TGFβ1 Regulates Cellular Composition of In Vitro Cardiac Perivascular Niche Based on Cardiospheres.

The cardiac perivascular niche is a cellular microenvironment of a blood vessel. The principles of niche regulation are still poorly understood. We studied the effect of TGFβ1 on cells forming the cardiac perivascular niche using 3D cell culture (cardiospheres).

Transplantation of Adipose-Tissue-Engineered Constructs with CRISPR-Mediated UCP1 Activation.

Thermogenic adipocytes have potential utility for the development of approaches to treat type 2 diabetes and obesity-associated diseases. Although several reports have proved the positive effect of beige and brown adipocyte transplantation in obese mice, translation to human cell therapy needs improvement. Here, we describe the application of CRISPR activation (CRISPRa) technology for generating safe and efficient adipose-tissue-engineered constructs with enhanced mitochondrial uncoupling protein 1 (UCP1) expression.

The Efficacy of HGF/VEGF Gene Therapy for Limb Ischemia in Mice with Impaired Glucose Tolerance: Shift from Angiogenesis to Axonal Growth and Oxidative Potential in Skeletal Muscle.

Background: Combined non-viral gene therapy (GT) of ischemia and cardiovascular disease is a promising tool for potential clinical translation. In previous studies our group has developed combined gene therapy by vascular endothelial growth factor 165 () + hepatocyte growth factor (). Our recent works have demonstrated that a bicistronic pDNA that carries both human and coding sequences has a potential for clinical application in peripheral artery disease (PAD).

Grain-Based Dietary Background Impairs Restoration of Blood Flow and Skeletal Muscle During Hindlimb Ischemia in Comparison With Low-Fat and High-Fat Diets.

Among vascular pathologies associated with obesity, peripheral artery disease (PAD) occupies the important position. In clinical practice, nutritional interventions are recommended for patients with PAD. In this work, we investigated how the different dietary backgrounds affect the regeneration rate of ischemic hindlimb in mice.

[Study of the structure and microflora of urethral tissues in urethral pain syndrome].

Unlabelled: Urethral pain syndrome (UPS) is characterized by the occurrence of persistent or recurrent pain in the urethra in the absence of a confirmed infection and other obvious local pathological changes. The study of its pathogenetic aspects is important first of all for understanding the causes of the disease, to prescribe effective treatment, specific recommendations for the prevention and treatment of this disease are also absent. This paper presents the advanced experience of our research group on the study of the urethral state by the in vivo cross-polarization optical coherence tomography (CP OCT) method, and also the results of the microbiota analysis in the urethral tissues.

Features of the Population of Mouse Peritoneal Macrophages Isolated after Stimulation with Concanavalin A and Thioglycolate.

Murine peritoneal macrophages isolated from the lavage fluid after administration of thioglycolate and concanavalin A are presented by two populations of cells of different diameters. Polarization of macrophages into a proinflammatory (M1) phenotype is accompanied by an increase in number of small cells. Macrophages obtained after administration of thioglycolate demonstrate higher tendency to anti-inflammatory (M2) phenotype, while macrophages isolated after administration of concanavalin A are committed in the proinflammatory direction.

Acute kidney injury in COVID-19: are kidneys the target or just collateral damage? A comprehensive assessment of viral RNA and AKI rate in patients with COVID-19.

Purpose Of Review: To investigate the possible effects of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) on kidney function and assess the rate of viral ribonucleic acid (RNA) shedding/detection in urine.

Recent Findings: Most of the research on the topic suggests that for the moment our ability to estimate whether SARS-CoV-2 is a direct causative agent in acute kidney injury (AKI) or whether it has a cytokine storm effect is limited. During our prospective assessment of 333 patients with COronaVIrus Disease 2019 (COVID-19) it was found that frequency of AKI of 9.

Therapeutic Angiogenesis by a "Dynamic Duo": Simultaneous Expression of HGF and VEGF165 by Novel Bicistronic Plasmid Restores Blood Flow in Ischemic Skeletal Muscle.

