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Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibitors from the components of fingerroot (Boesenbergia rotunda)

Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Abd Rahman N

In Silico Biol. (Gedrukt), 2011;11(1-2):29-37.
PMID: 22475750 DOI: 10.3233/ISB-2012-0442

Publication year=2011-2012
Binding of tetrabutylammonium bromide based deep eutectic solvent to DNA by spectroscopic analysis

Yusof R, Jumbri K, Ahmad H, Abdulmalek E, Abdul Rahman MB

Spectrochim Acta A Mol Biomol Spectrosc, 2021 May 15;253:119543.
PMID: 33636491 DOI: 10.1016/j.saa.2021.119543

The binding characteristics of DNA in deep eutectic solvents (DESs), particularly the binding energy and interaction mechanism, are not widely known. In this study, the binding of tetrabutylammonium bromide (TBABr) based DES of different hydrogen bond donors (HBD), including ethylene glycol (EG), glycerol (Gly), 1,3-propanediol (1,3-PD) and 1,5-pentanediol (1,5-PD), to calf thymus DNA was investigated using fluorescence spectroscopy. It was found that the shorter the alkyl chain length (2 carbons) and higher EG ratios of TBABr:EG (1:5) increased the binding constant (Kb) between DES and DNA up to 5.75 × 105 kJ mol-1 and decreased the binding of Gibbs energy (ΔGo) to 32.86 kJ mol-1. Through displacement studies, all synthesised DESs have been shown to displace DAPI (4',6-diamidino-2-phenylindole) and were able to bind on the minor groove of Adenine-Thymine (AT)-rich DNA. A higher number of hydroxyl (OH) groups caused the TBABr:Gly to form more hydrogen bonds with DNA bases and had the highest ability to quench DAPI from DNA, with Stern-Volmer constants (Ksv) of 115.16 M-1. This study demonstrated that the synthesised DESs were strongly bound to DNA through a combination of electrostatic, hydrophobic, and groove binding. Hence, DES has the potential to solvate and stabilise nucleic acid structures.
Computational-aided design: minimal peptide sequence to block dengue virus transmission into cells

Arumugam AC, Agharbaoui FE, Khazali AS, Yusof R, Abd Rahman N, Ahmad Fuaad AAH

J Biomol Struct Dyn, 2020 Dec 31.
PMID: 33382015 DOI: 10.1080/07391102.2020.1866074

Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series of small peptides inhibitors of DV antiviral activity targeting the entry process as the promising strategy to block DV infection. The peptides were designed based on our previously reported peptide sequence, DN58opt (TWWCFYFCRRHHPFWFFYRHN), to identify minimal effective inhibitory sequence through molecular docking and dynamics studies. The in silico designed peptides were synthesized using conventional Fmoc solid-phase peptide synthesis chemistry, purified by RP-HPLC and characterized using LCMS. Later, they were screened for their antiviral activity. One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation. This observation correlates well with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis - AC 001 showed the most favorable binding affinity through 60 ns simulations. Pairwise residue decomposition analysis has revealed four key residues that contributed to the binding of these peptides into the DV2 E protein pocket. This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study.Communicated by Ramaswamy H. Sarma.
Fulltext Development of solution-gated graphene transistor model for biosensors

Karimi H, Yusof R, Rahmani R, Hosseinpour H, Ahmadi MT

Nanoscale Res Lett, 2014;9(1):71.
PMID: 24517158 DOI: 10.1186/1556-276X-9-71

: The distinctive properties of graphene, characterized by its high carrier mobility and biocompatibility, have stimulated extreme scientific interest as a promising nanomaterial for future nanoelectronic applications. In particular, graphene-based transistors have been developed rapidly and are considered as an option for DNA sensing applications. Recent findings in the field of DNA biosensors have led to a renewed interest in the identification of genetic risk factors associated with complex human diseases for diagnosis of cancers or hereditary diseases. In this paper, an analytical model of graphene-based solution gated field effect transistors (SGFET) is proposed to constitute an important step towards development of DNA biosensors with high sensitivity and selectivity. Inspired by this fact, a novel strategy for a DNA sensor model with capability of single-nucleotide polymorphism detection is proposed and extensively explained. First of all, graphene-based DNA sensor model is optimized using particle swarm optimization algorithm. Based on the sensing mechanism of DNA sensors, detective parameters (Ids and Vgmin) are suggested to facilitate the decision making process. Finally, the behaviour of graphene-based SGFET is predicted in the presence of single-nucleotide polymorphism with an accuracy of more than 98% which guarantees the reliability of the optimized model for any application of the graphene-based DNA sensor. It is expected to achieve the rapid, quick and economical detection of DNA hybridization which could speed up the realization of the next generation of the homecare sensor system.
Spatial analysis and source profiling of beta-agonists and sulfonamides in Langat River basin, Malaysia

