Browsing by Author "Jamwal, Sumit"

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    Animal models of Huntington�s disease and their applicability to novel drug discovery and development
    (Taylor and Francis Ltd., 2023-04-12T00:00:00) Upadhayay, Shubham; Jamwal, Sumit; Kumar, Puneet
    Introduction: Huntington�s disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the CAG trinucleotide repeat in huntingtin (Htt) gene. The discovery of the HD-causing gene prompted the creation of new HD animal models, proving that mutations in the HD gene are linked to either loss of function of the wild-type (un-mutated) gene or toxic gain in the function of a mutated gene. Areas Covered: Animal models of HD have led to an increased understanding of its pathogenesis and resulted in the discovery of new therapeutic targets/drugs. The focus of this review is on the selection and validation of animal models for HD drug discovery. Furthermore, several drugs tested using various models in the preclinical phase have been compiled to demonstrate the applicability of these HD animal models. Expert opinion: The applicability of animal models for HD drug discovery has been well demonstrated. Nevertheless, despite the enormous progression made to date, the development of drug therapy to completely alleviate disease progression has not been achieved. Most of the pre-clinically tested drugs have shown promising results in alleviating HD-associated neurodegeneration and motor and non-motor symptoms, but only a few of them thrived to produce satisfactory results in the clinical phase. This failure has raised concerns about the selection of HD animal models and species, and new strategies for selection are mandated. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Bacillus Calmette-Gu�rin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats
    (2023-11-20T00:00:00) Yedke, Narhari Gangaram; Upadhayay, Shubham; Singh, Randhir; Jamwal, Sumit; Ahmad, Sheikh F.; Kumar, Puneet
    Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 � 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.
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    Neuroprotection through G-CSF: recent advances and future viewpoints
    (Springer Science and Business Media Deutschland GmbH, 2021-01-02T00:00:00) Rahi, Vikrant; Jamwal, Sumit; Kumar, Puneet
    Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of hematopoietic growth factors, is 19.6�kDa glycoprotein which is responsible for the proliferation, maturation, differentiation, and survival of neutrophilic granulocyte lineage. Apart from its proven clinical application to treat chemotherapy-associated neutropenia, recent pre-clinical studies have highlighted the neuroprotective roles of G-CSF i.e., mobilization of haemopoietic stem cells, anti-apoptotic, neuronal differentiation, angiogenesis and anti-inflammatory in animal models of neurological disorders. G-CSF is expressed by numerous cell types including neuronal, immune and endothelial cells. G-CSF is released in autocrine manner and binds to its receptor G-CSF-R which further activates numerous signaling transduction pathways including PI3K/AKT, JAK/STAT and MAP kinase, and thereby promote neuronal survival, proliferation, differentiation, mobilization of hematopoietic stem and progenitor cells. The expression of G-CSF receptors (G-CSF-R) in the different brain regions and their upregulation in response to neuronal insult indicates the autocrine protective signaling mechanism of G-CSF by inhibition of apoptosis, inflammation, and stimulation of neurogenesis. These observed neuroprotective effects of G-CSF makes it an attractive target to mitigate neurodegeneration associated with neurological disorders. The objective of the review is to highlight and summarize recent updates on G-CSF as a therapeutically versatile neuroprotective agent along with mechanisms of action as well as possible clinical applications in neurodegenerative disorders including AD, PD and HD. � 2021, Maj Institute of Pharmacology Polish Academy of Sciences.
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    An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development
    (Springer, 2023-02-04T00:00:00) Upadhayay, Shubham; Yedke, Narhari Gangaram; Rahi, Vikrant; Singh, Surbhi; Kumar, Sachin; Arora, Anchal; Chandolia, Priyanka; Kaur, Prabhsharan; Kumar, Mandeep; Koshal, Prashant; Jamwal, Sumit; Kumar, Puneet
    Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model. Graphical Abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Protocols in apoptosis identification and affirmation
    (Elsevier, 2020-10-16T00:00:00) Jamwal, Sumit; Kumar, Puneet; Kakkar, Vandita; Kumari, Parina; Chahal, Simerjeet Kaur
    Protocols are set of predefined written procedural documents that offer guidance or specifications for performing the experiments and its implementation. They are an essential component of good laboratory practice (GLP) and good clinical practice (GCP) regulations that establish the study�s rationale, objectives, design, and planned analyses of the results, as well as the conditions under which these procedures will be carried out. In addition to detailed procedures, protocols often include information on safety precautions, the calculation of results, and reporting standards, including statistical analysis and rules for predefining and documenting excluded data to avoid bias. The protocol is the heart of every experiment. It is the plan; it is a critical document for everyone involved in the conduct of the procedure�Rebecca Kush, President of CDISC Different protocols are available which provide signaling pathways of introduction to �Programmed cell death� which called �Apoptosis�. The course of programmed cell death or �Apoptosis� is generally regarded as a typical element of the human health and disease state. Normal homeostasis is sustained throughout by maintaining balance between cell death and cell division. Apoptosis is phenomenon that involves specific activation of death-signaling pathways leading to the removal of cells from tissue. The individual morphological features of apoptosis include cell shrinkage, chromatin condensation, membrane blebbing, and formation of apoptotic bodies. Inapt apoptosis is a key factor in many diseased conditions, including neurodegenerative diseases, cancer, I-R injury, and many more. In addition, the area of apoptosis research is growing at an alarming rate and till date vast research has been made on the clarification and analysis of the cell cycle mechanisms and signaling pathways regulating cell cycle. The aptitude to detect and quantify apoptosis and to understand its biochemistry related to regulatory genes and proteins is highly crucial for biomedical research. This chapter is an attempt to highlight various basic as well as advanced tools and techniques (like immunohistochemistry, TUNEL assay, in-situ end-labeling techniques in conjunction with standard flow cytometry) used in area of apoptosis research in addition to focus on protocols used in qualitative and quantitative determination of apoptosis to be followed during preclinical and clinical phase of drug development. The use of aforementioned techniques for apoptosis quantification will enable clinical investigators to accurately assess apoptosis in context of various diseases. � 2021 Elsevier Inc. All rights reserved.
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    Role of vitamins and minerals as immunity boosters in COVID-19
    (Springer Science and Business Media Deutschland GmbH, 2021-06-10T00:00:00) Kumar, Puneet; Kumar, Mandeep; Bedi, Onkar; Gupta, Manisha; Kumar, Sachin; Jaiswal, Gagandeep; Rahi, Vikrant; Yedke, Narhari Gangaram; Bijalwan, Anjali; Sharma, Shubham; Jamwal, Sumit
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19. � 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.