Department Of Pharmacology

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Author: search.filters.author.Navik, Umashanker

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    Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach
    (John Wiley and Sons Inc, 2023-10-04T00:00:00) Goyal, Falak; Chattopadhyay, Anandini; Navik, Umashanker; Jain, Aklank; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    mRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to antitumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system are precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with stimulator of interferon genes (STING) and tumor-infiltrating lymphocytes pathways, activating more CD8+ T-cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Nonformulated or vehicle-based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen-presenting cells and stimulate both innate and adaptive immune responses. Codelivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focuses on the current clinical approaches and challenges to consider when developing mRNA-based vaccine technology for cancer treatment. � 2023 Wiley-VCH GmbH.
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    Protective role of natural products and bioactive compounds in multiple sclerosis
    (Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Singh, Harsh Vikram; Sharma, Eva; Sehrawat, Abhishek; Mishra, Jayapriya; Navik, Umashanker; Hemachandra Reddy, P.; Bhatti, Jasvinder Singh
    Multiple sclerosis (MS), a chronic multifactorial disease characterized by progressive demyelination and neurodegeneration, is rising rapidly in young adults. The pathology of the disease is not yet understood completely. However, neuroinflammation, oxidative stress, and hyperactive autoimmune response appear to play a prominent role in the pathogenesis of the disease. Several genetic, nongenetic, and environmental factors are also found associated with this autoimmune disorder. Although, it is still a matter of debate whether diet and lifestyle have an influence during the course of MS. Recent studies have highlighted several beneficial characteristics of natural bioactive compounds such as anti-inflammatory, antioxidative, immunomodulatory, and other neuroprotective effects, indicating their therapeutic potential to reduce the risk or ameliorate the progression of MS. Basically, these bioactive compounds are the chemicals found in minute amounts naturally in plants with peculiar health benefits. In this chapter, we have briefly described various natural bioactive compounds with neuroprotective effects against MS, including the polyphenols, vitamins supplementation, and natural products such as ginger, ashwagandha, and it seems that these compounds play a notable role in the treatment of MS. Further research is required to extend our understanding in developing more effective therapeutic strategies against the disease with lesser side effects. � 2023 Elsevier Inc. All rights reserved.
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    A comparative study of colored wheat lines across laboratories for validation of their phytochemicals and antioxidant activity
    (Academic Press, 2023-06-07T00:00:00) Sharma, Anjali; Yadav, Mona; Tiwari, Apoorv; Ali, Usman; Krishania, Meena; Bala, Manju; Sharma, Paras; Goudar, Giridhar; Roy, Joy K.; Navik, Umashanker; Garg, Monika
    With aim of assessing inter-laboratory variations, phytochemical and antioxidant analysis of seventeen wheat lines were carried out in three well-equipped Indian laboratories viz- National Agri-Food Biotechnology Institute (NABI), Punjab, Central Institute of Post-Harvest Engineering & Technology (CIPHET), Punjab, and National Institute of Nutrition (NIN), Telangana. Protocols were rigorously discussed among laboratories, re-formulated, and uniformly executed for estimating anthocyanins, phenolics, flavonoid content and antioxidant activity measured by colorimetric assays (DPPH, ABTS, FRAP & MC). Compiled data complement each other, with minor inter-laboratory variations. Colored wheat lines show higher antioxidant activity and phytochemical profile than white wheat lines across the laboratories. Within colored wheat lines, black wheat lines have the best nutraceutical profile across the laboratories, with an observed order of black > blue > purple > white. Within black wheat varieties, one of the studied lines, Bk2, consistently outperformed across the laboratories and had highest antioxidant activity, mean anthocyanin content (150.19 mg/kg), phenolic content (277.67 mg/kg), flavonoid content (17.76 mg/kg). The factors that may contribute to the evaluation process include differences in the human resources involved, type and company of solvent, instrument model, and weather and humidity conditions during the measurement. This study validates the higher phytochemicals and antioxidant property of colored wheat through a multi-laboratory analysis. � 2023 Elsevier Ltd
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    Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond
    (Editions de Sante, 2023-06-08T00:00:00) Khurana, Amit; Allawadhi, Prince; Singh, Vishakha; Khurana, Isha; Yadav, Poonam; Sathua, Kshirod Bihari; Allwadhi, Sachin; Banothu, Anil Kumar; Navik, Umashanker; Bharani, Kala Kumar
    Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NF?B), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-?) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized. � 2023 Elsevier B.V.