Sakai N, Mohd Yusof R, Sapar M, Yoneda M, Ali Mohd M

Sci Total Environ, 2016 Apr 01;548-549:43-50.
PMID: 26799806 DOI: 10.1016/j.scitotenv.2016.01.040

Beta-agonists and sulfonamides are widely used for treating both humans and livestock for bronchial and cardiac problems, infectious disease and even as growth promoters. There are concerns about their potential environmental impacts, such as producing drug resistance in bacteria. This study focused on their spatial distribution in surface water and the identification of pollution sources in the Langat River basin, which is one of the most urbanized watersheds in Malaysia. Fourteen beta-agonists and 12 sulfonamides were quantitatively analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A geographic information system (GIS) was used to visualize catchment areas of the sampling points, and source profiling was conducted to identify the pollution sources based on a correlation between a daily pollutant load of the detected contaminant and an estimated density of human or livestock population in the catchment areas. As a result, 6 compounds (salbutamol, sulfadiazine, sulfapyridine, sulfamethazine, sulfadimethoxine and sulfamethoxazole) were widely detected in mid catchment areas towards estuary. The source profiling indicated that the pollution sources of salbutamol and sulfamethoxazole were from sewage, while sulfadiazine was from effluents of cattle, goat and sheep farms. Thus, this combination method of quantitative and spatial analysis clarified the spatial distribution of these drugs and assisted for identifying the pollution sources.
Fulltext Vicarious traumatization in healthcare providers in response to COVID-19 pandemic in Kelantan, Malaysia

Norhayati MN, Che Yusof R, Azman MY

PLoS One, 2021;16(6):e0252603.
PMID: 34086747 DOI: 10.1371/journal.pone.0252603

BACKGROUND: In the fight against the COVID-19 pandemic, frontline healthcare providers who are engaged in the direct diagnosis, treatment, and care of patients face a high risk of infection yet receive inadequate protection from contamination and minimal support to cope with overwork, frustration, and exhaustion. These problems have created significant psychological and mental health concerns for frontline healthcare providers. This study aimed to compare the levels of vicarious traumatization between frontline and non-frontline healthcare providers in response to the COVID-19 pandemic.
METHODOLOGY: All the subjects who met the inclusion criteria were recruited for this comparative cross-sectional study, which was conducted from May to July 2020 in two hospitals in Kelantan, Malaysia. A self-administered questionnaire, namely, the Malay-version Vicarious Traumatization Questionnaire and the Medical Outcome Study Social Support Survey were utilized. A descriptive analysis, independent t-test, and analysis of covariance were performed using SPSS Statistics version 26.
RESULTS: A total of 160 frontline and 146 non-frontline healthcare providers were recruited. Vicarious traumatization was significantly higher among the non-frontline healthcare providers (estimated marginal mean [95% CI]: 79.7 [75.12, 84.30]) compared to the frontline healthcare providers (estimated marginal mean [95% CI]: 74.3 [68.26, 80.37]) after adjusting for sex, duration of employment, and social support.
CONCLUSION: The level of vicarious traumatization was higher among non-frontline compared to frontline healthcare providers. However, the level of severity may differ from person to person, depending on how they handle their physical, psychological, and mental health. Hence, support from various resources, such as colleagues, family, the general public, and the government, may play an essential role in the mental health of healthcare providers.
Fulltext Depressive symptoms among frontline and non-frontline healthcare providers in response to the COVID-19 pandemic in Kelantan, Malaysia: A cross sectional study

