Browse publications by year: 2019

Fulltext Willingness to pay for hepatitis B vaccination in Selangor, Malaysia: A cross-sectional household survey

Rajamoorthy Y, Radam A, Taib NM, Rahim KA, Munusamy S, Wagner AL, et al.

PLoS One, 2019;14(4):e0215125.
PMID: 30964934 DOI: 10.1371/journal.pone.0215125

BACKGROUND: In Malaysia, one million individuals are estimated to be infected with the hepatitis B virus. A vaccine for infants has been compulsory since 1989, whereas those born before 1989 need to spend their own money to be vaccinated in private clinics or hospitals. The aim of this study was to investigate and ascertain the determinants of willingness to pay (WTP) for adult hepatitis B vaccine in Selangor, Malaysia.
METHODS: In 2016, 728 households were selected through a stratified, two stage cluster sample and interviewed. Willingness to pay for hepatitis B vaccine was estimated using the Contingent Valuation Method, and factors affecting WTP were modelled with logit regression.
RESULTS: We found that 273 (37.5%) of the households were willing to pay for hepatitis B vaccination. The mean and median of WTP was estimated at Ringgit Malaysia (RM)303 (approximately US$73) for the three dose series. The estimated WTP was significantly greater in those with higher levels of education, among Malays and Chinese (compared to others, predominantly Indians), and for those with greater perceived susceptibility to hepatitis B virus infection. Other factors-perceived severity, barriers, benefits and cues to action-were not significantly associated with WTP for adult hepatitis B vaccination.
CONCLUSION: Additional resources are needed to cover the households that are not willing to pay for hepatitis B vaccination. More awareness (particularly in regards to hepatitis B virus susceptibility) could change the national perception towards self-paid hepatitis B virus vaccination and increase hepatitis B vaccine coverage.

MeSH terms: Adult; Cross-Sectional Studies; Family Characteristics; Female; Hepatitis B/economics*; Hepatitis B/prevention & control; Hepatitis B/psychology; Hepatitis B/virology; Hepatitis B virus/drug effects*; Humans; Malaysia; Male; Middle Aged; Surveys and Questionnaires*; Vaccination/economics*; Vaccination/psychology*; Vaccination/statistics & numerical data; Hepatitis B Vaccines/economics*
Catalytic co-pyrolysis of sugarcane bagasse and waste high-density polyethylene over faujasite-type zeolite

Hassan H, Lim JK, Hameed BH

Bioresour Technol, 2019 Mar 28;284:406-414.
PMID: 30965196 DOI: 10.1016/j.biortech.2019.03.137

This study investigated the catalytic co-pyrolysis of sugarcane bagasse (SCB) and waste high-density polyethylene (HDPE) over faujasite-type zeolite derived from electric arc furnace slag (FAU-EAFS) in a fixed-bed reactor. The effects of reaction temperature, catalyst-to-feedstock ratio, and HDPE-to-SCB ratio on product fractional yields and chemical compositions were discussed. The co-pyrolysis of SCB and HDPE over FAU-EAFS increased the liquid yield and enhanced the quality of bio-oil. The maximum bio-oil (68.56 wt%) and hydrocarbon yield (74.55%) with minimum yield of oxygenated compounds (acid = 0.57% and ester = 0.67%) were achieved under the optimum experimental conditions of catalyst-to-feedstock ratio of 1:6, HDPE-to-SCB ratio of 40:60, and temperature of 500 °C. The oil produced by catalytic co-pyrolysis had higher calorific value than the oil produced by the pyrolysis of SCB alone.

