Regulation Of Blood Circulation Research Articles

Yixin-Fumai granules modulate autophagy through the PI3K/AKT/FOXO pathway and lead to amelioration of aging mice with sick sinus syndrome

ObjectiveBy employing network pharmacology alongside molecular docking techniques, we can delve into the intricate workings of Yixin-Fumai granules (YXFMs) and their impact on sick sinus syndrome (SSS) within wrinkles mice. Specifically, we aim to understand how YXFMs enhance autophagy through the PI3K/AKT/FOXO path.MethodsThe active ingredients and medicinal uses of Ginseng, ligusticum wallichii, Ophiopogon, Schisandra, salvia, and astragalus were compiled using the BATMAN-TCM database. We also used Genecards, OMIM, and Disgenet files to identify the disease goals. A hierarchical diagram of “disease-drug-key targets” was generated using the Cytoscape programs. In addition, we established a target protein interaction (PPI) network using the STRING database. Then, the Cluster Profiler R package was used to conduct GO functional enrichment evaluation and KEGG pathway enrichment analyses of the targets. Based on the PPI system, we chose the top communicating targets and substances over molecular docking. In vivo studies were performed to validate these selections further. The mouse model was induced to study the damaged sinoatrial node (SAN) in mice with lower heart rates due to age-related changes. Electrocardiogram and Masson staining assessments were performed to obtain the results. The transmission electron microscope was used to assess the autophagy level of SAN cells. Western blot was employed to analyze the impact of YXFMs on protein expression in the PI3K/AKT/FOXO signaling process throughout SSS therapy in aging mice.ResultsOne hundred forty-two active ingredients, 1858 targets, 1226 disease targets, and 266 intersection targets were obtained. The key targets of the PPI network encompassed TP53, AKT1, CTNNB1, INS, and TNF, among others. According to GO functional analysis, the mechanism underlying YXFMs in SSS treatment may primarily be associated with the control of ion transport across membranes, cardiac contraction, regulation of blood circulation, and other biological processes. Based on the results of KEGG pathway enrichment analysis, it was determined that they were mainly enriched in multiple pathways of signaling such as the PI3K-Akt signaling route, MAPK signaling process, AGE-RAGE signaling path, FOXO signaling path, HIF-1 signaling process, and several other paths. Molecular docking demonstrated that five compounds had excellent binding to the key candidate target proteins AKT1 and INS. Through the in vivo studies, we noticed notable effects when administering YXFMs. These effects included the suppression of aging-induced SSS, a decrease in the R-R interval, a rise in heart rate, a reduction in fibrosis, a boost in the autophagy process level, and a spike in the levels of expression of key protein molecules in the PI3K/AKT/FOXO signaling path.ConclusionThis research has made preliminary predictions about the potential of YXFMs in treating SSS. It suggests that YXFMs may have the ability to target key proteins and critical paths associated with the condition. Further testing has been conducted to discover new findings and evidence of ideas for tackling SSS triggered by aging.

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Gastrodiaelata Blume in the treatment of ischemic stroke.

Gastrodia elata Blume (GEB) is widely used to treat cardio-cerebrovascular disease in China and in traditional Chinese medicine it is considered to be a dispelling wind and dredging collateral. However, the mechanism and active components of the plant in treating ischemic stroke (IS) remain unclear. The present study aimed to identify the active components and mechanism of GEB in treating IS using network pharmacology and molecular docking technology. Network analysis predicted 752 potential targets from 14 compounds in GEB, sharing 32 key targets with IS-associated targets. Gene Ontology analysis of key targets showed that 'oxidative stress', 'immune response' and 'regulation of blood circulation' were significantly enriched. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the key targets regulated 11 representative pathways including 'arachidonic acid metabolism', 'lipid and galactose metabolism'. In the protein-protein interaction network, five core targets, including toll-like receptor agonist, STAT3, myeloperoxidase (MPO), prostaglandin-endoperoxide synthase and matrix metalloproteinase (MMP)9, were identified and successfully docked with four active components: Palmitic acid, alexandrin, para-hydroxybenzaldehyde and gastrodin. Alexandrin, para-hydroxybenzaldehyde, and gastrodin are closely related to brain ischemia/reperfusion damage and repair. Therefore, to further verify the mechanism of action of three active components in the second part, we established the HT22 oxygen-glucose deprivation-reperfusion (OGD/R) model. Cell Counting Kit-8 assay and western blot analysis demonstrated that these three active components of GEB regulated core targets of molecular docking, such as STAT3, MPO and MMP9. In vitro experiments showed that OGD/R decreased cell survival, while this effect was reversed by the three active components of GEB. In addition, western blot analysis indicated that alexandrin upregulated expression of phosphorylated-STAT3, para-hydroxybenzaldehyde downregulated MPO and gastrodin downregulated MMP9. Therefore, the present study showed that GEB may prevent and treat IS via interaction between the active components and the main targets, which is key for investigating the efficacy of traditional Chinese medicine.

