databases between the year 1995 and 2023. Words used to search were buckwheat, review, fertility, ovarian and mechanisms. The current review of the available literature demonstrates the high nutritional value of buckwheat, as well as high contents and number of regulatory molecules in this functional food plant. These molecules can, via multiple signalling pathways, affect a wide spectrum of physiological processes and illnesses, which suggests a therapeutic value of buckwheat substances. Furthermore, recent reports demonstrate ability of buckwheat extract to directly affect basic ovarian cell functions (proliferation, apoptosis, viability, steroidogenesis). On the other hand, understanding the character and applicability of buckwheat influence on female reproductive processes requires further studies. Keywords: Buckwheat, Nutrition, Health, Ovary, Signalling.

Pulse Wave Velocity (PWV) is widely used to assess arterial elasticity and is an independent risk factor for cardiovascular disease, but it is influenced by multiple factors. Objective is to assess the impact of blood pressure and heart rate on PWV. Twenty healthy young individuals were enlisted as subjects. Real-time blood pressure monitoring was performed by non-invasive continuous blood pressure measuring instrument during the detection of subjects' carotid PWV. During real-time blood pressure monitoring, exercise load caused fluctuations in blood pressure and heart rate, and PWV changes of each subject under different blood pressure and heart rate conditions were recorded simultaneously. Among the 20 subjects, PWV was associated with blood pressure in four subjects and heart rate in one subject. PWV increased with rising blood pressure when the systolic pressure fluctuation range was >=30mmHg, diastolic pressure fluctuation range was >=18mmHg, and mean arterial pressure fluctuation range was >=20mmHg. PWV increased with rising heart rate, when the heart rate fluctuation range was >30 beats/min. Blood pressure and heart rate have some influence on PWV. However, the fluctuation range of blood pressure and heart rate should reach a certain value, the impact is significant. Keywords: Pulse wave velocity, Blood pressure, Heart rate.

Adverse events during the perinatal period are associated with an increased risk to develop cardiometabolic diseases later in life. We established a murine model to study long-term effects of perinatal hypoxia (PH) on the pulmonary circulation. We previously demonstrated that PH led to an impaired regulation of pulmonary vascular tone in adulthood, linked to alterations in K+ channels in males and in the nitric oxide (NO)/cyclic guanosine monophosphate pathway in females. Moreover, simultaneous administration of inhaled NO (iNO) during PH exposure prevented adverse effects of PH on adult pulmonary vasculature in females. The present study showed that PH induced a significant increase in right ventricular pressure in males and females, and an enhanced sensitivity to acute hypoxia in females. PH significantly reduced acetylcholine-induced relaxation in pulmonary artery, to a greater extent in females than in males. PH led to right ventricular hypertrophy in adulthood, appearing earlier in males than in females. Morphometric measurements showed a significant increase in the number of 25-75-µm pulmonary vessels in male lungs following PH, probably resulting in increased pulmonary vascular resistance. The effects of prolonged hypoxia in adulthood differed between males and females. Perinatal iNO during PH prevented PH-induced alterations in the cardiopulmonary system, whereas perinatal iNO alone could have some adverse effects. Therefore, PH led to long-lasting alterations in the regulation of adult pulmonary circulation, which vary between males and females. In males, the increased pulmonary vascular resistance was associated with morphological changes besides functional alterations, whereas females showed an important pulmonary vascular dysfunction. Keywords: Perinatal hypoxia, Pulmonary circulation, Endothelium-dependent relaxation, Phosphodiesterases, Sex differences.

Pulmonary hypertension is a complex and heterogeneous condition with five main subtypes (groups). This review focuses on pulmonary hypertension caused by chronic hypoxia (hypoxic pulmonary hypertension, HPH, group 3). It is based mainly on our own experimental work, especially our collaboration with the group of Professor Herget, whose fifth anniversary of death we commemorate. We have found that oxidation and degradation of the extracellular matrix (ECM) in vitro, in either the presence or the absence of pro-inflammatory cells, activate vascular smooth muscle cell (VSMC) proliferation. Significant changes in the ECM of pulmonary arteries also occurred in vivo in hypoxic rats, namely a decrease in collagen VI and an increase in matrix metalloproteinase 9 (MMP-9) in the tunica media, which may also contribute to the growth activation of VSMCs. The proliferation of VSMCs was also enhanced in their co-culture with macrophages, most likely due to the paracrine production of growth factors in these cells. However, hypoxia itself has a dual effect: on the one hand, it can activate VSMC proliferation and hyperplasia, but on the other hand, it can also induce VSMC hypertrophy and increased expression of contractile markers in these cells. The influence of hypoxia-inducible factors, microRNAs and galectin-3 in the initiation and development of HPH, and the role of cell types other than VSMCs (endothelial cells, adventitial fibroblasts) are also discussed. Keywords: Vasoconstriction, Remodeling, Oxidation, Degradation, Extracellular matrix, Collagen, Proteolytic enzymes, Metalloproteinases, Macrophages, Mast cells, Smooth muscle cells, Endothelial cells, Fibroblasts, Mesenchymal stem cells, Hypoxia-inducible factor, microRNA, Galectins, Hyperplasia, Hypertrophy, Therapy of hypoxic pulmonary hypertension.