The Cutting Edge of Disease Modeling: Synergy of Induced Pluripotent Stem Cell Technology and Genetically Encoded Biosensors.

The development of cell models of human diseases based on induced pluripotent stem cells (iPSCs) and a cell therapy approach based on differentiated iPSC derivatives has provided a powerful stimulus in modern biomedical research development. Moreover, it led to the creation of personalized regenerative medicine. Due to this, in the last decade, the pathological mechanisms of many monogenic diseases at the cell level have been revealed, and clinical trials of various cell products derived from iPSCs have begun.

Generation of an induced pluripotent stem cell line, ICGi029-A, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.N515del mutation in MYBPC3.

Hypertrophic cardiomyopathy (HCM) is a common cardiovascular disease. However, effective methods of its therapy have not been developed so far. To date patient-specific induced pluripotent stem cell-derived cardiomyocytes are supposed to be a useful tool for studying HCM molecular mechanisms and to help find new approaches to HCM therapy.

Generation of an induced pluripotent stem cell line, ICGi028-A, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.E510Q mutation in HADHA.

Hypertrophic cardiomyopathy (HCM) is a frequent cardiovascular pathology caused by a huge number of mutations in sarcomere-associated proteins. This genetic diversity leads to differences in pathogenetic mechanisms and hampers HCM therapy. Cardiomyocytes derived from patient-specific induced pluripotent stem cells give new opportunities for studying underlying HCM mechanisms.

Intrinsic Connectivity Networks in the Self- and Other-Referential Processing.

Neuroimaging studies have revealed a multitude of brain regions associated with self- and other-referential processing, but the question how the distinction between self, close other, and distant other is processed in the brain still remains unanswered. The default mode network (DMN) is the primary network associated with the processing of self, whereas task-positive networks (TPN) are indispensable for the processing of external objects. We hypothesize that self- and close-other-processing would engage DMN more than TPN, whereas distant-other-processing would engage TPN to a greater extent.

Evaluation of the Effect of Plasma from Patients with Trophic Ulcers on the Function of Dermal Fibroblasts, Mesenchymal Stem Cells, and Endothelial Cells.

We studied the effect of platelet lysate and platelet-poor plasma from patients with trophic ulcers with and without type 2 diabetes mellitus on proliferation, migration, and apoptosis of human dermal fibroblast, mesenchymal stem cells, and endothelial cells. It is shown that plasma obtained from patients with type 2 diabetes mellitus produced inhibitory effects.

The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA.

MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e.

Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population.

ICGi021-A and ICGi022-A iPSC lines were obtained by reprogramming PBMCs of two healthy women of the Siberian population using episomal non-integrating vectors expressing Yamanaka factors. iPSC lines expressed pluripotency markers, had a normal karyotype and demonstrated the ability to differentiate into derivatives of the three germ layers. Clinical exome sequencing data of the original biosamples of the donors are available in the NCBI SRA database.

Generation of two induced pluripotent stem cell lines from peripheral blood mononuclear cells of a patient with Wilson's disease.

Wilson's disease is an inherited disorder associated with copper accumulation in the liver, brain and other vital organs. Wilson's disease is caused by mutations in the ATP7B gene. Over 300 mutations of ATP7B have been described.

[Predictors of neurological complications after cardiac surgical interventions in oldery patients.].

To identify predictors of neurological complications in the hospital period after coronary artery bypass grafting (CABG), 92 patients with coronary heart disease aged 70 years and over were analyzed. Intraoperative monitoring of cerebral oxygenation (rSO2, %) was carried out. At the stage of induction anesthesia, the average level of rSO2 for left and right hemispheres was 64-65% without significant changes during the operation.

Effect of Intraoperative Dexamethasone on Major Complications and Mortality Among Infants Undergoing Cardiac Surgery: The DECISION Randomized Clinical Trial.

Importance: Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain.

Objective: To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery.

Design, Setting, And Participants: The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia.

Generation of two clonal iPSC lines, ICGi019-A and ICGi019-B, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.M659I mutation in MYH7.

Hypertrophic cardiomyopathy (HCM) is one of the most frequent cardiovascular diseases but no methods to prevent its progression have been developed. Cardiomyocytes derived from patient-specific induced pluripotent stem cells can become a platform to study pathogenesis of the disease and to search for more effective therapy methods. We generated two iPSC lines from peripheral blood mononuclear cells of an HCM patient with heterozygous p.

Management of Coronary Disease in Patients with Advanced Kidney Disease.

