Gene expression of protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), solute carrier family 2 member 1 (SLC2A1) and mechanistic target of rapamycin (MTOR) in metformin-treated type 2 diabetes patients with COVID-19: impact on inflammation markers.

The COVID-19 pandemic has resulted in a global health crisis that has severely impacted patients with type 2 diabetes (T2D). T2D patients have a higher risk of experiencing severe COVID-19 symptoms, hospitalization, and mortality compared to patients without diabetes. The dysregulated immune response in T2D patients can exacerbate the severity of COVID-19 symptoms. Insulin therapy, a common treatment for T2D patients, has been linked to increased mortality in COVID-19 patients with T2D. However, metformin, an anti-diabetic medication, has been shown to have anti-inflammatory properties that may mitigate the cytokine storm observed in severe COVID-19 cases. In this study, we investigated how the PRKAA1, SLC2A1, and MTOR genes contribute to inflammation markers in COVID-19 patients with T2D, who were receiving either insulin or metformin therapy. Our findings revealed that metformin treatment was associated with reduced expression of genes involved in Th1/Th17 cell differentiation. These results suggest that metformin could be a potential treatment option for T2D patients with COVID-19 due to its anti-inflammatory properties, which may improve patient outcomes.

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.

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.

Surveillance of human leptospirosis infections in Ukraine between 2018 and 2023.

Leptospirosis is a bacterial disease that affects both humans and animals worldwide. Currently, a positional war is ongoing in Ukraine, and the military is encountering a significant number of rodents in trenches and dugouts, which are known reservoirs for Leptospira, the causative agent of leptospirosis-a potentially dangerous infectious disease with a high mortality rate. The civilian population is also at potential risk of leptospirosis. The destruction of the Kakhovka Dam on June 6, 2023, has led to widespread devastation and human suffering. In the short term, there is a significant risk of rodent-borne diseases such as leptospirosis. We utilized data from the Ukrainian Centre for Disease Prevention Control and observed a substantial increase in prevalence in 2023. The notification rate in Ukraine in 2023 was 1.06 per 100,000 persons, which is higher than that of other countries in the European Union. Particular attention is being given to Zakarpattia Oblast, located on the western border of Ukraine, which shares boundaries with Romania, Hungary, Poland, and Slovakia, with an extremely high incidence rate of 12.08 per 100,000 persons. Based on these findings, we recommend education and awareness campaigns, vaccination, personal protective measures, and improved surveillance to address the increasing incidence of leptospirosis in Ukraine.

COVID-19-associated encephalopathy: connection between neuroinflammation and microbiota-gut-brain axis.

While neurological complications of COVID-19, such as encephalopathy, are relatively rare, their potential significant impact on long-term morbidity is substantial, especially given the large number of infected patients. Two proposed hypotheses for the pathogenesis of this condition are hypoxia and the uncontrolled release of proinflammatory cytokines. The gut microbiota plays an important role in regulating immune homeostasis and overall gut health, including its effects on brain health through various pathways collectively termed the gut-brain axis. Recent studies have shown that COVID-19 patients exhibit gut dysbiosis, but how this dysbiosis can affect inflammation in the central nervous system (CNS) remains unclear. In this context, we discuss how dysbiosis could contribute to neuroinflammation and provide recent data on the features of neuroinflammation in COVID-19 patients.

Corticosteroid Treatment for Leptospirosis: A Systematic Review and Meta-Analysis.

Background: Leptospirosis, a zoonotic disease prevalent in tropical regions, often leads to severe complications such as Weil's disease and acute respiratory distress syndrome (ARDS). This pioneering meta-analysis investigated the role of corticosteroids in treating severe leptospirosis, addressing a critical gap in the current clinical knowledge. Methods: We systematically reviewed studies from PubMed and Scopus, focusing on randomized controlled trials and observational cohort studies involving adult patients diagnosed with leptospirosis. Five studies comprising 279 participants met the inclusion criteria. Results: Although some studies suggest potential benefits, particularly for pulmonary complications, the evidence remains inconclusive due to the limited number of studies and their methodological limitations. Notably, while four of the five reviewed studies indicated a possible positive role of corticosteroids, the single randomized controlled trial showed no significant benefit, highlighting the need for more robust research. Conclusions: While the current evidence provides a basis for potential benefits, it is not sufficient to make definitive clinical recommendations. Further research is essential to clarify the role of corticosteroids in the treatment of severe leptospirosis, with the aim of improving patient outcomes and guiding clinical practices effectively.

Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense.

Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes. A total of twenty-two antibiotic resistance genes that specifically target essential cellular processes such as cell wall synthesis, DNA replication, and protein synthesis have been identified. Significant among these were gidB, gdpD, and ggsA, each involved in separate aspects of antibiotic resistance. In addition, the investigation explored the defense mechanisms of bacteriophages, revealing the presence of defense islands that contain a range of anti-phage systems, including RM_Type_IV, PrrC, Borvo, CAS_Class1-Subtype-IC, and CAS_Class1-Subtype-IB. This comprehensive genomic analysis enhances our understanding of the molecular mechanisms that determine Leptospira's ability to adapt to various environments. The identified genetic factors linked to AMR and defense against phages not only enhance our scientific comprehension, but also provide a basis for focused interventions to reduce the impact of leptospirosis.