MeSH terms: Catalysis; Cellulose; Plant Oils; Temperature; Zeolites; Polyethylene; Saccharum; Polyphenols
Fulltext A case of cardiac arrest due to air embolism during scoliosis surgery

Haji Mohd Amin MZ, Beng JTB, Young BTY, Faruk Seman NA, Ching TS, Chek WC

J Orthop Surg (Hong Kong), 2019 4 9;27(2):2309499019840083.
PMID: 30955449 DOI: 10.1177/2309499019840083

Cardiac arrest during scoliosis surgery is rare in idiopathic scoliosis. We present a case of cardiorespiratory collapse during corrective surgery in a young patient with idiopathic scoliosis. A diagnosis of venous air embolism was made by exclusion. A cardiorespiratory resuscitation was performed in supine position. Patient recovered without any sequelae and had operation completed 6 weeks later.

MeSH terms: Echocardiography; Embolism, Air/complications*; Embolism, Air/diagnosis; Female; Heart Arrest/diagnosis; Heart Arrest/etiology*; Heart Arrest/therapy; Humans; Intraoperative Complications*; Lumbar Vertebrae/surgery; Pulmonary Embolism/complications*; Pulmonary Embolism/diagnosis; Scoliosis/surgery*; Spinal Fusion/adverse effects*; Thoracic Vertebrae/surgery; Cardiopulmonary Resuscitation/methods; Young Adult; Computed Tomography Angiography
Fulltext C1-C2 fusion with absence of C1 posterior arch and presence of C2 high-riding vertebral artery: Is it possible?

Wong TS, Abdul Rashid ML, Hasan MS, Chiu CK, Chan CYW, Kwan MK

J Orthop Surg (Hong Kong), 2019 4 9;27(2):2309499019840763.
PMID: 30955474 DOI: 10.1177/2309499019840763

The presence of anatomical anomalies such as absence of C1 posterior arch and presence of C2 high-riding vertebral artery may not allow a conventional C1-C2 fusion, and this patient will require occipitocervical fusion. A 62-year-old lady presented with cervical myelopathy. CT scan demonstrated an os odontoideum with C1-C2 dislocation. The posterior arch of atlas on right C1 vertebra was absent, and there was high-riding vertebral artery on left C2. MRI revealed severe cord compression with cord oedema. The chronic atlantoaxial dislocation was reduced successfully with skeletal traction. Hybrid C1-C2 fusion augmented with autogenous local bone graft with corticocancellous iliac crest bone graft was performed to avoid an unnecessary occipitocervical fusion. She was stable throughout surgery and discharged 6 days later. CT scan 6 months post-operation showed a solid posterior fusion mass. Hybrid C1-C2 fusion can be performed to avoid occipitocervical fusion despite presence of abnormal anatomy at C1 and C2 vertebrae.

MeSH terms: Atlanto-Axial Joint/surgery; Bone Screws*; Cervical Vertebrae/surgery*; Dislocations/complications; Dislocations/diagnosis; Dislocations/surgery*; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Spinal Cord Compression/diagnosis; Spinal Cord Compression/etiology; Spinal Cord Compression/surgery*; Spinal Fusion/methods*; Tomography, X-Ray Computed
Comparison of prediction model using spatial discriminant analysis for marine water quality index in mangrove estuarine zones

Samsudin MS, Azid A, Khalit SI, Sani MSA, Lananan F

Mar Pollut Bull, 2019 Apr;141:472-481.
PMID: 30955758 DOI: 10.1016/j.marpolbul.2019.02.045

The prediction models of MWQI in mangrove and estuarine zones were constructed. The 2011-2015 data employed in this study entailed 13 parameters from six monitoring stations in West Malaysia. Spatial discriminant analysis (SDA) had recommended seven significant parameters to develop the MWQI which were DO, TSS, O&G, PO4, Cd, Cr and Zn. These selected parameters were then used to develop prediction models for the MWQI using artificial neural network (ANN) and multiple linear regressions (MLR). The SDA-ANN model had higher R2 value for training (0.9044) and validation (0.7113) results than SDA-MLR model and was chosen as the best model in mangrove estuarine zone. The SDA-ANN model had also demonstrated lower RMSE (5.224) than the SDA-MLR (12.7755). In summary, this work suggested that ANN was an effective tool to compute the MWQ in mangrove estuarine zone and a powerful alternative prediction model as compared to the other modelling methods.