Therapeutic angiogenesis is a promising strategy for relief of ischemic conditions, and gene delivery was used to stimulate blood vessels' formation and growth. We have previously shown that intramuscular injection of a mixture containing plasmids encoding vascular endothelial growth factor (VEGF)165 and hepatocyte growth factor (HGF) leads to restoration of blood flow in mouse ischemic limb, and efficacy of combined delivery was superior to each plasmid administered alone. In this work, we evaluated different approaches for co-expression of HGF and VEGF165 genes in a panel of candidate plasmid DNAs (pDNAs) with internal ribosome entry sites (IRESs), a bidirectional promoter or two independent promoters for each gene of interest.

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction.

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF.

[Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL-1) in myocardium after experimental infarction in rats].

In heart attack, FSTL-1 is actively secreted by cardiomyocytes, accelerates growth of heart myofibrils and stimulates of vascular endothelial growth factor expression. The aim of this work was to investigate the effect of Etoxidol on synthesis of FSTL-1 in rats after myocardial infarction. The experiments were performed on Wistar rats weighing 250-350 g with simulated myocardial infarction or intact (group 5).

[Evaluation of the composition of the microbiota of the urethra in men with sexually transmitted infections].

Objective: to conduct a comparative study of the composition of the microbiota of the urethra in men with sexually transmitted infections (STIs), and healthy men.

Material And Methods: The study included 103 men aged 18 to 45 years: 42 men with urethritis caused by STIs and 61 clinically healthy men. Identification of pathogenic and conditionally pathogenic microorganisms in scrapings from the urethra was performed by PCR in real time (test system Androflor (DNA-Technology, Moscow).

Transplantation of Adipose Stromal Cell Sheet Producing Hepatocyte Growth Factor Induces Pleiotropic Effect in Ischemic Skeletal Muscle.

Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model.

C-Kit Cardiac Progenitor Cell Based Cell Sheet Improves Vascularization and Attenuates Cardiac Remodeling following Myocardial Infarction in Rats.

The adult heart contains small populations of multipotent cardiac progenitor cells (CPC) that present a convenient and efficient resource for treatment of myocardial infarction. Several clinical studies of direct CPC delivery by injection have already been performed but showed low engraftment rate that limited beneficial effects of procedure. Cell sheet technology has been developed to facilitate longer retention of grafted cells and show new directions for cell-based therapy using this strategy.

Angiogenic and pleiotropic effects of VEGF165 and HGF combined gene therapy in a rat model of myocardial infarction.

Since development of plasmid gene therapy for therapeutic angiogenesis by J. Isner this approach was an attractive option for ischemic diseases affecting large cohorts of patients. However, first placebo-controlled clinical trials showed its limited efficacy questioning further advance to practice.

Plasmid-based gene therapy with hepatocyte growth factor stimulates peripheral nerve regeneration after traumatic injury.

Peripheral nerve injury remains a common clinical problem with no satisfactory treatment options. Numerous studies have shown that hepatocyte growth factor (HGF) exerts neurotrophic effect in motor, sensory, and parasympathetic neurons in addition to mitogenic, morphogenic, angiogenic, antiapoptotic, antifibrotic, and anti-inflammatory effect on various tissues and cells. In our study we examined efficacy of gene therapy with HGF-bearing plasmid (pC4W-hHGF) to improve consequences of traumatic nerve injury in mice.

Comparison of cardiac stem cell sheets detached by Versene solution and from thermoresponsive dishes reveals similar properties of constructs.

Cell sheets (CS) from c-kit+ cardiac stem cell (CSC) hold a potential for application in regenerative medicine. However, manufacture of CS may require thermoresponsive dishes, which increases cost and puts one in dependence on specific materials. Alternative approaches were established recently and we conducted a short study to compare approaches for detachment of CS from c-kit+ CSC.

ISOLATION AND CHARACTERIZATION OF CARDIAC PROGENITOR CELLS OBTAINING FROM MYOCARDIAL RIGHT ATRIAL APPENDAGE TISSUE.