Exploring Key Genes and Pathways of Cardiac Hypertrophy Based on Bioinformatics

Objective This research is aimed at identifying the key genes and pathways of cardiac hypertrophy using bioinformatics and at providing a new target for the identification of cardiac hypertrophy. Methods Microarray data GSE1621 and GSE18801 were acquired from the GEO database. The DEGs of GSE1621 and GSE18801 were analyzed using the online tool GEO2R. “ggplot2” package of R software was utilized to generate the volcano plots. The top and bottom 10 genes were mapped as a heat map. GO functional annotation analysis and KEGG pathway enrichment analysis were performed separately for DEGs using the online software DAVID. Histograms were plotted using the R “ggplot2” package. The DEGs were imported into the STRING online database for constructing PPI networks and analyzing the DEG interaction relationships. Results In the present study, 469 DEGs were screened in GSE1621 and a total of 793 DEGs were screened in GSE18801. GO analyses indicate that DEGs were mainly involved in cardiac muscle contraction, regulation of blood circulation, regulation of muscle contraction, muscle contraction, striated muscle contraction, regulation of heart contraction, regulation of striated muscle contraction, and tissue remodeling. KEGG analyses indicate that DEGs were mainly involved in Th17 cell differentiation, Th1 and Th2 cell differentiation, HIF-1 signaling pathway, pathways in cancer, hematopoietic cell lineage, Chagas disease and cell adhesion molecules, viral myocarditis, central carbon metabolism in cancer, acute myeloid leukemia, and JAK-STAT signaling pathway. Eight hub genes were screened, including Akt1, Lox, Timp1, Col1al, Spp1, Ccnd1, Mmp3, and Egfr. Conclusions The DEGs associated with cardiac hypertrophy were screened via bioinformatics analysis, and eight hub genes were identified, including Akt1, Lox, Timp1, Col1al, Spp1, Ccnd1, Mmp3, and Egfr, which might be a new target for the identification of cardiac hypertrophy.

Long non-coding RNAs act as novel therapeutic targets by regulating molecular networks associated with ischemic stroke

Impaired blood supply to part of the brain results in an ischemic stroke leading to dysfunction of brain tissue. Several genetic and environmental factors can contribute to stroke. Age is one of the most important risk factors for ischemic stroke. An increased incidence of stroke related mortalities is associated with aging. The pathophysiological processes triggered by stroke, such as inflammation, apoptosis, angiogenesis, and post-stroke recovery, are well described. However, the molecular mechanisms underlying disease development remain to be studied in detail. The damage and recovery process triggered by stroke is coordinately regulated by genes involved in inflammation, immune response, and angiogenesis. The transcriptional dynamics of these key pathways determine the recovery of brain tissue from damage.The long intergenic non-coding RNAs are the key regulators of gene expression regulation. In the present study, we sought to uncover the potential lncRNAs associated with stroke and aging. In the comparison of young and old Middle cerebral artery occlusion models (MCAo) mouse models with the age-matched controls, we found an up-regulation of 27 and 89 lncRNAs in the young and old mice, respectively, after stroke induction. Similarly, we found down-regulation of 24 lncRNAs in the old mice. In our study, we also found an up-regulation of the host genes for the microRNAs miR142 and mir-675.The potential cis-targets of the up-regulated lncRNAs are related to blood vessel morphogenesis, vascular development, and the immune system. Among the cis-targets of down-regulated lncRNAs, we find enrichment of genes involved in membrane action potential and regulation of blood circulation. Importantly, the magnitude of the cellular and molecular response to stroke correlates with differential expression of lncRNAs and the target genes. In conclusion, we demonstrate the association of lncRNAs with pathophysiological processes during stroke, such as apoptosis, angiogenesis, inflammation, blood-brain barrier breakdown, and neurogenesis.

The potential mechanism of Bupleurum against anxiety was predicted by network pharmacology study and molecular docking.

Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear. Therefore, this unknown is predicted by network pharmacology study with molecular docking in the present study. The components of bupleurum were obtained from the databases. Genes associated with components and disease were also provided by databases. Overlapping genes between components and disease were analyzed. The network of medicine-components-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG) and molecular docking were conducted to predict the potential mechanisms of bupleurum on anxiety. A total of 9 bioactive components derived from bupleurum with 80 target genes were involved in anxiety. Neurotransmitter receptor activity, G protein-coupled amine receptor activity, regulation of blood circulation, neuroactive ligand-receptor interaction, calcium signaling pathway and salivary secretion may play significant roles in the anxiolytic of bupleurum. Molecular docking implicated that ACHE and MAOA showed high affinity for stigmasterol. Based on network pharmacology study with molecular docking, multi-component-multi-target-multi-pathway action mode of bupleurum on anxiety was elaborated. Stigmasterol might be the core bioactive component, while ACHE and MAOA might be the core target genes in the pharmacological profile of bupleurum on anxiety.

Influence of physical load of maximum aerobic power on hemodynamics and morpho-biochemical changes in erythrocytes in female volleyball players

Purpose: to study the types of cardiohemodynamic response of the organism and morpho-biochemical changes of erythrocytes of peripheral blood of volleyball players to physical activity of maximum aerobic capacity.
 Material and methods In 18 highly qualified volleyball players aged 22.0±0.60 years, cardiohemodynamics (by functional methods), functional changes (by biochemical methods) and the structure of erythrocytes (using scanning electron microscopy) were studied before and after the maximum (3.5 W/kg of body weight) of physical activity.
 Results. It was found that maximal physical activity causes significant changes in cardiohemodynamics, which result in morphological rearrangement of peripheral blood erythrocytes (increase in erythrocyte deformation index) and closely correlate with biochemical changes (decrease in ATP concentration and increase in magnesium concentration in erythrocytes). Possible mechanisms of realization of features of reaction of an organism of volleyball players to physical activity of the maximum aerobic power depending on type of regulation of blood circulation and morpho-biochemical changes of erythrocytes of peripheral blood are discussed.
 Conclusions. Physical activity of maximum aerobic power in highly qualified female volleyball players reveals the typological features of the cardiohemodynamic response of the body of volleyball players, which is expressed by conformational changes in peripheral blood erythrocytes and depends on the concentration of individual macroelements in these cells and on the type of cardiohemodynamics.

Sexual Dimorphisms of Protein-Coding Gene Profiles in Placentas From Women With Systemic Lupus Erythematosus.

BackgroundSystemic lupus erythematosus (SLE) may cause pathogenic changes in the placentas during human pregnancy, such as decreased placental weight, intraplacental hematoma, ischemic hypoxic change, placental infarction, and decidual vasculopathy, which contribute to high maternal and fetal mortality and morbidity. Sex-specific adaptations of the fetus are associated with SLE pregnancies. The present study aimed to determine the transcriptomic profiles of female and male placentas from women with SLE.MethodsRNA sequencing (RNA-seq) was performed to identify differentially expressed protein-coding genes (DEGs) in placentas from women with SLE vs. normal term (NT) pregnancies with female and male fetuses (n = 3-5/sex/group). Real-time-quantitative PCR was performed (n = 4 /sex/group) to validate the RNA-seq results. Bioinformatics functional analysis was performed to predict the biological functions and pathways of SLE-dysregulated protein-coding genes.ResultsCompared with NT-female (NT-F) placentas, 119 DEGs were identified in SLE-female (SLE-F) placentas. Among these 119 DEGs, five and zero are located on X- and Y-chromosomes, respectively, and four are located on the mitochondrial genome. Compared with NT-male (NT-M) placentas, 458 DEGs were identified in SLE-male (SLE-M) placentas, among which 16 are located on the X-chromosome and zero on the Y-chromosome and mitochondrial genome. Twenty-four DEGs were commonly dysregulated in SLE-F and -M placentas. Functional analysis showed that SLE-dysregulated protein-coding genes were associated with diverse biological functions and pathways, including angiogenesis, cellular response to growth factor stimulus, heparin-binding, HIF (hypoxia-inducible factor)-1 signaling pathway, and Interleukin-17 (IL-17) signaling pathway in both SLE-F and -M placentas. Biological regulations were differentially enriched between SLE-F and -M placentas. Regulation of blood circulation, response to glucocorticoid, and rhythmic process were all enriched in SLE-F, but not SLE-M placentas. In contrast, tumor necrosis factor production, Th17 cell differentiation, and MDA (melanoma differentiation-associated gene)-5 signaling pathway were enriched in SLE-M but not SLE-F placentas.ConclusionThis report investigated the protein-coding gene profiles of placenta tissues from SLE patients using RNA-seq. The results suggest that the SLE-dysregulated protein-coding genes in placentas may contribute to the pathophysiological progress of SLE pregnancies in a fetal sex-specific manner, leading to adverse pregnancy outcomes.

