dQuorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZresistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZmediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. Candidiasis is a prevalent fungal infection caused by species of the yeast genus Candida. There are more than Candida 20 species, the most common of which is Candida albicans. Candidiasis is the fourth most common cause of health care-associated bloodstream infections in India and the United States (1). This yeast normally lives on the skin and mucous membranes without causing infection. However, overgrowth of these microbes can cause superficial mycoses, invasive mucosal infections, and disseminated systemic disease, particularly in AIDS patients, transplant recipients, and other immunocompromised people (2, 3). It is well documented that the emergence of drug-resistant C. albicans is increasing at an alarming pace (4-6). Therefore, the need for effective anticandidal therapy is increasing, as the available drugs are still very restricted.Currently available therapies for candidiasis are based on antifungal drugs including azoles, echinocandins, and inhibitors of calcineurin, Hos2 deacetylase, and Hsp90 (7-10). Fluconazole (FCZ) is most widely used to treat candidiasis infections because of its high bioavailability and low toxicity (11-13). However, excessive and indiscriminate clinical use of FCZ has led to the emergence of multiple-drug-resistant (MDR) strains of C. albicans (5,14,15). Importantly, t...

No abstract

BackgroundThe quality of herbal medicine is determined by its secondary metabolites, which may vary according to growth, season and altitude etc.ObjectiveWe studied the variation in phytochemistry and biological activities of Thalictrum foliolosum (TF) roots collected from four sites at different altitudes.Material and methodsThe berberine content in different extracts of T. foliolosum roots collected from various altitudes was estimated using HPTLC. Total phenolic and flavonoid contents were determined using Folin-Ciocalteau reagent and aluminum chloride method respectively. The sensitivity of microbes for the extracts was studied using disc diffusion and the MIC was estimated using broth dilution method. Antioxidant capacity of the plant was studied using β-carotene bleaching assay, lipid peroxidation assay using goat liver, reducing power assay and DPPH free radical scavenging activity.ResultsBerberine content varied inversely with altitude; while phenol and flavonoid content of TF increased at higher altitudes. All the TF extracts showed moderate to high activity against Candida albicans, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Extracts with high berberine content were most effective against C. albicans and S. aureus and also showed relatively significant anti-lipid peroxidation, β-carotene bleaching and reducing power. TF extracts with higher phenol and flavonoid content showed better scavenging of DPPH free radicals. Berberine was used as a standard in all the antioxidant and antimicrobial experiments performed.ConclusionThalictrum from lower elevations can be explored as an alternate source of berberine and the plant has high antioxidant and antimicrobial properties owing to its berberine content.

Along with many adaptive strategies, dynamic changes in protein abundance seem to be the common strategy to cope up with abiotic stresses which can be best explored through proteomics. Understanding of drought response is the key to decipher regulatory mechanism of better adaptation. Rice (Oryza sativa L.) proteome represents a phenomenal source of proteins that govern traits of agronomic importance, such as drought tolerance. In this study, a comparison of root cytoplasmic proteome was done for a drought tolerant rice (Heena) cultivar in PEG induced drought conditions. A total of 510 protein spots were observed by PDQuest analysis and 125 differentially regulated spots were subjected for MALDI-TOF MS-MS analysis out of which 102 protein spots identified which further led to identification of 78 proteins with a significant score. These 78 differentially expressed proteins appeared to be involved in different biological pathways. The largest percentage of identified proteins was involved in bioenergy and metabolism (29%) and mainly consists of malate dehydrogenase, succinyl-CoA, putative acetyl-CoA synthetase, and pyruvate dehydrogenase etc. This was followed by proteins related to cell defense and rescue (22%) such as monodehydroascorbate reductase and stress-induced protein sti1, then by protein biogenesis and storage class (21%) e.g. putative thiamine biosynthesis protein, putative beta-alanine synthase, and cysteine synthase. Further, cell signaling (9%) proteins like actin and prolyl endopeptidase, and proteins with miscellaneous function (19%) like Sgt1 and some hypothetical proteins were also represented a large contribution toward drought regulatory mechanism in rice. We propose that protein biogenesis, cell defense, and superior homeostasis may render better drought-adaptation. These findings might expedite the functional determination of the drought-responsive proteins and their prioritization as potential molecular targets for perfect adaptation.

Herbo-metallic preparations such as bhasmas (ash) are used traditionally in Indian and Chinese medicinal systems.

No abstract

No abstract

The palladium-catalysed isocyanide insertion in 2-bromophenylthioureas leads to the formation of 4-substituted imino-4H-benzo[d][1,3]thiazin-2-amines via C–S cross coupling reaction of the intermediate imidoylpalladium species.