Identifying susceptible genes associated with the pathogenesis of atherosclerosis (ATH) may contribute toward better management of this condition. This preliminary study was aimed at assessing the expression levels of 11 candidate genes, namely tumor protein (TP53), transforming growth factor, beta receptor II (TGFBR2), cysthathionenine-beta-synthase (CBS), insulin receptor substrate 1 (IRS1), lipoprotein lipase (LPL), methylenetetrahydrofolate reductase (MTHFR), thrombomodulin (THBD), lecithin-cholesterol acyltransferase (LCAT), matrix metallopeptidase 9 (MMP9), low density lipoprotein receptor (LDLR), and arachidonate 5-lipoxygenase-activating protein (ALOX5AP) genes associated with ATH. Twelve human coronary artery tissues (HCATs) were obtained from deceased subjects who underwent post-mortem procedures. Six atherosclerotic coronary artery tissue (ACAT) samples representing the cases and non-atherosclerotic coronary artery tissue (NCAT) samples as controls were gathered based on predetermined inclusion and exclusion criteria. Gene expression levels were assessed using the GenomeLab Genetic Analysis System (GeXP). The results showed that LDLR, TP53, and MMP9 expression levels were significantly increased in ACAT compared to NCAT samples (p < 0.05). Thus, LDLR, TP53, and MMP9 genes may play important roles in the development of ATH in a Malaysian study population.
Toxic inorganic and organic chemicals are major contributors to environmental contamination and pose major health risks to human population. In this work, Dracaena reflexa and Podocarpus polystachyus were investigated for their potential to remove hydrocarbons from 2.5% and 1% diesel fuel-contaminated soil amended individually with 5% organic wastes (tea leaf, soy cake and potato skin) for a period of 270 days. Loss of 90% and 99% oil was recorded in soil contaminated with 2.5% and 1% oil with soy cake amendment, respectively, compared with 52% and 62% in unamended soil with D. reflexa at the end of 270 days. Similarly, 84% and 91% oil loss was recorded for P. polystachyus amended with organic wastes in 2.5% and 1% oil, respectively. Diesel fuel disappeared more rapidly in the soil amendment with SC than in other organic waste supplementation. It was evident that plants did not accumulate hydrocarbon from the soil, while the number of hydrocarbon-utilizing bacteria was high in the rhizosphere, thus suggesting that the mechanism of the oil degradation was rhizodegradation. The kinetic model result indicated a high rate of degradation in soil amendment with SC at 1% with D. reflexa compared with other treatments. Thus, a positive relationship was observed between diesel hydrocarbon degradation with plant biomass production. Dracaena reflexa with organic wastes amendment has a greater potential of restoring hydrocarbon-contaminated soil compared to P. polystachyus plant.
MeSH terms: Biodegradation, Environmental; Gasoline/analysis; Hydrocarbons/metabolism*; Random Allocation; Soil Microbiology; Soil Pollutants/metabolism*; Species Specificity; Dracaena/metabolism*; Coniferophyta/metabolism*; Environmental Restoration and Remediation/methods*; Rhizosphere
Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, --(SEA), --(THAI), --(FIL); two single-gene deletions, α-³·⁷ and -α⁴·²; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α-³·⁷ deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the --SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α-³·⁷ deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α⁺ thalassaemia traits, 973 heterozygous α⁰ thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.
Pseudogenes are considered to be nonfunctional genes that lack a physiological role. By screening 3985 Escherichia coli mutants using chemochromic membranes, we found four pseudogenes involved in hydrogen metabolism. Knockouts of pseudogenes ydfW and ypdJ had a defective hydrogen phenotype on glucose and formate, respectively. Also, the knockout of pseudogene yqiG formed hydrogen from formate but not from glucose. For the yqiG mutant, 100% hydrogen recovery was obtained by the complementation of YqiG via a plasmid. The knockout of pseudogene ylcE showed hydrogen deficiency in minimal media which suggested that the role of YlcE is associated with cell growth. Hence, the products of these four pseudogenes play an important physiological role in hydrogen production in E. coli.
The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian-Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome.
Activated carbons are regularly used the treatment of dye wastewater. They can be produced from various organics materials having high level of carbon content. In this study, a novel Pinang frond activated carbon (PFAC) was produced at various CO₂ flow rates in the range of 150-600 mL/min at activation temperature of 800°C for 3 hours. The optimum PFAC sample is found on CO₂ flow rate of 300 mL/min which gives the highest BET surface area and pore volume of 958 m²/g and 0.5469 mL/g, respectively. This sample shows well-developed pore structure with high fixed carbon content of 79.74%. The removal of methylene blue (MB) by 95.8% for initial MB concentration of 50 mg/L and 72.6% for 500 mg/L is achieved via this sample. The PFAC is thus identified to be a suitable adsorbent for removing MB from aqueous solution.
