Browsing by Author "Navik, Umashanker"

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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.
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.
ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine
(Bentham Science Publishers, 2023-04-13T00:00:00) Verma, Aarti; Yadav, Poonam; Rajput, Sonu; Verma, Saloni; Arora, Sahil; Kumar, Raj; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
Background: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. Objective: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line. Methods: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharma-cology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. Results: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dose-dependent (0-500 ?M) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 ??. The wound-healing assay showed that vincamine treatment (150 and 300 ?M) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. Conclusion: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects. � 2023 Bentham Science Publishers.
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.
Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO?1/NLRP3 and TGF-? expression
(John Wiley and Sons Inc, 2023-10-16T00:00:00) Patel, Dhaneshvaree; Yadav, Poonam; Singh, Sumeet K.; Tanwar, Sampat S.; Sehrawat, Abhishek; Khurana, Amit; Bhatti, Jasvinder S.; Navik, Umashanker
Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-?, and IL-6) and fibrosis-related genes (TGF-? and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN. � 2023 Wiley Periodicals LLC.
Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity
(Elsevier Inc., 2023-09-24T00:00:00) Jaiswal, Aiswarya; Rawat, Pushkar Singh; Singh, Sumeet Kumar; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca2+ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid ? generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8?hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction. � 2023 The Author(s)
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
Chemical composition, in�vitro and in silico evaluation of essential oil from Eucalyptus tereticornis leaves for lung cancer
(Taylor and Francis Ltd., 2022-08-08T00:00:00) Anju; Kumar, Amit; Yadav, Poonam; Navik, Umashanker; Jaitak, Vikas
Chemical composition of the essential oil (EO) of Eucalyptus tereticornis leaves was studied by gas chromatography�mass spectrometry. Forty-five constituents were identified in the oil hydrodistilled from the sample collected from Ghudda Village, Bathinda (Pb), India of which eucalyptol (34.39%) and ledol (9.92%) were the major constituents. In vitro antioxidant and anticancer potential of EO was analysed by DPPH 2,2-diphenylpicrylhydrazyl (DPPH) and MTT assay. The percentage free radical scavenging activity was found to be 63.77%. The antiproliferative activity was analysed using MTT assay in adenocarcinomic human alveolar basal epithelial A549 cancer cell line and showed IC50 value of 47.14 �g/ml. In silico study of EO, constituents were performed using Maestro 12.9 against EGFR (PDB ID-2RGP). Five constituents from EO showed high dockscore as compared to standard Mobicertinib which indicated the effectiveness of oil constituents against lung cancer. � 2022 Informa UK Limited, trading as Taylor & Francis Group.
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
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
Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management
(Elsevier Masson s.r.l., 2021-05-13T00:00:00) Rawat, Pushkar Singh; Jaiswal, Aiswarya; Khurana, Amit; Bhatti, Jasvinder Singh; Navik, Umashanker
Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca2+ homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC-1?), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) activity. Therefore, in the current review, we have provided a detailed update on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity. Further, we have provided some of the most plausible pharmacological strategies which have been tested against Dox-induced cardiotoxicity. � 2021 The Authors
Dynamin-Independent Mechanisms of Endocytosis and Receptor Trafficking
(MDPI, 2022-08-18T00:00:00) Gundu, Chayanika; Arruri, Vijay Kumar; Yadav, Poonam; Navik, Umashanker; Kumar, Ashutosh; Amalkar, Veda Sudhir; Vikram, Ajit; Gaddam, Ravinder Reddy
Endocytosis is a fundamental mechanism by which cells perform housekeeping functions. It occurs via a variety of mechanisms and involves many regulatory proteins. The GTPase dynamin acts as a �molecular scissor� to form endocytic vesicles and is a critical regulator among the proteins involved in endocytosis. Some GTPases (e.g., Cdc42, arf6, RhoA), membrane proteins (e.g., flotillins, tetraspanins), and secondary messengers (e.g., calcium) mediate dynamin-independent endocytosis. These pathways may be convergent, as multiple pathways exist in a single cell. However, what determines the specific path of endocytosis is complex and challenging to comprehend. This review summarizes the mechanisms of dynamin-independent endocytosis, the involvement of microRNAs, and factors that contribute to the cellular decision about the specific route of endocytosis. � 2022 by the authors.
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.
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.
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.
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
Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective
(Academic Press, 2022-09-06T00:00:00) Yadav, Poonam; Khurana, Amit; Bhatti, Jasvinder Singh; Weiskirchen, Ralf; Navik, Umashanker
Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH. � 2022 Elsevier Ltd