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Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years., Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders., Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages., Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nad(p)h: Quinone Oxidoreductase 1 (NQO1) is an antioxidant enzyme that catalyzes the two-electron reduction of several different classes of quinone-like compounds (quinones, quinone imines, nitroaromatics, and azo dyes). One-electron reduction of quinone or quinone-like metabolites is considered to generate semiquinones to initiate redox cycling that is responsible for the generation of reactive oxygen species and oxidative stress and may contribute to the initiation of adverse drug reactions and adverse health effects. On the other hand, the two-electron reduction of quinoid compounds appears important for drug activation (bioreductive activation) via chemical rearrangement or autoxidation. Two-electron reduction decreases quinone levels and opportunities for the generation of reactive species that can deplete intracellular thiol pools. Also, studies have shown that induction or depletion (knockout) of NQO1 were associated with decreased or increased susceptibilities to oxidative stress, respectively. Moreover, another member of the quinone reductase family, NRH: Quinone Oxidoreductase 2 (NQO2), has a significant functional and structural similarity with NQO1. The activity of both antioxidant enzymes, NQO1 and NQO2, becomes critically important when other detoxification pathways are exhausted. Therefore, this article summarizes the interactions of NQO1 and NQO2 with different pharmacological agents, endogenous biochemicals, and environmental contaminants that would be useful in the development of therapeutic approaches to reduce the adverse drug reactions as well as protection against quinone-induced oxidative damage. Also, future directions and areas of further study for NQO1 and NQO2 are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nocardia species can cause various types of infections including, pulmonary, cutaneous, disseminated & CNS diseases. Here, we report a case of disseminated nocardiosis, probably secondary to pulmonary foci, in an immunocompetent patient. Blood culture showed gram-positive bacilli, which on culture grew aerial chalky white growth showed the acid-fast, gram-positive filamentous bacteria. The culture was identified as Nocardia farcinica by MALDI-TOF. Unfortunately, the patient succumbed to the infection on the 5th day after admission., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Phenol red (PR) is the standard pH indicator in various cell and tissue culture media, as it provides a quick check for the health of the culture. PR has also been used in multiple protocols to detect cellular hydrogen peroxide as well as peroxidase activity from human peroxidase enzymes. The majority of promyelocytic leukemia cell lines (e.g. HL-60 cells) express myeloperoxidase (MPO), which may react with PR, especially as the latter is present in cell culture media at sufficient concentrations (~15 μM) to partake in redox reactions. Moreover, phenolic molecules are often efficient donor substrates for peroxidase enzymes. In this study, we hypothesized that MPO metabolism of PR via MPO-expressing HL-60 cells could result in PR metabolite(s) that could modulate cell viability. We used purified human MPO for UV-visible spectrophotometry, electron paramagnetic resonance (EPR) and LC-MS analyses to investigate PR peroxidation. 2-chloro-5,5-dimethyl-1,3-cyclohexanedione (monochloro-dimedone, MCD) was used to assess the effect of PR on MPO-catalyzed chlorination activity, and we assessed PR uptake by HL-60 cells using LC-MS analysis. Lastly, we investigated the impact of PR metabolism by intracellular MPO on cell viability (ATP, using CellTiter-Glo ® ), cytotoxicity (using trypan blue), and on reduced and oxidized glutathione (using GSH/GSSG-Glo™). Our results demonstrate that PR undergoes oxidative halogenation via MPO, resulting in its UV-vis spectral changes due to the formation of mono- and di-halogenated products. Moreover, a significant increase in MPO-catalyzed chlorination of MCD and an increase in glutathionyl radical detection (using EPR) were observed in the presence of PR. Our in-vitro studies revealed that PR is readily taken up by HL-60 cells and its metabolism by intracellular MPO leads to a significant decrease in cellular glutathione as well as a significant increase in glutathione disulphide formation. In spite of the latter, PR had no considerable effect on HL-60 cell viability. These results provide evidence that while no overt decrease in cell viability may be observed, PR does impart redox activity, which investigators should be wary of in experimental protocols., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD + ) by the mycobacterial catalase-peroxidase enzyme, KatG, was known to be the major component of the mode of action of isoniazid (INH), an anti-tuberculosis drug. However, there are other enzymes that may catalyze this reaction. We have previously reported that neutrophil myeloperoxidase (MPO) is capable of metabolizing INH through the formation of INH-NAD + adduct, which could be attributed to being a possible mode of action of INH. However, eosinophilic infiltration of the lungs is more pronounced and characteristic of granulomas in Mycobacterium tuberculosis-infected patients. Thus, the aim of the present study is to investigate the role of eosinophil peroxidase (EPO), a key eosinophil enzyme, during INH metabolism and the formation of its active metabolite, INH-NAD + using purified EPO and eosinophils isolated from asthmatic donors. UV-Vis spectroscopy revealed INH oxidation by EPO led to a new product (λ max  = 326 nm) in the presence