Institute for Medical Research IMR

Kuala Lumpur, Malaysia

Institute for Medical Research IMR

Kuala Lumpur, Malaysia
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PubMed | Sunway University, Institute for Medical Research IMR, Universiti Sains Malaysia and International Medical University
Type: | Journal: Journal of tropical medicine | Year: 2016

Curcumin, the major constituent of

PubMed | Institute for Medical Research IMR and Institute for Medical Research
Type: Journal Article | Journal: The Medical journal of Malaysia | Year: 2017

Trigeminal neuralgia is an agonising orofacial pain affecting unilaterally the distribution of the trigeminal nerve and it usually occurs in the middle and older age groups. Carbamazepine which is an anti-neuralgic as well as an anti-convulsant medication is the first line drug for treatment of trigeminal neuralgia. It is commonly taken as one tablet (200 mg) three times a day.This is an observational study carried out from April to September 2014 to determine how Muslim patients on carbamazepine treatment for trigeminal neuralgia cope with their neuralgic pain. The pattern of how the medication was taken during the fasting month of Ramadan was also observed.A total of 29 patients participated in this study and 27(93%) observed the fast. Ten of them adjusted the carbamazepine dose from three times pre-Ramadan to twice daily during the fasting month. Three patients continued fasting despite feeling the pain during the daytime while five patients had their pain under control with the newly adjusted dose.Medical professionals should advise trigeminal neuralgia patients on how to take and adjust their carbamazepine dose during the fasting month.

Govindasamy V.,k-Technology | Ronald V.S.,Institute for Medical Research IMR | Totey S.,k-Technology | Binti Din S.,Hospital Kuala Lumpur | And 3 more authors.
In Vitro Cellular and Developmental Biology - Animal | Year: 2010

Stem cells isolated from dental pulp possess the capacity for self-renewal and the potential for multi-lineage differentiation. However, dental pulp stem cells have different characteristics in terms of their culture conditions. The success of stem cells culture is governed by its micro-environmental niche. Therefore, we studied the effects of culture niche on long-term expansion of dental pulp stem cells in terms of cell morphology, growth kinetics, senescence pattern, cell surface marker expression differentiation capacity, and seeding plating density of dental pulp stem cells in four different, widely used media composition Among the various basal media tested, α-minimum essential media and knock out-minimum essential media supplemented with 10% fetal bovine serum were found to be the most optimal media composition in preserving the phenotypic characteristics and differentiation potential for prolonged periods as compared with DMEM-F12 and DMEM-LG. Plating density has been shown to affect overall yield. As a conclusion, the adoption of an appropriate culture system significantly improved cell yield, thus enabling the attainment of sufficient yields for therapeutic applications economizing in terms of cost of production and minimizing seeding cell density for maximum yield. © 2010 The Society for In Vitro Biology.

Prototheca wickerhamii isolated from blood of 61-year-old kidney transplant patient was described. Although it is classified as an alga (genus Chlorella), the disease, protothecosis, is included under mycoses because of its clinical pathological presentations. Colony characteristics of P. wickerhamii are indistinguishable from other yeast-like organisms like Cryptococcus and Candida. Fortunately, commercial identification system for yeast can be used to identify this organism to the species level. Electron microscopy demonstrated "morula" or daisy-like appearance of its endosporulating sporangia. The organism was sensitive to amphotericin B by E test method. Even though human protothecosis is uncommon, it cannot be ignored because it is emerging as an opportunistic infection in immunosuppressed individuals. To our knowledge, this is the first reported case of disseminated algaemia due to P. wickerhamii in Malaysia.

