Publications by authors named "Smriti Mittal"

Article Synopsis
  • - Erythropoiesis, the process of red blood cell formation, is influenced by numerous genes that are regulated not only by transcription but also by epigenetic factors like microRNAs (miRNAs), essential for both normal functioning and various blood disorders.
  • - Specific miRNAs regulate the stages of erythropoiesis and have been linked to hematological diseases, highlighting their potential as biomarkers and therapeutic targets in conditions such as anemia, β-thalassemia, and leukemia, with some showing promising results in clinical trials.
  • - Despite the advances in understanding miRNAs' roles, challenges remain in effectively delivering them for therapeutic use without unwanted effects, necessitating ongoing research to improve treatment strategies.
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Eukaryotic cells respond to stress by altering coding and non-coding gene expression programs. Alongside many approaches and regulatory mechanisms, long non-coding RNAs (lncRNA) are finding a significant place in gene regulation, suggesting an involvement in various cellular processes and pathophysiology. LncRNAs are regulated by many transcription factors, including SMAR1 and p53, which are tumor suppressor genes.

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Intracellular antioxidant glutaredoxin controls cell proliferation and survival. Based on the active site, structure, and conserved domain motifs, it is classified into two classes. Class I contains dithiol Grxs with two cysteines in the consensus active site sequence CXXC, while class II has monothiol Grxs with one cysteine residue in the active site.

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Obesity is defined as an abnormal accumulation of adipose tissue in the body and is a major global health problem due to increased morbidity and mortality. Adipose tissue is made up of adipocytes, which are fat-storing cells, and the differentiation of these fat cells is known as adipogenesis. Several transcription factors (TFs) such as CEBPβ, CEBPα, PPARγ, GATA, and KLF have been reported to play a key role in adipogenesis.

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Article Synopsis
  • The study investigates the antioxidant and anticancer properties of extracts from Ganoderma resinaceum and Serpula similis, marking the first exploration of their mycochemical potential.
  • Results show that both extracts exhibit significant cytotoxic effects on HCT 116 cancer cell lines, with G. resinaceum showing 12.7% and 13.7% cytotoxicity at different concentrations, while S. similis shows 6.7% and 25.5%.
  • The analysis identified various bioactive compounds, suggesting these mushroom extracts could be valuable in pharmaceuticals and food for their health benefits.
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Glutaredoxin (Grx) is an antioxidant redox protein that uses glutathione (GSH) as an electron donor. Grx plays a crucial role in various cellular processes, such as antioxidant defense, control of cellular redox state, redox control of transcription, reversible S-glutathionylation of specific proteins, apoptosis, cell differentiation, etc. In the current study, we have isolated and characterized dithiol glutaredoxin from Hydra vulgaris Ind-Pune (HvGrx1).

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Thioredoxin (Trx) and glutathione disulfide (GSSG), are regenerated in reduced state by thioredoxin reductase (TrxR) and glutathione reductase (GR) respectively. A novel protein thioredoxin glutathione reductase (TGR) capable of reducing Trx as well as GSSG, linking two redox systems, has only been reported so far from parasitic flat worms and mammals. For the first time, we report a multifunctional antioxidant enzyme TGR from the nonparasitic, nonmammalian cnidarian Hydra vulgaris (HvTGR) which is a selenoprotein with unusual fusion of a TrxR domain with glutaredoxin (Grx) domain.

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Adipogenesis involves commitment of stem cells and their differentiation into mature adipocytes. It is tightly regulated by hormones, nutrients and adipokines. Many natural compounds are being tested for their anti-adipogenic activity which can be attributed to apoptosis induction in adipocytes, blocking adipocyte differentiation, or inhibiting intracellular triglyceride synthesis and accumulation.

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Thioredoxins, small disulphide-containing redox proteins, play an important role in the regulation of cellular thiol redox balance through their disulfide reductase activity. In this study, we have identified, cloned, purified and characterized thioredoxin 1 (HvTrx1) from the Cnidarian Hydra vulgaris Ind-Pune. Bioinformatics analysis revealed that HvTrx1 contains an evolutionarily conserved catalytic active site Cys-Gly-Pro-Cys and shows a closer phylogenetic relationship with vertebrate Trx1.

