Displaying publications 1 - 20 of 32 in total

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  1. Kamal, M., Amini, F., Ramasamy, TS
    JUMMEC, 2016;19(1):23-32.
    MyJurnal
    Glaucoma is a common eye disease that can cause irreversible damage if left undiagnosed and untreated. It is one of the most common neurodegenerative diseases causing blindness. Pre-clinical studies have been carried out on animal models of glaucoma for stem cell therapy. We carried out a systematic review to determine whether stem cell therapy had the potential to treat glaucoma. Nine studies were selected based on the predetermined inclusion and exclusion criteria. Of these nine studies, eight focused on neuroprotection conferred by stem cells, and the remaining one on neuroregeneration. Results from these studies showed that there was a potential in stem cell based therapy in treating glaucoma, especially regarding neuroprotection via neurotrophic factors. The studies revealed that a brain-derived neurotrophic factor expressed by stem cells promoted the survival of retinal ganglion cells in murine glaucoma models. The transplanted cells survived without any side effects. While these studies proved that stem cells provided neuroprotection in glaucoma, improvement of vision could not be determined. Clinical studies would be required to determine whether the protection of RGC correlated with improvement in visual function. Furthermore, these murine studies could not be translated into clinical therapy due to the heterogeneity of the experimental methods and the
    use of different cell lines. In conclusion, the use of stem cells in the clinical therapy of glaucoma will be an important step in the future as it will transform present-day treatment with the hope of restoring sight to patients with glaucoma.
  2. Ayob AZ, Ramasamy TS
    In Vitro Cell Dev Biol Anim, 2021 Oct;57(9):896-911.
    PMID: 34750738 DOI: 10.1007/s11626-021-00625-y
    Tumour hypoxia drives resistance and aggressiveness, and in large part, contributes to treatment failure thereby causing cancer-related deaths. The rapid and uncontrolled tumour growth develops not only a hypoxic niche but also a nutrient-deprived condition due to insufficient blood supply; together, these create a stressful tumour niche, further promoting higher aggressiveness and resistance features of cancer. However, how cellular responses in the prolonged stress is associated with cancer stem cells (CSCs), which is linked to these features, remains unclear. Here, we established HepG2 tumoursphere culture in a hypoxic and serum-free condition that recapitulated differential responses to prolonged tumour growth pressures, evident by their progressive changes in the morphology of tumoursphere formation over a course of 15-day culture. HepG2 tumourspheres formed larger sphere sizes of > 200 μm in hypoxic conditions, concomitant with higher cell yield and upregulation of PCNA marker at day 7, corresponding with higher self-renewal capacity when cultured in SFM compared to SM. Notably, prolonged growth of HepG2 tumourspheres for 15 days under hypoxic and SFM condition increased their sphere counts, yet significantly reduced their cell yield along with downregulation of PCNA expression. Gene expression analysis showed that HepG2 tumourspheres on day 15 exhibited enhanced expression of markers of quiescence, stemness, EMT, and chemoresistance. Interestingly, analysis of HIF1α and HIF2α and their target gene expression indicated complementary HIF expression with preferential upregulation of HIF2α was observed in HepG2 tumourspheres in prolonged hypoxic and serum-free conditions, suggesting HIF2α-dependency and plausibility of the HIF1α-HIF2α switch that govern their survival by promoting CSC-like programmes. Altogether, these findings suggest the implication of prolonged hypoxia and nutrient deprivation stress in promoting CSC-like programmes in cancer cells recapitulating their plasticity, hence having opened many research directions that enable development of effective targeting of CSCs and precision medicine for treating cancer.
  3. Ong ALC, Ramasamy TS
    Ageing Res Rev, 2018 May;43:64-80.
    PMID: 29476819 DOI: 10.1016/j.arr.2018.02.004
    Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members of its kind in histone deacetylase family in governing multiple cellular fates, is predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner to inhibit transcription activity of p53, in turn modulate pathways that are implicated in regulation of tissue homoeostasis and many disease states. In this review, we discuss the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which are implicated in cellular aging, cancer and reprogramming. It is noteworthy that these cellular events share few common regulatory pathways, including SIRT1-p53-LDHA-Myc, miR-34a,-Let7 regulatory network, which forms a positive feedback loop that controls cell cycle, metabolism, proliferation, differentiation, epigenetics and many others. In the context of aging, SIRT1 expression is reduced as a protective mechanism against oncogenesis and for maintenance of tissue homeostasis. Interestingly, its activation in aged cells is evidenced in response to DNA damage to protect the cells from p53-dependent apoptosis or senescence, predispose these cells to neoplastic transformation. Importantly, the dual roles of SIRT1-p53 axis in aging and tumourigenesis, either as tumour suppressor or tumour promoter are determined by SIRT1 localisation and type of cells. Conceptualising the distinct similarity between tumorigenesis and cellular reprogramming, this review provides a perspective discussion on involvement of SIRT1 in improving efficiency in the induction and maintenance of pluripotent state. Further research in understanding the role of SIRT1-p53 pathway and their associated regulators and strategies to manipulate this regulatory axis very likely foster the development of therapeutics and strategies for treating cancer and aging-associated degenerative diseases.
  4. Ayob AZ, Ramasamy TS
    J Biomed Sci, 2018 Mar 06;25(1):20.
    PMID: 29506506 DOI: 10.1186/s12929-018-0426-4
    BACKGROUND: Cancer stem cells (CSCs) are subpopulations of cancer cells sharing similar characteristics as normal stem or progenitor cells such as self-renewal ability and multi-lineage differentiation to drive tumour growth and heterogeneity. Throughout the cancer progression, CSC can further be induced from differentiated cancer cells via the adaptation and cross-talks with the tumour microenvironment as well as a response from therapeutic pressures, therefore contributes to their heterogeneous phenotypes. Challengingly, conventional cancer treatments target the bulk of the tumour and are unable to target CSCs due to their highly resistance nature, leading to metastasis and tumour recurrence.

