Browse publications by year: 2019

  1. Lee JY, Chan CKY, Chua SS, Paraidathathu T, Lee KK, Tan CSS, et al.
    BMJ Open, 2019 Oct 22;9(10):e026575.
    PMID: 31640990 DOI: 10.1136/bmjopen-2018-026575
    OBJECTIVE: Telemedicine has been promoted as an economical and effective way to enhance patient care, but its acceptance among patients in low-income and middle-income countries is poorly understood. This study is aimed to explore the experiences and perspectives of people with type 2 diabetes mellitus that used telemedicine to manage their condition.

    DESIGN: In-depth and focus group interviews were conducted with participants who have engaged in telemedicine. Questions included were participants' perception on the programme being used, satisfaction as well as engagement with the telemedicine programme. All interviews and focus groups were audio-recorded and transcribed verbatim. Data were analysed using a thematic approach.

    PARTICIPANTS AND SETTING: People with type 2 diabetes (n=48) who participated in a randomised controlled study which examined the use of telemedicine for diabetes management were recruited from 11 primary care clinics located within the Klang Valley.

    RESULTS: Twelve focus groups and two in-depth interviews were conducted. Four themes emerged from the analysis: (1) generational difference; (2) independence and convenience, (3) sharing of health data and privacy and (4) concerns and challenges. The main obstacles found in patients using the telemedicine systems were related to internet connectivity and difficulties experienced with system interface. Cost was also another significant concern raised by participants. Participants in this study were primarily positive about the benefits of telemedicine, including its ability to provide real-time data and disease monitoring and the reduction in clinic visits.

    CONCLUSION: Despite the potential benefits of telemedicine in the long-term care of diabetes, there are several perceived barriers that may limit the effectiveness of this technology. As such, collaboration between educators, healthcare providers, telecommunication service providers and patients are required to stimulate the adoption and the use of telemedicine.NCT0246680.

    MeSH terms: Age Factors; Attitude to Computers; Confidentiality; Costs and Cost Analysis; Diabetes Mellitus, Type 2/epidemiology*; Female; Humans; Interviews as Topic; Malaysia/epidemiology; Male; Middle Aged; Self Care*; Computer Security; Focus Groups; Telemedicine*; Personal Autonomy; Information Dissemination
  2. Ariff N, Abdullah A, Azmai MNA, Musa N, Zainathan SC
    Vet World, 2019 Aug;12(8):1273-1284.
    PMID: 31641308 DOI: 10.14202/vetworld.2019.1273-1284
    Background and Aim: Viral nervous necrosis (VNN) is a serious disease of several marine fish species. VNN causes 100% mortality in the larval stages, while lower losses have been reported in juvenile and adult fish. This study aimed to detect the occurrence of VNN while identifying its associated risk factors and the genotypes of its causative agent in a hybrid grouper hatchery in Malaysia.

    Materials and Methods: A batch of newly hatched hybrid grouper fry (Epinephelus fuscoguttatus × Epinephelus lanceolatus) were followed from the larval stage to market size. Samples of the hybrid groupers, water, live feed, and artificial fish pellets were collected periodically from day 0 to 180 in the hybrid grouper hatchery. Reverse transcription-polymerase chain reaction (RT-PCR) and nested PCR amplifications were carried out on VNN-related sequences. The phylogenetic tree including the sampled causative agent of VNN was inferred from the coat protein genes from all known Betanodavirus species using Molecular Evolutionary Genetics Analysis (MEGA). Pearson's correlation coefficient values were calculated to determine the strength of the correlation between the presence of VNN in hybrid grouper samples and its associated risk factors.

    Results: A total of 113 out of 146 pooled and individual samples, including hybrid grouper, water, and artificial fish pellet samples, demonstrated positive results in tests for the presence of VNN-associated viruses. The clinical signs of infection observed in the samples included darkened skin, deformation of the backbone, abdominal distension, skin lesions, and fin erosion. VNN was present throughout the life stages of the hybrid groupers, with the first detection occurring at day 10. VNN-associated risk factors included water temperature, dissolved oxygen content, salinity, ammonia level, fish size (adults more at risk than younger stages), and life stage (age). Detection of VNN-associated viruses in water samples demonstrated evidence of horizontal transmission of the disease. All the nucleotide sequences found in this study had high nucleotide identities of 88% to 100% to each other, striped jack nervous necrosis virus (SJNNV), and the reassortant strain red-spotted grouper NNV/SJNNV (RGNNV/SJNNV) isolate 430.2004 (GenBank accession number JN189932.1) (n=26). The phylogenetic analysis showed that quasispecies was present in each VNN-causing virus-positive sample, which differed based on the type of sample and life stage.

