Browse publications by year: 2020

  1. Vohra MS, Ahmad B, Serpell CJ, Parhar IS, Wong EH
    Differentiation, 2020 08 23;115:62-84.
    PMID: 32891960 DOI: 10.1016/j.diff.2020.08.003
    Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology.
    MeSH terms: Adipose Tissue/growth & development*; Adipose Tissue/metabolism; Animals; Adipose Tissue, Brown/growth & development; Adipose Tissue, Brown/metabolism*; Cell Differentiation/genetics; Humans; Obesity/genetics*; Obesity/metabolism; Obesity/pathology; Adipocytes/metabolism*; Adipogenesis/genetics*; Mice; In Vitro Techniques
  2. Kang X, Handayani DOD, Chong PP, Acharya UR
    Comput Biol Med, 2020 10;125:103970.
    PMID: 32892114 DOI: 10.1016/j.compbiomed.2020.103970
    Nowadays human behavior has been affected with the advent of new digital technologies. Due to the rampant use of the Internet by children, many have been addicted to pornography. This addiction has negatively affected the behaviors of children including increased impulsiveness, learning ability to attention, poor decision-making, memory problems, and deficit in emotion regulation. The children with porn addiction can be identified by parents and medical practitioners as third-party observers. This systematic literature review (SLR) is conducted to increase the understanding of porn addiction using electroencephalogram (EEG) signals. We have searched five different databases namely IEEE, ACM, Science Direct, Springer and National Center for Biotechnology Information (NCBI) using addiction, porn, and EEG as keywords along with 'OR 'operation in between the expressions. We have selected 46 studies in this work by screening 815,554 papers from five databases. Our results show that it is possible to identify children with porn addiction using EEG signals.
    MeSH terms: Child; Electroencephalography; Erotica*; Humans
  3. Shafie AA, Vasan Thakumar A
    Eur J Health Econ, 2020 Dec;21(9):1411-1420.
    PMID: 32892230 DOI: 10.1007/s10198-020-01233-5
    OBJECTIVE: This study aimed to test multiplicative modelling with EQ-5D-3L time-trade-off (TTO) and visual analogue scale (VAS) values.

    METHODS: A multi-stage sampling design was adopted for the study and data collection took place in three phases in 2010, 2011, and 2012 in the Northern region of Malaysia. Face-to-face interviews involved respondents answering both 13 TTO and 15 VAS valuation tasks were carried out. Both additive and multiplicative model specifications were explored using the valuation data. Model performance was evaluated using out-of-sample predictive accuracy by applying the cross-validation technique. The distribution of the model values was also graphically compared on Bland-Altman plots and kernel density distribution curves.

    RESULTS: Data from 630 and 611 respondents were included for analyses using TTO and VAS models, respectively. In terms of main-effects specifications, cross-validation results revealed a slight superiority of multiplicative models over its additive counterpart in modelling TTO values. However, both main-effects models had roughly equal predictive accuracy for VAS models. The non-linear multiplicative model with I32 term, MULT7_TTO, performed best for TTO models; while, the linear additive model with N3 term, ADD11_VAS, outperformed the other VAS models. Multiplicative modelling neither altered the dimensional rankings of importance nor did it change the distribution of values of the health states.

    CONCLUSION: Using EQ-5D-3L valuation data, multiplicative modelling was shown to improve out-of-sample predictive accuracy of TTO models but not of VAS models.

