Search

Abstract Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

IntroductionPost-COVID-19 syndrome (PCS) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition characterized by long-term violations of physical and mental health. People with type 2 diabetes (T2D) are at high risk for severe COVID-19 and PCS.AimThe current study aimed to define the predictors of PCS development in people with T2D for further planning of preventive measures and improving patient outcomes.Materials and methodsThe data were collected through the national survey targeting persons with T2D concerning the history of COVID-19 course and signs and symptoms that developed during or after COVID-19 and continued for more than 12 weeks and were not explained by an alternative diagnosis. In total, 469 patients from different regions of Ukraine were enrolled in the study. Among them, 227 patients reported PCS development (main group), while 242 patients did not claim PCS symptoms (comparison group). Stepwise multivariate logistic regression and probabilistic neural network (PNN) models were used to select independent risk factors.ResultsBased on the survey data, 8 independent factors associated with the risk of PCS development in T2D patients were selected: newly diagnosed T2D (OR 4.86; 95% CI 2.55–9.28; p

Contemporary research in the field of microbiota shows that commensal bacteria influence physiological activity of different organs and systems of a human organism, such as brain, lungs, immune and metabolic systems. This influence is realized by various processes. One of them is trough modulation of immune mechanisms. Interactions between microbiota and the human immune system are known to be complex and ambiguous. Dendritic cells (DCs) are unique cells, which initiate the development and polarization of adaptive immune response. These cells also interconnect native and specific immune reactivity. A large set of biochemical signals from microbiota in the form of different microbiota associated molecular patterns (MAMPs) and bacterial metabolites that act locally and distantly in the human organism. As a result, commensal bacteria influence the maturity and activity of dendritic cells and affect the overall immune reactivity of the human organism. It then determines the response to pathogenic microorganisms, inflammation, associated with different pathological conditions and even affects the effectiveness of vaccination.

IntroductionThere is growing evidence from animal and clinical studies suggesting probiotics can positively affect type 2 diabetes (T2D). In a previous randomized clinical study, we found that administering a live multistrain probiotic and absorbent smectite once a day for eight weeks to patients with T2D could reduce chronic systemic inflammatory state, insulin resistance, waist circumference and improve the glycemic profile. However, there is a lack of evidence supporting the efficacy of probiotic co-supplementation with absorbent smectite on pancreatic β-cell function in T2D.AimThis secondary analysis aimed to assess the effectiveness of an alive multistrain probiotic co-supplementation with absorbent smectite vs placebo on β-cell function in T2D patients.Material and methodsWe performed a secondary analysis on a previously published randomized controlled trial (NCT04293731, NCT03614039) involving 46 patients with T2D. The main inclusion criteria were the presence of β-cell dysfunction (%B

BackgroundBladder cancer (BC) is an aggressive disease with a poor prognosis. A bladder tumor, like other malignant neoplasms, is characterized by the presence of both cancer cells and stromal cells which secrete cytokines, chemokines, growth factors, and proteolytic enzymes. One such class of proteolytic enzymes are serine proteases, which take part in the tumor microenvironment formation via supporting and contributing to tumor progression. This study aims to evaluate the proteolytic activity and serine protease contribution in plasma from BC patients.MethodsThe research involved patients of Alexandrovsky city clinical hospital aged 52–76 with transitional cell carcinoma of the bladder. All examined patients were divided into five groups: the control group included conditionally healthy donors, while other patients were grouped according to their tumor stage (I, II, III and IV). Plasma plasminogen levels were determined by enzyme-linked immunosorbent assay, and the potential activity was measured by chromogenic plasminogen assay. Serine proteases fractions were obtained by the affinity chromatography method, and enzyme concentration in the selected fractions were determined by the Bradford method. Serine proteases distribution was investigated by electrophoresis in a polyacrylamide gel.ResultsIt was determined that the concentration, potential activity of plasminogen, and the total amount of serine proteases in plasma from BC patients were greater than the values of the corresponding indicators in healthy donors. This could be one of the factors contributing to increased proteolysis seen in the process of carcinogenesis. Plasminogen concentration in BC patients with stage IV disease; however, displayed a tendency to be reduced compared to earlier stages, and the potential activity of plasminogen was significantly lower in patients with stages III – IV BC. Futhermore, a tumor stage specific gradual decline in the serine protease plasma content was shown. The results of electrophoretic analysis established a significant diminishment in the percentage of high molecular weight components (under non-reducing conditions) and their complete disappearance (under reducing conditions) in plasma serine protease fractions from BC patients. A decline in the percentage of heavy and light plasmin chains in BC patients was also observed. Additionally, a rise in the degraded forms of plasminogen/plasmin content was seen in BC samples, as well as the presence of fractions corresponding to trypsin and NE (under non-reducing conditions) that were absent in the control samples.ConclusionThe results indicate significant changes in the proteolytic activity of plasma, from BC patients when compared to healthy controls, which is accompanied by alterations in serine protease distribution caused by tumor microenvironment pecularlities at the different stages of oncopathology.

