Browse publications by year: 2016

  1. Tee WV, Ripen AM, Mohamad SB
    Sci Rep, 2016 Oct 27;6:35937.
    PMID: 27786277 DOI: 10.1038/srep35937
    Crystal structures of holo vitamin D receptor (VDR) revealed a canonical conformation in which the ligand is entrapped in a hydrophobic cavity buried in the ligand-binding domain (LBD). The mousetrap model postulates that helix 12 is positioned away from the domain to expose the interior cavity. However, the extended form of helix 12 is likely due to artifacts during crystallization. In this study, we set out to investigate conformational dynamics of apo VDR using molecular dynamics simulation on microsecond timescale. Here we show the neighboring backbones of helix 2-helix 3n and beta strand 2-helix 6 of LBD, instead of the helix 12, undergo large-scale motion, possibly gating the entrance of ligand to the ligand binding domain. Docking analysis to the simulated open structure of VDR with the estimated free energy of -37.0 kJ/mol, would emphasise the role of H2-H3n and S2-H6 in facilitating the entrance of calcitriol to the LBD of VDR.
    MeSH terms: Apoproteins/metabolism; Apoproteins/chemistry; Binding Sites; Humans; Ligands; Models, Molecular; Protein Conformation; Receptors, Calcitriol/metabolism; Receptors, Calcitriol/chemistry*; Principal Component Analysis; Molecular Dynamics Simulation; Molecular Docking Simulation; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand
  2. Nazree NE, Mohamed Z, Reynolds GP, Mohd Zain S, Masiran R, Sidi H, et al.
    Asia Pac Psychiatry, 2016 Dec;8(4):260-268.
    PMID: 27787964 DOI: 10.1111/appy.12210
    INTRODUCTION: The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population.

    METHODS: This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction.

    RESULTS: The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013).

    DISCUSSION: This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs.

    MeSH terms: Adult; Cross-Sectional Studies; Depressive Disorder, Major/drug therapy*; Female; Humans; Methionine/genetics; Middle Aged; Polymorphism, Genetic; Sexual Dysfunction, Physiological/chemically induced*; Sexual Dysfunction, Physiological/genetics*; Sexual Dysfunction, Physiological/psychology; Valine/genetics; Serotonin Uptake Inhibitors/adverse effects*; Brain-Derived Neurotrophic Factor/genetics*; Family Conflict/psychology*
  3. Norahmad NA, Mohd Abd Razak MR, Abdullah NR, Sastu UR, Imwong M, Muniandy PK, et al.
    PLoS One, 2016;11(10):e0165515.
    PMID: 27788228 DOI: 10.1371/journal.pone.0165515
    Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.
    MeSH terms: Adult; Alleles; Antimalarials/pharmacology*; Antimalarials/therapeutic use; Child; Chloroquine/pharmacology; Chloroquine/therapeutic use; Drug Combinations; Drug Resistance/genetics*; Humans; Malaysia; Plasmodium falciparum/genetics*; Plasmodium falciparum/physiology*; Pyrimethamine/pharmacology; Pyrimethamine/therapeutic use; Sulfadoxine/pharmacology; Sulfadoxine/therapeutic use; Biomarkers/metabolism; Protozoan Proteins/genetics; Malaria, Falciparum/drug therapy*; Point Mutation; Gene Dosage
  4. Mostafa H, Amin AM, Teh CH, Murugaiyah V, Arif NH, Ibrahim B
    Drug Alcohol Depend, 2016 12 01;169:80-84.
    PMID: 27788404 DOI: 10.1016/j.drugalcdep.2016.10.016
    BACKGROUND: Alcohol-dependence (AD) is a ravaging public health and social problem. AD diagnosis depends on questionnaires and some biomarkers, which lack specificity and sensitivity, however, often leading to less precise diagnosis, as well as delaying treatment. This represents a great burden, not only on AD individuals but also on their families. Metabolomics using nuclear magnetic resonance spectroscopy (NMR) can provide novel techniques for the identification of novel biomarkers of AD. These putative biomarkers can facilitate early diagnosis of AD.

