Browse publications by year: 2018

  1. Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.
    J Med Food, 2018 Mar;21(3):289-301.
    PMID: 29420109 DOI: 10.1089/jmf.2017.4008
    The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.
    MeSH terms: Animals; Antihypertensive Agents/administration & dosage; Antihypertensive Agents/pharmacology; Antihypertensive Agents/therapeutic use*; Antihypertensive Agents/chemistry; Aorta, Thoracic; Calcium Channel Blockers/administration & dosage; Calcium Channel Blockers/pharmacology; Calcium Channel Blockers/therapeutic use; Calcium Channel Blockers/chemistry; Dose-Response Relationship, Drug; Endothelium, Vascular/drug effects; Endothelium, Vascular/physiology; Endothelium, Vascular/physiopathology; Hypertension/drug therapy*; Hypertension/metabolism; Hypertension/physiopathology; Malaysia; Male; Medicine, Traditional; Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/physiology; Muscle, Smooth, Vascular/physiopathology; Plant Extracts/administration & dosage; Plant Extracts/pharmacology; Plant Extracts/therapeutic use*; Plant Extracts/chemistry; Rats, Inbred SHR; Seeds/chemistry*; Vasoconstriction/drug effects; Vasodilation/drug effects; Vasodilator Agents/administration & dosage; Vasodilator Agents/pharmacology; Vasodilator Agents/therapeutic use*; Vasodilator Agents/chemistry; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Ethnopharmacology; Meliaceae/chemistry*; In Vitro Techniques
  2. Jaudan A, Sharma S, Malek SNA, Dixit A
    PLoS One, 2018;13(2):e0191523.
    PMID: 29420562 DOI: 10.1371/journal.pone.0191523
    Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.
    MeSH terms: Cell Cycle/drug effects; Uterine Cervical Neoplasms/metabolism; Uterine Cervical Neoplasms/pathology*; DNA Damage; Drug Screening Assays, Antitumor; Female; Humans; Phosphatidylserines/metabolism; Apoptosis/drug effects*; Reactive Oxygen Species/metabolism; Flavanones/pharmacology*; Cell Line, Tumor; Cell Proliferation/drug effects
  3. Kolivand H, Fern BM, Rahim MSM, Sulong G, Baker T, Tully D
    PLoS One, 2018;13(2):e0191447.
    PMID: 29420568 DOI: 10.1371/journal.pone.0191447
    In this paper, we present a new method to recognise the leaf type and identify plant species using phenetic parts of the leaf; lobes, apex and base detection. Most of the research in this area focuses on the popular features such as the shape, colour, vein, and texture, which consumes large amounts of computational processing and are not efficient, especially in the Acer database with a high complexity structure of the leaves. This paper is focused on phenetic parts of the leaf which increases accuracy. Detecting the local maxima and local minima are done based on Centroid Contour Distance for Every Boundary Point, using north and south region to recognise the apex and base. Digital morphology is used to measure the leaf shape and the leaf margin. Centroid Contour Gradient is presented to extract the curvature of leaf apex and base. We analyse 32 leaf images of tropical plants and evaluated with two different datasets, Flavia, and Acer. The best accuracy obtained is 94.76% and 82.6% respectively. Experimental results show the effectiveness of the proposed technique without considering the commonly used features with high computational cost.
    MeSH terms: Plants/classification*; Plant Leaves/anatomy & histology*
  4. Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S
    PLoS One, 2018;13(2):e0192416.
    PMID: 29420594 DOI: 10.1371/journal.pone.0192416