Revealing the Angiopathy of Lacrimal Gland Lesion in Type 2 Diabetes

For a better understanding of diabetic angiopathy (DA), the potential biomarkers in lacrimal DA and its potential mechanism, we evaluated the morphological and hemodynamic alterations of lacrimal glands (LGs) in patients with type 2 diabetes and healthy counterparts by color Doppler flow imaging (CDFI). We further established a type 2 diabetic mice model and performed hematoxylin-eosin (HE) staining, immunofluorescence staining of CD31, RNA-sequencing analysis, and connectivity map (CMap) analysis. We found atrophy and ischemia in patients with type 2 diabetes and mice models. Furthermore, we identified 846 differentially expressed genes (DEGs) between type 2 diabetes mellitus (T2DM) and vehicle mice by RNA-seq. The gene ontology (GO) analysis indicated significant enrichment of immune system process, regulation of blood circulation, apoptotic, regulation of secretion, regulation of blood vessel diameter, and so on. The molecular complex detection (MCODE) showed 17 genes were involved in the most significant module, and 6/17 genes were involved in vascular disorders. CytoHubba revealed the top 10 hub genes of DEGs, and four hub genes (App, F5, Fgg, and Gas6) related to vascular regulation were identified repeatedly by MCODE and cytoHubba. GeneMANIA analysis demonstrated functions of the four hub genes above and their associated molecules were primarily related to the regulation of circulation and coagulation. CMap analysis found several small molecular compounds to reverse the altered DEGs, including disulfiram, bumetanide, genistein, and so on. Our outputs could empower the novel potential targets to treat lacrimal angiopathy, diabetes dry eye, and other diabetes-related diseases.

The role of gaseous mediators (CO, NO and H2S) in the regulation of blood circulation: analysis of the participation of blood cell microrheology

Among the signaling molecules involved in the regulation of intra- and intercellular systems in various types of cells, a special place is occupied by gaseous compounds – gasotransmitters (GTs). Currently, the most studied are three molecules: nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). For them, the enzymatic systems of intracellular synthesis and degradation have been determined, the physiological effect has been proved, and the intracellular mechanisms have been determined. Changes in the work of these mechanisms under the influence of GTs causes the development of physiological and/or pathophysiological reactions. These GTs are involved in the regulation of various organs and systems of the human body under normal and pathological conditions, including the structure and function of the circulatory system. In this article, special attention is paid to the influence of all three GTs and their donors on the vascular and hemorheological aspect of the work of blood circulation, and especially on an underdeveloped problem – the microrheology of erythrocytes. It has been shown that all three GTs, along with the well-known vasodilating effect, reduce the adhesion and aggregation of platelets and leukocytes, as well as moderately stimulate the deformability of erythrocytes and strongly inhibit their aggregation. The performed analysis of the data indicates that, along with the specific signaling cascades for each GT, the use of a common signaling pathway associated with soluble guanylate cyclase and NO synthase was also revealed in microrheological responses. The intersection of signaling pathways triggered by NO, CO and H2S on common effectors, as well as their interaction with each other (cross-talk), can determine the final, resulting functional response of the cell.

Нeart rate variability of children aged 8-11 with deprivation of auditory function

