Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected with .

Background: Tuberculosis (TB) remains a major global health threat, contributing substantially to high morbidity and mortality rates. This underscores the urgent need for more effective interventions. Recent studies highlight the potential of host-directed therapy approaches to enhance immune defences against TB.

Impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases: A systematic review and meta-analysis.

While numerous studies have extensively documented the pleiotropic effects of statins, including their capacity to reduce inflammation, there is a lack of research estimating the anti-inflammatory effectiveness of statins among individuals with chronic diseases. This meta-analysis evaluates the effect of statin therapy on inflammatory markers and the lipid profile in patients with chronic diseases by analysing evidence from randomized controlled trials (RCTs). We conducted a systematic review and searched articles published between 1st January 1999 and 31st December 2023 in databases including PubMed, Web of Science, Scopus, and Cochrane.

Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study).

Background: Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB (EPTB) has received little attention. Diagnosis of EPTB remains challenging due to the invasive procedures required for sample collection.

Multi-level tuberculosis of the spine identified by 18 F-FDG-PET/CT and concomitant urogenital tuberculosis: a case report from the spinal TB X cohort.

Background: Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and typically infects the lungs. However, extrapulmonary forms of TB can be found in approximately 20% of cases. It is suggested, that up to 10% of extrapulmonary TB affects the musculoskeletal system, in which spinal elements (spinal tuberculosis, STB) are involved in approximately 50% of the cases.

Identifying quantitative sncRNAs signature using global sequencing as a potential biomarker for tuberculosis diagnosis and their role in regulating host response.

Objectives: The study aimed to identify a quantitative signature of circulating small non-coding RNAs (sncRNAs) as a biomarker for pulmonary tuberculosis disease (active-TB/ATB) and explore their regulatory roles in host-pathogen interactions and disease progression.

Methods: We conducted a cross-sectional study recruiting subjects diagnosed with active-TB (drug-sensitive and drug-resistant) and healthy controls. Sera samples were collected and utilized for preparing small RNA libraries.

To treat or not to treat tuberculosis -clinical decision making in patients with previous pulmonary tuberculosis using 18F-FDG PET/CT.

Post-tuberculosis (TB) radiological changes and symptoms can mimic TB. PCR-based diagnostic tests can show positive results, suggesting the presence of DNA in the absence of viable bacteria. We present a case with two episodes of previous TB.

Antisense Therapy for Infectious Diseases.

Infectious diseases, particularly Tuberculosis (TB) caused by , pose a significant global health challenge, with 1.6 million reported deaths in 2021, making it the most fatal disease caused by a single infectious agent. The rise of drug-resistant infectious diseases adds to the urgency of finding effective and safe intervention therapies.

COVID-19Base v3: Update of the knowledgebase for drugs and biomedical entities linked to COVID-19.

COVID-19 has taken a huge toll on our lives over the last 3 years. Global initiatives put forward by all stakeholders are still in place to combat this pandemic and help us learn lessons for future ones. While the vaccine rollout was not able to curb the spread of the disease for all strains, the research community is still trying to develop effective therapeutics for COVID-19.

Lyl1-deficiency promotes inflammatory responses and increases mycobacterial burden in response to infection in mice.

Lymphoblastic leukemia 1 (Lyl1) is a well-studied transcription factor known to exhibit oncogenic potential in various forms of leukemia with pivotal roles in hematopoietic stem cell biology. While its role in early hematopoiesis is well established, its function in mature innate cells is less explored. Here, we identified Lyl1 as a drastically perturbed gene in the () infected mouse macrophage transcriptome.

Host-Directed Targeting of LincRNA-MIR99AHG Suppresses Intracellular Growth of .

Tuberculosis (TB) caused by (Mtb) kills 1.6 million people worldwide every year, and there is an urgent need for targeting host-pathogen interactions as a strategy to reduce mycobacterial resistance to current antimicrobials. Noncoding RNAs are emerging as important regulators of numerous biological processes and avenues for exploitation in host-directed therapeutics.

Intranasally administered S-MGB-364 displays antitubercular activity and modulates the host immune response to Mycobacterium tuberculosis infection.

Background: Previously, we evaluated the intracellular mycobactericidal activity of the minor groove binder, S-MGB-364 against the clinical Mycobacterium tuberculosis (Mtb) strain HN878 in macrophages.

Objectives: To assess the mycobactericidal activity of S-MGB-364 in Mtb-infected mice. Further, we investigated a plausible DNA binding mechanism of action of S-MGB-364.

Targeting Molecular Inflammatory Pathways in Granuloma as Host-Directed Therapies for Tuberculosis.

Globally, more than 10 million people developed active tuberculosis (TB), with 1.4 million deaths in 2020. In addition, the emergence of drug-resistant strains in many regions of the world threatens national TB control programs.