Norhayati MN, Che Yusof R, Azman MY

PLoS One, 2021;16(8):e0256932.
PMID: 34464399 DOI: 10.1371/journal.pone.0256932

BACKGROUND: Healthcare providers are vulnerable in the fight against COVID-19 and may experience significant psychological and mental health consequences. This study aimed to compare the levels of depressive symptoms among frontline and non-frontline healthcare providers in response to the COVID-19 pandemic.
METHODS: A comparative cross-sectional study was conducted in two government hospitals managing COVID-19-related cases in Kelantan, Malaysia from May to July 2020 to identify and compared depressive symptoms levels of frontline and non-frontline healthcare providers. Convenient sampling was applied in the selection of eligible participants and those diagnosed as having any psychiatric illnesses were excluded. The self-administered questionnaires for the Malay versions of the Hospital Anxiety and Depression Scale to measure depressive symptoms score and the Medical Outcome Study Social Support Survey to measure social support score as an important confounder. A descriptive analysis, independent t-test and ANCOVA were performed using SPSS version 26.
RESULTS: A total of 306 respondents from healthcare providers were recruited which 160 were frontline healthcare providers and 146 were non-frontline healthcare providers. The level of depressive symptoms (HADS score >8) was 27.5% for the frontline healthcare providers and 37.7% for the non-frontline healthcare providers. The mean depressive symptoms score for the non-frontline healthcare providers was 0.75 points higher than that of the frontline healthcare providers after adjusting for gender, duration of employment and social support.
CONCLUSION: Non-frontline healthcare providers are also experiencing psychological distress during the COVID-19 pandemic even though they do not have direct contact with COVID-19 patients.
Fulltext Prevalence of Psychological Impacts on Healthcare Providers during COVID-19 Pandemic in Asia

Norhayati MN, Che Yusof R, Azman MY

Int J Environ Res Public Health, 2021 Aug 30;18(17).
PMID: 34501747 DOI: 10.3390/ijerph18179157

COVID-19 has impacted people psychologically globally, including healthcare providers. Anxiety, depression, and stress are the most common impacts that have affected these people. Thus, this study was aimed to ascertain the estimated prevalence of psychological impacts among healthcare providers in the Asian region. A systematic search was performed in the MEDLINE, CINAHL, and Scopus databases for original research articles published between 2020 and April 2021. Only studies published in English were included. The quality of data was assessed using the Joanna Briggs Institute Meta-Analysis, and the analysis was performed using generic inverse variance with a random-effects model by Review Manager software. A total of 80 studies across 18 countries in Asia region were pooled to assess the data prevalence on anxiety (34.81% (95% CI: 30.80%, 38.83%)), depression (34.61% (95% CI: 30.87%, 38.36%)), stress (31.72% (95% CI: 21.25%, 42.18%)), insomnia (37.89% (95% CI: 25.43%, 50.35%)), and post-traumatic stress disorder (15.29% (95% CI: 11.43%, 19.15%)). Subgroup analyses were conducted across regions, type of healthcare providers, sex, and occupation. This review has identified a high prevalence of anxiety, depression, stress, and insomnia but a low prevalence of post-traumatic stress disorder among healthcare providers in Asia regions. Effective intervention support programs are urgently needed to improve psychological health of healthcare providers and maintaining the health system.
Fulltext Systematic Review and Meta-Analysis of COVID-19 Vaccination Acceptance

Norhayati MN, Che Yusof R, Azman YM

Front Med (Lausanne), 2021;8:783982.
PMID: 35155467 DOI: 10.3389/fmed.2021.783982

INTRODUCTION: Vaccination is an essential intervention to curb the coronavirus disease 2019 (COVID-19) pandemic. This review aimed to estimate the pooled proportion of COVID-19 vaccine acceptance worldwide.
METHODS: A systematic search of the MEDLINE (PubMed) database using "COVID-19," "vaccine" and "acceptance" to obtain original research articles published between 2020 and July 2021. Only studies with full text and that were published in English were included. The Joanna Briggs Institute meta-analysis was used to assess the data quality. The meta-analysis was performed using generic inverse variance with a random-effects model using the Review Manager software.
RESULTS: A total of 172 studies across 50 countries worldwide were included. Subgroup analyses were performed with regard to vaccine acceptance, regions, population, gender, vaccine effectiveness, and survey time. The pooled proportion of COVID-19 vaccine acceptance was 61% (95% CI: 59, 64). It was higher in Southeast Asia, among healthcare workers, in males, for vaccines with 95% effectiveness, and during the first survey.
CONCLUSION: COVID-19 vaccine acceptance needs to be increased to achieve herd immunity to protect the population from the disease. It is crucial to enhance public awareness of COVID-19 vaccination and improve access to vaccines.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2021, identifier CRD42021268645.
Fulltext A Unified Framework for Brain Segmentation in MR Images

Yazdani S, Yusof R, Karimian A, Riazi AH, Bennamoun M

Comput Math Methods Med, 2015;2015:829893.
PMID: 26089978 DOI: 10.1155/2015/829893

