Role In Blood Circulation Research Articles

Architecture and activation of single-pass transmembrane receptor guanylyl cyclase.

The heart, in addition to its primary role in blood circulation, functions as an endocrine organ by producing cardiac hormone natriuretic peptides. These hormones regulate blood pressure through the single-pass transmembrane receptor guanylyl cyclase A (GC-A), also known as natriuretic peptide receptor 1. The binding of the peptide hormones to the extracellular domain of the receptor activates the intracellular guanylyl cyclase domain of the receptor to produce the second messenger cyclic guanosine monophosphate. Despite their importance, the detailed architecture and domain interactions within full-length GC-A remain elusive. Here we present cryo-electron microscopy structures, functional analyses and molecular dynamics simulations of full-length human GC-A, in both the absence and the presence of atrial natriuretic peptide. The data reveal the architecture of full-length GC-A, highlighting the spatial arrangement of its various functional domains. This insight is crucial for understanding how different parts of the receptor interact and coordinate during activation. The study elucidates the molecular basis of how extracellular signals are transduced across the membrane to activate the intracellular guanylyl cyclase domain.

Three-dimensional structure of liver vessels and spatial distribution of hepatic immune cells

As the largest internal organ of the human body, the liver has an extremely complex vascular network and multiple types of immune cells. It plays an important role in blood circulation, material metabolism, and immune response. Optical imaging is an effective tool for studying fine vascular structure and immunocyte distribution of the liver. Here, we provide an overview of the structure and composition of liver vessels, the three-dimensional (3D) imaging of the liver, and the spatial distribution and immune function of various cell components of the liver. Especially, we emphasize the 3D imaging methods for visualizing fine structure in the liver. Finally, we summarize and prospect the development of 3D imaging of liver vessels and immune cells.

Metabolic correction of sports horses, their adaptation to active muscular and nervous activity in the prize period

In modern conditions, sports horses are constantly exposed to stressful factors, in which significant clinical and biochemical changes occur in organs and systems, which leads to metabolic diseases, low athletic results andsignificant economic damage. Intensive training has a significant impact on the biochemical parameters of blood, clinical and physiological condition and muscular activity of sports horses. The busy schedule of the competitive period is accompanied by excessive stress of metabolic processes, which leads to rapidfatigue, decreased agility and sports horses lose their athletic form for a long time. Hematological, biochemical and physico-chemical parameters of the blood of sports horses are subject to changes under the influence of muscle work, metabolic processes and the stressful situation of the competitive period. The adaptation of the body to intense muscular activity consists in the peculiarities of training sportshorses. The level of adaptation of the body is characterized by an indicator of the functional state of the cardiovascular system - a change in the pulse rate, which reflects the activity of the heart and has a smaller number of heartbeats at rest. The degree of decrease in the pulse rate, which is the result of functional and morphological changes in the body, depends on the intensity of muscle loads, the type of equestrian sport and the duration of sports operation of the horse. Higher muscle activity is provided by the cardiovascular system, increasing the necessary blood flow and increasing energy metabolism, thus carrying out the transfer of oxygen to the tissues of the body. The role of blood circulation in the body is determined by the ability to keep the amount of oxygen delivered per unit of time by arterial blood to tissues at a level adequate to oxygen consumption in a given period. The amount of oxygen consumption characterizes the level ofredox processes in the body, and the measure of the participation of the processes of anaerobic energy formation in muscle activity is oxygen debt. The sum of these values, that is, oxygen consumption during work and oxygen debt, is the level of oxygen demand and is an indicator of the energy consumption of the body. All processes occurring in the body of sports horses and the connection with the external environment are regulated by the nervous system.

Concentration-dependent viscosity effect on magnetonano peristaltic flow of Powell-Eyring fluid in a divergent-convergent channel

The viscosity of fluids has an essential role in blood circulation through veins and arteries. So, this paper focuses on the influences of dependent-viscosity on the peristaltic flow of Powell-Eyring fluid in a divergent-convergent channel. Viscosity is supposed to vary with the temperature and concentration fluid. A theoretical relation to the concentration-dependent viscosity is introduced mathematically for the Powell-Eyring nanofluid for the first time in our literature. The formulation of the model contains a highly nonlinear system of PDEs that converted to ODEs by physical assumptions to low Reynolds number and long wavelength. A semi-analytical solution was obtained in different theoretical cases of the divergent-convergent channel using the generalized differential transform method (GDTM). Results for velocity profile, temperature distribution, and concentration distribution as well as extra stress tensor profile versus various values flow parameters have been constructed. Results show that the variation parameters of viscosity α, and β can control with flow velocity at each part of channel wall making them improve/get better the blood circulation in veins (Circulatory system). Furthermore, the concentration-dependent viscosity parameter increases the temperature distribution of fluid while it declines the nanoparticle diameter of fluid.