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    Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions
    (Elsevier Inc., 2023-06-24T00:00:00) Sharma, Garvita; Biswas, Shristi Saroj; Mishra, Jayapriya; Navik, Umashanker; Kandimalla, Ramesh; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches. � 2023 Elsevier Inc.
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    Advances in therapeutic applications of silver nanoparticles
    (Elsevier Ireland Ltd, 2023-06-01T00:00:00) Kaushal, Ashutosh; Khurana, Isha; Yadav, Poonam; Allawadhi, Prince; Banothu, Anil Kumar; Neeradi, Dinesh; Thalugula, Sunitha; Barani, Percy Jasmine; Naik, Ramavath Redya; Navik, Umashanker; Bharani, Kala Kumar; Khurana, Amit
    Nanotechnology is one of the most appealing area for developing new applications in biotechnology and medicine. For decades, nanoparticles have been extensively studied for a variety of biomedical applications. Silver has evolved into a potent antibacterial agent that can be used in a variety of nanostructured materials of various shapes and sizes. Silver nanoparticles (AgNP) based antimicrobial compounds are employed in a wide range of applications, including medicinal uses, surface treatment and coatings, the chemical and food industries, and agricultural productivity. When designing formulations for specific applications, the size, shape, and surface area of AgNPs are all crucial structural aspects to consider. Different methods for producing AgNPs with varying sizes and forms that are less harmful have been devised. The anticancer, anti-inflammatory, antibacterial, antiviral, and anti-angiogenic properties of AgNPs have been addressed in this review, as well as their generation and processes. Herein, we have reviewed the advances in therapeutic applications of AgNPs, as well as their limitations and barriers for future applications. � 2023 Elsevier B.V.
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    Dysregulated autophagy: A key player in the pathophysiology of type 2 diabetes and its complications
    (Elsevier B.V., 2023-02-14T00:00:00) Sehrawat, Abhishek; Mishra, Jayapriya; Mastana, Sarabjit Singh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of ?-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications. � 2023 Elsevier B.V.
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    Exogenous fetuin-A protects against sepsis-induced myocardial injury by inhibiting oxidative stress and inflammation in mice
    (John Wiley and Sons Inc, 2023-01-17T00:00:00) Sidheeque Hassan, V.; Hanifa, Mohd; Navik, Umashanker; Bali, Anjana
    Sepsis-induced myocardial injury is a consequence of septicemia and is one of the major causes of death in intensive care units. A serum glycoprotein called fetuin-A is secreted largely by the liver, tongue, placenta, and adipose tissue. Fetuin-A has a variety of biological and pharmacological properties. The anti-inflammatory and antioxidant glycoprotein fetuin-A has shown its efficacy in a number of inflammatory disorders including sepsis. However, its protective role against sepsis-induced myocardial injury remains elusive. The purpose of this work is to explore the role of fetuin-A in mouse models of myocardial injury brought on by cecal ligation and puncture (CLP). CLP significantly induced the myocardial injury assessed in terms of elevated myocardial markers (serum CK-MB, cTnI levels), inflammatory markers (IL-6, TNF-?) in the serum, and oxidative stress markers (increased MDA levels and decreased reduced glutathione) in heart tissue homogenate following 24 h of ligation and puncture. Further, hematoxylin and eosin (H&E) staining showed considerable histological alterations in the myocardial tissue of sepsis-developed mice. Interestingly, fetuin-A pretreatment (50 and 100 mg/kg) for 4 days before the CLP procedure significantly improved the myocardial injury and was evaluated in perspective of a reduction in the CK-MB, cTnI levels, IL-6, and TNF-? in sepsis-developed animals. Fetuin-A pretreatment significantly attenuated the oxidative stress and improved the myocardial morphology in a dose-dependent manner. The present study provides preliminary evidence that fetuin-A exerts protection against sepsis-induced cardiac dysfunction in vivo via suppression of inflammation and oxidative damage. � 2023 Soci�t� Fran�aise de Pharmacologie et de Th�rapeutique.
