Displaying publications 1 - 20 of 23 in total

  1. Ch'ng ASH, Yong KTW, Ng DWH, Heyzer L, Lim WS
    J Am Med Dir Assoc, 2017 06 01;18(6):544-545.
    PMID: 28431910 DOI: 10.1016/j.jamda.2017.02.018
    Matched MeSH terms: Translational Medical Research*
  2. Shankar EM, Vignesh R, Dash AP
    Med Microbiol Immunol, 2018 Aug;207(3-4):167-174.
    PMID: 29936565 DOI: 10.1007/s00430-018-0547-0
    T-cell exhaustion reportedly leads to dysfunctional immune responses of antigen-specific T cells. Investigations have revealed that T cells expand into functionally defective phenotypes with poor recall/memory abilities to parasitic antigens. The exploitation of co-inhibitory pathways represent a highly viable area of translational research that has very well been utilized against certain cancerous conditions. Malaria, at times, evolve into a sustained chronic state where T cells express several co-inhibitory molecules (negative immune checkpoints) facilitating parasite escape and sub-optimal protective responses. Experimental evidence suggests that blockade of co-inhibitory molecules on T cells in malaria could result in the sustenance of protective responses together with dramatic parasite clearance. The role of several co-inhibitory molecules in malaria infection largely remain unclear, and here we discussed the potential applicability of co-inhibitory molecules in the management of malaria with a view to harness protective host responses against chronic disease and associated consequences.
    Matched MeSH terms: Translational Medical Research/trends*
  3. Ramzi AB
    Adv Exp Med Biol, 2018 11 2;1102:81-95.
    PMID: 30382570 DOI: 10.1007/978-3-319-98758-3_6
    In the modern era of next-generation genomics and Fourth Industrial Revolution, there is a growing demand for translational research that brings about not only impactful research but also potential commercialisation of R- and D-based products. Advancement of metabolic engineering and synthetic biology has put forward a viable and innovative biotechnological platform for bioproduct development especially using microbial chassis. In this chapter, readers will be introduced on the concepts of metabolic engineering, synthetic biology and microbial chassis and the applications of these biological engineering (BioE) components in the advancement of industrial and agricultural biotechnology. Main strategies in employing BioE platform are discussed especially for waste bioconversion and value-added product development. More importantly, this chapter will also discuss current endeavours in integrating systems and synthetic biology for microbial production of natural products by introducing flavonoid biosynthesis genes of Polygonum minus, a medicinally important tropical plant in engineered yeast.
    Matched MeSH terms: Translational Medical Research
  4. Yadav V, Krishnan A, Vohora D
    J Ethnopharmacol, 2020 Jan 30;247:112255.
    PMID: 31568819 DOI: 10.1016/j.jep.2019.112255
    ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant.

    MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019.

    RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom.

    CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.

