Malaysian Institute of Pharmaceuticals and Nutraceuticals

Malaysian, Malaysia

Malaysian Institute of Pharmaceuticals and Nutraceuticals

Malaysian, Malaysia
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Teoh P.-H.,Universiti Sains Malaysia | Shu-Chien A.C.,Universiti Sains Malaysia | Shu-Chien A.C.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Chan W.-K.,National University of Singapore
Developmental Dynamics | Year: 2010

pbx1, a TALE (three-amino acid loop extension) homeodomain transcription factor, is involved in a diverse range of developmental processes. We examined the expression of pbx1 during zebrafish development by in situ hybridization. pbx1 transcripts could be detected in the central nervous system and pharyngeal arches from 24 hpf onwards. In the swim bladder anlage, pbx1 was detected as early as 28 hpf, making it the earliest known marker for this organ. Morpholino-mediated gene knockdown of pbx1 revealed that the swim bladder failed to inflate, with eventual lethality occurring by 8 dpf. The knockdown of pbx1 did not perturb the expression of prdc and foxA3, with both early swim bladder markers appearing normally at 36 and 48 hpf, respectively. However, the expression of anxa5 was completely abolished by pbx1 knockdown at 60 hpf suggesting that pbx1 may be required during the late stage of swim bladder development. © 2010 Wiley-Liss, Inc.


Tan S.-H.,Universiti Sains Malaysia | Chung H.-H.,Universiti Sains Malaysia | Shu-Chien A.C.,Universiti Sains Malaysia | Shu-Chien A.C.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Biochemical and Biophysical Research Communications | Year: 2010

Despite the known importance of long-chained polyunsaturated fatty acids (LC-PUFA) during development, very little is known about their utilization and biosynthesis during embryogenesis. Combining the advantages of the existence of a complete range of enzymes required for LC-PUFA biosynthesis and the well established developmental biology tools in zebrafish, we examined the expression patterns of three LC-PUFA biosynthesis genes, Elovl2-like elongase (elovl2), Elovl5-like elongase (elovl5) and fatty acyl desaturase (fad) in different zebrafish developmental stages. The presence of all three genes in the brain as early as 24 hours post fertilization (hpf) implies LC-PUFA synthesis activity in the embryonic brain. This expression eventually subsides from 72 hpf onwards, coinciding with the initiation of elovl2 and fad expression in the liver and intestine, 2 organs known to be involved in adult fish LC-PUFA biosynthesis. Collectively, these patterns strongly suggest the necessity for localized production of LC-PUFA in the brain during in early stage embryos prior to the maturation of the liver and intestine. Interestingly, we also showed a specific expression of elovl5 in the proximal convoluted tubule (PCT) of the zebrafish pronephros, suggesting a possible new role for LC-PUFA in kidney development and function. © 2010 Elsevier Inc. All rights reserved.


Ramachandran H.,Universiti Sains Malaysia | Iqbal N.M.,Universiti Sains Malaysia | Sipaut C.S.,Universiti Malaysia Sabah | Abdullah A.A.-A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Applied Biochemistry and Biotechnology | Year: 2011

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolymer was produced using Cupriavidus sp. USMAA2-4 via one-step cultivation process through combination of various carbon sources such as 1,4-butanediol or γ-butyrolactone with either 1-pentanol, valeric acid, or 1-propanol. Oleic acid was added to increase the biomass production. The composition of 3HV and 4HB monomers were greatly affected by the concentration of 1,4-butanediol and 1-pentanol. Terpolymers with 3HV and 4HB molar fractions ranging from 2 to 41 mol.% and 5 to 31 mol.%, respectively, were produced by varying the concentration of carbon precursors. The thermal and mechanical properties of the terpolymers containing different proportions of the constituent monomers were characterized using gel permeation chromatography (GPC), DSC, and tensile machine. GPC analysis showed that the molecular weights (M w) of the terpolymer produced were within the range of 346 to 1,710 kDa. The monomer compositions of 3HV and 4HB were also found to have great influences on the thermal and mechanical properties of the terpolymer P(3HB-co-3HV-co-4HB) produced. © 2011 Springer Science+Business Media, LLC.


Ramachandran H.,Universiti Sains Malaysia | Amirul A.A.,Universiti Sains Malaysia | Amirul A.A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Journal of Chemical Technology and Biotechnology | Year: 2013

Background: Development of bacterial strains that can utilize cheap and renewable carbon substrate will make the prices of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] competitive with synthetic plastics. Disposal of glycerine pitch, which is a scheduled waste from the oleochemicals industry, has raised awareness among communities as burning the waste literally means producing acrolein which is well known for its toxicity and adverse effects. Therefore, discovering potential application of glycerine pitch as carbon substrate is believed to overcome the waste management problem and reduce the P(3HB-co-4HB) production cost. Results: Cupriavidus sp. USMAHM13, a novel yellow-pigmented bacterium produced the highest 4HB composition (43 mol%) with cell dry weight and PHA content of 6.0 g L-1 and 49 wt%, respectively, through combination of glycerine pitch (5 g L-1) and 1,4-butanediol (5 g L-1) via one-stage cultivation. The yellow pigment extracts were analyzed using UV-VIS spectrophotometry and high performance liquid chromatography - mass spectrometry (HPLC-MS), which revealed that the yellow pigment might represent a new compound in the carotenoid group. Conclusion: Biosynthesis of P(3HB-co-4HB) by a novel yellow-pigmented Cupriavidus sp. using glycerine pitch together with 1,4-butanediol enhanced cost efficiency and sustainability in the production of P(3HB-co-4HB). © 2012 Society of Chemical Industry.


