Host-directed therapies: a potential solution to combat COVID-19.

Coronavirus disease 2019 (COVID-19) characterized by immuno-pathological host responses including pneumonia, lymphopenia, and cytokine storm that leads to severe lung inflammation, developed in acute respiratory distress syndrome (ARDS). In the absence of an effective vaccine or any definitive cure, the use of host-directed therapies is an effective alternative and demanding treatment option in the current pandemic outbreak of COVID-19.

Activating transcription factor 3 modulates the macrophage immune response to Mycobacterium tuberculosis infection via reciprocal regulation of inflammatory genes and lipid body formation.

Infection of macrophages by Mycobacterium tuberculosis elicits an immune response that clears the bacterium. However, the bacterium is able to subvert the innate immune response. Differential expression of transcription factors (TFs) is central to the dynamic balance of this interaction.

Legume lectins: Potential use as a diagnostics and therapeutics against the cancer.

Legume lectins are carbohydrate-binding protein and widely distributed in a variety of species of leguminous plants and have drawn increased attention toward cancer. Nowadays, the lectins have been studied for the screening of potential biomarkers which increased its importance in cancer research. Few plant lectins have been shown to destroy cancer cells, suggesting that lectins may have biological potential in cancer treatments.

Genotypic diversity of Mycobacterium tuberculosis isolates from North-Central Indian population.

Background: Different strains of Mycobacterium tuberculosis (MTB) are known to have different epidemiological and clinical characteristics. Some of them are widely distributed and associated with drug resistance, whereas others are locally predominated. Molecular epidemiological investigations have always been beneficial in identifying new strains and studying their transmission dynamics.

Sub-national TB prevalence surveys in India, 2006-2012: Results of uniformly conducted data analysis.

Setting: Community based tuberculosis (TB) prevalence surveys in ten sites across India during 2006-2012.

Objective: To re-analyze data of recent sub-national surveys using uniform statistical methods and obtain a pooled national level estimate of prevalence of TB.

Methods: Individuals ≥15 years old were screened by interview for symptoms suggestive of Pulmonary TB (PTB) and history of anti-TB treatment; additional screening by chest radiography was undertaken in five sites.

HPMA-PLGA Based Nanoparticles for Effective In Vitro Delivery of Rifampicin.

Purpose: Tuberculosis (TB) chemotherapy witnesses some major challenges such as poor water-solubility and bioavailability of drugs that frequently delay the treatment. In the present study, an attempt to enhance the aqueous solubility of rifampicin (RMP) was made via co-polymeric nanoparticles approach. HPMA (N-2-hydroxypropylmethacrylamide)-PLGA based polymeric nanoparticulate system were prepared and evaluated against Mycobacterium tuberculosis (MTB) for sustained release and bioavailability of RMP to achieve better delivery.

Smartly Engineered PEGylated Di-Block Nanopolymeric Micelles: Duo Delivery of Isoniazid and Rifampicin Against Mycobacterium tuberculosis.

In an attempt to deliver multiple drugs through a nanoparticulate platform, the present study was designed to deliver isoniazid (INH) and rifampicin (RMP) together through conjugation/encapsulation approaches using PEG-PLA (polyethylene glycol-poly-L-lactic acid) polymeric micelles. The objective of this study is to identify the preparation and evaluation of PEGylated polymeric micelles with dual drug delivery of INH and RMP for the effective treatment of tuberculosis (TB). Synthesized PEG-PLA di-block-copolymer was further conjugated to INH-forming PEG-PLA-INH (PPI) conjugate.

Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection.

Background & Objectives: Central nervous system (CNS) infection caused by Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited studies are available on CNS-TB animal model development. The present study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.

Biological evaluation of novel curcumin-pyrazole-mannich derivative active against drug-resistant Mycobacterium tuberculosis.

Aim: Our objective was to identify a more potent curcumin derivative with specific activity against Mycobacterium tuberculosis.

Materials & Methods: A total of 21 curcumin derivatives were synthesized and detailed bio-evaluation was carried out including determination of static/cidality, synergy with front-line antituberculosis drugs and determination of efficacy in the murine model of M. tuberculosis infection.

Prioritization of natural compounds against mycobacterium tuberculosis 3-dehydroquinate dehydratase: A combined in-silico and in-vitro study.

Enormous efforts have been endeavored to develop inhibitors against the potential therapeutic target, mycobacterium tuberculosis 3-dehydroquinate dehydratase (MtbDHQase) to combat resistance. Over a dozen of small molecules have been crystallized to characterize the structural basis of the inhibition. However, the studies accomplished so far, have not incorporated all the essential interactions of these complexes simultaneously, to identify the novel inhibitors.

Identification of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase inhibitors: A combined in-silico and in-vitro analysis.

