Displaying publications 61 - 80 of 186 in total

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  1. Mutalib HA, Kaur S, Ghazali AR, Chinn Hooi N, Safie NH
    PMID: 25802534 DOI: 10.1155/2015/135987
    Purpose. An open-label pilot study of virgin coconut oil (VCO) was conducted to determine the safety of the agent as ocular rewetting eye drops on rabbits. Methods. Efficacy of the VCO was assessed by measuring NIBUT, anterior eye assessment, corneal staining, pH, and Schirmer value before instillation and at 30 min, 60 min, and two weeks after instillation. Friedman test was used to analyse any changes in all the measurable variables over the period of time. Results. Only conjunctival redness with instillation of saline agent showed significant difference over the period of time (P < 0.05). However, further statistical analysis had shown no significant difference at 30 min, 60 min, and two weeks compared to initial measurement (P > 0.05). There were no changes in the NIBUT, limbal redness, palpebral conjunctiva redness, corneal staining, pH, and Schirmer value over the period of time for each agent (P > 0.05). Conclusion. VCO acts as safe rewetting eye drops as it has shown no significant difference in the measurable parameter compared to commercial brand eye drops and saline. These study data suggest that VCO is safe to be used as ocular rewetting agent on human being.
  2. Teoh AN, Kaur S, Shafie SR, Shukri NHM, Bustami NA, Takahashi M, et al.
    BMC Pregnancy Childbirth, 2023 Jul 04;23(1):491.
    PMID: 37403031 DOI: 10.1186/s12884-023-05796-y
    Chrononutrition emerges as a novel approach to promote circadian alignment and metabolic health by means of time-of-the-day dietary intake. However, the relationship between maternal circadian rhythm and temporal dietary intake during pregnancy remains understudied. This study aimed to determine the change in melatonin levels in pregnant women across gestation and its association with temporal energy and macronutrient intake. This was a prospective cohort involving 70 healthy primigravidas. During the second and third trimesters, pregnant women provided salivary samples collected at 9:00, 15:00, 21:00, and 3:00 h over a 24 h day for melatonin assay. Data on chrononutrition characteristics were collected using a 3-day food record. Parameters derived from melatonin measurements including mean, amplitude, maximal level, area under the curve with respect to increase (AUCI), and area under the curve with respect to ground (AUCG) were computed. A rhythmic melatonin secretion over the day that remained stable across trimesters was observed among the pregnant women. There was no significant elevation in salivary melatonin levels as pregnancy advanced. In the second trimester, higher energy intake during 12:00-15:59 h and 19:00-06:59 h predicted a steeper melatonin AUCI (β=-0.32, p = 0.034) and higher AUCG (β = 0.26, p = 0.042), respectively. Macronutrient intake within 12:00-15:59 h was negatively associated with mean melatonin (Fat: β=-0.28, p = 0.041) and AUCG (Carbohydrate: β=-0.37, p = 0.003; Protein: β=-0.27, p = 0.036; Fat: β=-0.32, p = 0.014). As pregnant women progressed from the second to the third trimester, a flatter AUCI was associated with a reduced carbohydrate intake during 12:00-15:59 h (β=-0.40, p = 0.026). No significant association was detected during the third trimester. Our findings show that higher energy and macronutrient intakes particularly during 12:00-15:59 h and 19:00-06:59 h are associated with the disparities in maternal melatonin levels. Findings suggest the potential of time-based dietary approaches to entrain circadian rhythm in pregnant women.
  3. Hairol MI, Ahmad S, Sharanjeet-Kaur S, Hum Wee L, Abdullah F, Ahmad M
    PLoS One, 2021;16(11):e0259782.
    PMID: 34752486 DOI: 10.1371/journal.pone.0259782
