Displaying publications 21 - 40 of 40 in total

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  1. Current approaches in antiviral drug discovery against the Flaviviridae family
    Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.
    Curr Pharm Des, 2014;20(21):3428-44.
    PMID: 24001228
    Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.
    Matched MeSH terms: Drug Discovery/methods*
  2. Search for antibacterial agents from Malaysian rainforest and tropical plants
    Othman M, Genapathy S, Liew PS, Ch'ng QT, Loh HS, Khoo TJ, et al.
    Nat Prod Res, 2011 Nov;25(19):1857-64.
    PMID: 21838540 DOI: 10.1080/14786419.2010.537274
    The world's rainforests hold untold potential for drug discovery. Rainforest plants are thought to contain evolved defensive active metabolites of greater diversity compared to plants from temperate regions. In recent years, the interest and overall output from pharmaceutical companies on novel antibacterial agents has diminished at a time when there is a critical need for them to fight the threat of resistance. In this study, we have investigated the antimicrobial properties of 21 flowering plants from 16 different families against six bacterial strains consisting of two Gram negative and four Gram positive. Using the pour plate disc diffusion technique, almost all extracts from these plants were found to be active against some of the bacterial strains tested. The most interesting and active plants with broad spectrum activities include Duabanga grandiflora, Acalypha wilkesiana and Pseuduvaria macrophylla where the minimum inhibitory concentration, minimum bactericidal concentration and phytochemical analysis were carried out. This is the first report describing the antimicrobial and phytochemical properties of D. grandiflora and P. macrophylla. Our findings support the utilisation of higher plant species in the search for new antimicrobial molecules to combat new emerging infective diseases and the problem of drug resistant pathogens.
    Matched MeSH terms: Drug Discovery/methods*
  3. Exploring Antimicrobials from the Flora and Fauna of Marine: Opportunities and Limitations
    Venkateskumar K, Parasuraman S, Chuen LY, Ravichandran V, Balamurgan S
    Curr Drug Discov Technol, 2020;17(4):507-514.
    PMID: 31424372 DOI: 10.2174/1570163816666190819141344
    About 95% of earth living space lies deep below the ocean's surface and it harbors extraordinary diversity of marine organisms. Marine biodiversity is an exceptional reservoir of natural products, bioactive compounds, nutraceuticals and other potential compounds of commercial value. Timeline for the development of the drug from a plant, synthetic and other alternative sources is too lengthy. Exploration of the marine environment for potential bioactive compounds has gained focus and huge opportunity lies ahead for the exploration of such vast resources in the ocean. Further, the evolution of superbugs with increasing resistance to the currently available drugs is alarming and it needs coordinated efforts to resolve them. World Health Organization recommends the need and necessity to develop effective bioactive compounds to combat problems associated with antimicrobial resistance. Based on these factors, it is imperative to shift the focus towards the marine environment for potential bioactive compounds that could be utilized to tackle antimicrobial resistance. Current research trends also indicate the huge strides in research involving marine environment for drug discovery. The objective of this review article is to provide an overview of marine resources, recently reported research from marine resources, challenges, future research prospects in the marine environment.
    Matched MeSH terms: Drug Discovery/methods*
  4. Fulltext A side-effect free method for identifying cancer drug targets
    Ashraf MI, Ong SK, Mujawar S, Pawar S, More P, Paul S, et al.
    Sci Rep, 2018 04 27;8(1):6669.
    PMID: 29703908 DOI: 10.1038/s41598-018-25042-2
    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.
    Matched MeSH terms: Drug Discovery/methods*
  5. Fulltext Comparison of apoptotic responses in Blastocystis sp. upon treatment with Tongkat Ali and Metronidazole
    Girish S, Kumar S, Aminudin N, Hashim NM
    Sci Rep, 2021 04 09;11(1):7833.
    PMID: 33837230 DOI: 10.1038/s41598-021-81418-x