Current treatment options for leptospirosis: a mini-review.

Leptospirosis, one of the most common global zoonotic infections, significantly impacts global human health, infecting more than a million people and causing approximately 60,000 deaths annually. This mini-review explores effective treatment strategies for leptospirosis, considering its epidemiology, clinical manifestations, and current therapeutic approaches. Emphasis is placed on antibiotic therapy, including recommendations for mild and severe cases, as well as the role of probiotics in modulating the gut microbiota. Furthermore, novel treatment options, such as bacteriophages and newly synthesized/natural compounds, are discussed, and the findings are expected to provide insights into promising approaches for combating leptospirosis.

Comprehensive Analysis of Antiphage Defense Mechanisms: Serovar-Specific Patterns.

Leptospirosis is a major zoonotic disease caused by pathogenic spirochetes in the genus Leptospira, affecting over a million people annually and causing approximately 60,000 deaths. Leptospira interrogans, a key causative agent, likely possesses defense systems against bacteriophages (leptophages), yet these systems are not well understood. We analyzed 402 genomes of L. interrogans using the DefenseFinder tool to identify and characterize the antiphage defense systems. We detected 24 unique systems, with CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins), PrrC, Borvo, and Restriction-Modification (R-M) being the most prevalent. Notably, Cas were identified in all strains, indicating their central role in phage defense. Furthermore, there were variations in the antiphage system distribution across different serovars, suggesting unique evolutionary adaptations. For instance, Retron was found exclusively in the Canicola serovar, while prokaryotic Argonaute proteins (pAgo) were only detected in the Grippotyphosa serovar. These findings significantly enhance our understanding of Leptospira's antiphage defense mechanisms. They reveal the potential for the development of serovar-specific phage-based therapies and underscore the importance of further exploring these defense systems.

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 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.

Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis.

Introduction: Posttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD. Aim: The purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD. Methods: Relevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part). Results: The meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62-0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed. Conclusion: This meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023476590.

Impact of Antibiotic and Steroid Therapy on Leptospirosis Outcomes: A Retrospective Cohort Study in Transcarpathia, Ukraine.

Leptospirosis presents a significant health challenge in the Transcarpathian region of Ukraine, with higher incidence rates and mortality compared to national averages. We conducted a retrospective cohort study to investigate the effects of antibiotic and steroid treatments on outcomes in leptospirosis patients. Our analysis of clinical and laboratory data from a single center revealed that dexamethasone showed significant effects on various clinical variables, as did investigated antibiotics. Notable differences in clinical and laboratory outcomes were observed, particularly in direct bilirubin levels, which were significantly higher in non-survivors. ROC analysis demonstrated high sensitivity and specificity of direct bilirubin as a predictor of mortality. These findings highlight the importance of targeted treatment strategies and the potential of specific laboratory markers in improving leptospirosis management.

Exploring the complex interplay: gut microbiome, stress, and leptospirosis.

Leptospirosis, a re-emerging zoonotic disease, remains a significant global health concern, especially amid floods and disasters such as the Kakhovka Dam destruction. As is known, the stress that occurs in the conditions of military conflicts among civilian and military personnel significantly affects susceptibility to infectious diseases and possibly even influences their course. This review aims to explore how the gut microbiome and stress mediators (such as catecholamines and corticosteroids) might impact the leptospirosis disease course. The review opens new horizons for research by elucidating the connections between the gut microbiome, stress, and leptospirosis.

Gut microbiota in patients with COVID-19 and type 2 diabetes: A culture-based method.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) continues to affect people around the world, with one of the most frequent comorbidities being Type 2 Diabetes (T2D). Studies have suggested a link between disbalances in gut microbiota and these diseases, as well as with COVID-19, potentially due to inflammatory dysfunction. This study aims to analyze the changes in gut microbiota in COVID-19 patients with T2D using a culture-based method. Methods: The stool samples were taken from 128 patients with confirmed COVID-19. Changes in the composition of gut microbiota were analyzed by culture-based method. The study used chi-squared and t-test to find significant differences in gut bacteria between samples and non-parametric correlation analysis to examine relationship between gut bacteria abundance, C-reactive protein (CRP) levels and length of stay (LoS) in COVID-19 patients without T2D. Results: The gut microbiota of T2D patients with COVID-19 showed increased Clostridium spp., Candida spp., and decreased Bifidobacterium spp., Lactobacillus spp. Metformin-treated patients with T2D and COVID-19 without antibiotic treatment showed increased Bacteroides spp., Lactobacillus spp., and decreased Enterococcus, Clostridium compared to the same group with antibiotic treatment. The study also found a positive correlation between the abundance of certain gut microbiota genera, such as Klebsiella spp. and Enterococcus spp., and CRP levels and LoS in COVID-19 patients without and with T2D, while the abundance of other genera, such as Bifidobacterium spp. and Lactobacillus spp., was found to have a negative correlation. Conclusion: In conclusion, this study provides important insights into the gut microbiota composition of SARS-CoV-2-infected individuals with T2D and its potential impact on the course of the disease. The findings suggest that certain gut microbiota genera may be associated with increased CRP levels and longer hospital stays. The significance of this study lies in the fact that it highlights the potential role of gut microbiota in the progression of COVID-19 in patients with T2D, and may inform future research and treatment strategies for this patient population. The future impact of this study could include the development of targeted interventions to modulate gut microbiota in order to improve outcomes for COVID-19 patients with T2D.

