Browse publications by year: 2019

  1. Fatemian T, Moghimi HR, Chowdhury EH
    Pharmaceutics, 2019 Sep 03;11(9).
    PMID: 31484456 DOI: 10.3390/pharmaceutics11090458
    : Pharmacotherapy as the mainstay in the management of breast cancer suffers from various drawbacks, including non-targeted biodistribution, narrow therapeutic and safety windows, and also resistance to treatment. Thus, alleviation of the constraints from the pharmacodynamic and pharmacokinetic profile of classical anti-cancer drugs could lead to improvements in efficacy and patient survival in malignancies. Moreover, modifications in the genetic pathophysiology of cancer via administration of small nucleic acids might pave the way towards higher response rates to chemotherapeutics. Inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized in this study to efficiently deliver various classes of therapeutics into cancer cells. Co-delivery of drugs and genetic materials was successfully attained through a carbonate apatite delivery device. On 4T1 cells, siRNAs against AKT and ERBB2 plus paclitaxel or docetaxel resulted in the largest increase in anti-cancer effects compared to CA/paclitaxel or CA/docetaxel. Therefore, these ingredients were selected for further in vivo investigations. Animals receiving injections of CA/paclitaxel or CA/docetaxel loaded with siRNAs against AKT and ERBB2 possessed significantly smaller tumors compared to CA/drug-treated mice. Interestingly, synergistic interactions in target protein knock down with combinations of CA/AKT/paclitaxel, CA/ERBB2/docetaxel were documented via western blotting.
    MeSH terms: Animals; Antineoplastic Agents; Apatites; Breast Neoplasms; Pharmaceutical Preparations; Humans; Tissue Distribution; Blotting, Western; Paclitaxel; Receptor, ErbB-2; RNA, Small Interfering; Taxoids; Proto-Oncogene Proteins c-akt; Mice; Nanoparticles
  2. Hussin M, Abdul Hamid A, Abas F, Ramli NS, Jaafar AH, Roowi S, et al.
    Molecules, 2019 Sep 03;24(17).
    PMID: 31484470 DOI: 10.3390/molecules24173208
    Herbs that are usually recognized as medicinal plants are well known for their therapeutic effects and are traditionally used to treat numerous diseases, including aging. This study aimed to evaluate the metabolite variations among six selected herbs namely Curcurmalonga, Oenanthejavanica, Vitex negundo, Plucheaindica, Cosmoscaudatus and Persicariaminus using proton nuclear magnetic resonance (1H-NMR) coupled with multivariate data analysis (MVDA). The free radical scavenging activity of the extract was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assay. The anti-aging property was characterized by anti-elastase and anti-collagenase inhibitory activities. The results revealed that P. minus showed the highest radical scavenging activities and anti-aging properties. The partial least squares (PLS) biplot indicated the presence of potent metabolites in P. minus such as quercetin, quercetin-3-O-rhamnoside (quercitrin), myricetin derivatives, catechin, isorhamnetin, astragalin and apigenin. It can be concluded that P. minus can be considered as a potential source for an anti-aging ingredient and also a good free radical eradicator. Therefore, P. minus could be used in future development in anti-aging researches and medicinal ingredient preparations.
    MeSH terms: Biphenyl Compounds; Catechin; Flavonoids; Free Radicals; Pancreatic Elastase; Picrates; Plants, Medicinal; Protons; Quercetin; Sulfonic Acids; Least-Squares Analysis; Collagenases; Vitex; Kaempferols; Apigenin; Benzothiazoles; Proton Magnetic Resonance Spectroscopy; Oxygen Radical Absorbance Capacity
  3. Kwong SC, Jamil AHA, Rhodes A, Taib NA, Chung I
    J Lipid Res, 2019 11;60(11):1807-1817.
    PMID: 31484694 DOI: 10.1194/jlr.M092379
    Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high-energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentiviral particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231, cells. FABP7-overexpressing Hs578T (Hs-FABP7) cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling.
    MeSH terms: Female; Humans; Tumor Cells, Cultured; Signal Transduction*; Cell Death; Tumor Suppressor Proteins/metabolism*; PPAR alpha/metabolism*; Triple Negative Breast Neoplasms/metabolism*; Triple Negative Breast Neoplasms/pathology; Fatty Acid-Binding Protein 7/metabolism*
  4. Sabetian S, Shamsir MS
    Bioinformation, 2019;15(7):513-522.
    PMID: 31485137 DOI: 10.6026/97320630015513
    Proteins can interact in various ways, ranging from direct physical relationships to indirect interactions in a formation of protein-protein interaction network. Diagnosis of the protein connections is critical to identify various cellular pathways. Today constructing and analyzing the protein interaction network is being developed as a powerful approach to create network pharmacology toward detecting unknown genes and proteins associated with diseases. Discovery drug targets regarding therapeutic decisions are exciting outcomes of studying disease networks. Protein connections may be identified by experimental and recent new computational approaches. Due to difficulties in analyzing in-vivo proteins interactions, many researchers have encouraged improving computational methods to design protein interaction network. In this review, the experimental and computational approaches and also advantages and disadvantages of these methods regarding the identification of new interactions in a molecular mechanism have been reviewed. Systematic analysis of complex biological systems including network pharmacology and disease network has also been discussed in this review.