Kardia E.,Universiti Sains Malaysia | Yusoff N.M.,Universiti Sains Malaysia | Zakaria Z.,Institute for Medical Research IMR | Yahaya B.,Universiti Sains Malaysia
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2014

Background: Cell-based therapy has great potential to treat patients with lung diseases. The administration of cells into an injured lung is one method of repairing and replacing lost lung tissue. However, different types of delivery have been studied and compared, and none of the techniques resulted in engraftment of a high number of cells into the targeted organ. In this in vitro study, a novel method of cell delivery was introduced to investigate the possibility of delivering aerosolized skin-derived fibroblasts. Methods: Skin-derived fibroblasts were trypsinized and resuspended in growth medium. A syringe filled with cells (105 cells/mL) was attached to MicroSprayer® Aerosolizer, a device that can modify a liquid into an aerosol. The tip of the MicroSprayer Aerosolizer was channeled into a T25 flask containing growth medium. Survivability following aerosolization was observed on a daily basis. HeLa cells were used for comparison. The same aerosolization and culture methods were used to treat HeLa cells. Results: One day following aerosolization, skin-derived fibroblasts showed no sign of vacuolation due to cell stress. They attached to the surface of the flask, indicating that most of them survived aerosolization. The surviving cells were also able to proliferate rapidly, forming a confluent monolayer of cells at day 4. In contrast, HeLa cells were unable to proliferate even after 21 days of culture. Conclusions: This study provides the first evidence that cells can be aerosolized without the risk of low cell survivability and stress. The high survival rate of fibroblast cells following aerosolization illustrates the potential for delivering of such cells in future aerosol cell-based therapy to treat lung diseases. © Copyright 2014, Mary Ann Liebert, Inc.

Halim N.S.S.A.,Universiti Sains Malaysia | Fakiruddin K.S.,Institute for Medical Research IMR | Ali S.A.,Universiti Sains Malaysia | Yahaya B.H.,Universiti Sains Malaysia
International Journal of Molecular Sciences | Year: 2014

Mesenchymal stem cells (MSCs) hold tremendous potential for therapeutic use in stem cell-based gene therapy. Ex vivo genetic modification of MSCs with beneficial genes of interest is a prerequisite for successful use of stem cell-based therapeutic applications. However, genetic manipulation of MSCs is challenging because they are resistant to commonly used methods to introduce exogenous DNA or RNA. Herein we compared the effectiveness of several techniques (classic calcium phosphate precipitation, cationic polymer, and standard electroporation) with that of microporation technology to introduce the plasmid encoding for angiopoietin-1 (ANGPT-1) and enhanced green fluorescent protein (eGFP) into human adipose-derived MSCs (hAD-MSCs). The microporation technique had a higher transfection efficiency, with up to 50% of the viable hAD-MSCs being transfected, compared to the other transfection techniques, for which less than 1% of cells were positive for eGFP expression following transfection. The capability of cells to proliferate and differentiate into three major lineages (chondrocytes, adipocytes, and osteocytes) was found to be independent of the technique used for transfection. These results show that the microporation technique is superior to the others in terms of its ability to transfect hAD-MSCs without affecting their proliferation and differentiation capabilities. Therefore, this study provides a foundation for the selection of techniques when using ex vivo gene manipulation for cell-based gene therapy with MSCs as the vehicle for gene delivery. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Chen C.D.,University of Malaya | Nazni W.A.,Institute for Medical Research IMR | Lee H.L.,Institute for Medical Research IMR | Norma-Rashid Y.,University of Malaya | And 2 more authors.
Tropical Biomedicine | Year: 2013

Larvae of Aedes albopictus obtained from dengue endemic areas in Selangor, Malaysia were evaluated for their susceptibility to operational dosage of temephos (1 mg/L). Larval bioassays were carried out in accordance to modified WHO standard methods. Biochemical microassay of enzymes in Ae. albopictus was conducted to detect the emergence of insecticide resistance and to define the mechanisms involved in temephos resistance. The 50% mortality lethal time (LT50) for Ae. albopictus tested against temephos ranged between 58.65 to 112.50 minutes, with resistance ratio ranging from 0.75 - 1.45. This study addressed the fluctuation of time-related susceptibility status of Ae. albopictus towards insecticide. Significant difference on the weekly enzyme levels of non-specific esterases, mixed function oxidases and glutathione S-transferases was detected (p < 0.05). No significant correlation was found between temephos resistance and enzyme activity (p > 0.05). Only glutathione Stransferases displayed high level of activity, indicating that Ae. albopictus may be resistant to other groups of insecticide. The insensitive acetylcholinesterase was detected in some field collected Ae. albopictus populations, indicating the possibility of emergence of carbamate or other organophosphate resistance in the field populations. Continuous resistance monitoring should be conducted regularly to confirm the efficacy of insecticides for dengue control.