MeSH terms: Malaysia; Models, Theoretical*; Discriminant Analysis; Linear Models; Neural Networks (Computer); Wetlands*; Water Quality*; Estuaries*
Incremental benefits of EEG informed fMRI in the study of disorders related to meso-corticolimbic dopamine pathway dysfunction: A systematic review of recent literature

Syed Nasser N, Ibrahim B, Sharifat H, Abdul Rashid A, Suppiah S

J Clin Neurosci, 2019 Jul;65:87-99.
PMID: 30955950 DOI: 10.1016/j.jocn.2019.03.054

Functional magnetic resonance imaging (fMRI) is a non-invasive imaging modality that enables the assessment of neural connectivity and oxygen utility of the brain using blood oxygen level dependent (BOLD) imaging sequence. Electroencephalography (EEG), on the other hands, looks at cortical electrical impulses of the brain thus detecting brainwave patterns during rest and thought processing. The combination of these two modalities is called fMRI with simultaneous EEG (fMRI-EEG), which has emerged as a new tool for experimental neuroscience assessments and has been applied clinically in many settings, most commonly in epilepsy cases. Recent advances in imaging has led to fMRI-EEG being utilized in behavioural studies which can help in giving an objective assessment of ambiguous cases and help in the assessment of response to treatment by providing a non-invasive biomarker of the disease processes. We aim to review the role and interpretation of fMRI-EEG in studies pertaining to psychiatric disorders and behavioral abnormalities.

MeSH terms: Adult; Brain/physiopathology; Brain Mapping/methods; Electroencephalography/methods*; Epilepsy/physiopathology; Humans; Magnetic Resonance Imaging/methods*; Male; Oxygen/blood; Rest; Brain Waves/physiology; Dopaminergic Neurons
Reflecting on the role of a pharmacist during the two major earthquakes of 2015: Are we prepared for similar future disasters?

Shrestha S, Kandel P, Danekhu K, Bhuvan KC

Res Social Adm Pharm, 2019 Dec;15(12):1500-1501.
PMID: 30956094 DOI: 10.1016/j.sapharm.2019.03.006
Fulltext TREM-1 modulation produces positive outcome on the histopathology and cytokines release profile of Plasmodium berghei-infected mice

Chin VK, Asyran AMY, Zakaria ZA, Abdullah WO, Chong PP, Nordin N, et al.

J Parasit Dis, 2019 Mar;43(1):139-153.
PMID: 30956457 DOI: 10.1007/s12639-018-1070-3

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic target for various inflammatory diseases. Despite that, the role of TREM-1 during malaria pathogenesis remains obscure with present literature suggesting a link between TREM-1 with severe malaria development. Therefore, this study aims to investigate the role of TREM-1 and TREM-1 related drugs during severe malaria infection in Plasmodium berghei-infected mice model. Our findings revealed that TREM-1 concentration was significantly increased throughout the infection periods and TREM-1 was positively correlated with malaria parasitemia development. This suggests a positive involvement of TREM-1 in severe malaria development. Meanwhile, blocking of TREM-1 activation using rmTREM-1/Fc and TREM-1 clearance by mTREM-1/Ab had significantly reduced malaria parasitemia and suppressed the production of pro- inflammatory cytokines (TNF-α, IL-6 and IFN-γ) and anti-inflammatory cytokine (IL-10). Furthermore, histopathological analysis of TREM-1 related drug treatments, in particular rmTREM-1/Fc showed significant improvements in the histological conditions of major organs (kidneys, spleen, lungs, liver and brain) of Plasmodium berghei-infected mice. This study showed that modulation of TREM-1 released during malaria infection produces a positive outcome on malaria infection through inhibition of pro-inflammatory cytokines secretion and alleviation of histopathological conditions of affected organs. Nevertheless, further investigation on its optimal dosage and dose dependant study should be carried out to maximise its full potential as immunomodulatory or as an adjuvant in line with current antimalarial agents.

