Pharmacology - Research Publications

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    Exploring the role of exosomes in rheumatoid arthritis
    (Springer Science and Business Media Deutschland GmbH, 2022-11-22T00:00:00) Singh, Anuja; Behl, Tapan; Sehgal, Aayush; Singh, Sukhbir; Sharma, Neelam; Naqwi, Maaz; Mavi, Anil; Singh, Randhir
    In prosperous countries, autoimmune illnesses affect minimum 7% of the community. Rheumatoid Arthritis (RA) as an autoimmune illness is thought to be induced through a variety of genomic, physiological, and biological factors. Many experts in the field of nanomedicine have looked to stem cells as a viable strategy to repair human tissue; however, exosomes have demonstrated greater potential in recent years. Exosomes, produced from stem cells in particular, have exhibited a high propensity to give therapeutic effects. To resist local cellular stress, they are secreted in a paracrine manner from cells. As a result, exosomes produced from stem cells can provide enormous health uses. If treatment is not given, autoantibodies produce synovial inflammation and arthritis, which can lead to chronic inflammation, and impairment. Exosomes could be administered for the treatment of RA, by acting as therapeutic vectors. Exosomes are murine extracellular vesicles that influence biological mechanisms and signal transduction by transporting genetic and protein components. Diseases like RA and bone fractures could be treated using cell-free therapeutic strategies if exosomes could be isolated from stem cells efficiently and packaged with specific restorative substances. To get to this position, many breakthroughs must be achieved, and the following review summarises the most recent developments in stem cell-derived exosomes, with a focus on the important literature on exosome dynamics in RA. Graphical abstract: [Figure not available: see fulltext.]. � 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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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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    L-Methionine supplementation attenuates high-fat fructose diet-induced non-alcoholic steatohepatitis by modulating lipid metabolism, fibrosis, and inflammation in rats
    (Royal Society of Chemistry, 2022-03-31T00:00:00) Navik, Umashanker; Sheth, Vaibhav G.; Sharma, Nisha; Tikoo, Kulbhushan
    Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied. We, therefore, hypothesized that l-methionine supplementation would ameliorate the progression of hepatic injury in a diet-induced non-alcoholic steatohepatitis (NASH) model and aimed to investigate the underlying mechanism. NASH was developed in male Sprague Dawley rats by feeding them with a high-fat-fructose diet (HFFrD) for 10 weeks. The results demonstrated that l-methionine supplementation to NASH rats for 16 weeks improved the glycemic, lipid, and liver function profiles in NASH rats. Histological analysis of liver tissue revealed a remarkable improvement in the three classical lesions of NASH: steatosis, inflammation, and ballooning. Besides, l-methionine supplementation ameliorated the HFFrD-induced enhanced lipogenesis and lipid peroxidation. An anti-inflammatory effect of l-methionine was also observed through the inhibition of the release of proinflammatory cytokines. Furthermore, the hepatic SIRT1/AMPK signaling pathway was associated with the beneficial effects of l-methionine. This study demonstrates that l-methionine supplementation in HFFrD-fed rats improves their liver pathology via regulation of lipogenesis, inflammation, and the SIRT1/AMPK pathway, thus encouraging its clinical evaluation for the treatment of NASH. � 2022 The Royal Society of Chemistry.
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    Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis
    (Elsevier Ltd, 2021-11-22T00:00:00) Allawadhi, Prince; Singh, Vishakha; Govindaraj, Kannan; Khurana, Isha; Sarode, Lopmudra P.; Navik, Umashanker; Banothu, Anil Kumar; Weiskirchen, Ralf; Bharani, Kala Kumar; Khurana, Amit
    Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis. � 2021 Elsevier Ltd
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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.