    This study aimed to evaluate the effects of metabolic syndrome (MetS) induced by high-carbohydrate high-fat (HCHF) diet on bone mineral density (BMD), histomorphometry and remodelling markers in male rats. Twelve male Wistar rats aged 12 weeks old were randomized into two groups. The normal group was given standard rat chow while the HCHF group was given HCHF diet to induce MetS. Abdominal circumference, blood glucose, blood pressure, and lipid profile were measured for the confirmation of MetS. Bone mineral density, histomorphometry and remodelling markers were evaluated for the confirmation of bone loss. The HCHF diet caused central obesity, hyperglycaemia, hypertension, and dyslipidaemia in male rats. No significant difference was observed in whole body bone mineral content and BMD between the normal and HCHF rats (p>0.05). For bone histomorphometric parameters, HCHF diet-fed animals had significantly lower osteoblast surface, osteoid surface, osteoid volume, and significantly higher eroded surface; resulting in a reduction in trabecular bone volume (p<0.05). Feeding on HCHF diet caused a significantly higher CTX-1 level (p<0.05), but did not cause any significant change in osteocalcin level compared to normal rats (p>0.05). In conclusion, HCHF diet-induced MetS causes imbalance in bone remodelling, leading to the deterioration of trabecular bone structure.
    MeSH terms: Animals; Body Composition; Male; Biomarkers/metabolism*; Absorptiometry, Photon; Bone Density*; Bone Remodeling*; Rats, Wistar; Metabolic Syndrome X/physiopathology*; Rats
  5. Goh YK, Hasim HM, Antonopoulos CG
    PLoS One, 2018;13(2):e0192160.
    PMID: 29420644 DOI: 10.1371/journal.pone.0192160
    In this paper, we study data from financial markets, using the normalised Mutual Information Rate. We show how to use it to infer the underlying network structure of interrelations in the foreign currency exchange rates and stock indices of 15 currency areas. We first present the mathematical method and discuss its computational aspects, and apply it to artificial data from chaotic dynamics and to correlated normal-variates data. We then apply the method to infer the structure of the financial system from the time-series of currency exchange rates and stock indices. In particular, we study and reveal the interrelations among the various foreign currency exchange rates and stock indices in two separate networks, of which we also study their structural properties. Our results show that both inferred networks are small-world networks, sharing similar properties and having differences in terms of assortativity. Importantly, our work shows that global economies tend to connect with other economies world-wide, rather than creating small groups of local economies. Finally, the consistent interrelations depicted among the 15 currency areas are further supported by a discussion from the viewpoint of economics.
    MeSH terms: Economics*; Investments*
  6. Widyasti E, Shikata A, Hashim R, Sulaiman O, Sudesh K, Wahjono E, et al.
    Enzyme Microb Technol, 2018 Apr;111:21-28.
    PMID: 29421033 DOI: 10.1016/j.enzmictec.2017.12.009
    Oil palm trunk (OPT) is one of the most promising lignocellulosic bioresources. To develop effective biodegradation, thermophilic, anaerobic microorganisms were screened from bovine manure compost using fibrillated OPT (f-OPT) pretreated by wet disk milling as the substrate. One thermophilic, anaerobic bacterium, strain CL-2, whose 16S rDNA gene has 98.6% sequence identity with that of Caldicoprobacter faecale DSM 20678T, exhibited high degradation activity (32.7% reduction in total dry solids of f-OPT). Strain CL-2 did not use cellulose as a carbon source, but used hemicelluloses such as xylan, arabinoxylan, starch and pectin at 70 °C. Phylogenetic and morphologic analyses and the polysaccharide use suggest that CL-2 may be classified as a novel species of Caldicoprobacter, named Caldicoprobacter sp. CL-2. To characterize enzymatic activities of CL-2, extracellular enzymes were prepared from culture broth using beechwood xylan as the carbon source. The extracellular enzymes showed high xylanase activity, but low cellulase activity, suggesting that f-OPT degradation may depend on xylanase activity. To understand the xylanase system of CL-2, a major xylanase was cloned and characterized. The xylanase (CalXyn11A) had a modular structure consisting of a glycoside hydrolase (GH) family-11 domain and a family 36 carbohydrate-binding module. CalXyn11A did not show f-OPT degradation activity, but a strong synergistic effect was observed when CalXyn11A was added to the extracellular enzyme preparation. These results indicate that, rather than working alone, CalXyn11A has an important role in enhancing total lignocellulose degradation activity by cooperation with other GHs.
