Aims
The study is aimed at understanding the novel molecular mechanisms governing drug resistance in the opportunistic fungi belonging to the genus Candida.
Methods and results
This is a multipronged study wherein different assays like drug susceptibility and whole cell proteome analysis, stress tolerance assay, measurement of total internal glycerol content, western blot analysis, ROS measurement, glucose uptake, lactate production, ATP generation, and NADPH measurements were made.
The study reveals an incidence of different species of Candida in the northern most part of India (Kashmir valley). Resistant isolates, mostly resistant to azoles were reported across all the species. The study revealed a difference in resistance mechanisms between C. albicans and C. glabrata clinical isolates. Further, such resistance mechanism (in the case of C. albicans) was mostly mediated by Hexokinase 2 (Hxk2) and Glucose-6-phosphate dehydrogenase (G6pd). Increased expression of Hxk2 was associated with increased glucose uptake, more lactate production, and more ATP generation in drug-resistant C. albicans. At the same time, increased G6pd expression was responsible for the increased production of NADPH, which imparts a better ROS scavenging potential. While in C. glabrata the resistance was linked with glycerol metabolism, where the drug-resistant isolate tends to accumulate more glycerol as an osmolyte in response to external stresses. This glycerol accumulation was found to be triggered by the HOG1-MAPK pathway.
Conclusion
The study concludes that, like various human malignant tumors, there is a strong correlation between drug resistance and aberrant cellular metabolism in the opportunistic fungi belonging to the genus Candida.
The flowers of Artemisia dubia wall ex Bess., on hydrodistillation provided a refreshing violet-blue viscous essential oil with sweet woody odour. The oil was found to be a complex mixture of monoterpenes, sesquiterpenes and their esters. A total of 67 chemical constituents comprising 79.43 % of the oil were characterized with the help of gas chromatography and mass spectrometry (GC/MS). Major chemical constituents of the oil were characterized as nerylisovalerate (9.79 %), 1,8-cineole (8.32 %), neryl-2-methyl-butanoate (7.32 %), chamazulene (5.92 %), linalool (4.15 %), camphor (4.10 %), germacrene D (4.04 %), nerol (3.37 %), linalyl propionate (3.32 %). The investigations performed on the flower essential oil of A. dubia allowed the distinction of this plant growing in the temperate Kashmir region of western Himalayas from the same plant with different varieties growing in different parts of the world. The essential oil was evaluated for its antifungal activity against Candida species and was found to be active against the tested strains with more sensitivity against C. paropsilosis and C. krusei strains. The antioxidant activity evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and thiobarbituric acid reactive substances (TBARS) assay evidenced that the essential oil has moderate antioxidant activity. The antiproliferative ability of the oil was evaluated by MTT assay against the two cell lines A549 (human lung adenocarcinoma epithelial cells) and HCT-116 (human colon cancer cells). The essential oil effectively inhibits the growth of A549 and HCT-116 cancer cells at 62.5 and 31.25 μg/mL concentration, respectively.
Background: Plants have a well-developed defensive machinery for minimizing the reactive oxygen species (ROS) associated damages in the form of enzymatic and non-enzymatic antioxidants. The in-vitro mechanism of antioxidant action of plant extracts may involve direct inhibition of the ROS generation or ROS scavenging. The antioxidant activity of the extracts may be due to active constituents alone or the combination of constituents. However, the amount of constituents are known to vary according to the change in environment. Method: In our study, antioxidant activity of Amaranthus caudatus L. from two different sites (elevation sites) was investigated at three stages, (vegetative, pre flowering and post flowering) using ethanolic extract (EtOH). Result: The phenolic and flavonoid content increased at all stages from site 1 to site 2. The total reducing power, Ferrous reducing antioxidative power (FRAP), diphenyl picryl hydrazine (DPPH) radical scavenging assay, superoxide dismutase scavenging (SOD) assay and hydrogen peroxide (H 2 O 2) scavenging activity increased from site 1 to site 2 at all the three stages. Conclusion: The results reveal that the altitude and the growth stage have a significant effect on antioxidative potential of Amaranthus.
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