    Postpartum depression (PPD) is one of the mental health complications that may arise following childbirth. This cross-sectional study explores the association between socioeconomic factors and PPD literacy with PPD incidence in 350 participants (mean age: 30.58±4.72 years) at one to six months postpartum, who attended the Kuala Lumpur Health Clinic from May to October 2020. PPD incidence and literacy were assessed using the validated Malay versions of the Edinburgh Postpartum Depression Scale (EPDS) and the Postpartum Depression Literacy Scale (PoDLiS), respectively. The participants' socioeconomic characteristics were collected using a self-administered questionnaire. Chi-square tests were performed to determine the association between these factors and PPD incidence. Binary logistic regression models were used to determine the odds ratios (OR). The incidence of postpartum depressive symptoms was 14.29%. Those with low household income were twice likely to have PPD symptoms (OR:2.58, 95% CI:1.23-5.19; p = 0.01) than those with higher incomes. Unemployment (i.e., participants who were housewives/homemakers) was associated with higher PPD incidence (Χ2(2, 350) = 6.97, p = 0.03), but it was not a significant PPD predictor. In conclusion, PPD incidence in the sample of Kuala Lumpur postpartum mothers is significantly associated with low household income. Other socioeconomic characteristics, including PPD literacy, were not significant predictors of PPD incidence.
  4. Mok KT, Tung SEH, Kaur S, Chin YS, Martini MY, Ulaganathan V
    Nutr Health, 2023 Mar;29(1):9-20.
    PMID: 36330727 DOI: 10.1177/02601060221134997
    Background: One of the key importance of vegetable consumption is to obtain sufficient micronutrients, dietary fibre, and for the prevention of childhood obesity. Most Malaysian children did not meet the recommended intake of vegetable consumption, and this is especially vulnerable among the urban poor population due to food insecurity. Efforts are needed to promote vegetable consumption that fall short of the recommended intake level. Aim: This trial aims to examine the effectiveness of the "GrowEat" project, as a nutrition intervention programme integrated with home gardening activities to improve vegetable consumption among urban poor children in Kuala Lumpur, Malaysia. Methods: This is a single-blinded parallel two-arm cluster randomised controlled trial (RCT) that include 134 children. Two zones in Kuala Lumpur will be randomly selected, and three low-cost housing flats from each zone will be selected as the intervention and control groups respectively. The trial is designed based on the social cognitive theory (SCT). Children from the intervention group (n = 67) will attend a 12-week programme, which consists of home garden-based activities, gardening and nutrition education session. Assessment will be conducted for both groups at three time points: baseline, post-intervention and follow-up phase at 3 months after the intervention. Conclusion: We anticipate positive changes in vegetable consumption and its related factors after the implementation of the "GrowEat" project. The current intervention may also serve as a model and can be extended to other urban poor population for similar interventions in the future to improve vegetable consumption, agriculture and nutrition awareness.
  5. Kok EY, Kaur S, Mohd Shukri NH, Abdul Razak N, Takahashi M
    Nutr Health, 2024 Dec;30(4):645-654.
    PMID: 38584399 DOI: 10.1177/02601060241246354
    Introduction: Emerging evidence has been explored to determine the factors affecting the development of infant circadian rhythm. While fetal programming happens during the pregnancy period, external environmental cues and infant nutritional programming can have substantial effects on the infant circadian rhythm. Understanding prenatal and postnatal factors determining infant circadian rhythm can improve future interventions in optimizing maternal and infant health. Methods: This is a prospective observational cohort study, targeting 216 pregnant women from government maternity clinics in Kuala Lumpur, Malaysia. Pregnant women will be recruited at third trimester (baseline), and follow up at 3 months, and 6 months. A subsample will be collected for salivary cortisol analysis to determine circadian rhythm of the mother and infant at third trimester and 3 months. Data of eating misalignment, light exposure, chronotype, infant temperament, sleep quality, and mood will be collected via validated questionnaires. Anthropometric data and birth outcomes will be collected from antenatal and postnatal health records. Summary: Studies on infant circadian rhythm development have yet to be explored and established, hence this study presents a novel approach to identify the factors from prenatal to postnatal periods on infant circadian rhythm and its influence on growth and temperament. Findings from this study will provide insights in the critical timing which has larger effects on infant circadian rhythm development for future interventions to be conducted.
