Can supervise: YES
Malyla, V, Paudel, KR, Shukla, SD, Donovan, C, Wadhwa, R, Pickles, S, Chimankar, V, Sahu, P, Bielefeldt-Ohmann, H, Bebawy, M, Hansbro, PM & Dua, K 2020, 'Recent advances in experimental animal models of lung cancer', Future Medicinal Chemistry.View/Download from: Publisher's site
Mehta, M, Satija, S, Paudel, KR, Liu, G, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases', Future Medicinal Chemistry, vol. 12, no. 10, pp. 873-875.View/Download from: Publisher's site
Paudel, KR, Wadhwa, R, Mehta, M, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro', Toxicology in Vitro, pp. 104961-104961.View/Download from: Publisher's site
Aggarwal, T, Wadhwa, R, Gupta, R, Paudel, KR, Collet, T, Chellapan, DK, Gupta, G, Perumalsamy, H, Mehta, M, Satija, S, Hansbro, PM, Dua, K & Maurya, PK 2020, 'MicroRNAs as Biomarker for Breast Cancer.', Endocrine, metabolic & immune disorders drug targets.View/Download from: Publisher's site
Regardless of advances in detection and treatment, breast cancer is a major cause of women death and affecting about 1.5 million women all over the world. Since the last decade, genome wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute large family of non-coding RNAs which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus for more studies on the role of microRNAs in breast cancer.
Chellappan, DK, Yee, LW, Xuan, KY, Kunalan, K, Rou, LC, Jean, LS, Ying, LY, Wie, LX, Chellian, J, Mehta, M, Satija, S, Singh, SK, Gulati, M, Dureja, H, Da Silva, MW, Tambuwala, MM, Gupta, G, Paudel, KR, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases', DRUG DEVELOPMENT RESEARCH, vol. 81, no. 4, pp. 419-436.View/Download from: Publisher's site
Chin, LH, Hon, CM, Chellappan, DK, Chellian, J, Madheswaran, T, Zeeshan, F, Awasthi, R, Aljabali, AA, Tambuwala, MM, Dureja, H, Negi, P, Kapoor, DN, Goyal, R, Paudel, KR, Satija, S, Gupta, G, Hsu, A, Wark, P, Mehta, M, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Molecular mechanisms of action of naringenin in chronic airway diseases', European Journal of Pharmacology, vol. 879.View/Download from: Publisher's site
© 2020 Elsevier B.V. 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.
Hardwick, J, Taylor, J, Mehta, M, Satija, S, Paudel, KR, Hansbro, PM, Chellappan, DK, Bebawy, M & Dua, K 2020, 'Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems.', Current pharmaceutical design.View/Download from: Publisher's site
Curcumin is a major curcuminoid present in turmeric. The compound is attributed with various therapeutic properties, which include, anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as, nanoparticle based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary on nanoparticle based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as, biotechnology, nutraceutical, and functional food industries.
Kim, T-M, Paudel, KR & Kim, D-W 2020, 'Eriobotrya japonica leaf extract attenuates airway inflammation in ovalbumin-induced mice model of asthma.', Journal of Ethnopharmacology, vol. 253.View/Download from: Publisher's site
ETHNOPHARMACOLOGICAL RELEVANCE:Eriobotrya japonica leaves has a very long history of medicinal use as an anti-inflammatory and antitussive agent for bronchial inflammation. AIM OF THE STUDY:The aim of this study was to evaluate the anti-inflammatory activities of Eriobotrya japonica (EJ) leaf water extract in an ovalbumin (OVA)-induced murine asthma model and human tracheal smooth muscle cell (HTSMC). MATERIALS AND METHODS:Mice were sensitized by intra peritoneal OVA and challenged with nebulized OVA. EJ extract was administered orally at various dose. Bronchoalveolar lavage fluid (BALF) was quantified for nitric oxide (NO), eosinophil peroxidase (EPO), interleukin (IL)-4, IL-13 level and immunoglobulin (Ig) E was quantified in serum. Lung tissue sections were stained with hematoxylin and eosin for assessment of inflammatory cell infiltration whereas mucus production and goblet cell hyperplasia were studied by periodic acid schiff staining. Western blot was done for analysis of pERK1/2 expression and NFκB translocation in HTSMC whereas iNOS and COX-2 expression in RAW264.7 cell. RESULTS:EJ significantly reduced the levels of BALF's NO, EPO, MMPs, IL-4, IL-13, and serum IgE. It also decreases inflammatory cell infiltration and mucus production. EJ also attenuated the proliferation of HTSMC, inhibits overexpression of ERK 1/2 and translocation of NFκB in HTSMC as well as iNOS and COX-2 expression in RAW 264.7 cell. CONCLUSION:Present study suggest that, EJ effectively protects against allergic airway inflammation thus possessing potential therapeutic option for allergic asthma management.
