Browsing by Author "Astha Shukla"

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Arbortristoside-A and 7-O-trans-cinnamoyl-6β-hydroxyloganin isolated from Nyctanthes arbortristis possess anti-ulcerogenic and ulcer-healing properties
(2013) Vaibhav Mishra; Astha Shukla; Sukanya Pandeti; Manoj Kumar Barthwal; Haushila Prasad Pandey; Gautam Palit; Tadigoppula Narender
Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery program on Indian medicinal plants, we isolated arbortristoside-A (AT) and 7-O-trans-cinnamoyl-6β-hydroxyloganin (6-HL) from the seeds of N. arbortristis. AT and 6-HL exhibited anti ulcer activity in experimentally induced ulcer models including cold restraint stress (CRU), alcohol (AL), pylorus ligation-induced gastric ulcer (PL) models and they also showed ulcer healing effect in chronic acetic acid-induced ulcer model (AC). © 2013 Elsevier GmbH. All rights reserved.
Hypoxia-Induced miR-101 Impairs Endothelial Barrier Integrity Through Altering VE-Cadherin and Claudin-5
(Springer, 2024) Astha Shukla; Utkarsh Bhardwaj; Apoorva; Pankaj Seth; Sunit K. Singh
Stroke is a life-threatening medical condition across the world that adversely affects the integrity of the blood–brain barrier (BBB). The brain microvascular endothelial cells are the important constituent of the BBB. These cells line the blood vessels and form a semipermeable barrier. Disruptions in adherens junction and tight junction proteins of brain microvascular endothelial cells compromise the integrity of BBB. The Vascular Endothelial (VE)-cadherin is an integral adherens junction protein required for the establishment and maintenance of the endothelial barrier integrity. This study aims to investigate the role of miRNA in hypoxia-induced endothelial barrier disruption. In this study, brain endothelial cells were exposed to hypoxic conditions for different time points. Western blotting, overexpression and knockdown of miRNA, real-time PCR, TEER, and sodium fluorescein assay were used to examine the effect of hypoxic conditions on brain endothelial cells. Hypoxic exposure was validated using HIF-1α protein. Exposure to hypoxic conditions resulted to a significant decrease in endothelial barrier resistance and an increase in sodium fluorescein migration across the endothelial barrier. Reduction in endothelial barrier resistance demonstrated compromised barrier integrity, whereas the increase in migration of sodium fluorescein across the barrier indicated the increase in barrier permeability. The present study revealed microRNA-101 decreases the expression of VE-cadherin and claudin-5 in brain endothelial cells exposed to the hypoxic conditions. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023.
Multidimensional Roles of Microglial Cells in Neuroviral Infections
(Springer Nature, 2022) Meghana Rastogi; Neha Pandey; Astha Shukla; Saurabh Singh; Sunit K. Singh
Microglial cells are the brain resident macrophages which are involved in maintaining CNS homeostasis. During CNS infections, the microglial cells get activated and trigger immune response. Neuroviral infections often lead to encephalitis, encephalopathy, and meningitis. This chapter highlights the roles of microglial cells during several neuroviral infections. Microglia, as the first responders to neuroviral infections, generate pro-inflammatory and antiviral response, affect the adaptive immune response and perturb the cell death pathways. The mechanisms behind most of these responses are poorly understood and require further studies in order to understand the pathophysiological mechanisms during neuroviral infections. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.
Proteome profiling of human lung epithelial cells unveils distinct patterns of protein expression in response to SARS-CoV-2 ORF3a
(Elsevier B.V., 2025) Apoorva; Astha Shukla; Atul Kumar; Saurabh B. Singh; Sunit Kumar Singh
The COVID-19 pandemic caused by SARS-CoV-2 remains an ongoing global health concern. Understanding the roles of SARS-CoV-2 accessory proteins is essential for developing effective therapeutic strategies. We present a comprehensive proteomic analysis of human lung epithelial cells in response to SARS-CoV-2 ORF3a. Through, the high-resolution mass spectrometry analysis, we observed significant alterations in the cellular proteome of human lung epithelial cells transfected with SARS-CoV-2 ORF3a. We identified a total of 56 proteins with differential expression patterns. Among these, 17 proteins showed upregulation, while 39 proteins exhibited downregulation in response to SARS-CoV-ORF3a. The pathway enrichment analysis led to the identification of proteins like NEU1, CTSH, ABCE1, Nup155, and KLC1, having important roles in innate immunity, adaptive immunity, cytokine signaling, and antiviral mechanisms. Furthermore, the protein-protein interaction (PPI) network analysis revealed USP10, HELZ, and EXOSC4 as hub proteins. These proteins may play a role in modulating the host's cellular immune functions in response to SARS-CoV-2 ORF3a. Taken together, the present study demonstrates key proteins involved in ORF3a-mediated dampened immune response in human lung epithelial cells, which may facilitate viral replication. These findings may pave the way for understanding the molecular pathogenesis of SARS-CoV-2 and developing novel therapeutic interventions targeting viral accessory proteins. © 2025 The Authors
SARS coronavirus 2: from genome to infectome
(BioMed Central Ltd, 2020) Meghana Rastogi; Neha Pandey; Astha Shukla; Sunit K. Singh
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths. The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders. © 2020, The Author(s).
Zika virus NS1 suppresses the innate immune responses via miR-146a in human microglial cells
(Elsevier B.V., 2021) Astha Shukla; Meghana Rastogi; Sunit K. Singh
Zika virus (ZIKV) is a positive-single strand RNA virus that belongs to the Flaviviridae family. ZIKV infection causes congenital ZIKV syndrome (CZS) in children and Guillain Barre Syndrome (GBS) in adults. ZIKV infected cells secrete non-structural protein 1 (sNS1), which plays an important role in viral replication and immune evasion. The microglial cells are the brain resident macrophages that mediate the immune responses in CNS. The miRNAs are small non-coding RNAs that regulate the expression of their target genes by binding to the 3’UTR region. The present study highlights the bystander effect of ZIKV-NS1 via miR-146a. The Real-Time PCR, Immunoblotting, overexpression, knockdown studies, and reactive oxygen species measurement have been done to study the immunomodulatory effects of ZIKV-NS1 in human microglial cells. ZIKV-NS1 induced the expression of miR-146a and suppressed the ROS activity in human microglial cells. The up-regulated miR-146a led to the decreased expression of TRAF6 and STAT-1. The reduced expression of TRAF6 in turn led to the suppression of pNF-κBp65 and TNF-α downstream. The miR-146a suppressed the pro-inflammatory and cellular antiviral responses in microglial cells. Our findings demonstrate the bystander role of ZIKV-NS1 in suppressing the pro-inflammatory and cellular antiviral responses through miR-146a in human microglial cells. © 2021 Elsevier B.V.