    MAIN BODY: This review highlights the roles of CSCs in tumour initiation, progression and metastasis with a focus on the cellular and molecular regulators that influence their phenotypical changes and behaviours in the different stages of cancer progression. We delineate the cross-talks between CSCs with the tumour microenvironment that support their intrinsic properties including survival, stemness, quiescence and their cellular and molecular adaptation in response to therapeutic pressure. An insight into the distinct roles of CSCs in promoting angiogenesis and metastasis has been captured based on in vitro and in vivo evidences.

    CONCLUSION: Given dynamic cellular events along the cancer progression and contributions of resistance nature by CSCs, understanding their molecular and cellular regulatory mechanism in a heterogeneous nature, provides significant cornerstone for the development of CSC-specific therapeutics.

  5. Liau MT, Amini F, Ramasamy TS
    Tissue Eng Regen Med, 2016 Oct;13(5):455-464.
    PMID: 30603427 DOI: 10.1007/s13770-016-9093-2
    Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is usually seen in those above 50 years old. Current medical treatments only provide symptomatic relief but cannot cure the disease. There are claims that PD can be cured by stem cell transplant. The present study is aimed to assess the clinical potency and safety of stem cell in treating PD. A total of eleven articles were included for analysis, with four randomised control trials (RCTs), five non-RCTs and 2 follow up studies. All the four non-RCTs showed improvement of Unified Parkinson's Disease Rating Scale with no adverse events. However, results from RCTs showed no significant differences in the rating score among the transplant group and the Sham surgery group. The secondary analysis of one study showed a significant improvement of the rating score in those patients aged 60 and younger. Transplant group also associated with an overall higher incidence of adverse events. In conclusion, the RCTs and non-RCTs produced opposite results. When the studies were performed as non-RCTs in small number of patients, they showed promising result in the patients. It could say that currently the use of stem cell/progenitor cells in treating PD need much research despite having the implanted stem cell to be able to survive and integrated. The survival of implanted dopamine neurons in the striatum, however, does not indicate a success in correcting PD symptoms. Further investigations will shed light on the application and mechanism of action of stem cells in treating PD.

    Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s13770-016-9093-2 and is accessible for authorized users.

  6. Ramasamy TS, Yee YM, Khan IM
    Front Cell Dev Biol, 2021;9:625497.
    PMID: 34336816 DOI: 10.3389/fcell.2021.625497
    Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.
  7. Sundararajan V, Sarkar FH, Ramasamy TS
    Cell Oncol (Dordr), 2018 06;41(3):223-252.
    PMID: 29667069 DOI: 10.1007/s13402-018-0378-4
    BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules.