    Conclusion: This study was the first to confirm the existence of a reassortant strain (RGNNV/SJNNV) in hybrid groupers from Malaysia and Southeast Asia. However, the association between the mode of transmission and the risk factors of this virus needs to be investigated further to understand the evolution and potential new host species of the reassortant strain.

    MeSH terms: Ammonia; Animals; Base Sequence; Bass; Genotype; Larva; Malaysia; Nucleotides; Oxygen; Phylogeny; Risk Factors; Satellite Viruses; Temperature; Water; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Nodaviridae; Databases, Nucleic Acid; Capsid Proteins; Reverse Transcription; Salinity
  3. Harnentis H, Nurmiati N, Marlida Y, Adzitey F, Huda N
    Vet World, 2019 Aug;12(8):1352-1357.
    PMID: 31641319 DOI: 10.14202/vetworld.2019.1352-1357
    Aim: This study aimed at optimizing γ-aminobutyric acid (GABA) production using lactic acid bacteria (LAB) of an Indonesian indigenous fermented buffalo milk (dadih) origin. This study utilized LAB previously cultured from dadih that has the ability to produce GABA.

    Materials and Methods: The study started with the identification of selected LAB by 16S rRNA, followed by optimization of GABA production by culture conditions using different initial pH, temperature, glutamate concentration, incubation time, carbon, and nitrogen sources. 16S rRNA polymerase chain reaction and analysis by phylogenetic were used to identify Lactobacillus plantarum (coded as N5) responsible for the production of GABA.

    Results: GABA production by high-performance liquid chromatography was highest at pH of 5.5, temperature of 36°C, glutamate concentration of 500 mM, and incubation time of 84 h. Peptone and glucose served as the nitrogen and carbon sources, respectively, whereas GABA was produced at optimum fermentation condition of 211.169 mM.

    Conclusion: Production of GABA by L. plantarum N5 was influenced by initial pH of 5.5, glutamic acid concentration, nitrogen source, glucose as carbon source, and incubation temperature and time.

