Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis.

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

Differential intracellular localization of Hsp70 in the gill and heart tissue of fresh water prawn Macrobrachium malcolmsonii during thermal stress.

Exposure of organisms to heat stress induces the expression of evolutionarily conserved proteins called the stress proteins or heat shock proteins (HSPs). At the cellular level, HSPs by acting as molecular chaperone prevents the heat induced aggregation of denatured proteins and play a significant role in adaptation to temperature. Among different HSP family members, Hsp70 is the highly conserved and ubiquitously expressed protein. The present study is carried out to detect changes in the localization of Hsp70/Hsc70 in gill and heart tissues of control and heat shocked juveniles of Macrobrachium malcolmsonii that could be correlated with the functional significance of these two isoforms. Two groups of prawn acclimated at 30 °C were exposed to reported optimum Hsp70 induction temperatures of 36 °C and 38 °C for heart and gill, respectively, for a duration of 48 h. These tissues were processed by immunocytochemical methods to detect intra-cellular localization of Hsp70/Hsc70. Western blotting analysis was performed to determine the cytoplasmic or nuclear localization of Hsp70/Hsc70 and band intensity was detected in total lysate, cytosolic and nuclear extracts of gill and heart tissue. The present investigation clearly shows that there are alterations in the intracellular localization of Hsp70/Hsc70 in the cells of the gill and heart tissues of M. malcolmsonii following heat stress. The western blotting results corroborate the results obtained by immunohistochemical localisation. The differential intracellular localization of Hsp70/Hsc70 appears to indicate the functional roles of this stress protein during exposure to thermal stress.

Enhanced cell-wall damage mediated, antibacterial activity of core-shell ZnO@Ag heterojunction nanorods against Staphylococcus aureus and Pseudomonas aeruginosa.

Hybrid ZnO@Ag core-shell nanorods have been synthesized by a synthetic strategy based on seed mediated growth. Formation of core-shell nanostructures was confirmed by UV- diffused reflectance spectroscopy (UV-DRS), X-ray diffraction studies, field emission scanning electron microscopy and high resolution transmission electron microscopy. UV-DRS analysis of hybrid core-shell nanorods suggests the possibility of interfacial electron transfer between surface anchored Ag nanoclusters and ZnO nanorods. Successful decoration of Ag nanoclusters with an average diameter of ~7 ± 0.5 nm was observed forming the heterojunctions on the surface of the ZnO nanorods. An enhanced antibacterial property was observed for the ZnO@Ag core-shell nanorods against both Staphylococcus aureus and Pseudomonas aeruginosa lbacteria. The synergetic antibacterial activity of ZnO@Ag nanorods was found to be more prominent against Gram-positive bacteria than Gram-negative bacteria. The plausible reason for this enhanced antibacterial activity of the core-shell nanorods can be attributed to the physical damage caused by the interaction of the material with outer cell wall layer due to the production of reactive oxygen species by interfacial electron transfer between ZnO nanorods and plasmonic Ag nanoclusters. Overall, the ZnO@Ag core-shell nanorods were found to be promising materials that could be developed further as an effective antibacterial agent against wide range of microorganisms to control spreading and persistence of bacterial infections.