Resident stem cells of the heart are denoted as heterogeneous population of immature cells, which reside in the myocardium and characterized by their ability to self-renewal and are multipotent differentiation capacity into cardiomyocyte-like and vascular like cells. CSCs were originally isolated directly by long enzymatic digestion of heart tissue and selection using stem cell markers. However, long exposure to enzymatic digestion and small myocardial sample size can affect the possibility of obtaining a significant amount of viable cells.

Enhanced angiogenesis in ischemic skeletal muscle after transplantation of cell sheets from baculovirus-transduced adipose-derived stromal cells expressing VEGF165.

Introduction: Cell therapy using adipose-derived stromal cells (ADSC) is an intensively developing approach to promote angiogenesis and regeneration. Administration technique is crucial and among others minimal constructs - cell sheets (CS) have certain advantages. Delivery of CS allows transplantation of cells along with matrix proteins to facilitate engraftment.

Regulation of Adipose Tissue Stem Cells Angiogenic Potential by Tumor Necrosis Factor-Alpha.

Tissue regeneration requires coordinated "teamwork" of growth factors, proteases, progenitor and immune cells producing inflammatory cytokines. Mesenchymal stem cells (MSC) might play a pivotal role by substituting cells or by secretion of growth factors or cytokines, and attraction of progenitor and inflammatory cells, which participate in initial stages of tissue repair. Due to obvious impact of inflammation on regeneration it seems promising to explore whether inflammatory factors could influence proangiogenic abilities of MSC.

Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in inhabitants of Astana, the capital city of Kazakhstan.

Background: Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations.

Methodology/principal Findings: A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci.

[The parietal intestinal microflora in patients with chronic pancreatitis].

The article presents the results of the proximal small intestine parietal microbiocenosis research in patients with chronic pancreatitis by polymerase chain reaction in real time. The study includes an assessment of the pharmacological correction's efficiency in this category of patients.

[The composition of the gastrointestinal mucosa-associated microbiota in irritable bowel syndrome patients].

The Aim Of This Study: To investigate and analyse the gastrointestinal mucosal-associated microbiota in the samples from diarrhea-predominant IBS (D-IBS), constipation--predominant IBS (C-IBS) patients and healthy controls.

Methods: Oral cavity, duodenal, colonic and rectal mucosal samples were obtained from 40 IBS patients (20 C-IBS, 20 D-IBS) and 14 healthy controls. Duodenal and colonic tissue was collected during a flexible duodenoscopy and colonoscopy.

[Immunogenetic aspects of early rheumatoid arthritis].

The study is aimed to investigate the distribution of alleles of HLA-DRB1 gene in patients with early rheumatoid arthritis and healthy individuals in Russian population, and evaluate their significance as molecular genetic markers of rheumatoid arthritis predisposition and protection. The association between alleles of HLA-DRB1 genes, antibodies to cyclic citrullinated peptides and IgM rheumatoid factor was also studied. Low and high resolution HLA-DRB1 genotyping were compared.

[Comparative study of results of coronary angiography in patients with first and repetitive myocardial infarction].

We compared coronary angiography data from 65 patients with first myocardial infarction (fMI) and 65 patients with repetitive MI (reMI). Coronary angiographic status in both patients with fMI and reMI was characterized by predominance of multivessel lesions with stenoses localized in branches of both coronary arteries (CA). Contrary to fMI patients with reMI had more severe right CA involvement, greater number of occlusions and diffuse lesions in CA bed.

Transplantation of modified human adipose derived stromal cells expressing VEGF165 results in more efficient angiogenic response in ischemic skeletal muscle.

Background: Modified cell-based angiogenic therapy has become a promising novel strategy for ischemic heart and limb diseases. Most studies focused on myoblast, endothelial cell progenitors or bone marrow mesenchymal stromal cells transplantation. Yet adipose-derived stromal cells (in contrast to bone marrow) are abundantly available and can be easily harvested during surgery or liposuction.