Displaying publications 1 - 20 of 59 in total

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  1. Vitamin D, Calbindin, and calcium signaling: Unraveling the Alzheimer's connection
    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.
  2. Fulltext The viral capsid as novel nanomaterials for drug delivery
    Aljabali AA, Hassan SS, Pabari RM, Shahcheraghi SH, Mishra V, Charbe NB, et al.
    Future Sci OA, 2021 Oct;7(9):FSO744.
    PMID: 34737885 DOI: 10.2144/fsoa-2021-0031
    The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.
  3. Fulltext Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113
    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 [...].
  4. COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development
    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.

  5. A Potential MRI Agent and an Anticancer Drug Encapsulated within CPMV Virus-Like Particles
    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.

  6. Fulltext Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy
    Alomari G, Al-Trad B, Hamdan S, Aljabali A, Al-Zoubi M, Bataineh N, et al.
    Drug Deliv Transl Res, 2020 Feb;10(1):216-226.
    PMID: 31637677 DOI: 10.1007/s13346-019-00675-6
    Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.
  7. Fulltext Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats
    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.
  8. Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome
    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.
  9. Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications
    Altamish M, Samuel VP, Dahiya R, Singh Y, Deb PK, Bakshi HA, et al.
    Drug Dev Res, 2020 02;81(1):23-31.
    PMID: 31785110 DOI: 10.1002/ddr.21627
    The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1-, β2-, and β3-adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
  10. Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies
    Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
  11. Fulltext Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis
    Bakshi HA, Mishra V, Satija S, Mehta M, Hakkim FL, Kesharwani P, et al.
    Inflammation, 2019 Dec;42(6):2032-2036.
    PMID: 31377947 DOI: 10.1007/s10753-019-01065-3
    Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.
  12. Fulltext Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
    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.
  13. Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne
    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.
  14. Fulltext Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne
    Bisht A, Hemrajani C, Upadhyay N, Nidhi P, Rolta R, Rathore C, et al.
    Ther Deliv, 2022 Jan;13(1):13-29.
    PMID: 34842461 DOI: 10.4155/tde-2021-0059
    Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management.
  15. Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms
    Chan Y, Ng SW, Xin Tan JZ, Gupta G, Tambuwala MM, Bakshi HA, et al.
    Chem Biol Interact, 2019 Nov 28;315:108911.
    PMID: 31786185 DOI: 10.1016/j.cbi.2019.108911
    Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
  16. Fulltext Advances in nanotechnology-based drug delivery in targeting PI3K signaling in respiratory diseases
    Chan Y, MacLoughlin R, Zacconi FC, Tambuwala MM, Pabari RM, Singh SK, et al.
    Nanomedicine (Lond), 2021 07;16(16):1351-1355.
    PMID: 33998829 DOI: 10.2217/nnm-2021-0087
  17. Small interfering RNA for cancer treatment: overcoming hurdles in delivery
    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.
  18. A new era in oxygen therapeutics? From perfluorocarbon systems to haemoglobin-based oxygen carriers
    Charbe NB, Castillo F, Tambuwala MM, Prasher P, Chellappan DK, Carreño A, et al.
    Blood Rev, 2022 Jan 21.
    PMID: 35094845 DOI: 10.1016/j.blre.2022.100927
    Blood transfusion is the key to life in case of traumatic emergencies, surgeries and in several pathological conditions. An important goal of whole blood or red blood cell transfusion is the fast delivery of oxygen to vital organs and restoration of circulation volume. Whole blood or red blood cell transfusion has several limitations. Free haemoglobin not only loses its tetrameric configuration and extracts via the kidney leading to nephrotoxicity but also scavenges nitric oxide (NO), leading to vasoconstriction and hypertension. PFC based formulations transport oxygen in vivo, the contribution in terms of clinical outcome is challenging. The oxygen-carrying capacity is not the only criterion for the successful development of haemoglobin-based oxygen carriers (HBOCs). This review is a bird's eye view on the present state of the PFCs and HBOCs in which we analyzed the current modifications made or which are underway in development, their promises, and hurdles in clinical implementation.
  19. Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases
    Chellappan DK, Yee LW, Xuan KY, Kunalan K, Rou LC, Jean LS, et al.
    Drug Dev Res, 2020 06;81(4):419-436.
    PMID: 32048757 DOI: 10.1002/ddr.21648
    Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
  20. Molecular mechanisms of action of naringenin in chronic airway diseases
    Chin LH, Hon CM, Chellappan DK, Chellian J, Madheswaran T, Zeeshan F, et al.
    Eur J Pharmacol, 2020 Jul 15;879:173139.
    PMID: 32343971 DOI: 10.1016/j.ejphar.2020.173139
    Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.
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