    Blastocystis sp. infection, although many remain asymptomatic, there is growing data in recent studies that suggests it is a frequent cause of gastrointestinal symptoms in children and adults. This proposes that treatment against this infection is necessary however metronidazole (MTZ), which is the current choice of treatment, has expressed non-uniformity in its efficacy in combating this infection which has led to the study of alternative treatment. In our previous study, it was established that Tongkat Ali fractions exhibited promising anti-protozoal properties which leads to the current aim of the study, to further narrow down the purification process in order to identify the specific active compound promoting the anti-protozoal effect through HPLC analysis. Based on the data analysis and in-vitro susceptibility assay, the collected Tongkat Ali fraction that demonstrated anti-blastocystis property was shown to contain eurycomanone. Previous studies have suggested that there is a mechanism in Blastocystis sp. that regulates the apoptotic process to produce higher number of viable cells when treated. In reference to this, our current study also aims to investigate the apoptotic response of Tongkat Ali extract and eurycomanone across different subtype groups with comparison to MTZ. Based on our investigation, both Tongkat Ali extract and eurycomanone induced the high apoptotic rate however exhibited a reduction in viable cell count (p 
    Matched MeSH terms: Drug Discovery/methods
  6. Fulltext Optimization: Molecular Communication Networks for Viral Disease Analysis Using Deep Leaning Autoencoder
    Junejo AR, Kaabar MKA, Li X
    Comput Math Methods Med, 2021;2021:9949328.
    PMID: 34938362 DOI: 10.1155/2021/9949328
    Developing new treatments for emerging infectious diseases in infectious and noninfectious diseases has attracted a particular attention. The emergence of viral diseases is expected to accelerate; these data indicate the need for a proactive approach to develop widely active family specific and cross family therapies for future disease outbreaks. Viral disease such as pneumonia, severe acute respiratory syndrome type 2, HIV infection, and Hepatitis-C virus can cause directly and indirectly cardiovascular disease (CVD). Emphasis should be placed not only on the development of broad-spectrum molecules and antibodies but also on host factor therapy, including the reutilization of previously approved or developing drugs. Another new class of therapeutics with great antiviral therapeutic potential is molecular communication networks using deep learning autoencoder (DL-AEs). The use of DL-AEs for diagnosis and prognosis prediction of infectious and noninfectious diseases has attracted a particular attention. MCN is map to molecular signaling and communication that are found inside and outside the human body where the goal is to develop a new black box mechanism that can serve the future robust healthcare industry (HCI). MCN has the ability to characterize the signaling process between cells and infectious disease locations at various levels of the human body called point-to-point MCN through DL-AE and provide targeted drug delivery (TDD) environment. Through MCN, and DL-AE healthcare provider can remotely measure biological signals and control certain processes in the required organism for the maintenance of the patient's health state. We use biomicrodevices to promote the real-time monitoring of human health and storage of the gathered data in the cloud. In this paper, we use the DL-based AE approach to design and implement a new drug source and target for the MCN under white Gaussian noise. Simulation results show that transceiver executions for a given medium model that reduces the bit error rate which can be learned. Then, next development of molecular diagnosis such as heart sounds is classified. Furthermore, biohealth interface for the inside and outside human body mechanism is presented, comparative perspective with up-to-date current situation about MCN.
    Matched MeSH terms: Drug Discovery/methods
  7. Fulltext Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review
    Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB
    Int J Mol Sci, 2021 Aug 20;22(16).
    PMID: 34445667 DOI: 10.3390/ijms22168962
    Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.
    Matched MeSH terms: Drug Discovery/methods
  8. Fulltext Induced pluripotent stem cells in research and therapy
    Teoh HK, Cheong SK
    Malays J Pathol, 2012 Jun;34(1):1-13.
    PMID: 22870592 MyJurnal
    Induced pluripotent stem cells (iPSC) are derived from human somatic cells through ectopic expression of transcription factors. This landmark discovery has been considered as a major development towards patient-specific iPSC for various biomedical applications. Unlimited self renewal capacity, pluripotency and ease of accessibility to donor tissues contribute to the versatility of iPSC. The therapeutic potential of iPSC in regenerative medicine, cell-based therapy, disease modelling and drug discovery is indeed very promising. Continuous progress in iPSC technology provides clearer understanding of disease pathogenesis and ultimately new optimism in developing treatment or cure for human diseases.
    Matched MeSH terms: Drug Discovery/methods
  9. Fulltext Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening
    Teo CY, Shave S, Chor AL, Salleh AB, Rahman MB, Walkinshaw MD, et al.
    BMC Bioinformatics, 2012;13 Suppl 17:S4.
    PMID: 23282142 DOI: 10.1186/1471-2105-13-S17-S4
    BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.

