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  1. Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis
    Wei LK, Au A, Menon S, Griffiths LR, Kooi CW, Irene L, et al.
    J Stroke Cerebrovasc Dis, 2017 Nov;26(11):2482-2493.
    PMID: 28760411 DOI: 10.1016/j.jstrokecerebrovasdis.2017.05.048
    INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies.

    METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study.

    RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks.

    CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

  2. A lignan with glucose uptake activity in 3T3-L1 adipocytes from the stem bark of Knema patentinervia
    Taher M, Amiroudine MZAM, Jaffri JM, Amri MS, Susanti D, Abd Hamid S, et al.
    Pak J Pharm Sci, 2017 Jul;30(4):1335-1339.
    PMID: 29039334
    A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.
  3. Fulltext Essential oils of aromatic Egyptian plants repel nymphs of the tick Ixodes ricinus (Acari: Ixodidae)
    El-Seedi HR, Azeem M, Khalil NS, Sakr HH, Khalifa SAM, Awang K, et al.
    Exp Appl Acarol, 2017 Sep;73(1):139-157.
    PMID: 28864886 DOI: 10.1007/s10493-017-0165-3
    Due to the role of Ixodes ricinus (L.) (Acari: Ixodidae) in the transmission of many serious pathogens, personal protection against bites of this tick is essential. In the present study the essential oils from 11 aromatic Egyptian plants were isolated and their repellent activity against I. ricinus nymphs was evaluated Three oils (i.e. Conyza dioscoridis L., Artemisia herba-alba Asso and Calendula officinalis L.) elicited high repellent activity in vitro of 94, 84.2 and 82%, respectively. The most active essential oil (C. dioscoridis) was applied in the field at a concentration of 6.5 µg/cm2 and elicited a significant repellent activity against I. ricinus nymphs by 61.1%. The most repellent plants C. dioscoridis, C. officinalis and A. herba-alba yielded essential oils by 0.17, 0.11 and 0.14%, respectively. These oils were further investigated using gas chromatography-mass spectrometry analysis. α-Cadinol (10.7%) and hexadecanoic acid (10.5%) were the major components of C. dioscoridis whereas in C. officinalis, α-cadinol (21.2%) and carvone (18.2%) were major components. Artemisia herba-alba contained piperitone (26.5%), ethyl cinnamate (9.5%), camphor (7.7%) and hexadecanoic acid (6.9%). Essential oils of these three plants have a potential to be used for personal protection against tick bites.
  4. The Use of Engineered Bilayered Skin (MyDermTM) in the Management of Massive Skin Defect in Grade III Gustilo-Anderson Open Fracture
    Mohamed Haflah NH, Ng MH, Mohd Yunus MH, Naicker AS, Htwe O, Fahmi M, et al.
    Int J Low Extrem Wounds, 2017 Sep;16(3):212-216.
    PMID: 28862056 DOI: 10.1177/1534734617724974
    Open fracture Gustilo-Anderson grade IIIC is associated with higher risk of infection and problems with soft tissue coverage. Various methods have been used for soft tissue coverage in open fractures with large skin defect. We report a case of a patient who had grade IIIC open fracture of the tibia with posterior tibial artery injury. The patient underwent external fixation and reduction. Because of potential compartment syndrome after vascular repair, fasciotomy of the posterior compartment was performed. This wound, however, became infected and because of further debridement, gave rise to a large skin defect. A tissue engineered skin construct, MyDermTM was employed to cover this large defect. Complete wound closure was achieved 35 days postimplantation. The patient then underwent plating of the tibia for nonunion with no adverse effect to the grafted site. The tibia eventually healed 5 months postplating, and the cosmetic appearance of the newly formed skin was satisfactory.
  5. Fulltext The Effect of 4-hydroxybenzaldehyde on the γ-aminobutyric Acid Type A Receptor
    Zhang J, Mohamad H, Wong JH, Bilal M, Ismail AHB, Lloyd AJ, et al.
    Malays J Med Sci, 2017 Mar;24(2):94-99.
    PMID: 28894409 DOI: 10.21315/mjms2017.24.2.12
    The α1β2γ2 subtype of GABAA receptors is the most commonly found GABAA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a α1β2γ2S/L subtype for application as an in vitro model for the screening of compounds that modulate receptor activities. In fact, 4-hydroxybenzaldehyde (4-HB) has been identified as one of the major components in Dendrocalamus asper bamboo shoots in our previous study, and the current study showed that at 101.7 μM, 4-HB significantly reduced the GABA-induced chloride current of GABAA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations.
  6. Fulltext Polygonumins A, a newly isolated compound from the stem of Polygonum minus Huds with potential medicinal activities
    Ahmad R, Sahidin I, Taher M, Low C, Noor NM, Sillapachaiyaporn C, et al.
    Sci Rep, 2018 03 09;8(1):4202.
    PMID: 29523802 DOI: 10.1038/s41598-018-22485-5
    Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound's structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure differences were located at C-3″″'. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p 
  7. Unravelling the adaptation strategies employed by Glaciozyma antarctica PI12 on Antarctic sea ice
    Bharudin I, Abu Bakar MF, Hashim NHF, Mat Isa MN, Alias H, Firdaus-Raih M, et al.
    Mar Environ Res, 2018 Jun;137:169-176.
    PMID: 29598997 DOI: 10.1016/j.marenvres.2018.03.007
    Glaciozyma antarctica PI12, is a psychrophilic yeast isolated from Antarctic sea. In this work, Expressed Sequence Tags (EST) from cells exposed to three different temperatures; 15 °C, 0 °C and -12 °C were generated to identify genes associated with cold adaptation. A total of 5376 clones from each library were randomly picked and sequenced. Comparative analyses from the resulting ESTs in each condition identified several groups of genes required for cold adaptation. Additionally, 319 unique transcripts that encoded uncharacterised functions were identified in the -12 °C library and are currently unique to G. antarctica. Gene expression analysis using RT-qPCR revealed two of the unknown genes to be up-regulated at -12 °C compared to 0 °C and 15 °C. These findings further contribute to the collective knowledge into G. antarctica cold adaptation and as a resource for understanding the ecological and physiological tolerance of psychrophilic microbes in general.
  8. Fulltext Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
    Zamrus SNH, Akhtar MN, Yeap SK, Quah CK, Loh WS, Alitheen NB, et al.
    Chem Cent J, 2018 Mar 19;12(1):31.
    PMID: 29556774 DOI: 10.1186/s13065-018-0398-1
    BACKGROUND: Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies.

    RESULTS: Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1-10, acetone 11-17 and cyclopentanone 18-24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1-24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11-17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed1H NMR, IR, UV-Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure-activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases.

    CONCLUSIONS: Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.

  9. Fulltext Genetic diversity of toxigenic Vibrio cholerae O1 from Sabah, Malaysia 2015
    Zaw MT, Emran NA, Ibrahim MY, Suleiman M, Awang Mohd TA, Yusuff AS, et al.
    J Microbiol Immunol Infect, 2019 Aug;52(4):563-570.
    PMID: 29428381 DOI: 10.1016/j.jmii.2018.01.003
    BACKGROUND: Cholera is an important health problem in Sabah, a Malaysian state in northern Borneo; however, Vibrio cholerae in Sabah have never been characterized. Since 2002, serogroup O1 strains having the traits of both classical and El Tor biotype, designated as atypical El Tor biotype, have been increasingly reported as the cause of cholera worldwide. These variants are believed to produce clinically more severe disease like classical strains.

    PURPOSE: The purpose of this study is to investigate the genetic diversity of V.cholerae in Sabah and whether V.cholerae in Sabah belong to atypical El Tor biotype.

    METHODS: ERIC-PCR, a DNA fingerprinting method for bacterial pathogens based on the enterobacterial repetitive intergenic consensus sequence, was used to study the genetic diversity of 65 clinical V.cholerae O1 isolates from 3 districts (Kudat, Beluran, Sandakan) in Sabah and one environmental isolate from coastal sea water in Kudat district. In addition, we studied the biotype-specific genetic traits in these isolates to establish their biotype.