    MeSH terms: Clostridiales/enzymology*; Clostridiales/genetics; Clostridiales/isolation & purification*; Anaerobiosis; Animals; Bacterial Proteins/genetics; Bacterial Proteins/isolation & purification; Bacterial Proteins/metabolism*; Biodegradation, Environmental; Biotransformation; Cattle/microbiology; Genes, Bacterial; Kinetics; Lignin; Phylogeny; Substrate Specificity; Biomass; Arecaceae/ultrastructure; Arecaceae/chemistry*; Endo-1,4-beta Xylanases/genetics; Endo-1,4-beta Xylanases/isolation & purification; Endo-1,4-beta Xylanases/metabolism*; Biofuels
  7. Sidi N, Aris AZ, Mohamat Yusuff F, Looi LJ, Mokhtar NF
    Mar Pollut Bull, 2018 Jan;126:113-118.
    PMID: 29421077 DOI: 10.1016/j.marpolbul.2017.10.041
    Revealing the potential of seagrass as a bioindicator for metal pollution is important for assessing marine ecosystem health. Trace metal (111Cd, 63Cu, 60Ni, 208Pb, 66Zn) concentrations in the various parts (root, rhizome, and blade) of tape seagrass (Enhalus acoroides) collected from Merambong shoal of Sungai Pulai estuary, Johor Strait, Malaysia were acid-extracted using a microwave digester and analysed via inductively coupled plasma-mass spectrometry (ICP-MS). The ranges of trace metal concentrations (in μgg-1 dry weight) were as follows: Cd (0.05-0.81), Cu (1.62-27.85), Ni (1.89-9.35), Pb (0.69-4.16), and Zn (3.44-35.98). The translocation factor revealed that E. acoroides is a hyperaccumulator plant, as its blades can accumulate high concentrations of Cd, Cu, Ni, and Zn, but not Pb. The plant limits Pb mobility to minimize Pb's toxic impact. Thus, E. acoroides is a potential bioindicator of metal pollution by Cd, Cu, Ni, and Zn in estuarine environments.
    MeSH terms: Cadmium/analysis; Environmental Monitoring/methods*; Environmental Pollution/analysis; Isotopes; Malaysia; Metals/analysis; Trace Elements/analysis; Water Pollutants, Chemical/analysis; Plant Leaves/chemistry*; Metals, Heavy/analysis*; Rhizome/chemistry*; Hydrocharitaceae/chemistry*; Estuaries
  8. Sit PS, Teh CSJ, Idris N, Ponnampalavanar S
    Infect Genet Evol, 2018 04;59:132-141.
    PMID: 29421224 DOI: 10.1016/j.meegid.2018.01.031
    Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious infection that can result in significant morbidity and mortality. A retrospective cohort study was conducted to determine the predictors of mortality in patient with MRSA bacteremia correlating with clinical, phenotypic and genotypic characteristics of the relevant strains. Most of the bacteremia cases were healthcare-associated (P 
    MeSH terms: Adult; Aged; Aged, 80 and over; Cross Infection/microbiology; Cross Infection/mortality; Cross Infection/epidemiology; Female; Hospitals, Teaching; Humans; Malaysia/epidemiology; Male; Middle Aged; Retrospective Studies; Risk Factors; Staphylococcal Infections/microbiology*; Staphylococcal Infections/mortality; Staphylococcal Infections/epidemiology; Bacteremia/microbiology*; Bacteremia/mortality; Bacteremia/epidemiology; Tertiary Care Centers
  9. Ude CC, Shamsul BS, Ng MH, Chen HC, Ohnmar H, Amaramalar SN, et al.
    Exp Gerontol, 2018 04;104:43-51.
    PMID: 29421350 DOI: 10.1016/j.exger.2018.01.020
    BACKGROUND: Hyaline articular cartilage, which protects the bones of diarthrodial joints from forces associated with load bearing, frictions, and impacts has very limited capacities for self-repair. Over the years, the trend of treatments has shifted to regenerations and researchers have been on the quest for a lasting regeneration. We evaluated the treatment of osteoarthritis by chondrogenically induced ADSCs and BMSCs for a long time functional recovery.

    METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of ACL and medial meniscus. Stem cells from sheep were induced to chondrogenic lineage. Test sheep received 5 mls single doses of 2 × 107 autologous PKH26-labelled ADSCs or BMSCs, while controls received basal medium. Functional recovery of the knees was evaluated via electromyography.

    RESULTS: Induced ADSCs had 625, 255, 393, 908, 409, 157 and 1062 folds increases of collagen I, collagen II, aggrecan, SOX9, cartilage oligomeric protein, chondroadherin and fibromodullin compare to uninduced cells, while BMSCs had 702, 657, 321, 276, 337, 233 and 1163 respectively; p = .001. Immunocytochemistry was positive for these chondrogenic markers. 12 months post-treatment, controls scored 4 in most regions using ICRS, while the treated had 8; P = .001. Regenerated cartilages were positive to PKH26 and demonstrated the presence of condensing cartilages on haematoxylin and eosin; and Safranin O. OA degenerations caused significant amplitude shift from right to left hind limb. After treatments, controls persisted with significant decreases; while treated samples regained balance.

    CONCLUSIONS: Both ADSCs and BMSCs had increased chondrogenic gene expressions using TGF-β3 and BMP-6. The treated knees had improved cartilage scores; PKH26 can provide elongated tracking, while EMG results revealed improved joint recoveries. These could be suitable therapies for osteoarthritis.

    MeSH terms: Adipose Tissue/cytology; Animals; Arthroscopy; Bone Marrow Cells/cytology; Cartilage, Articular/pathology; Cartilage, Articular/physiopathology*; Cartilage, Articular/surgery; Cell Differentiation; Cell Separation; Cell Survival; Disease Models, Animal; Male; Regeneration*; Sheep; Gene Expression; Cell Culture Techniques; Chondrogenesis*; Osteoarthritis, Knee/physiopathology; Osteoarthritis, Knee/therapy*; Multipotent Stem Cells/cytology; Mesenchymal Stem Cell Transplantation*; Cell Proliferation; Transforming Growth Factor beta3/pharmacology; Bone Morphogenetic Protein 6/pharmacology; Cell Tracking
  10. Tham LP, Wah W, Phillips R, Shahidah N, Ng YY, Shin SD, et al.
    Resuscitation, 2018 04;125:111-117.
    PMID: 29421664 DOI: 10.1016/j.resuscitation.2018.01.040
    BACKGROUND: The Pan Asian Resuscitation Outcomes Study (PAROS) is a retrospective study of out- of-hospital cardiac arrest(OHCA), collaborating with EMS agencies and academic centers in Japan, South Korea, Malaysia, Singapore, Taiwan, Thailand and UAE-Dubai. The objectives of this study is to describe the characteristics and outcomes, and to find factors associated with survival after paediatric OHCA.

    METHODS: We studied all children less than 17 years of age with OHCA conveyed by EMS and non-EMS transports from January 2009 to December 2012. We did univariate and multivariate logistic regression analyses to assess the factors associated with survival-to-discharge outcomes.

    RESULTS: A total of 974 children with OHCA were included. Bystander cardiopulmonary resuscitation rates ranged from 53.5% (Korea), 35.6% (Singapore) to 11.8% (UAE). Overall, 8.6% (range 0%-9.7%) of the children survived to discharge from hospital. Adolescents (13-17 years) had the highest survival rate of 13.8%. 3.7% of the children survived with good neurological outcomes of CPC 1 or 2. The independent pre-hospital factors associated with survival to discharge were witnessed arrest and initial shockable rhythm. In the sub-group analysis, pre-hospital advanced airway [odds ratio (OR) = 3.35, 95% confidence interval (CI) = 1.23-9.13] was positively associated with survival-to-discharge outcomes in children less than 13 years-old. Among adolescents, bystander CPR (OR = 2.74, 95%CI = 1.03-7.3) and initial shockable rhythm (OR = 20.51, 95%CI = 2.15-195.7) were positive factors.

    CONCLUSION: The wide variation in the survival outcomes amongst the seven countries in our study may be due to the differences in the delivery of pre-hospital interventions and bystander CPR rates.

