Browsing by Author "Swati Chandra"

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Cellular internalization and stress response of ingested amorphous silica nanoparticles in the midgut of Drosophila melanogaster
(2013) Ashutosh Pandey; Swati Chandra; Lalit Kumar Singh Chauhan; Gopeshwar Narayan; Debapratim Kar Chowdhuri
Background: Amorphous silica nanoparticles (aSNPs) are used for various applications including food industry. However, limited in vivo studies are available on absorption/internalization of ingested aSNPs in the midgut cells of an organism. The study aims to examine cellular uptake of aSNPs (< 30 nm) in the midgut of Drosophila melanogaster (Oregon R+) owing to similarities between the midgut tissue of this organism and human and subsequently cellular stress response generated by these nanoparticles. Methods: Third instar larvae of D. melanogaster were exposed orally to 1-100 μg/mL of aSNPs for 12-36 h and oxidative stress (OS), heat shock genes (hsgs), membrane destabilization (Acridine orange/Ethidium Bromide staining), cellular internalization (TEM) and apoptosis endpoints. Results: A significant increase was observed in OS endpoints in the midgut cells of exposed Drosophila in a concentration- and time-dependent manner. Significantly increased expression of hsp70 and hsp22 along with caspases activation, membrane destabilization and mitochondrial membrane potential loss was also observed. TEM analysis showed aSNPs-uptake in the midgut cells of exposed Drosophila via endocytic vesicles and by direct membrane penetration. Conclusion: aSNPs after their internalization in the midgut cells of exposed Drosophila larvae show membrane destabilization along with increased cellular stress and cell death. General significance: Ingested aSNPs show adverse effects on the cells of GI tract of the exposed organism thus their industrial use as a food-additive may raise concern to human health. © 2012 Elsevier B.V. © 2012 Elsevier B.V. All rights reserved.
Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster
(Kluwer Academic Publishers, 2014) Ashutosh Pandey; Divya Vimal; Swati Chandra; Sanjay Saini; Gopeshwar Narayan; Debapratim Kar Chowdhuri
Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, we evaluate cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 μg/ml) using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 h to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. We also examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. We observed mild OS and induction of antioxidant defense system in 20.0 μg/ml DCA-exposed organism after 24 h. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA. © 2014 American Aging Association.
Role of miRNAs in development and disease: Lessons learnt from small organisms
(Elsevier Inc., 2017) Swati Chandra; Divya Vimal; Divya Sharma; Vipin Rai; Subash Chandra Gupta; D. Kar Chowdhuri
MicroRNAs (miRNAs) constitute a class of small (18–22 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation. The miRNAs associated with fragile X syndrome, Parkinson's disease, Alzheimer's disease, diabetes, cancer, malaria, infectious diseases and several other human diseases have been identified from small organisms. These organisms have been used as platforms in deciphering the functions of miRNAs in the pathogenesis of human diseases and to study miRNA biogenesis. Small organisms have also been used in the development of miRNA-based diagnostic, prognostic and therapeutic strategies. The molecular techniques such as genome sequencing, northern blot analysis, and quantitative RT-PCR, have been used in deciphering the functions of miRNAs in small organisms. How miRNAs from small organisms especially those from Drosophila and C. elegans regulate development and disease pathogenesis is the focus of this review. The outstanding questions raised by our current understanding are discussed. © 2017 Elsevier Inc.