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  1. Sharma A, Sethi G, Tambuwala MM, Aljabali AAA, Chellappan DK, Dua K, et al.
    Curr Neuropharmacol, 2021;19(2):248-264.
    PMID: 32348224 DOI: 10.2174/1570159X18666200429013041
    All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
  2. Acharya M, Singh N, Gupta G, Tambuwala MM, Aljabali AAA, Chellappan DK, et al.
    Cell Signal, 2024 Apr;116:111043.
    PMID: 38211841 DOI: 10.1016/j.cellsig.2024.111043
    Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
  3. Khanuja HK, Awasthi R, Mehta M, Satija S, Aljabali AAA, Tambuwala MM, et al.
    Recent Pat Nanotechnol, 2021;15(4):351-366.
    PMID: 33357187 DOI: 10.2174/1872210514666201224103010
    BACKGROUND: Nanosuspensions are colloidal systems consisting of pure drug and stabilizers, without matrix or lyophilized into a solid matrix. Nanosuspensions improve the solubility of the drug both in the aqueous and organic phases. Nanosuspensions are also known as brick dust molecules, as they increase the dissolution of a system and improve absorption.

    METHODS: Extensive information related to nanosuspensions and its associated patents were collected using Pub Med and Google Scholar.

    RESULTS: Over the last decade nanosuspensions have attracted tremendous interest in pharmaceutical research. It provides unique features including, improved solubility, high drug loading capacity, and passive targeting. These particles are cost-effective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention.

    CONCLUSION: Nanosuspensions play a vital role in handling the numerous drug entities with difficult physico-chemical characteristics such as solubility and can further aid with a range of routes that include nasal, transdermal, ocular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.

  4. Rawat S, Gupta G, Pathak S, Singh SK, Singh H, Mishra A, et al.
    EXCLI J, 2020;19:635-640.
    PMID: 32536834
  5. Wadhwa R, Paudel KR, Mehta M, Shukla SD, Sunkara K, Prasher P, et al.
    CNS Neurol Disord Drug Targets, 2020;19(9):698-708.
    PMID: 33109069 DOI: 10.2174/1871527319999200817112427
    Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer 's disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
  6. Gandhi H, Mahant S, Sharma AK, Kumar D, Dua K, Chellappan DK, et al.
    Biofactors, 2024;50(2):232-249.
    PMID: 37702264 DOI: 10.1002/biof.2009
    Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.
  7. Charbe NB, Amnerkar ND, Ramesh B, Tambuwala MM, Bakshi HA, Aljabali AAA, et al.
    Acta Pharm Sin B, 2020 Nov;10(11):2075-2109.
    PMID: 33304780 DOI: 10.1016/j.apsb.2020.10.005
    In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
  8. Aljabali AAA, Bakshi HA, Satija S, Metha M, Prasher P, Ennab RM, et al.
    Pharm Nanotechnol, 2020;8(4):323-353.
    PMID: 32811406 DOI: 10.2174/2211738508999200817163335
    BACKGROUND: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.

    OBJECTIVES: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.

    METHODS: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.

    RESULTS: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.

    Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.

  9. Gupta G, Dahiya R, Singh Y, Mishra A, Verma A, Gothwal SK, et al.
    Chem Biol Interact, 2020 Feb 01;317:108975.
    PMID: 32032593 DOI: 10.1016/j.cbi.2020.108975
    In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.
  10. Altamish M, Dahiya R, Singh AK, Mishra A, Aljabali AAA, Satija S, et al.
    Crit Rev Eukaryot Gene Expr, 2020;30(3):245-252.
    PMID: 32749111 DOI: 10.1615/CritRevEukaryotGeneExpr.2020033451
    Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.
  11. Prasher P, Sharma M, Aljabali AAA, Gupta G, Negi P, Kapoor DN, et al.
    Drug Dev Res, 2020 11;81(7):837-858.
    PMID: 32579723 DOI: 10.1002/ddr.21704
    Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
  12. Bisht A, Hemrajani C, Rathore C, Dhiman T, Rolta R, Upadhyay N, et al.
    Drug Deliv Transl Res, 2021 Nov 15.
    PMID: 34782995 DOI: 10.1007/s13346-021-01092-4
    Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index  90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris.
  13. Aljabali AAA, Alzoubi L, Hamzat Y, Alqudah A, Obeid MA, Al Zoubi MS, et al.
    Comb Chem High Throughput Screen, 2021;24(10):1557-1571.
    PMID: 32928083 DOI: 10.2174/1386207323666200914110012
    BACKGROUND: Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition.

    OBJECTIVES: The plant virus Cowpea Mosaic Virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty Virus-Like Particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications.

    METHODS: The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid.

    RESULTS: Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis exhibited a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 μM and 3.9 μM, respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents.

    CONCLUSION: Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines with its potency increased by 2.3-folds.

  14. Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, Serrano-Aroca Á, Mishra V, et al.
    Cell Signal, 2022 Jul;95:110334.
    PMID: 35461900 DOI: 10.1016/j.cellsig.2022.110334
    Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.
  15. Rathore C, Hemrajani C, Sharma AK, Gupta PK, Jha NK, Aljabali AAA, et al.
    Drug Deliv Transl Res, 2023 Jan;13(1):292-307.
    PMID: 35831776 DOI: 10.1007/s13346-022-01193-8
    Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (
  16. Alomari G, Al-Trad B, Hamdan S, Aljabali AAA, Al Zoubi MS, Al-Batanyeh K, et al.
    IET Nanobiotechnol, 2021 Jul;15(5):473-483.
    PMID: 34694755 DOI: 10.1049/nbt2.12026
    This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.
  17. Aljabali AAA, Bakshi HA, Hakkim FL, Haggag YA, Al-Batanyeh KM, Zoubi MSA, et al.
    Cancers (Basel), 2020 Nov 30;12(12).
    PMID: 33266353 DOI: 10.3390/cancers12123587
    The authors wish to make the following corrections to this paper [...].
  18. Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
  19. Bakshi HA, Zoubi MSA, Hakkim FL, Aljabali AAA, Rabi FA, Hafiz AA, et al.
    Nutrients, 2020 06 26;12(6).
    PMID: 32604971 DOI: 10.3390/nu12061901
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
  20. Shahcheraghi SH, Aljabali AAA, Al Zoubi MS, Mishra V, Charbe NB, Haggag YA, et al.
    Life Sci, 2021 Aug 01;278:119632.
    PMID: 34019900 DOI: 10.1016/j.lfs.2021.119632
    Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.
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