Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene.

Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the development of the disease, to identify targets for therapeutic intervention and to test potential drugs to prevent neuronal death.

Generation of Isogenic iPSC Lines for Studying the Effect of the p.N515del (c.1543_1545delAAC) Variant on MYBPC3 Function and Hypertrophic Cardiomyopathy Pathogenesis.

The clinical significance of numerous cardiovascular gene variants remains to be determined. CRISPR/Cas9 allows for the introduction and/or correction of a certain variant in induced pluripotent stem cells (iPSCs). The resulting isogenic iPSC lines can be differentiated into cardiomyocytes and used as a platform to assess the pathogenicity of the variant.

Generation of iPSCs from a Patient with the M694V Mutation in the Gene Associated with Familial Mediterranean Fever and Their Differentiation into Macrophages.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear.

A Knockout of Poly(ADP-Ribose) Polymerase 1 in a Human Cell Line: An Influence on Base Excision Repair Reactions in Cellular Extracts.

Base excision repair (BER) is the predominant pathway for the removal of most forms of hydrolytic, oxidative, and alkylative DNA lesions. The precise functioning of BER is achieved via the regulation of each step by regulatory/accessory proteins, with the most important of them being poly(ADP-ribose) polymerase 1 (PARP1). PARP1's regulatory functions extend to many cellular processes including the regulation of mRNA stability and decay.

iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.

Defects in the low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. LDLR deficiency in hepatocytes leads to elevated blood cholesterol levels, which damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully understood.

Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.

The spectrum of neurodegenerative diseases known today is quite extensive. The complexities of their research and treatment lie not only in their diversity. Even many years of struggle and narrowly focused research on common pathologies such as Alzheimer's, Parkinson's, and other brain diseases have not brought cures for these illnesses.

Usnic Acid Derivatives Inhibit DNA Repair Enzymes Tyrosyl-DNA Phosphodiesterases 1 and 2 and Act as Potential Anticancer Agents.

Tyrosyl-DNA phosphodiesterase 1 and 2 (Tdp1 and Tdp2) are DNA repair enzymes that repair DNA damage caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reason for resistance to such widely used drugs such as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid.

Generation of three induced pluripotent stem cell lines (RAUi001-A, RAUi001-B and RAUi001-C) from peripheral blood mononuclear cells of a healthy Armenian individual.

The study of pathological processes in cells carrying mutations should be carried out in comparison with a healthy control group. Familial Mediterranean fever (FMF), which is caused by a mutation in the MEFV gene, is predominantly found in people of Armenian nationality with the prevalence of 14-100 per 10000. We have obtained induced pluripotent stem cells (iPSCs) from Armenian healthy patient, which will be included as a control group in the study of this disease.

Calling and Phasing of Single-Nucleotide and Structural Variants of the Gene Using Oxford Nanopore MinION.

The locus has clinical significance for lipid metabolism, Mendelian familial hypercholesterolemia (FH), and common lipid metabolism-related diseases (coronary artery disease and Alzheimer's disease), but its intronic and structural variants are underinvestigated. The aim of this study was to design and validate a method for nearly complete sequencing of the gene using long-read Oxford Nanopore sequencing technology (ONT). Five PCR amplicons from of three patients with compound heterozygous FH were analyzed.

PARP1 Gene Knockout Suppresses Expression of DNA Base Excision Repair Genes.

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common "hubs" for binding BER proteins, has changed the most.

Constitutive heterochromatin propagation contributes to the X chromosome inactivation.

Imprinted X chromosome inactivation (iXCI) balances the expression of X-linked genes in preimplantation embryos and extraembryonic tissues in rodents. Long noncoding Xist RNA drives iXCI, silencing genes and recruiting Xist-dependent chromatin repressors. Some domains on the inactive X chromosome include repressive modifications specific to constitutive heterochromatin, which show no direct link to Xist RNA.

Generation of induced pluripotent stem cell line, ICGi033-A, by reprogramming peripheral blood mononuclear cells from a patient with Huntington's disease.

Huntington's disease (HD) is a hereditary autosomal dominant neurodegenerative disease caused by the polyglutamine stretch expansion in the huntingtin (HTT) protein. In HD, dysregulation of multiple cellular processes occurs, resulting in the death of medium spiny neurons of striatum. A line of induced pluripotent stem cells (iPSCs) ICGi033-A was obtained from peripheral blood mononuclear cells of a patient carrying 77 CAG repeats in the HTT gene.

Mitomycin-Treated Endothelial and Smooth Muscle Cells Suitable for Safe Tissue Engineering Approaches.

In our previous study, we showed that discarded cardiac tissue from the right atrial appendage and right ventricular myocardium is an available source of functional endothelial and smooth muscle cells for regenerative medicine and tissue engineering. In the study, we aimed to find out what benefits are given by vascular cells from cardiac explants used for seeding on vascular patches engrafted to repair vascular defects . Additionally, to make the application of these cells safer in regenerative medicine we tested an approach that arrested mitotic division to avoid the potential tumorigenic effect of dividing cells.

Induced pluripotent stem cell line ICGi037-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to heterozygous p.Trp443Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder increasing premature cardiovascular diseases risk due to atherosclerosis. Pathogenic mutations in the LDLR gene cause most FH cases. Available treatments are effective not for all LDLR mutations.

Induced pluripotent stem cell line ICGi038-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to compound heterozygous c.1246C > T/c.940 + 3_940 + 6del mutations in LDLR.

The development of cellular models for familial hypercholesterolemia (FH) is an important direction for creating new approaches to atherosclerosis treatment. Pathogenic mutations in the LDLR gene are the main FH source. We generated an iPSC line from peripheral blood mononuclear cells of the patient with compound heterozygous c.

Generation of induced pluripotent stem cell line, ICGi034-A, by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease associated with GBA mutation.

Mutation in the glucocerebrosidase encoding gene (GBA) is one of the most frequent genetic cause of Parkinson's disease. ICGi034-A induced pluripotent stem cell (iPSC) line obtained by reprogramming peripheral blood mononuclear cells (PBMCs) of a patient with heterozygous c.1226A > G (p.

Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is a monogenic disease, leading to atherosclerosis due to a high level of low-density lipoprotein cholesterol. Most cases of the disease are based on pathological variants in the LDLR gene. Hepatocyte-like and endothelial cells derived from individual iPSCs are a good model for developing new approaches to therapy.

Identification of specific gene methylation patterns during motor neuron differentiation from spinal muscular atrophy patient-derived iPSC.

Spinal muscular atrophy is a progressive motor neuron disorder caused by deletions or point mutations in the SMN1 gene. It is not known why motor neurons are particularly sensitive to a decrease in SMN protein levels and what factors besides SMN2 underlie the high clinical heterogeneity of the disease. Here we studied the methylation patterns of genes on sequential stages of motor neuron differentiation from induced pluripotent stem cells derived from the patients with SMA type I and II.

Genetically Encoded Fluorescent Biosensors for Biomedical Applications.

One of the challenges of modern biology and medicine is to visualize biomolecules in their natural environment, in real-time and in a non-invasive fashion, so as to gain insight into their physiological behavior and highlight alterations in pathological settings, which will enable to devise appropriate therapeutic strategies. Genetically encoded fluorescent biosensors constitute a class of imaging agents that enable visualization of biological processes and events directly in situ, preserving the native biological context and providing detailed insight into their localization and dynamics in cells. Real-time monitoring of drug action in a specific cellular compartment, organ, or tissue type; the ability to screen at the single-cell resolution; and the elimination of false-positive results caused by low drug bioavailability that is not detected by in vitro testing methods are a few of the obvious benefits of using genetically encoded fluorescent biosensors in drug screening.