Human Genetics And Molecular Medicine - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107

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Author: search.filters.author.Bhatti, Jasvinder SinghStart date: 2010

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    Nanotheranostics revolutionizing neurodegenerative diseases: From precision diagnosis to targeted therapies
    (Editions de Sante, 2023-10-16T00:00:00) Joshi, Riya; Missong, Hemi; Mishra, Jayapriya; Kaur, Satinder; Saini, Sumant; Kandimalla, Ramesh; Reddy, P. Hemachandra; Babu, Arockia; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Neurodegenerative disorders pose a significant burden on global healthcare systems, and the development of effective therapeutics and diagnostics remains a critical challenge. Nanotheranostics, the integration of nanotechnology-based diagnostic and therapeutic modalities, has emerged as a promising strategy to address these challenges. This review article provides a comprehensive analysis of the latest advancements in nanotheranostics for the treatment and monitoring of neurological disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The application of targeted drug delivery systems, gene therapy, and non-invasive imaging techniques are explored in-depth, highlighting the potential of nanotheranostics to revolutionize the management of neurological disorders. The article delves into the design and synthesis of various nanocarriers, such as liposomes, dendrimers, and polymeric nanoparticles, which enable the targeted delivery of therapeutic agents across the blood-brain barrier. Gene therapy approaches, including CRISPR/Cas9 and RNA interference demonstrating the potential of nanotheranostics to enable precise genetic modifications in the treatment of neurological disorders. Additionally, non-invasive imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are examined in the context of their integration with nanotheranostics for real-time monitoring of treatment efficacy and disease progression. The review also identifies current challenges and limitations in the field of nanotheranostics, such as toxicity, immunogenicity, and issues with large-scale production. Furthermore, it outlines future research directions and potential strategies to overcome these limitations, paving the way for the clinical translation of nanotheranostics as next-generation therapeutics in neurological disorders. � 2023
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    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)
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    Recent advances in microwave-assisted nanocarrier based drug delivery system: Trends and technologies
    (Editions de Sante, 2023-08-09T00:00:00) Virlley, Shachi; Shukla, Shipra; Arora, Sanchit; Shukla, Deeksha; Nagdiya, Deepak; Bajaj, Tania; Kujur, Sima; Garima; Kumar, Arun; Bhatti, Jasvinder Singh; Singh, Arti; Singh, Charan
    Microwave irradiation technology has a lot of applications in the field of food processing, organic synthesis, pharmaceuticals, and biomedical therapy. The basic mechanisms observed in microwave-assisted syntheses are dipolar polarization and conduction. Of late, it has gained tremendous attention in the synthesis of drug delivery systems for enhanced solubility, dissolution rate, and biopharmaceutical attributes. Considering the myriads of advantages over conventional heating such as high percentage yield, lesser reaction time, deep penetration of heat, and improved product quality; microwave-assisted technology holds potential in the development of nano- and microparticle-based drug delivery systems with improved physicochemical characteristics and thereby, bioavailability. In this review, we have discussed the formulation of drug delivery systems which includes lipidic, polymeric, metallic, and micellar nanoparticles. We have also summarized solid dispersion, dendrimers, and carbon nanotubes in this manuscript. However, it is possible to expedite the extraction process, save expenses, and increase the effectiveness, reliability, and simplicity of responses. Therefore, microwave technology provides a new avenue for the development of drug delivery systems in various biomedical applications. � 2023 Elsevier B.V.
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    Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease
    (Elsevier Inc., 2023-08-02T00:00:00) Kaur, Satinder; Sehrawat, Abhishek; Mastana, Sarabjit Singh; Kandimalla, Ramesh; Sharma, Pushpender Kumar; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory. � 2023 Elsevier Inc.
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    Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks
    (Multidisciplinary Digital Publishing Institute (MDPI), 2023-07-12T00:00:00) Ghosh, Nilanjan; Chacko, Leena; Vallamkondu, Jayalakshmi; Banerjee, Tanmoy; Sarkar, Chandrima; Singh, Birbal; Kalra, Rajkumar Singh; Bhatti, Jasvinder Singh; Kandimalla, Ramesh; Dewanjee, Saikat
    An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies. � 2023 by the authors.