    MeSH terms: Health Status*; Malaysia; Quality of Life*; Surveys and Questionnaires; Models, Statistical*; Visual Analog Scale*
  4. Quah SY, Tan MS, Ho KL, Manan NA, Gorfe AA, Deb PK, et al.
    Future Med Chem, 2020 09;12(18):1611-1631.
    PMID: 32892640 DOI: 10.4155/fmc-2020-0104
    Background: Andrographolide and its benzylidene derivatives, SRJ09 and SRJ23, potentially bind oncogenic K-Ras to exert anticancer activity. Their molecular interactions with K-Ras oncoproteins that lead to effective biological activity are of major interest. Methods & results: In silico docking and molecular dynamics simulation were performed using Glide and Desmond, respectively; while saturation transfer difference NMR was performed using GDP-bound K-RasG12V. SRJ23 was found to bind strongly and selectively to K-RasG12V, by anchoring to a binding pocket (namely p2) principally via hydrogen bond and hydrophobic interactions. The saturation transfer difference NMR analysis revealed the proximity of protons of functional moieties in SRJ23 to K-RasG12V, suggesting positive binding. Conclusion: SRJ23 binds strongly and interacts stably with K-RasG12V to exhibit its inhibitory activity.
    MeSH terms: Binding Sites/drug effects; Diterpenes/pharmacology*; Diterpenes/chemistry; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry; Humans; Models, Molecular; Molecular Conformation; Magnetic Resonance Spectroscopy; Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors*; Proto-Oncogene Proteins p21(ras)/genetics; Proto-Oncogene Proteins p21(ras)/metabolism
  5. Ishaqui AA, Khan AH, Sulaiman SA, Alsultan M, Khan I
    Saudi Med J, 2020 Sep;41(9):1015-1021.
    PMID: 32893285 DOI: 10.15537/smj.2020.9.25249
    OBJECTIVES: To assess the comparative efficacy of oseltamivir alone and oseltamivir-antibiotic therapy for early relief of symptoms associated with severe influenza-A (non-H1N1) and influenza-B infection hospitalized patients.

    METHODS: In this retrospective multicenter study conducted from 2016-2019, enrolled patients were divided into 2 treatment groups. Group 1 patients were started on Antiviral drug (oseltamivir) alone therapy. Group 2 patients were initiated on Antiviral drug (oseltamivir) in combination with Antibiotic therapy. Using acute respiratory illness scoring, symptom severity score was assessed daily for 8 symptoms namely, fever, fatigue, headache, cough, sore throat, wheezing, muscle ache and nasal congestion. For each symptom the severity was scored from scale 0-3. Results: Overall mean ARI severity score was statistically significantly lower (p less than 0.05) on day 2 (14.65-vs-13.68), day 3 (12.95-vs-11.67) and day 4 (10.31-vs-9.12 ) for influenza-A (non-H1N1) while day 3 (12.52-vs-11.87) and day 4 (11.21-vs-10.18) for influenza-B patients for patients who were initiated on oseltamivir-antibiotic combination therapy. Fever, cough and nasal congestion showed statistically significant improvement within 4 days of initiation of combination treatment. Fatigue, sore throat and muscle ache improvement pattern was same for both treatment protocols.

    CONCLUSION: Oseltamivir-antibiotic combination treatment showed early resolution of some symptoms with cumulatively reduced mean symptom severity score in severe influenza infection hospitalized patients.

