Statins or 3-hydroxy-3-methylglutaryl coenzyme A inhibitors are a class of cholester-ol-lowering drugs that are widely used in clinical practice for primary and secondary prevention of cardiovascular and cerebrovascular diseases associated with atherosclerosis. In recent years, there has been an increase in scientific and clinical interest in studying the relationship between statins and non-regulating ribonucleic acids circulating in the systemic bloodstream, known as circulating microRNAs. On the one hand, microRNAs play a crucial role in regulating the ex-pression of genes associated with the therapeutic response to statins, including the expression of key isoenzymes of statin metabolism in the liver, as well as directly and indirectly regulate the metabolism of high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). On the other hand, statins can affect the expression levels of specific microRNAs circulating in the systemic bloodstream and affecting the epigenetic mecha-nisms regulating the expression of genes encoding key pathways of atherogenesis. This narrative review provides an update on the understanding of microRNAs' role as epigenetic regulators of interindividual differences in the therapeutic response to statins, as well as their potential as next-generation lipid-lowering medications in the long run. The influence of statins on altering the expression of microRNAs involved in various mechanisms of atherogenesis is also high-lighted.

The ABCB1 transporter protein (also known as P-glycoprotein, P-gp) plays a crucial role in the pharmacokinetics of antipsychotics (APs), determining their bioavailability and distribution in the body. The ABCB1 genetic polymorphisms significantly contributes to interindividual dif-ferences in response to AP therapy in patients with schizophrenia spectrum disorders (SSDs). Increased P-gp functional activity is associated with the development of pseudoresistance to APs, while decreased activity is linked to the development of AP-induced adverse drug reactions. This review aims to systematize current data on the population frequencies of ABCB1 gene allelic variants that influence the activity of P-gp and to establish a scientific foundation for the devel-opment of domestic, ethnically-oriented pharmacogenetic diagnostic test systems. A search was conducted in the databases PubMed, eLIBRARY.RU, Google Scholar, PharmGKB, DrugBank, the Geography of Genetic Variants Browser, ClinVar, dbSNP, SNPedia, Drugs@FDA, Russian State Register of Medicines, the Database of Population Frequencies of Genetic Variants in the Russian Population, the RUSeq Browser, The Rubricator of Clinical Recommendations. Available data on the population frequencies of the most extensively studied high-function (n = 5), low-function (n = 15), and loss-of-function (n = 5) allelic variants of the ABCB1 gene were retrieved and analyzed. The frequency of variant alleles of the ABCB1 gene is heterogeneous across different global populations, a critical factor to consider in the development of pharmacogenetic diagnostic test systems. The ethno-territorial heterogeneity of the Russian gene pool necessitates the develop-ment and subsequent validation of local (region-specific) pharmacogenetic diagnostic test sys-tems, based on large-scale population studies conducted within specific administrative-territorial units.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multi-system disorder whose pathogenesis is associated with metabolic and immune dysfunction. Dysfunction of cholesterol metabolism and vitamin D deficiency are considered potential path-ogenic factors. The DHCR7 gene, encoding 7-dehydrocholesterol reductase, catalyzes the final step in cholesterol biosynthesis and simultaneously determines the availability of provitamin D. Pathogenic DHCR7 mutations, leading to the development of Smith-Lemli-Opitz syndrome (SLOS) in the homozygous state, are characterized by a high prevalence in the population as heterozygous carriers (~1%). Therefore, it was hypothesized that heterozygous carriage of DHCR7 mutations may be associated with an increased predisposition to the development of ME/CFS. Materials and Methods: We used open-source genetic data from the DecodeME project (n = 15,579 ME/CFS patients, 259,909 controls). We analyzed the frequency of 11 pathogenic DHCR7 mutations: IVS8-1G>C, W151X, T93M, V326L, R404C, R352W, E448K, R352Q, G410S, R242C, and F302L. The association with the ME/CFS phenotype was assessed using a χ² test in six datasets (the overall sample (gwas_1), subsamples of men (gwas_1_male), women (gwas_1_female), spontaneous CFS development (gwas_1_non-infectious_onset), CFS development with infectious onset (gwas_1_infectious_onset), and a subsample with a 1:10 patient: control ratio (gwas_2)). Results. Only the IVS8-1G>C mutation was detected in the DecodeME data (carrier frequency ~1%). A statistically significant association (p-value ≈ 0.013) was observed in only one subsample (gwas_2) but was not replicated in the others. The remaining mutations were not detected in the DecodeME data. Conclusions. The obtained results do not support the hypothesis of a link be-tween carriage of SLOS-inducing DHCR7 mutations and ME/CFS. This negative result is im-portant for the correct refinement of metabolic hypotheses regarding pathogenesis and the pri-oritization of research areas. Further study of sterol metabolism and metabolomic biomarkers in patient subgroups is recommended.