  6. Kaur S, Zainal NZ, Low WY, Ramasamy R, Sidhu JS
    Asia Pac J Public Health, 2015 May;27(4):450-60.
    PMID: 24807887 DOI: 10.1177/1010539514533719
    The Hospital Anxiety and Depression Scale (HADS) is a common screening instrument used to determine the levels of anxiety and depression experienced by a patient and has been extensively used in patients with coronary artery disease (CAD). This study aimed to establish the factor structure of HADS in a Malaysian sample of 189 patients with CAD. Factor analysis of HADS using principal component analysis with varimax rotation yielded 3 factors. Confirmatory factor analysis supported the use of HADS in assessing 3 distinct dimensions of psychological distress--namely, anxiety, anhedonia, and psychomotor retardation. The HADS showed good internal consistency and was found to be a valid measure of psychological distress among Malaysian patients with CAD. However, low mean scores on the original 2 factors--that is, anxiety and depression--and also on the 2 depression subscales--anhedonia and psychomotor retardation--suggests that the recommended cutoff score to screen for psychological distress among CAD patients be reevaluated. Further research to determine the generalizability and consistency for the tridimensional structure of the HADS in Malaysia is recommended.
  7. Teoh AN, Kaur S, Mohd Shukri NH, Shafie SR, Ahmad Bustami N, Takahashi M, et al.
    Chronobiol Int, 2021 07;38(7):959-970.
    PMID: 33779445 DOI: 10.1080/07420528.2021.1902338
    Psychological distress during pregnancy may increase the risk of adverse maternal and infant outcomes. Past studies have demonstrated the association between circadian disturbances with psychological health. However, the roles of chronotype and social jetlag on psychological state during pregnancy are yet to be identified. We aimed to examine the psychological state in pregnant women and its relations to chronotype, social jetlag (SJL), sleep quality and cortisol rhythm. The current study included a subsample of participants from an ongoing cohort study. A total of 179 primigravidas (mean age 28.4 ± 4.0 years) were recruited. Chronotype and sleep quality during the second trimester were assessed using the Morning-Eveningness Questionnaire (MEQ) and Pittsburgh Sleep Quality Index (PSQI), respectively. SJL was calculated based on the difference between mid-sleep on workdays and free days. Psychological state of participants was evaluated using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Subsamples (n = 70) provided salivary samples at 5 time points over a 24 h period during the second trimester for cortisol assay. A higher proportion of pregnant women experienced moderate to severe anxiety symptoms (n = 77, 43.0%), followed by depressive (n = 17, 9.5%) and stress (n = 14, 7.8%) symptoms. No association was observed between chronotype and psychological distress during pregnancy. There was no significant difference in cortisol rhythms in relation to psychological distress. SJL and sleep quality were significantly associated with stress symptoms among pregnant women in the second trimester. Poor sleep quality, particularly daytime dysfunction (β = 0.37, p = .006) and sleep disturbances (β = 0.23, p = .047), were significantly associated with psychological distress (depressive, anxiety and stress symptoms) during the second trimester. The findings suggest that sleep is a potential modifiable lifestyle factor that can be targeted to improve psychological health among pregnant women.
  8. Koo HC, Kaur S, Chan KQ, Soh WH, Ang YL, Chow WS, et al.
    J Hum Nutr Diet, 2020 10;33(5):670-677.
    PMID: 32250007 DOI: 10.1111/jhn.12753
    INTRODUCTION: Little is known about the relationship of whole-grain intake with dietary fatty acids intake. The present study aimed to assess the whole-grain intake and its relationships with dietary fatty acids intake among multiethnic schoolchildren in Kuala Lumpur, Malaysia.