  5. Hashim Fauzy F, Mohd Zainudin M, Ismawi HR, Elshami TFT
    PMID: 31485247 DOI: 10.1155/2019/7198592
    Piper sarmentosum is a tropical plant in Southeast Asia known for its traditional use in curing various ailments including hypertension. Previous research works have provided evidence for the herb's antihypertensive property. However, the exact mechanisms involved are still in question. The present study investigated the effects of Piper sarmentosum leaves aqueous extract (PSAE) treatment on vascular endothelin system in spontaneously hypertensive rats (SHRs). Four groups of SHRs were treated for 28 consecutive days, with negative and positive control groups receiving distilled water and 3 mg/kg perindopril, respectively. Another two groups are the treatment groups, which received PSAE and combination of 1.5 mg/kg perindopril and PSAE. Weekly measurements of blood pressure showed that PSAE significantly reduced the systolic, diastolic, and mean arterial pressures (P < 0.05) of the rats. PSAE also increased mesenteric artery nitric oxide (NO) level (P < 0.05) and reduced endothelin-1 (ET-1) level (P < 0.05) in the treatment groups. Our results demonstrate that oral administration of PSAE reduced blood pressure in SHRs by reducing the ET-1 level while increasing NO production.
    MeSH terms: Administration, Oral; Animals; Antihypertensive Agents; Asia, Southeastern; Blood Pressure; Blood Pressure Determination; Hypertension; Mesenteric Arteries; Nitric Oxide; Rats, Inbred SHR; Systole; Endothelins; Endothelin-1; Perindopril; Piper; Control Groups; Rats
  6. Vanagas G, Krilavičius T, Man KL
    Comput Math Methods Med, 2019 08 14;2019:2945021.
    PMID: 31485256 DOI: 10.1155/2019/2945021
    MeSH terms: Decision Making*; Decision Support Techniques*; Humans; Outcome Assessment (Health Care)/statistics & numerical data; Mathematical Concepts
  7. Koh CT, Tonsomboon K, Oyen ML
    Interface Focus, 2019 Oct 06;9(5):20190012.
    PMID: 31485308 DOI: 10.1098/rsfs.2019.0012
    Amnion is a membrane that surrounds and structurally protects the developing fetus during pregnancy. The rupture of amniotic membranes prior to both normal and preterm deliveries involves stretch forces acting on a biochemically triggered weak zone of the membranes. Fracture toughness is an important mechanical property describing how the membranes containing a defect resist fracture, but this property has never been investigated in amniotic membranes. In this work, the fracture toughness of many samples cut from four pieces of amniotic membrane from different mothers was examined by uniaxial and pure shear (mode I) fracture tests. The measurement was checked for dependence on the sample geometry and notch length. Results from the uniaxial tensile test show J-shaped stress-strain curves and confirm that the amniotic membrane is a nonlinear material. The measured fracture toughness of four amniotic membranes ranged from 0.96 ± 0.11 to 1.83 ± 0.18 kJ m-2. Despite considering the effect of the presence of the defect on mechanical property measurement, similar fracture behaviour was observed for pre-notched and unnotched specimens, indicating that the membranes were extremely tolerant to defects. This defect-tolerant characteristic provides insight into the understanding of fetal membrane rupture.
    MeSH terms: Amnion; Female; Fetal Membranes, Premature Rupture; Fetus; Humans; Infant, Newborn; Membranes; Mothers; Pregnancy; Precipitating Factors; Fractures, Bone
  8. Lim CY, Duski S, Chye PC
    Case Rep Orthop, 2019;2019:5156032.
    PMID: 31485364 DOI: 10.1155/2019/5156032
    Intramuscular myxomas are rare, benign mesenchymal tumors. Tumor location in the forearm is very rare among all the intramuscular myxomas. To the best of our knowledge, there were two cases of supinator intramuscular myxoma reported in the literature, and we intend to report the third case of supinator myxoma with encasement of the posterior interosseous nerve (PIN). A 67-year-old lady presented with history of left proximal forearm swelling for the past 5 years. Magnetic resonance imaging showed a lobulated multiseptated lesion seen within left supinator muscle, which was hyperintense on T2-weighted images (T2WI) and hypointense on T1-weighted images (T1WI), with peripheral enhancement post contrast. The tissue diagnosis of myxoma was confirmed via an open biopsy. She underwent en bloc resection of the tumor. The PIN was encased by the tumor; it was preserved and carefully released from the tumor. The nerve sheath served as an excision margin. In conclusion, we present a rare case of an intramuscular myxoma in the supinator muscle. In view of the location, extra attention should be paid during excision surgery to locate the PIN and to avoid damaging the surrounding structures.
    MeSH terms: Attention; Biopsy; Female; Forearm; Magnetic Resonance Imaging; Myxoma; Muscle, Skeletal; Margins of Excision
  9. Liu Y, Uemura H, Ye D, Lee JY, Chiong E, Pu YS, et al.
    Prostate Int, 2019 Sep;7(3):108-113.
    PMID: 31485435 DOI: 10.1016/j.prnil.2018.12.001
    Background: The incidence of prostate cancer (PC) in Asian countries is increasing for reasons that are not clear. Data describing how PC is diagnosed and treated are fragmented across Asia, with marked intercountry and intracountry differences in outcome and knowledge gaps in clinical diagnostic and treatment practices. To address these knowledge gaps, we have established a PC disease registry with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome, population characteristics, and comorbidities in real-world clinical practice in Asia.

