Department Of Pharmacology

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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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    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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    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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    Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
    (Springer Singapore, 2022-09-28T00:00:00) Bhatti, Gurjit Kaur; Pahwa, Paras; Gupta, Anshika; Sidhu, Inderpal Singh; Navik, Uma Shanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    Mitochondria are essential for the metabolism of energy, regulation of apoptosis, and cell signaling. Overproduction of reactive oxidation species (ROS) in mitochondria is one of the indications of cancer cells. Moreover, this boosts the proliferation of cancerous cells by causing genomic instability and altering gene expressions. Mitochondrial and nuclear DNA mutations caused by oxidative damage impair the mechanism of oxidative phosphorylation and can lead to more mitochondrial ROS output, genome instability, and cancer development. The classic approach to target mitochondria of cancerous cells with novel targeted therapeutics helps in targeting the mitochondrial apoptotic proteins and changing energy metabolism. A key benefit of selective drug delivery is that it reduces the drug�s toxicity and increases specificity. A better understanding of the mitochondrial role in tumor growth will help design more therapeutic agents with better selectivity. � Springer Nature Singapore Pte Ltd. 2022.
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    Zebrafish as an emerging tool for drug discovery and development for thyroid diseases
    (Academic Press, 2022-09-06T00:00:00) Yadav, Poonam; Sarode, Lopmudra P.; Gaddam, Ravinder Reddy; Kumar, Puneet; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
    Zebrafish is a useful model for understanding human genetics and diseases and has evolved into a prominent scientific research model. The genetic structure of zebrafish is 70% identical to that of humans. Its small size, low cost, and transparent embryo make it a valuable tool in experimentation. Zebrafish and mammals possess the same molecular mechanism of thyroid organogenesis and development. Thus, thyroid hormone signaling, embryonic development, thyroid-related disorders, and novel genes involved in early thyroid development can all be studied using zebrafish as a model. Here in this review, we emphasize the evolving role of zebrafish as a possible tool for studying the thyroid gland in the context of physiology and pathology. The transcription factors nkx2.1a, pax2a, and hhex which contribute a pivotal role in the differentiation of thyroid primordium are discussed. Further, we have described the role of zebrafish as a model for thyroid cancer, evaluation of defects in thyroid hormone transport, thyroid hormone (TH) metabolism, and as a screening tool to study thyrotoxins. Hence, the present review highlights the role of zebrafish as a novel approach to understand thyroid development and organogenesis. � 2022 Elsevier Ltd
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    Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
    (Springer Nature, 2022-01-31T00:00:00) Bhatti, Gurjit Kaur; Pahwa, Paras; Gupta, Anshika; Navik, Uma Shanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
    Mitochondria are important for the metabolism of energy, regulation of apoptosis and cell signaling. Overproduction of reactive oxidation species (ROS) in mitochondria is one of the indications of cancer cells; moreover, this boosts the proliferation of cancerous cells by causing genomic instability and altering gene expressions. Mitochondrial and nuclear DNA mutations, caused by oxidative damage which impairs the mechanism of oxidative phosphorylation, can lead to more mitochondrial ROS output, genome instability, and the development of the cancer. Classic approach to target mitochondria of cancerous cells with novel-targeted therapeutics helps in targeting the mitochondrial apoptotic proteins and changing energy metabolism. Key benefit of selective drug delivery is it reduces the toxicity of drug and increases specificity. Better understanding of mitochondrial role in tumor growth will help to design more therapeutic agents with better selectivity. � Springer Nature Singapore Pte Ltd. 2022.
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    Methionine as a double-edged sword in health and disease: Current perspective and future challenges
    (Elsevier Ireland Ltd, 2021-10-25T00:00:00) Navik, Umashanker; Sheth, Vaibhav G.; Khurana, Amit; Jawalekar, Snehal Sainath; Allawadhi, Prince; Gaddam, Ravinder Reddy; Bhatti, Jasvinder Singh; Tikoo, Kulbhushan
    Methionine is one of the essential amino acids and plays a vital role in various cellular processes. Reports advocate that methionine restriction and supplementation provide promising outcomes, and its regulation is critical for maintaining a healthy life. Dietary methionine restriction in houseflies and rodents has been proven to extend lifespan. Contrary to these findings, long-term dietary restriction of methionine leads to adverse events such as bone-related disorders, stunted growth, and hyperhomocysteinemia. Conversely, dietary supplementation of methionine improves hepatic steatosis, insulin resistance, inflammation, fibrosis, and bone health. However, a high level of methionine intake shows adverse effects such as hyperhomocysteinemia, reduced body weight, and increased cholesterol levels. Therefore, dietary methionine in a safe dose could have medicinal values. Hence, this review is aimed to provide a snapshot of the dietary role and regulation of methionine in the modulation of health and age-related diseases. � 2021 Elsevier B.V.
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    Therapeutic Strategies Targeting Signaling Pathways in Lung Cancer
    (Springer Nature, 2021-07-02T00:00:00) Bhatti, Gurjit Kaur; Pahwa, Paras; Gupta, Anshika; Navik, Umashanker; Bhatti, Jasvinder Singh
    Recent knowledge of the role of signaling pathways and their underlying mechanisms in the pathogenesis of several diseases may lead to the development of therapeutic strategies. In the recent time, several drug molecules have been developed which target the cell signaling pathways and may be used in combination with other standard therapies for the synergistic effects in reducing the lung cancer pathophysiology across the world. Further, some of predictive biomarkers have been identified. The current chapter deals with the involvement of signaling pathways in the development of lung cancer and further new therapeutic approaches that intend to pave the way for the development of improved clinical treatment of lung cancer. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.
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    Various Cellular and Molecular Axis Involved in the Pathogenesis of Asthma
    (Springer Nature, 2021-07-02T00:00:00) Bhatti, Gurjit Kaur; Khurana, Amit; Garabadu, Debapriya; Gupta, Prashant; Jawalekar, Snehal Sainath; Bhatti, Jasvinder Singh; Navik, Umashanker
    Asthma is a chronic inflammatory disease described by impaired lung function, airway hyperresponsiveness, episodic wheezing, and dyspnea. Asthma prevalence has risen drastically, and it is estimated that more than 339 million individuals worldwide had asthma with marked heterogeneity in pathophysiology and etiology. Several factors involved in the progression and development of asthma include allergens, pollutants, obesity, viruses, antigens, and many more, eliciting strong inflammatory and immune responses, causing airflow obstruction, and tightening of respiratory smooth muscle causing the characteristic asthma symptoms. Multiple complex molecular pathways are involved in asthma pathophysiologies such as immunoglobulin E, cytokines, nitric oxide, dendritic cells, leukotrienes, oxidative stress, and inflammatory infiltrate of mast cells, neutrophils, eosinophils, lymphocytes, innate immunity, and many more. The current chapter focuses on illustrating the various molecular pathways that contribute to asthma development and its progression. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.