MeSH terms: Animals; Anti-Inflammatory Agents; Antimalarials; Brain; Disease Models, Animal; Pharmaceutical Preparations; Kidney; Liver; Lung; Malaria; Plasmodium berghei; Bodily Secretions; Spleen; Tumor Necrosis Factor-alpha; Interleukin-6; Cytokines; Interleukin-10; Parasitemia; Mice
Effect of Chitosan Nanoparticle-Loaded Thymus serpyllum on Hydrogen Peroxide-Induced Bone Marrow Stromal Cell Damage

Baig S, Azizan AHS, Raghavendran HRB, Natarajan E, Naveen S, Murali MR, et al.

Stem Cells Int, 2019;2019:5142518.
PMID: 30956670 DOI: 10.1155/2019/5142518

We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loaded TS on hydrogen peroxide-induced cell death of mesenchymal stromal cells (MSCs) in vitro. Gas chromatography-mass spectroscopy confirmed the spectrum of active components in the extract. Out of the three different extracts, the hexane extract showed significant free radical scavenging activity. Treatment of MSCs with H2O2 (hydrogen peroxide) significantly increased intracellular cell death; however, pretreatment with TS extract and nanoparticle-loaded TS (200 μg/ml) suppressed H2O2-induced elevation of Cyt-c and MMP13 and increased the survival rates of MSCs. H2O2-induced (0.1 mM) changes in cytokines were attenuated in the extract and nanoparticles by pretreatment and cotreatment at two time points (p < 0.05). H2O2 increased cell apoptosis. In contrast, treatment with nanoparticle-loaded TS suppressed the percentage of apoptosis considerably (p < 0.05). Therefore, TS may be considered as a potential candidate for enhancing the effectiveness of MSC transplantation in cell therapy.

MeSH terms: Chromatography, Gas; Combined Modality Therapy; Hexanes; Hydrogen Peroxide; Mass Spectrometry; Survival Rate; Cytokines; Cell Death; Apoptosis; Matrix Metalloproteinase 13; Nanoparticles; Cell- and Tissue-Based Therapy
Momordica charantia (Indian and Chinese Bitter Melon) Extracts Inducing Apoptosis in Human Lung Cancer Cell Line A549 via ROS-Mediated Mitochodria Injury

Thiagarajan S, Arapoc DJ, Husna Shafie N, Keong YY, Bahari H, Adam Z, et al.

Evid Based Complement Alternat Med, 2019;2019:2821597.
PMID: 30956678 DOI: 10.1155/2019/2821597

Lung cancer is the leading cause of cancer related deaths worldwide with about 40% occurring in developing countries. The two varieties of Momordica charantia, which are Chinese and Indian bitter melon, have been subjected to antiproliferative activity in human non-small cell lung cells A549. The A549 cells were treated with hot and cold aqueous extraction for both the bitter melon varieties, and the antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic mechanism of action on A549 human lung cancer cells was evaluated first morphologically using Hoechst 33358, and cytoskeleton staining using Filamentous-actin (F-actin) cytoskeleton FICT and DAPI followed by caspase-3/7, reactive oxygen species (ROS), and p53 activity. Chinese hot aqueous extraction (CHA) exhibited potent antiproliferative activity against A549 human lung cancer cells. The morphological analysis of mitochondria destruction and the derangement of cytoskeleton showed apoptosis-inducing activity. CHA increased the caspase-3/7 activity by 1.6-fold and the ROS activity by 5-fold. Flow cytometric analysis revealed 34.5% of apoptotic cells significantly (p<0.05) compared to cisplatin-treated A549 human cancer cells. CHA is suggested to induce apoptosis due to their rich bioactive chemical constituents. These findings suggest that the antiproliferative effect of CHA was due to apoptosis via ROS-mediated mitochondria injury.

