👤 Satyadeo Choubey

Multidrug-resistant tuberculosis continues to be a major threat to mankind and is a major social and economic burden to society. Line probe assay (LPA) is a method for detecting Mycobacterium tuberculosis (MTb) in combination with resistance to rifampicin and isoniazid by first-line LPA, resistance to fluoroquinolones (FQ) and second-line injectable drugs (SLID) by second-line LPA in sputum smear-positive specimens (direct testing) and cultured isolates (indirect testing). LPA uses a DNA-based reverse hybridization method, which determines the drug resistance profile through the pattern of binding of DNA amplicons to probes that target specific areas of the MTb genome for MTb detection and to most common mutations conferring resistance to various drugs and/or the corresponding wild-type DNA sequence. LPA is endorsed by the National Tuberculosis Elimination Programme (NTEP), but very limited data are available, especially from high-burden areas such as Bihar, where a rapid, accurate, cost-effective technique like LPA can play a crucial role in early diagnosis and initiation of treatment and ultimately contribute to the effective elimination of the disease. This cross-sectional study was performed at Indira Gandhi Institute of Medical Sciences, Patna, a tertiary care centre, and aimed at the molecular characterization of Rifampicin resistant tuberculosis (RR-TB) isolates using the line probe assay method. The study was conducted between November 2022 and May 2024 with 116 samples obtained from both pulmonary tuberculosis(PTB) and extrapulmonary tuberculosis(EPTB) cases that were found to be rifampicin-resistant on CBNAAT (Cartridge based nucleic acid amplification test-Gene Xpert Mtb/RIF). In this study, 116 patients were enrolled, of whom 80(68.9 %) were pre-XDR-TB cases and 36(31 %) were MDR-TB cases. The most common pattern of mutation associated with rifampicin rpoB gene was WT8 MUT3 S531L and, Isoniazid inhA gene was WT1 MUT1 c-15 t. High-level isoniazid resistance involving KatG mutation was present in 111 (95.7 %) cases and the most common mutation associated was MUT1 -S315T1. Overall prevalence of fluoroquinolone resistance in this study was 68.9 %. There is a wide prevalence of high-level isoniazid resistance and fluoroquinolone resistance among RR-TB patients, indicating the rapid emergence and transmission of resistant strains in the community. This underscores the need for enforced interventions, such as screening for MDR-TB before starting therapy and surveillance of fluoroquinolone susceptibility. Molecular characterization of RR-TB strains by Line probe assay method can play a critical role in the rapid determination of pattern of resistance in the circulating strains and hence guide tailored therapy at the earliest opportunity especially in high burden setting with limited infrastructure. Show less

Overconsumption of sucrose and other sugars has been associated with nonalcoholic fatty liver disease (NAFLD). Reports suggest hepatic de novo lipogenesis (DNL) as an important contributor to and regulator of carbohydrate-induced hepatic lipid accumulation in NAFLD. The mechanisms responsible for the increase in hepatic DNL due to overconsumption of carbohydrate diet are less than clear; however, literatures suggest high carbohydrate diet to activate the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP), which further transcribes genes involved in DNL. Here, we provide an evidence of an unknown link between nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and increased DNL. Our data indicates high carbohydrate diet to enforce nuclear shuttling of hepatic NF-κB p65 and repress transcript levels of sorcin, a cytosolic interacting partner of ChREBP. Reduced sorcin levels, further prompted ChREBP nuclear translocation, leading to enhanced DNL and intrahepatic lipid accumulation both in vivo and in vitro. We further report that pharmacological inhibition of NF-κB abrogated high carbohydrate diet-mediated sorcin repression and thereby prevented ChREBP nuclear translocation and this, in turn, attenuated hepatic lipid accumulation both in in vitro and in vivo. Additionally, sorcin knockdown blunted the lipid-lowering ability of the NF-κB inhibitor in vitro. Together, these data suggest a heretofore unknown role for NF-κB in regulating ChREBP nuclear localization and activation, in response to high carbohydrate diet, for further explorations in lines of NAFLD therapeutics. Show less