    Matched MeSH terms: Translational Medical Research/methods*; Translational Medical Research/trends
  5. Mitropoulos K, Al Jaibeji H, Forero DA, Laissue P, Wonkam A, Lopez-Correa C, et al.
    Hum Genomics, 2015 Jun 18;9:11.
    PMID: 26081768 DOI: 10.1186/s40246-015-0033-3
    In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.
    Matched MeSH terms: Translational Medical Research/economics; Translational Medical Research/trends*
  6. Shen CL, Klein A, Chin KY, Mo H, Tsai P, Yang RS, et al.
    Ann N Y Acad Sci, 2017 Aug;1401(1):150-165.
    PMID: 28891093 DOI: 10.1111/nyas.13449
    Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research.
    Matched MeSH terms: Translational Medical Research/methods*; Translational Medical Research/trends
  7. Mak JW
    There is no substantial difference in conducting research that is both ethical and responsive to the health needs in developing and developed nations. Differences are in financial constraints, technological expertise in identification and addressing needs, and in the perception of equal partnership of all stakeholders. There will be differences in emphasis of research but this is slowly blurred due to globalisation. Public health emergencies in developing countries need timely and effective global collaborative research to implement control strategies. Research needs should be based on predictive models with learning from past emergencies, technological advances, strategic critical appraisal of local and global health information, and dialogue with all stakeholders. Adequate funding will be challenging and resources from national, international and aid
    foundations will be needed. Issues associated with such funding include deployment of international rapid response teams, collaborating researchers, transfer of technology, and intellectual property ownership. While all types of research ranging from basic, applied, clinical
    studies, meta-analysis, and translational research are relevant, the relative importance and specific allocation of resources to these may differ. Is the choice related to responsiveness or based on researchers’ perception of their contributions to evidence-based practice and research? Ethical issues relating to vulnerable groups, risk distribution, quality issues, research integrity and oversight are just as important. Internationally funded
    research including clinical trials must be sensitive to such issues to avoid allegations of exploitation. Thus the potential of utilisation and buy-in of research findings and recommendations must be considered.
    Matched MeSH terms: Translational Medical Research
  8. Malik JA, Yaseen Z, Thotapalli L, Ahmed S, Shaikh MF, Anwar S
    Mol Biol Rep, 2023 Apr;50(4):3767-3785.
    PMID: 36692676 DOI: 10.1007/s11033-023-08241-7
    Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.
    Matched MeSH terms: Translational Medical Research
  9. Park JY, Ngan HY, Park W, Cao Z, Wu X, Ju W, et al.
    J Gynecol Oncol, 2015 Jan;26(1):68-74.
    PMID: 25609163 DOI: 10.3802/jgo.2015.26.1.68
    The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.
    Matched MeSH terms: Translational Medical Research/methods
  10. Kamarul T
    Expert Rev Clin Pharmacol, 2013 Jul;6(4):363-5.
    PMID: 23927663 DOI: 10.1586/17512433.2013.811804
    The World Stem Cells & Regenerative Medicine Congress Asia 2013 held in Singapore from 19-21 March 2013 was attended by over 2000 industry attendees and 5000 registered visitors. The focus of the congress was to discuss potential uses of stem cells for various diagnostic and therapeutic applications, their market opportunity and the latest R&D, which would potentially find its way into the market in not too distant future. In addition to the traditional lectures presented by academic and industry experts, there were forums, discussions, posters and exhibits, which provided various platforms for researchers, potential industry partners and even various interest groups to discuss prospective development of the stem cell-related industry.
    Matched MeSH terms: Translational Medical Research/trends*
  11. Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R
    Cytotherapy, 2016 Jan;18(1):13-24.
    PMID: 26631828 DOI: 10.1016/j.jcyt.2015.10.008
    The unique properties of mesenchymal stromal/stem cells (MSCs) to self-renew and their multipotentiality have rendered them attractive to researchers and clinicians. In addition to the differentiation potential, the broad repertoire of secreted trophic factors (cytokines) exhibiting diverse functions such as immunomodulation, anti-inflammatory activity, angiogenesis and anti-apoptotic, commonly referred to as the MSC secretome, has gained immense attention in the past few years. There is enough evidence to show that the one important pathway by which MSCs participate in tissue repair and regeneration is through its secretome. Concurrently, a large body of MSC research has focused on characterization of the MSC secretome; this includes both soluble factors and factors released in extracellular vesicles, for example, exosomes and microvesicles. This review provides an overview of our current understanding of the MSC secretome with respect to their potential clinical applications.
    Matched MeSH terms: Translational Medical Research
  12. Negrini S, Arienti C, Engkasan JP, Gimigliano F, Grubisic F, Howe T, et al.
    Eur J Phys Rehabil Med, 2019 Apr;55(2):314-318.
    PMID: 30938139 DOI: 10.23736/S1973-9087.19.05785-X