Unveiling the potential pleiotropic effects of metformin in treating COVID-19: a comprehensive review.

This review article explores the potential of metformin, a medication commonly used for type 2 diabetes, as an antiviral and anti-inflammatory agent in the context of coronavirus disease 2019 (COVID-19). Metformin has demonstrated inhibitory effects on the growth of SARS-CoV-2 in cell culture models and has shown promising results in reducing viral load and achieving undetectable viral levels in clinical trials. Additionally, metformin exhibits anti-inflammatory properties by reducing the production of pro-inflammatory cytokines and modulating immune cell function, which may help prevent cytokine storms associated with severe COVID-19. The drug's ability to regulate the balance between pro-inflammatory Th17 cells and anti-inflammatory Treg cells suggests its potential in mitigating inflammation and restoring T cell functionality. Furthermore, metformin's modulation of the gut microbiota, particularly changes in bacterial taxa and the production of short-chain fatty acids, may contribute to its therapeutic effects. The interplay between metformin, bile acids, the gut microbiome, glucagon-like peptide-1 secretion, and glycemic control has implications for the management of diabetes and potential interventions in COVID-19. By refreshing the current evidence, this review highlights the potential of metformin as a therapeutic option in the management of COVID-19, while also exploring its effects on the gut microbiome and immunometabolism.

The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin.

The pandemic of COVID-19 has highlighted the intricate relationship between gut microbiome and overall health. Recent studies have shown that the Firmicutes/Bacteroidetes ratio in the gut microbiome may be linked to various diseases including COVID-19 and type 2 diabetes (T2D). Understanding the link between gut microbiome and these diseases is essential for developing strategies for prevention and treatment. In this study, 115 participants were recruited and divided into three groups: 1st group: T2D patients and healthy controls, 2nd group: COVID-19 patients with and without T2D, 3rd group: T2D patients with COVID-19 treated with or without metformin. Gut microbial composition at the phylum level was assessed using qRT-PCR with universal primers targeting the bacterial 16 S rRNA gene and specific primers for Firmicutes and Bacteroidetes. Data was analyzed using one-way ANOVA, logistic regression, and Spearman's rank correlation coefficient. The study found that the ratio of Firmicutes to Bacteroidetes (F/B) was higher in patients with both T2D and COVID-19 compared to those with only T2D or COVID-19. Additionally, the F/B ratio was positively correlated with C-reactive protein (CRP) in T2D and COVID-19 patients. The study also suggests that metformin treatment may affect this correlation. Logistic regression analysis showed that the F/B ratio was significantly associated with CRP. These findings suggest that the F/B ratio may be a potential biomarker for inflammation in T2D and COVID-19 patients and metformin treatment may have an effect on the correlation between F/B and CRP levels.

Identifying risk factors and disease severity in leptospirosis: A meta-analysis of clinical predictors.

Leptospirosis is a bacterial zoonosis with a wide spectrum of clinical presentations. In order to identify potential risk factors and predictors of disease severity, a meta-analysis of the clinical features of severe and non-severe leptospirosis patients was conducted. PubMed was searched to collect studies on the difference in clinical characteristics of severe and nonsevere patients, and data were analyzed using Comprehensive Meta-Analysis V3 software. Results showed that patients with severe outcomes were more likely to have dyspnoea, oliguria, and hemorrhagic symptoms than nonsevere patients. Determining these predictors in the early stages of the disease could thus significantly reduce the development of severe cases and related mortality.

Infectious diseases during the Russian-Ukrainian war - Morbidity in the Transcarpathian region as a marker of epidemic danger on the EU border.

•The Transcarpathian region in Ukraine has received over 350,000 Internally Displaced Persons (IDPs) since the beginning of the invasion, making the region vulnerable to outbreaks of communicable diseases.•The coverage of vital vaccination programs has been substantially harmed since the invasion began, with many children displaced without documentation and their vaccination status unknown.•The conditions in which IDPs in Transcarpathia reside risk local outbreaks of infectious diseases and their transmission into EU countries, making it vital to continue supporting Ukrainian healthcare authorities on the pivotal issue of vaccination.

Tyrosine Kinase Inhibitors Target B Lymphocytes.

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body's proteins, it leads to various autoimmune disorders. Additionally, when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.