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Fulltext Computational prediction of changes in brain metabolic fluxes during Parkinson's disease from mRNA expression

Supandi F, van Beek JHGM

PLoS One, 2018;13(9):e0203687.
PMID: 30208076 DOI: 10.1371/journal.pone.0203687

BACKGROUND: Parkinson's disease is a widespread neurodegenerative disorder which affects brain metabolism. Although changes in gene expression during disease are often measured, it is difficult to predict metabolic fluxes from gene expression data. Here we explore the hypothesis that changes in gene expression for enzymes tend to parallel flux changes in biochemical reaction pathways in the brain metabolic network. This hypothesis is the basis of a computational method to predict metabolic flux changes from post-mortem gene expression measurements in Parkinson's disease (PD) brain.
RESULTS: We use a network model of central metabolism and optimize the correspondence between relative changes in fluxes and in gene expression. To this end we apply the Least-squares with Equalities and Inequalities algorithm integrated with Flux Balance Analysis (Lsei-FBA). We predict for PD (1) decreases in glycolytic rate and oxygen consumption and an increase in lactate production in brain cortex that correspond with measurements (2) relative flux decreases in ATP synthesis, in the malate-aspartate shuttle and midway in the TCA cycle that are substantially larger than relative changes in glucose uptake in the substantia nigra, dopaminergic neurons and most other brain regions (3) shifts in redox shuttles between cytosol and mitochondria (4) in contrast to Alzheimer's disease: little activation of the gamma-aminobutyric acid shunt pathway in compensation for decreased alpha-ketoglutarate dehydrogenase activity (5) in the globus pallidus internus, metabolic fluxes are increased, reflecting increased functional activity.
CONCLUSION: Our method predicts metabolic changes from gene expression data that correspond in direction and order of magnitude with presently available experimental observations during Parkinson's disease, indicating that the hypothesis may be useful for some biochemical pathways. Lsei-FBA generates predictions of flux distributions in neurons and small brain regions for which accurate metabolic flux measurements are not yet possible.

Matched MeSH terms: Brain/metabolism*
Fulltext Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain

Gavai AK, Supandi F, Hettling H, Murrell P, Leunissen JA, van Beek JH

PLoS One, 2015;10(3):e0119016.
PMID: 25806817 DOI: 10.1371/journal.pone.0119016

Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the large user community for the R computing environment, a simple implementation of flux analysis in R appears desirable and will facilitate easy interaction with computational tools to handle gene expression data. We extended the R software package BiGGR, an implementation of metabolic flux analysis in R. BiGGR makes use of public metabolic reconstruction databases, and contains the BiGG database and the reconstruction of human metabolism Recon2 as Systems Biology Markup Language (SBML) objects. Models can be assembled by querying the databases for pathways, genes or reactions of interest. Fluxes can then be estimated by maximization or minimization of an objective function using linear inverse modeling algorithms. Furthermore, BiGGR provides functionality to quantify the uncertainty in flux estimates by sampling the constrained multidimensional flux space. As a result, ensembles of possible flux configurations are constructed that agree with measured data within precision limits. BiGGR also features automatic visualization of selected parts of metabolic networks using hypergraphs, with hyperedge widths proportional to estimated flux values. BiGGR supports import and export of models encoded in SBML and is therefore interoperable with different modeling and analysis tools. As an application example, we calculated the flux distribution in healthy human brain using a model of central carbon metabolism. We introduce a new algorithm termed Least-squares with equalities and inequalities Flux Balance Analysis (Lsei-FBA) to predict flux changes from gene expression changes, for instance during disease. Our estimates of brain metabolic flux pattern with Lsei-FBA for Alzheimer's disease agree with independent measurements of cerebral metabolism in patients. This second version of BiGGR is available from Bioconductor.

Matched MeSH terms: Brain/metabolism*
Fulltext Neuropsychological Consequences for Survivors of Childhood Brain Tumor in Malaysia

Alias H, Lau SCD, Schuitema I, de Sonneville LMJ

Front Psychol, 2018;9:703.
PMID: 29896137 DOI: 10.3389/fpsyg.2018.00703

Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor. Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7-18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92-12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures. Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition. Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.