Brain MRI segmentation is an important issue for discovering the brain structure and diagnosis of subtle anatomical changes in different brain diseases. However, due to several artifacts brain tissue segmentation remains a challenging task. The aim of this paper is to improve the automatic segmentation of brain into gray matter, white matter, and cerebrospinal fluid in magnetic resonance images (MRI). We proposed an automatic hybrid image segmentation method that integrates the modified statistical expectation-maximization (EM) method and the spatial information combined with support vector machine (SVM). The combined method has more accurate results than what can be achieved with its individual techniques that is demonstrated through experiments on both real data and simulated images. Experiments are carried out on both synthetic and real MRI. The results of proposed technique are evaluated against manual segmentation results and other methods based on real T1-weighted scans from Internet Brain Segmentation Repository (IBSR) and simulated images from BrainWeb. The Kappa index is calculated to assess the performance of the proposed framework relative to the ground truth and expert segmentations. The results demonstrate that the proposed combined method has satisfactory results on both simulated MRI and real brain datasets.
Association of dietary patterns with sociodemographic and health-related factors among coronary artery disease (CAD) patients

Esmaili H, Mohd Yusof R, Abu Saad H, Ghaemian A, Darani Zad N

Ecol Food Nutr, 2015;54(1):4-19.
PMID: 25347717 DOI: 10.1080/03670244.2014.930031

This study aimed to identify the association of dietary patterns with sociodemographic and health-related characteristics among coronary artery disease patients. In this cross-sectional study, the participants were 250 patients coronary artery disease aged ≥ 40 years old. Data collection was done using questionnaires related to sociodemographics, health-related factors, and food-frequency intake information. Three dietary patterns (traditional, western, and healthy) were obtained using principal component analysis. The result showed that dietary patterns were associated with sociodemographic and health-related factors. According to the result, all the factors were taken very seriously when planning a promotional program for healthy lifestyle in prevention of CAD.
Differential expression of aldolase, alpha tubulin and thioredoxin peroxidase in peripheral blood mononuclear cells from dengue fever and dengue hemorrhagic fever patients

Thayan R, Huat TL, See LL, Khairullah NS, Yusof R, Devi S

Southeast Asian J. Trop. Med. Public Health, 2009 Jan;40(1):56-65.
PMID: 19323035

We determined the differential expression levels of proteins in peripheral blood mononuclear cells of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Proteins were subjected to two-dimensional electrophoresis, mass spectrometry and Western blot analysis. We identified 8 proteins that were 2-fold or more up-regulated in patients compared to healthy control, three of which, aldolase, thioredoxin peroxidase and alpha tubulin, were related to dengue infection. Both thioredoxin peroxidase and alpha tubulin were over-expressed 4.9 and 3.3 times respectively in DHF compared to DF patients while aldolase was up-regulated 2.2 times in DF compared to DHF patients. Alpha tubulin and thioredoxin peroxidase have the potential to be utilized as biomarkers for DHF.
The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever

Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, et al.

Trans R Soc Trop Med Hyg, 2009 Apr;103(4):413-9.
PMID: 19203772 DOI: 10.1016/j.trstmh.2008.12.018

Dengue infection is a major public health problem affecting millions of people living in tropical countries. With no suitable vaccines and specific antiviral drugs, treatment for dengue is usually symptomatic and supportive. Early diagnosis and recognition of severe disease is therefore crucial for better management of the patient. Two-dimension electrophoresis was used to identify disease-associated proteins that can be used for diagnosis and as drug targets for treatment. Two markers, identified by mass spectrometry analysis as alpha1-antitrypsin and NS1 proteins were found to be upregulated in dengue fever (DF; n=10) and dengue haemorrhagic fever (DHF; n=10) patients compared with healthy individuals (n=8). Both alpha1-antitrypsin and NS1 proteins were overexpressed two-fold in DHF patients compared with DF patients. Our study suggests that alpha1-antitrypsin and NS1 protein could be used as biomarkers as early indicators of DHF risk among patients with suspected dengue infection.
Fulltext Small molecule grp94 inhibitors block dengue and Zika virus replication

Rothan HA, Zhong Y, Sanborn MA, Teoh TC, Ruan J, Yusof R, et al.