    MeSH terms: Animals; Buffaloes; Carbon; Chromatography, High Pressure Liquid; Fermentation; gamma-Aminobutyric Acid; Glucose; Indonesia; Milk; Nitrogen; Peptones; Phylogeny; RNA, Ribosomal, 16S; Temperature; Polymerase Chain Reaction; Bison; Glutamic Acid; Bioreactors; Lactobacillus plantarum; Lactobacillales
  4. Kamaruzzaman MA, Chin KY, Mohd Ramli ES
    PMID: 31641368 DOI: 10.1155/2019/8543618
    Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.
    MeSH terms: Animals; Antioxidants; Biological Products; Honey; Humans; Osteoporosis; Bone Remodeling; Dietary Supplements; Models, Animal; Functional Food; Polyphenols
  5. Wainwright BJ, Zahn GL, Zushi J, Lee NLY, Ooi JLS, Lee JN, et al.
    Ecol Evol, 2019 Oct;9(19):11288-11297.
    PMID: 31641473 DOI: 10.1002/ece3.5631
    Marine fungal biodiversity remains vastly understudied, and even less is known of their biogeography and the processes responsible for driving these distributions in marine environments. We investigated the fungal communities associated with the seagrass Enhalus acoroides collected from Singapore and Peninsular Malaysia to test the hypothesis that fungal communities are homogeneous throughout the study area. Seagrass samples were separated into different structures (leaves, roots, and rhizomes), and a sediment sample was collected next to each plant. Amplicon sequencing of the fungal internal transcribed spacer 1 and subsequent analysis revealed significant differences in fungal communities collected from different locations and different structures. We show a significant pattern of distance decay, with samples collected close to each other having more similar fungal communities in comparison with those that are more distant, indicating dispersal limitations and/or differences in habitat type are contributing to the observed biogeographic patterns. These results add to our understanding of the seagrass ecosystem in an understudied region of the world that is also the global epicenter of seagrass diversity. This work has implications for seagrass management and conservation initiatives, and we recommend that fungal community composition be a consideration for any seagrass transplant or restoration programme.
  6. Gill AR, Hassan S, Haseeb M
    Environ Sci Pollut Res Int, 2019 Nov;26(33):34468-34478.
    PMID: 31642017 DOI: 10.1007/s11356-019-06565-1
    This research article aims to investigate the moderating role of financial development in Environmental Kuznets Curve (EKC) in the context of Malaysia for the period 1970-2016. As the time series variables are integrated of different order therefore, Auto-Regressive Distributed Lag (ARDL) model has been employed to estimate the long-run equilibrium relationship among the variables. The results indicate that EKC does exist for Malaysia and financial development has negative impact on carbon emission. Moreover, financial development is found to have significant moderating impact on income environment relation. More financial development brings early turning point of the EKC. The results recommend that financial development can be used as one of the policy measures to reduce the environmental cost of economic growth in Malaysia.
    MeSH terms: Carbon Dioxide/analysis; Environmental Pollution/statistics & numerical data*; Income; Malaysia; Economic Development*
  7. Yeap JS, Saad HM, Tan CH, Sim KS, Lim SH, Low YY, et al.
    J Nat Prod, 2019 11 22;82(11):3121-3132.
    PMID: 31642315 DOI: 10.1021/acs.jnatprod.9b00712
    A methanol extract of the stem bark of the Malayan Alstonia penangiana provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, 1-6) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, 7). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (1-6) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC50 values: 0.02-9.0 μM).
    MeSH terms: Alkaloids/chemical synthesis*; Alkaloids/pharmacology*; Antineoplastic Agents, Phytogenic/chemical synthesis*; Antineoplastic Agents, Phytogenic/pharmacology*; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Drug Resistance, Neoplasm/drug effects; HT29 Cells; Indole Alkaloids/chemical synthesis*; Indole Alkaloids/pharmacology*; Alstonia/chemistry*; Cell Line, Tumor; Cell Proliferation; A549 Cells
  8. Vashe A, Devi V, Rao R, Abraham RR, Pallath V, Umakanth S
    Adv Physiol Educ, 2019 Dec 01;43(4):522-528.
    PMID: 31642706 DOI: 10.1152/advan.00067.2019
    Today most education institutions around the world have adopted the philosophy of outcome-based education. The emphasis in outcome-based education is achievement of outcomes; hence the curriculum should be designed in a way that it includes the components targeted specifically at achieving these outcomes. A discipline-based approach results in fragmentation of learning and lack of clinical applicability. Integrated teaching could be a solution to achieve required outcomes in a holistic way. Hence, the aim of this study was to develop, implement, and evaluate an integrated teaching module. Temporal coordination of the basic sciences, along with correlation of learned topics to clinical settings, was done in the first year of the undergraduate medical program. The module was evaluated by obtaining qualitative and quantitative feedback from students. Student assessment was conducted with a test that had case vignettes and multiple-choice questions. In addition, students' change in learning approaches and self-directed learning readiness were collected. Students' perception regarding the educational environment was also obtained. Analysis of the data showed positive feedback from the students regarding the integrated teaching. Students' average score in the test was 86%. There was a significant increase in the scores for the deep approach and self-directed learning readiness in the posttest compared with the pretest. Moreover, students were found to be satisfied with the educational environment. Evaluation of integrated teaching revealed that it was well accepted by the students. Moreover, it facilitated the achievement of the students' outcomes.
    MeSH terms: Attitude of Health Personnel; Clinical Competence; Curriculum; Education, Medical, Undergraduate/methods*; Educational Measurement; Educational Status; Humans; India; Health Knowledge, Attitudes, Practice; Learning*; Students, Medical/psychology*; Teaching*; Comprehension
  9. Chan HH, Koh RY, Lim CL, Leong CO
    Curr Alzheimer Res, 2019;16(10):907-918.
    PMID: 31642777 DOI: 10.2174/1567205016666191023102422
    Alzheimer's Disease (AD) is an age-dependent neurodegenerative disorder, the most common type of dementia that is clinically characterized by the presence of beta-amyloid (Aβ) extracellularly and intraneuronal tau protein tangles that eventually leads to the onset of memory and cognition impairment, development of psychiatric symptoms and behavioral disorders that affect basic daily activities. Current treatment approved by the U.S Food and Drug Administration (FDA) for AD is mainly focused on the symptoms but not on the pathogenesis of the disease. Recently, receptor-interacting protein kinase 1 (RIPK1) has been identified as a key component in the pathogenesis of AD through necroptosis. Furthermore, genetic and pharmacological suppression of RIPK1 has been shown to revert the phenotype of AD and its mediating pathway is yet to be deciphered. This review is aimed to provide an overview of the pathogenesis and current treatment of AD with the involvement of autophagy as well as providing a novel insight into RIPK1 in reverting the progression of AD, probably through an autophagy machinery.
    MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/genetics; Alzheimer Disease/metabolism*; Animals; Autophagy/drug effects; Autophagy/physiology; Humans; Amyloid beta-Peptides/administration & dosage; Amyloid beta-Peptides/metabolism; Drug Delivery Systems/methods*; Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors*; Receptor-Interacting Protein Serine-Threonine Kinases/genetics; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
  10. Chaisakul J, Alsolaiss J, Charoenpitakchai M, Wiwatwarayos K, Sookprasert N, Harrison RA, et al.
    PLoS Negl Trop Dis, 2019 10;13(10):e0007338.
    PMID: 31644526 DOI: 10.1371/journal.pntd.0007338
    BACKGROUND: Daboia siamensis (Eastern Russell's viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell's viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand against D. siamensis venoms from four geographical locales: Myanmar, Taiwan, China and Thailand.

    METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.

    CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.

    MeSH terms: Animals; Antivenins/pharmacology*; Antivenins/therapeutic use*; Blood Coagulation Disorders/drug therapy; Blood Urea Nitrogen; Myanmar; China; Creatinine/blood; Kidney/pathology; Lethal Dose 50; Male; Snake Bites/therapy; Taiwan; Thailand; Venoms; Viper Venoms/antagonists & inhibitors; Viper Venoms/immunology; Viper Venoms/toxicity*; Rats, Sprague-Dawley; Russell's Viper; Rats; Renal Insufficiency/chemically induced*; Renal Insufficiency/pathology; Renal Insufficiency/prevention & control*
  11. Surendra NK, Abdul Manaf MR, Hooi LS, Bavanandan S, Mohamad Nor FS, Firdaus Khan SS, et al.
    PLoS One, 2019;14(10):e0218422.
    PMID: 31644577 DOI: 10.1371/journal.pone.0218422
    OBJECTIVES: In Malaysia, there is exponential growth of patients on dialysis. Dialysis treatment consumes a considerable portion of healthcare expenditure. Comparative assessment of their cost effectiveness can assist in providing a rational basis for preference of dialysis modalities.

    METHODS: A cost utility study of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was conducted from a Ministry of Health (MOH) perspective. A Markov model was also developed to investigate the cost effectiveness of increasing uptake of incident CAPD to 55% and 60% versus current practice of 40% CAPD in a five-year temporal horizon. A scenario with 30% CAPD was also measured. The costs and utilities were sourced from published data which were collected as part of this study. The transitional probabilities and survival estimates were obtained from the Malaysia Dialysis and Transplant Registry (MDTR). The outcome measures were cost per life year (LY), cost per quality adjusted LY (QALY) and incremental cost effectiveness ratio (ICER) for the Markov model. Sensitivity analyses were performed.

    RESULTS: LYs saved for HD was 4.15 years and 3.70 years for CAPD. QALYs saved for HD was 3.544 years and 3.348 for CAPD. Cost per LY saved was RM39,791 for HD and RM37,576 for CAPD. The cost per QALY gained was RM46,595 for HD and RM41,527 for CAPD. The Markov model showed commencement of CAPD in 50% of ESRD patients as initial dialysis modality was very cost-effective versus current practice of 40% within MOH. Reduction in CAPD use was associated with higher costs and a small devaluation in QALYs.