    OBJECTIVES: To identify novel biomarkers able to discriminate between alcohol-dependent, non-AD alcohol drinkers and controls using metabolomics.

    METHOD: Urine samples were collected from 30 alcohol-dependent persons who did not yet start AD treatment, 54 social drinkers and 60 controls, who were then analysed using NMR. Data analysis was done using multivariate analysis including principal component analysis (PCA) and orthogonal partial least square-discriminate analysis (OPLS-DA), followed by univariate and multivariate logistic regression to develop the discriminatory model. The reproducibility was done using intraclass correlation coefficient (ICC).

    RESULTS: The OPLS-DA revealed significant discrimination between AD and other groups with sensitivity 86.21%, specificity 97.25% and accuracy 94.93%. Six biomarkers were significantly associated with AD in the multivariate logistic regression model. These biomarkers were cis-aconitic acid, citric acid, alanine, lactic acid, 1,2-propanediol and 2-hydroxyisovaleric acid. The reproducibility of all biomarkers was excellent (0.81-1.0).

    CONCLUSION: This study revealed that metabolomics analysis of urine using NMR identified AD novel biomarkers which can discriminate AD from social drinkers and controls with high accuracy.

    MeSH terms: Adult; Alcohol Drinking/epidemiology*; Alcohol Drinking/urine*; Alcoholism/diagnosis; Alcoholism/epidemiology*; Alcoholism/urine*; Cross-Sectional Studies; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Magnetic Resonance Spectroscopy/methods; Phenotype*; Valerates/urine; Reproducibility of Results; Biomarkers/urine; Metabolomics/methods*; Young Adult
  5. Huy BV, Teeraananchai S, Oanh LN, Tucker J, Kurniati N, Hansudewechakul R, et al.
    Journal of virus eradication, 2016 Oct 05;2(4):227-231.
    PMID: 27781105
    An analysis of the impact of orphanhood at antiretroviral therapy (ART) initiation on HIV outcomes in Asia included 4300 children; 51% were male. At ART initiation, 1805 (42%) were non-orphans (median age: 3 years), 1437 (33%) were single orphans (6 years) and 1058 (25%) were double orphans (7 years). Ten-year post-ART survival was 93.4-95.2% across orphan categories. Clinic transfers were higher among single and double orphans than non-orphans (41% vs 11%, P<0.001). On multivariate analysis, children ≥3 years at ART initiation (hazard ratio 1.58 vs <3 years, 95% confidence interval: 1.11-2.24) were more likely to be lost to follow-up. Although post-ART mortality and retention did not differ by orphan status, orphans were at greater risk of starting ART at older ages, and with more severe immunosuppression and poorer growth.
    MeSH terms: Aged; Ambulatory Care Facilities; Asia; Child; Child, Preschool; Female; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; HIV Infections; Multivariate Analysis; Confidence Intervals; Child, Orphaned; Lost to Follow-Up
  6. Latip W, Raja Abd Rahman RNZ, Chor Leow AT, Mohd Shariff F, Mohamad Ali MS
    PeerJ, 2016;4:e2420.
    PMID: 27781152 DOI: 10.7717/peerj.2420
    A gene encoding a thermotolerant lipase with broad pH was isolated from an Antarctic Pseudomonas strain AMS3. The recombinant lipase AMS3 was purified by single-step purification using affinity chromatography, yielding a purification fold of approximately 1.52 and a recovery of 50%. The molecular weight was approximately ∼60 kDa including the strep and affinity tags. Interestingly, the purified Antarctic AMS3 lipase exhibited broad temperature profile from 10-70 °C and stable over a broad pH range from 5.0 to pH 10.0. Various mono and divalent metal ions increased the activity of the AMS3 lipase, but Ni(2+) decreased its activity. The purified lipase exhibited the highest activity in the presence of sunflower oil. In addition, the enzyme activity in 25% v/v solvents at 50 °C particularly to n-hexane, DMSO and methanol could be useful for catalysis reaction in organic solvent and at broad temperature.
    MeSH terms: Methanol; Antarctic Regions; Catalysis; Chromatography, Affinity; Dimethyl Sulfoxide; Hydrogen-Ion Concentration; Ions; Lipase; Molecular Weight; Pseudomonas; Solvents; Temperature; Thermotolerance
  7. Moradipoor S, Ismail P, Etemad A, Wan Sulaiman WA, Ahmadloo S
    Biomed Res Int, 2016;2016:1845638.
    PMID: 27781209 DOI: 10.1155/2016/1845638
    Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM) and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT(2) Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.
    MeSH terms: Cardiovascular Diseases/genetics; Cardiovascular Diseases/metabolism; Diabetes Mellitus, Type 2/genetics*; Diabetes Mellitus, Type 2/metabolism*; Female; Humans; Malaysia; Male; Middle Aged; Prediabetic State*; Prediabetic State/genetics*; Prediabetic State/metabolism*; Down-Regulation/genetics; Up-Regulation/genetics; Endothelial Cells/metabolism*; Transcriptome/genetics*
  8. Gupta A, Low WL, Radecka I, Britland ST, Mohd Amin MC, Martin C
    J Microencapsul, 2016 Dec;33(8):725-734.
    PMID: 27781557 DOI: 10.1080/02652048.2016.1253796
    Wounds that remain in the inflammatory phase for a prolonged period of time are likely to be colonised and infected by a range of commensal and pathogenic microorganisms. Treatment associated with these types of wounds mainly focuses on controlling infection and providing an optimum environment capable of facilitating re-epithelialisation, thus promoting wound healing. Hydrogels have attracted vast interest as moist wound-responsive dressing materials. In the current study, biosynthetic bacterial cellulose hydrogels synthesised by Gluconacetobacter xylinus and subsequently loaded with silver were characterised and investigated for their antimicrobial activity against two representative wound infecting pathogens, namely S. aureus and P. aeruginosa. Silver nitrate and silver zeolite provided the source of silver and loading parameters were optimised based on experimental findings. The results indicate that both AgNO3 and AgZ loaded biosynthetic hydrogels possess antimicrobial activity (p 
    MeSH terms: Anti-Bacterial Agents/administration & dosage*; Anti-Bacterial Agents/pharmacology; Cellulose/chemistry*; Polysaccharides, Bacterial/chemistry*; Pseudomonas aeruginosa/drug effects; Pseudomonas Infections/drug therapy; Silver/administration & dosage*; Silver/pharmacology; Staphylococcal Infections/drug therapy; Staphylococcus aureus/drug effects; Wound Infection/drug therapy; Drug Delivery Systems/methods; Hydrogels/chemistry; Gluconacetobacter xylinus/chemistry*
  9. Lim TS
    Curr Pharm Des, 2016 10 27;22(43):6477-6479.
    PMID: 27781936 DOI: 10.2174/1381612822999161019110228
    MeSH terms: Antibodies, Monoclonal/genetics; Antibodies, Monoclonal/immunology*; Bacteriophages/genetics*; Humans; Peptide Library
  10. Paka C, Kamisan Atan I, Rios R, Dietz HP
    Female Pelvic Med Reconstr Surg, 2016 10 27;23(4):238-243.
    PMID: 27782978 DOI: 10.1097/SPV.0000000000000350
    OBJECTIVE: The aim of this study was to investigate the association of the anatomic integrity of the external anal sphincter (EAS) detected on transperineal ultrasound (TPUS) with symptoms of anal incontinence (AI) as measured by St Mark's Incontinence Score (SMIS) and the visual analog scale (VAS).

    METHODS: This is an observational, cross-sectional analysis of 486 women who presented to a tertiary urogynecological center between May 2013 and August 2014. They underwent a standardized interview and an examination that involved 3-dimensional/4-dimensional TPUS. The SMIS and VAS were administered if they answered positively to a question on AI. The association between defects of the EAS and symptoms of AI was evaluated using bivariate tests, as well as adjusting for pertinent covariates using multiple linear regression modeling.