of NAD + . This adduct was confirmed to be INH-NAD + using LC-MS analysis where the intact adduct was detected (m/z = 769). Furthermore, EPO catalyzed the oxidation of INH and formed several free radical intermediates as assessed by electron paramagnetic resonance (EPR) spin-trapping; a carbon-centred radical, which is considered to be the reactive metabolite that binds with NAD + , was found when superoxide dismutase was included in the reaction. Our findings suggest that eosinophilic EPO may also play a role in the pharmacological activity of INH through the formation of INH-NAD + adduct, and supports further evidence that human cells and enzymes are capable of producing the active metabolite involved in tuberculosis treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Isoniazid (INH) is one of the oldest drugs for the treatment of tuberculosis (TB) and is of continual clinical and research interest. The aim of the current study is to investigate the ability of INH to induce monocyte differentiation and the underlying signaling pathway involved in this phenomenon using HL-60 cells. In this study, HL-60 cells were treated with different non-cytotoxic concentrations of INH or vitamin D (a well-known inducer of monocytic differentiation) to determine key functional changes in the phenotype of these cells using several biochemical and cytobiological experiments. HL-60 cells are derived from human promyelocytic leukemia and bear some resemblance to promyelocytes, which differentiate into various cell types. INH-induced differentiation was confirmed to occur in a concentration-dependent manner through several functional markers such as nonspecific esterase activity, NADPH oxidase activity and expression of surface markers CD14 and CD16 (characteristic of monocytes). INH-induced monocytic-like differentiation in HL-60 cells and demonstrated that at least 25% of cells were differentiated within the range of the pharmacological concentrations of INH. To determine the effects of INH on HL-60 cells, we applied quantitative proteomics that revealed 32 proteins were altered significantly in pathways that could involve differentiation signals. Lastly, INH activated the ERK-1/MAPK signaling pathway based on detection of phosphorylated ERK-1. These in vitro findings in HL-60 cells warrant further study using promyelocytes or hematopoietic stem cells to evaluate the physiological capability of INH to induce monocytic differentiation that may aid in host defense against TB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Several lines of evidence have pointed towards the potential therapeutic benefit of NSAIDs in cancer therapy. In this study, we have investigated the acute bio-activation of NSAIDs and their metabolites via myeloperoxidase (MPO), a highly-expressed peroxidase enzyme in acute myeloid leukemia. As bio-activation involves the formation of reactive metabolites, we hypothesized that NSAIDs which produced reactive metabolites would be correlated with leukemia cell toxicity. We tested the enzymatic peroxidation of three NSAIDs, namely diclofenac, indomethacin, and naproxen in comparison with their hepatic metabolites, 4'- hydroxydiclofenac (4'-OHD), 5-hydroxydiclofenac (5-OHD), O-desmethyl-N-deschlorobenzoylindomethacin (DMBI), O-desmethylindomethacin (DMI) and O-desmethylnaproxen (ODN). Firstly, we used purified peroxidases in kinetic UV-vis kinetic spectrophotometry, and electron paramagnetic resonance (EPR) experiments to determine oxidation of ascorbic acid and glutathione (GSH), respectively. We then used HL-60 cells, as a model of acute myelogenous leukemia to carry out trypan blue exclusion, cellular ATP analysis, mitochondrial membrane potential (MMP) and cytofluorometric GSH assays. Our results present evidence that diclofenac, 4'-OHD, 5-OHD, DMBI and DMI demonstrated significant cytotoxic effect in the leukemic cells through oxidation by intracellular MPO. In the same vein, only diclofenac and its two metabolites caused a significant drop in the MMP and cellular ATP level; however, the cell death induced by indomethacin metabolites reflected a subtle effect on MMP or GSH content. Interestingly, only diclofenac and 4'-OHD (and not 5- OHD) caused a significant drop in HL-60 cells' GSH content. Among diclofenac compounds, only 4'-OHD also generated GS radical and caused a significant increase in ascorbate co-oxidation rate. Lastly, even though ODN also generated GS radical and potently cooxidized ascorbate, it showed no significant cytotoxicity. These results provide evidence of a correlation between acute cytotoxicity and MPO-bioactivated NSAIDs, though this was not correlated for all compounds (e.g., ODN). Further studies are required to determine both the MPO-dependent and MPO-independent mechanisms of cytotoxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Traceability through the entire food supply chain from conception to consumption is a pressing need for the food industry, consumers and government regulators. A robust, whole-chain traceability system is needed that will effectively address food quality, food safety and food defense issues by providing real-time, transparent and reliable information from beef production through slaughter and distribution to the consumer. Traceability is an expanding part of the food safety continuum that minimizes the risk of foodborne diseases, assures quality and cold-chain integrity. Traceability can be a positive competitive marketing edge for beef producers who can verify specific quality attributes such as humane production or grass fed or Certified Organic. In this review we address the benefits as well as the remaining issues for whole-chain traceability in the beef industry, with particular focus on ground beef for the markets in the United States., (Copyright © 2013 Elsevier Ltd. All rights reserved.)