ntroduction.Currently, there are quite a number of publications on the peculiarities of heart rate in children with hearing impairments. However, such studies were conducted with individuals who had varying degrees of deafness and virtually did not examine children with congenital deafness.Children with congenital deafness are likely to have significant changes in cardiovascular system (CVS) indicators compared to their healthy peers. Purpose.The aim of the study was to elucidate the mechanisms of heart rate regulation in children with deprivation of auditory function during active orthostatic testing. Methods. The study involved 15 children: boys (7 individuals) and girls (8 individuals) aged 8-11 with congenital deafness and 17 almost healthy peers. Cardiorhythmograms were recorded with spectral characteristics of heart rate: (VLFms2, less than 0.05 Hz), low (LFms2, 0.05--0.4 Hz) frequencies; the ratio of LF/HF was considered.Results.The results of the study suggest that a group of childrenwith hearing deprivation in all indicators of spectral analysis of HRV had a much lower reactivity of the CVScompared to their healthy peers. The LF indicator did not change significantly, and therefore the sympathetic link of regulation did not play a significant role. However, the contribution of the parasympathetic system, which can be judged by HF, was significantly reduced in both groups. Thus, we can assume that the regulation of blood circulation was due to reduced activation of the parasympatheticlink with constant sympathetic. This feature is indicated by the indicator of vagosympathetic balance of the LF / HF ratio. Its changes reached quite significant values: 87.5% in deaf and 262.5% in healthy children. This indicates the leading role of the sympathetic system in the regulation of heart rhythm in children 8-11 years during orthostasis. However, the differences in the reactivity of the CVSof representatives of different groups indicated a less pronounced degree of activation of this link in the regulation of children with derivation of auditory function.The ratio of the length and width of the autocorrelation cloud (L / W) indicated a similar dependence. The dynamics of this indicator in the direction of increase may indicate a change in the intensity of the autonomic circuit regulation of cardiac activity. 202159In healthy subjects, these changes occurred with a greater degree of activation of central regulatory mechanisms than in children with hearing impairments.Because TP is an almost complete physiological analogue of SDNN, its decrease during orthostasis in children with hearing deprivation by 20.1% and 44.2% in healthy people indicates that the total effect of central regulation mechanisms decreases.Originality.Currently, there are virtuallyno data on reactive changes in the cardiovascular system of children with hearing impairments to postural gravitational loads, especially in relation to children with congenital deafness. This is important given that information about the reactions of thecardiovascular system of children with hearing impairments will allow you to adjust the exercise, choose the optimal motor mode and predict possible deviations or pathologies.Conclusion.Children with the deprivation of auditory function are characterized by more pronounced maladaptive responses of the cardiovascular system to orthostatic load than their healthypeers. Central regulatory mechanisms in deaf children have less pronounced activation compared to healthy children. At orthostatic test, in both groups of subjects, regulation of blood circulation is carried out mainly at the expense of a parasympathetic link of an autonomic nervous system.Keywords. deprivation of auditory function, heart rate variability, spectral analysis

Deciphering underlying mechanism of Sars-CoV-2 infection in humans and revealing the therapeutic potential of bioactive constituents from Nigella sativa to combat COVID19: in-silico study

COVID-19, emerged at the end of 2019 have dramatically threatened the health, economy, and social mobility of people around the world and till date no medication is available for its treatment. An amazing herb, Nigella sativa, having antiviral, antihypertensive, anti- diarrhoeal, analgesics, and anti-bacterial properties, needs to be explored for its efficacy against SARS-CoV-2, the causative agent of COVID-19. In-silico studies were carried out to understand the role of its bioactive constituents in COVID-19 treatment and prevention. Firstly, the disease network was prepared by using ACE2 (Angiotensin-II receptor), as it is the entry site for virus. It was used to decipher the mechanism of SARS-COV-2 infection in humans. Second, the target receptors for N. sativa were predicted and protein interaction studies were conducted. Further, docking studies were also performed to analyse it for treatment purpose as well. This study concludes that pathways undertaken by N. sativa bioactive constituents were similar to the pathways followed in SARS-COV-2 pathology, like renin-angiotensin system, kidney functions, regulation of blood circulation, blood vessel diameter, etc. Also, in docking studies, the constituents of N. sativa, α-hederin, Thymohydroquinone and Thymoquinone were observed to be efficiently binding to ACE2. Also, the bioactive phytoconstituents are involved in molecular pathways like HIF1, VEGF, IL-17, AGE-RAGE, chemokine and calcium signaling pathways which can be majorly helpful in combating hypoxia and inflammation caused due to compromised immune system and oxidative stress. Therefore, N. sativa standardized extract having the above phytoconstituents could be useful in COVID-19 and hence opens a new treatment line.

Genome-wide analysis of prognostic-related lncRNAs, miRNAs and mRNAs forming a competing endogenous RNA network in lung squamous cell carcinoma.