    Methods: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.gov NCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes.

    Results: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3.

    Discussion: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments.

    MeSH terms: Asia; Humans; Male; Neoplasm Recurrence, Local; Policy Making; Prognosis; Prospective Studies; Prostatic Neoplasms; Quality of Life; Registries; Risk Factors; Comorbidity; Incidence; Treatment Outcome; Disease Progression
  10. Syimir Fizal AN, Sohrab Hossain M, Alkarkhi AFM, Oyekanmi AA, Hashim SRM, Khalil NA, et al.
    Heliyon, 2019 Aug;5(8):e02368.
    PMID: 31485542 DOI: 10.1016/j.heliyon.2019.e02368
    Understanding the tanker driver hazard awareness on chemical exposure is important to ensure that they are fortified with the appropriate information regarding the risk of their occupation. This present study was conducted to determine the awareness of the petrol tanker driver on the chemical exposure during transportation petroleum product. The assessment on hazardous awareness of the petrol tank driver was conducted through questionnaire survey. Wherein, the questionnaire was designed with considering the variables of age of the driver, working experience, working hours in a day and knowledge on chemical hazard presence in the petroleum oil. A reliability test of Cronbach's Alpha was performed to validate the questionnaire and the Chi-Square test was conducted to determine the correlation among the studied variables. The findings of the present study revealed that the drivers who are frequently come into direct contact with petrol cannot identify the spillage had occurred during working. The study identified that there is an urgency to conduct training on safe handling of petroleum oil in order to eliminate the risk of chemical hazards exposure to the tanker driver.
  11. Thomson DR, Linard C, Vanhuysse S, Steele JE, Shimoni M, Siri J, et al.
    J Urban Health, 2019 Oct;96(5):792.
    PMID: 31486003 DOI: 10.1007/s11524-019-00387-9
    Readers should note an additional Acknowledgment for this article: Dana Thomson is funded by the Economic and Social Research Council grant number ES/5500161/1.
  12. Adrus M, Zainuddin R, Ahmad Khairi NH, Ahamad M, Abdullah MT
    J Med Primatol, 2019 12;48(6):357-363.
    PMID: 31486088 DOI: 10.1111/jmp.12437
    BACKGROUND: Nasalis larvatus are well-known attraction for tourists in the mangrove forest of Bako National Park (BNP). Little is known regarding the infestation of helminth parasites in proboscis monkeys. Therefore, the objectives of this study are to determine the prevalence species of major helminth parasites of public health importance in proboscis monkeys in BNP.