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    Targeting dynamin-related protein-1 as a potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease
    (Elsevier B.V., 2023-06-29T00:00:00) Bhatti, Jasvinder Singh; Kaur, Satinder; Mishra, Jayapriya; Dibbanti, Harikrishnareddy; Singh, Arti; Reddy, Arubala P.; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
    Alzheimer's disease (AD) is a neurodegenerative disease that manifests its pathology through synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, accumulation of amyloid ? (A?) and phosphorylated Tau in the brains of AD patients. Despite extensive research, the effective treatment of AD is still unknown. Tau hyperphosphorylation and mitochondrial abnormalities are involved in the loss of synapses, defective axonal transport and cognitive decline in patients with AD. Mitochondrial dysfunction is evidenced by enhanced mitochondrial fragmentation, impaired mitochondrial dynamics, mitochondrial biogenesis and defective mitophagy in AD. Hence, targeting mitochondrial proteins might be a promising therapeutic strategy in treating AD. Recently, dynamin-related protein 1 (Drp1), a mitochondrial fission protein, has gained attention due to its interactions with A? and hyperphosphorylated Tau, altering mitochondrial morphology, dynamics, and bioenergetics. These interactions affect ATP production in mitochondria. A reduction in Drp1 GTPase activity protects against neurodegeneration in AD models. This article provides a comprehensive overview of Drp1's involvement in oxidative damage, apoptosis, mitophagy, and axonal transport of mitochondria. We also highlighted the interaction of Drp1 with A? and Tau, which may contribute to AD progression. In conclusion, targeting Drp1 could be a potential therapeutic approach for preventing AD pathology. � 2023
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    Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds
    (Elsevier Masson s.r.l., 2023-07-30T00:00:00) Abdul Rahman, S. Maheen; Bhatti, Jasvinder Singh; Thareja, Suresh; Monga, Vikramdeep
    Malaria is among one of the most devastating and deadliest parasitic disease in the world claiming millions of lives every year around the globe. It is a mosquito-borne infectious disease caused by various species of the parasitic protozoan of the genus Plasmodium. The indiscriminate exploitation of the clinically used antimalarial drugs led to the development of various drug-resistant and multidrug-resistant strains of plasmodium which severely reduces the therapeutic effectiveness of most frontline medicines. Therefore, there is urgent need to develop novel structural classes of antimalarial agents acting with unique mechanism of action(s). In this context, design and development of hybrid molecules containing pharmacophoric features of different lead molecules in a single entity represents a unique strategy for the development of next-generation antimalarial drugs. Research efforts by the scientific community over the past few years has led to the identification and development of several heterocyclic small molecules as antimalarial agents with high potency, less toxicity and desired efficacy. Triazole derivatives have become indispensable units in the medicinal chemistry due to their diverse spectrum of biological profiles and many triazole based hybrids and conjugates have demonstrated potential in vitro and in vivo antimalarial activities. The manuscript compiled recent developments in the medicinal chemistry of triazole based small heterocyclic molecules as antimalarial agents and discusses various reported biologically active compounds to lay the groundwork for the rationale design and discovery of triazole based antimalarial compounds. The article emphasised on biological activities, structure activity relationships, and molecular docking studies of various triazole based hybrids with heterocycles such as quinoline, artemisinins, naphthyl, naphthoquinone, etc. as potential antimalarial agents which could act on the dual stage and multi stage of the parasitic life cycle. � 2023 Elsevier Masson SAS
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    Recent advances in the omics-based assessment of microbial consortia in the plastisphere environment: Deciphering the dynamic role of hidden players
    (Institution of Chemical Engineers, 2023-06-10T00:00:00) Malik, Naveen; Lakhawat, Sudarshan Singh; Kumar, Vikram; Sharma, Vinay; Bhatti, Jasvinder Singh; Sharma, Pushpender Kumar
    Continuous disposal of plastic waste and its accretion in the environment is the biggest challenge the world has ever faced. Breaking its terrestrial bounds, plastic waste has now extended its outreach to aquatic territories including marine ecosystems. Photooxidation-mediated partial degradation converts plastic polymers to micrometric dimensions, thus augmenting their biomagnification in the food chains. Besides contaminating the food chains, microplastics also act as potential carriers of pollutants and pathogenic microbes. The slow and inefficient biodegradation of plastic by microorganisms in their natural habitats offers an opportunity to explore biotechnological interventions to overcome and mitigate the hazardous effects of plastic waste. Microorganisms utilize plastic polymer as a carbon source thus deriving energy from its oxidation and mineralization. The whole microbial consortium in the plastisphere interacts during the biodegradation process. The emergence of these novel plastic-dwelling microbial communities makes plastic degradation a very complex and finetuned process, where the expression of novel plastic-degrading genes and resultant pathways and interaction networks all contribute towards biodegradation. Thus, it is quite challenging to study such vast consortia of microbial communities by conventional approach to fully understand the degradation pattern of plastics. The techniques like shotgun metagenomics, transcriptomics and meta transcriptomics, next-generation amplicon sequencing, proteomics and metaproteomic, etc. have been successfully employed in recent years for identifying novel microbial species, gene pool, interactions network, and reaction pathways from different microbial consortia. Among several classes of bacteria, the Flavobacteriaceae, Rhodobacteriaceae, and Phycobactereaceae have shown their remarkable presence in different plastisphere. Omics approaches have also revealed high-level expression of plastic-degrading enzymes like esterases, depolymerases, hydrolases, and reductases. The applicability of these techniques in context to the studies of microbiota in the degradation of plastics is defined by their high accuracy, quickness, and sensitivity. The current review accentuates the significance of omics-based studies in identifying specific microbiota, dynamic gene pool, functional pathways, and metabolic networks of the plastisphere microbial consortia. � 2023 The Institution of Chemical Engineers
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    Stem cells in the treatment of Alzheimer's disease � Promises and pitfalls
    (Elsevier B.V., 2023-04-06T00:00:00) Bhatti, Jasvinder Singh; Khullar, Naina; Mishra, Jayapriya; Kaur, Satinder; Sehrawat, Abhishek; Sharma, Eva; Bhatti, Gurjit Kaur; Selman, Ashley; Reddy, P. Hemachandra
    Alzheimer's disease (AD) is the most widespread form of neurodegenerative disorder that causes memory loss and multiple cognitive issues. The underlying mechanisms of AD include the build-up of amyloid-? and phosphorylated tau, synaptic damage, elevated levels of microglia and astrocytes, abnormal microRNAs, mitochondrial dysfunction, hormonal imbalance, and age-related neuronal loss. However, the etiology of AD is complex and involves a multitude of environmental and genetic factors. Currently, available AD medications only alleviate symptoms and do not provide a permanent cure. Therefore, there is a need for therapies that can prevent or reverse cognitive decline, brain tissue loss, and neural instability. Stem cell therapy is a promising treatment for AD because stem cells possess the unique ability to differentiate into any type of cell and maintain their self-renewal. This article provides an overview of the pathophysiology of AD and existing pharmacological treatments. This review article focuses on the role of various types of stem cells in neuroregeneration, the potential challenges, and the future of stem cell-based therapies for AD, including nano delivery and gaps in stem cell technology. � 2023 Elsevier B.V.
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    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.