As a type of cancer with the highest morbidity and mortality, lung squamous cell carcinoma (LUSC) has a very poor prognosis. Long-non-coding RNA (lncRNA) has recently attracted attentions because it can play the role of competing endogenous RNA (ceRNA) to inhibit microRNA (miRNA) functions. In this study, we aimed to find prognosis-related lncRNAs, miRNAs and mRNAs and construct a prognosis-related ceRNA network. The original LUSC RNA-sequencing data and miRNA profiles data were downloaded from the cancer genome atlas (TCGA) database. Differentially expressed lncRNAs, miRNAs and mRNAs were then identified between patients with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis was performed to find the survival-associated lncRNAs, miRNAs and mRNAs. Subsequently, prognostic-related ceRNA network was established. By multivariate Cox regression analysis, three lncRNA signatures and three mRNA signatures were developed and used for predicting LUSC patients' survival. A total of 224 lncRNAs, 160 miRNAs, 913 mRNAs were identified between samples with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis showed that, among them, 28 lncRNAs, 8 miRNAs, 105 mRNAs were significantly associated with patients' overall survival time. Further pathway and enrichment analysis suggested that these mRNAs were associated with the regulation of transmembrane transport, regulation of blood circulation, plasma lipoprotein particle organization. Then we constructed a survival-related ceRNA network including 9 lncRNAs, 8 miRNAs and 23 mRNAs. Additionally, a multivariate Cox regression analysis demonstrated that three lncRNAs (AL161431.1, LINC02389, APCDD1L.DT) and three mRNAs (KLK6, SLITRK5, CCDC177) had a significant prognostic value. Risk score indicated that lncRNA signature and mRNA signature could independently predict overall survival in LUSC patients. The current study provided a better understanding of the ceRNA network in the progression of LUSC and laid a theoretical foundation for LUSC prognosis.

Comparative analysis of parameters of cardiointervalometry, ergoreflex and data of 6 minute walk test in patients with chronic obstructive pulmonary disease

Aim. To study the relationship between parameters of cardiointervalometry and ergoreflex, and 6-minute walk test data in patients with chronic obstructive pulmonary disease (COPD).
 Materials and Methods. The study included 103 men, of them 63 patients with COPD, 40 patients of the control group. Functional assessment of external respiration and a 6-minute walk test were performed using Spiropalm 6MWT equipment (Cosmed, Italy). The autonomic status and the influence of the ergoreflex on it were assessed by the method of cardiointervalometry before, during and after the test with external peripheral vascular occlusion using Varicard hardware and software complex (LLC Ramena, Ryazan, Russia).
 Results. When performing a 6-minute walk test, significant differences were obtained between the groups of patients with COPD and of the control group in the majority of the studied parameters (p0.01). In 18 of 63 patients with COPD, the level of SpO2 in 6-minute walk test decreased by 4% (p0.01). The obtained result is of considerable importance for assessment of exercise tolerance in patients with COPD. In tests with external peripheral vascular occlusion in patients with COPD and of the control group, the index of activity of regulatory systems (IARS) increased in both groups. However, after completion of the test, the index in patients with COPD decreased below the initial values (p0.05), and in patients of the control group the changes were even more pronounced (p0.01). Patients with COPD were divided into groups depending on the distance covered in 6-minute walk test. Analysis of the data revealed a moderate positive correlation between the covered distance and the forced expiratory volume in the 1st second (FEV1, R=0.45, p0.01).The maximum level of the total effect of the autonomic regulation of blood circulation was recorded in patients who covered the minimum distance (227.7748.13 m) in 6-minute walk test. Besides, a moderate negative correlation between IARS and the results of 6-minute test was recorded (R=-0.34, p0.01).
 Conclusions. 1. For assessment of the functional status of patients in 6-minute walk test it is important to take measurement of saturation throughout the whole test. 2. The change in IARS values in the test with external peripheral vascular occlusion can be regarded as a reduction of the influence of reflex from the lower limb ergoreceptors on the functional condition of patients. 3. Patients with COPD showed a marked autonomic imbalance. IARS showed a moderate negative correlation with the distance covered in 6-minute walk test. 4. Maximum value of IARS was obtained in patients with the minimal distance covered in 6-minute walk test.

A18782 Prognostic value of hemodynamic parameters and autonomic regulation of blood circulation in the disease course of hypertensive patients

A18782 Prognostic value of hemodynamic parameters and autonomic regulation of blood circulation in the disease course of hypertensive patients