    METHODS: This cross-sectional study was conducted among 392 schoolchildren aged 9-11 years, cluster sampled from five randomly selected schools in Kuala Lumpur. Whole-grain and fatty acids intakes were assessed by 3-day, 24-h diet recalls. All whole-grain foods were considered irrespective of the amount of whole grain they contained.

    RESULTS: In total, 55.6% (n = 218) were whole-grain consumers. Mean (SD) daily intake of whole grain in the total sample was 5.13 (9.75) g day-1 . In the whole-grain consumer's only sample, mean (SD) intakes reached 9.23 (11.55) g day-1 . Significant inverse associations were found between whole-grain intake and saturated fatty acid (SAFA) intake (r = -0.357; P 

  9. Hong W, Li J, Chang Z, Tan X, Yang H, Ouyang Y, et al.
    J Antibiot (Tokyo), 2017 Jul;70(7):832-844.
    PMID: 28465626 DOI: 10.1038/ja.2017.55
    The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents.
  10. Khurana RK, Beg S, Burrow AJ, Vashishta RK, Katare OP, Kaur S, et al.
    Eur J Pharm Biopharm, 2017 Dec;121:42-60.
    PMID: 28887099 DOI: 10.1016/j.ejpb.2017.09.001
    The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul <5min, Dnm <100nm, Rel15min >85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS.
  11. Ouyang Y, Yang H, Zhang P, Wang Y, Kaur S, Zhu X, et al.
    Molecules, 2017 Sep 22;22(10).
    PMID: 28937657 DOI: 10.3390/molecules22101592
    Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays.
  12. Vasudevan A, Majumder N, Sharma I, Kaur I, Sundarrajan S, Venugopal JR, et al.
    ACS Biomater Sci Eng, 2023 Nov 13;9(11):6357-6368.
    PMID: 37847169 DOI: 10.1021/acsbiomaterials.3c01216
    Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 μm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.
  13. Kaur S, Teoh AN, Shukri NHM, Shafie SR, Bustami NA, Takahashi M, et al.
    BMC Pregnancy Childbirth, 2020 Feb 11;20(1):96.
    PMID: 32046676 DOI: 10.1186/s12884-020-2797-2
    BACKGROUND: Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.

    METHODS: Ten government maternal and child health clinics in Kuala Lumpur, Malaysia will be randomly selected. Sample size of 438 first-trimester pregnant women will be followed-up until the birth of their infant. Salivary melatonin and cortisol concentration among subsample will be determined using enzyme-linked immunosorbent assay. Data on sleep quality, psychological distress and morningness/eveningness chronotype of pregnant women will be collected using validated questionnaires. Pedometer will be used to measure 5-day physical activity data. Total gestational weight gain will be determined at the end of pregnancy. Utilization of 3-day food record is to capture meal timing and nutrient intake. All measurements will be done in 2nd and 3rd trimester. Birth outcomes will be collected through clinic records and Centers for Disease Control and Prevention (CDC) Neonatal questionnaire. Infants will be followed-up at 6 and 12 months old to obtain anthropometric measurements.

    DISCUSSION: There is a growing recognition of the role of maternal circadian rhythm, which entrains fetal circadian rhythms that may subsequently have long-term health consequences. The present study will identify the effect of circadian rhythm on pregnancy outcomes and infant growth in the first year of life.

  14. Wong HS, Tay JEF, Kaur S, Gan WY, Che'Ya NN, Tan CH, et al.
    Nutr Health, 2022 Aug 28.
    PMID: 36036393 DOI: 10.1177/02601060221122182
    Background: Anaemia has been identified as a major public health problem that affects both developed and developing countries, including Malaysia. To prevent anaemia, knowledge is a key parameter for changing attitudes and practices. Aim: This present study aims to determine the association of knowledge and practices in preventing nutritional anaemia with anaemia status of urban poor adolescents in Kuala Lumpur, Malaysia. Methods: A total of 209 urban poor adolescents (50.7% males and 49.3% females) aged 10 to 17 years old were recruited from eight low-cost flats (People Housing Programme) in Kuala Lumpur, Malaysia. A self-administered questionnaire was used to assess the sociodemographic characteristics, knowledge and practices in preventing nutritional anaemia. Anaemia status from the haemoglobin level concentration was determined using HemoCue® 201  +  hemoglobinometer. Results: The prevalence of anaemia among urban poor adolescents was 58.4%, particularly prevalent among females (p 
  15. Tay JEF, Kaur S, Tham WW, Gan WY, Ya NNC, Tan CH, et al.
    Nutr Res Pract, 2023 Apr;17(2):269-283.
    PMID: 37009138 DOI: 10.4162/nrp.2023.17.2.269
    BACKGROUND/OBJECTIVES: This study aimed to examine the food security status of urban poor adolescents and its association with diet quality.

    SUBJECTS/METHODS: A cross-sectional survey was conducted among 188 adolescents aged 13-18 yrs living in Kuala Lumpur, Malaysia. Household food insecurity and dietary intake data were collected using the Radimer/Cornell hunger and food insecurity instrument and 2-day 24-h dietary recalls, respectively. Diet quality was determined using the Malaysian Healthy Eating Index (HEI). Weight and height were measured and body mass index-for-age, as well as height-for-age z scores were calculated.

