Effect of Piper nigrum (Linn.) seeds extract and second line anti-tuberculosis drugs on a few Mycobacterium tuberculosis strains

Piper nigrum (Linn.) belonging to the family Piperaceae have been reported for its multitudinous medicinal values. The present study was undertaken to examine the direct effect of Ethionamide (ETH), Para amino salicylic acid (PAS), ethanolic extracts of P. nigrum on Mycobacterium tuberculosis (MTB) strain H37Rv and Multi drug-resistant (MDR)-strains-12, 19 and 21. The proportion method was used to detect the anti-mycobacterial drug susceptibility testing for mycobacteria using Lowenstein Jensen (LJ) medium. It was found that P. nigrum does not interfere with single or in the combination of both ETH and PAS showing the bioenhancer activity. In vitro study of ethanolic extract of P. nigrum observed that the extract inhibited the growth of H37Rv strains and MDR strains-12, MDR strains 19, and MDR strains 21. The present results will pave new avenues to find a new medicine that possesses P. nigrum alone or in combination with drugs to combat MDR-strains controlling tuberculosis.

Biochemical Characterization of Arylamine N-acetyltransferases From Vibrio vulnificus

Vibrio vulnificus is a zoonotic bacterium that is capable of causing highly lethal diseases in humans; this pathogen is responsible for 95% of all seafood-related deaths in the United States. Arylamine N-acetyltransferases (NAT, E.C. 2.3.1.5) is a major family of xenobiotic-metabolizing enzymes that can biotransform aromatic amine chemicals. In this research, to evaluate the effect of NAT on acetyl group transformation in arylamine antibiotics, we first used sequence alignment to study the structure of V. vulnificus NAT [(VIBVN)NAT]. The nat gene encodes a protein of 260 amino acids, which has an approximate molecular mass of 30 kDa. Then we purified recombinant (VIBVN)NAT and determined the enzyme activity by PNPA and DTNB methods. The DTNB method indicates that this prokaryotic NAT has a particular substrate specificity towards aromatic substrates. However, (VIBVN)NAT lost most of its activity after treatment with high concentrations of urea and H2O2. In addition, we also explored the stability of the enzyme at different temperatures and pH values. In analyzing the influence of metal ions, the enzyme activity was significantly inhibited by Zn2+ and Cu2+. The kinetic parameters Km and Vmax were determined using hydralazine, isoniazid, 4-amino salicylic acid, and 4-chloro-3-methylaniline as substrates, and the Tm, Tagg and size distribution of (VIBVN)NAT were observed. In particular, a molecular docking study on the structure of (VIBVN)NAT was conducted to understand its biochemical traits. These results showed that (VIBVN)NAT could acetylate various aromatic amine substrates and contribute to arylamine antibiotic resistance in V. vulnificus.

Inhibition of PD-1 Protects against TNBS-Induced Colitis via Alteration of Enteric Microbiota

Background and Aim. The enteric microbiota is able to cross-talk with factors involved in the blockade of programmed cell death protein 1 (PD-1) and also plays an important role in the predisposition and onset of inflammatory bowel disease (IBD). The current study used a mouse model of experimental colitis to determine the pathogenic connection between PD-1 inhibition, gut microbiota, and IBD. Methods. Colitis was induced in mice using 2,4,6-trinitrobenzene-sulfonic acid (TNBS), and mice were subsequently treated with either a PD-1 inhibitor or 5-amino-salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high-throughput 16S rRNA sequencing of fecal samples from the experimental mice. Results. TNBS caused mice to experience IBD-like symptoms, which were attenuated by the PD-1 inhibitor, as indicated by a decrease in DAI scores ( p = 0.0002 ). Furthermore, in this mouse model of IBD, PD-1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short-chain fatty acid- (SCFA-) producing bacteria of the Firmicutes ( p < 0.05 ) and Bacteroidetes ( p < 0.05 ) phyla but depopulated Proteobacteria ( p < 0.05 ). Conclusion. PD-1 inhibition can partly mitigate TNBS-induced colitis and restore the enteric microbiota by enriching the abundance of SCFA-producing bacteria.

Ni-Doped ZrO2 nanoparticles decorated MW-CNT nanocomposite for the highly sensitive electrochemical detection of 5-amino salicylic acid

Ni-ZrO2/MWCNT/GCE for highly sensitive electrochemical detection of 5-ASA in biofluids.