    METHODS: A total of 65 faecal samples screened for helminth parasites via sodium nitrate floatation and faecal sedimentation techniques.

    RESULTS: A total of 14 helminth parasite species comprising of eight genera of nematodes, two species of cestodes and two trematodes were identified. Eggs of Trichuris trichiura were the most frequently encountered in proboscis monkeys.

    CONCLUSION: This is the first survey on the fauna of helminth parasites of proboscis monkeys living in mangrove forests, and therefore, it implies the important baseline information that increases our current knowledge for future research regarding parasite-host ecology in primates.

    MeSH terms: Animals; Borneo/epidemiology; Helminthiasis, Animal/epidemiology*; Helminthiasis, Animal/parasitology; Helminths/classification; Helminths/physiology*; Malaysia/epidemiology; Monkey Diseases/epidemiology*; Monkey Diseases/parasitology
  13. Leja M, Grinberga-Derica I, Bilgilier C, Steininger C
    Helicobacter, 2019 Sep;24 Suppl 1:e12635.
    PMID: 31486242 DOI: 10.1111/hel.12635
    This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross-sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project-a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori-related disease was demonstrated by applying the modeling.
    MeSH terms: Humans; Risk Factors; Global Health; Prevalence; Helicobacter pylori/isolation & purification*; Helicobacter Infections/epidemiology*
  14. Siddique AB, Krebs M, Alvarez S, Greenspan I, Patel A, Kinsolving J, et al.
    JMIR Mhealth Uhealth, 2019 09 04;7(9):e12604.
    PMID: 31486408 DOI: 10.2196/12604
    BACKGROUND: Numerous free and low-cost mobile apps for the care management of kidney disease have become available in recent years. Although these appear to be promising tools, they have not been evaluated comparatively based on standard mobile app metrics, and thus, limited evidence is available regarding their efficacy. This study systematically cataloged and assessed mobile apps designed to assist medication compliance and nutrition tracking that are useful to the chronic kidney disease (CKD) and the end-stage renal disease (ESRD) patients who are on dialysis.

    OBJECTIVE: The objective of this study was to comprehensively evaluate mobile apps used for medication compliance and nutrition tracking for possible use by CKD and ESRD patients.

    METHODS: A systematic review framework was applied to the search, screening, and assessment of apps identified and downloaded from the iOS and Android app stores. We selected apps using 13 relevant search terms, narrowed down based on a set of inclusion and exclusion criteria, and then used the Mobile App Rating Scale (MARS), a widely adopted app evaluation tool to assess the effectiveness of apps. The internal consistency and interrater reliability were tested using Cronbach alpha and interclass correlation coefficients (ICCs), respectively.

    RESULTS: The MARS total score had excellent internal consistency (Cronbach alpha=.90) and a moderate level of interrater reliability (2-way mixed ICC 0.65). Overall, 11 out of the 12 reviewed apps met the minimum acceptable score of 3.0 in MARS rating. The 3 apps with the highest combined scores were My Kidneys, My Health Handbook (MARS=4.68); My Food Coach (MARS=4.48); and National Kidney Foundation Malaysia (MARS=4.20). The study identified 2 general weaknesses in the existing apps: the apps fell short of accommodating advanced interactive features such as providing motivational feedback and promoting family member and caregiver participations in the app utilization.