    MeSH terms: Adult; Aged; Anti-Bacterial Agents/administration & dosage*; Antiviral Agents/administration & dosage*; Drug Therapy, Combination; Female; Hospitalization; Humans; Influenza, Human/drug therapy*; Inpatients*; Male; Middle Aged; Influenza A virus*; Influenza B virus*; Retrospective Studies; Severity of Illness Index; Time Factors; Cohort Studies; Multicenter Studies as Topic; Treatment Outcome; Oseltamivir/administration & dosage*
  6. Haris SM, Mustafa FB, Raja Ariffin RN
    Environ Manage, 2020 11;66(5):816-825.
    PMID: 32893336 DOI: 10.1007/s00267-020-01355-9
    Environmental nongovernmental organizations (ENGOs) are considered key players for engendering good climate change governance to address both climate change and sustainable development. The participation of ENGOs in climate change governance occurs in a four-phase policy cycle. They include (1) identification of policy options, (2) policy formulation, (3) policy implementation, and (4) policy monitoring and evaluation. The ENGOs, however, have been criticized for their lack of effectiveness, and their roles in tackling climate change remain unclear. To date, the study on the roles and activities of Southeast Asian ENGOs in climate change governance has been under-researched. This study, therefore, applies a systematic literature review of 19 published articles from Scopus and Web of Science-indexed journal to understand the current state of the Southeast Asian ENGOs participation in climate change governance based on the four-phase policy cycle. The findings show that the ENGOs in Southeast Asia are involved directly and indirectly in climate change governance. They are significant actors in the implementation of the climate change policy, but they play a minimal role in the formulation of said policy. It implies that they could also be a vital partner to the government in the climate change governance process as they can bring effective policy improvements. Lastly, this review will recommend future avenues of research for scholars.
    MeSH terms: Asia, Southeastern; Government; Organizations*; Climate Change*
  7. Looi ML, Wong AKH, Gnapragasan SA, Japri AZ, Rajedadram A, Pin KY
    J Zhejiang Univ Sci B, 2020 9 8;21(9):745-748.
    PMID: 32893531 DOI: 10.1631/jzus.B2000278
    Piper betle (PB), also known as "betel" in Malay language, is a tropical Asian vine. PB leaves are commonly chewed by Asians along with betel quid. It contains phenols such as eugenol and hydroxychavicol along with chlorophyll, β-carotene, and vitamin C (Salehi et al., 2019). Extracts from PB leaves have various medicinal properties including anticancer, antioxidant, anti-inflammatory, and antibacterial effects (Salehi et al., 2019). Previous research has shown that PB induces cell cycle arrest at late S or G2/M phase and causes apoptosis at higher doses (Wu et al., 2014; Guha Majumdar and Subramanian, 2019). A combination of PB leaf extract has also been shown to enhance the cytotoxicity of the anticancer drug, 5-fluorouracil (5-FU), in cancer cells (Ng et al., 2014).
    MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Cell Movement/drug effects; Humans; Microtubules/drug effects*; Plant Extracts/pharmacology*; Plant Leaves; HT29 Cells; Piper betle*
  8. Ng KH, Kemp R
    J Zhejiang Univ Sci B, 2020 9 8;21(9):752-754.
    PMID: 32893533 DOI: 10.1631/jzus.B2000228
    The world is now plagued by a pandemic of unprecedented nature caused by a novel, emerging, and still poorly understood infectious disease, coronavirus disease 2019 (COVID-19) (Wu and McGoogan, 2020). In addition to the rapidly growing body of scientific and medical literature that is being published, extensive public reports and stories in both the traditional media and social media have served to generate fear, panic, stigmatization, and instances of xenophobia (Zarocostas, 2020).
    MeSH terms: Fear*; Health Education; Humans; Panic; Pneumonia, Viral/epidemiology; Pneumonia, Viral/psychology*; Coronavirus Infections/epidemiology; Coronavirus Infections/psychology*; Trust; Pandemics; Social Media
  9. Chung HH, Anak Kamar CK, Kit Lim LW, Roja JS, Liao Y, Tsan-Yuk Lam T, et al.
    J Genet, 2020;99.
    PMID: 32893838
    The yellowtail rasbora (Rasbora tornieri) is a miniature ray-finned fish categorized under the genus Rasbora in the family of Cyprinidae. In this study, a complete mitogenome sequence of R. tornieri was sequenced using four primers targeting two halves of the mitogenome with overlapping flanking regions. The size of mitogenome was 16,573 bp, housing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organization was detected between this species and other members of Rasbora genus. The heavy strand encompassed 28 genes while the light strand accommodated the other nine genes. Most protein-coding genes execute ATG as start codon, excluding COI and ND3 genes, which utilized GTG instead. The central conserved sequence blocks (CSB-E, CSB-F and CSB-D), variable sequence blocks (CSB-1, CSB-3 and CSB-2) as well as the terminal associated sequence (TAS) were conserved within the control region. The maximum likelihood phylogenetic family tree revealed the divergence of R. tornieri from the basal region of the Rasbora clade, where its evolutionary relationships with other Rasbora members are poorly resolved as indicated by the low bootstrap values. This work acts as window for further population genetics and molecular evolution studies of Rasbora genus in future.
    MeSH terms: Animals; Cypriniformes/genetics*; Biological Evolution*; Mitochondria/genetics*; Phylogeny; Sequence Analysis, DNA/methods*; Fish Proteins/genetics*; Genome, Mitochondrial/genetics*
  10. Surien O, Ghazali AR, Masre SF
    Histol Histopathol, 2020 Oct;35(10):1159-1170.
    PMID: 32893871 DOI: 10.14670/HH-18-247
    BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model.