Zakaria N.,Universiti Sains Malaysia | Yusoff N.M.,Universiti Sains Malaysia | Zakaria Z.,Institute for Medical Research IMR | Lim M.N.,Institute for Medical Research IMR | And 3 more authors.
BMC Cancer | Year: 2015

Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC). Methods: We isolated putative lung CSCs from lung adenocarcinoma cells (A549 and H2170) and normal stem cells from normal bronchial epithelial cells (PHBEC) on the basis of positive expression of stem cell surface markers (CD166, CD44, and EpCAM) using fluorescence-activated cell sorting. The isolated cells were then characterised for their self-renewal characteristics, differentiation capabilities, expression of stem cell transcription factor and in vivo tumouregenicity. The transcriptomic profiles of putative lung CSCs then were obtained using microarray analysis. Significantly regulated genes (p <0.05, fold change (FC) > 2.0) in putative CSCs were identified and further analysed for their biological functions using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: The putative lung CSCs phenotypes of CD166+/CD44+ and CD166+/EpCAM+ showed multipotent characteristics of stem cells, including the ability to differentiate into adipogenic and osteogenic cells, self-renewal, and expression of stem cell transcription factors such as Sox2 and Oct3/4. Moreover, the cells also shows the in vivo tumouregenicity characteristic when transplanted into nude mice. Microarray and bioinformatics data analyses revealed that the putative lung CSCs have molecular signatures of both normal and cancer stem cells and that the most prominent biological functions are associated with angiogenesis, migration, pro-apoptosis and anti-apoptosis, osteoblast differentiation, mesenchymal cell differentiation, and mesenchyme development. Additionally, self-renewal pathways such as the Wnt and hedgehog signalling pathways, cancer pathways, and extracellular matrix (ECM)-receptor interaction pathways are significantly associated with the putative lung CSCs. Conclusion: This study revealed that isolated lung CSCs exhibit the characteristics of multipotent stem cells and that their genetic composition might be valuable for future gene and stem cells therapy for lung cancer. © Zakaria et al.

PubMed | Institute for Medical Research IMR and Universiti Sains Malaysia
Type: Journal Article | Journal: Oncology reports | Year: 2015

Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem-like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10-40 M) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 M) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double-positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin-induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase-9 activation in the double-positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.

PubMed | Institute for Medical Research IMR and Universiti Sains Malaysia
Type: | Journal: Advances in virology | Year: 2016

Nanometre-sized vesicles, also known as exosomes, are derived from endosomes of diverse cell types and present in multiple biological fluids. Depending on their cellular origins, the membrane-bound exosomes packed a variety of functional proteins and RNA species. These microvesicles are secreted into the extracellular space to facilitate intercellular communication. Collective findings demonstrated that exosomes from HIV-infected subjects share many commonalities with Human Immunodeficiency Virus Type I (HIV-1) particles in terms of proteomics and lipid profiles. These observations postulated that HIV-resembled exosomes may contribute to HIV pathogenesis. Interestingly, recent reports illustrated that exosomes from body fluids could inhibit HIV infection, which then bring up a new paradigm for HIV/AIDS therapy. Accumulative findings suggested that the cellular origin of exosomes may define their effects towards HIV-1. This review summarizes the two distinctive roles of exosomes in regulating HIV pathogenesis. We also highlighted several additional factors that govern the exosomal functions. Deeper understanding on how exosomes promote or abate HIV infection can significantly contribute to the development of new and potent antiviral therapeutic strategy and vaccine designs.

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