    During its second year of existence, Cochrane Rehabilitation worked hard to accomplish new and old goals. The Review Committee completed the massive task of identifying and "tagging" all rehabilitation reviews in the Cochrane library. The Publication Committee signed agreements with several international journals and started the publication of Cochrane Corners. The Education Committee performed educational activities such as workshops in International Meetings. The Methodology Committee has completed a two days Cochrane Rehabilitation Methodological Meeting in Paris of which the results will soon be published. The Communication Committee reaches almost 5,000 rehabilitation professionals through social media, and is working on the translation of contents in Italian, Spanish, French, Dutch, Croatian and Japanese. Memoranda of Understanding have been signed with several National and International Rehabilitation Scientific Societies, Universities, Hospitals, Research Centres and other organizations. The be4rehab (best evidence for rehabilitation) project has been started with the World Health Organisation (WHO) to extract from Cochrane reviews and clinical guidelines the best currently available evidence to produce the WHO Minimum Package of Rehabilitation Interventions. The Cochrane Rehabilitation ebook is under development as well as a priority setting exercise with 39 countries from all continents.
    Matched MeSH terms: Translational Medical Research
  13. Kundap UP, Bhuvanendran S, Kumari Y, Othman I, Shaikh MF
    Front Pharmacol, 2017;8:76.
    PMID: 28289385 DOI: 10.3389/fphar.2017.00076
    A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.
    Matched MeSH terms: Translational Medical Research
  14. Chai AWY, Lim KP, Cheong SC
    Semin Cancer Biol, 2020 04;61:71-83.
    PMID: 31542510 DOI: 10.1016/j.semcancer.2019.09.011
    Oral squamous cell carcinomas (OSCC) are a heterogeneous group of cancers arising from the mucosal lining of the oral cavity. A majority of these cancers are associated with lifestyle risk habits including smoking, excessive alcohol consumption and betel quid chewing. Cetuximab, targeting the epidermal growth factor receptor was approved for the treatment of OSCC in 2006, and remains the only molecular targeted therapy available for OSCC. Here, we reviewed the current findings from genomic analyses of OSCC and discuss how these studies inform on the biological mechanisms underlying OSCC. Exome sequencing revealed that the significantly mutated genes are mainly tumour suppressors. Mutations in FAT1, CASP8, CDKN2A, and NOTCH1 are more frequently found in OSCC when compared to non-OSCC head and neck cancers and other squamous cell carcinomas, and HRAS and PIK3CA are the only significantly mutated oncogenes. The distribution of these mutations also differs in populations with distinct risk habits. Gene expression-based molecular classification showed that OSCC can be divided into distinct subtypes and these have a preferential response to different types of therapies, suggesting that these classifications could have clinical implications. More recently, with the approval of checkpoint inhibitors for the treatment of cancers including OSCC, genomics studies also dissected the genetic signatures of the immune compartment to delineate immune-active and -exhausted subtypes that could inform on the immune status of OSCC patients and guide the development of novel therapies to improve response to immunotherapy. Taken together, genomics studies are informing on the biology of both the epithelial and stromal compartments underlying OSCC development, and we discuss the opportunities and challenges in using these to derive clinical benefit for OSCC patients.
    Matched MeSH terms: Translational Medical Research*
  15. Mustapha M, Nassir CMNCM, Aminuddin N, Safri AA, Ghazali MM
    Front Physiol, 2019;10:1317.
    PMID: 31708793 DOI: 10.3389/fphys.2019.01317
    Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and imaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. Unlike large vessels, it is a challenge to visualize small vessels in vivo, hence the difficulty to directly monitor the natural progression of the disease. CSVD might progress for many years during the early stage of the disease as it remains asymptomatic. Prevalent among elderly individuals, CSVD has been alarmingly reported as an important precursor of full-blown stroke and vascular dementia. Growing evidence has also shown a significant association between CSVD's radiological manifestation with dementia and Alzheimer's disease (AD) pathology. Although it remains contentious as to whether CSVD is a cause or sequelae of AD, it is not far-fetched to posit that effective therapeutic measures of CSVD would mitigate the overall burden of dementia. Nevertheless, the unifying theory on the pathomechanism of the disease remains elusive, hence the lack of effective therapeutic approaches. Thus, this chapter consolidates the contemporary insights from numerous experimental animal models of CSVD, to date: from the available experimental animal models of CSVD and its translational research value; the pathomechanical aspects of the disease; relevant aspects on systems biology; opportunities for early disease biomarkers; and finally, converging approaches for future therapeutic directions of CSVD.
    Matched MeSH terms: Translational Medical Research
  16. Liou AT, Liao CC, Chou SF, Chang YS, Chang CS, Shih C
    J Biomed Sci, 2019 Nov 11;26(1):93.
    PMID: 31711481 DOI: 10.1186/s12929-019-0585-y
    BACKGROUND: Enterovirus 71 (EV71 or EV-A71) was first identified in California about half a century ago. In recent years, outbreaks of EV-A71 were prevalent worldwide, including Taiwan, Malaysia, Singapore, Japan, and China. Between 2008 and 2011, China alone reported 1894 deaths associated with EV-A71 infection. In mild cases, EV-A71 can cause herpangina and hand-foot-and-mouth disease (HFMD). However, in severe cases, it could cause neurological disorders, including meningitis and encephalitis. Cardiopulmonary failure is common among hospitalized children with EV-A71 infection. No effective FDA-approved therapeutics against EV-A71 are clinically available.

    METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.

    RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.

    CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.

    Matched MeSH terms: Translational Medical Research
  17. Rasiah S, Jaafar S, Yusof S, Ponnudurai G, Chung KPY, Amirthalingam SD
    BMJ Open, 2020 01 23;10(1):e028061.
    PMID: 31980505 DOI: 10.1136/bmjopen-2018-028061
    INTRODUCTION: The aim of this scoping review is to systematically search the literature to identify the nature and or level of trust between the patient, the users of health services (eg, clients seeking health promotion and preventive healthcare services) and the individual healthcare providers (doctors, nurses and physiotherapists/ occupational therapists), across public and private healthcare sectors, at all levels of care from primary through secondary to tertiary care. It also aims to identify the factors that influence trust between patients, users of health services (clients) and providers of healthcare at all levels of care from primary care to tertiary care, and across all health sectors (public and private). The study will also identify the tools used to measure trust in the healthcare provider.

    METHODS AND ANALYSIS: The scoping review will be conducted based on the methodology developed by Arksey and O'Malley's scoping review methodology, and Levac et al's methodological enhancement. An experienced information specialist (HM) searched the following databases MEDLINE, EMBASE, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature. The search terms were both keywords in the title and/or abstract and subject headings (eg, MeSH, EMTREE) as appropriate. Search results were downloaded, imported and stored into a 'Refworks' folder specifically created for reference management. The preliminary search was conducted between 7 December 2017 and 14 December 2017. Quantitative methods using content analysis will be used to categorise study findings on factors associated with trust between patients, clients and healthcare providers. The collection of studies will be also examined for heterogeneity. Qualitative analysis on peer reviewed articles of qualitative interviews and focus group discussion will be conducted; it allows clear identification of themes arising from the data, facilitating prioritisation, higher order abstraction and theory development. A consultation exercise with stakeholders may be incorporated as a knowledge translation component of the scoping study methodology.

    ETHICS AND DISSEMINATION: Ethical approval will be obtained for the research project from the Institutional Review Board. The International Medical University will use the findings of this scoping review research to improve the understanding of trust in healthcare, in its endeavour to improve health services delivery in its healthcare clinics and hospitals, and in its teaching and learning curriculum. The findings will also help faculty make evidence based decisions to focus resources and research as well as help to advance the science in this area. Dissemination of the results of the scoping review will be made through peer-reviewed publications, research reports and presentations at conferences and seminars.