    RESULTS: The present study revealed that 47.9% of the adolescents experienced household food insecurity, 24.5% experienced individual food insecurity, 18.6% household food security, and 9.0% child hunger. The mean score of diet quality was 56.83 ± 10.09, with a significantly lower HEI score among food insecure adolescents (household food insecure, individual food insecure, and child hunger) than household food secure adolescents (P = 0.001). The differences between food secure and food insecure households were found to be significant for energy (P = 0.001) and nutrients including proteins (P = 0.006), carbohydrates (P = 0.005), dietary fiber (P = 0.001), folate (P < 0.001), and vitamin C (P = 0.006). The multiple linear regression showed that adolescents who experienced food insecurity (β = -0.328; P = 0.003) were found to be significantly associated with poor diet quality (F = 2.726; P < 0.01), wherein 13.3% of the variation in the diet quality was explained by the food security status.

    CONCLUSIONS: Experiencing food insecurity contributed to poor diet quality among urban poor adolescents. Further longitudinal studies are needed to comprehensively understand this association to improve food insecurity and diet quality among urban poor communities.

  16. Chan KG, Loke MF, Ong BL, Wong YL, Hong KW, Tan KH, et al.
    PeerJ, 2015;3:e1367.
    PMID: 26587340 DOI: 10.7717/peerj.1367
    Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Biolog Phenotype Microarray analysis, protein profiling with liquid chromatography-mass spectrometry, repetitive sequence-based PCR typing and whole genome sequencing followed by phylogenomic analyses. Results. The isolates were shown to be possibly novel slow-growing schotochromogens with highly similar biological and genotypic characteristics. Both strains have a genome size of 5.2 Mbp, G+C content of 68.8%, one rRNA operon and 52 tRNAs each. They qualified for classification into the same species with their average nucleotide identity of 99.98% and tetranucleotide correlation coefficient of 0.99999. At the subspecies level, both strains showed 98.8% band similarity in the Diversilab automated repetitive sequence-based PCR typing system, 96.2% similarity in protein profiles obtained by liquid chromatography mass spectrometry, and a genomic distance that is close to zero in the phylogenomic tree constructed with conserved orthologs. Detailed epidemiological tracking revealed that the elephants shared a common habitat eight years apart, thus, strengthening the possibility of a clonal relationship between the two strains.
  17. Hong W, Wang Y, Chang Z, Yang Y, Pu J, Sun T, et al.
    Sci Rep, 2015;5:15328.
    PMID: 26471125 DOI: 10.1038/srep15328
    It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR.
  18. Yap LB, Eng DT, Sivalingam L, Rusani BI, Umadevan D, Muhammad Z, et al.
    Clin Appl Thromb Hemost, 2016 Nov;22(8):792-797.
    PMID: 25962393 DOI: 10.1177/1076029615584664
    BACKGROUND: The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke.
    METHODS: A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013.
    RESULTS: Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59).
    CONCLUSION: There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF.
    KEYWORDS: dabigatran; non-valvular atrial fibrillation; novel anticoagulant; stroke prevention; warfarin
  19. Sharma P, Mehta M, Dhanjal DS, Kaur S, Gupta G, Singh H, et al.
    Chem Biol Interact, 2019 Aug 25;309:108720.
    PMID: 31226287 DOI: 10.1016/j.cbi.2019.06.033
    Cancer is one of the major diseases that cause a high number of deaths globally. Of the major types of cancers, lung cancer is known to be the most chronic form of cancer in the world. The conventional management of lung cancer includes different medical interventions like chemotherapy, surgical removal, and radiation therapy. However, this type of approach lacks specificity and also harms the adjacent normal cells. Lately, nanotechnology has emerged as a promising intervention in the management and treatment of lung cancers. Nanotechnology has revolutionized the existing modalities and focuses primarily on reducing toxicity and improving the bioavailability of anticancer drugs to the target tumor cells. Nanocarrier systems are being currently used extensively to exploit and to overcome the obstructions induced by cancers in the lungs. The nano-carrier-loaded therapeutic drug delivery methods have shown promising potential in treating lung cancer as its target is to control the growth of tumor cells. In this review, various modes of nano drug delivery options like liposomes, dendrimers, quantum dots, carbon nanotubes and metallic nanoparticles have been discussed. Nano-carrier drug delivery systems emerge as a promising approach and thus is expected to provide newer and advanced avenues in cancer therapeutics.
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