The effect of certain pharmacological agents on the amount of circulating blood in animals

In recent years, in connection with the work of Barcroft'a, Wollheim'a and others, among clinicians, there has been an increased interest in the dynamics of blood circulation and the method of determining it. If earlier the center of gravity of the circulatory mechanism was reduced almost exclusively to the state of the central organ of the system - the heart, nowadays the clinic attaches no less importance to the active role in blood circulation to the state of the arterial and venous network and the amount of blood circulating in the vessels.

Strategies of Prevascularization in Tissue Engineering and Regeneration of Craniofacial Tissues.

Craniofacial tissue defects caused by trauma, developmental malformation, or surgery are critical issues of high incidence, which are harmful to physical and psychological health. Transplantation of engineered tissues or biomaterials is a potential method to repair defects and regenerate the craniofacial tissues. Revascularization is essential to ensure the survival and regeneration of the grafts. Since microvessels play a critical role in blood circulation and substance exchange, the pre-establishment of the microvascular network in transplants provides a technical basis for the successful regeneration of the tissue defect. In this study, we reviewed the recent development of strategies and applications of prevascularization in tissue engineering and regeneration of craniofacial tissues. We focused on the cellular foundation of the in vitro prevascularized microvascular network, the cell source for prevascularization, and the strategies of prevascularization. Several key strategies, including coculture, microspheres, three-dimensional printing and microfluidics, and microscale technology, were summarized and the feasibility of these technologies in the clinical repair of craniofacial defects was discussed. Impact statement Prevascularization is an effective strategy to promote the survival and regeneration of the graft after transplantation. This review focuses on recent development in the technique of prevascularization and discusses the advantages and limits of current technologies. Furthermore, we summarized the progress in the repair of craniofacial tissue defect with prevascularization strategies. The development raised promising prospects of prevascularization strategies in the regeneration of cranial facial tissue defects in the future.

Heart Rate Monitoring System Abnormal Using a Microcontroller

The heart is an organ of the human body that plays an important role in blood circulation and is one of the bases for knowing the physical health of every human being. The heart rate monitoring system used by health institutions is quite good but it costs a lot of usages. In the design carried out by researcher produced a tool that can detect all ages process for 60 seconds. The results after heart rate detection provide condition information and BPM (Beat Per Minute) of the heart. This tool uses a pulse sensor as a heart rate detector with a 3x4 keypad as input for age data and is displayed on a 16x2 LCD with the results of heart conditions and BPM. During testing, the researcher tested approximately 20 respondents as counted tests to put their data in a comparison table. From the results of tests that have been done are classified into two systems testing. The final result of manually testing produces a relative error percentage of 2.40%. While testing, by comparison, using a stethoscope produces a relative error percentage of 1.65%.

Polycomb and Heart Development

Heart plays an important role in blood circulation, and normal heart development is necessary for maintaining cardiac function. Therefore, the regulatory mechanisms underlying cardiac development are widely explored by scientists. Polycomb protein complexes are a group of protein which inhibits the transcription of related genes and regulates the expression of genes involved in the development of various tissues and organs. A better understanding of the molecular mechanism that controls heart development, coupled with an identification of novel roles of Polycomb, could provide the new insight for congenital heart diseases. Here, we mainly expound the relationship between the Polycomb protein complexes and heart development from the perspective of epigenetics.

Absence of venous valves in mice lacking Connexin37

Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell–cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.

Genome-Wide Association Studies Suggest Shared Polymorphisms Are Associated with Severity of Sickle Cell Anemia and Exceptional Longevity.