    RESULTS: Different fingerprint patterns were seen in isolates from these three districts but one of the patterns was seen in more than one district. Clinical isolates and environmental isolate have different patterns. In addition, Sabah isolates harbor genetic traits specific to both classical biotype (ctxB-1, rstRCla) and El Tor biotype (rstRET, rstC, tcpAET, rtxC, VC2346).

    CONCLUSION: This study revealed that V.cholerae in Sabah were genetically diverse and were atypical El Tor strains. Fingerprint patterns of these isolates will be useful in tracing the origin of this pathogen in the future.

  10. Fulltext Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist
    Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, et al.
    Int J Med Sci, 2018;15(4):300-308.
    PMID: 29511366 DOI: 10.7150/ijms.22732
    Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.
  11. Fulltext Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
    Abu Bakar A, Akhtar MN, Mohd Ali N, Yeap SK, Quah CK, Loh WS, et al.
    Molecules, 2018 Mar 08;23(3).
    PMID: 29518053 DOI: 10.3390/molecules23030616
    Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure-activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by ¹H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.
  12. Fulltext Capacity-building in clinical skills of rehabilitation workforce in low- and middle-income countries
    Khan F, Amatya B, de Groote W, Owolabi M, Syed IM, Hajjoui A, et al.
    J Rehabil Med, 2018 May 08;50(5):472-479.
    PMID: 29487941 DOI: 10.2340/16501977-2313
    OBJECTIVE: Despite the prevalence of disability in low-and middle-income countries, the clinical skills of the rehabilitation workforce are not well described. We report health professionals' perspectives on clinical skills in austere settings and identify context-specific gaps in workforce capacity.

    METHODS: A cross-sectional pilot survey (Pakistan, Morocco, Nigeria, Malaysia) of health professionals' working in rehabilitation in hospital and community settings. A situational-analysis survey captured assessment of clinical skills required in various rehabilitation settings. Responses were coded in a line-by-line process, and linked to categories in domains of the International Classification of Functioning, Disability and Health (ICF).

    RESULTS: Respondents (n = 532) from Pakistan 248, Nigeria 159, Morocco 93 and Malaysia 32 included the following: physiotherapists (52.8%), nurses (8.8%), speech (5.3%) and occupational therapists (8.5%), rehabilitation physicians (3.8%), other doctors (5.5%) and prosthetist/orthotists (1.5%). The 10 commonly used clinical skills reported were prescription of: physical activity, medications, transfer-techniques, daily-living activities, patient/carer education, diagnosis/screening, behaviour/cognitive interventions, comprehensive patient-care, referrals, assessments and collaboration. There was significant overlap in skills listed irrespective of profession. Most responses linked with ICF categories in activities/participation and personal factors.

    CONCLUSION: The core skills identified reflect general rehabilitation practice and a task-shifting approach, to address shortages of health workers in low-and middle-income countries.