    RESULTS: Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC50 values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.

    CONCLUSION: Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.

    Matched MeSH terms: Drug Discovery/methods*
  10. Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism
    Hasan WNW, Chin KY, Jolly JJ, Ghafar NA, Soelaiman IN
    Endocr Metab Immune Disord Drug Targets, 2018;18(5):450-457.
    PMID: 29683099 DOI: 10.2174/1871530318666180423122409
    BACKGROUND: Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.

    OBJECTIVE: This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.

    DISCUSSION: Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.

    CONCLUSION: Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.

    Matched MeSH terms: Drug Discovery/methods*
  11. Fulltext Molecular modulators of celastrol as the keystones for its diverse pharmacological activities
    Ng SW, Chan Y, Chellappan DK, Madheswaran T, Zeeshan F, Chan YL, et al.
    Biomed Pharmacother, 2019 Jan;109:1785-1792.
    PMID: 30551432 DOI: 10.1016/j.biopha.2018.11.051
    In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
    Matched MeSH terms: Drug Discovery/methods*
  12. In silico identification and validation of a novel hypothetical protein in Cryptosporidium hominis and virtual screening of inhibitors as therapeutics
    Shrivastava AK, Kumar S, Sahu PS, Mahapatra RK
    Parasitol Res, 2017 May;116(5):1533-1544.
    PMID: 28389892 DOI: 10.1007/s00436-017-5430-1
    Computational approaches to predict structure/function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are ineffective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical protein (TU502HP) in the C. hominis genome from the CryptoDB database. A three-dimensional model of the protein was generated using the Iterative Threading ASSEmbly Refinement server through an iterative threading method. Functional annotation and phylogenetic study of TU502HP protein revealed similarity with human transportin 3. The model is further subjected to a virtual screening study form the ZINC database compound library using the Dock Blaster server. A docking study through AutoDock software reported N-(3-chlorobenzyl)ethane-1,2-diamine as the best inhibitor in terms of docking score and binding energy. The reliability of the binding mode of the inhibitor is confirmed by a complex molecular dynamics simulation study using GROMACS software for 10 ns in the water environment. Furthermore, antigenic determinants of the protein were determined with the help of DNASTAR software. Our findings report a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for treatment and prophylaxis of cryptosporidiosis among humans and animals.
    Matched MeSH terms: Drug Discovery/methods*
  13. Recent discovery of non-nucleobase thymidine phosphorylase inhibitors targeting cancer
    Bera H, Chigurupati S
    Eur J Med Chem, 2016 Nov 29;124:992-1003.
    PMID: 27783978 DOI: 10.1016/j.ejmech.2016.10.032
    Thymidine phosphorylase (TP, EC 2.4.2.4), an enzyme involved in pyrimidine salvage pathway, is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is extremely upregulated in a variety of solid tumours. The TP amplification is associated with concomitant overexpression of many angiogenic factors such as matrix metalloproteases (MMPs), interleukins (ILs), vascular endothelial growth factor (VEGF) etc., resulting in promotion of angiogenesis and cancer metastasis. In addition, overshooting TP level protects tumour cells from apoptosis and helps cell survival. Thus, TP is identified as a prime target for developing novel anticancer therapies. Pioneering research activities investigated a large number of TP inhibitors, most of which are pyrimidine or purine analogues. Recently, an array of structurally diverse non-nucleobase derivatives was designed, synthesized and established as promising TP inhibitors. This review, following an outline on the TP structure and functions, gives an overview of the recent advancement of various non-nucleobase TP inhibitors as novel anti-cancer agents.
    Matched MeSH terms: Drug Discovery/methods*
  14. Protein and Peptide Biopharmaceuticals: An Overview
    Agyei D, Ahmed I, Akram Z, Iqbal HM, Danquah MK
    Protein Pept Lett, 2017;24(2):94-101.
    PMID: 28017145 DOI: 10.2174/0929866523666161222150444
    Bioactive proteins and peptides are recognised as novel therapeutic molecules with varying biological properties for potential medical applications. Development of protein and peptidebased therapeutic products for human use is growing steadily as they continue to receive an increasing rate of approval by the United States Food and Drugs Administration (US FDA). In this short review, we describe the current status and methodologies involved in the synthesis of protein and peptide biopharmaceuticals with an emphasis on the drivers and restrains to their exploitation in the therapeutic products sector.
    Matched MeSH terms: Drug Discovery/methods*
  15. Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study
    Lajis AFB, Ariff AB
    J Cosmet Dermatol, 2019 Jun;18(3):703-727.
    PMID: 30866156 DOI: 10.1111/jocd.12900
    Human skin pigmentation is a result of constitutive and facultative pigmentation. Facultative pigmentation is frequently stimulated by UV radiation, pharmacologic drugs, and hormones whereby leads to the development of abnormal skin hyperpigmentation. To date, many state-of-art depigmenting compounds have been studied using in vitro model to treat hyperpigmentation problems for cosmetic dermatological applications; little attention has been made to compare the effectiveness of these depigmenting compounds and their mode of actions. In this present article, new and recent depigmenting compounds, their melanogenic pathway targets, and modes of action are reviewed. This article compares the effectiveness of these new depigmenting compounds to modulate several melanogenesis-regulatory enzymes and proteins such as tyrosinase (TYR), TYR-related protein-1 (TRP1), TYR-related protein-2 (TRP2), microphthalmia-associated transcription factor (MITF), extracellular signal-regulated kinase (ERK) and N-terminal kinases (JNK) and mitogen-activated protein kinase p38 (p38 MAPK). Other evidences from in vitro assays such as inhibition on melanosomal transfer, proteasomes, nitric oxide, and inflammation-induced melanogenesis are also highlighted. This article also reviews analytical techniques in different assays performed using in vitro model as well as their advantages and limitations. This article also provides an insight on recent finding and re-examination of some protocols as well as their effectiveness and reliability in the evaluation of depigmenting compounds. Evidence and support from related patents are also incorporated in this present article to give an overview on current patented technology, latest trends, and intellectual values of some depigmenting compounds and protocols, which are rarely highlighted in the literatures.
    Matched MeSH terms: Drug Discovery/methods*
  16. Fulltext Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach
    Chai TT, Koh JA, Wong CC, Sabri MZ, Wong FC
    Molecules, 2021 Dec 06;26(23).
    PMID: 34885982 DOI: 10.3390/molecules26237396
    Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.
    Matched MeSH terms: Drug Discovery/methods*
  17. A High-throughput Quantitative Expression Analysis of Cancer-related Genes in Human HepG2 Cells in Response to Limonene, a Potential Anticancer Agent
    Hafidh RR, Hussein SZ, MalAllah MQ, Abdulamir AS, Abu Bakar F
    Curr Cancer Drug Targets, 2018;18(8):807-815.
    PMID: 29141549 DOI: 10.2174/1568009617666171114144236
    BACKGROUND: Citrus bioactive compounds, as active anticancer agents, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted.