    METHODS: A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10mg/kg PS (PS10) and 50mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis.

    RESULTS: All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium.

    CONCLUSIONS: The underlying molecular mechanisms of PS in lung SCC should be further studied.

    MeSH terms: Animals; Carcinoma, Squamous Cell/chemically induced; Carcinoma, Squamous Cell/metabolism; Carcinoma, Squamous Cell/pathology; Carcinoma, Squamous Cell/prevention & control*; Carmustine/analogs & derivatives; Disease Models, Animal; Female; Lung/drug effects*; Lung/metabolism; Lung/pathology; Lung Neoplasms/chemically induced; Lung Neoplasms/metabolism; Lung Neoplasms/pathology; Lung Neoplasms/prevention & control*; Mice, Inbred BALB C; Stilbenes/pharmacology*; Anticarcinogenic Agents/pharmacology*; Keratin-6/metabolism; Keratin-15/metabolism
  11. Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.
    BMC Nephrol, 2020 09 07;21(1):388.
    PMID: 32894076 DOI: 10.1186/s12882-020-02052-9
    BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

    METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

    RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

    CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

    MeSH terms: Aged; Blood Glucose; Creatinine; Diabetes Mellitus; Ethnic Groups; Fasting; Female; Genotype; Graft Survival; Renal Dialysis; Humans; Kidney Diseases; Malaysia; Male; Mannose; Prednisolone; Regression Analysis; Silver; Interleukin-7; Body Mass Index; Multivariate Analysis; Confidence Intervals; Kidney Transplantation; Tacrolimus; Cyclosporine; Receptors, Interleukin-7; Polymorphism, Single Nucleotide; Leptin; Asian Continental Ancestry Group; Calcineurin Inhibitors
  12. Lee SH, Reed-Newman T, Anant S, Ramasamy TS
    Stem Cell Rev Rep, 2020 12;16(6):1185-1207.
    PMID: 32894403 DOI: 10.1007/s12015-020-10031-8
    Quiescence in cancer cells is considered a therapeutic challenge as it confers dormancy in tumour, hence circumventing inherent anti-neoplastic surveillance system and standard-of-care cancer therapeutics including chemotherapy and radiotherapy. Since majority of the therapeutics target actively proliferating cancer cells, cancer cells eventually develop quiescent nature as mechanism of survival and cancer progression under both niche and therapeutic pressures. Quiescence state in cancer cells, eventually, confers resistant and aggressive nature to conventional cancer therapies, resulting in disease progression and relapse. Therefore, targeting quiescent cancer cells or cancer stem cells is a promising therapeutic approach, however an extensive review of the relevant information is needed in order to device an effective therapy. While the evidence of quiescence regulation in CSCs is rather a complex molecular and cellular network, herein, we aim to provide a comprehensive understanding of both intrinsic and extrinsic regulation in association with the function of CSCs. Findings on induction of quiescent state in CSCs population, its regulation at both cellular and molecular level, key molecular regulators, cellular events and processes including potential targets to develop therapeutics are extensively reviewed. This review also highlights the impact of CSC plasticity on quiescence which capturing the key challenge of targeting the cells in this state. Beyond understanding the mechanisms underlying quiescence nature of cancer cells, this review provides insightful perspective and future direction on insight in targeting these populations, hence collapse the tumour dormancy programme in order to eradicate tumour mass as a whole. Capability of CSCs to establish quiescent state as a mechanism of survival during unfavorable conditions, as well as its impact in cancer progression and subsequent relapse, including the potential therapeutic strategy to eradicate this CSCs sub-population in the tumor mass as an effective cancer therapy.
    MeSH terms: Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Humans; Neoplasm Recurrence, Local/pathology; Neoplasms/mortality; Neoplasms/pathology; Neoplastic Stem Cells/drug effects; Neoplastic Stem Cells/pathology*; Tumor Microenvironment/drug effects
  13. Tan AH, Lim SY, Mahadeva S, Loke MF, Tan JY, Ang BH, et al.
    Mov Disord, 2020 12;35(12):2250-2260.
    PMID: 32894625 DOI: 10.1002/mds.28248
    BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD).

    OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms.

    METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test.

    RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results.

    CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

    MeSH terms: Double-Blind Method; Humans; Quality of Life; Surveys and Questionnaires; Helicobacter pylori*
  14. Ghoshal R, Sharanjeet-Kaur S, Fadzil NM, Ghosh S, Ngah NF, Aziz RAA
    PMID: 32887213 DOI: 10.3390/ijerph17176378
    Polypoidal choroidal vasculopathy (PCV), a subtype of neovascular age-related macular degeneration, requires repeated treatment. The objective of this pilot study was to evaluate and compare vision-targeted quality of life (QOL) at baseline and after 6 months of treatment in patients with PCV. Naive PCV patients were recruited. Visual functions assessed were distance visual acuity (DVA), near visual acuity (NVA), contrast sensitivity (CS), reading speed (RS), and QOL at baseline and after 6 months of treatment. Thirty patients (average age of 67.62 ± 8.05 years) revealed mean DVA and NVA improvements of 0.24 logMAR and 0.30 logMAR, respectively. Mean CS and RS improved by 0.39 log contrast and 25.58 words per minute, respectively. The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) composite score significantly increased from a baseline of 66.73 ± 13.74 to 73.54 ± 14.26. Twenty-eight of the patients showed overall improvement in QOL score by 5 units or more or remained stable. Subscales of NEI-VFQ-25 significantly improved, with general vision, mental health, and role difficulties improving by 10 or more units. The present pilot study reports a significant improvement of QOL in PCV patients after 6 months of treatment, with mental health, role difficulties, social functioning, and distance vision activities being the most improved subscales.
    MeSH terms: Aged; Humans; Middle Aged; Pilot Projects; Quality of Life*; Surveys and Questionnaires; Visual Acuity; Patient Satisfaction
  15. Ghoshal R, Sharanjeet-Kaur S, Mohamad Fadzil N, Mutalib HA, Ghosh S, Ngah NF, et al.
    PMID: 32887214 DOI: 10.3390/ijerph17176379
    In early and intermediate age related macular degeneration (ARMD), visual acuity alone has failed to explain the complete variation of vision. The aim of the present study was to determine correlation between different visual functions and retinal morphology in eyes with early and intermediate ARMD. In this single center cross sectional study, patients diagnosed as early or intermediate ARMD in at least one eye were recruited. Visual functions measured were best- corrected distance visual acuity (DVA), near vision acuity (NVA), reading speed (RS), and contrast sensitivity (CS). Parameters such as thickness (RT) and volume (RV) of the retina, outer retinal layer thickness (ORLT) and volume (ORLV), outer nuclear layer thickness (ONLT) and volume (ONLV), retinal pigment epithelium layer-Bruch's membrane complex thickness (RPET) and volume (RPEV) were assessed employing semi-auto segmentation method of Spectralis optical coherence tomography (OCT). Twenty-six eyes were evaluated. DVA, CS, and RS showed significantly good correlation with RPET, ONLT, and ONLV, whereas NVA showed good correlation with ONLV and RPET. The present study concluded that RS, CS, NVA, and DVA represent the morphological alteration in early stages and should be tested in clinical settings. ONLT, ONLV, and RPET morphological parameters can be employed as important biomarkers in diagnosis of early to intermediate ARMD.
    MeSH terms: Aged; Cross-Sectional Studies; Female; Humans; Macular Degeneration*; Male; Middle Aged; Visual Acuity*; Tomography, Optical Coherence
  16. Zulkipli NN, Zakaria R, Long I, Abdullah SF, Muhammad EF, Wahab HA, et al.
    Molecules, 2020 Sep 02;25(17).
    PMID: 32887218 DOI: 10.3390/molecules25173991
    Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