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Aims: PPARγ is a crucial transcription factor involved in development of hepatic steatosis, an early stage of NAFLD. PPARγ is tightly regulated through various positive and negative regulators including miRNAs. In this study, we report for the first time miR-3666 as a negative regulator of PPARγ and its involvement in development of hepatic steatosis.

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Scaffold/matrix attachment regions (S/MARs) are DNA elements that serve to compartmentalize the chromatin into structural and functional domains. These elements are involved in control of gene expression which governs the phenotype and also plays role in disease biology. Therefore, genome-wide understanding of these elements holds great therapeutic promise.

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Andrographis paniculata Nees and its principal compound andrographolide are well known for exerting beneficial effects by modulating signaling pathways in different biological systems. Our earlier studies have demonstrated the ability of andrographolide as well as andrographolide enriched extracts to activate Nrf2/HO-1 pathway through adenosine A receptor. Present study investigated ability of andrographolide to regulate Nrf2 induced antioxidant defense systems by miRNAs using HepG2 cells.

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Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood.

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Geraniin is a hydrolysable tannin, widely present in many plant species, specifically used in traditional medicines. It has been shown to exhibit strong antioxidant activity in vitro. This study was performed to investigate hepatoprotective activity of geraniin against carbon tetrachloride (CCl) induced damage in Swiss albino mice.

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Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIP-sequencing.

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Background: Andrographolide, principle constituent of Andrographis paniculata Nees is used in traditional medicine in Southeast Asia and is known to exhibit various biological activities. Its antioxidant activity is due to its ability to activate one of the antioxidant enzymes, heme oxygenase-1 (HO-1) which is regulated transcriptionally through Nrf-2. However, molecular mechanism underlying activation of Nrf-2/HO-1 has not yet been clearly understood.

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The new world hookworm, Necator americanus is a soil-transmitted nematode responsible for Necatoriasis (a type of helminthiasis) in hosts such as humans, dogs, and cats. N. americanus genome and transcriptome has been sequenced and a draft assembly analysis has been published highlighting protein coding genes and possible drug target proteins.

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The heme-regulated inhibitor (HRI), a regulator of translation initiation, is known to be activated and upregulated, and it acts as either a cytoprotective player promoting cell survival or as an inducer of apoptosis during stress. However, the exact role of HRI in these two responses has not been elucidated. In the present investigation, using human cell lines, we attempted to unravel the molecular mechanism(s) of HRI-mediated differential response and the involved signaling pathways.

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Erythropoiesis is controlled by a complex interplay of several signaling pathways and key transcription factors, as well as microRNAs (miRNAs). MicroRNAs function as critical modulators of gene expression for cellular processes. In the present study, we found that miR-320a inhibits erythroid differentiation by targeting Matrix Attachment Region binding protein SMAR1.

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Acetylation of p53 is indispensable for its transcriptional activities and induction of apoptosis upon DNA damage. Here, we show that chromatin remodelling protein SMAR1 inhibits p53 acetylation and p53 dependent apoptosis by repressing p300 expression in response to DNA damage. The repression of p300 expression by SMAR1 is relieved upon treatment with proteosomal inhibitors MG132 and Lactacystin.

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Article Synopsis
  • The study explores how the tumour suppressor p53 differentiates between cell cycle arrest and apoptosis, revealing a complex interaction involving SMAR1 and the MAR element in the promoters of BAX and PUMA.
  • When mild DNA damage occurs, SMAR1 represses BAX and PUMA, resulting in cell cycle arrest rather than apoptosis.
  • Conversely, severe DNA damage enhances apoptotic processes by promoting p53 acetylation and reducing SMAR1's ability to bind to BAX and PUMA, ultimately leading to cell death.
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Oxidative stress leads to perturbation of a variety of cellular processes resulting in inhibition of cell proliferation. This study has determined the effect of oxidative stress on protein synthesis in human K562 cells using a hydrophilic peroxyl radical initiator, AAPH and H(2)O(2). The results indicated that oxidative stress leads to a significant decrease in the rate of protein synthesis caused due to induced activation as well as expression of the erythroid cell-specific eIF-2alpha kinase, called the Heme Regulated Inhibitor (HRI).

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