    RESULTS: Of the included patients, 17.1% reported AI, and 15.2% had significant EAS defects (≥4 slices) on TPUS imaging. A significant sonographic defect was diagnosed in 23% of women with AI versus 14% of those without (P = 0.033). Women with symptoms of AI were more likely to have a significant defect on TPUS (odds ratio, 1.878; 95% confidence interval, 1.05-3.37). No significant findings were seen when analyzing SMIS, its components, and VAS against sonographic EAS defects.

    CONCLUSIONS: The symptom of AI is associated with significant EAS defects detected on TPUS. However, this study failed to show an association between significant EAS defects and the SMIS and VAS.

    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Fecal Incontinence/etiology*; Fecal Incontinence/physiopathology; Female; Humans; Middle Aged; Pain Measurement; Surveys and Questionnaires; Risk Factors; Ultrasonography; Linear Models; Case-Control Studies; Imaging, Three-Dimensional; Young Adult
  11. Suriawati AA, Majid HA, Al-Sadat N, Mohamed MN, Jalaludin MY
    Nutrients, 2016 Oct 24;8(10).
    PMID: 27783041
    BACKGROUND: Dietary calcium and vitamin D are essential for bone development. Apart from diet, physical activity may potentially improve and sustain bone health.

    OBJECTIVE: To investigate the relationship between the dietary intake of calcium and vitamin D, physical activity, and bone mineral content (BMC) in 13-year-old Malaysian adolescents.

    DESIGN: Cross-sectional.

    SETTING: Selected public secondary schools from the central and northern regions of Peninsular Malaysia.

    PARTICIPANTS: The subjects were from the Malaysian Health and Adolescents Longitudinal Research Team Cohort study (MyHeARTs).

    METHODS: The data included seven-day diet histories, anthropometric measurements, and the BMC of calcaneal bone using a portable broadband ultrasound bone densitometer. Nutritionist Pro software was used to calculate the dietary calcium and vitamin D intakes from the diet histories, based on the Nutrient Composition of Malaysian Food Database guidance for the dietary calcium intake and the Singapore Energy and Nutrient Composition of Food Database for vitamin D intake.

    RESULTS: A total of 289 adolescents (65.7% females) were recruited. The average dietary intakes of calcium and vitamin D were 377 ± 12 mg/day and 2.51 ± 0.12 µg/day, respectively, with the majority of subjects failing to meet the Recommended Nutrient Intake (RNI) of Malaysia for dietary calcium and vitamin D. All the subjects had a normal Z-score for the BMC (-2.00 or higher) with a mean of 0.55 ± 0.01. From the statistical analysis of the factors contributing to BMC, it was found that for those subjects with a higher intake of vitamin D, a higher combination of the intake of vitamin D and calcium resulted in significantly higher BMC quartiles. The regression analysis showed that the BMC might have been influenced by the vitamin D intake.

    CONCLUSIONS: A combination of the intake of vitamin D and calcium is positively associated with the BMC.