    OBJECTIVES: The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene.

    METHODS: The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of the pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. Highthroughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development.

    RESULTS: In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene- driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from the most to the least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins.

    CONCLUSION: The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines.

    Matched MeSH terms: Drug Discovery/methods
  18. Fulltext The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges
    Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, et al.
    Cells, 2019 Sep 20;8(10).
    PMID: 31547193 DOI: 10.3390/cells8101118
    Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
    Matched MeSH terms: Drug Discovery/methods
  19. The use of transgenic parasites in malaria vaccine research
    Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM
    Expert Rev Vaccines, 2017 Jul;16(7):1-13.
    PMID: 28525963 DOI: 10.1080/14760584.2017.1333426
    INTRODUCTION: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
    Matched MeSH terms: Drug Discovery/methods*
  20. Gingerol and Its Role in Chronic Diseases
    Mohd Yusof YA
    Adv Exp Med Biol, 2016;929:177-207.
    PMID: 27771925
    Since antiquity, ginger or Zingiber officinale, has been used by humans for medicinal purposes and as spice condiments to enhance flavor in cooking. Ginger contains many phenolic compounds such as gingerol, shogaol and paradol that exhibit antioxidant, anti-tumor and anti-inflammatory properties. The role of ginger and its constituents in ameliorating diseases has been the focus of study in the past two decades by many researchers who provide strong scientific evidence of its health benefit. This review discusses research findings and works devoted to gingerols, the major pungent constituent of ginger, in modulating and targeting signaling pathways with subsequent changes that ameliorate, reverse or prevent chronic diseases in human studies and animal models. The physical, chemical and biological properties of gingerols are also described. The use of ginger and especially gingerols as medicinal food derivative appears to be safe in treating or preventing chronic diseases which will benefit the common population, clinicians, patients, researchers, students and industrialists.
    Matched MeSH terms: Drug Discovery/methods*
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