Mycobacterium tuberculosis (Mtb), had developed evolutionary changes in its genome to adapt for survival and thereby generated multi-drug resistant strains. However, novel drug targets that remained unchanged for their biochemical role has impressed the research community to target such proteins. The comprehensive analysis of multiple protein targets has influenced us to make a consensus structural rule exploited by pharmacophore and other allied techniques from a large repository of protein structures.

Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

Purpose: First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF.

Proteomics of Culture Filtrate of Prevalent Strains: 2D-PAGE Map and MALDI-TOF/MS Analysis.

Although diverse efforts have been done to identify biomarkers for control of tuberculosis using laboratory strain H37Rv, the disease still poses a threat to mankind. There are many emerging strains, and proteomic profiling of these strains might be important to find out potential targets for diagnosis and/or prevention of tuberculosis. We evaluated the comparative proteomic profiling of culture filtrate (CF) proteins from prevalent strains (Central Asian or Delhi type; CAS1_Del, East African-Indian; EAI-3 and Beijing family) by 2D polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

Comparative study of genotypes of Mycobacterium tuberculosis from a Northern Indian setting with strains reported from other parts of India and neighboring countries.

This study was carried out to characterize Mycobacterium tuberculosis population in Ghatampur, Kanpur, North India, by spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTRs) typing. A total of 335 isolates were genotyped by spoligotyping and Central Asian (CAS) sub-lineage was the most prevalent, comprising 59.1% of all isolates.

Current status of subspecies infection in animals & humans in India: What needs to be done?

Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as a major health problem for domestic livestock and human beings. Reduced per animal productivity of domestic livestock seriously impacts the economics of dairy farming globally. High to very high bioload of MAP in domestic livestock and also in the human population has been reported from north India.

Trends in spoligotype patterns of strains in central India.

This study aims to understand trends in spoligotype patterns of Mycobacterium tuberculosis (MTB) in Central India. Elucidation of these trends may provide baseline information to understand the transmission dynamics of strains of MTB in the region. Spoligotyping was carried out on 340 MTB strains isolated from clinical samples received from 2007 to 2011.

Murine model of TB meningitis.

Background: Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.

Assessing genetic diversity of Mycobacterium tuberculosis by spoligotyping and IS6110-based restriction fragment length polymorphism in North India.

Objective/background: Molecular epidemiology methods are very useful for differentiating between strains, assessing their diversity, and measuring the prevalence of the most circulating strain in an area. Various molecular typing methods using different molecular markers have been utilized worldwide, such as restriction fragment length polymorphism (RFLP), spoligotyping, Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeat (MIRU-VNTR), and Double repetitive element-PCR (DRE-PCR) typing, for simultaneous detection and epidemiologic typing of Mycobacterium tuberculosis. The present study is conducted to assess the genetic diversity of M.

Inhalable Particles for "Pincer Therapeutics" Targeting Nitazoxanide as Bactericidal and Host-Directed Agent to Macrophages in a Mouse Model of Tuberculosis.

Nitazoxanide (NTZ) has moderate mycobactericidal activity and is also an inducer of autophagy in mammalian cells. High-payload (40-50% w/w) inhalable particles containing NTZ alone or in combination with antituberculosis (TB) agents isoniazid (INH) and rifabutin (RFB) were prepared with high incorporation efficiency of 92%. In vitro drug release was corrected for drug degradation during the course of study and revealed first-order controlled release.

Genetic diversity of Mycobacterium tuberculosis isolates from central India.

Background & Objectives: There is a paucity of data available on genetic biodiversity of Mycobacterium tuberculosis isolates from central India. The present study was carried out on isolates of M. tuberculosis cultured from diagnostic clinical samples of patients from Bhopal, central India, using spoligotyping as a method of molecular typing.

Preparation and Preclinical Evaluation of Inhalable Particles Containing Rapamycin and Anti-Tuberculosis Agents for Induction of Autophagy.

Purpose: Mycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs.

Methods: PLGA and drugs were spray-dried.

Airborne infection control in India: Baseline assessment of health facilities.

Background: Tuberculosis transmission in health care settings represents a major public health problem. In 2010, national airborne infection control (AIC) guidelines were adopted in India. These guidelines included specific policies for TB prevention and control in health care settings.

Status of multidrug resistant tuberculosis (MDR-TB) among the Sahariya tribe of North Central India.

Background: The incidence/prevalence of tuberculosis (TB) is reported to be high in the Sahariya tribe of North Central India. The outbreaks of different drug-resistant isolates of Mycobacterium tuberculosis emphasized the need for continuous monitoring of resistance to anti-tuberculosis drugs. This study aimed to assess the profile of multidrug resistant TB among the Sahariya tribe and their non-tribal neighbors for first line drugs through field-based investigations.