WITHDRAWN: Downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

// Zhibing Qiu 1, * , Bin Ye 2, * , Li Yin 1 , Wen Chen 1 , Yueyue Xu 1 and Xin Chen 1 1 Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China 2 Department of Anesthesiology, Yangzhou Maternal and Child Health Hospital, Yangzhou 225002, Jiangsu Province, China * These authors have contributed equally to this work Correspondence to: Xin Chen, email: chenxinCX66@163.com Keywords: dilated cardiomyopathy; differentially expressed gene; lncRNA; Weighted Gene Coexpression Network Analysis Abbreviations: DCM: dilated cardiomyopathy; DEGs: differentially expressed genes; DELs: DE lncRNAs; WGCNA: Weighted Gene Coexpression Network Analysis Received: September 30, 2017 Accepted: December 05, 2017 Published: January 02, 2018 ABSTRACT Purpose: This study aimed to explore lncRNAs implicated in dilated cardiomyopathy (DCM) using high-throughput sequencing. Methods: From February 2016 to May 2017, ten samples of failing hearts collected from the left ventricles of DCM patients undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, raw data were processed, and differentially expressed genes (DEGs) and lncRNAs between samples from patients with DCM and controls were screened, followed by functional enrichment analysis and Weighted Gene Coexpression Network Analysis (WGCNA). Five key lncNRAs were validated through real-time PCR. Results: After processing sequence data, 1398 DEGs were identified between DCM and control groups, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark-green, and green-yellow) were significantly correlated with the DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LINGO1-AS1, and RP11-557H15.4, in the green-yellow module were associated with functions of neurotransmitter secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in the black module co-regulated functions associated with the regulation of blood circulation and heart contraction. AC061961.2, LINGO1-AS1, and RP11-13E1.5 were confirmed to be downregulated in DCM tissues by real-time PCR. Conclusion: The present study suggests that downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with DCM progression, and these may serve as key diagnostic biomarkers and therapeutic targets for DCM.

Norepinephrine-secreting paraganglioma: a clinical case

Among the rare causes of secondary hypertension pheochromocytoma is traditionally considered. It represents a chromaffin tumor of the adrenal glands. Paraganglioma is an extra-adrenal chromaffinoma. High blood pressure due to the neurohormonal excess accelerates target organ damage. Variable manifestations of pheochromocytoma/paragangliomaclinical make more difficult timely diagnosis and dictate the need of multidisciplinary approach. We present a clinical case of norepinephrine-secreting retroperitoneal paraganglioma in a middle-aged female. An integrated approach to the diagnosis and the assessment of target organ damage is suggested. The features of renin status are highlighted. The case also demonstrates appropriate dynamics of the cardiovascular parameters, neurohormonal regulation of blood circulation, and carbohydrate metabolism after successful surgical treatment of chromaffin tumor.

Оценка задержки в связи между низкочастотными контурами вегетативной регуляции кровообращения у пациентов с артериальной гипертонией

Оценка задержки в связи между низкочастотными контурами вегетативной регуляции кровообращения у пациентов с артериальной гипертонией

Histological and immunocytochemical investigation of human coronary vessel development with anti-CD34 antibodies

Information about embryonic development of coronary endothelium is the main clue for the creation of new methods in tissue engineering for treatment of ischemic heart diseases. The purpose of the research was to describe human coronary vessels development on early stages of the prenatal ontogenesis. The first step in human coronary vessels development is the formation of endothelium de novo by transformation of some epicardial and, possibly, endocardial cells. The next step is the ingrowth of sinus venosus endothelium in subepicardium over ventricles and atria, which gives rise to the coronary vessels. Only after 7 days does the primitive coronary plexus of the heart communicate with aorta (third step). During this period, some subepicardial vessels invade myocardium and some intramyocardial vessels contact with the heart cavity. Such intercommunications could help in regulation of blood circulation in primitive coronary plexus before establishment of effective contacts between arterial and venous vessels—excess of blood could be discharged directly into the heart cavity. Additional population of CD34+ cells were revealed inside condensed mesenchyme of the conotruncus; it participates in the formation of vasa vasorum in the aorta. Epicardium and sinus venosus generate endothelium of coronary vessels by neovasculo- and angiogenesis, respectively. During a week after ingrowth of vessels from SV and before their ingrowth to the aorta, ventriculo-coronary communications could be found in the heart.

Jules Tinel (1879-1952).