Mehta, M, Dhanjal, DS, Paudel, KR, Singh, B, Gupta, G, Rajeshkumar, S, Thangavelu, L, Tambuwala, MM, Bakshi, HA, Chellappan, DK, Pandey, P, Dureja, H, Charbe, NB, Singh, SK, Shukla, SD, Nammi, S, Aljabali, AA, Wich, PR, Hansbro, PM, Satija, S & Dua, K 2020, 'Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update', INFLAMMOPHARMACOLOGY, vol. 28, no. 4, pp. 795-817.View/Download from: Publisher's site
Paudel, KR, Oak, M-H & Kim, D-W 2020, 'Smooth Muscle Cell Derived Microparticles Acts as Autocrine Activation of Smooth Muscle Cell Proliferation by Mitogen Associated Protein Kinase Upregulation', Journal of Nanoscience and Nanotechnology, vol. 20, no. 9, pp. 5746-5750.View/Download from: Publisher's site
Microparticles (MP); also know as microvesicles are extracellular vesicles (0.1 to 1.0 μm) released by cells in response to cell activation or apoptosis. The high level of circulating MP is one of the important indicators of altered vascular function. Vascular smooth muscle cell (VSMC) derived MP could mediate proliferation and migration of VSMC leading to vascular inflammation. Proliferation of VSMC is mediated by mitogen associated protein kinase (MAPK) and proliferation cell nuclei antigen (PCNA) signaling pathway whereas migration is mediated by metalloproteinase and cytoskeletal remodeling pathway. In this study, VSMC-MP were isolated from confluent VSMC stimulated with tumor necrosis factor (TNF)-α. VSMC-MP were treated to VSMC to investigate the VSMC proliferation marker using in vitro assay. In comparison to normal (VSMC-MP untreated group), VSMC-MP treatment results in proliferation of VSMC as revealed by MTT assay. VSMC-MP and TNF-α induce proliferation by 34% and 67% respectively. VSMC-MP also induce over expression of PCNA in both immuno-fluorescence and western blot experiment. VSMC-MP and TNF-α increase the PCNA expression by 1.86-fold and 1.95-fold respectively. Similarly, VSMC-MP treatment results in over expression of MAPK pathway protein expression in VSMC. As compared to normal, the MAPK protein (pERK1/2, pP38 and pJNK) were increased by 1.41-fold, 1.42-fold and 1.48-fold, respectively in VSMC-MP treated VSMC. Our results provide the evidence of VSMC-MP involvement in proliferation of VSMC. Thus, VSMC-MP could be considered as a potential marker of vascular inflammatory disorder such as atherosclerosis.
Prasher, P, Sharma, M, Mehta, M, Paudel, KR, Satija, S, Chellappan, DK, Dureja, H, Gupta, G, Tambuwala, MM, Negi, P, Wich, PR, Hansbro, NG, Hansbro, PM & Dua, K 2020, 'Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective', Chemico-Biological Interactions, vol. 325.View/Download from: Publisher's site
© 2020 Elsevier B.V. The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.
Manandhar, B, Paudel, KR, Sharma, B & Karki, R 2018, 'Phytochemical profile and pharmacological activity of Aegle marmelos Linn', JOURNAL OF INTEGRATIVE MEDICINE-JIM, vol. 16, no. 3, pp. 153-163.View/Download from: Publisher's site
Panth, N, Paudel, KR, Gong, D-S & Oak, M-H 2018, 'Vascular Protection by Ethanol Extract of Morus alba Root Bark: Endothelium-Dependent Relaxation of Rat Aorta and Decrease of Smooth Muscle Cell Migration and Proliferation', EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE.View/Download from: Publisher's site
Jun, MY, Karki, R, Paudel, KR, Sharma, BR, Adhikari, D & Kim, D-W 2016, 'Alkaloid rich fraction from Nelumbo nucifera targets VSMC proliferation and migration to suppress restenosis in balloon-injured rat carotid artery', ATHEROSCLEROSIS, vol. 248, pp. 179-189.View/Download from: Publisher's site
Lee, H-H, Paudel, KR, Jeong, J, Wi, A-J, Park, W-S, Kim, D-W & Oak, M-H 2016, 'Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats', EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE.View/Download from: Publisher's site
Panth, N, Paudel, KR & Karki, R 2016, 'Phytochemical profile and biological activity of Juglans regia', Journal of Integrative Medicine, vol. 14, no. 5, pp. 359-373.View/Download from: Publisher's site
© 2016 Journal of Integrative Medicine Editorial Office. E-edition published by Elsevier (Singapore) Pte Ltd. All rights reserved. Juglans regia Linn. (Juglandaceae), popularly known as English or Persian walnut, is a valuable medicinal plant with a potency to cure various diseases in traditional medicine. Since ancient time, different local ethnic groups have used various part of J. regia for a wide array of ailments including helminthiasis, diarrhea, sinusitis, stomach ache, arthritis, asthma, eczema, scrofula, skin disorders, diabetes mellitus, anorexia, thyroid dysfunction, cancer and infectious diseases. Biological activities of J. regia have been reported in several peer review journals and scientific attention is increasing. The present review attempts to provide comprehensive information on plant description, ethnobotanical use, toxicity, phytochemical profile, pharmacology, clinical studies and current research prospective of the J. regia. Currently, there is an immense interest on isolation/identification of active constituents from walnut and screening those active compounds for pharmacological activities. In addition, researchers are performing clinical trials as well as screening various solvent extracts or fractions of J. regia in several animal diseases models to identify promising therapeutic benefits. In the present work, we review the latest information based on published scientific investigations of J. regia.
