Browse publications by year: 2018

Fulltext Polymethoxyflavones fromNicotiana plumbaginifolia(Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice

Shajib MS, Rashid RB, Ming LC, Islam S, Sarker MMR, Nahar L, et al.

Front Pharmacol, 2018;9:85.
PMID: 29515437 DOI: 10.3389/fphar.2018.00085

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties.Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone (1), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone (3), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified fromN. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds1,3, and4(12.5-25 mg/kg b.w.) exhibited dose-dependent and significant (p< 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound1,3, and4(12.5 mg/kg b.w.) demonstrated significant (p< 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAAreceptor in the action of compound3and4was evident from the reversal effects of flumazenil. In addition, compounds1and4(12.5-25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1-4) fromN. Plumbaginifoliacould be considered as suitable candidates for the development of analgesic and anxiolytic agents.

MeSH terms: Adenosine Triphosphate; Analgesics; Anti-Inflammatory Agents; Carrageenan; Edema; Flavonoids; Flumazenil; Formaldehyde; Glyburide; Naloxone; Pain; Tobacco; Anti-Anxiety Agents; Maze Learning; Acetic Acid
Fulltext Resveratrol-Potential Antibacterial Agent against Foodborne Pathogens

Ma DSL, Tan LT, Chan KG, Yap WH, Pusparajah P, Chuah LH, et al.

Front Pharmacol, 2018;9:102.
PMID: 29515440 DOI: 10.3389/fphar.2018.00102

Bacterial foodborne pathogens are a significant health burden and the recent emergence of pathogenic resistant strains due to the excessive use of antibiotics makes it more difficult to effectively treat infections as a result of contaminated food. Awareness of this impending health crisis has spurred the search for alternative antimicrobials with natural plant antimicrobials being among the more promising candidates as these substances have good acceptability and likely low toxicity levels as they have long been used in traditional medicines. Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring stilbenoid which has been gaining considerable attention in medical field due to its diverse biological activities - it has been reported to exhibit antioxidant, cardioprotective, anti-diabetic, anticancer, and antiaging properties. Given that resveratrol is phytoalexin, with increased synthesis in response to infection by phytopathogens, there has been interest in exploring its antimicrobial activity. This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.

MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents; Antioxidants; Attention; Sesquiterpenes; Stilbenes; Food Packaging
Fulltext Human Hand Motion Analysis during Different Eating Activities

Hussain Z, Zainul Azlan N, Yusof AZB

Appl Bionics Biomech, 2018;2018:8567648.
PMID: 29515649 DOI: 10.1155/2018/8567648

The focus of this research is to analyse both human hand motion and force, during eating, with respect to differing food characteristics and cutlery (including a fork and a spoon). A glove consisting of bend and force sensors has been used to capture the motion and contact force exerted by fingers during different eating activities. The Pearson correlation coefficient has been used to show that a significant linear relationship exists between the bending motion of the fingers and the forces exerted during eating. Analysis of variance (ANOVA) and independent samplest-tests are performed to establish whether the motion and force exerted by the fingers while eating is influenced by the different food characteristics and cutlery. The middle finger motion showed the least positive correlation with index fingertip and thumb-tip force, irrespective of the food characteristics and cutlery used. The ANOVA andt-test results revealed that bending motion of the index finger and thumb varies with respect to differing food characteristics and the type of cutlery used (fork/spoon), whereas the bending motion of the middle finger remains unaffected. Additionally, the contact forces exerted by the thumb tip and index fingertip remain unaffected with respect to differing food types and cutlery used.
Fulltext Sugarcane juice derived carbon dot-graphitic carbon nitride composites for bisphenol A degradation under sunlight irradiation

