Current issue

Gastric cancer (GC) is one of the leading causes of cancer death in the world (http://globocan.iarc.fr). In the Russian Federation, cancer of this localization ranks sixth among all malignant tumors in terms of incidence and second in mortality. Our study used a sample consisting of DNA samples isolated from the peripheral venous blood of patients with gastric cancer and healthy donors aged 21 to 88 years living in the Republic of Bashkortostan. The group of patients consisted of 156 people. As a control, a group of unrelated healthy donors without any gastrointestinal diseases was studied, consisting of 307 people of various ethnicities also living in the Republic of Bashkortostan. One of the promising areas is the study of mitochondrial dysfunction as a consequence of changes in energy metabolism, which are one of the signs of malignancy (Lee et al., 2014). In our study, we screened for known mutations of mtDNA molecules in patients with gastric cancer. The results of our studies show that all three loci we examined - a 4977 bp deletion located in the 8483-13459 mtDNA region, single nucleotide substitutions 15767 C>G in the CYB gene and 7080 T>C in the COI gene - most likely do not play a role as driver events in the occurrence of gastric cancer in individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan.

Aging is a natural and inevitable process that worsens the quality of life and shortens its duration. In the process of aging, the cardiovascular system undergoes significant restructuring, diastolic dysfunction is observed, vascular stiffness increases and vasodilation decreases. α₂-ARs are widely distributed in the body and are involved in the regulation of heart and vascular functions. In pathological conditions, there is an increase in the expression of α₂-AR subtypes, a violation of their functions, and a decrease in the effectiveness of the associated signalling cascades. The study aimed to investigate the effect of the α₂-AR agonist clonidine hydrochloride at concentrations of 10^-9-10^-6 M on the inotropy, chronotropy and coronary flow of the old rats isolated heart. α₂-AR stimulation changes all the studied parameters of the old rats isolated heart. The force of left the ventricular myocardium contraction decreases at concentrations of 10^-9 and 10^-8 M, and increases at concentrations of 10^-7 and 10^-6 M. The α₂-AR agonist causes a decrease in heart rate in all studied concentrations. Stimulation of α₂-AR in lower concentrations (10^-9 - 10^-7 M) reduces coronary flow, and the maximum concentration of clonidine hydrochloride (10^-6 M) increases.

The study examined the possibility of using vesicular mRNA for diagnostic purposes using real-time PCR as a tool for analyzing the stage of development of changes in the body in response to prolonged alcohol intake. The study simulated the intermittent nature of prolonged alcohol consumption in Wistar rats, which reflects the pattern of alcohol consumption typical of individuals who abuse alcohol. Extracellular vesicles were isolated from the blood plasma of rats using differential ultracentrifugation. Their presence was confirmed by scanning electron microscopy. Total RNA extraction, cDNA synthesis, and real-time PCR were performed using commercial reagent kits.  The study revealed elevated levels of several pro-inflammatory mRNAs in extracellular vesicles isolated from blood plasma. In the group of animals with prolonged alcoholization, the levels of Tnfα mRNA were increased, and the presence of Hmgb1 mRNA was confirmed. In the conditions of the cancellation of long-term alcoholization, on the 10th day, an increased level of pro-inflammatory mRNA Tnfα and Il1β were revealed and the content of mRNA Hmgb1 was again found. The obtained data show the diagnostic value of vesicular mRNA and open the prospect for subsequent research in this direction.

Breast cancer (BC) remains one of the leading causes of cancer-related mortality in women worldwide. Recent studies have explored the role of myokines, signaling proteins released during muscle contraction, in regulating tumor growth, metastasis, and the tumor microenvironment. This study investigates the correlation between myokines and breast cancer progression, focusing on the role of irisin and decorin. The study was conducted at two oncology centers in Baghdad, Iraq, from May to December 2022. A total of 88 Iraqi women, aged 20-70, were enrolled in the study across six groups: healthy controls (G1) and women with different treatment regimens (G2-G6). Blood samples were collected after fasting, and myokine concentrations were measured using ELISA. Additionally, histopathological examinations were performed on tissue biopsies to assess the presence of lobular carcinoma in situ (LCIS). The study found significant differences in myokine concentrations across the groups. Irisin levels were highest in the metastatic group (G6), while decorin levels showed significant variations across the different patient groups. Histological analysis revealed characteristic changes of LCIS, including irregular lobular structures, hyperplasia, and inflammatory cell infiltration. This study highlights the potential role of myokines, particularly irisin and decorin, as biomarkers for breast cancer progression. Elevated irisin levels in advanced stages suggest its involvement in tumor development and metastasis.

Familial hypercholesterolemia (FH) is a prevalent inherited lipid disorder marked by elevated low-density lipoprotein cholesterol (LDL-C) from early life, significantly increasing the risk of premature atherosclerotic cardiovascular disease (ASCVD). Recent advances in pharmacotherapy have transformed treatment possibilities, particularly for patients unresponsive to traditional therapies. This review synthesizes current evidence on emerging lipid-lowering agents, including PCSK9 monoclonal antibodies (e.g., evolocumab), small interfering RNA-based therapies (e.g., inclisiran), and angiopoietin-like protein 3 (ANGPTL3) inhibitors (e.g., evinacumab). Clinical trials demonstrate that these agents achieve substantial LDL-C reductions – often exceeding 40% – with favorable safety profiles, even in homozygous FH patients with null LDL receptor activity. Additionally, advances in genomic research have enabled more precise classification of pathogenic variants in genes such as APOB and ANGPTL3, improving diagnostic accuracy and guiding targeted therapy. The integration of these pharmacologic and genetic strategies represents a significant shift toward individualized management of FH. Further long-term and population-based studies are needed to validate these approaches and ensure equitable access across healthcare settings.