Jules Tinel was born on 13 October 1879 in Rouen in France to a family with many generations of surgeons and doctors. He showed both scientific and sports talents from early childhood. He organised sports teams and showed an interest in painting and literature, and even contributed to local literary magazines. His other artistic attempts involved writing music. Tinel started his education in a catholic school, and then he started his studies for a degree in medicine at the University of Rouen. From 1900, he studied medicine in Paris, where he was awarded the degree of externe des hopitaux, the first degree in medical education. He completed his studies in 1906. Influenced by one of his tutors, Joseph Jules Dejerine (1849–1917), he started to specialise in neurology. In 1910, he received a doctorate for his work on neurological consequences of syphilis [1]. In 1911, Tinel became head of the Pitie-Salpetriere Hospital in Paris and 2 years later also the head of the hospital laboratory. In 1914, Tinel was accepted as a member of the Societe de Neurologie and in 1936 he became the president of the institution. In 1914, Tinel was appointed head doctor of the neurology unit in a hospital in Le Mans. After the First World War broke out, he was mobilised and became an assistant doctor in an infantry regiment. It was at that time that he became interested in consequences of damage to peripheral nerves resulting from ballistic trauma. At that time doctors had already been aware of sensation disorders and paresthesias related to nerve damage, yet these were not considered to be of any clinical or diagnostic significance [2]. Tinel’s detailed research resulted in a description of an effect where tapping of the damaged nerve generated paresthesis (tingling sensation). He also discovered that progressing regeneration of the damaged nerve, still without myelin sheath, gives a more peripheral occurrence of the sign [3]. This sign was named after Tinel. His next work was based on the observations of 693 patients [4]. In the decades to follow the sign was observed also in nerve compression syndromes, as for example in carpal tunnel syndrome [5]. The sign attributed to Tinel had been described by German doctor, Paul Hoffmann (1884–1962) several months before Tinel did. Hoffmann was a doctor on the other side of the frontline. His first publication was dated March 1915, the next one came out several months later [6, 7]. Because of the information blockade neither author was aware of the other’s papers. The news of Hoffman’s discovery failed to reach a wider audience due to a lower rank of the periodical and censorship affecting publications from the Central Powers. His contribution to the discovery was neglected throughout the first half of the 20th century. Undoubtedly, contrary to Hoffmann’s work, Tinel’s descriptions are much more detailed and insightful. He clearly separated pain from tingling, and found that the latter had a high prognostic value, and was a sign that the nerve was regenerating. He also found that if the tingling no longer progressed, a surgical intervention was required as it was a signal of a mechanical obstacle to nerve regeneration. Tinel also linked sensation disorders and nerve regeneration with the presence of neuroma. He described not only the regeneration of sensory nerves, but also accurately predicted that tingling was also a sign that motor nerves would regenerate [3, 4]. The name predominantly used in pertinent literature nowadays is Tinel-Hoffmann’s sign, which seems to be the most accurate. After the War ended and Tinel was demobilised, he focused his efforts on psychosomatic diseases and symptoms of encephalitis. In 1922, Tinel and his team were the first to describe paroxysmal hypertension in pheochromocytoma [8]. From 1922 to 1936 he worked at La Rochefoucauld, where he managed to set up a research laboratory despite insufficient facilities. He concentrated on research into measurements of intracranial pressure and studies of the autonomic system [9], the impact of histamines on blood vessels and regulation of blood circulation in the brain [10]. From 1936 Tinel worked in Clichy and in 1940 he returned to Paris. During the Second World War Tinel was involved in the French resistance movement. He organised a network for transporting to Spain wounded pilots whose planes were shot down over France. His son Jacques Tinel, who was actively involved in these actions, was arrested and sent to the concentration camp in Mittlebau-Dora, where he died. Tinel himself, together with his wife and the other son, were arrested in France and released from prison after a few months. In 1945, Tinel retired, but continued his work in Paris. In 1947, he suffered from cerebral ischemia and aphasia, but he recovered. He died of heart failure on 4 March 1952.

What has been overlooked on study of Chinese materia medica in the West?

Chinese materia medica (CMM), including Chinese herbal, animal, and mineral medicine, has been widely researched in the past century for their biological and pharmacological activities. However, their mechanism and clinical efficacy studies did not always give expected results. For example, the most commonly used Chinese herb for menstrual disorders, Radix Angelicae sinensis, showed neither estrogenic nor progesteronic activity in laboratory and clinical studies. Its efficacy should not be denied simply based on such results, because it is mostly used together with other herbs in formulae. Moreover, its regulation on menstruation may take effect through other mechanisms, such as regulation of blood circulation. The key difference of Chinese medicine (CM) from conventional medicine is its unique holistic view on human body and diseases. CMM is mostly applied in clinic in the form of formulae. Study on individual CMM, simply using methods for development of conventional drugs, is unable to thoroughly reveal the power of CMM formulae. The reason may partly result from improper design due to the lack understanding about application principle of CMMs in CM, and/or to current lack of knowledge about the causes of some symptoms and diseases. This paper will introduce the importance of qi and blood in CM etiology and pathology, Zheng differentiation, formulation of CMMs, and explain why one formula can treat different diseases and one disease can be treated with different formulae. Examples in the paper will demonstrate that proper studies on Zheng and its corresponding clinically proven formulae could help scientists find new direction to explain and treat symptoms and diseases that so far modern medicine has been unable to, provided that the designer properly understands CM theories, etiology and pathology of CM, as well as modern medicine. Strategy suggestions about research methods for CMM and its formulae will be given at the end.