    MeSH terms: Everolimus/pharmacology; Everolimus/chemistry; Computer Simulation*; Humans; Hydrogen Bonding; Malaysia; Plants/chemistry*; Triterpenes/pharmacology*; Triterpenes/chemistry; Cell Death/drug effects; Cell Line, Tumor; Protein Kinase Inhibitors/pharmacology*; Protein Kinase Inhibitors/chemistry; Pentacyclic Triterpenes/pharmacology*; Pentacyclic Triterpenes/chemistry; Hydrophobic and Hydrophilic Interactions; TOR Serine-Threonine Kinases/antagonists & inhibitors*; TOR Serine-Threonine Kinases/metabolism; Molecular Docking Simulation
  17. Coste C, Gérard N, Dinh CP, Bruguière A, Rouger C, Leong ST, et al.
    Biomolecules, 2020 09 02;10(9).
    PMID: 32887413 DOI: 10.3390/biom10091266
    Modulation of major histocompatibility complex (MHC) expression using drugs has been proposed to control immunity. Phytochemical investigations on Garcinia species have allowed the isolation of bioactive compounds such as polycyclic polyprenylated acylphloroglucinols (PPAPs). PPAPs such as guttiferone J (1), display anti-inflammatory and immunoregulatory activities while garcinol (4) is a histone acetyltransferases (HAT) p300 inhibitor. This study reports on the isolation, identification and biological characterization of two other PPAPs, i.e., xanthochymol (2) and guttiferone F (3) from Garcinia bancana, sharing structural analogy with guttiferone J (1) and garcinol (4). We show that PPAPs 1-4 efficiently downregulated the expression of several MHC molecules (HLA-class I, -class II, MICA/B and HLA-E) at the surface of human primary endothelial cells upon inflammation. Mechanistically, PPAPs 1-4 reduce MHC proteins by decreasing the expression and phosphorylation of the transcription factor STAT1 involved in MHC upregulation mediated by IFN-γ. Loss of STAT1 activity results from inhibition of HAT CBP/p300 activity reflected by a hypoacetylation state. The binding interactions to p300 were confirmed through molecular docking. Loss of STAT1 impairs the expression of CIITA and GATA2 but also TAP1 and Tapasin required for peptide loading and transport of MHC. Overall, we identified new PPAPs issued from Garcinia bancana with potential immunoregulatory properties.
    MeSH terms: Acylation; Benzophenones/isolation & purification; Benzophenones/pharmacology; Benzophenones/chemistry; Humans; Interferon-gamma/metabolism; Major Histocompatibility Complex/drug effects; Major Histocompatibility Complex/genetics; Nuclear Proteins/metabolism; Phloroglucinol/analogs & derivatives*; Phloroglucinol/isolation & purification; Phloroglucinol/pharmacology*; Phloroglucinol/chemistry; Polycyclic Compounds/isolation & purification; Polycyclic Compounds/pharmacology*; Polycyclic Compounds/chemistry; Terpenes/pharmacology; Terpenes/chemistry; Trans-Activators/metabolism; Down-Regulation/drug effects; Membrane Transport Proteins/metabolism; Garcinia/chemistry*; Endothelial Cells/drug effects; STAT1 Transcription Factor/metabolism; p300-CBP Transcription Factors/antagonists & inhibitors; p300-CBP Transcription Factors/chemistry; GATA2 Transcription Factor/metabolism; Prenylation; Primary Cell Culture; Molecular Docking Simulation; Antigen Peptide Transporter-1/metabolism
  18. Johari MZ, Abdullah Z, Mohd Hanafiah AN, Mohammed Nadzri NI, Razli SA, Kong YL
    BMC Fam Pract, 2020 09 04;21(1):182.
    PMID: 32887562 DOI: 10.1186/s12875-020-01254-2
    BACKGROUND: Implementation of the new Enhanced Primary Health Care (EnPHC) intervention aims to improve service quality and experience at primary healthcare clinics; especially to newly diagnosed patients. This was achieved by restructuring and improving existing services to better manage non-communicable diseases amongst patients. Objectives of this study are to explore patients' experiences of the EnPHC intervention, to document their feedback and to determine effects of EnPHC intervention on patients.