MeSH terms: Actins; Cisplatin; Cytoskeleton; Developing Countries; Humans; Lung Neoplasms; Mitochondria; Staining and Labeling; Tetrazolium Salts; Thiazoles; Tumor Suppressor Protein p53; Apoptosis; Reactive Oxygen Species; Momordica charantia; Caspase 3; A549 Cells
Synthesis and modelling of the mechanical properties of Ag, Au and Cu nanowires

Lah NAC, Trigueros S

Sci Technol Adv Mater, 2019;20(1):225-261.
PMID: 30956731 DOI: 10.1080/14686996.2019.1585145

The recent interest to nanotechnology aims not only at device miniaturisation, but also at understanding the effects of quantised structure in materials of reduced dimensions, which exhibit different properties from their bulk counterparts. In particular, quantised metal nanowires made of silver, gold or copper have attracted much attention owing to their unique intrinsic and extrinsic length-dependent mechanical properties. Here we review the current state of art and developments in these nanowires from synthesis to mechanical properties, which make them leading contenders for next-generation nanoelectromechanical systems. We also present theories of interatomic interaction in metallic nanowires, as well as challenges in their synthesis and simulation.

MeSH terms: Attention; Color; Copper; Gold; Miniaturization; Silver; Nanotechnology; Nanowires
Comparison of Clinical Results and Pathological Examinations Between Locally Synthesized Bone-derived Hydroxyapatite and Medpor® Orbital Implants in Animal Models

Roslinah M, Wan Hitam WH, Md Salleh MS, Abdul Hamid SS, Shatriah I

Cureus, 2019 Jan 25;11(1):e3954.
PMID: 30956907 DOI: 10.7759/cureus.3954

We aimed to compare clinical and pathological reactions towards locally synthesized bovine bone derived from hydroxyapatite (bone docosahexaenoic acid (dHA)) and commercially available porous polyethylene (Medpor®, Porex Surgical Incorporation, Georgia, USA) orbital implants in animal models. An experimental study was performed on 14 New Zealand white rabbits. Group A (n=7) was implanted with bovine bone dHA and group B (n=7) was implanted with Medpor®. Clinical examinations were performed on Days 1, 7, 14, 28, and 42 post-implantation. The implanted eyes were enucleated on Day 42 and were sent for pathological evaluation. Serial clinical examinations included urine color and odor; feeding and physical activity demonstrated normal wellbeing in all the subjects. Localized minimal infection was observed in both groups during the first two weeks following implantation, and the subjects responded well to topical moxifloxacin. Both groups exhibited evidence of wound breakdown. No signs of implant migration or extrusion were observed in either group. The histopathological examination revealed no statistically significant difference in inflammatory cell reactions and fibrovascular tissue maturation between both types of implants. However, all (100%) of the bovine bone dHA implants displayed complete fibrovascular ingrowth compared to Medpor® implants (57.1%) at six weeks post-implantation (p=0.001). In conclusion, bovine bone dHA and Medpor® orbital implants were well-tolerated clinically and displayed similar inflammatory reactions and fibrovascular tissue maturation. Locally synthesized bovine bone dHA orbital implants displayed significantly greater complete fibrovascular ingrowth in comparison with Medpor® implants.

MeSH terms: Animals; Cattle; Docosahexaenoic Acids; Georgia; Rabbits; Surgical Wound Dehiscence; Porosity; Durapatite; Orbital Implants; Polyethylene; Models, Animal
Fulltext Dendrimer entrapped microsponge gel of dithranol for effective topical treatment

Tripathi PK, Gorain B, Choudhury H, Srivastava A, Kesharwani P

Heliyon, 2019 Mar;5(3):e01343.
PMID: 30957038 DOI: 10.1016/j.heliyon.2019.e01343

Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes. However, its application is troublesome and inconvenient because of its associated side effects, including staining, burning sensation, irritation, and necrotizing effect on the diseased cells as well as on the normal cells. The purpose of the current investigation was to explore the potential of poly(amido) amine (PAMAM) dendrimers in the topical delivery of dithranol through a novel microsponge based gel. Generation-4 (G4) dendrimers were incorporated into the microsponge based gel formulation by quasi-emulsion solvent diffusion method with varying concentration of polymers, and evaluated for the morphology of the formulation, encapsulation efficiency and skin irritation potential. Percentage yield of the formulation was found to be 66.28%, whereas encapsulation efficiency was ranged between 71.33% to 49.21%, and an average particle size was ranged between 28 ± 1.12 μm to 130 ± 1.01 μm. Surface morphology of developed microsponge was confirmed by scanning electron microscopy, revealed micro-porous nature. The optimized microsponge formulation was found to be stable and recorded non-irritant during cutaneous application of the experimental animals. Further, the pharmacokinetic outcomes of study were showed prolong penetration of the drug through the skin, equivalent to the marketed formulation of dithranol. Therefore, it could be conferred that the microsponge formulation of the PAMAM entrapped dithranol can produce prolonged efficacy without producing toxicities to the skin, and thus can effectively be projected in the treatment of diseases like psoriasis.
Do not judge doctors for not telling the truth to young children

Khoo EJ

J Paediatr Child Health, 2019 Apr;55(4):487-488.
PMID: 30957328 DOI: 10.1111/jpc.14416
Molecular Insight and Mode of Inhibition of α-Glucosidase and α-Amylase by Pahangensin A from Alpinia pahangensis Ridl

Loo KY, Leong KH, Sivasothy Y, Ibrahim H, Awang K

Chem Biodivers, 2019 Jun;16(6):e1900032.
PMID: 30957403 DOI: 10.1002/cbdv.201900032

The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC50 =114.80 μm) and α-glucosidase (IC50 =153.87 μm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.

MeSH terms: alpha-Amylases/antagonists & inhibitors; alpha-Amylases/metabolism*; alpha-Glucosidases/metabolism*; alpha-Glucosidases/chemistry; Binding Sites; Diterpenes/isolation & purification; Diterpenes/metabolism; Diterpenes/chemistry*; Enzyme Inhibitors/metabolism; Enzyme Inhibitors/chemistry; Kinetics; Plant Extracts/chemistry; Catalytic Domain; Alpinia/metabolism; Alpinia/chemistry*; Molecular Docking Simulation
Changes in skeletal muscle thickness and echogenicity and plasma creatinine concentration as indicators of protein and intramuscular fat mobilization in periparturient dairy cows

Megahed AA, Hiew MWH, Ragland D, Constable PD

J Dairy Sci, 2019 Jun;102(6):5550-5565.
PMID: 30954258 DOI: 10.3168/jds.2018-15063

High-producing dairy cows experience a state of negative energy balance in the periparturient period that is partially addressed by increasing the rate of fat and protein mobilization. Previous studies have focused on the rate of fat mobilization, and consequently the rate of protein mobilization has not been well characterized. The objective of this study was therefore to determine the change in indicators of muscle mass during early lactation using ultrasonographic measurement of muscle thickness and changes in plasma creatinine concentration. The maximum thickness of the gluteus medius and longissimus dorsi muscles of 106 Holstein cows (34 primiparous, 72 multiparous) was determined ultrasonographically on d -3, 0, 3, 7, 14, 21, and 28 relative to the day of parturition. Plasma creatinine concentration was measured periodically during the same period. Mixed models analysis and Passing-Bablok regression were used to analyze the data. Gluteus medius thickness, longissimus dorsi loin thickness (LDLT), and longissimus dorsi thoracic thickness (LDTT) were decreased at 28 d postpartum compared with d 3 antepartum. Plasma creatinine concentration was weakly associated with gluteus medius thickness, LDLT, and LDTT (Spearman's rho = 0.31, 0.39, and 0.32, respectively). Plasma creatinine concentration in primiparous and multiparous cows at 28 d postpartum decreased by 0.24 and 0.30 mg/dL, respectively, compared with values 3 d antepartum. We concluded that ultrasonographic measurement of LDLT and LDTT and change in plasma creatinine concentration may provide practical methods for monitoring the rate of protein mobilization in periparturient dairy cows. Ultrasonographic examination of LDLT and LDTT therefore complements ultrasonographic measurement of backfat thickness and may be useful in the evaluation of energy reserve mobilization in periparturient dairy cows.

MeSH terms: Animals; Cattle/blood*; Cattle/growth & development; Cattle/physiology; Creatinine/blood*; Energy Metabolism; Fats/metabolism*; Female; Lactation; Milk/metabolism; Pregnancy; Proteins/metabolism*; Muscle, Skeletal/growth & development; Muscle, Skeletal/metabolism*; Parturition; Postpartum Period/blood; Postpartum Period/physiology
Fulltext Lactobacillus plantarum DR7 improved upper respiratory tract infections via enhancing immune and inflammatory parameters: A randomized, double-blind, placebo-controlled study

Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, et al.

J Dairy Sci, 2019 Jun;102(6):4783-4797.
PMID: 30954261 DOI: 10.3168/jds.2018-16103

The aims of this study were to investigate the effects of Lactobacillus plantarum DR7 isolated from bovine milk against upper respiratory tract infections (URTI) and elucidate the possible mechanisms underlying immunomodulatory properties. The DR7 strain (9 log cfu/d) was administered for 12 wk in a randomized, double-blind, and placebo-controlled human study involving 109 adults (DR7, n = 56; placebo, n = 53). Subjects were assessed for health conditions monthly via questionnaires, and blood samples were evaluated for cytokine concentrations, peroxidation and oxidative stress, and gene expression in T cells and natural killer (NK) cells. The administration of DR7 reduced the duration of nasal symptoms (mean difference 5.09 d; 95% CI: 0.42-9.75) and the frequency of URTI (mean difference 0.32; 95% CI: 0.01-0.63) after 12 and 4 wk, respectively, compared with the placebo. The DR7 treatment suppressed plasma proinflammatory cytokines (IFN-γ, TNF-α) in middle-aged adults (30 to 60 yr old), while enhancing anti-inflammatory cytokines (IL-4, IL-10) in young adults (<30 yr old), accompanied by reduced plasma peroxidation and oxidative stress levels compared with the placebo. Young adults who received DR7 showed higher expression of plasma CD44 and CD117 by 4.50- and 2.22-fold, respectively, compared with the placebo. Meanwhile, middle-aged adults showed lower expression of plasma CD4 and CD8 by 11.26- and 1.80-fold, respectively, compared with the placebo, indicating less T-cell activation. In contrast, both young and middle-aged adults who received DR7 showed enhanced presence of nonresting and mature NK cells compared with those who received the placebo. We postulate that DR7 alleviated the symptoms of URTI by improving inflammatory parameters and enhancing immunomodulatory properties.

MeSH terms: Adolescent; Adult; Animals; Double-Blind Method; Female; Humans; Killer Cells, Natural/immunology; Male; Middle Aged; Cytokines/immunology; Interleukin-10/immunology; Young Adult
Establishment of an immunofluorescence assay to detect IgM antibodies to Nipah virus using HeLa cells expressing recombinant nucleoprotein

Kaku Y, Park ES, Noguchi A, Inoue S, Lunt R, Malbas FF, et al.

J Virol Methods, 2019 07;269:83-87.
PMID: 30954461 DOI: 10.1016/j.jviromet.2019.03.009

A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.

