There is still much to learn about the epigenetic mechanisms controlling gene expression during carcinogenesis. When researching aberrant DNA methylation, active proliferative tumor cells from head and neck squamous cell cancer (HNSCC) can be used as a model. The aim of the study was to investigate the methylation status of CDKN1, CDKN2A, MYC, Smad3, SP1, and UBC genes in tumor tissue (control-normal tissue) in 50 patients (37 men and 13 women) with HPV-negative HNSCC. Methods: Bisulfite conversion methods and methyl-sensitive analysis of high-resolution melting curves were used to quantify the methylation of genes. In all patients and across various subgroups (tongue carcinoma, laryngeal and other types of carcinomas T2, T3, T4 status; age before and after 50 years; smoking and non-smoking), there are consistent differences in the methylation levels in the SP1 gene in tumor DNA compared to normal. Results: The methylation of the SP1 gene in tumor DNA suppresses its expression, hinders HNSCC cell proliferation regulation, and could be a molecular indicator of malignant cell growth. The study of DNA methylation of various genes involved in carcinogenesis is promising because hypermethylated promoters can serve as potential biomarkers of disease.

Background: Arterial hypertension (AH) and insulin-dependent diabetes mellitus (DM) are major comorbid risk factors for accelerated myocardial damage, yet the behavior of key stress-adaptive heat shock proteins HSP70 and HSP90 under combined stress remains unclear. This study aimed to characterize the expression profiles of HSP70 and HSP90 in left ventricular cardiomyocytes during isolated and comorbid AH and DM, and to evaluate their association with structural remodeling and expansion of interstitial elements. Methods: The study was conducted in accordance with the European Convention for the Protection of Vertebrate Animals (ethical approval No. 26, RUDN Institute of Medicine, 18 February 2021) on 25 male rats divided into five groups (n = 5 each): control—38-week-old Wistar–Kyoto (WKY) rats; AH—38-week-old spontaneously hypertensive rats (SHR); long-term AH—57-week-old SHR; DM—38-week-old WKY rats with streptozotocin-induced insulin-dependent DM (65 mg/kg, i.p.); AH+DM—38-week-old SHR with STZ-induced DM. After 30 days of DM, left ventricular (LV) tissue was analyzed by immunohistochemistry (IHC) for HSP70/HSP90 protein expression and by RT-qPCR for mRNA levels. Increased stromal elements in myocardium were quantified morphometrically as interstitial stromal volume fraction (%) on hematoxylin and eosin-stained sections. Results: HSP90 was significantly upregulated in all pathological groups. The most pronounced increase occurred in isolated DM, with a 4.0-fold rise in HSP90-positive area (21.80% vs. 5.45% in control) and a 1.82-fold increase in mRNA. In the AH+DM group, HSP90 mRNA expression was extremely elevated (25.93-fold), accompanied by a 3.7-fold increase in protein. In contrast, HSP70 protein was elevated only in the 38-week AH group (27.68% vs. 19.70% control, p ≤ 0.05), remained unchanged in isolated DM (19.50%), and was significantly reduced in AH+DM (14.71%, p ≤ 0.05), despite a modest 1.64-fold mRNA upregulation in DM. Morphometric analysis revealed progressive expansion of interstitial elements, most severe in AH+DM (9.43% stromal volume vs. 4.81% in control, p ≤ 0.05). Conclusions: Comorbid AH and DM provoke synergistic HSP90 upregulation, while HSP70 expression is markedly suppressed, indicating a shift from an adaptive to a maladaptive cellular-stress response. The imbalance between HSP90 and HSP70 may represent a key molecular mechanism underlying accelerated structural and functional deterioration of the myocardium in cardiometabolic comorbidity.

Head and neck squamous cell carcinoma (HNSCC) takes the sixth place among the most common cancers in the world. Abnormal methylation can be one of the reasons for this cancer. The aim of this study was to investigate the DNA promotor methylation status of cancer-associated genes (ATM, APC, CDO1, RB1, TP53, WIF1) in patients with HNSCC. Bisulfite Conversion and Methylation-Sensitive High-Resolution Melting was used for analysis of the DNA methylation level of normal and tumor tissues in 44 patients. There were significant differences in DNA methylation level between patient’s tumor and normal tissues for CDO1 and WIF1 genes in all subjects and subgroups (p<0.05). In T3 subgroup there was significant correlation between CDO1 gene methylation and age in the normal tissue. The same correlation was detected also for the WIF1 gene methylation in tumor tissue samples in the subgroup with T3 and in normal tissue samples in the subgroup with T4 (p<0,05). In all genes no significant differences were found between the subgroups (T2, T3, T4 stage, primary/recurrent lesion, non-keratinizing/keratinizing SCC, age before/ after 50, smokers/non-smokers) of the patients. Thus, changes in the expression of the CDO1 and WIF1 genes can affect mechanisms of the occurrence and development of HNSCC.

Relevance. Familial hypercholesterolemia (FH) is a monogenic hereditary disorder characterized by impaired lipid metabolism. The prevalence of FH in the general population averages 0.32% (95% CI: 0.26-0.39%). The disease can have both autosomal dominant and autosomal recessive inheritance patterns. Eight FH phenotypes associated with mutations in the LDLRAP1, PCSK9, APOA2, APOB, GHR, GSBS, EPHX2, and LDLR genes are known, which can lead to early manifestation of the pathology. The aim of this review is to comprehensively analyze current literature data on the molecular genetics, biological, and psychological aspects of FH. Analysis of signaling pathways in FH revealed three clusters of genes and their encoded proteins responsible for the following processes: assembly, remodeling, and clearance of plasma lipoproteins (genes: LDLR, LDLRAP1, VLDLR, NPC1L1, APOC1, LPA, CETP, MTTP, APOB, PCSK9); cholesterol metabolism (gene: PPP1R17);regulation of plasma lipoprotein particle levels (gene: ANGPTL3). The proteins PCSK9, APOB, and MTTP were identified as key elements (central hubs) of these metabolic networks. The PPP1R17 protein is involved in the mechanisms of long-term depression, a form of synaptic plasticity. Furthermore, the literature describes an association of FH with five other genes: ABCG5, ABCG8, STAP1, CYP7A1, LIPA, and PNPLA5. Conclusion. Thus, for the early diagnosis and effective management of patients with FH, it is necessary to consider not only the expanded spectrum of associated genes and proteins but also the psychological state of patients, particularly their levels of anxiety, depression, and stress.

Background. The pandemic of coronavirus disease COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the performing of current medical activities throughout the world in XXI. Infection with SARS-CoV-2 has systemic damages to lungs, heart, and kidney, nervous and reproductive systems. Many published studies to date have pointed out that COVID-19 could also affect fertility and disrupt the functions of the reproductive system. Main content. This literature review presents current scientific data on the short-term and potential long-term consequences of COVID-19 on male fertility, including an analysis of the reversibility of impairments and the risk of infertility. The possible impairment of the male reproductive system is because angiotensin-converting enzyme 2 (ACE2) receptors are in an increased number in the testes, seminiferous duct cells, spermatogonia, Leydig cells and Sertoli cells. COVID-19 infection affects sperm quality, DNA fragmentation index (DFI) and hormonal status. Conclusion. The numerous scientific data confirm the impairment of spermatogenesis during the Covid-19 infection. The timing and extent of reproductive function recovery after infection in the long-term period remain unknown. The uncertainty of long-term consequences, amid a global trend of declining spermatogenesis, underscores the high clinical and social significance of this problem.

We thank the commentators for their thoughtful and constructive review of our work