    MeSH terms: Adolescent; Anthropometry; Calcaneus/physiology; Calcium, Dietary/analysis*; Cross-Sectional Studies; Diet; Diet Surveys; Eating/physiology*; Female; Humans; Longitudinal Studies; Malaysia; Male; Regression Analysis; Students*; Vitamin D/analysis*; Exercise*; Absorptiometry, Photon; Bone Density*
  12. Bera H, Chigurupati S
    Eur J Med Chem, 2016 Nov 29;124:992-1003.
    PMID: 27783978 DOI: 10.1016/j.ejmech.2016.10.032
    Thymidine phosphorylase (TP, EC 2.4.2.4), an enzyme involved in pyrimidine salvage pathway, is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is extremely upregulated in a variety of solid tumours. The TP amplification is associated with concomitant overexpression of many angiogenic factors such as matrix metalloproteases (MMPs), interleukins (ILs), vascular endothelial growth factor (VEGF) etc., resulting in promotion of angiogenesis and cancer metastasis. In addition, overshooting TP level protects tumour cells from apoptosis and helps cell survival. Thus, TP is identified as a prime target for developing novel anticancer therapies. Pioneering research activities investigated a large number of TP inhibitors, most of which are pyrimidine or purine analogues. Recently, an array of structurally diverse non-nucleobase derivatives was designed, synthesized and established as promising TP inhibitors. This review, following an outline on the TP structure and functions, gives an overview of the recent advancement of various non-nucleobase TP inhibitors as novel anti-cancer agents.
    MeSH terms: Animals; Antineoplastic Agents/pharmacology*; Antineoplastic Agents/therapeutic use; Antineoplastic Agents/chemistry; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/therapeutic use; Enzyme Inhibitors/chemistry; Humans; Neoplasms/drug therapy*; Neoplasms/enzymology*; Neoplasms/pathology; Thymidine Phosphorylase/antagonists & inhibitors*; Thymidine Phosphorylase/metabolism; Thymidine Phosphorylase/chemistry; Drug Discovery/methods*; Carcinogenesis/drug effects
  13. Freisling H, Pisa PT, Ferrari P, Byrnes G, Moskal A, Dahm CC, et al.
    Eur J Nutr, 2016 Sep;55(6):2093-104.
    PMID: 26303194 DOI: 10.1007/s00394-015-1023-x
    PURPOSE: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.

    METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.

    RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.

    CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

    MeSH terms: Adult; Aged; Ascorbic Acid/administration & dosage; Calcium, Dietary/administration & dosage; Diet*; Dietary Fiber/administration & dosage; Dietary Proteins/administration & dosage; Europe; Female; Folic Acid/administration & dosage; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Surveys and Questionnaires; Riboflavin/administration & dosage; Weight Gain*; Nutrition Assessment; Linear Models; Phosphorus, Dietary/administration & dosage; beta Carotene/administration & dosage
  14. Duarte-Salles T, Misra S, Stepien M, Plymoth A, Muller D, Overvad K, et al.
    Cancer Prev Res (Phila), 2016 Sep;9(9):758-65.
    PMID: 27339170 DOI: 10.1158/1940-6207.CAPR-15-0434
    We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and α-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. Cancer Prev Res; 9(9); 758-65. ©2016 AACR.
    MeSH terms: Adult; Aged; Aged, 80 and over; alpha-Fetoproteins/analysis; Europe; Female; Carcinoma, Hepatocellular/blood*; Carcinoma, Hepatocellular/epidemiology; Humans; Liver Neoplasms/blood*; Liver Neoplasms/epidemiology; Male; Middle Aged; ROC Curve; Biomarkers, Tumor/blood*; Incidence; Odds Ratio; Case-Control Studies; Area Under Curve; Osteopontin/blood*; Early Detection of Cancer/methods*; Young Adult
  15. Farooqui M, Hassali MA, Shatar AK, Farooqui MA, Saleem F, Haq NU, et al.
    J Tradit Complement Med, 2016 Oct;6(4):321-326.
    PMID: 27774413
    The use of Complementary and Alternative Medicine (CAM; bǔ chōng yǔ tì dài yī xué) has been rapidly increasing among cancer patients. However, this pervasiveness is still largely unexplored among Malaysian cancer patients. The current study aimed to evaluate the patterns of CAM use among cancer patients from a local hospital in Malaysia. In addition, the study focused on the information-seeking behavior and CAM use disclosure to doctors. Of 393 patients, 184 (46.1%) had used CAM for their cancers. CAM usage was significantly associated with gender (p = 0.021), level of education (p = 0.001), employment status (p = 0.02), and monthly income (p 
    MeSH terms: Complementary Therapies; Cross-Sectional Studies; Hospitals; Humans; Malaysia; Neoplasms
  16. Singh H, Prakash A, Kalia AN, Majeed AB
    J Tradit Complement Med, 2016 Oct;6(4):370-376.
    PMID: 27774421
    Previously explored combination therapies mostly involved the use of bioactive molecules. It is believed that herbal compounds containing multiple plant products have synergistic hepatoprotective effects and could enhance the desired actions. To investigate the combination of ethanolic fruits extract of Solanum xanthocarpum (SX) and Juniperus communis (JC) against Paracetamol (PCM) and Azithromycin (AZM) induced liver toxicity in rats. Liver toxicity was induced by combine oral administration of PCM (250 mg/kg) and AZM (200 mg/kg) for 7 days in Wistar rats. Fruit extract of SX (200 and 400 mg/kg) and JC (200 and 400 mg/kg) were administered daily for 14 days. The hepatoprotective activity was assessed using liver functional test, oxidative parameters and histopathological examination. The results demonstrated that combine administration of AZM and PCM significantly produced liver toxicity by increasing the serum level of hepatic enzymes and oxidative parameters in liver of rats. Histopathological examination also indicated that AZM and PCM produced liver damage in rats. Chronic treatment of SX and JC extract significantly and dose-dependently attenuated the liver toxicity by normalizing the biochemical factors and no gross histopathological changes were observed in liver of rats. Furthermore, combine administration of lower dose of SX and JC significantly potentiated their hepatoprotective effect which was significant as compared to their effect per se. The results clearly indicated that SX and JC extract has hepatoprotective potential against AZM and PCM induced liver toxicity due to their synergistic anti-oxidant properties.
  17. Zhou J, Lam B, Neogi SG, Yeo GS, Azizan EA, Brown MJ
    Hypertension, 2016 12;68(6):1424-1431.
    PMID: 27777363
