ABSTRACT
This study investigates the PM2.5 bound metals using yearlong measurements at a regionally representative suburban site in the Northwest Indo-Gangetic Plain (NWIGP). The order of the measured annual average concentrations of PM2.5 bound metals is Fe > Zn > Ba > Sn > Pb > Cd > Ni > Mn > Cr > Li. Lithium bound to airborne PM2.5 has been reported for the first time in NWIGP. Ni (72.4 ng m-3) and Cd (36.9 ng m-3) have exceeded the acceptable limits set by NAAQS, India. Estimated the hazard quotient (HQ > 1) of Mn and hazard index (HI > 1) of measured metals exceeded the threshold limits indicating the potential non-carcinogenic health risk due to inhalation exposure of PM2.5 bound trace metals. Further, excessive lifetime cancer risk due to inhalation exposure to Cd, Ni and Cr was estimated and found to exceed the threshold limit set by the USEPA for adults and children.
ABSTRACT
Huntington's disease (HD) is an incurable and progressive neurodegenerative disease affecting the basal ganglia of the brain. HD is caused due to expansion of the polyglutamine tract in the protein Huntingtin resulting in aggregates. The increased PolyQ length results in aggregation of protein Huntingtin leading to neuronal cell death. Vitamin B6, B12 and folate are deficient in many neurodegenerative diseases. We performed an integrated analysis of transcriptomic, metabolomic and cofactor-protein network of vitamin B6, B12 and folate was performed. Our results show considerable overlap of pathways modulated by Vitamin B6, B12 and folate with those obtained from transcriptomic and metabolomic data of HD patients and model systems. Further, in yeast model of HD we showed treatment of B6, B12 or folate either alone or in combination showed impaired aggregate formation. Transcriptomic analysis of yeast model treated with B6, B12 and folate showed upregulation of pathways like ubiquitin mediated proteolysis, autophagy, peroxisome, fatty acid, lipid and nitrogen metabolism. Metabolomic analysis of yeast model shows deregulation of pathways like aminoacyl-tRNA biosynthesis, metabolism of various amino acids, nitrogen metabolism and glutathione metabolism. Integrated transcriptomic and metabolomic analysis of yeast model showed concordance in the pathways obtained. Knockout of Peroxisomal (PXP1 and PEX7) and Autophagy (ATG5) genes in yeast increased aggregates which is mitigated by vitamin B6, B12 and folate treatment. Taken together our results show a role for Vitamin B6, B12 and folate mediated modulation of pathways important for preventing protein aggregation with potential implications for HD. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03525-y.
ABSTRACT
A UHPLC-QTOF-MS method was developed to separate and identify 70 triterpenes present in each of the 18 strains of Ganoderma spp. Collected from various parts of India. A PCDL MS library was used to retrieve and identify these 70 triterpenes by meticulous analysis of MS/MS fragments. The MS data from these 18 strains were further statistically analysed to arrive at meaningful conclusions. Heatmap analysis suggested that Ganoderma spp. G44, G25 and G36 were the top three strains of Ganoderma mushrooms based on their metabolic concentration in Indian biota. From the PCA loading plot, it was observed that the triterpenes Ganoderic acid A, Ganoderic acid D, Ganoderic acid F, Ganoderic acid J, Ganoderic acid M, Ganoderic acid N, Ganoderenic acid B, Ganoderiol H, 3ß,7ß-Dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid, 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid and 20 - hydroxy ganoderic acid AM1 were identified as the principal contributors for the discrimination of a particular strain of the mushroom. We have also identified the samples obtained from different regions of India with the highest concentration of metabolites with potent biological activity. The results presented here could be very helpful for both scientific and industrial applications such as quality control of various medicines and food additives containing triterpenes.