Biodiversity and Bioactive Potential of Actinomycetes from Unexplored High Altitude Regions of Kargil, India.

The effectiveness of currently available antimicrobials and anticancer medications is steadily declining due to the emergence of drug resistance. Since actinobacteria are important producers of bioactive substances, we have isolated them from the soil samples of exotic North-Western Himalayan terrains. Out of 128 isolates, 39 strains were prioritized based on their bioactive potential. The diversity analysis revealed higher abundance distribution of actinomycetes in the soil of an open field (68.7%), followed by the mountainside (34.9%), from which most of the bioactive strains were obtained. The extract of the strain S26-11 was found to be highly active against Gram-positive Staphylococcus aureus and Bacillus subtilis with a MIC of 0.5 µg/mL and 1 µg/mL respectively. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines (PC-3, MCF-7, A-549, and HCT-116). The extract of the strain S26-11 showed cytotoxic activity against all cancer cell lines with an IC50 of 2 µg/mL against PC-3, 1.9 µg/mL against MCF-7, 0.52 µg/mL against A-549, and 0.83 µg/mL against HCT-116. Moreover, the antioxidant activity was assessed using a DPPH-based assay and the results revealed that the S17-8 isolate showed the highest antioxidant activity with IC50 of 114.136 µg/mL. The Response Surface Methodology (RSM) had helped to optimize the physical parameters for scaling up of the bioactive strain S26-11. The unexplored soil niches of Kargil (UT, Ladakh), India, is rich in actinomycetes which are having potential bioactivities, would be worth to explore for the discovery of bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01133-1.

Unravelling the mechanism of polarization transfer from spin-1/2 to spin-1 system in solids.

An analytic theory based on the concept of "effective-fields" is proposed to explain the mechanism of polarization transfer from spin I = 1/2 to spin S = 1 in non-rotating (static) solids. Employing an isolated two-spin model system, the matching conditions responsible for polarization transfer in cross-polarization (CP) experiments are identified and described in terms of the single-transition operators. In contrast to other existing treatments, the polarization transfer among spins is quantified through analytic expressions highlighting the individual contributions emerging from all plausible CP matching conditions. The interplay between the CP matching conditions observed in experiments is outlined in both isotropic and anisotropic systems and verified through comparison between simulations based on analytic and exact numerical methods. The predictions emerging from the analytic theory are verified over a wide range of experimentally relevant parameters and could be beneficial in the optimization of the CP experiments.

Determination of the relative orientation between 15N-1H dipolar coupling and 1H chemical shift anisotropy tensors under fast MAS solid-state NMR.

In this work, we have proposed a proton-detected three-dimensional (3D) 15N-1H dipolar coupling (DIP)/1H chemical shift anisotropy (CSA)/1H chemical shift (CS) correlation experiment to measure the relative orientation between the 15N-1H dipolar coupling and the 1H CSA tensors under fast magic angle spinning (MAS) solid-state NMR. In the 3D correlation experiment, the 15N-1H dipolar coupling and 1H CSA tensors are recoupled using our recently developed windowless C-symmetry-based C331-ROCSA (recoupling of chemical shift anisotropy) DIPSHIFT and C331-ROCSA pulse-based methods, respectively. The 2D 15N-1H DIP/1H CSA powder lineshapes extracted using the proposed 3D correlation method are shown to be sensitive to the sign and asymmetry of the 1H CSA tensor, a feature that allows the determination of the relative orientation between the two correlating tensors with improved accuracy. The experimental method developed in this study is demonstrated on a powdered U-15N L-Histidine.HCl·H2O sample.

Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis.

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7th day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis.