AMR mechanisms in L. interrogans serovars: a comprehensive study

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century. Data regarding AMR mechanisms in Leptospira interrogans, the causative agents of leptospirosis, have been relatively limited. Therefore, our study aimed to identify resistance genes and explore potential resistance mechanisms specific to particular serovars. We conducted a comprehensive analysis of 98 Leptospira strains, representing 10 common serovars, using whole-genome sequencing (WGS) FASTA files. Employing the PATRIC tool from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), we scrutinized the genomes for AMR genes. Our investigation revealed 32 genes associated with AMR, with 20 key genes consistently prevalent across most strains. Notably, we identified unique efflux pump systems in serovar Pomona, indicating distinctive resistance mechanisms in this serovar. In summary, our findings shed light on the genetic landscape of AMR in Leptospira, uncovering both common and serovar-specific resistance elements. The presence of unique efflux pump systems in serovar Pomona introduces a novel dimension to our understanding of resistance mechanisms. These insights underscore the importance of tailored intervention strategies and collaborative efforts between human and veterinary healthcare professionals, as well as environmental scientists, to address the complex dynamics of leptospirosis and its implications for antibiotic resistance

Extracellular host DNA contributes to pathogenic biofilm formation during periodontitis

Introduction: Periodontal diseases are known to be associated with polymicrobial biofilms and inflammasome activation. A deeper understanding of the subgingival cytological (micro) landscape, the role of extracellular DNA (eDNA) during periodontitis, and contribution of the host immune eDNA to inflammasome persistence, may improve our understanding of the mechanisms underlaying severe forms of periodontitis.Methods: In this work, subgingival biolfilms developing on biologically neutral polyethylene terephthalate films placed in gingival cavities of patients with chronic periodontitis were investigated by confocal laser scanning microscopy (CLSM). This allowed examination of realistic cytological landscapes and visualization of extracellular polymeric substances (EPS) including amyloids, total proteins, carbohydrates and eDNA, as well as comparison with several single-strain in vitro model biofilms produced by oral pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus gordonii, S. sanguinis and S. mitis. Fluorescence in situ hybridization (FISH) analysis was also used to identify eDNA derived from eubacteria, streptococci and members of the Bacteroides–Porphyromonas–Prevotella (BPP) group associated with periodontitis.Results: Analysis of subgingival biofilm EPS revealed low levels of amyloids and high levels of eDNA which appears to be the main matrix component. However, bacterial eDNA contributed less than a third of the total eDNA observed, suggesting that host-derived eDNA released in neutrophil extracellular traps may be of more importance in the development of biofilms causing periodontitis.Discussion: eDNA derived from host immunocompetent cells activated at the onset of periodontitis may therefore be a major driver of bacterial persistence and pathogenesis

Table_1_AMR mechanisms in L. interrogans serovars: a comprehensive study.xlsx

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century. Data regarding AMR mechanisms in Leptospira interrogans, the causative agents of leptospirosis, have been relatively limited. Therefore, our study aimed to identify resistance genes and explore potential resistance mechanisms specific to particular serovars. We conducted a comprehensive analysis of 98 Leptospira strains, representing 10 common serovars, using whole-genome sequencing (WGS) FASTA files. Employing the PATRIC tool from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), we scrutinized the genomes for AMR genes. Our investigation revealed 32 genes associated with AMR, with 20 key genes consistently prevalent across most strains. Notably, we identified unique efflux pump systems in serovar Pomona, indicating distinctive resistance mechanisms in this serovar. In summary, our findings shed light on the genetic landscape of AMR in Leptospira, uncovering both common and serovar-specific resistance elements. The presence of unique efflux pump systems in serovar Pomona introduces a novel dimension to our understanding of resistance mechanisms. These insights underscore the importance of tailored intervention strategies and collaborative efforts between human and veterinary healthcare professionals, as well as environmental scientists, to address the complex dynamics of leptospirosis and its implications for antibiotic resistance.</p

Communicable diseases in Ukraine during the period of 2018–2023: Impact of the COVID-19 pandemic and war