Antiviral Res, 2019 11;171:104590.
PMID: 31421166 DOI: 10.1016/j.antiviral.2019.104590

Two major flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), cause severe health and economic burdens worldwide. Recently, genome-wide screenings have uncovered the importance of regulators of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway for flavivirus replication in host cells. Here we report the identification of the compound Bardoxolone methyl (CDDO-me) as a potent inhibitor of the Hrd1 ubiquitin ligase-mediated ERAD, which possesses a broad-spectrum activity against both DENV and ZIKV. Cellular thermal shift assay (CETSA) suggested that CDDO-me binds to grp94, a key component of the Hrd1 pathway, at a low nanomolar concentration, whereas interaction was not detected with its paralog Hsp90. CDDO-me and the grp94 inhibitor PU-WS13 substantially suppressed DENV2 replication and the cytopathic effects caused by DENV and ZIKV infection. The antiviral activities of both compounds were demonstrated for all four DENV serotypes and four ZIKV strains in multiple human cell lines. This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
Fulltext Iodine status among pregnant women in rural Sabah, Malaysia

Lim KK, Chan YY, Teh CH, Ismail H, Yusof R, Muhi J, et al.

Asia Pac J Clin Nutr, 2017 8 15;26(5):861-866.
PMID: 28802296 DOI: 10.6133/apjcn.092016.06

BACKGROUND AND OBJECTIVES: In 2000, legislation on mandatory universal salt iodisation was enacted in Sabah, Malaysia, to reduce the incidence of iodine deficiency disorders among its population. To evaluate the iodine levels among pregnant women from selected rural divisions in Sabah 13 years after the enactment of the universal salt iodisation programme.
METHODS AND STUDY DESIGN: This cross-sectional study was conducted from 1 May to 30 June, 2013, in three rural divisions of Sabah (the Interior, the West Coast, and Kudat). Data regarding domestic iodised salt use and iodine-containing supplement consumption were obtained from respondents through face-to-face interviews; goitre enlargement was examined through palpation and graded according to the World Health Organization classification. Spot urine samples were also obtained to assess urinary iodine levels by using an in-house modified micromethod.
RESULTS: In total, 534 pregnant women participated. The prevalence of goitre was 1.0% (n=5), noted only in the West Coast and Kudat divisions. Although all pregnant women consumed iodised salt, overall median urinary iodine concentration was only 106 μg/L, indicating insufficient iodine intake, with nearly two-thirds of the women (60%) having a median urinary iodine concentrations of <150 μg/L.
CONCLUSIONS: Pregnant women from the rural divisions in Sabah still exhibit iodine deficiency disorder despite the mandatory universal salt iodisation programme. Iodine supplementation programmes targeting pregnant women are warranted.
Averrhoa bilimbi pectin-based edible films: Effects of the linearity and branching of the pectin on the physicochemical, mechanical, and barrier properties of the films

Shafie MH, Yusof R, Samsudin D, Gan CY

Int J Biol Macromol, 2020 Nov 15;163:1276-1282.
PMID: 32673725 DOI: 10.1016/j.ijbiomac.2020.07.109

The potential of Averrhoa bilimbi pectin (ABP) as a source of biopolymer for edible film (EF) production was explored, and deep eutectic solvent (DES) (1% w/w) containing choline chloride-citric acid monohydrate at a molar ratio of 1:1 was used as the plasticizer. The EF-ABP3:1, which was produced from ABP with large branch size, showed a higher value of melting temperature (175.30 °C), tensile stress (7.32 MPa) and modulus (33.64 MPa). The EF-ABP3:1 also showed better barrier properties by obtaining the lowest water vapor transmission rates (1.10-1.18 mg/m2.s) and moisture absorption values (2.61-32.13%) depending on the relative humidity compared to other EF-ABPs (1.39-1.83 mg/m2.s and 3.48-51.50%, respectively) that have linear structure with smaller branch size. From these results, it was suggested that the galacturonic acid content, molecular weight, degree of esterification and pectin structure of ABP significantly influenced the properties of EFs. The interaction of highly branched pectin chains was stronger than the linear chains, thus reduced the effect of plasticizer and produced a mechanically stronger EF with better barrier properties. Hence, it was suggested that these EFs could be used as alternative degradable packaging/coating materials.
Deep eutectic solvents (DES) mediated extraction of pectin from Averrhoa bilimbi: Optimization and characterization studies

Shafie MH, Yusof R, Gan CY

Carbohydr Polym, 2019 Jul 15;216:303-311.
PMID: 31047070 DOI: 10.1016/j.carbpol.2019.04.007