Sim LC, Wong JL, Hak CH, Tai JY, Leong KH, Saravanan P

Beilstein J Nanotechnol, 2018;9:353-363.
PMID: 29515949 DOI: 10.3762/bjnano.9.35

Carbon dots (CDs) and graphitic carbon nitride (g-C3N4) composites (CD/g-C3N4) were successfully synthesized by a hydrothermal method using urea and sugarcane juice as starting materials. The chemical composition, morphological structure and optical properties of the composites and CDs were characterized using various spectroscopic techniques as well as transmission electron microscopy. X-ray photoelectron spectroscopy (XPS) results revealed new signals for carbonyl and carboxyl groups originating from the CDs in CD/g-C3N4 composites while X-ray diffraction (XRD) results showed distortion of the host matrix after incorporating CDs into g-C3N4. Both analyses signified the interaction between g-C3N4 and CDs. The photoluminescence (PL) analysis indicated that the presence of too many CDs will create trap states at the CD/g-C3N4 interface, decelerating the electron (e-) transport. However, the CD/g-C3N4(0.5) composite with the highest coverage of CDs still achieved the best bisphenol A (BPA) degradation rate at 3.87 times higher than that of g-C3N4. Hence, the charge separation efficiency should not be one of the main factors responsible for the enhancement of the photocatalytic activity of CD/g-C3N4. Instead, the light absorption capability was the dominant factor since the photoreactivity correlated well with the ultraviolet-visible diffuse reflectance spectra (UV-vis DRS) results. Although the CDs did not display upconversion photoluminescence (UCPL) properties, the π-conjugated CDs served as a photosensitizer (like organic dyes) to sensitize g-C3N4 and injected electrons to the conduction band (CB) of g-C3N4, resulting in the extended absorption spectrum from the visible to the near-infrared (NIR) region. This extended spectral absorption allows for the generation of more electrons for the enhancement of BPA degradation. It was determined that the reactive radical species responsible for the photocatalytic activity were the superoxide anion radical (O2•-) and holes (h+) after performing multiple scavenging tests.
Evaluation of the Persistence and Leaching Behaviour of Thiram Fungicide in Soil, Water and Oil Palm Leaves

Maznah Z, Halimah M, Ismail BS

Bull Environ Contam Toxicol, 2018 May;100(5):677-682.
PMID: 29516138 DOI: 10.1007/s00128-018-2312-x

The residual levels and persistence of thiram in the soil, water and oil palm seedling leaves were investigated under field conditions. The experimental plots were carried out on a clay loam soil and applied with three treatments namely; manufacturer's recommended dosage (25.6 g a.i. plot-1), manufacturer's double recommended dosage (51.2 g a.i. plot-1), and control (water) were applied. Thiram residues were detected in the soil from day 0 to day 3 in the range of 0.22-27.04 mg kg-1. Low concentrations of thiram were observed in the water and leave samples in the range of 0.27-2.52 mg L-1 and 1.34-12.28 mg kg-1, respectively. Results have shown that thiram has a rapid degradation and has less persistence due to climatic factors. These findings suggest that thiram is safe when applied at manufacturer's recommended dosage on oil palm seedlings due to low residual levels observed in soil and water bodies.

MeSH terms: Environmental Monitoring; Fungicides, Industrial/analysis*; Soil/chemistry; Soil Pollutants/analysis; Thiram/analysis*; Water; Water Pollutants, Chemical/analysis; Plant Leaves/chemistry
Fulltext Prevalence of and risk factors for anal high-risk HPV among HIV-negative and HIV-positive MSM and transgender women in three countries at South-East Asia

Somia IKA, Teeratakulpisarn N, Jeo WS, Yee IA, Pankam T, Nonenoy S, et al.

Medicine (Baltimore), 2018 Mar;97(10):e9898.
PMID: 29517698 DOI: 10.1097/MD.0000000000009898

This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439 cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P

MeSH terms: Adult; Anal Canal/virology; Female; HIV Seropositivity/blood; HIV Seropositivity/epidemiology*; HIV Seropositivity/virology; Humans; Indonesia/epidemiology; Malaysia/epidemiology; Male; Middle Aged; Prospective Studies; Risk Factors; Thailand/epidemiology; HIV Infections/blood; HIV Infections/epidemiology*; HIV Infections/virology; Prevalence; HIV Seronegativity; CD4 Lymphocyte Count; Papillomaviridae; Papillomavirus Infections/blood; Papillomavirus Infections/epidemiology*; Papillomavirus Infections/virology; Transgender Persons/statistics & numerical data*; Sexual Minorities/statistics & numerical data*
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.

MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/chemistry*; Binding Sites; Cell Survival/drug effects; Drug Screening Assays, Antitumor; Flavonoids/chemical synthesis; Flavonoids/pharmacology*; Flavonoids/chemistry*; Humans; Magnetic Resonance Spectroscopy; Protein Binding; Structure-Activity Relationship; Drug Design*; Molecular Structure; Catalytic Domain; Chalcones/chemical synthesis; Chalcones/pharmacology*; Chalcones/chemistry*; Cell Proliferation/drug effects; Chemistry Techniques, Synthetic; MCF-7 Cells; Molecular Docking Simulation*
Fulltext Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis

Yu D, Zheng W, Johansson M, Lan Q, Park Y, White E, et al.

J Natl Cancer Inst, 2018 Aug 01;110(8):831-842.
PMID: 29518203 DOI: 10.1093/jnci/djx286

BACKGROUND: The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.
METHODS: We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated.
RESULTS: During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC.
CONCLUSIONS: The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.

MeSH terms: Adult; Aged; Female; Humans; Lung Neoplasms/etiology; Lung Neoplasms/epidemiology*; Male; Middle Aged; Obesity/complications; Obesity/epidemiology*; Risk Factors; Cohort Studies; Body Mass Index; Waist-Hip Ratio; Waist Circumference; Obesity, Abdominal/complications; Obesity, Abdominal/epidemiology*
Dentoalveolar Cleft Treatment Outcome Using Modified Huddart-Bodenham Index and Regression Analysis of Associated Factors

Arshad AI, Alam MK, Khamis MF

Cleft Palate Craniofac J, 2018 05;55(5):682-687.
PMID: 29518343 DOI: 10.1177/1055665618758278

OBJECTIVES: The aim of this study is to assess the treatment outcome of complete unilateral cleft lip and palate (CUCLP) patients using modified Huddart/Bodenham scoring system (MHB). To determine whether there is an association of congenital and postnatal factors with the treatment outcome.
DESIGN: Retrospective observational study.
SETTING: Two regional cleft-referral centers.
MAIN OUTCOME MEASURES: In the current study, 101 pairs of dental models of non-syndromic CUCLP patients were retrieved from hospital archives. Each occlusal relationship from central incisor till the first permanent molars were scored except the lateral incisor. Sum of 10 occlusal relationships in each study sample gave a total occlusion score. The primary outcome was the mean total occlusion score.
RESULTS: According to MHB, a mean (standard deviation) total occlusion score of -8.92 (6.89) was determined. Based on treatment outcome, 66 cases were favorable (grades 1, 2, and 3) and 35 cases were unfavorable (grades 4 and 5). Chi-square tests indicated, difference of cheiloplasty ( P = .001) and palatoplasty ( P < .001) statistically significant. Five variables-gender, family history of cleft, cleft side, cheiloplasty, and palatoplasty-were analyzed with a logistic regression model.
CONCLUSIONS: Final model indicated that cases treated with modified Millard technique (cheiloplasty) and Veau-Wardill-Kilner method (palatoplasty) had higher odds of unfavorable treatment outcome.

MeSH terms: Child; Cleft Lip/surgery*; Cleft Palate/surgery*; Dental Arch/abnormalities; Dental Models; Dental Occlusion*; Female; Humans; Male; Pakistan; Regression Analysis; Retrospective Studies; Treatment Outcome; Reconstructive Surgical Procedures/methods*
Fulltext Genetic and clinical characteristics of Chinese children with Glucokinase-maturity-onset diabetes of the young (GCK-MODY)

Li X, Ting TH, Sheng H, Liang CL, Shao Y, Jiang M, et al.

BMC Pediatr, 2018 03 06;18(1):101.
PMID: 29510678 DOI: 10.1186/s12887-018-1060-8

BACKGROUND: There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY.

METHODS: Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China. Clinical data were obtained from medical records. Blood was collected from the patients and their parents for glucokinase (GCK) gene analysis. Parents without diabetes were tested for fasting glucose and HbA1c. Clinical information and blood for GCK gene analysis were obtained from grandparents with diabetes. GCK gene mutational analysis was performed by polymerase chain reaction and direct sequencing. Patients without a GCK gene mutation were screened by targeted next-generation sequencing (NGS) technology for other MODY genes.