Matched MeSH terms: Brain Neoplasms
Fulltext Impact of the additive effect of angiotensin-converting enzyme inhibitors and /or statins with antiplatelet medication on mortality after acute ischaemic stroke

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Basic Clin Pharmacol Toxicol, 2012 Apr;110(4):370-7.
PMID: 22023326 DOI: 10.1111/j.1742-7843.2011.00825.x

There has been recent interest in combining antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post-stroke in-hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18-month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In-hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke onset versus those who were taking antiplatelets alone or in combination with either ACEIs, statins or both. Data analysis was performed using SPSS version 15. Overall, 637 patients met the study inclusion criteria. After controlling for the effects of confounders, adding ACEIs or statins to antiplatelets significantly decreased the incidence of death after stroke attack by 68% (p = 0.036) and 81% (p = 0.010), respectively, compared to patients on antiplatelets alone or none of these medications. Additionally, the addition of both ACEIs and statins to antiplatelet medication resulted in the highest reduction (by 94%) of the occurrence of death after stroke attack (p < 0.001). Our results suggest that adding ACEIs and/or statins to antiplatelets for patients at risk of developing stroke, either as a primary or as a secondary preventive regimen, was associated with a significant reduction in the incidence of mortality after ischaemic stroke than antiplatelets alone. These results might help reduce the rate of ischaemic stroke morbidity and mortality by enhancing the application of specific therapeutic and management strategies for patients at a high risk of acute stroke.

Matched MeSH terms: Brain Ischemia/drug therapy; Brain Ischemia/mortality
Effect of prestroke use of angiotensin-converting enzyme inhibitors alone versus combination with antiplatelets and statin on ischemic stroke outcome

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Clin Neuropharmacol, 2011 Nov-Dec;34(6):234-40.
PMID: 21996648 DOI: 10.1097/WNF.0b013e3182348abe

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs), antiplatelets (APs), and statin are increasingly being prescribed for ischemic stroke prevention.
OBJECTIVES: The objective of the study was to examine whether previous combination therapy of ACEI with AP and/or statin has additive effect compared with ACEI alone on functional outcome after ischemic stroke. Furthermore, factors associated with improving functional outcome were investigated.
METHODS: Ischemic stroke patients attending a Malaysian hospital in 2008 were categorized according to Barthel Index at discharge. Favorable outcome was defined as Barthel Index of 75 or greater. Data included demographic information, clinical characteristics, and previous medications with particular attention to ACEI, AP, and statin.
RESULTS: Overall, 505 patients were included. Variables associated with good functional outcome were younger age (P = 0.002), first-ever attack (P = 0.016), lacunar (P = 0.015) or posterior circulation infarct stroke subtype (P = 0.034), minor Glasgow Coma Scale (P < 0.001), and previous use of ACEI alone or combined with AP and/or statin (P = 0.002). Using ACEI alone as the reference for ACEI + AP, ACEI + statin, or ACEI + AP + statin combinations, there was no significant difference among combinations on improving functional outcome (P = 0.852).
CONCLUSIONS: Prestroke use of ACEI either alone or combined with AP and/or statin was associated with better functional outcome. Previous use of ACEI in combination with AP and/or statin did not significantly differ from ACEI alone in their effect on outcome. Our study provides a potential rationale for optimizing the use of ACEI among individuals at risk of developing ischemic stroke.

Matched MeSH terms: Brain Ischemia/blood; Brain Ischemia/drug therapy*; Brain Ischemia/pathology
Statin use prior to ischemic stroke onset is associated with decreased in-hospital mortality

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Fundam Clin Pharmacol, 2011 Jun;25(3):388-94.
PMID: 20608996 DOI: 10.1111/j.1472-8206.2010.00846.x

Statins can reduce the risk of stroke in at-risk populations and improve survival after acute ischemic stroke (AIS) among patients with previous statin use. This study aimed to investigate the impact of statin use before AIS onset on in-hospital mortality and identify the factors related to in-hospital mortality among patients with and without previous statin use. A retrospective cohort study of all patients with AIS attending hospital from June 1, 2008 to December 31, 2008. Data were collected from medical records including demographic information, diagnostic information, risk factors, previous statin use, and vital discharge status. Chi-square, Fisher's exact tests, student's t-test, and Mann-Whitney U test, whatever appropriate, were used to test the significance between the variables, and multiple logistic regression was used to identify factors associated with in-hospital mortality. Altogether, 386 patients with AIS were studied, of which 113 (29.3%) had a documented previous statin use. A total of 62 (16.1%) patients with AIS died in hospital. In-hospital mortality was significantly lower among previous statin users (P = 0.013). The presence of atrial fibrillation (AF) increased in-hospital mortality among patients with or without previous statin use. The independent predictors for in-hospital mortality among AIS patients without previous statin use were the presence of diabetes mellitus (P = 0.047), AF (P = 0.045), and renal impairment (P < 0.001). The prophylactic administration of statins significantly reduces post-AIS in-hospital mortality. Furthermore, the identification of predictors of in-hospital mortality might reduce death rates and enhance the application of specific therapeutic and management strategies to patients at a high risk of dying.

