Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Published: December 2019
AI Article Synopsis
Article Abstract
The known mode of action of isoniazid (INH) is to inhibit bacterial cell wall synthesis following activation by the bacterial catalase-peroxidase enzyme KatG in Mycobacterium tuberculosis (Mtb). This simplistic model fails to explain (a) how isoniazid penetrates waxy granulomas with its very low lipophilicity, (b) how isoniazid kills latent Mtb lacking a typical cell wall, and (c) why isoniazid treatment time is remarkably long in contrast to most other antibiotics. To address these questions, a novel comprehensive mode of action of isoniazid has been proposed here. Briefly, isoniazid eradicates latent tuberculosis (TB) by prompting slow differentiation of pro-inflammatory monocytes and providing protection against reactive species-induced "self-necrosis" of phagocytes. In the case of active TB, different immune cells form INH-NAD adducts to inhibit Mtb's cell wall biosynthesis. This additionally suggests that the antibacterial properties of INH do not rely on KatG of Mtb. As such, isoniazid-resistant TB needs to be re-evaluated.
The evolutionary arms race between plants and insects has led to key adaptive innovations that drive diversification. Alkaloids are well-documented anti-herbivory compounds in plant chemical defences, but how these specialized metabolites are allocated to cope with both biotic and abiotic stresses concomitantly is largely unknown. To examine how plants prioritize their metabolic resources responding to herbivory and cold, we integrated dietary toxicity bioassay in insects with co-expression analysis, hierarchical clustering, promoter assay, and protein-protein interaction in plants.
Photosensitizing compounds are eco-friendly promising organic dyes for managing insect pests without facing the risk of resistance. The photodynamic efficacy of four Photosensitizing compounds (rose Bengal, rhodamine B, methylene blue and methyl violet) was monitored against the third larval instar of Spodoptera littoralis (Boisduval), after exposure to sunlight. The LC values of the four compounds; rose Bengal, rhodamine B, methylene blue and methyl violet recorded 0.
The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in Candida albicans. Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses.
In order to develop new antifungal molecules and explore further applications of natural products, 25 novel amide-urea compounds were synthesized from anethole in this work by a few simple reactions, and structural confirmation was conducted using 1H-NMR, 13C-NMR, HRMS, and FT-IR. Preliminary bioactivity tests were performed against eight plant pathogens. The results demonstrated that all compounds exhibited antifungal activity against the tested fungi, and 5p exhibited the most potent antifungal activity.
Introduction: Osteoarthritis (OA) is a common chronic musculoskeletal disease with heterogeneous clinical manifestations and variable responses to different treatments. Unfortunately, there is no effective disease modifying therapy at present that can alter the natural course of the disease. Cell therapy based on mesenchymal stromal cells (MSCs) may offer an attractive therapeutic option for OA with their multiple modes of action, particularly immune-regulatory and regenerative capacities.
