MiRNA-34a, miRNA-145, and miRNA-222 Expression, Matrix Metalloproteinases, TNF-α and VEGF in Patients with Different Phenotypes of Coronary Artery Disease.

The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers).

MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease.

Unlabelled: MicroRNAs and the WNT signaling cascade regulate the pathogenetic mechanisms of atherosclerotic coronary artery disease (CAD) development.

Objective: To evaluate the expression of microRNAs (miR-21a, miR-145, and miR-221) and the role of the WNT signaling cascade (WNT1, WNT3a, WNT4, and WNT5a) in obstructive CAD and ischemia with no obstructive coronary arteries (INOCA).

Method: The cross-sectional observational study comprised 94 subjects.

Chromosomal Instability in Gastric Cancer: Role in Tumor Development, Progression, and Therapy.

According to the Cancer Genome Atlas (TCGA), gastric cancers are classified into four molecular subtypes: Epstein-Barr virus-positive (EBV+), tumors with microsatellite instability (MSI), tumors with chromosomal instability (CIN), and genomically stable (GS) tumors. However, the gastric cancer (GC) with chromosomal instability remains insufficiently described and does not have effective markers for molecular and histological verification and diagnosis. The CIN subtype of GC is characterized by chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells.

Genetic markers associated with adverse reactions of radioiodine therapy in thyroid cancer patients.

Objectives: Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes of DNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients.

Methods: The study included 181 patients (37 men, 144 women; median age 56 [41; 66.

Genetic markers associated with adverse reactions of radioiodine therapy in thyroid cancer patients.

Objectives: Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes of DNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients.

Methods: The study included 181 patients (37 men, 144 women; median age 56 [41; 66.

Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions.

Chromatin remodeling is the one of the main epigenetic mechanisms of gene expression regulation both in normal cells and in pathological conditions. In recent years, a growing number of investigations have confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. Genes encoding protein subunits of chromatin remodeling complexes are often mutated and change their expression in diseases, as well as non-coding RNAs (ncRNAs).

The ANKK1/DRD2 gene TaqIA polymorphism (rs1800497) is associated with the severity of extrapyramidal side effects of haloperidol treatment in CYP2D6 extensive metabolizers with schizophrenia spectrum disorders.

Objectives: Extrapyramidal symptoms (EPS) are one of the most prominent side effects of haloperidol. Variability of EPS severity may be associated with the genetic factors, affecting both haloperidol pharmacokinetics (e.g.

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis.

In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers.

Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of , , , , , , and ; and by RT-PCR for HLA-DRB1 and HLA-B.

MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring.

Objectives: The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation.

Methods: The study involved 57 patients with median (ME) age 87 years [80-94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations.

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance.

Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown.

Parental Origin of the Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma.

Our aim was to identify alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an mutation affects its phenotypic expression. By NGS and MLPA, mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an mutation.

Mutations in Epigenetic Regulation Genes in Gastric Cancer.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority ( = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority ( = 41), in histone modifier genes, among which mutations were most commonly found in and .

MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring.

Objectives: The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation.

Methods: The study involved 57 patients with median (ME) age 87 years [80-94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations.

Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder.

Background: Previous studies have shown that cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of fluvoxamine, the activity of which is highly dependent, inter alia, on the polymorphism of the gene encoding it. The objective of our study was to investigate the effect of 1846G>A polymorphism of the CYP2D6 gene on the efficacy and safety of fluvoxamine, using findings on CYP2D6 enzymatic activity and on CYP2D6 expression level in patients with depressive disorders comorbid with alcohol use disorder.

Study Question: Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder.

Methylation and Noncoding RNAs in Gastric Cancer: Everything Is Connected.

Despite recent progress, gastric cancer remains one of the most common cancers and has a high mortality rate worldwide. Aberrant DNA methylation pattern and deregulation of noncoding RNA expression appear in the early stages of gastric cancer. Numerous investigations have confirmed their significant role in gastric cancer tumorigenesis and their high potential as diagnostic and prognostic biomarkers.

Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells.

Exosomes are the small vesicles that are secreted by different types of normal and tumour cells and can incorporate and transfer their cargo to the recipient cells. The main goal of the present work was to study the tumour exosomes' ability to accumulate the parent mutant DNA or RNA transcripts with their following transfer to the surrounding cells. The experiments were performed on the MCF7 breast cancer cells that are characterized by the unique coding mutation in the gene.

Analysis of miRNA Expression in Patients with Rheumatoid Arthritis during Olokizumab Treatment.

Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide. Epigenetic alternations of microRNAs (miRNAs) can contribute to its pathogenesis and progression. As the first line therapy with DMARDs is not always successful, other drugs and therapeutic targets should be applied.

Upregulation of Akt/Raptor signaling is associated with rapamycin resistance of breast cancer cells.

mTOR inhibitors are considered today to be one of the most promising anticancer drugs. Here to study the mechanism of the acquired resistance of MCF-7 breast cancer cells to mTOR inhibitors two different models of the cell resistance were used: rapamycin-resistant MCF-7/Rap subline developed under long-term rapamycin treatment, and metformin-resistant MCF-7/M subline obtained by long-term metformin treatment. We have found that both resistant sublines were characterized by common features: increased expression of mTOR-interacting Raptor protein, increased phosphorylation of Akt, and activation of growth-related transcriptional factor AP-1.

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response.

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors.

Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing.

Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel.

Epigenetic Changes in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world's population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors.

Roles of E-cadherin and Noncoding RNAs in the Epithelial-mesenchymal Transition and Progression in Gastric Cancer.

The epithelial-mesenchymal transition (EMT) is thought to be at the root of invasive and metastatic cancer cell spreading. E-cadherin is an important player in this process, which forms the structures that establish and maintain cell-cell interactions. A partial or complete loss of E-cadherin expression in the EMT is presumably mediated by mechanisms that block the expression of E-cadherin regulators and involve the E-cadherin-associated transcription factors.