  13. Fulltext Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds
    Al-Sanea MM, Ali Khan MS, Abdelazem AZ, Lee SH, Mok PL, Gamal M, et al.
    Molecules, 2018 Jan 31;23(2).
    PMID: 29385071 DOI: 10.3390/molecules23020297
    A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a-n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a-e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines.
  14. Fulltext Prevalence, Awareness, Treatment and Control of hypertension in the Malaysian population: findings from the National Health and Morbidity Survey 2006-2015
    Ab Majid NL, Omar MA, Khoo YY, Mahadir Naidu B, Ling Miaw Yn J, Rodzlan Hasani WS, et al.
    J Hum Hypertens, 2018 Sep;32(8-9):617-624.
    PMID: 29899376 DOI: 10.1038/s41371-018-0082-x
    Hypertension is strongly associated with chronic diseases such as myocardial infarction, stroke, heart failure, and renal failure. The objective of this study is to determine the trend of prevalence, awareness, treatment, and control of hypertension among Malaysian population since 2006 to 2015. The study used the data from National Health and Morbidity Survey (NHMS) 2006, 2011, and 2015. It was a cross-sectional with two-stage stratified random sampling throughout Malaysia for eligible respondents 18 years old and above. Respondents were interviewed face to face and blood pressure was recorded as the average reading from two electronic pressure monitoring measurements. Data was analyzed using the Complex sample module in SPSS Version 20. The prevalence of hypertension in Malaysia was 34.6% (95% CI: 33.9, 35.3) in 2006, 33.6% (95% CI: 32.6, 34.6) in 2011 and 35.3% (95% CI: 34.5, 36.3) in 2015. Awareness of hypertension in 2006, 2011, and 2015 was 35.6% (95% CI: 34.6, 36.6), 40.7% (95% CI: 39.3, 42.1), and 37.5% (95% CI: 36.1, 38.9) respectively. The trend of receiving treatment from 2006 to 2015 was 78.9% (95% CI: 77.5, 80.2) to 83.2% (95% CI: 81.3, 84.8). The control of hypertension increased significantly from 27.5% (95% CI: 25.9, 29.2) in 2006 to 37.4% (95% CI: 35.3, 39.5) in 2015. Despite higher proportions receiving treatment over time, the control of hypertension remained below 40% since NHMS 2006 until 2015. The strategies to further reduce the prevalence and increase awareness of hypertension should be enhanced particularly among the targeted age group to ensure early detection, treatment, and control thus preventing from long-term complications.
  15. Contribution of transposable elements in the plant's genome
    Sahebi M, Hanafi MM, van Wijnen AJ, Rice D, Rafii MY, Azizi P, et al.
    Gene, 2018 Jul 30;665:155-166.
    PMID: 29684486 DOI: 10.1016/j.gene.2018.04.050
    Plants maintain extensive growth flexibility under different environmental conditions, allowing them to continuously and rapidly adapt to alterations in their environment. A large portion of many plant genomes consists of transposable elements (TEs) that create new genetic variations within plant species. Different types of mutations may be created by TEs in plants. Many TEs can avoid the host's defense mechanisms and survive alterations in transposition activity, internal sequence and target site. Thus, plant genomes are expected to utilize a variety of mechanisms to tolerate TEs that are near or within genes. TEs affect the expression of not only nearby genes but also unlinked inserted genes. TEs can create new promoters, leading to novel expression patterns or alternative coding regions to generate alternate transcripts in plant species. TEs can also provide novel cis-acting regulatory elements that act as enhancers or inserts within original enhancers that are required for transcription. Thus, the regulation of plant gene expression is strongly managed by the insertion of TEs into nearby genes. TEs can also lead to chromatin modifications and thereby affect gene expression in plants. TEs are able to generate new genes and modify existing gene structures by duplicating, mobilizing and recombining gene fragments. They can also facilitate cellular functions by sharing their transposase-coding regions. Hence, TE insertions can not only act as simple mutagens but can also alter the elementary functions of the plant genome. Here, we review recent discoveries concerning the contribution of TEs to gene expression in plant genomes and discuss the different mechanisms by which TEs can affect plant gene expression and reduce host defense mechanisms.
  16. Fulltext Genotype-phenotype association of Hbe/β thalassemia disease and the role of genetic modifiers
    HanafI S, Abdullah WZ, Adnan RA, Bahar R, Johan MF, Azman NF, et al.
    Malaysian Journal of Paediatrics and Child Health, 2016;22(1):1-16.
    MyJurnal