IntroductionAccording to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary.AimTo determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures.Material and methodsAntimicrobial activity of Del-Immune V® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative (Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive (Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast (Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures.ResultsThe MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC—12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant.ConclusionsIt was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents.

BackgroundThe disease COVID-19, caused by SARS-CoV-2 infection, has a systemic effect and is associated with a number of pathophysiological mechanisms that mobilize a wide range of biomolecules. Cytokines and growth factors (GFs) are critical regulators of tissue damage or repair in osteoarthritis (OA) and are being recognized as key players in the pathogenesis of COVID-19. A clear understanding of the long-term consequences of SARS-CoV-2 infection, especially in patients with concomitant chronic diseases, is limited and needs to be elucidated. The study aimed to evaluate the degree of inflammation and levels of pro-angiogenic and hypoxic factors, as well as heat shock proteins HSP60 and HSP70 in plasma, of patients with OA after recovery from COVID-19.MethodsThe research involved patients of an orthopedic specialty clinic aged 39 to 80 diagnosed with knee OA. All examined patients were divided into three groups: the Control group included conditionally healthy donors, group OA included patients with knee OA mainly stage II or III and the group of OA and COVID-19 included patients with OA who had COVID-19. The plasma levels of pro-inflammatory molecules IL-1β, IL-6, TNF-α, NF-κB, angiogenic factors VEGF, FGF-2, PDGF, hypoxic factor HIF-1α and molecular chaperones HSP60 and HSP70 were measured by enzyme-linked immunosorbent assay.ResultsThe study showed that in both groups of patients, with OA and convalescent COVID-19, there was an increase in the plasma level of IL-1β and a decrease in TNF-α and NF-κB levels when compared to healthy controls. Systemic deregulation of the cytokine profile was accompanied by reduction in plasma levels of pro-angiogenic growth factors, most pronounced in cases of VEGF and PDGF. This analysis did not reveal any significant difference in the plasma level of HIF-1α. A decrease in the level of stress protein HSP60 in the blood of patients with OA, as well as those patients who have had SARS-CoV-2 infection, has been established.ConclusionThe results suggest the potential role pro-inflammatory cytokines and angiogenesis-related growth factors in pathogenesis of both joint pathologies and long-term systemic post-COVID-19 disorders.

IntroductionGrowing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC.AimThis study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC.Material and methodsPatients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy–mesalazine–at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score ≤2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes.ResultsClinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 ± 1.21 and in the FMT group−3.15±1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 ± 1.44 vs. 2.14 ± 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group.ConclusionsFTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&draw=2&rank=4, identifier: NCT05538026.

IntroductionResearch in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified.AimThe study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT’s safety, clinical and microbiological efficacy in patients with PI-IBS.Materials and methodsPatients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale).ResultsFMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted.ConclusionThis comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.

Background The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC. Methods Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status. Results TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P

Background and Objectives: Coronary artery disease (CAD) is the foremost cause of adult disability and mortality. There is an urgent need to focus on the research of new approaches for the prevention and treatment of CAD. Materials and Methods: The effects of peptides isolated from the blood plasma of CAD patients on endothelial cell secretion using the in vitro model have been tested. Human endothelial progenitor cells (HEPCs) were incubated for 24 h with peptides isolated from the plasma of healthy subjects or patients with stable angina, progressive unstable angina, and myocardial infarction. The contents of some soluble anticoagulant as well as procoagulant mediators in HEPC culture treated with peptide pools were then compared. Results and Conclusion: The results show that peptides from the plasma of patients with myocardial infarction promote endothelial cells to release both von Willebrand factor and endothelin-1, increasing vasoconstriction and shifting hemostatic balance toward a prothrombotic state. In contrast, peptides from the plasma of patients with progressive unstable angina suppress the secretion of endothelin-1 by HEPCs, while the secretion of both von Willebrand factor and tissue plasminogen activator was increased. As can be seen from the results obtained, disease derived peptides may contribute to the homeostasis of living organisms or the progression of pathological processes.

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.