Genome-wide association studies (GWAS) allow an assessment of associations between single nucleotide polymorphisms (SNPs) and phenotypes or traits of interest in a non-hypothesis driven manner. Previously, based on limited candidate gene association analysis, we showed that survival in sickle cell anemia and exceptional longevity (EL) in the general population share common genetic modifiers (Blood , 52a, 2007). This preliminary result suggested that aging mechanisms and associated genes might play a role in the variability of sickle cell anemia. Using GWAS, we now report strong evidence supporting this conjecture. We conducted a GWAS using an Illumina platform that permits genotyping up to 1 million haplotype-tagging SNPs spread across the genome, as well as other types of genetic variation, in large populations. We used the Illumina 610K SNP array to discover SNPs that are associated with different degrees of severity of sickle cell anemia in 684 patients. Patients were assigned to either a severe or mild disease category based on an integrated measure of sickle cell anemia severity that was determined by a network model that assigns a score predicting the risk of death (Blood 110: 272, 2007). In parallel, we used the Illumina 370K SNP and the Illumina 1M SNP arrays to discover SNPs associated with EL in 877 centenarians enrolled in the New England Centenarian Study and 1,850 younger controls. In both studies, each SNP was tested for association with the traits of severe or less severe sickle cell anemia and EL using Bayesian tests of general, dominant and recessive associations (BMC Genet. 9, 2008). We then identified those SNPs satisfying these 3 criteria:at least one model of association was 10 times more likely than no association in the GWAS of EL;the same model of association was at least 3 times more likely (because of the smaller sample size) than no association in the GWAS of sickle cell anemia severity,the same allele was more frequent in centenarians and in sickle cell anemia patients with milder disease.This analysis identified 140 SNPs in more than 50 genes and some intergenic regions that showed robust and consistent associations. This number is more than twice the number that would be expected by chance. Among the most ‘significant’ genes with associated SNPs were ARFGEF2, ADAMTS12, DOK5, DPP10, FGF21, KCNQ1, IRF4, MYO3B NAIF1, TNNI3K; more than one SNP was found in ARFGEF2, NAIF1, DPP10, SORCS3, TNNI3K. KCNQ1 has a putative role in blood circulation and regulation of heart contraction. The frequency of the common genotype for SNP rs108961 increases by almost 60% in sickle cell anemia patients with severe disease (27% versus 43%). The same common genotype in random Caucasian controls has frequency 34% that decreases to 29% in centenarians. Mutations in this gene are associated with long and short QT syndrome, with familial atrial fibrillation, heart disease and sudden death. SNPs in 2 of the genes (HAO2, a peroxisome protein involved in fatty acid oxidation, and MAP2K1, a MAP kinase involved in multiple biochemical signals) that were significantly associated with both sickle cell disease severity and EL in our earlier candidate gene studies, were also associated in the GWAS. GWAS also revealed significant association with CDKN2A, a cyclin-dependent kinase that has been associated with Type 2 diabetes, risk of myocardial infarction and triglyceride levels in several GWAS, and with FGF21, the fibroblast growth factor 21 precursor that has been shown to regulate glucose metabolism. CDKN2A has been associated with disease free survival in other studies. Common metabolic pathways are likely to influence the chance of developing complications of Mendelian and multigenic diseases and the likelihood of achieving EL. This might explain the commonality of genes whose SNPs are associated with the vascular complications of sickle cell anemia, arteriosclerosis and diabetes. A new paradigm suggests that hitherto unexpected genetic differences modulate a limited number of pathways that form a common route toward determining good health and disease.

Endothelial Signals Modulate Hepatocyte Apicobasal Polarization in Zebrafish

Emerging evidence indicates that paracrine signals from endothelial cells play a role in tissue differentiation and organ formation [1-3]. Here, we identify a novel role for endothelial cells in modulating hepatocyte polarization during liver organogenesis. We find that in zebrafish, the apical domain of the hepatocytes predicts the location of the intrahepatic biliary network. The refinement of hepatocyte polarization coincides with the invasion of endothelial cells into the liver, and these endothelial cells migrate along the maturing basal surface of the hepatocytes. Using genetic, pharmacological, and transplantation experiments, we provide evidence that endothelial cells influence the polarization of the adjacent hepatocytes. This influence of endothelial cells on hepatocytes is mediated at least in part by the cell-surface protein Heart of glass and contributes to the establishment of coordinately aligned hepatocyte apical membranes and evenly spaced intrahepatic conduits.

Protective effect of quercetin against cigarette tar extract-induced impairment of erythrocyte deformability

Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is one of the most abundant flavonol-type flavonoids rich in diet and suggested to possess a beneficial role in blood circulation. This study was conducted to know the effect of quercetin aglycone and one of its possible metabolite, quercetin-3- O-β- D-glucuronide on cigarette tar extract-induced impairment of erythrocyte deformability. Erythrocyte suspension containing quercetin aglycone, quercetin-3- O-β- D-glucuronide or quercetin-3- O-β- D-glucoside was forced to flow through microchannels with equivalent diameter of 7 μm and its transit time was measured as an index of erythrocyte deformability using microchannel array method. Both quercetin aglycone and quercetin-3- O-β- D-glucuronide, but not quercetin-3- O-β- D-glucoside, substantially increased erythrocyte deformability indicating that the former two compounds affect the physicochemical state of erythrocyte by interacting with its membranes. Aqueous cigarette tar extract caused marked decrease in erythrocyte deformability with concomitant increase of membranous lipid peroxidation. In that case, quercetin aglycone suppressed the impairment of erythrocyte deformability as well as membranous lipid peroxidation. The same effect was found in quercetin-3- O-β- D-glucuronide, eventhough its effect was lower than that of quercetin aglycone. Thus, not only quercetin aglycone but also its conjugate metabolite protects erythrocyte membrane from the damage of smoking by scavenging reactive oxygen species generated from cigarette tar. Intake of quercetin-rich food may be helpful to protect membranous damage in erythrocytes from smoking.