RESULTS: Nine children tested positive for GCK gene mutations while two were negative. The nine GCK-MODY patients were from unrelated families, aged 1 month to 9 years and 1 month at first detection of hyperglycaemia. Fasting glucose was elevated (6.1-8.5 mmol/L), HbA1c 5.2-6.7% (33.3-49.7 mmol/mol), both remained stable on follow-up over 9 months to 5 years. Five detected mutations had been previously reported: p.Val182Met, c.679 + 1G > A, p.Gly295Ser, p.Arg191Gln and p.Met41Thr. Four mutations were novel: c.483 + 2 T > A, p.Ser151del, p.Met57GlyfsX29 and p.Val374_Ala377del. No mutations were identified in the other two patients, who were also tested by NGS.

CONCLUSIONS: GCK gene mutations are detected in Chinese children and their family members with typical clinical features of GCK-MODY. Four novel mutations are detected.

MeSH terms: Child; Child, Preschool; China; Diabetes Mellitus, Type 2/diagnosis*; Diabetes Mellitus, Type 2/genetics*; DNA Mutational Analysis; Female; Follow-Up Studies; Genetic Markers; Glucokinase/genetics*; Humans; Infant; Male; Mutation; Prognosis
Fulltext Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia

Teo FMS, Nyo M, Wong AA, Tan NWH, Koh MT, Chan YF, et al.

Sci Rep, 2018 03 06;8(1):4087.
PMID: 29511232 DOI: 10.1038/s41598-018-22379-6

Hand, foot and mouth disease (HFMD) is a prevalent contagious childhood disease typically associated with fever, oral lesions and limb exanthema. While HFMD is caused by a plethora of serotypes of viruses under the genus Enterovirus within the Picornaviridae family, Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are considered the main etiological agents. In recent years however, other viruses have also been isolated in considerable numbers from infected individuals in many regions, joining the legion commonly associated with HFMD. The present study investigated the cytokine and chemokine profiles of HFMD patients from Singapore and Malaysia for the first time. Comparative cohort studies of EV-A71-associated HFMD cases revealed that the Malaysia cohort had a distinct profile from the Singapore cohort, and this could be partly attributed by different EV-A71 genotypes. As the isolation of CV-A6, instead of CV-A16, had become prevalent in the Singapore cohort, it was also of particular interest to study the differential cytokine and chemokine profiles. Our data revealed that overlapping as well as unique profiles exist between the two major causative clinical isolates in the Singapore cohort. Having a better understanding of the respective immunological profiles could be useful for more accurate HFMD diagnosis, which is imperative for disease transmission control until multi-valent vaccines and/or broad-spectrum anti-viral drugs become available.

MeSH terms: Enterovirus/classification*; Enterovirus/genetics; Enterovirus/isolation & purification*; Hand, Foot and Mouth Disease/pathology*; Hand, Foot and Mouth Disease/virology; Humans; Malaysia; Singapore; Cohort Studies; Cytokines/blood*
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.

MeSH terms: Animals; Bone Resorption/blood; Bone Resorption/drug therapy*; Bone Resorption/physiopathology; Buserelin/administration & dosage*; Calcium/blood; Disease Models, Animal; Humans; Gonadotropin-Releasing Hormone/blood; Gonadotropin-Releasing Hormone/agonists; Male; Orchiectomy; Osteoporosis/blood; Osteoporosis/chemically induced; Osteoporosis/drug therapy*; Osteoporosis/physiopathology; Prostatic Neoplasms/complications; Prostatic Neoplasms/drug therapy*; Testosterone/blood; Testosterone/deficiency; Rats
Fulltext Assessment of self-reporting reading of medicine's labels and the resources of information about medicines in general public in Malaysia

Dawood OT, Hassali MA, Saleem F, Ibrahim IR

Pharmacol Res Perspect, 2018 04;6(2):e00387.
PMID: 29511566 DOI: 10.1002/prp2.387

This study was undertaken to assess the people's self-reported reading of medicine labels and its associated factors and to assess the sources of information about medicines among general public. A cross-sectional study was carried out among general public in the State of Penang, Malaysia. A total of 888 participants were conveniently selected and completed the survey. A self-administered questionnaire was used to obtain the data from all the participants. Most of the participants (74.2%) reported that they have adequate information about medicines provided on their medicine labels. In addition, 86.9% of them reported that they read their medicine's label for the directions of usage and 84.3% for the dosage instruction. However, 42.1% of the participants do not read their medicine's label for the active ingredients, and 33% of them do not read their medicine's label for the safety information. In addition, 36.5% of the respondents did not read the label of medicine for the symptoms which can be used for. However, females, Malay respondents, and higher education level (college/university) were more likely to self-reported the reading medicine's label. Females were more likely to read the labels of medicines compared with males (OR = 1.6, 95% CI 1.20-2.13, P = .001). The reading of medicine labels was predicted by females, Malay respondents, and higher educated people. Health educational programs are needed to clarify label's information that can help in concept of patient safety.

MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia; Male; Middle Aged; Surveys and Questionnaires; Reading*; Young Adult; Self Report
Fulltext Genetic variation and DNA fingerprinting of durian types in Malaysia using simple sequence repeat (SSR) markers

Siew GY, Ng WL, Tan SW, Alitheen NB, Tan SG, Yeap SK

PeerJ, 2018;6:e4266.
PMID: 29511604 DOI: 10.7717/peerj.4266

Durian (Durio zibethinus) is one of the most popular tropical fruits in Asia. To date, 126 durian types have been registered with the Department of Agriculture in Malaysia based on phenotypic characteristics. Classification based on morphology is convenient, easy, and fast but it suffers from phenotypic plasticity as a direct result of environmental factors and age. To overcome the limitation of morphological classification, there is a need to carry out genetic characterization of the various durian types. Such data is important for the evaluation and management of durian genetic resources in producing countries. In this study, simple sequence repeat (SSR) markers were used to study the genetic variation in 27 durian types from the germplasm collection of Universiti Putra Malaysia. Based on DNA sequences deposited in Genbank, seven pairs of primers were successfully designed to amplify SSR regions in the durian DNA samples. High levels of variation among the 27 durian types were observed (expected heterozygosity,H
E
= 0.35). The DNA fingerprinting power of SSR markers revealed by the combined probability of identity (PI) of all loci was 2.3×10-3. Unique DNA fingerprints were generated for 21 out of 27 durian types using five polymorphic SSR markers (the other two SSR markers were monomorphic). We further tested the utility of these markers by evaluating the clonal status of shared durian types from different germplasm collection sites, and found that some were not clones. The findings in this preliminary study not only shows the feasibility of using SSR markers for DNA fingerprinting of durian types, but also challenges the current classification of durian types, e.g., on whether the different types should be called "clones", "varieties", or "cultivars". Such matters have a direct impact on the regulation and management of durian genetic resources in the region.

MeSH terms: Adaptation, Physiological; Agriculture; Asia; DNA; Feasibility Studies; Fruit; Malaysia; Probability; United States; Genetic Variation; DNA Fingerprinting; DNA Primers; Microsatellite Repeats; Databases, Nucleic Acid; Bombacaceae
Fulltext Data on antibiogram and resistance genes harboured bySalmonellastrains and their Pulsed-field gel electrophoresis clusters

Chuah LO, Shamila Syuhada AK, Mohamad Suhaimi I, Farah Hanim T, Rusul G

Data Brief, 2018 Apr;17:698-702.
PMID: 29511712 DOI: 10.1016/j.dib.2018.01.098

This article describes the Pulsed-field gel electrophoresis clustering of the predominantSalmonellastrains (Salmonellaser. Albany,Salmonellaser. Brancaster, andSalmonellaser. Corvallis) isolated from poultry and processing environment in wet market and small-scale processing plant in Penang and Perlis, the northern states of Malaysia. Agar disk diffusion assay was performed to determine the phenotypic antibiotic resistance of theseSalmonellastrains. The most common antibiograms among the three predominantSalmonellaserovars were reported. The presence of integrase genes and antibiotic resistance genes conferring to resistance against β-lactams, aminoglycosides, tetracyclines, quinolones, sulphonamides and chloramphenicol, was detected via PCR amplification.

MeSH terms: Agar; Aminoglycosides; Animals; Anti-Bacterial Agents; Chloramphenicol; Drug Resistance, Microbial; Malaysia; Microbial Sensitivity Tests; Poultry; Protein Synthesis Inhibitors; Sulfonamides; Tetracyclines; Quinolones; Electrophoresis, Gel, Pulsed-Field; Integrases; beta-Lactams
Engineering ellipsoidal cap-like hydrogel particles as building blocks or sacrificial templates for three-dimensional cell culture

Zhang W, Huang G, Ng K, Ji Y, Gao B, Huang L, et al.