Background: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.

Methods: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction.

The Panel of 12 Cell-Free MicroRNAs as Potential Biomarkers in Prostate Neoplasms.

Prostate cancer is a global biological, medical, and social issue aggravated by the lack of reliable, highly specific, and sensitive non-invasive tests for diagnosis and staging of prostate cancer. One prospective source of biomarkers are the cell-free miRNAs present in various biological fluids. In the present study, we validated the diagnostic potential of cell-free miRNAs: miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, and miR-660; we estimated the required sample size and the minimal miRNA set for a subsequent large-scale validation study.

Cytokine Profile in Experimental Models of Critical Limb Ischemia in Rats.

We studied the effect of intramuscular administration of a cellular product (mesenchymal stem cells, conditioned media, and erythropoietin) on cytokine levels in blood serum, conditioned media of bone marrow mononuclears, and calf muscles in Wistar rats with hind limb ischemia. It is shown that the cellular product reduces the proinflammatory background at the early stages of the experiment and increases the content proangiogenic factors.

Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.

Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers.

Dysfunction telomeres in embryonic fibroblasts and cultured pluripotent stem cells of (Rodentia, Muridae).

We studied the level of spontaneous telomere dysfunction in Rattus norvegicus (Berkenhout, 1769) (Rodentia, Muridae) embryonic fibroblasts (rEFs) and in cultured in vitro rat pluripotent stem cells (rPSCs), embryonic stem cells (rESCs) and induced pluripotent stem cells (riPSCs), on early passages and after prolonged cultivation. Among studied cell lines, rESCs showed the lowest level of telomere dysfunction, while the riPSCs demonstrated an elevated level on early passages of cultivation. In cultivation, the frequency of dysfunctional telomeres has increased in all studied cell lines; this is particularly true for dysfunctional telomeres occurring in G1 stage in riPSCs.

Balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.

Aim: To evaluate the effectiveness of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Materials And Methods: Forty patients with inoperable CTEPH were enrolled in this study. The indications were determined by multidisciplinary team.

Generation of two iPSC lines (ICGi008-A and ICGi008-B) from skin fibroblasts of a patient with early-onset Alzheimer's disease caused by London familial APP mutation (V717I).

The induced pluripotent stem cell (iPSC) lines ICGi008-A and ICGi008-B were generated from dermal fibroblasts using episomal vectors expressing pluripotency factors. Dermal fibroblasts were obtained from a 55 year old male Сaucasian familial Alzheimer's disease (AD) patient carrying heterozygous V717I mutation in the APP gene. The generated iPSC lines maintained the original APP genotype, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into cell types of the three germ layers.

Extracorporeal cardiopulmonary resuscitation after pulmonary artery rupture.

Pulmonary artery rupture during pulmonary balloon valvuloplasty is a rare and life-threatening complication. Here, we present a pulmonary artery rupture in a 10-month-old infant. The patient had a tamponade, ineffective cardiac massage for 40 minutes and extreme hemodilution due to blood loss.

Prospective, randomized trial of bioresorbable scaffolds vs. everolimus-eluting stents in patients undergoing coronary stenting for myocardial infarction: the Intracoronary Scaffold Assessment a Randomized evaluation of Absorb in Myocardial Infarction (ISAR-Absorb MI) trial.

Aims: Bioresorbable scaffolds (BRS) provide short-term coronary artery scaffolding and drug delivery. Although prior trials showed a higher rate of device failure compared with conventional drug-eluting stents (DES), only a single trial investigated patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). We aimed to compare outcomes with BRS vs.

Polyunsaturated Fatty Acids and Their Correlations with Parameters of Oxidative/Antioxidant Potential of the Blood and Lipoprotein-Associated Phospholipase A2 in Coronary Atherosclerosis.

We studied serum content of some polyunsaturated fatty acids and their correlations with parameters of oxidative stress (FORT), antioxidant protection (FORD), lipoprotein-associated phospholipase A2 (LP-PLA2), and serum level of LPO products in male patients with coronary atherosclerosis. The mass fraction of polyunsaturated fatty acids and FORD were lower, while LP-PLA2, FORT, and concentration of LPO products were higher than in the control group (conventionally healthy men). Negative correlations of medium strength of polyunsaturated fatty acids with inflammation markers and oxidative stress were revealed, which can indicate that the decrease in polyunsaturated fatty acids content is associated with enhanced generation of free radicals, and consequently with increased risk of early atherosclerosis development.