Background: By examining 2018–2023 data, this study explored the intricate impact of the Russian invasion, ongoing COVID-19 pandemic, and environmental disruptions on communicable diseases in Ukraine. This conflict exacerbates challenges in disease surveillance and healthcare, compounding stress among the population. Methods: Leveraging the Centers for Disease Prevention Control's surveillance system, the study employs active and passive surveillance, utilizing medical records and laboratory reports. Notification rates gauge the incidence of communicable diseases, offering insights into trends during the study period. Results: While salmonellosis, shigellosis, and rotavirus incidence are decreasing overall, there is a surge in viral hepatitis A, chronic hepatitis B, and C. This conflict hampers hepatitis C management, as evidenced by decreased numbers of treatment centers and patient enrollment. The prevalence of cough cases will increase in 2023, emphasizing the importance of sustained vaccination. The incidence of tuberculosis will increase in 2023 despite a general decrease. Conclusion: This study underscores the urgent need for sustained efforts and adequate resources, infrastructure, and international support to mitigate public health challenges in conflict-ridden Ukraine. Prioritizing vaccination programmes and enhancing healthcare accessibility in affected regions are crucial

Metformin Alters mRNA Expression of <i>FOXP3</i>, <i>RORC</i>, and <i>TBX21</i> and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes

COVID-19 remains a significant global concern, particularly for individuals with type 2 diabetes who face an elevated risk of hospitalization and mortality. Metformin, a primary treatment for type 2 diabetes, demonstrates promising pleiotropic properties that may substantially mitigate disease severity and expedite recovery. Our study of the gut microbiota and the mRNA expression of pro-inflammatory and anti-inflammatory T-lymphocyte subpopulations showed that metformin increases bacterial diversity while modulating gene expression related to T-lymphocytes. This study found that people who did not take metformin had a downregulated expression of FOXP3 by 6.62-fold, upregulated expression of RORC by 29.0-fold, and upregulated TBX21 by 1.78-fold, compared to the control group. On the other hand, metformin patients showed a 1.96-fold upregulation in FOXP3 expression compared to the control group, along with a 1.84-fold downregulation in RORC expression and an 11.4-fold downregulation in TBX21 expression. Additionally, we found a correlation with gut microbiota (F/B ratio and alpha-diversity index) and pro-inflammatory biomarkers. This novel observation of metformin’s impact on T-cells and gut microbiota opens new horizons for further exploration through clinical trials to validate and confirm our data. The potential of metformin to modulate immune responses and enhance gut microbiota diversity suggests a promising avenue for therapeutic interventions in individuals with type 2 diabetes facing an increased risk of severe outcomes from COVID-19

GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population

Objective. Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population

Effect of the GHRL gene (rs696217) polymorphism on the metabolic disorders in patients with obesity in the Ukrainian population

Objective. Over the past four decades, the prevalence of obesity has tripled and limited genetic studies with specific SNPs have been conducted, but no investigations using ghrelin and obestatin prepropeptide (GHRL) gene have been reported in the Ukrainians population. The aim of this study was to evaluate changes in the level of metabolic hormones in the blood of obese patients in relation to the GHRL (rs696217) polymorphism

Modulatory Roles of <i>AHR</i>, <i>FFAR2</i>, <i>FXR</i>, and <i>TGR5</i> Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients. Methods: We investigated gene expression levels of AHR, FFAR2, FXR, and TGR5 in patients with MAFLD and COVID-19 compared to controls. We examined associations between gene expression and clinical outcomes. Results: COVID-19 patients displayed altered AHR expression, potentially impacting immune response and recovery. Downregulated AHR in patients with MAFLD correlated with increased coagulation parameters. Elevated FFAR2 expression in patients with MAFLD was linked to specific immune cell populations and hospital stay duration. A significantly lower FXR expression was observed in both MAFLD and severe COVID-19. Conclusion: Our findings suggest potential modulatory roles for AHR, FFAR2, and FXR in COVID-19 and MAFLD

Optimization of the Search for Neuroprotectors among Bioflavonoids

For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules—quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate—according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20% as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to a decrease in the neurodegradation markers in the cytosol of rats, with EAE: NSE by 37% and S-100 by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of the bioflavonoid selection with the help of a virtual screening program

Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives

Potassium 8-R1-9-R2-10-R3-3-R-2-oxo-2Н-[1,2,4]triazino[2,3-с]quinazoline-6-thiolates 2.1–2.26 were synthesized via cyclocondensation of 6-R-3-(3-R1-4-R2-5-R3-aminophenyl)-1,2,4-triazin-5-ones 1.1–1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1–3.26 were obtained by treatment of 2.1–2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R1-4-R2-5-R3-amino-phenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods (1H, 13C NMR, LC–MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25–100 μg/mL, MBC 12.5–200 μg/mL) to the synthesized compounds