Biomater Sci, 2018 Mar 07.
PMID: 29511758 DOI: 10.1039/c7bm01186e

Hydrogel particles that can be engineered to compartmentally culture cells in a three-dimensional (3D) and high-throughput manner have attracted increasing interest in the biomedical area. However, the ability to generate hydrogel particles with specially designed structures and their potential biomedical applications need to be further explored. This work introduces a method for fabricating hydrogel particles in an ellipsoidal cap-like shape (i.e., ellipsoidal cap-like hydrogel particles) by employing an open-pore anodic aluminum oxide membrane. Hydrogel particles of different sizes are fabricated. The ability to produce ellipsoidal cap-like magnetic hydrogel particles with controlled distribution of magnetic nanoparticles is demonstrated. Encapsulated cells show high viability, indicating the potential for using these hydrogel particles as structure- and remote-controllable building blocks for tissue engineering application. Moreover, the hydrogel particles are also used as sacrificial templates for fabricating ellipsoidal cap-like concave wells, which are further applied for producing size controllable cell aggregates. The results are beneficial for the development of hydrogel particles and their applications in 3D cell culture.
Functional identification of the prnABCD operon and its regulation in Serratia plymuthica

Liu X, Yu X, Yang Y, Heeb S, Gao S, Chan KG, et al.

Appl Microbiol Biotechnol, 2018 Apr;102(8):3711-3721.
PMID: 29511844 DOI: 10.1007/s00253-018-8857-0

The antibiotic pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite that plays an important role in the biocontrol of plant diseases due to its broad-spectrum of antimicrobial activities. The PRN biosynthetic gene cluster remains to be characterised in Serratia plymuthica, though it is highly conserved in PRN-producing bacteria. To better understand PRN biosynthesis and its regulation in Serratia, the prnABCD operon from S. plymuthica G3 was cloned, sequenced and expressed in Escherichia coli DH5α. Furthermore, an engineered strain prnind which is a conditional mutant of G3 prnABCD under the control of the Ptac promoter was constructed. This mutant was able to overproduce PRN with isopropylthiogalactoside (IPTG) induction by overexpressing prnABCD, whilst behaving as a conditional mutant of G3 prnABCD in the absence of IPTG. These results confirmed that prnABCD is responsible for PRN biosynthesis in strain G3. Further experiments involving lux-/dsRed-based promoter fusions, combined with site-directed mutagenesis of the putative σS extended -10 region in the prnA promoter, and liquid chromatography-mass spectrometry (LC-MS) analysis extended our previous knowledge about G3, revealing that quorum sensing (QS) regulates PRN biosynthesis through cross talk with RpoS, which may directly activated prnABCD transcription. These findings suggest that PRN in S. plymuthica G3 is produced in a tightly controlled manner, and has diverse functions, such as modulation of cell motility, in addition to antimicrobial activities. Meanwhile, the construction of inducible mutants could be a powerful tool to improve PRN production, beyond its potential use for the investigation of the biological function of PRN.

MeSH terms: Mutation; Operon/genetics*; Pyrrolnitrin/biosynthesis*; Serratia/genetics*; Gene Expression Regulation, Bacterial*; Quorum Sensing/physiology
Selective isolation and characterisation of novel members of the family Nocardiopsaceae and other actinobacteria from a marine sediment of Tioman Island

Ng ZY, Tan GYA

Antonie Van Leeuwenhoek, 2018 May;111(5):727-742.
PMID: 29511956 DOI: 10.1007/s10482-018-1042-8