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    Repurposing artemisinins as neuroprotective agents: a focus on the PI3k/Akt signalling pathway
    (Springer Science and Business Media Deutschland GmbH, 2022-12-05T00:00:00) Arthur, Richmond; Navik, Umashanker; Kumar, Puneet
    Artemisinin and its derivatives, since their discovery by professor Tu Youyou in the early 1970s, have been the bedrock for the management of malaria globally. Recent works have implied that they could be used to manage other diseases including neurodegenerative disorders. Neurodegenerative disorders mainly occur in the adult population resulting from a progressive deterioration of neuronal structures. These include Parkinson�s disease (PD), Alzheimer�s disease (AD), Huntington�s disease (HD), and Multiple sclerosis (MS), among others. The PI3K/Akt signaling pathway plays a significant role in the central nervous system. It has been investigated extensively for its role in central nervous system physiological processes such as cell survival, autophagy, neuronal proliferation, and synaptic plasticity. Therefore, the modulation of this pathway will be crucial in the management of neurodegenerative disorders. This review seeks to compile most of the research findings on the possible neuroprotective role of artemisinins with special emphasis on their modulatory role on the PI3k/Akt pathway. A literature survey was conducted on PubMed, EBSCO, Web of Science, and EMBASE using the keyword artemisinins, and a total of 10,281 articles were retrieved from 1956 to 2022. Among these, 120 articles were examined using Mesh words like PI3k/Akt, neurodegeneration, and neuroinflammation coupled with boolean operators. Most research revealed that artemisinins could help neurodegenerative disorders by modulating the PI3k/Akt with subsequent inhibition of oxidative stress, neuroinflammation, and apoptosis. This paper illustrates that artemisinins could be repurposed as a neuroprotective agent. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Spotlight on liver macrophages for halting liver disease progression and injury
    (Taylor and Francis Ltd., 2022-10-07T00:00:00) Khurana, Amit; Navik, Umashanker; Allawadhi, Prince; Yadav, Poonam; Weiskirchen, Ralf
    Introduction: Over the past two decades, understanding of hepatic macrophage biology has provided astounding details of their role in the progression and regression of liver diseases. The hepatic macrophages constitute resident macrophages, Kupffer cells, and circulating bone marrow monocyte-derived macrophages, which play a diverse role in liver injury and repair. Imbalance in the macrophage population leads to pathological consequences and is responsible for the initiation and progression of acute and chronic liver injuries. Further, distinct populations of hepatic macrophages and their high heterogeneity make their complex role enigmatic. The unique features of distinct phenotypes of macrophages have provided novel biomarkers for defining the stages of liver diseases. The distinct mechanisms of hepatic macrophages polarization and recruitment have been at the fore front of research. In addition, the secretome of hepatic macrophages and their immune regulation has provided clinically relevant therapeutic targets. Areas covered: Herein, we have highlighted the current understanding in the area of hepatic macrophages, and their role in the progression of liver injury. Expert opinion: It is essential to ascertain the physiological and pathological role of evolutionarily conserved distinct macrophage phenotypes in different liver diseases before viable approaches may see a clinical translation. � 2022 Informa UK Limited, trading as Taylor & Francis Group.