    METHODS: This phenomenological qualitative study focussed on patients' experiences in relation to EnPHC interventions. Participants were purposely selected from a group of patients who attended the eight intervention primary healthcare clinics in Johor and Selangor regularly for treatment. Data collection was conducted between April to July 2018. Semi-structured interviews were conducted at average an hour per interview for four to five patients per clinic. Interviews were audio recorded, transcribed verbatim, coded and analysed using a thematic analysis approach.

    RESULTS: A total of 35 patients participated. Analysis revealed five main themes about patient experiences receiving the EnPHC intervention. These are: (1) health assessment in disease progress monitoring, (2) patient-doctor relationship and continuity of care, (3) professionalism in service delivery, (4) ensuring compliance in achieving health targets and (5) communication skills. Each theme represents an important aspect of the service, how it should be delivered within the patient expectations and how it can improve patient's health through their lens.

    CONCLUSION: Even though patients were not able to exactly identify the EnPHC intervention components implemented, they are able to describe the process changes that occurred; enabling them to improve their healthcare status. Engagement is necessary to better inform patients of the EnPHC intervention, its purpose, mechanisms, changes and importance for healthcare. It would reduce resistance and increase awareness amongst patients at the clinic.

    MeSH terms: Health Personnel*; Humans; Patient Compliance; Primary Health Care; Qualitative Research
  19. Bukhari SNA, Alotaibi NH, Ahmad W, Alharbi KS, Abdelgawad MA, Al-Sanea MM, et al.
    Med Chem, 2020 Sep 05.
    PMID: 32888274 DOI: 10.2174/1573406416666200905125038
    BACKGROUND: Ligustrazine and chalcones have been reported previously for various biological activities including anticancer effects.

    OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine based chalcones, in current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on growth of five different types of cancer cells.

    METHODS: All compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.

    RESULTS: Majority of compounds exhibited strong inhibition of cancer cells especially synthetic compounds 4a and 4b bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in main structural backbone were found most powerful inhibitors of cancer cell growth. Most active 9 compounds among whole series were selected for further studies related to different cancer targets including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.

    CONCLUSION: Synthetic derivatives including 4a-b and 5a-b showed multitarget approach and showed strong inhibitory effects on EGFR, FAK and BRAF while three compounds including 3e bearing methoxy substitution, 4a and 4b with 1- pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.

    MeSH terms: Biphenyl Compounds; Cell Line; Chalcone; Fluorescence; Propidium; Pyrazines; Tubulin; Chalcones; Proto-Oncogene Proteins B-raf; Polymerization; ErbB Receptors
  20. Mohammed Modawe Alshik Edris N, Sulaiman Y
    Ecotoxicol Environ Saf, 2020 Oct 15;203:111026.
    PMID: 32888594 DOI: 10.1016/j.ecoenv.2020.111026
    The detection of phenolic compounds, i.e. resorcinol (RC) catechol (CC) and hydroquinone (HQ) are important due to their extremely hazardous impact and poor environmental degradation. In this work, a novel and sensitive composite of electrochemically reduced graphene oxide-poly(Procion Red MX-5B)/gold nanoparticles modified glassy carbon electrode (GCE/ERGO-poly(PR)/AuNPs) was assembled for voltammetric detection of benzenediol isomers (RC, CC, and HQ). The nanocomposite displayed high peak currents towards the oxidation of RC, HQ, and CC compared to non-modified GCE. The peak-to-peak separations were 0.44 and 0.10 V for RC-CC and CC-HQ, respectively. The limit of detections were 53, 53, and 79 nM for HQ, CC, and RC with sensitivities of 4.61, 4.38, and 0.56 μA/μM (S/N = 3), respectively. The nanocomposite displayed adequate reproducibility, besides good stability and acceptable recoveries for wastewater and cosmetic samples analyses.
    MeSH terms: Azo Compounds/chemistry*; Benzene Derivatives/analysis*; Cosmetics/chemistry; Electrodes; Gold/chemistry*; Graphite/chemistry*; Oxidation-Reduction; Water Pollutants, Chemical/analysis*; Reproducibility of Results; Nanocomposites/chemistry*; Metal Nanoparticles/chemistry; Electrochemical Techniques/methods*; Waste Water/chemistry
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