    CONCLUSIONS: This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

  8. Sundararajan V, Sarkar FH, Ramasamy TS
    Cell Oncol (Dordr), 2018 08;41(4):463.
    PMID: 30047093 DOI: 10.1007/s13402-018-0396-2
    In the title of above mentioned article the word 'versatile' had been replaced by 'multifaceted'.
  9. Ramasamy TS, Ong ALC, Cui W
    Adv Exp Med Biol, 2018 10 26;1077:41-66.
    PMID: 30357683 DOI: 10.1007/978-981-13-0947-2_4
    Generation of functional hepatocytes from human pluripotent stem cells (hPSCs) is a vital tool to produce large amounts of human hepatocytes, which hold a great promise for biomedical and regenerative medicine applications. Despite a tremendous progress in developing the differentiation protocols recapitulating the developmental signalling and stages, these resulting hepatocytes from hPSCs yet achieve maturation and functionality comparable to those primary hepatocytes. The absence of 3D milieu in the culture and differentiation of these hepatocytes may account for this, at least partly, thus developing an optimal 3D culture could be a step forward to achieve this aim. Hence, review focuses on current development of 3D culture systems for hepatic differentiation and maturation and the future perspectives of its application.
  10. Wong PF, Dharmani M, Ramasamy TS
    Drug Discov Today, 2023 Jan;28(1):103424.
    PMID: 36332835 DOI: 10.1016/j.drudis.2022.103424
    Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.
  11. Sawai S, Wong PF, Ramasamy TS
    Crit Rev Biochem Mol Biol, 2022 Aug;57(4):351-376.
    PMID: 35900938 DOI: 10.1080/10409238.2022.2088684
    Hypoxia is a common feature of the tumor microenvironment (TME) of nearly all solid tumors, leading to therapeutic failure. The changes in stiffness of the extracellular matrix (ECM), pH gradients, and chemical balance that contribute to multiple cancer hallmarks are closely regulated by intratumoral oxygen tension via its primary mediators, hypoxia-inducible factors (HIFs). HIFs, especially HIF-1α, influence these changes in the TME by regulating vital cancer-associated signaling pathways and cellular processes including MAPK/ERK, NF-κB, STAT3, PI3K/Akt, Wnt, p53, and glycolysis. Interestingly, research has revealed the involvement of epigenetic regulation by hypoxia-regulated microRNAs (HRMs) of downstream target genes involved in these signaling. Through literature search and analysis, we identified 48 HRMs that have a functional role in the regulation of 5 key cellular processes: proliferation, metabolism, survival, invasion and migration, and immunoregulation in various cancers in hypoxic condition. Among these HRMs, 17 were identified to be directly associated with HIFs which include miR-135b, miR-145, miR-155, miR-181a, miR-182, miR-210, miR-224, miR-301a, and miR-675-5p as oncomiRNAs, and miR-100-5p, miR-138, miR-138-5p, miR-153, miR-22, miR-338-3p, miR-519d-3p, and miR-548an as tumor suppressor miRNAs. These HRMs serve as a potential lead in the development of miRNA-based targeted therapy for advanced solid tumors. Future development of combined HIF-targeted and miRNA-targeted therapy is possible, which requires comprehensive profiling of HIFs-HRMs regulatory network, and improved formula of the delivery vehicles to enhance the therapeutic kinetics of the targeted cancer therapy (TCT) moving forward.
  12. Aung SW, Abu Kasim NH, Ramasamy TS
    Methods Mol Biol, 2019;2045:323-335.
    PMID: 31201682 DOI: 10.1007/7651_2019_242