Bipolar disorder (BD) is associated with elevated cardiometabolic morbidity and mortality, partly mediated by systemic inflammation. Sex differences in immune function and metabolic regulation are well-established, yet their impact on inflammation-related metabolic risk during pharmacotherapy remains understudied. Objective: To examine sex-specific associations between peripheral inflammatory indices and individual components of metabolic syndrome in patients with BD, testing the hypothesis that immuno-metabolic patterns differ between men and women. Materials and Methods: In this retrospective cross-sectional study 102 patients with BD (41 men, 61 women) were included. We assessed associations between inflammatory markers—including absolute cell counts, derived hematological ratios, and composite indices based on high-density lipoprotein cholesterol (HDL-C)—and individual components of metabolic syndrome (hyperglycemia, low HDL-C, hypertriglyceridemia, increased waist circumference). Results: Sex-specific patterns emerged: men with hyperglycemia demonstrated elevated neutrophil-to-lymphocyte ratio (p = 0.014) and absolute neutrophil counts (p-value = 0.044); men with hypertriglyceridemia exhibited elevated absolute lymphocytes (p-value = 0.010) and white blood cells (p-value = 0.031). In women, low HDL-C was associated with elevated neutrophil-to-HDL-C ratio (p-value = 0.031) and platelet-to-HDL-C ratio     (p-value = 0.009); hypertriglyceridemia with elevated neutrophil-to-HDL-C ratio (p-value = 0.042) and lymphocyte-to-HDL-C ratio (p-value = 0.027). No associations were found for cellular inflammatory markers in women, nor for increased waist circumference in either sex. Conclusions: Inflammation-metabolism relationships in BD are sex-specific: men exhibit cellular inflammatory markers linked to glucose and triglyceride dysregulation, while women show lipid-dependent inflammatory indices associated with HDL-C and triglyceride abnormalities. These preliminary findings suggest that risk stratification and metabolic monitoring during BD pharmacotherapy may benefit from sex-specific approaches, though replication in prospective cohorts is required before clinical translation.

Despite the documented efficacy and widespread clinical application of lidase magnetophoresis (LMP) and endonasal retinalamin electrophoresis (ERE) in Russia for the management of retinal vein occlusion (RVO), the synergistic potential of these methods remains insufficiently studied in current literature. Purpose: To evaluate the efficacy of LMP and ERE combined with intravitreal ranibizumab for the management of non-ischemic superior temporal RVO by analyzing longitudinal changes in central retinal thickness and total macular volume immediately post-treatment and at a three-month follow-up. Materials and Methods: In this retrospective, single-center, three-arm cohort study, we analyzed the clinical records of patients with non-ischemic superior temporal RVO who underwent LMP and ERE in combination with anti-VEGF therapy. In the final analysis were included 71 patients who underwent anti-VEGF monotherapy (control group). Additional to anti-VEGF therapy 71 patients passed LMP (LMP group) and 72 patients completed LMP and ERE (LMP + ERE group). Central retinal thickness and total macular volume were measured using optical coherence tomography at baseline, at one- and three-months post-treatment, and at the end of the follow-up period. Best-corrected visual acuity was evaluated at the same intervals. Results: A comparative analysis with anti-VEGF monotherapy revealed that combined application of ERE and LMP offers superior efficacy in reducing central retinal thickness by an additional 12.2% (t = 4.21, p-value = 0.0001, Cohen's d = 0.72) and total macular volume by 13.3% (t = 4.31, p-value = 0.0001, Cohen's d = 0.76) and in im-proving visual function by 66.7 (t = 30.2, p-value = 0.0001, Cohen's d = 6.5). Conclusions: Innovative complex use of ERE and LMP in the second month after the start of treatment with intravitreal anti-VEGF therapy enhances the protective and regenerative effect of anti-VEGF therapy. Application of this method leads to a more rapid reduction in central retinal thickness and total macular volume, which is critical for preventing permanent vision loss, scotoma, and optic nerve atrophy in patients following RVO.