The Box-Behnken design was applied to optimize the extraction of pectin from Averrhoa bilimbi (ABP) using deep eutectic solvents (DES). The four variables of extraction were percentage of DES (X1), extraction time (X2), temperature (X3), and molar ratio of DES components (X4). The quadratic regression equation was established as a predicted model with R2 value of 0.9375. The optimal condition was X1 = 3.74% (w/v), X2 = 2.5 h, X3 = 80 °C, and X4 = 1:1. No significant difference between the predicted (14.70%) and experimental (14.44%) maximum yield of sample was noted. Characterization of physico-chemical properties characterization of ABP was performed. The main components of ABP were galacturonic acids, arabinoses, and xyloses. ABP also showed good functional properties such as water holding capacity (3.70 g/g), oil holding capacity (2.40 g/g), and foaming capacity (133.33%). The results also showed that ABP exhibited free radical scavenging activity (41.46%) and ferric reducing antioxidant power (1.15 mM).
Characterization of bio-based plastic made from a mixture of Momordica charantia bioactive polysaccharide and choline chloride/glycerol based deep eutectic solvent

Shafie MH, Samsudin D, Yusof R, Gan CY

Int J Biol Macromol, 2018 Oct 15;118(Pt A):1183-1192.
PMID: 29944943 DOI: 10.1016/j.ijbiomac.2018.06.103

Momordica charantia bioactive polysaccharide (MCBP) was used as an alternative source for the production of bio-based plastics (BPs) with choline chloride/glycerol-based deep eutectic solvent (DES) as a plasticizer. In this study, MCBP was initially extracted using 0.1 M citric acid at temperature 80 °C for 2 h, precipitated using ethanol, and then lyophilized. Subsequently, seven BPs were prepared: MCBP without plasticizer (MCBP), with 1% (w/w) of glycerol (MCBP-G), or with 1% (w/w) of DES at different choline chloride/glycerol molar ratios (i.e. 1.5:1, 1:1, 1:1.5, 1:2, and 1:3). The properties of these BPs were then investigated. Results showed that the tensile strains, stresses and moduli were in the range of 1.3-13.3%, 4.8-19.1 MPa and 132-2487 MPa, respectively. The melting temperatures were found in the range of 92.6-111.4 °C whereas the moisture absorptions and water vapour transmission rates (WVTR) of BPs were 1.4-6.5% and 3.6-5.4 mg/m2·s, respectively. The results also showed that these BPs exhibited bioactivities, such as microbial inhibitory activity (19.5-32.3 mm), free radical scavenging activity (10.3-18.3%) and ferric reducing antioxidant power (FRAP, 16.1-20.0 mM). In addition, it was observed that using DES as a plasticizer had improved the properties of BP, such as tensile strain (354.7-937.5%), melting temperature (4.6-20.3%), radical scavenging activity (0.6-88.6%), FRAP (0.9-18.7%) and antimicrobial activity (12.3-33.6%) compared to MCBP, due to the fact DES has caused different degrees of plasticization via hydrogen bonds and ionic bonds with the polymer chains, and induced a lower pH condition. Therefore, it was suggested that these BPs with DES could contribute to food preservation properties.
Patients with nasopharyngeal carcinoma demonstrate enhanced serum and tissue ceruloplasmin expression

Doustjalali SR, Yusof R, Govindasamy GK, Bustam AZ, Pillay B, Hashim OH

J. Med. Invest., 2006 Feb;53(1-2):20-8.
PMID: 16537992

The proteomics approach was adopted to study the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC). We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with WHO type III NPC to two-dimensional gel electrophoresis (2-DE) and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data demonstrated that the serum high abundance 2-DE protein profiles of NPC patients were generally similar to that of the controls, with exception of the ceruloplasmin (CPL) spots (identified by mass spectrometric analysis and MASCOT database search), which showed higher expression. The enhanced expression of CPL in the patients' sera was confirmed by competitive ELISA. Immunohistochemical analysis of nasopharyngeal lesions of NPC patients demonstrated moderate to strong positive CPL staining in the cytoplasm of cells at the regions of malignancy but only weak cytoplasmic staining at normal epithelial lining areas. When follow-up 2-DE and ELISA studies were performed on five of the NPC patients who responded positively to six months treatment, the difference in CPL expression was no longer significant.
Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors

Doustjalali SR, Yusof R, Yip CH, Looi LM, Pillay B, Hashim OH

Electrophoresis, 2004 Jul;25(14):2392-401.
PMID: 15274022

We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.

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