    MeSH terms: Adolescent; Asia/epidemiology; Child; Child, Preschool; Emergency Medical Services/statistics & numerical data; Female; Humans; Infant; Infant, Newborn; Male; Population Surveillance; Prospective Studies; Cardiopulmonary Resuscitation/statistics & numerical data*; Outcome Assessment (Health Care)*; Out-of-Hospital Cardiac Arrest/mortality*
  11. Mohan V, Paungmali A, Sitilerpisan P, Hashim UF, Mazlan MB, Nasuha TN
    Nurs Health Sci, 2018 Jun;20(2):224-230.
    PMID: 29421851 DOI: 10.1111/nhs.12406
    Non-specific low back pain (NS-LBP) is known to cause respiratory dysfunction. In this study, we investigated alterations in breathing, respiratory strength and endurance, core stability, diaphragm mobility, and chest expansion among patients with NS-LBP and healthy individuals. The specific aim of the study was to correlate between respiratory function and other variables among NS-LBP patients. Thirty four patients with NS-LBP were matched with 34 healthy participants before undergoing total faulty breathing scale, spirometer, respiratory pressure meter, chest expansion, ultrasound, and pressure biofeedback measurements. There were signs of faulty breathing in the NS-LBP patients when compared to the healthy participants. Diaphragmatic mobility and respiratory muscle endurance were lower in the NS-LBP group. Chest expansion exhibited a significant decrease at the level of the fourth intercostal space in the NS-LBP group, but respiratory muscle strength and core stability were not significant between the two groups. Positive correlations were found to be fairly significant regarding respiratory muscle strength. The findings of this study indicated altered respiratory characteristics in the NS-LBP patients, and suggested that they would improve through respiratory exercises.
    MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Middle Aged; Pain Measurement/methods; Pain Measurement/psychology; Respiratory Mechanics/physiology*; Low Back Pain/classification*; Statistics, Nonparametric
  12. Diong TW, Haflah NHM, Kassim AYM, Habshi SMIA, Shukur MH
    J Hand Surg Asian Pac Vol, 2018 Mar;23(1):26-32.
    PMID: 29409409 DOI: 10.1142/S2424835518500030
    BACKGROUND: The use of volar locking plate in distal radius fracture can lead to extensor tendon rupture due to dorsal screw penetration. The aim of our study was to investigate the occurrence of dorsal and intra-articular screw penetration using CT scan after volar distal radius osteosynthesis for distal radius fractures.

    METHODS: Thirty patients who underwent distal volar locking plate for distal radius fracture were included in a retrospective study. In all 30 patients no dorsal and intra-articular screw penetration were detected on standard AP and lateral views of a plain radiograph. CT scan of the operated wrist was performed to determine the number of intra-articular and dorsal screw penetrations. Clinical examination was performed to determine the wrist functions in comparison to the normal wrist.

    RESULTS: Nineteen wrists were noted to have screw penetration either dorsally or intraarticularly. The highest incidence is in the 2nd extensor compartment where 13 screws had penetrated with a mean of 2.46 mm. Six screws penetrated into the distal radial ulnar joint and five screws into the wrist joint with a mean of 2.83 mm and 2.6 mm, respectively. However, there was no incidence of tendon irritation or rupture.

    CONCLUSIONS: This study demonstrated a high incidence of dorsal and intra-articular screw penetration detected by CT scan which was not apparent in plain radiograph. We recommend that surgeons adhere to the principle of only near cortex fixation and downsizing the locking screw length by 2 mm.

    MeSH terms: Adult; Aged; Aged, 80 and over; Bone Plates*; Bone Screws/adverse effects*; Female; Fracture Fixation, Internal*; Humans; Male; Middle Aged; Radius Fractures/surgery*; Retrospective Studies; Tomography, X-Ray Computed*; Young Adult
  13. Vasaikar S, Tsipras G, Landázuri N, Costa H, Wilhelmi V, Scicluna P, et al.
    BMC Cancer, 2018 02 06;18(1):154.
    PMID: 29409474 DOI: 10.1186/s12885-018-4012-7
    BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.

    METHODS: Data from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.

    RESULTS: By bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.

    CONCLUSIONS: ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.