Matched MeSH terms: Brain Ischemia/complications; Brain Ischemia/drug therapy; Brain Ischemia/prevention & control*
Antiplatelet therapy in diabetic ischemic stroke patients: associated factors and outcomes

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Int J Clin Pharmacol Ther, 2011 Oct;49(10):605-13.
PMID: 21961485 DOI: 10.5414/cp201574

BACKGROUND: Patients with diabetes mellitus (DM) are more prone to develop atherosclerotic complications including stroke. Moreover, as a primary and secondary prevention of stroke, antiplatelet therapy is recommended by clinical guidelines for patients with DM.

AIMS: This study aimed to determine the prevalence of antiplatelet therapy use prior to current stroke in diabetic ischemic stroke patients, to examine the factors associated with the use of this important therapy and to assess the impact of the previous use of antiplatelet therapy on ischemic stroke outcomes.

METHODS: An observational study of diabetic acute ischemic stroke patients attending a Malaysian hospital during a 1-year period was carried out. Demographic information, risk factors, previous antiplatelet use and variables used to assess stroke outcomes were collected from medical records.

RESULTS: Overall, 295 diabetic stroke patients were analyzed. The prevalence of previous antiplatelet use among diabetic patients was 38.3%. The independent variables associated with the previous use of antiplatelet medication were previous stroke attack (p < 0.001) and ischemic heart disease (p < 0.001). Better outcomes as measured by a minor Glasgow Coma Scale at admission (p = 0.032), and a higher Modified Barthel index at discharge (p = 0.027) were observed among patients on previous antiplatelet therapy.

CONCLUSION: Our data suggest that antiplatelet therapy is under prescribed among such diabetic stroke patients, particularly in primary prevention. Effective methods to increase antiplatelet use and to enhance the adherence of clinical practice guidelines should be considered at the national and community level.

Matched MeSH terms: Brain Ischemia/drug therapy*
Comparative effects of alpha-tocopherol and gamma-tocotrienol against hydrogen peroxide induced apoptosis on primary-cultured astrocytes

Mazlan M, Sue Mian T, Mat Top G, Zurinah Wan Ngah W

J Neurol Sci, 2006 Apr 15;243(1-2):5-12.
PMID: 16442562

Oxidative stress is thought to be one of the factors that cause neurodegeneration and that this can be inhibited by antioxidants. Since astrocytes support the survival of central nervous system (CNS) neurons, we compared the effect of alpha-tocopherol and gamma-tocotrienol in minimizing the cytotoxic damage induced by H(2)O(2), a pro-oxidant. Primary astrocyte cultures were pretreated with either alpha-tocopherol or gamma-tocotrienol for 1 h before incubation with 100 microM H(2)O(2) for 24 h. Cell viability was then assessed using the MTS assay while apoptosis was determined using a commercial ELISA kit as well as by fluorescent staining of live and apoptotic cells. The uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes were also determined using HPLC. Results showed that gamma-tocotrienol is toxic at concentrations >200 microM but protects against H(2)O(2) induced cell loss and apoptosis in a dose dependent manner up to 100 microM. alpha-Tocopherol was not cytotoxic in the concentration range tested (up to 750 microM), reduced apoptosis to the same degree as that of gamma-tocotrienol but was less effective in maintaining the viable cell number. Since the uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes is similar, this may reflect the roles of these 2 vitamin E subfamilies in inhibiting apoptosis and stimulating proliferation in astrocytes.