    The therapeutic potential of human mesenchymal stromal stem cells (hMSCs) for cell-based therapeutic is greatly influenced by the in vitro culture condition including the culture conditions. Nevertheless, there are many technical challenges needed to be overcome prior to the clinical use including the quantity, quality, and heterogeneity of the cells. Therefore, it is necessary to develop a stem cell culture procedure or protocol for cell expansion in order to generate reproducible and high-quality cells in accordance with good manufacturing practice for clinical and therapeutic purposes. Here we assessed the MSCs characteristic of human Wharton's jelly mesenchymal stromal cells in in vitro culture according to the criteria established by the International Society for Cellular Therapy. Besides, the viability of the WJMSCs was determined in order to increase the confidence that the cells are employed to meet the therapeutic efficacy.
  13. Aung SW, Kasim NHA, Shamsuddin SAA, Ramasamy TS
    Stem Cell Rev Rep, 2020 08;16(4):809-810.
    PMID: 32681231 DOI: 10.1007/s12015-020-09968-7
    The original version of this article unfortunately contained a mistake.
  14. Lee SH, Reed-Newman T, Anant S, Ramasamy TS
    Stem Cell Rev Rep, 2020 12;16(6):1185-1207.
    PMID: 32894403 DOI: 10.1007/s12015-020-10031-8
    Quiescence in cancer cells is considered a therapeutic challenge as it confers dormancy in tumour, hence circumventing inherent anti-neoplastic surveillance system and standard-of-care cancer therapeutics including chemotherapy and radiotherapy. Since majority of the therapeutics target actively proliferating cancer cells, cancer cells eventually develop quiescent nature as mechanism of survival and cancer progression under both niche and therapeutic pressures. Quiescence state in cancer cells, eventually, confers resistant and aggressive nature to conventional cancer therapies, resulting in disease progression and relapse. Therefore, targeting quiescent cancer cells or cancer stem cells is a promising therapeutic approach, however an extensive review of the relevant information is needed in order to device an effective therapy. While the evidence of quiescence regulation in CSCs is rather a complex molecular and cellular network, herein, we aim to provide a comprehensive understanding of both intrinsic and extrinsic regulation in association with the function of CSCs. Findings on induction of quiescent state in CSCs population, its regulation at both cellular and molecular level, key molecular regulators, cellular events and processes including potential targets to develop therapeutics are extensively reviewed. This review also highlights the impact of CSC plasticity on quiescence which capturing the key challenge of targeting the cells in this state. Beyond understanding the mechanisms underlying quiescence nature of cancer cells, this review provides insightful perspective and future direction on insight in targeting these populations, hence collapse the tumour dormancy programme in order to eradicate tumour mass as a whole. Capability of CSCs to establish quiescent state as a mechanism of survival during unfavorable conditions, as well as its impact in cancer progression and subsequent relapse, including the potential therapeutic strategy to eradicate this CSCs sub-population in the tumor mass as an effective cancer therapy.
  15. Kalra K, Chandrabose ST, Ramasamy TS, Kasim NHBA
    Curr Drug Targets, 2018;19(13):1463-1477.
    PMID: 29874998 DOI: 10.2174/1389450119666180605112917
    Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.
  16. Samuel S, Ahmad RE, Ramasamy TS, Manan F, Kamarul T
    Injury, 2018 Apr;49(4):775-783.
    PMID: 29503013 DOI: 10.1016/j.injury.2018.02.020
    BACKGROUND: It has been previously suggested that the use of regenerative promoters, which include bone marrow-derived mesenchymal stem cells (MSCs) or natural growth factors supplement such as platelet-rich concentrate (PRC) could promote cartilage regeneration. However, the notion that the concurrent use of both promoters may provide a synergistic effect that improves the repair outcome of focal cartilage injury has not been previously demonstrated. This study was thus conducted to determine whether the concomitant use of PRC could further enhance the reparative potential of MSCs encapsulated in alginate transplanted into focal cartilage injury in rabbits.