    MeSH terms: Adult; Aged; Brain Neoplasms/drug therapy; Brain Neoplasms/genetics*; Brain Neoplasms/metabolism; Brain Neoplasms/pathology; Female; Glioblastoma/drug therapy; Glioblastoma/genetics*; Glioblastoma/metabolism; Humans; Male; Middle Aged; Prognosis; Biomarkers, Tumor/genetics*; Biomarkers, Tumor/metabolism; Gene Expression Regulation, Neoplastic*; Gene Expression Profiling*; Receptor, Endothelin B/genetics*; Receptor, Endothelin B/metabolism; Kaplan-Meier Estimate; Gene Regulatory Networks; Molecular Targeted Therapy; Endothelin Receptor Antagonists/therapeutic use
  14. Tabandeh M, Salman AA, Goh EW, Heidelberg T, Hussen RSD
    Chem Phys Lipids, 2018 05;212:111-119.
    PMID: 29409839 DOI: 10.1016/j.chemphyslip.2018.01.011
    A new synthesis approach towards biantennary lipids of Guerbet glycoside type was developed based on oleic acid as sustainable resource. Functionalization of the double bond provided access to primary alcohols with α-branched C19-skeleton. Formulation studies with corresponding lactosides indicated formation of vesicles with high assembly stability. A relatively narrow bimodal size distribution of the latter, which turns into a narrow unimodal distribution of small vesicles upon addition of an ionic cosurfactant, suggests potential for a vesicular drug delivery system.
    MeSH terms: Glycolipids/chemical synthesis; Glycolipids/chemistry*; Glycosides/chemistry; Surface-Active Agents/chemistry; Temperature; Oleic Acid/chemistry; Unilamellar Liposomes/chemistry
  15. Kongkaew C, Scholfield NC, Dhippayom T, Dilokthornsakul P, Saokaew S, Chaiyakunapruk N
    J Ethnopharmacol, 2018 Apr 24;216:162-174.
    PMID: 29409850 DOI: 10.1016/j.jep.2018.01.028
    ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham (commonly termed P. mirifica, PM) growing in upland Thailand has a long history as a postmenopausal rejuvenant therapy for indigenants. Its amelioration of menopause symptoms in clinical trials was assessed.

    MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.

    RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.

    CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.

    MeSH terms: Adult; Clinical Trials as Topic; Female; Humans; Phytotherapy; Menopause/blood; Menopause/drug effects*; Middle Aged; Plant Extracts/adverse effects; Plant Extracts/isolation & purification; Plant Extracts/therapeutic use*; Plants, Medicinal; Biomarkers/blood; Treatment Outcome; Risk Assessment; Evidence-Based Medicine
  16. Chong ETJ, Neoh JWF, Lau TY, Lim YA, Chua KH, Lee PC
    Acta Trop, 2018 May;181:35-39.
    PMID: 29409854 DOI: 10.1016/j.actatropica.2018.01.018
    Malaria is a notorious disease which causes major global morbidity and mortality. This study aims to investigate the genetic and haplotype differences of Plasmodium knowlesi (P. knowlesi) isolates in Malaysian Borneo and Peninsular Malaysia based on the molecular analysis of the cytochrome b (cyt b) gene. The cyt b gene of 49 P. knowlesi isolates collected from Sabah, Malaysian Borneo and Peninsular Malaysia was amplified using PCR, cloned into a commercialized vector and sequenced. In addition, 45 cyt b sequences were retrieved from humans and macaques bringing to a total of 94 cyt b gene nucleotide sequences for phylogenetic analysis. Genetic and haplotype analyses of the cyt b were analyzed using MEGA6 and DnaSP ver. 5.10.01. The haplotype genealogical linkage of cyt b was generated using NETWORK ver. 4.6.1.3. Our phylogenetic tree revealed the conservation of the cyt b coding sequences with no distinct cluster across different geographic regions. Nucleotide analysis of cyt b showed that the P. knowlesi isolates underwent purifying selection with population expansion, which was further supported by extensive haplotype sharing between the macaques and humans from Malaysian Borneo and Peninsular Malaysia in the median-joining network analysis. This study expands knowledge on conservation of the zoonotic P. knowlesi cyt b gene between Malaysian Borneo and Peninsular Malaysia.
    MeSH terms: Animals; Haplotypes*; Malaysia; Phylogeny; Genetic Variation; Plasmodium knowlesi/classification; Plasmodium knowlesi/enzymology; Plasmodium knowlesi/genetics*; Cytochromes b/genetics*; Cytochromes b/chemistry
  17. Jamalpour S, Zain SM, Mosavat M, Mohamed Z, Omar SZ
    Gene, 2018 Apr 15;650:34-40.
    PMID: 29410004 DOI: 10.1016/j.gene.2018.01.091
    BACKGROUND: Although the influence of a common variant in the glucokinase regulatory gene (GCKR rs780094) in type 2 diabetes mellitus has been well documented, less data however, is available of its role in gestational diabetes mellitus (GDM). We carried out a case control study to assess the association between GCKR rs780094 and GDM in the Asian, and also a meta-analysis to further assess the strength of the association.