    Primary aldosteronism is present in ≈10% of hypertensives. We previously performed a microarray assay on aldosterone-producing adenomas and their paired zona glomerulosa and fasciculata. Confirmation of top genes validated the study design and functional experiments of zona glomerulosa selective genes established the role of the encoded proteins in aldosterone regulation. In this study, we further analyzed our microarray data using AmiGO 2 for gene ontology enrichment and Ingenuity Pathway Analysis to identify potential biological processes and canonical pathways involved in pathological and physiological aldosterone regulation. Genes differentially regulated in aldosterone-producing adenoma and zona glomerulosa were associated with steroid metabolic processes gene ontology terms. Terms related to the Wnt signaling pathway were enriched in zona glomerulosa only. Ingenuity Pathway Analysis showed "NRF2-mediated oxidative stress response pathway" and "LPS (lipopolysaccharide)/IL-1 (interleukin-1)-mediated inhibition of RXR (retinoid X receptor) function" were affected in both aldosterone-producing adenoma and zona glomerulosa with associated genes having up to 21- and 8-fold differences, respectively. Comparing KCNJ5-mutant aldosterone-producing adenoma, zona glomerulosa, and zona fasciculata samples with wild-type samples, 138, 56, and 59 genes were differentially expressed, respectively (fold-change >2; P<0.05). ACSS3, encoding the enzyme that synthesizes acetyl-CoA, was the top gene upregulated in KCNJ5-mutant aldosterone-producing adenoma compared with wild-type. NEFM, a gene highly upregulated in zona glomerulosa, was upregulated in KCNJ5 wild-type aldosterone-producing adenomas. NR4A2, the transcription factor for aldosterone synthase, was highly expressed in zona fasciculata adjacent to a KCNJ5-mutant aldosterone-producing adenoma. Further interrogation of these genes and pathways could potentially provide further insights into the pathology of primary aldosteronism.
    MeSH terms: Adenoma/genetics*; Adenoma/physiopathology; Adrenal Cortex/pathology; Adrenal Cortex/physiology; Aldosterone/metabolism*; Gene Expression Regulation; Humans; Hyperaldosteronism/genetics*; Hyperaldosteronism/physiopathology; Pheochromocytoma/genetics; Pheochromocytoma/physiopathology; Sampling Studies; Transcription Factors/genetics*; Zona Fasciculata/metabolism; Zona Glomerulosa/metabolism; Up-Regulation; Gene Expression Profiling; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics*; Wnt Signaling Pathway
  18. Gaffney D, Small B, Kitchener H, Young Ryu S, Viswanathan A, Trimble T, et al.
    Int. J. Gynecol. Cancer, 2016 11;26(9):1690-1693.
    PMID: 27779548
    Eighty-seven percent of cervix cancer occurs in less-developed regions of the world, and there is up to an 18-fold difference in mortality rate for cervix cancer depending on the region of the world. The Cervix Cancer Research Network (CCRN) was founded through the Gynecologic Cancer InterGroup with the aim of improving access to clinical trials in cervix cancer worldwide, and in so doing improving standards of care. The CCRN recently held its first international educational symposium in Bangkok. Sixty-two participants attended from 16 different countries including Pakistan, India, Bangladesh, Thailand, Malaysia, Singapore, Philippines, Taiwan, China, Vietnam, Korea, Japan, Columbia, Brazil, Canada, and the United States. The focus of this symposium was to evaluate progress, to promote new clinical trials for the CCRN, and to provide education regarding the role of brachytherapy in the treatment of cervical cancer.
    MeSH terms: Brachytherapy; Uterine Cervical Neoplasms/radiotherapy*; Developing Countries*; Female; Humans
  19. Leong XY, Thanikachalam PV, Pandey M, Ramamurthy S
    Biomed Pharmacother, 2016 Dec;84:1051-1060.
    PMID: 27780133 DOI: 10.1016/j.biopha.2016.10.044
    BACKGROUND: Swertiamarin, is a secoiridoid glycoside found in genera of Enicostemma Species (Enicostemma littorale and Enicostemma axillare) belonging to the family of gentianaceae, which has been reported to cure many diseases such as diabetes, hypertension, atherosclerosis, arthritis, malaria and abdominal ulcers. However, to the best of our knowledge, till date systematic studies to understand the molecular basis of cardiac and metabolic disease preventing properties of swertiamarin has not been reported.