    HbE/β-thalassemia is the most common severe form of thalassemia particularly in SEA region including Malaysia and globally, it comprised of a significant severe form of β-thalassemia disorder. It has various clinical manifestations ranging from very mild anemia to severe manifestation similar to beta thalassemia major. Many different syndromes are observed in HbE/β-thalassemia. Several genetic modifiers have been reported to play important role in contributing to phenotypic variability. The true reasons underlying this phenotypic variability remain unknown. The most reliable predictive factor of the disease phenotype is the nature of the beta globin gene mutation itself. However, the degree of severity is also believed to be affected by other genetic modifiers. For instance, high HbF level ameliorates the clinical severity of β thalassemia patients. Therefore, identification of these genetic modifiers is very important. The association of severe clinical manifestation and the specific β-globin gene mutation has been known. But the wide scope and other potential predictors have been only recently appreciated. This review therefore aimed to reveal the potential genetic modifiers of HbE/βthalassemia patients based on the previous reported studies. A better understanding on the mechanisms underlying the variety of phenotypes of this disease may lead to the direction for a better future management plans. This also promotes “personalized medicine” in patient care.
  17. Influence of pH Adjustment Parameter for Sol-Gel Modification on Structural, Microstructure, and Magnetic Properties of Nanocrystalline Strontium Ferrite
    Azis RS, Sulaiman S, Ibrahim IR, Zakaria A, Hassan J, Muda NNC, et al.
    Nanoscale Res Lett, 2018 May 23;13(1):160.
    PMID: 29796949 DOI: 10.1186/s11671-018-2562-x
    Synthesis of nanocrystalline strontium ferrite (SrFe12O19) via sol-gel is sensitive to its modification parameters. Therefore, in this study, an attempt of regulating the pH as a sol-gel modification parameter during preparation of SrFe12O19 nanoparticles sintered at a low sintering temperature of 900 °C has been presented. The relationship of varying pH (pH 0 to 8) on structural, microstructures, and magnetic behaviors of SrFe12O19 nanoparticles were characterized by X-ray diffraction (XRD), field emission scanning microscope (FESEM), and vibrating sample magnetometer (VSM). Varying the pH of precursor exhibited a strong effect on the sintered density, crystal structure and magnetic properties of the SrFe12O19 nanoparticles. As the pH is 0, the SrFe12O19 produced relatively largest density, saturation magnetization, Ms, and coercivity, Hc, at a low sintering temperature of 900 °C. The grain size of SrFe12O19 is obtained in the range of 73.6 to 133.3 nm. The porosity of the sample affected the density and the magnetic properties of the SrFe12O19 ferrite. It is suggested that the low-temperature sintered SrFe12O19 at pH 0 displayed Ms of 44.19 emu/g and Hc of 6403.6 Oe, possessing a significant potential for applying in low-temperature co-fired ceramic permanent magnet.
  18. Fulltext Nuclear IHC enumeration: A digital phantom to evaluate the performance of automated algorithms in digital pathology
    Niazi MKK, Abas FS, Senaras C, Pennell M, Sahiner B, Chen W, et al.
    PLoS One, 2018;13(5):e0196547.
    PMID: 29746503 DOI: 10.1371/journal.pone.0196547
    Automatic and accurate detection of positive and negative nuclei from images of immunostained tissue biopsies is critical to the success of digital pathology. The evaluation of most nuclei detection algorithms relies on manually generated ground truth prepared by pathologists, which is unfortunately time-consuming and suffers from inter-pathologist variability. In this work, we developed a digital immunohistochemistry (IHC) phantom that can be used for evaluating computer algorithms for enumeration of IHC positive cells. Our phantom development consists of two main steps, 1) extraction of the individual as well as nuclei clumps of both positive and negative nuclei from real WSI images, and 2) systematic placement of the extracted nuclei clumps on an image canvas. The resulting images are visually similar to the original tissue images. We created a set of 42 images with different concentrations of positive and negative nuclei. These images were evaluated by four board certified pathologists in the task of estimating the ratio of positive to total number of nuclei. The resulting concordance correlation coefficients (CCC) between the pathologist and the true ratio range from 0.86 to 0.95 (point estimates). The same ratio was also computed by an automated computer algorithm, which yielded a CCC value of 0.99. Reading the phantom data with known ground truth, the human readers show substantial variability and lower average performance than the computer algorithm in terms of CCC. This shows the limitation of using a human reader panel to establish a reference standard for the evaluation of computer algorithms, thereby highlighting the usefulness of the phantom developed in this work. Using our phantom images, we further developed a function that can approximate the true ratio from the area of the positive and negative nuclei, hence avoiding the need to detect individual nuclei. The predicted ratios of 10 held-out images using the function (trained on 32 images) are within ±2.68% of the true ratio. Moreover, we also report the evaluation of a computerized image analysis method on the synthetic tissue dataset.
  19. Fulltext Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice
    Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Nasaruddin ML, Mori M, et al.
    J Alzheimers Dis, 2018;64(1):249-267.
    PMID: 29889072 DOI: 10.3233/JAD-170880
    We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.
  20. Fulltext Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease
    Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, et al.
    Nutrients, 2018 Aug 09;10(8).
    PMID: 30096951 DOI: 10.3390/nu10081057
    The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
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