Hema R.,Universiti Sains Malaysia | Ng P.N.,Universiti Sains Malaysia | Amirul A.A.,Universiti Sains Malaysia | Amirul A.A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Polymer Bulletin | Year: 2013

Polyhydroxyalkanoates (PHAs) are emerging as the candidate of biodegradable material for the future, which in combination with nanoclay reinforcement can produce nanobiocomposites for a variety of applications. Thus, this project was intended to develop nanobiocomposites using various biodegradable PHAs: poly(3-hydroxybutyrate) [P(3HB)], poly(3-hydroxybutyrate-co-6 %3-hydroxyvalerate) [P(3HB-co-6 %3HV)] copolymer, poly(3-hydroxybutyrate-co-70 %4-hydroxybutyrate) [P(3HB-co-70 %4HB)] copolymer and poly(3-hydroxybutyrate-co- 10 %3-hydroxyvalerate-co-10 %4-hydroxybutyrate) [P(3HB-co-10 %3HV-co-10 %4HB)] terpolymer through solvent casting method. Pronounced improvement in the optical transparency, mechanical and thermal properties were achieved through reinforcement of 5 wt% Claytone into P(3HB-co-70 %4HB) having the lowest molecular weight as compared to the other polymers. P(3HB-co-70 %4HB)/5 wt% Claytone composite also exhibited enhancement in the antimicrobial performance which increased with the clay concentrations. P(3HB-co-70 %4HB), a biocompatible and biodegradable nanocomposite which had demonstrated salient features with comparable good performance is believed to create new prospects with special incidence in regenerative medicine and as environmentally friendly materials (green nanocomposites). © 2012 Springer-Verlag.


Rennukka M.,Universiti Sains Malaysia | Amirul A.A.,Universiti Sains Malaysia | Amirul A.A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Polymer Bulletin | Year: 2013

A new blend material was fabricated from poly(3-hydroxybutyrate-co- 4-hydroxybutyrate) [P(3HB-co-4HB)] and chitosan through simple solvent casting method. In this investigation, the impact of different contents of chitosan and molar fractions of 4HB monomer towards the hybrid films was determined. The hydrophobic nature of the P(3HB-co-4HB) copolymer was modified by blending with a hydrophilic polymer-chitosan. Thus, the water-absorption capacity and solubility of the blend films were increased proportionally with the increasing content of chitosan. Miscibility of the blend films between the pure components was detected through Fourier transform infrared analysis. The thermal property was altered in terms of melting temperature, whereas the thermal stability of the blend films was greatly increased. Moreover, the scanning electron microscope images indicated that the surface of the blend films was homogenous and porous. Impregnation of chitosan enabled the blend films to exhibit antimicrobial activity against both Gram-negative and Gram-positive bacteria. The blend films with 20 wt% of chitosan were more hydrophilic, porous, biocidal and they have a wider opportunity in various applications such as wound dressing and tissue engineering than the native P(3HB-co-4HB) copolymer. © Springer-Verlag Berlin Heidelberg 2013.


Iq K.C.,Universiti Sains Malaysia | Shu-Chien A.C.,Universiti Sains Malaysia | Shu-Chien A.C.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
PLoS ONE | Year: 2011

Mouthbrooding is an elaborate form of parental care displayed by many teleost species. While the direct benefits of mouthbrooding such as protection and transportation of offsprings are known, it is unclear if mouthbrooding offers additional benefits to embryos during incubation. In addition, mouthbrooding could incur negative costs on parental fish, due to limited feeding opportunities. Parental tilapia fish (Oreochromis spp.) display an elaborated form of parental care by incubating newly hatched embryos in oral buccal cavity until the complete adsorption of yolk sac. In order to understand the functional aspects of mouthbrooding, we undertake a proteomics approach to compare oral mucus sampled from mouthbrooders and non-mouthbrooders, respectively. Majority of the identified proteins have also been previously identified in other biological fluids or mucus-rich organs in different organisms. We also showed the upregulation of 22 proteins and down regulation of 3 proteins in mucus collected from mouthbrooders. Anterior gradient protein, hemoglobin beta-A chain and alpha-2 globin levels were lower in mouthbrooder samples. Mouthbrooder oral mucus collectively showed increase levels of proteins related to cytoskeletal properties, glycolytic pathway and mediation of oxidative stress. Overall the findings suggest cellular stress response, probably to support production of mucus during mouthbrooding phase. © 2011 Iq, Shu-Chien.


Khor B.-S.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Jamil M.F.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Adenan M.I.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Adenan M.I.,Malaysian Forest Research Institute | And 2 more authors.
PLoS ONE | Year: 2011

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. © 2011 Khor et al.


Kuah M.-K.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Jaya-Ram A.,Universiti Sains Malaysia | Shu-Chien A.C.,Universiti Sains Malaysia
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

The endogenous production of long-chain polyunsaturated fatty acids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh.Wealso functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the Δ4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores. © 2014 Elsevier B.V. All rights reserved.


Tan H.K.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Moad A.I.H.,Universiti Sains Malaysia | Tan M.L.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Tan M.L.,Universiti Sains Malaysia
Asian Pacific Journal of Cancer Prevention | Year: 2014

The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

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