    AIM OF THE REVIEW: The present review aims to compile an up-to-date information on the progress made in the protective role of swertiamarin in cardiac and metabolic diseases with the objective of providing a guide for future research on this bioactive molecule.

    MATERIALS AND METHODS: Information on the swertiamarin was collected from major scientific databases (Pubmed, Springer, google scholar, and Web of Science) for publication between1974-2016. In this review, the protective role of swertiamarin on cardiac and metabolic diseases was discussed.

    RESULTS: Swertiamarin reported to exhibit a wide range of biological activities such as anti-atherosclerotic, antidiabetic, anti-inflammatory and antioxidant effects. These activities were mainly due to its effect on various signaling pathways associated with cardiac remodeling events such as inhibition of NF-kB expression, LDL oxidation, apoptosis, inflammatory and lipid peroxidation markers and stimulation of antioxidant enzymes.

    CONCLUSION: Sweriamarin exhibit a wide range of biological activities. This review presents evidence supporting the point of view that swertiamarin should be considered a potential therapeutic agent against cardiac and metabolic diseases, giving rise to novel applications in their prevention and treatment.

    MeSH terms: Animals; Anti-Inflammatory Agents/adverse effects; Anti-Inflammatory Agents/pharmacokinetics; Anti-Inflammatory Agents/therapeutic use*; Antioxidants/adverse effects; Antioxidants/pharmacokinetics; Antioxidants/therapeutic use*; Cardiovascular Diseases/drug therapy*; Humans; Hypoglycemic Agents/adverse effects; Hypoglycemic Agents/pharmacokinetics; Hypoglycemic Agents/therapeutic use*; Phytotherapy; Metabolic Diseases/drug therapy*; Plants, Medicinal; Pyrones/adverse effects; Pyrones/pharmacokinetics; Pyrones/therapeutic use*; Gentianaceae; Iridoid Glucosides/adverse effects; Iridoid Glucosides/pharmacokinetics; Iridoid Glucosides/therapeutic use*
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