    CONCLUSIONS: These findings suggest provision of both modalities is fiscally feasible; increasing CAPD as initial dialysis modality would be more cost-effective.

    MeSH terms: Cost-Benefit Analysis; Female; Humans; Kidney Failure, Chronic/economics*; Malaysia; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory/economics*; Registries*; Health Care Costs*; Models, Economic*; Quality-Adjusted Life Years*
  12. Egedigwe-Ekeleme CA, Ijeh II, Okafor PN, Eleazu CO, Egedigwe UO
    PMID: 30806328 DOI: 10.2174/1871530319666190222163159
    Bentham Science has decided to withdraw this article from the journal in accordance with BSP Editorial Policies and apologizes to its readers for any inconvenience this may cause.

    BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

  13. Xing SC, Mi JD, Chen JY, Xiao L, Wu YB, Liang JB, et al.
    Sci Total Environ, 2019 Nov 25;693:133490.
    PMID: 31635006 DOI: 10.1016/j.scitotenv.2019.07.296
    Lead is among the most common toxic heavy metals and its contamination is of great public concern. Bacillus coagulans is the probiotic which can be considered as the lead absorption sorbent to apply in the lead contaminant water directly or indirectly. A better understanding of the lead resistance and tolerance mechanisms of B. coagulans would help further its development and utilization. Wild-type Bacillus coagulans strain R11 isolated from a lead mine, was acclimated to lead-containing culture media over 85 passages, producing two lead-adapted strains, and the two strains shown higher lead intracellular accumulation ability (38.56-fold and 19.36-fold) and reducing ability (6.94-fold and 7.44-fold) than that of wild type. Whole genome sequencing, genome resequencing, and comparative transcriptomics identified lead resistance and tolerance process significantly involved in these genes which regulated glutathione and sulfur metabolism, flagellar formation and metal ion transport pathways in the lead-adapted strains, elucidating the relationships among the mechanisms regulating lead deposition, deoxidation, and motility and the evolved tolerance to lead. In addition, the B. coagulans mutants tended to form flagellar and chemotaxis systems to avoid lead ions rather than export it, suggesting a new resistance strategy. Based on the present results, the optimum lead concentration in environment should be considered when employed B. coagulans as the lead sorbent, due to the bacteria growth ability decreased in high lead concentration and physiology morphology changed could reduce the lead removal effectiveness. The identified deoxidization and compound secretion genes and pathways in B. coagulans R11 also are potential genetic engineering candidates for synthesizing glutathione, cysteine, methionine, and selenocompounds.
    MeSH terms: Lead*; Stress, Physiological*; Probiotics*; Bacillus coagulans/physiology*
  14. Zaulkffali AS, Md Razip NN, Syed Alwi SS, Abd Jalil A, Abd Mutalib MS, Gopalsamy B, et al.
    Nutrients, 2019 Oct 19;11(10).
    PMID: 31635074 DOI: 10.3390/nu11102525
    This study investigated the effects of vitamins D and E on an insulin-resistant model and hypothesized that this treatment would reverse the effects of Alzheimer's disease (AD) and improves insulin signalling. An insulin-resistant model was induced in SK-N-SH neuronal cells with a treatment of 250 nM insulin and re-challenged with 100 nM at two different incubation time (16 h and 24 h). The effects of vitamin D (10 and 20 ng/mL), vitamin E in the form of tocotrienol-rich fraction (TRF) (200 ng/mL) and the combination of vitamins D and E on insulin signalling markers (IR, PI3K, GLUT3, GLUT4, and p-AKT), glucose uptake and AD markers (GSK3β and TAU) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The results demonstrated an improvement of the insulin signalling pathway upon treatment with vitamin D alone, with significant increases in IR, PI3K, GLUT3, GLUT4 expression levels, as well as AKT phosphorylation and glucose uptake, while GSK3β and TAU expression levels was decreased significantly. On the contrary, vitamin E alone, increased p-AKT, reduced the ROS as well as GSK3β and TAU but had no effect on the insulin signalling expression levels. The combination of vitamins D and E only showed significant increase in GLUT4, p-AKT, reduced ROS as well as GSK3β and TAU. Thus, the universal role of vitamin D, E alone and in combinations could be the potential nutritional agents in restoring the sensitivity of neuronal cells towards insulin and delaying the pathophysiological progression of AD.
    MeSH terms: Gene Expression Regulation/drug effects; Humans; Insulin Resistance; Neuroblastoma; Neurons/drug effects*; Vitamin D/pharmacology*; Vitamin E/pharmacology*; Signal Transduction/drug effects*; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism*; Cell Line, Tumor; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism*
  15. Goh KM, Shahar S, Chan KG, Chong CS, Amran SI, Sani MH, et al.
    Microorganisms, 2019 Oct 18;7(10).
    PMID: 31635256 DOI: 10.3390/microorganisms7100468
    Thousands of prokaryotic genera have been published, but methodological bias in the study of prokaryotes is noted. Prokaryotes that are relatively easy to isolate have been well-studied from multiple aspects. Massive quantities of experimental findings and knowledge generated from the well-known prokaryotic strains are inundating scientific publications. However, researchers may neglect or pay little attention to the uncommon prokaryotes and hard-to-cultivate microorganisms. In this review, we provide a systematic update on the discovery of underexplored culturable and unculturable prokaryotes and discuss the insights accumulated from various research efforts. Examining these neglected prokaryotes may elucidate their novelties and functions and pave the way for their industrial applications. In addition, we hope that this review will prompt the scientific community to reconsider these untapped pragmatic resources.
  16. Subramaniam M, Arshad NM, Mun KS, Malagobadan S, Awang K, Nagoor NH
    Biomolecules, 2019 10 18;9(10).
    PMID: 31635311 DOI: 10.3390/biom9100626
    Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1'-S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.
    MeSH terms: Animals; Antineoplastic Agents/chemical synthesis; Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry; Benzyl Alcohols/chemical synthesis; Benzyl Alcohols/pharmacology*; Benzyl Alcohols/chemistry; Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cisplatin/chemical synthesis; Cisplatin/pharmacology*; Cisplatin/chemistry; Drug Combinations; Drug Screening Assays, Antitumor; Female; Mice, Inbred BALB C; Mycobacterium/isolation & purification*; Cytokines/blood; Apoptosis/drug effects; Cell Proliferation/drug effects; Mice
  17. Ezhilarasu H, Ramalingam R, Dhand C, Lakshminarayanan R, Sadiq A, Gandhimathi C, et al.
    Int J Mol Sci, 2019 Oct 18;20(20).
    PMID: 31635374 DOI: 10.3390/ijms20205174
    Aloe vera (AV) and tetracycline hydrochloride (TCH) exhibit significant properties such as anti-inflammatory, antioxidant and anti-bacterial activities to facilitate skin tissue engineering. The present study aims to develop poly-ε-caprolactone (PCL)/ AV containing curcumin (CUR), and TCH loaded hybrid nanofibrous scaffolds to validate the synergistic effect on the fibroblast proliferation and antimicrobial activity against Gram-positive and Gram-negative bacteria for wound healing. PCL/AV, PCL/CUR, PCL/AV/CUR and PCL/AV/TCH hybrid nanofibrous mats were fabricated using an electrospinning technique and were characterized for surface morphology, the successful incorporation of active compounds, hydrophilicity and the mechanical property of nanofibers. SEM revealed that there was a decrease in the fiber diameter (ranging from 360 to 770 nm) upon the addition of AV, CUR and TCH in PCL nanofibers, which were randomly oriented with bead free morphology. FTIR spectra of various electrospun samples confirmed the successful incorporation of AV, CUR and TCH into the PCL nanofibers. The fabricated nanofibrous scaffolds possessed mechanical properties within the range of human skin. The biocompatibility of electrospun nanofibrous scaffolds were evaluated on primary human dermal fibroblasts (hDF) by MTS assay, CMFDA, Sirius red and F-actin stainings. The results showed that the fabricated PCL/AV/CUR and PCL/AV/TCH nanofibrous scaffolds were non-toxic and had the potential for wound healing applications. The disc diffusion assay confirmed that the electrospun nanofibrous scaffolds possessed antibacterial activity and provided an effective wound dressing for skin tissue engineering.
    MeSH terms: Aloe/chemistry*; Anti-Bacterial Agents/administration & dosage; Biocompatible Materials/chemistry*; Cell Survival; Fibroblasts; Humans; Materials Testing; Microbial Sensitivity Tests; Skin*; Spectrum Analysis; Tetracycline/administration & dosage*; Tetracycline/chemistry; Wound Healing; Biomarkers; Tissue Engineering*; Cell Proliferation; Mechanical Phenomena; Drug Liberation
  18. Ng TYS, Chew TL, Yeong YF, Jawad ZA, Ho CD
    Sci Rep, 2019 10 21;9(1):15062.
    PMID: 31636339 DOI: 10.1038/s41598-019-51460-x
    In recent years, there are increasing interest on applying ultrasonic irradiation for the synthesis of zeolite due to its advantages including remarkable shortened synthesis duration. In this project, the potential of ultrasonic irradiation treatment on the synthesis of zeolite RHO was investigated. Ultrasonic irradiation treatment time was varied from 30 to 120 minutes for the synthesis of zeolite RHO. The zeolite RHO solid samples were characterized with X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA) and nitrogen adsorption-desorption analysis. The application of ultrasonic irradiation treatment in this study has accelerated the synthesis of zeolite RHO where the synthesis duration has been significantly shortened to 2 days compared to 8 days required by conventional hydrothermal heating without ultrasonic irradiation treatment. Highly crystalline zeolite RHO crystals in truncated octahedron morphology were successfully formed.
    MeSH terms: Adsorption; Heating; Heterocyclic Compounds; Microscopy, Electron, Scanning; Nitrogen; Time Factors; Ultrasonics; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Zeolites
  19. Mohideen SK, Mustangin M, Kamaruddin NA, Muhammad R, Jamal ARA, Sukor N, et al.
    PMID: 31636604 DOI: 10.3389/fendo.2019.00666
    Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.
    MeSH terms: Adenoma; Adrenal Glands; Adrenalectomy; Aldosterone; Cytoplasm; Female; Genotype; Humans; Hyperaldosteronism; Immunohistochemistry; Male; Mutation; Staining and Labeling; Cohort Studies; Zona Fasciculata; Prevalence; Sequence Analysis, DNA; Cytochrome P-450 CYP11B2
  20. Aldoghachi AF, Baharudin A, Ahmad U, Chan SC, Ong TA, Yunus R, et al.
    Dis Markers, 2019;2019:3875147.
    PMID: 31636736 DOI: 10.1155/2019/3875147
    The ceramide synthase 2 (CERS2) gene has been linked to tumour recurrence and invasion in many different types of cancers including bladder cancer. In this study, the expression levels of CERS2 in bladder cancer cell lines were analysed using qRT-PCR and the protein expression in clinical bladder cancer histopathological specimens were examined via immunohistochemistry. The potential utility of CERS2 as a predictive biomarker of response to oncolytic virotherapy was assessed by correlating the CERS2 mRNA expression to IC50 values of cells treated with the Newcastle disease virus (NDV), AF2240 strain. This study demonstrates that CERS2 is differentially expressed in different types of bladder cancer cell lines and that the siRNA-mediated downregulation of the expression of CERS2 reduces the migratory potential of UMUC1 bladder cancer cells. However, there were no significant correlations between the expression levels of the CERS2 protein with bladder cancer grade/stage or between the IC50 values of cells treated with NDV and CERS2 expression. Although the utility of CERS2 expression may be limited, its potential as an antimigration cancer therapeutic should be further examined.
    MeSH terms: Urinary Bladder Neoplasms/metabolism*; Cell Movement; Humans; Membrane Proteins/metabolism*; Neoplasm Recurrence, Local; Newcastle disease virus; Phenotype; Biomarkers, Tumor/metabolism*; Gene Expression Regulation, Neoplastic*; Inhibitory Concentration 50; Tumor Suppressor Proteins/metabolism*; RNA, Small Interfering/metabolism; Cell Line, Tumor; Oncolytic Virotherapy; Sphingosine N-Acyltransferase/metabolism*
External Links