Department Of Pharmacology

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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.
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.
Apoptosis and Pharmacological Therapies for Targeting Thereof for Cancer Therapeutics
(MDPI, 2022-04-08T00:00:00) Singh, Vishakha; Khurana, Amit; Navik, Umashanker; Allawadhi, Prince; Bharani, Kala Kumar; Weiskirchen, Ralf
Apoptosis is an evolutionarily conserved sequential process of cell death to maintain a homeostatic balance between cell formation and cell death. It is a vital process for normal eukaryotic development as it contributes to the renewal of cells and tissues. Further, it plays a crucial role in the elimination of unnecessary cells through phagocytosis and prevents undesirable immune responses. Apoptosis is regulated by a complex signaling mechanism, which is driven by interactions among several protein families such as caspases, inhibitors of apoptosis proteins, B-cell lymphoma 2 (BCL-2) family proteins, and several other proteases such as perforins and granzyme. The signaling pathway consists of both pro-apoptotic and pro-survival members, which stabilize the selection of cellular survival or death. However, any aberration in this pathway can lead to abnormal cell proliferation, ultimately leading to the development of cancer, autoimmune disorders, etc. This review aims to elaborate on apoptotic signaling pathways and mechanisms, interacting members involved in signaling, and how apoptosis is associated with carcinogenesis, along with insights into targeting apoptosis for disease resolution. � 2022 by the authors.
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
Can bilirubin nanomedicine become a hope for the management of COVID-19?
(Churchill Livingstone, 2021-02-15T00:00:00) Khurana, Isha; Allawadhi, Prince; Khurana, Amit; Srivastava, Amit Kumar; Navik, Umashanker; Banothu, Anil Kumar; Bharani, Kala Kumar
Bilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications. � 2021 Elsevier Ltd
A comprehensive overview of CRISPR/Cas 9 technology and application thereof in drug discovery
(John Wiley and Sons Inc, 2022-09-21T00:00:00) Khurana, Amit; Sayed, Nilofer; Singh, Vishakha; Khurana, Isha; Allawadhi, Prince; Rawat, Pushkar Singh; Navik, Umashanker; Pasumarthi, Sravan Kumar; Bharani, Kala Kumar; Weiskirchen, Ralf
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas technology possesses revolutionary potential to positively affect various domains of drug discovery. It has initiated a rise in the area of genetic engineering and its advantages range from classical science to translational medicine. These genome editing systems have given a new dimension to our capabilities to alter, detect�and annotate specified gene sequences. Moreover, the ease, robustness�and adaptability of the CRISPR/Cas9 technology have led to its extensive utilization in research areas in such a short period of time. The applications include the development of model cell lines, understanding disease mechanisms, discovering disease targets, developing transgenic animals and plants, and transcriptional modulation. Further, the technology is rapidly growing; hence, an overlook of progressive success is crucial. This review presents the current status of the CRISPR�Cas technology in a tailor-made format from its discovery to several advancements for drug discovery alongwith future trends associated with possibilities and hurdles including ethical concerns. � 2022 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.
Decorin as a possible strategy for the amelioration of COVID-19
(Churchill Livingstone, 2021-05-20T00:00:00) Allawadhi, Prince; Singh, Vishakha; Khurana, Isha; Rawat, Pushkar Singh; Renushe, Akshata Patangrao; Khurana, Amit; Navik, Umashanker; Allwadhi, Sachin; Kumar Karlapudi, Satish; Banothu, Anil Kumar; Bharani, Kala Kumar
Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19. � 2021 Elsevier Ltd
Evolution of Zebrafish as a Novel Pharmacological Model in Endocrine Research
(Springer Nature, 2022-05-30T00:00:00) Navik, Umashanker; Rawat, Pushkar Singh; Allawadhi, Prince; Khurana, Amit; Banothu, Anil Kumar; Bharani, Kala Kumar
Zebrafish is a powerful platform in the modern era of phenotype-based drug discovery and eminent vertebrate model to study disease progression and its pathophysiology. Zebrafish possess several advantages over rodent model including low cost, females that lay up to 300 eggs per week, the optical clarity of embryo, external fertilization, and highly amenable to transgenic modifications using various genetic toolkits. Zebrafish have almost 70% genetic homology with humans, and 82% of disease-causing human proteins are orthologue to zebrafish. The bottleneck in drug discovery is high cost, laborious, and time taking processes to generate hits. Zebrafish provide a novel option to overcome this bottleneck and have enabled rapid drug discovery in the area of cancer, cardiovascular diseases, endocrine diseases, and many more. However, zebrafish cannot completely replace the mammalian model in drug discovery, but it can form a bridge between cell-based assays and mammalian models, thus reducing the overall cost and time in lead generation. Therefore, in this chapter, we have discussed the role of zebrafish as an emerging vertebrate model in the area of endocrinology disorders. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.
Gene therapy: Comprehensive overview and therapeutic applications
(Elsevier Inc., 2022-02-03T00:00:00) Sayed, Nilofer; Allawadhi, Prince; Khurana, Amit; Singh, Vishakha; Navik, Umashanker; Pasumarthi, Sravan Kumar; Khurana, Isha; Banothu, Anil Kumar; Weiskirchen, Ralf; Bharani, Kala Kumar
Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short tandem repeats (CRISPR)/CRISPR-associated protein (Cas)-associated nucleases. Transfer of gene is either through transformation where under specific conditions the gene is directly taken up by the bacterial cells, transduction where a bacteriophage is used to transfer the genetic material and lastly transfection that involves forceful delivery of gene using either viral or non-viral vectors. The non-viral transfection methods are subdivided into physical, chemical and biological. The physical methods include electroporation, biolistic, microinjection, laser, elevated temperature, ultrasound and hydrodynamic gene transfer. The chemical methods utilize calcium- phosphate, DAE-dextran, liposomes and nanoparticles for transfection. The biological methods are increasingly using viruses for gene transfer, these viruses could either integrate within the genome of the host cell conferring a stable gene expression, whereas few other non-integrating viruses are episomal and their expression is diluted proportional to the cell division. So far, gene therapy has been wielded in a plethora of diseases. However, coherent and innocuous delivery of genes is among the major hurdles in the use of this promising therapy. Hence this review aims to highlight the current options available for gene transfer along with the advantages and limitations of every method. � 2022
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.
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.

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