The antioxidant activities based on the free radical scavenging, reducing power, and bleaching inhibition were investigated for the three commonly used honeys in Malaysia, namely, tualang, gelam, and acacia honey. The antioxidant capacity of the honey samples was correlated with their biochemical constituents such as total phenol, total flavonoid content, and total water-soluble vitamins (vitamin B1, B2, B3, B9, B12, and vitamin C). The total flavonoid content of honey samples was strongly correlated with the three antioxidative processes (r = 0.9276-0.9910). In contrast, the total water-soluble vitamins was found to be well correlated with the free radical scavenging activity (r = 0.8226). Vitamin B3 was likely to be in the highest concentration, which covered for 69-80% of the total vitamin content. A number of five phenolic acids, three flavonoids, and two organic acids had also been detected from the honey samples using UPLC-MS/MS, without sugar-removal procedure.
In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse.
Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.
Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P
Wavelet packet transform decomposes a signal into a set of orthonormal bases (nodes) and provides opportunities to select an appropriate set of these bases for feature extraction. In this paper, multi-level basis selection (MLBS) is proposed to preserve the most informative bases of a wavelet packet decomposition tree through removing less informative bases by applying three exclusion criteria: frequency range, noise frequency, and energy threshold. MLBS achieved an accuracy of 97.56% for classifying normal heart sound, aortic stenosis, mitral regurgitation, and aortic regurgitation. MLBS is a promising basis selection to be suggested for signals with a small range of frequencies.
MeSH terms: Heart Sounds/physiology*; Heart Valve Diseases/physiopathology; Humans; Phonocardiography/classification*; Signal Processing, Computer-Assisted*; Signal-To-Noise Ratio; Support Vector Machine
Diabetes mellitus (DM) affects considerable number of people in the world and the number of cases is increasing every year. Due to a strong link to the genetic basis of the disease, it is extremely difficult to cure. However, it can be controlled to prevent severe consequences, such as organ damage. Therefore, diabetes diagnosis and monitoring of its treatment is very important. In this paper, we have proposed a non-invasive diagnosis support system for DM. The system determines whether or not diabetes is present by determining the cardiac health of a patient using heart rate variability (HRV) analysis. This analysis was based on nine nonlinear features namely: Approximate Entropy (ApEn), largest Lyapunov exponet (LLE), detrended fluctuation analysis (DFA) and recurrence quantification analysis (RQA). Clinically significant measures were used as input to classification algorithms, namely AdaBoost, decision tree (DT), fuzzy Sugeno classifier (FSC), k-nearest neighbor algorithm (k-NN), probabilistic neural network (PNN) and support vector machine (SVM). Ten-fold stratified cross-validation was used to select the best classifier. AdaBoost, with least squares (LS) as weak learner, performed better than the other classifiers, yielding an average accuracy of 90%, sensitivity of 92.5% and specificity of 88.7%.
MeSH terms: Adult; Aged; Diabetes Mellitus/physiopathology*; Electrocardiography/methods; Female; Heart Rate/physiology*; Humans; Male; Middle Aged; Signal Processing, Computer-Assisted*; Reproducibility of Results; Case-Control Studies; Nonlinear Dynamics; Support Vector Machine
The structural comparison of proteins is a vital step in structural biology that is used to predict and analyse a new unknown protein function. Although a number of different techniques have been explored, the study to develop new alternative methods is still an active research area. The present paper introduces a text modelling-based technique for the structural comparison of proteins. The method models the secondary and tertiary structure of proteins in two linear sequences and then applies them to the comparison of two structures. The technique used for pairwise comparison of the sequences has been adopted from computational linguistics and its well-known techniques for analysing and quantifying textual sequences. To this end, an n-gram modelling technique is used to capture regularities between sequences, and then, the cross-entropy concept is employed to measure their similarities. Several experiments are conducted to evaluate the performance of the method and compare it with other commonly used programs. The assessments for information retrieval evaluation demonstrate that the technique has a high running speed, which is similar to other linear encoding methods, such as 3D-BLAST, SARST, and TS-AMIR, whereas its accuracy is comparable to CE and TM-align, which are high accuracy comparison tools. Accordingly, the results demonstrate that the algorithm has high efficiency compared with other state-of-the-art methods.
The aim of this study is to investigate the feasibility of eliminating the nephrographic phase from the four-phase renal computed tomography (CT) imaging to a three-phase protocol without affecting its diagnostic value. Thirty patients undergoing four-phase renal CT scans for assessment of renal lesions (>10 mm) were included in the study. A three-phase renal CT, without nephrographic phase, had similar diagnostic ability to a four-phase renal CT in the detection and characterization of renal lesions. A three-phase CT (plain, corticomedullary, and excretory phase) is therefore adequate in the clinical diagnosis of renal lesions.