MeSH terms: Animals; Antibodies, Viral/blood*; HeLa Cells; Humans; Immunoglobulin M/blood*; Macaca/immunology; Macaca/virology; Recombinant Proteins/immunology; Serologic Tests/methods; Fluorescent Antibody Technique, Indirect/methods*; Capsid Proteins/genetics*; Capsid Proteins/immunology; Nipah Virus; Henipavirus Infections/blood; Henipavirus Infections/diagnosis*; Henipavirus Infections/immunology
Comprehensive spectroscopic studies of synergism between Gadong starch based carbon dots and bovine serum albumin

Sonthanasamy RSA, Sulaiman NMN, Tan LL, Lazim AM

Spectrochim Acta A Mol Biomol Spectrosc, 2019 Jul 05;218:85-96.
PMID: 30954801 DOI: 10.1016/j.saa.2019.03.108

Carbon dots (C-dots) were used to study the binding mechanisms with serum protein, bovine serum albumin (BSA) by using two notable binding systems known as non-covalent and covalent interaction. Interaction between C-dots and BSA were estimated by Stern-Volmer equation and Double Log Regression Model (DLRM). According to the fluorescent intensity, quenching of model carrier protein by C-dots was due to dynamic quenching for non-covalent and static quenching for covalent binding. The binding site constant, KA and number of binding site, for covalent interaction is 1754.7L/mol and n≈1 (0.6922) were determined by DLRM on fluorescence quenching results. The blue shift of the fluorescence spectrum, from 450nm to 421nm (non-covalent) and 430nm (covalent) and suggested that both the microenvironment of C-dots and protein changed in relation to the protein concentration. The fluorescence intensity results show that protein structure has a significant role in Protein-C-dots interactions and type of binding influence physicochemical properties of C-dots differently. Understanding to this bio interface is important to utilize both quantum dots and biomolecules for biomedical field. It can be a useful guideline to design further applications in biomedical and bioimaging.

MeSH terms: Animals; Binding Sites; Carbon/metabolism*; Carbon/chemistry; Cattle; Protein Binding; Serum Albumin, Bovine/metabolism*; Serum Albumin, Bovine/chemistry; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Starch/metabolism; Starch/chemistry; Thermodynamics; Quantum Dots/metabolism*; Quantum Dots/ultrastructure; Quantum Dots/chemistry; Immobilized Proteins/metabolism; Immobilized Proteins/chemistry; Molecular Docking Simulation
Small molecules enhance neurogenic differentiation of dental-derived adult stem cells

Heng BC, Jiang S, Yi B, Gong T, Lim LW, Zhang C

Arch Oral Biol, 2019 Jun;102:26-38.
PMID: 30954806 DOI: 10.1016/j.archoralbio.2019.03.024

OBJECTIVE: Dental-derived stem cells originate from the embryonic neural crest, and exhibit high neurogenic potential. This study aimed to investigate whether a cocktail of eight small molecules (Valproic acid, CHIR99021, Repsox, Forskolin, SP600125, GO6983, Y-27632 and Dorsomorphin) can enhance the in vitro neurogenic differentiation of dental pulp stem cells (DPSCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs), as a preliminary step towards clinical applications.
MATERIALS AND METHODS: Neural induction was carried out with a small molecule cocktail based two-step culture protocol, over a total duration of 14 days. At the 8 and 14 day timepoints, the cells were analyzed for expression of neural markers with immunocytochemistry, qRT-PCR and Western Blot. The Fluo 4-AM calcium flux assay was also performed after a further 14 days of neural maturation.
RESULTS: More pronounced morphological changes characteristic of the neural lineage (i.e. neuritogenesis) were observed in all three cell types treated with small molecules, as compared to the untreated controls. This was corroborated by the immunocytochemistry, qRT-PCR and western blot data, which showed upregulated expression of several early and mature neural markers in all three cell types treated with small molecules, versus the corresponding untreated controls. Finally, the Fluo-4 AM calcium flux assay showed consistently higher calcium transient (F/Fo) peaks for the small molecule-treated versus untreated control groups.
CONCLUSIONS: Small molecules can enhance the neurogenic differentiation of DPSCs, SCAPs and GMSCs, which offer much potential for therapeutic applications.

MeSH terms: Adult; Cell Differentiation; Cells, Cultured; Dental Pulp; Humans; Stem Cells; Adult Stem Cells*; Neurogenesis

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