    CONCLUSIONS: The MARS rating system performed well in the app evaluation. The 3 highest ranked apps scored consistently high across the 5 dimensions specified in MARS. These apps were developed in collaboration with reputable organizations and field experts, demonstrating the importance of expert guidance in developing medical apps.

    MeSH terms: Humans; Information Services/statistics & numerical data; Kidney Failure, Chronic/psychology; Kidney Failure, Chronic/therapy*; Renal Insufficiency, Chronic/psychology; Renal Insufficiency, Chronic/therapy*; Mobile Applications/trends; Mobile Applications/statistics & numerical data*
  15. Jahangir MA, Gilani SJ, Muheem A, Jafar M, Aslam M, Ansari MT, et al.
    Pharm Nanotechnol, 2019;7(3):234-245.
    PMID: 31486752 DOI: 10.2174/2211738507666190429113906
    BACKGROUND: The amalgamation of biological sciences with nano stuff has significantly expedited the progress of biological strategies, greatly promoting practical applications in biomedical fields.

    OBJECTIVE: With distinct optical attributes (e.g., robust photostability, restricted emission spectra, tunable broad excitation, and high quantum output), fluorescent quantum dots (QDs) have been feasibly functionalized with manageable interfaces and considerably utilized as a new class of optical probe in biological investigations.

    METHODS: In this review article, we structured the current advancements in the preparation methods and attributes of QDs. Furthermore, we extend an overview of the outstanding potential of QDs for biomedical research and radical approaches to drug delivery.

    CONCLUSION: Notably, the applications of QDs as smart next-generation nanosystems for neuroscience and pharmacokinetic studies have been explained. Moreover, recent interests in the potential toxicity of QDs are also apprised, ranging from cell investigations to animal studies.

    MeSH terms: Animals; Biological Transport; Cell Line; Drug Carriers/toxicity; Drug Carriers/chemistry*; Fluorescent Dyes/toxicity; Fluorescent Dyes/chemistry*; Humans; Immunoassay/methods; Particle Size; Surface Properties; Biosensing Techniques/methods; Quantum Dots/toxicity; Quantum Dots/chemistry*; Optical Imaging/methods
  16. Lim YY, Lim TS, Choong YS
    J Mol Model, 2019 Sep 05;25(10):301.
    PMID: 31486892 DOI: 10.1007/s00894-019-4192-3
    The sigma-E transcription factor (σETF) can be found in most of the bacteria cells including Bacillus thuringiensis. However, the cellular regulatory mechanisms of these transcription factors in the mass production of δ-endotoxins during sporulation stage are yet to be revealed. In addition, the recognition of DNA towards σETF DNA binding motifs that led to the transcription activities is also being poorly studied. Therefore, this work studied the possible DNA binding motifs of σETF by utilising in silico approaches. The structure of σETF was first built via three different computational methods. A cognate DNA sequence was then docked to the predicted σETF DNA-binding motifs. The binding free energy calculated using molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) for triplicate 50 ns simulation of σETF-DNA complex revealed favourable binding energy of DNA to σETF (average ∆Gbind = -34.57 kcal/mol) mainly driven by non-polar interactions. This study revealed that σETF LYS131, ARG133, PHE138, TRP146, ARG222, LYS225 and ARG226 are most likely the key residues upon the binding and recognition of DNA prior to transcription actives. Since determination of genome-regulating protein which recognises specific DNA sequence is important to discriminate between the proteins preferences for different genes, this study might provide some understanding on the possible σETF-DNA recognition prior to transcription initiated for the δ-endotoxins production.
    MeSH terms: Bacillus thuringiensis; Base Sequence; DNA; Endotoxins; Spores, Bacterial; Transcription Factors; Transcriptional Activation; Genome; Molecular Dynamics Simulation
  17. Gopalai AA, Lim JL, Li HH, Zhao Y, Lim TT, Eow GB, et al.
    Mol Genet Genomic Med, 2019 Nov;7(11):e604.
    PMID: 31487119 DOI: 10.1002/mgg3.604
    BACKGROUND: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.

    METHODS: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay.