Cardiovascular diseases (CVDs) have been the prime cause of mortality worldwide for decades. However, the underlying mechanism of their pathogenesis is not fully clear yet. It has been already established that reactive oxygen species (ROS) play a vital role in the progression of CVDs. ROS are chemically unstable reactive free radicals containing oxygen, normally produced by xanthine oxidase, nicotinamide adenine dinucleotide phosphate oxidase, lipoxygenases, or mitochondria or due to the uncoupling of nitric oxide synthase in vascular cells. When the equilibrium between production of free radicals and antioxidant capacity of human physiology gets altered due to several pathophysiological conditions, oxidative stress is induced, which in turn leads to tissue injury. This review focuses on pathways behind the production of ROS, its involvement in various intracellular signaling cascades leading to several cardiovascular disorders (endothelial dysfunction, ischemia-reperfusion, and atherosclerosis), methods for its detection, and therapeutic strategies for treatment of CVDs targeting the sources of ROS. The information generated by this review aims to provide updated insights into the understanding of the mechanisms behind cardiovascular complications mediated by ROS.
Paudel, KR, Karki, R & Kim, D-W 2016, 'Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular inflammatory responses mediated by RAW264.7', TOXICOLOGY IN VITRO, vol. 34, pp. 16-25.View/Download from: Publisher's site
Paudel, KR, Lee, UW & Kim, DW 2016, 'Chungtaejeon, a Korean fermented tea, prevents the risk of atherosclerosis in rats fed a high-fat atherogenic diet', Journal of Integrative Medicine, vol. 14, no. 2, pp. 134-142.View/Download from: Publisher's site
© 2016 Journal of Integrative Medicine Editorial Office. Objective Hypercholesterolemia is one of the well-established risk factors for cardiovascular mortality and morbidity in coronary heart disease. The aim of this study was to investigate the anti-atherogenic effect of Chungtaejeon (CTJ, a Korean fermented tea) aqueous extract on proliferation and migration of human aortic smooth muscle cells (HASMCs) in vivo and in vitro. Methods The authors used high-fat atherogenic diet (HFAD) to induce hyperlipidemia in Wistar rats in in vivo animal experiments and used HASMCs for in vitro cell experiments. For the in vitro cell experiment, the proliferation of asms was evaluated using the MTT assay. Similarly, the expression of matrix metalloproteinases (MMPs) in HASMCs was measured using gelatin zymography. Antimigratory activity of CTJ was revealed using the wound-healing model and Boyden's chamber assay. In the in vivo experiment, CTJ was administered in three different doses for 20 d from the initiation of the HFAD. After 20 d, the serum lipid profile and total lipid contents in liver were measured. Results Treatment with CTJ for 24 h dose-dependently inhibited the proliferation and migration of HASMCs and expression of MMP-2 in HASMCs. The oral administration of CTJ at concentrations of 200 and 400 mg/kg decreased the levels of low-density lipoprotein cholesterol, total serum cholesterol and hepatic cholesterol of HFAD-fed rats. Conclusion CTJ possessed strong antiproliferative, antimigratory, as well as lipid-lowering activities. Thus, CTJ can be considered as a therapeutic option in the treatment of high-fat diet-induced atherosclerosis.
Copyright © 2016 Keshav Raj Paudel et al. The levels of circulating microparticles (MPs) are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs) described as complex submicron (0.1 to 1.0 μm) vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.
Lee, H-H, Paudel, KR & Kim, D-W 2015, 'Terminalia chebula Fructus Inhibits Migration and Proliferation of Vascular Smooth Muscle Cells and Production of Inflammatory Mediators in RAW 264.7', EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE.View/Download from: Publisher's site
Sahu, P, Donovan, C, Pickles, S, Chimankar, V, Shukla, S, Gomez, H, Budden, K, Malyla, V, Paudel, KR, Dua, K & Hansbro, P 2019, 'Investigating the Pathogenesis of Early Stage Squamous Cell Lung Carcinoma Using Murine Models', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, WILEY, pp. 19-20.
Wadhwa, R, Paudel, KR, Nee, TX, Xin Lau, NJ, Zeeshan, F, Madheswaran, T, Panneerselvam, J, Reddy, K, Hsu, A, Oliver, B, Hansbro, P, Chellappan, DK & Dua, K 2019, 'Preparation, characterisation and biological applications of Rutin loaded liquid crystalline nanoparticles in targeting airway diseases', Sydney New Horizons-2019.