An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.
Cosmos caudatus (ulam raja) contains high mineral content and possesses high antioxidant activity which may be beneficial in bone disorder such as postmenopausal osteoporosis. The effects of C. caudatus on bone metabolism biomarkers in ovariectomized rats were studied. 48 Sprague-Dawley rats aged three months were divided into 6 groups. One group of rats was sham-operated while the remaining rats were ovariectomized. The ovariectomized rats were further divided into 5 groups: the control, three groups force-fed with C. caudatus at the doses of 100mg/kg, 200mg/kg or 300mg/kg and another group supplemented with calcium 1% ad libitum. Treatments were given 6 days per week for a period of eight weeks. Blood samples were collected twice; before and after treatment. Parameters measured were bone resorbing cytokine; interleukin-1 and the bone biomarkers; osteocalcin and pyridinoline. Serum IL-1 and pyridinoline levels were significantly increased in ovariectomized rats. Supplementation of C. caudatus was able to prevent the increase of IL-1 and pyridinoline in ovariectomized rats. Besides that, C. caudatus showed the same effect as calcium 1% on biochemical parameters of bone metabolism in ovariectomized rats. In conclusion, Cosmos caudatus was as effective as calcium in preventing the increase in bone resorption in ovariectomized rats.
MeSH terms: Amino Acids/blood; Animals; Bone and Bones/drug effects*; Bone and Bones/metabolism; Calcium/pharmacology; Disease Models, Animal; Female; Interleukin-1/blood; Phytotherapy; Osteoporosis/blood; Osteoporosis/drug therapy*; Ovariectomy*; Plant Extracts/pharmacology*; Plants, Medicinal; Time Factors; Biomarkers/blood; Osteocalcin/blood; Bone Remodeling/drug effects*; Rats, Sprague-Dawley; Dietary Supplements; Rats
Natural glycopeptide antibiotics like vancomycin and teicoplanin have played a significant role in countering the threat posed by Gram-positive bacterial infections. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among Gram-positive organisms has been increasing steadily during the past several decades and the current development of antibiotics falls short of meeting the needs. Oritavancin (LY-333328 diphosphate), a promising novel second-generation semisynthetic lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has concentration-dependent activity against a variety of Gram-positive organisms specially methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant Staphylococcus aureus (VISA), Streptococcus pneumoniae and vancomycin-resistant enterococcus. It is rapidly bactericidal against many species and in particular for enterococci where vancomycin and teicoplanin are only bacteriostatic even against susceptible strains. The pharmacokinetic profile of oritavancin has not been fully described; however, oritavancin has a long half-life of about 195.4 hours and is slowly eliminated by renal means. Oritavancin is not metabolized by the liver in animals. Oritavancin will most probably be prescribed as a once-daily dose and it demonstrates concentration-dependent bactericidal activity. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and II clinical trials. In a Phase III clinical trial, oritavancin has achieved the primary efficacy end point in the treatment of complicated Gram-positive skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being administration site complaints, headache, rhinitis, dry skin, pain, increases in liver transaminases and accumulation of free cholesterol and phospholipids in phagocytic (macrophages) and nonphagocytic (fibroblast) cells. Oritavancin appears to be a promising antimicrobial alternative to vancomycin (with additional activity against Staphylococcus and Enterococcus resistant to vancomycin) for the treatment of complicated Gram-positive skin and skin-structure infections. Additional clinical data are required to fully explore its use.
Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.
This study aims to provide security solutions for implementing electronic medical records (EMRs). E-Health organizations could utilize the proposed method and implement recommended solutions in medical/health systems. Majority of the required security features of EMRs were noted. The methods used were tested against each of these security features. In implementing the system, the combination that satisfied all of the security features of EMRs was selected. Secure implementation and management of EMRs facilitate the safeguarding of the confidentiality, integrity, and availability of e-health organization systems. Health practitioners, patients, and visitors can use the information system facilities safely and with confidence anytime and anywhere. After critically reviewing security and data transmission methods, a new hybrid method was proposed to be implemented on EMR systems. This method will enhance the robustness, security, and integration of EMR systems. The hybrid of simple object access protocol/extensible markup language (XML) with advanced encryption standard and secure hash algorithm version 1 has achieved the security requirements of an EMR system with the capability of integrating with other systems through the design of XML messages.
MeSH terms: Confidentiality; Humans; Soaps*; Computer Security; Electronic Health Records*