    METHODS: Demographic, clinical and genotype data were determined for 1122 women (267 cases and 855 controls) recruited from the University of Malaya Medical Centre in the Klang Valley, Kuala Lumpur. Relevant articles were identified from Pubmed, Embase, MEDLINE, and Web of Science. Extraction of data was carried out and summary estimates of the association between rs780094 and GDM were examined.

    RESULTS: The frequency of risk allele C was significantly higher in the cases than controls (OR 1.34, 95% CI 1.09-1.66, P = 0.006). The C allele was also associated with increased level of random 2-hour fasting plasma glucose and pregravid body mass index. Meta-analysis further confirmed the association of the GCKR rs780094 with GDM (OR 1.32, 95% CI 1.14-1.52, P = 0.0001).

    CONCLUSION: This study strongly suggests that GCKR rs780094-C is associated with increased risk of GDM.

    MeSH terms: Adolescent; Adult; Female; Gene Frequency; Humans; Malaysia; Middle Aged; Pregnancy; Case-Control Studies; Diabetes, Gestational/genetics*; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide*; Adaptor Proteins, Signal Transducing/genetics*; Young Adult
  18. Mayurasakorn K, Hasanah N, Homma T, Homma M, Rangel IK, Garza AE, et al.
    Metabolism, 2018 Jun;83:92-101.
    PMID: 29410348 DOI: 10.1016/j.metabol.2018.01.012
    BACKGROUND AND PURPOSE: The plasma membrane protein caveolin-1 (CAV-1) has been shown to be involved in modulating glucose homeostasis and the actions of the renin-angiotensin-aldosterone system (RAAS). Caloric restriction (CR) is widely accepted as an effective therapeutic approach to improve insulin sensitivity and reduce the severity of diabetes. Recent data indicate that polymorphisms of the CAV-1 gene are strongly associated with insulin resistance, hypertension and metabolic abnormalities in non-obese individuals. Therefore, we sought to determine whether CR improves the metabolic and cardiovascular (CV) risk factors in the lean CAV-1 KO mice.

    MATERIALS/METHODS: Twelve- to fourteen-week-old CAV-1 knockout (KO) and genetically matched wild-type (WT) male mice were randomized by genotype to one of two dietary regimens: ad libitum (ad lib) food intake or 40% CR for 4 weeks. Three weeks following the onset of dietary restriction, all groups were assessed for insulin sensitivity. At the end of the study, all groups were assessed for fasting glucose, insulin, HOMA-IR, lipids, corticosterone levels and blood pressure (BP). Aldosterone secretion was determined from acutely isolated Zona Glomerulosa cells.

    RESULTS: We confirmed that the CAV-1 KO mice on the ad lib diet display a phenotype consistent with the cardiometabolic syndrome, as shown by higher systolic BP (SBP), plasma glucose, HOMA-IR and aldosterone levels despite lower body weight compared with WT mice on the ad lib diet. CAV-1 KO mice maintained their body weight on the ad lib diet, but had substantially greater weight loss with CR, as compared to caloric restricted WT mice. CR-mediated changes in weight were associated with dramatic improvements in glucose and insulin tolerance in both genotypes. These responses to CR, however, were more robust in CAV-1KO vs. WT mice and were accompanied by reductions in plasma glucose, insulin and HOMA-IR in CAV-1KO but not WT mice. Surprisingly, in the CAV-1 KO, but not in WT mice, CR was associated with increased SBP and aldosterone levels, suggesting that in CAV-1 KO mice CR induced an increase in some CV risk factors.

