7 research outputs found

    Effects of Ionizing Radiation on Chromosome Replication and its Modification by HDAC Inhibitors

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    Ionizing radiation causes lethal injuries either directly or indirectly inducing damage to the biological macromolecules, most importantly the genetic material or DNA. Cells transiently halt their cell cycle progression to provide sufficient time for repair machinery to act on for the repair of radiation-induced DNA damages. This may include delay in replication or S-phase of cell cycle besides activating other cell cycle checkpoints. Multiple replicons (replicon cluster equivalent to a chromosome band) along the length of a chromosome fire in a definite pattern for the timely completion of replication. Histone deacetylase inhibitors (HDACi) have been shown to alter the pattern of DNA replication origin activity including earlier replication in S-phase of normally late replicating chromosome bands. This may also indicate an acceleration of repair steps since DNA damage acts as an impediment for replication. Trichostatin A (TSA), a well-known HDACi, was studied for its effect on replication initiation using Indian Muntjac cell as a model. It was found that TSA treatment enhanced the replication rate and increased the number of replicon clusters firing at any given time per chromosome. It also compensated the decline of replication rate in irradiated cells, helped in their revival and brought them to the control level

    Radiation Countermeasures: Current Status

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    Deleterious effects of ionising radiation leading to significant morbidity and mortality have been studied elaborately. A range of synthetic, semisynthetic and herbal compounds have been screened as radiation countermeasure agents and a number of promising radiation countermeasure agents are under development. Amifostin is the only drug which has been approved by the United State Food and Drug Administration (US-FDA), but that too for use in a defined population under strict medical supervision. Granulocyte Colony Stimulating Factor/filgrastim, γ-tocotrienol, genistein are at an advanced stage of development and are tested on higher animal models as per required norms of FDA. Herbal compounds are also considered very safe and of high value as radiation countermeasure agents owing to various properties like antioxidant, immunomodulation activity etc. Histone deacetylase inhibitors such as Trichostatin A, Diallyl sulphide, Sulforaphane are being viewed as very promising radiomitigating agents by our laboratory and active research in the same direction is going on. Infusion of hematopoietic stem cells and growth factors are in practice as potent therapeutics. This review gives an overview on various radioprotectors, radiomitigators and therapeutic agents either available or under development currently

    Role of some epigenetic factors in DNA damage response pathway

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    The current review gives a brief account of the DNA damage response pathway and involvement of various epigenetic mechanisms in DNA damage response pathway. The main focus is on histone modifications leading to structural alterations in chromatin since the compact chromatin structure poses a major limitation in the DNA repair process. Based on this hypothesis, our laboratory has also evaluated certain histone deacetylase inhibitors as potential radiomitigators and the same has been discussed in brief at the end of the review

    Morbidity Profile of Cotton Textile Workers

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    IL-10 Producing Regulatory B Cells Mediated Protection against Murine Malaria Pathogenesis

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    Various immune cells are known to participate in combating infection. Regulatory B cells represent a subset of B cells that take part in immunomodulation and control inflammation. The immunoregulatory function of regulatory B cells has been shown in various murine models of several disorders. In this study, a comparable IL-10 competent B-10 cell subset (regulatory B cells) was characterized during lethal and non-lethal infection with malaria parasites using the mouse model. We observed that infection of Balb/c mice with P. yoelii I 7XL was lethal, and a rapid increase in dynamics of IL-10 producing B220+CD5+CD1d+ regulatory B cells over the course of infection was observed. However, animals infected with a less virulent strain of the parasite P. yoelii I7XNL attained complete resistance. It was observed that there is an increase in the population of regulatory B cells with an increase of parasitemia; however, a sudden drop in the frequency of these cells was observed with parasite clearance. Adoptive transfer of regulatory B cells to naïve mice followed by infection results in slow parasite growth and enhancement of survival in P. yoelii 17XL (lethal) infected animals. Adoptively transferred regulatory B cells also resulted in decreased production of pro-inflammatory cytokine (IFN-γ) and enhanced production of anti-inflammatory cytokine (IL-10). It infers that these regulatory B cells may contribute in immune protection by preventing the inflammation associated with disease and inhibiting the parasite growth

    Prioritization of Physio-Biochemical Selection Indices and Yield-Attributing Traits toward the Acquisition of Drought Tolerance in Chickpea (<i>Cicer arietinum</i> L.)

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    Chickpea is widely grown in rainfed areas of developing countries because of its nutritional abundance and adaptability. To overcome the environmental effect of drought on yield, a characteristic-linked selection strategy is proved as well-thought-out and advantageous for the development of drought-tolerant cultivars. To precisely understand the contribution of various physio-biochemical and yield-attributing traits toward drought tolerance in chickpea (Cicer arietinum L.), forty chickpea genotypes were evaluated in the years 2020–2021 and 2021–2022 under normal irrigated as well as drought-stressed conditions. Among the studied genotypes, genotype ICC4958 retained the highest chl content (0.55 mg g−1 FW), minimal electrolyte leakage, and superoxide dismutase (1.48 U/mg FW) and peroxidase (2.21 µmol/min/g FW) activities while cultivar JG11 maintained the maximum relative water content and proline accumulation. The principal-component-based biplots prioritized the physio-biochemical and yield-accrediting characteristics based on their association significance and contribution to terminal drought tolerance. Under drought stress, grain yield per plant was depicted to have a strongly positive association with canopy temperature depression, catalase, superoxide dismutase, and peroxidase activities as well as total soluble sugar, proline, and chlorophyll content, along with the numbers of pods and biological yield per plant. These identified physio-biochemical and yield-attributing traits can be further deployed to select drought-tolerant chickpea genotypes for the breeding of climate-smart chickpea genotypes
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