Osteoarthritis (OA) is a highly heterogeneous joint disease characterized by joint pain and a progressive loss of articular cartilage. The therapeutic potential of using probiotics to treat OA has only recently been recognized, with a small number of animal and human studies having been undertaken. Transfigurations of gut microbiota, as well as the favorable results associated with it, can be reached by maintaining a healthy lifestyle, including physical exercises, healthy diet enriched with vitamins, minerals, prebiotics and probiotics, and regular sleeping habits. The mechanisms of cartilage degradation in osteoarthritis are multifactorial and several nutritional constituents can be aimed at numerous pathways, what brings out corresponding results. We considered, that the treatment with probiotics and/or prebiotics plus chondroprotectors and/or glucosamine may increase the chances for successful convalescence. Still there are very few studies evidencing the results of such treatment option. Future research should focus on describing the mode of action and efficacy of this kind of combined treatment, taking into account personal characteristics of patients.

The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.

Встановлено, що нанокристалічний діоксид церію посилював у старих щурів моторну активність шлунка та товстої кишки на відміну від церукалу та сенаде. Нанокристалічний діоксид церію – ефективніший прокі-нетику, ніж сучасні. Отримані результати можуть бути підґрунтям для створення на основі нанокриста-лічногодіоксиду церію протизакрепних засобів нового покоління.

Досліджено терапевтичні властивості нової сполуки 2-(2-гідроксифенокси)ацетил)-L-пролінату натрію при стресовій, етаноловій, індометациновій та аспіриновій моделях виразкоутворення в слизовій оболонці шлунка щурів. Антивиразкові властивості сполуки були асоційовані зі зменшенням вмісту прозапальних цитокінів у крові та збільшенням вмісту антизапальних цитокінів і простагландину Е2.

Epidemiological data showed that the number of obese people increases swiftly in all countries. Obesity can evoke metabolic syndrome or second type diabetes (T2D). So, the aim of our study was to investigate the influence of 2-[4-(benzyloxy) phenoxy] acetic acid on metabolic parameters of monosodium glutamate (MSG)-induced obesity in rats. We divided the rats as follows: 1- control group, 2 - MSG-group, 3 - MSG + 2-[4-(benzyloxy) phenoxy] acetic acid group. We investigated anthropometric parameters and blood biochemistry. It was established that MSG induced the development of visceral obesity in rats, in particular, it increased the Lee index, body mass index, deposits of subcutaneous, gonadal and visceral adipose tissue. The administration of 2-[4-(benzyloxy) phenoxy] acetic acid decreased metabolic parameters evoked by MSG. After obesity induction, there was recorded significant growth of cholesterol, triglycerides, and LDL cholesterol blood levels and significant decline in HDL cholesterol blood levels. There was a significant reduction in triglycerides, LDL cholesterol and VLDL, in 2-[4-(benzyloxy) phenoxy] acetic acid - treated group. Our results represent the basis for development of new treatment of obesity and associated conditions. Keywords: Obesity, Monosodium glutamate, Metabolic syndrome, 2-[4-(benzyloxy) phenoxy] acetic acid

Introduction and aim. Today probiotics have been suggested as a treatment for the prevention of non-alcoholic fatty liver disease (NAFLD). Smectite is a natural silicate that binds to digestive mucous and has the ability to bind endo- and exotoxins. The present study was designed to determine whether probiotics plus smectite is superior to probiotic alone on the monosodium glutamate (MSG) induced NAFLD model in rats.Materials and methods. We included 60 rats divided into 4 groups 15 animals in each. Rats of group I were intact. Newborns rats of groups II-IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic “Symbiter” containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter+Smectite) groups received “Symbiter Forte” combination of probiotic biomass with smectite gel (250 mg).Results. In both interventional groups reduction of total NAS score as compared to MSG-obesity was observed. Indeed similar values of steatosis score (0.93 ± 0.22 vs. 0.87 ± 0.16) in both treatment groups, we observed that lower total score for Symbiter+ Smectite are associated with more pronounced reduction of lobular inflammation (0.13 ± 0.09 vs. 0.33 ± 0.15) as compared to administration of probiotic alone. This data accompanied with significant reduction of IL-1 and restoration of IL-10 between these 2 groups.Conclusions. Additional to alive probiotic administration of smectite gel due to his absorbent activity and mucus layer stabilization properties can impact on synergistic enhancement of single effect which manifested with reduction of lobular inflammation and at list partly steatohepatitis prevention.

The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism. NAFLD has been proven to be associated with abnormal FXR activity. Obeticholic acid (OCA) is a first-in-class selective FXR agonist with anticholestatic and hepato-protective properties. Currently, OCA is registered for the treatment of primary biliary cholangitis. However, promising effects of OCA on NASH and its metabolic features have been reported in several studies.