    RESULTS: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H.

    CONCLUSION: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

    MeSH terms: Female; Follow-Up Studies; Genotype; Haplotypes; Humans; Malaysia/epidemiology; Male; Middle Aged; Mutation*; Parkinson Disease/genetics*; Parkinson Disease/epidemiology; Prognosis; Cohort Studies; Case-Control Studies; Genetic Predisposition to Disease*; Asian Continental Ancestry Group/genetics*; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics*
  18. Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
    MeSH terms: Alleles; Brain/drug effects; Brain/metabolism; Brain/physiopathology; Humans; Parkinson Disease/etiology*; Biomarkers*; Computational Biology/methods; Genetic Predisposition to Disease*; Gene Expression Profiling; Drug Discovery; Molecular Sequence Annotation; Molecular Targeted Therapy
  19. Mohd Radzuan NA, Sulong AB, Hui D, Verma A
    Polymers (Basel), 2019 Aug 30;11(9).
    PMID: 31480276 DOI: 10.3390/polym11091425
    Polymer composites have been extensively fabricated given that they are well-fitted for a variety of applications, especially concerning their mechanical properties. However, inadequate outcomes, mainly regarding their electrical performance, have limited their significant potential. Hence, this study proposed the use of multiple fillers, with different geometries, in order to improve the electrical conductivity of a polymer composite. The fabricated composite was mixed, using the ball milling method, before being compressed by a hot press machine at 3 MPa for 10 min. The composite plate was then measured for both its in-plane and through-plane conductivities, which were 3.3 S/cm, and 0.79 S/cm, respectively. Furthermore, the experimental data were then verified using a predicted electrical conductivity model, known as a modified fibre contact model, which considered the manufacturing process, including the shear rate and flow rate. The study indicated that the predicted model had a significant trend and value, compared to the experimental model (0.65 S/cm for sample S1). The resultant fabricated composite materials were found to possess an excellent network formation, and good electrical conductivity for bipolar plate application, when applying compression pressure of 3 MPa for 10 min.
    MeSH terms: Bipolar Disorder; Electric Conductivity; Electricity; Manufactured Materials; Models, Theoretical; Polymers; Pressure
  20. Veno J, Rahman RNZRA, Masomian M, Ali MSM, Kamarudin NHA
    Molecules, 2019 Aug 30;24(17).
    PMID: 31480403 DOI: 10.3390/molecules24173169
    Thermostability remains one of the most desirable traits in many lipases. Numerous studies have revealed promising strategies to improve thermostability and random mutagenesis often leads to unexpected yet interesting findings in engineering stability. Previously, the thermostability of C-terminal truncated cold-adapted lipase from Staphylococcus epidermidis AT2 (rT-M386) was markedly enhanced by directed evolution. The newly evolved mutant, G210C, demonstrated an optimal temperature shift from 25 to 45 °C and stability up to 50 °C. Interestingly, a cysteine residue was randomly introduced on the loop connecting the two lids and accounted for the only cysteine found in the lipase. We further investigated the structural and mechanistic insights that could possibly cause the significant temperature shift. Both rT-M386 and G210C were modeled and simulated at 25 °C and 50 °C. The results clearly portrayed the effect of cysteine substitution primarily on the lid stability. Comparative molecular dynamics simulation analysis revealed that G210C exhibited greater stability than the wild-type at high temperature simulation. The compactness of the G210C lipase structure increased at 50 °C and resulted in enhanced rigidity hence stability. This observation is supported by the improved and stronger non-covalent interactions formed in the protein structure. Our findings suggest that the introduction of a single cysteine residue at the lid region of cold-adapted lipase may result in unexpected increased in thermostability, thus this approach could serve as one of the thermostabilization strategies in engineering lipase stability.
    MeSH terms: Cations; Cold Temperature*; Cysteine/genetics*; Enzyme Stability; Glycine/genetics*; Hydrogen Bonding; Lipase/genetics*; Lipase/chemistry; Models, Molecular; Mutation/genetics*; Salts/chemistry; Solvents; Staphylococcus/enzymology*; Mutant Proteins/metabolism; Molecular Dynamics Simulation
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