Evaluation of Berberine as an Adjunct to TB Treatment.

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function.

IL-4i1 Regulation of Immune Protection During Mycobacterium tuberculosis Infection.

Background: Interleukin 4 (IL-4i1)-induced gene 1 encodes L-phenylalanine oxidase that catabolizes phenylalanine into phenylpyruvate. IL-4i1 is mainly expressed by antigen-presenting cells (APCs), inhibits T-cell proliferation, regulates B-cell activation, modulates T cell responses, and drives macrophage polarization, but its role in bacterial infections is understudied.

Methods: We evaluated IL-4i1 deletion in macrophages and mice on infection with virulent H37Rv and W-Beijing lineage hypervirulent HN878 Mycobacterium tuberculosis (Mtb) strains.

MIREyA: a computational approach to detect miRNA-directed gene activation.

Emerging studies demonstrate the ability of microRNAs (miRNAs) to activate genes via different mechanisms. Specifically, miRNAs may trigger an enhancer promoting chromatin remodelling in the enhancer region, thus activating the enhancer and its target genes. Here we present MIREyA, a pipeline developed to predict such miRNA-gene-enhancer trios based on an expression dataset which obviates the need to write custom scripts.

IL-4-Responsive B Cells Are Detrimental During Chronic Tuberculosis Infection in Mice.

In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in human and mice. Of interest, () does increase IL-4 Receptor-alpha (IL4Rα) expression in murine B cells. To better understand the role of IL4Rα signalling in B cells, we compared wild type mice with B cell-specific IL4Rα deficient mice (mb1IL-4Rα mice).

Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to infection.

Peptidoglycan (PG), a heteropolysaccharide component of the mycobacterial cell wall can be shed during tuberculosis infection with immunomodulatory consequences. As such, changes in PG structure are expected to have important implications on disease progression and host responses during infection with . Mycobacterial amidases have important roles in remodeling of PG during cell division and are implicated in susceptibility to antibiotics.

Toward Preparing a Knowledge Base to Explore Potential Drugs and Biomedical Entities Related to COVID-19: Automated Computational Approach.

Background: Novel coronavirus disease 2019 (COVID-19) is taking a huge toll on public health. Along with the non-therapeutic preventive measurements, scientific efforts are currently focused, mainly, on the development of vaccines and pharmacological treatment with existing drugs. Summarizing evidences from scientific literatures on the discovery of treatment plan of COVID-19 under a platform would help the scientific community to explore the opportunities in a systematic fashion.

Protocol for systematic review and meta-analysis: impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases.

Introduction: Statins, also known as 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, are lipid-lowering agents that are central in preventing or reducing the complications of atherosclerotic cardiovascular disease. Because statins have anti-inflammatory properties, there is considerable interest in their therapeutic potential in other chronic inflammatory conditions. We aim to identify the statin with the greatest ability to reduce systemic inflammation, independent of the underlying disease entity.

Intervening along the spectrum of tuberculosis: meeting report from the World TB Day nanosymposium in the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town.

Tuberculosis (TB), caused by the highly infectious  , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 (range 230,000-428,000) people were infected with TB in 2017, and a quarter of them lost their lives due to the disease.

The gut microbiome in tuberculosis susceptibility and treatment response: guilty or not guilty?

Although tuberculosis (TB) is a curable disease, it remains the foremost cause of death from a single pathogen. Globally, approximately 1.6 million people died of TB in 2017.

Differential Targeting of c-Maf, Bach-1, and Elmo-1 by microRNA-143 and microRNA-365 Promotes the Intracellular Growth of in Alternatively IL-4/IL-13 Activated Macrophages.

(Mtb) can subvert the host defense by skewing macrophage activation toward a less microbicidal alternative activated state to avoid classical effector killing functions. Investigating the molecular basis of this evasion mechanism could uncover potential candidates for host directed therapy against tuberculosis (TB). A limited number of miRNAs have recently been shown to regulate host-mycobacterial interactions.

Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection.

Background: Tuberculosis is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M.tb). M.

Batf2 differentially regulates tissue immunopathology in Type 1 and Type 2 diseases.

Basic leucine zipper transcription factor 2 (Batf2) activation is detrimental in Type 1-controlled infectious diseases, demonstrated during infection with Mycobacterium tuberculosis (Mtb) and Listeria monocytogenes Lm. In Batf2-deficient mice (Batf2), infected with Mtb or Lm, mice survived and displayed reduced tissue pathology compared to infected control mice. Indeed, pulmonary inflammatory macrophage recruitment, pro-inflammatory cytokines and immune effectors were also decreased during tuberculosis.