    Matched MeSH terms: Translational Medical Research
  18. Chin KY, Pang KL
    Nutrients, 2017 Sep 26;9(10).
    PMID: 28954409 DOI: 10.3390/nu9101060
    Osteoarthritis is a major cause of morbidity among the elderly worldwide. It is a disease characterized by localized inflammation of the joint and destruction of cartilage, leading to loss of function. Impaired chondrocyte repair mechanisms, due to inflammation, oxidative stress and autophagy, play important roles in the pathogenesis of osteoarthritis. Olive and its derivatives, which possess anti-inflammatory, antioxidant and autophagy-enhancing activities, are suitable candidates for therapeutic interventions for osteoarthritis. This review aimed to summarize the current evidence on the effects of olive and its derivatives, on osteoarthritis and chondrocytes. The literature on animal and human studies has demonstrated a beneficial effect of olive and its derivatives on the progression of osteoarthritis. In vitro studies have suggested that the augmentation of autophagy (though sirtuin-1) and suppression of inflammation by olive polyphenols could contribute to the chondroprotective effects of olive polyphenols. More research and well-planned clinical trials are required to justify the use of olive-based treatment in osteoarthritis.
    Matched MeSH terms: Translational Medical Research/methods*
  19. Maki MAA, Cheah SC, Bayazeid O, Kumar PV
    Sci Rep, 2020 10 15;10(1):17468.
    PMID: 33060727 DOI: 10.1038/s41598-020-74467-1
    Galectin-3 (Gal-3) is a carbohydrate-binding protein, that promotes angiogenesis through mediating angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). There is strong evidence confirming FGF involvement in tumor growth and progression by disrupting cell proliferation and angiogenesis. In this study, we investigated the effect of β-cyclodextrin:everolimus:FGF-7 inclusion complex (Complex) on Caco-2 cell migration, cell motility and colony formation. In addition, we examined the inhibitory effect of the Complex on the circulating proteins; Gal-3 and FGF-7. Swiss Target Prediction concluded that Gal-3 and FGF are possible targets for β-CD. Results of the chemotaxis cell migration assay on Caco-2 cell line revealed that the Complex has higher reduction in cell migration (78.3%) compared to everolimus (EV) alone (58.4%) which is possibly due to the synergistic effect of these molecules when used as a combined treatment. Moreover, the Complex significantly decreased the cell motility in cell scratch assay, less than 10% recovery compared to the control which has ~ 45% recovery. The Complex inhibited colony formation by ~ 75% compared to the control. Moreover, the Complex has the ability to inhibit Gal-3 with minimum inhibitory concentration of 33.46 and 41 for β-CD and EV, respectively. Additionally, β-CD and β-CD:EV were able to bind to FGF-7 and decreased the level of FGF-7 more than 80% in cell supernatant. This confirms Swiss Target Prediction result that predicted β-CD could target FGF. These findings advance the understanding of the biological effects of the Complex which reduced cell migration, cell motility and colony formation and it is possibly due to inhibiting circulating proteins such as; Gal-3 and FGF-7.
    Matched MeSH terms: Translational Medical Research
  20. Sulaiman I, Lim JC, Soo HL, Stanslas J
    Pulm Pharmacol Ther, 2016 Oct;40:52-68.
    PMID: 27453494 DOI: 10.1016/j.pupt.2016.07.005
    Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs. New drug candidates with their putative targets that have shown promising results in the preclinical and/or clinical trials are summarised. Examples of these interventions include restoration of Th1/Th2 balance by the use of newly developed immunomodulators such as toll-like receptor-9 activators (CYT003-QbG10 and QAX-935). Clinical trials revealed the safety and effectiveness of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists such as OC0000459, BI-671800 and ARRY-502 in the restoration of Th1/Th2 balance. Regulation of cytokine activity by the use of newly developed biologics such as benralizumab, reslizumab, mepolizumab, lebrikizumab, tralokinumab, dupilumab and brodalumab are at the stage of clinical development. Transcription factors are potential targets for asthma therapy, for example SB010, a GATA-3 DNAzyme is at its early stage of clinical trial. Other candidates such as inhibitors of Rho kinases (Fasudil and Y-27632), phosphodiesterase inhibitors (GSK256066, CHF 6001, roflumilast, RPL 554) and proteinase of activated receptor-2 (ENMD-1068) are also discussed. Preclinical results of blockade of calcium sensing receptor by the use of calcilytics such as calcitriol abrogates cardinal signs of asthma. Nevertheless, successful translation of promising preclinical data into clinically viable interventions remains a major challenge to the development of novel anti-asthmatics.
    Matched MeSH terms: Translational Medical Research
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