Background: Ulcerative colitis (UC) is an idiopathic and heterogeneous large intestine disease, characterized by chronic mucosa and submucosa inflammation. Alteration of the intestinal microbiome in UC may be responsible for modifications in metabolite production. Aim: To investigate the microbiota status and trimethylamine-N-oxide (TMAO) metabolite levels in patients with UC according to clinical and endoscopic activity. Methods: As part of a grant project AP14871959 from September 2022 to October 2023, 31 patients with UC and 15 healthy volunteers over 18 years at the Clinic of NCJSC “KMU” were assessed for blood TMAO level and metagenomic sequencing of fecal microbiome. Results: A significant depletion of the main representatives of Bacteroides, Parabacteroides, Prevotella; and an increase in the relative abundance of the genera Actinomyces, Klebsiella, Limosilactobacillus, Streptococcus, Escherichia-Shigella were detected in patients with UC. The number of p_Actinobacteria (g_Collinsella) and p_Eubacterium (g_Xylanophilum) representatives with genes encoding TMA-trimethylamine conversion is significantly reduced in UC patients. TMAO levels were significantly lower in UC patients than in healthy individuals (0.233 µmol/L, p = 0.004). TMAO decreased with disease severity and significantly differed between patients with different activities (p = 0.034). Conclusions: The composition of the intestinal microbiome changes and the level of TMAO decreases in patients with UC at different activities.

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.

Lagged Poincaré plots have been successful in characterizing abnormal cardiac function. However, the current research practices do not favour any specific lag of Poincaré plots, thus complicating the comparison of results of different researchers in their analysis of heart rate of healthy subjects and patients. We researched the informative nature of lagged Poincaré plots in different states of the autonomic nervous system. It was tested in three models: different age groups, groups with different balance of autonomous regulation, and in hypertensive patients. Correlation analysis shows that for lag l = 6, SD1/SD2 has weak (r = 0.33) correlation with linear parameters of heart rate variability (HRV). For l more than 6 it displays even less correlation with linear parameters, but the changes in SD1/SD2 become statistically insignificant. Secondly, surrogate data tests show that the real SD1/SD2 is statistically different from its surrogate value and the conclusion could be made that the heart rhythm has nonlinear properties. Thirdly, the three models showed that for different functional states of the autonomic nervous system (ANS), SD1/SD2 ratio varied only for lags l = 5 and 6. All of this allow to us to give cautious recommendation to use SD1/SD2 with lags 5 and 6 as a nonlinear characteristic of HRV. The received data could be used as the basis for continuing the research in standardisation of nonlinear analytic methods.

Background. Given the high rates of morbidity and mortality from cardiovascular disease (CVD), the primary and secondary CVD prevention is one of the public health priority. Inflammation and endothelial dysfunction are the major drivers of atherosclerosis development and progression. In this regard, the study of the biomarker application as a tool to better identify high-risk individuals is an up-to-date sector of modern cardiology. The simultaneous measurement of multiple biomarkers can increase the risk stratification for people who are not known to have cardiovascular events in their history. The study aimed to investigate the predictive value of chemokine (C-X-C motif) ligand 16 (CXCL16), endocan, and heart-type fatty acid binding protein (H-FABP) in the cardiovascular event development in people who are not known to have cardiovascular events in their history. Method. We examined 363 people aged 30 to 65 who have been living permanently in the city of Saran, Karaganda region. The selected participants were people registered at a clinic at the city of Saran, who were screened between August and September 2014. Results. The follow-up period was 48 months (from August-September 2014 to November 2018). The results showed that CXCL16 (p<0.001), endocan (p<0.001), and H-FABP (p=0.002) biomarker levels are significantly higher in outcome groups compared with those of the no-outcome group. Univariate regression analysis proved the prognostic significance of all biomarkers in cardiovascular events development. The multivariate regression analysis after the adjustment confirmed that the CXCL16 increase was associated with the “composite endpoint” (CE) development (p<0.001) while the endocan increased due to the development of major cardiovascular events (MACE) (p=0.008); we did not find the association of the risks of event development with the H-FABP level increase (p=0.83).

Crohn’s disease (CD) is a multifactorial inflammatory bowel disease whose pathogenetic mechanisms are a field of ongoing study. Changes in the intestinal microbiome in CD may influence metabolite production and reflect the disease’s severity. We investigate the relationship between trimethylamine N-oxide (TMAO) and lipopolysaccharide-binding protein (LPS) levels and changes in the gut microbiome in patients with CD of various degrees of activity. Methods: In total, 29 CD patients and 15 healthy individuals were investigated for their levels of TMAO by HPLC-MS, and LPS protein by ELISA and metagenomic 16 s-sequencing of feces was performed. Results: We found significant differences in TMAO levels in patients in the remission/mild and moderate/severe groups compared to the control group (p = 0.02 and p = 0.014), changes in alpha diversity with the Shannon index (p = 0. 0151 and p = 0.0018) and in beta diversity (ANOSIM p = 0.009 and PERMANOVA p = 0.005) in both groups compared to controls. Strongly positive correlations in TMAO levels and mixed correlations of LPS with alpha diversity metrics were found, as well as significant correlations with microbiota species. Conclusions: Changes in the level of metabolites may reflect specific disturbances in the composition of the intestinal microbiome at different degrees of severity of CD.

Aim: The study aimed to investigate the potential association of 1,5-AG and cardiovascular events in patients with type 2 diabetes mellitus. Methods: The study was an observational non-matched case-control study. The study included 114 patients with type 2 diabetes mellitus; 42 were with STEMI (STEMI group) and 72 without STEMI (non-STEMI group). Clinical data, fasting blood glucose, HbA1c, and 1,5 Anhydro-D-glucitol were analyzed. The Mann-Whitney U-test and the χ2 test was used for categorical variables to assess the significance of differences between the groups. The binary logistic regression was used to determine the association of 1,5-AG and STEMI. Results: There were 43.86% men and 56.14% women among the investigated patients. The median age of patients in the STEMI and non-STEMI groups were 61 (Q25-75 54-71) and 53 (Q25-15 75 57-60) years of age, р=0.027. Median fasting plasma glycemia in the STEMI group was 9.81 mmol/l (Q25-75 7.7-14.8), in the non-STEMI group (8.55 mmol/l, Q25-75 6.72-10.07, р=0.012). 1,5-AG was significantly lower in the STEMI group than in the non-STEMI (the STEMI group: Ме=215.85, Q25-75 186.35-19 280.77; the non-STEMI group Ме=314.64, Q25-75 250.83-415.08, р=0.000). No significant difference in concentration of HbA1c was found between the groups. The logistic regression model adjusted on confounders demonstrated that low plasma 1,5-AG concentration increases the odds ratio of STEMI in diabetic patients [OR 3,217 (95% CI 2,567–7,732), p = 0,002]. Conclusion: The association between 1,5-AG and STEMI in patients with T2DM suggests the potential beneficial role of 1,5-AG as a cardiovascular risk marker in patients with type 2 diabetes mellitus.