    METHODS: Artifically created full thickness cartilage defects were made on the weight-bearing region of medial femoral condyles in bilateral knees of New Zealand White rabbits (N = 30). After one month, the right knee was treated with either i) PRC (n = 10), ii) MSCs (n = 10), or, iii) a combination of PRC and MSCs (PRC + MSC) (n = 10), all encapsulated in alginate. The left knee remained untreated (control). Rabbits were sacrificed at 3 and 6 months after treatment. Cartilage tissue regeneration was accessed using ICRS morphologic scoring, histologic grading by O'Driscoll scoring, immunohistochemical staining and quantitative analysis of glycosaminoglycans (GAG) per total protein content.

    RESULTS: At 3 months, transplantation using PRC alone was equally effective as MSCs in inducing the repair of cartilage defects. However, PRC + MSC resulted in significantly higher ICRS and O'Driscoll scores (p 

  17. Ramasamy TS, Velaithan V, Yeow Y, Sarkar FH
    Curr Stem Cell Res Ther, 2018;13(4):252-264.
    PMID: 29336267 DOI: 10.2174/1574888X13666180115093800
    BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach different from conventional medicine. Ethical issues that rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine. Despite the number of studies that have been initiated to characterize their molecular signature, research on developing approaches to maintain and enhance their regenerative potential is urgently needed and must be developed.

    AIM: Thus, this review is focused on understanding their potential uses and factors influencing their pluripotent status in vitro.

    CONCLUSION: In short, this cell source could be an ideal cellular resource for pluripotent cells for potential applications in allogeneic cellular replacement therapies, fetal tissue engineering, pharmaceutical screening, and in disease modelling.

  18. Sawai S, Mohktar MS, Safwani WKZW, Ramasamy TS
    Anticancer Agents Med Chem, 2018;18(9):1258-1266.
    PMID: 29521251 DOI: 10.2174/1871520618666180307143229
    BACKGROUND: Konjac Glucomannan (KGM) is a water-soluble dietary fibre extracted from Amorphophallus konjac K. Koch (Araceae). Konjac fibre has been clinically proven as an effective antioxidant agent in weight control but its traditionally known tumour suppression property remains to be explored.

    OBJECTIVE: The main objective of this study is to determine the potential anti-proliferative effect of KGM on cancer and normal human liver cell lines, HepG2 and WRL68, respectively.

    METHOD: HepG2 and WRL68 cells were treated with KGM, D-mannose, KGM-D-mannose and 5-fluorouracil. The morphological changes in those treated cells were observed. Cytotoxic effect of the treatments on cell viability and proliferation, and apoptosis genes expression were assessed by cytotoxicity assay, flow cytometry and RT-PCR analyses.

    RESULTS: The results show that KGM treatment resulted in reduced viability of HepG2 cells significantly, in line with the apoptosis-like morphological changes. Up-regulation of BAX and down-regulation of BCL2 genes as reflected by high Bax to Bcl 2 ratio suggests that the inhibitory effect of KGM on HepG2 cells most likely via Bcl2/Bax protein pathway. Despite the effectiveness of standard drug 5-FU in suppressing the viability and proliferation of HepG2 cells, it however, exhibited no selective inhibition of cancer cells as compared to KGM.

    CONCLUSION: Current findings suggested that KGM is a potential anti-cancer compound/drug entity, which could be an alternative preventive agent against liver cancer.

  19. Srijaya TC, Ramasamy TS, Kasim NH
    J Transl Med, 2014;12:243.
    PMID: 25182194 DOI: 10.1186/s12967-014-0243-9
    The inadequacy of existing therapeutic tools together with the paucity of organ donors have always led medical researchers to innovate the current treatment methods or to discover new ways to cure disease. Emergence of cell-based therapies has provided a new framework through which it has given the human world a new hope. Though relatively a new concept, the pace of advancement clearly reveals the significant role that stem cells will ultimately play in the near future. However, there are numerous uncertainties that are prevailing against the present setting of clinical trials related to stem cells: like the best route of cell administration, appropriate dosage, duration and several other applications. A better knowledge of these factors can substantially improve the effectiveness of disease cure or organ repair using this latest therapeutic tool. From a certain perspective, it could be argued that by considering certain proven clinical concepts and experience from synthetic drug system, we could improve the overall efficacy of cell-based therapies. In the past, studies on synthetic drug therapies and their clinical trials have shown that all the aforementioned factors have critical ascendancy over its therapeutic outcomes. Therefore, based on the knowledge gained from synthetic drug delivery systems, we hypothesize that by employing many of the clinical approaches from synthetic drug therapies to this new regenerative therapeutic tool, the efficacy of stem cell-based therapies can also be improved.
  20. Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R
    BMC Infect Dis, 2012;12:314.
    PMID: 23171075 DOI: 10.1186/1471-2334-12-314
    Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not available at the moment. In this study, we report retrocyclin-1 (RC-1) production in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro.
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