Tioman Island is one of many sources for underexplored actinobacterial diversity in Malaysia. Selective isolation, molecular profiling, 16S rRNA gene sequencing and phylogenetic analyses were carried out to highlight the diversity of the marine actinobacterial community in a sediment collected off Tioman Island. A high number of diverse actinobacteria were recovered using skim milk/HEPES pre-treatment on a mannitol-based medium. A total of 123 actinobacterial strains were isolated, including thirty obligate marine actinobacteria putatively identified as Salinispora spp. Molecular fingerprinting profiles obtained with a double digestion approach grouped the remaining non-Salinispora-like strains into 24 different clusters, with Streptomyces and Blastococcus as the major clusters. A total of 17 strains were identified as novel actinobacterial species within the genera Streptomyces (n = 6), Blastococcus (n = 5), Marinactinospora (n = 3), Nocardiopsis (n = 1), Agromyces (n = 1) and Nonomuraea (n = 1) based on 16S rRNA gene sequence analyses. Polyphasic data from three putative Marinactinospora spp. showed that the strains represent a new genus in the Nocardiopsaceae family. Crude extracts from the strains were also found to inhibit the growth of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Providencia alcalifaciens) pathogens. Hierarchical clustering of the bioactivities of an active fraction revealed a unique profile, which is closely related that of fosfomycin.

MeSH terms: Anti-Bacterial Agents/pharmacology; Culture Media; DNA, Bacterial/genetics; Malaysia; Phylogeny*; RNA, Ribosomal, 16S/genetics; Cluster Analysis; Geologic Sediments/microbiology*; Actinobacteria/classification*; Actinobacteria/genetics; Actinobacteria/isolation & purification; Actinobacteria/physiology*; Biodiversity*; Islands
Occurrence of sweet refuse at disposal sites: rainwater retention capacity and potential breeding opportunities for Aedes aegypti

Dieng H, Satho T, Meli NKKB, Abang F, Nolasco-Hipolito C, Hakim H, et al.

Environ Sci Pollut Res Int, 2018 May;25(14):13833-13843.
PMID: 29512008 DOI: 10.1007/s11356-017-1078-8

Nectar is the staple diet of adult mosquitoes in the wild, but its availability is inconsistent and can be affected by rainfall. In urban centers, Aedes vectors commonly use man-made containers as their major habitat; however, they can colonize any items replenished by rainfall. Garbage output has increased significantly in recent years, at a time when collection frequency is reducing. Such garbage usually includes organic components, some of which are sweet and can be fed upon by other animals or become can containers for rainwater. Despite evidence that Aedes larvae can thrive in containers comprised of organic waste material, which can be produced by rodents gnawing on fruits or vegetables, and that adults can survive on sweet waste fluids, the capacity of organic waste materials to accumulate rainwater and act as egg deposition sites has not been examined. It is also unknown for how long sweet extracts can sustain the life of adult vectors. Here, we investigated the abundance of sweet leftovers at garbage sites and the rainwater retention capacity of some organic materials through a field survey and laboratory bioassays. We also examined whether sweet waste fluids impact egg hatching success and longevity of Aedes aegypti. The results of this study indicated that sweet products with leftovers are highly prevalent in garbage. When exposed to rain, food items (BAFrc, banana fruit resembling container; and BSPrc, boiled sweet potato resembling container) and the packaging of sweet foods (SMIc, sweetened condensed milk can) retained water. When provided an opportunity to oviposit in cups containing BAF extract (BAFex), BSP extract (BSPex), and SMI extract (SMIex), eggs were deposited in all media. Egg maturation in the BAFex environment resulted in similar larval eclosion success to that resulting from embryo development in a water milieu. Adults maintained on sweet waste extracts had long lifespans, although shorter than that of their sugar solution (SUS)-fed counterparts. Taken together, these results indicated that sweet waste materials are useful to dengue mosquitoes, acting both as oviposition sites and energy sources.

MeSH terms: Aedes/growth & development; Aedes/physiology*; Animals; Feeding Behavior; Garbage; Larva/growth & development; Larva/physiology; Longevity; Oviposition*; Rain*; Reproduction; Waste Disposal Facilities*
GENIPAC: A Genomic Information Portal for Head and Neck Cancer Cell Systems

Lee BKB, Gan CP, Chang JK, Tan JL, Fadlullah MZ, Abdul Rahman ZA, et al.

J Dent Res, 2018 07;97(8):909-916.
PMID: 29512401 DOI: 10.1177/0022034518759038

Head and neck cancer (HNC)-derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .

MeSH terms: Head and Neck Neoplasms/genetics*; Humans; Mutation; RNA, Messenger/analysis; Genome, Human; Internet*; Gene Expression Profiling; Genomics/methods*; Databases, Genetic*; Cell Line, Tumor*; DNA Copy Number Variations

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