    CONCLUSIONS: CR improved the metabolic phenotype in CAV-1 KO mice by increasing insulin sensitivity; nevertheless, this intervention also increased CV risk by inappropriate adaptive responses in the RAAS and BP.

    MeSH terms: Animals; Blood Glucose/metabolism*; Blood Pressure/physiology; Cardiovascular Diseases/genetics*; Cardiovascular Diseases/metabolism*; Homeostasis/genetics; Insulin Resistance/genetics; Male; Renin-Angiotensin System/physiology; Risk Factors; Mice, Knockout; Metabolic Syndrome X/genetics*; Metabolic Syndrome X/metabolism*; Caveolin 1/genetics*; Mice
  19. Rose JP, Kleist TJ, Löfstrand SD, Drew BT, Schönenberger J, Sytsma KJ
    Mol Phylogenet Evol, 2018 05;122:59-79.
    PMID: 29410353 DOI: 10.1016/j.ympev.2018.01.014
    Inferring interfamilial relationships within the eudicot order Ericales has remained one of the more recalcitrant problems in angiosperm phylogenetics, likely due to a rapid, ancient radiation. As a result, no comprehensive time-calibrated tree or biogeographical analysis of the order has been published. Here, we elucidate phylogenetic relationships within the order and then conduct time-dependent biogeographical and diversification analyses by using a taxon and locus-rich supermatrix approach on one-third of the extant species diversity calibrated with 23 macrofossils and two secondary calibration points. Our results corroborate previous studies and also suggest several new but poorly supported relationships. Newly suggested relationships are: (1) holoparasitic Mitrastemonaceae is sister to Lecythidaceae, (2) the clade formed by Mitrastemonaceae + Lecythidaceae is sister to Ericales excluding balsaminoids, (3) Theaceae is sister to the styracoids + sarracenioids + ericoids, and (4) subfamilial relationships with Ericaceae suggest that Arbutoideae is sister to Monotropoideae and Pyroloideae is sister to all subfamilies excluding Arbutoideae, Enkianthoideae, and Monotropoideae. Our results indicate Ericales began to diversify 110 Mya, within Indo-Malaysia and the Neotropics, with exchange between the two areas and expansion out of Indo-Malaysia becoming an important area in shaping the extant diversity of many families. Rapid cladogenesis occurred along the backbone of the order between 104 and 106 Mya. Jump dispersal is important within the order in the last 30 My, but vicariance is the most important cladogenetic driver of disjunctions at deeper levels of the phylogeny. We detect between 69 and 81 shifts in speciation rate throughout the order, the vast majority of which occurred within the last 30 My. We propose that range shifting may be responsible for older shifts in speciation rate, but more recent shifts may be better explained by morphological innovation.
    MeSH terms: Animals; Chloroplasts/genetics; Far East; Fossils/history; Mitochondria/genetics; Phylogeny*; Ribosomes/genetics; Angiosperms/classification*; Angiosperms/genetics; Biodiversity*; History, Ancient; Genetic Speciation; Phylogeography/history
  20. Tindall SM, Vallières C, Lakhani DH, Islahudin F, Ting KN, Avery SV
    Sci Rep, 2018 02 06;8(1):2464.
    PMID: 29410428 DOI: 10.1038/s41598-018-20816-0
    Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
    MeSH terms: Amodiaquine/pharmacology; Animals; Antimalarials/pharmacology*; Biological Transport; Chloroquine/pharmacology; Drug Resistance/genetics; Humans; Mutation; Plasmodium falciparum/drug effects; Plasmodium falciparum/genetics*; Plasmodium falciparum/metabolism; Quinine/pharmacology; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/drug effects*; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Mefloquine/pharmacology; Protozoan Proteins/genetics*; Protozoan Proteins/metabolism; Gene Expression; Plasmodium chabaudi/drug effects; Plasmodium chabaudi/genetics; Plasmodium chabaudi/metabolism; Conserved Sequence; Transgenes; Polymorphism, Single Nucleotide; Amino Acid Transport Systems/genetics*; Amino Acid Transport Systems/metabolism; Saccharomyces cerevisiae Proteins/genetics*; Saccharomyces cerevisiae Proteins/metabolism
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