Matched MeSH terms: Brain/drug effects*; Brain/metabolism
Fulltext Gunshot-like wound caused by sling shot injury - a case report

Vinuthinee N, Azreen-Redzal A, Juanarita J, Zunaina E

Int Med Case Rep J, 2015;8:47-50.
PMID: 25709507 DOI: 10.2147/IMCRJ.S75198

We report a rare case of sling shot injury that presented with a gunshot-like wound with preseptal cellulitis, in a toddler. An 11-month-old Malay child presented with a gunshot-like wound over the forehead following sling shot injury. On examination, he had a deep circular laceration wound over the forehead, measuring 2.0 cm in diameter, with minimal bleeding. There was no obvious foreign body seen inside the wound and no palpable foreign body surrounding the wound. The gunshot-like wound was associated with left preseptal cellulitis. A skull X-ray showed a white opaque foreign body in the left frontal bone. Computed tomography (CT) scan of orbit and brain revealed a left comminuted fracture of the left orbital roof, and left frontal brain contusion with prelesional edema. Wound exploration was performed and revealed a 0.5 cm unshattered marble embedded in the left frontal bone. The marble and bone fragments were removed. The left preseptal cellulitis responded well to intravenous antibiotic and topical antibiotic.

Matched MeSH terms: Brain; Brain Contusion
Fulltext A Brief Psychotic Episode with Depressive Symptoms in Silent Right Frontal Lobe Infarct

Badrin S, Mohamad N, Yunus NA, Zulkifli MM

Korean J Fam Med, 2017 Nov;38(6):380-382.
PMID: 29209479 DOI: 10.4082/kjfm.2017.38.6.380

Psychiatric symptoms may be related to a silent cerebral infarct, a phenomenon that has been described previously in literature. Acute psychosis or other neuropsychiatric symptoms including depression may present in stroke patients and patients with lesions either within the prefrontal or occipital cortices, or in subcortical areas such as the basal ganglia, thalamus, mid-brain, and brainstem. Psychosis in clinical stroke or in silent cerebral infarction is uncommon and not well documented in the literature. Neurological deficits are the most common presentation in stroke, and nearly a third of patients that suffer a stroke may experience psychological disorders such as depression and anxiety, related to physical disability. The present case report describes an elderly female patient who presented with hallucinations and depressive symptoms, and was discovered to have a recent right frontal brain infarction, without other significant neurological deficits.

Matched MeSH terms: Brain; Brain Stem; Brain Infarction
Diagnostic Accuracy of Cytology Smear and Frozen Section in Glioma

Mat Zin AA, Zulkarnain S

Asian Pac J Cancer Prev, 2019 Feb 26;20(2):321-325.
PMID: 30803189

Glioma is the commonest primary intracranial tumour and it has been the most predominant tumour in many studies.
It accounts for 24.7% of all primary brain tumour and 74.6% of malignant brain tumour. Intraoperative diagnosis
plays a crucial role in determining the patient management. Frozen section has been the established technique in
providing rapid and accurate intraoperative diagnosis. However due to some disadvantages like ice crystal artefact,
high expenditure and requirement of skilled technician, there is increase usage of cytology smear either replacing or
supplementing frozen section technique. The aim of this review is to determine the diagnostic accuracy of cytology
smear and frozen section in glioma and to see whether there is significant difference between those techniques. The
overall diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% while for cytology smear, the
diagnostic accuracy ranging from 50% to 100%. Based on certain literatures, no statistically difference was observed
in diagnostic accuracy of cytology smear and frozen section. Thus, cytology smear provides an alternative method in
establishing intraoperative diagnosis. Both cytology smear and frozen section are complimentary to each other. It is
recommended to use both techniques to improve the diagnostic accuracy in addition with adequate knowledge, clinical
history, neuroimaging and intraoperative findings.

Matched MeSH terms: Brain Neoplasms/diagnosis*
Sturge-Weber syndrome without facial nevus: an unusual cause of neonatal seizures

Wong SW, Kyaw L, Ong LC, Zulfiqar AM

J Paediatr Child Health, 2011 Apr;47(4):237-9.
PMID: 20500432 DOI: 10.1111/j.1440-1754.2010.01739.x

Sturge-Weber syndrome is a neurocutaneous syndrome characterised by facial port wine stain, ipsilateral leptomeningeal angioma and vascular eye abnormalities. We report a rare case of Sturge-Weber syndrome without facial nevus presenting with neonatal seizures.

Matched MeSH terms: Brain/radiography
Motor function outcome in postnatal insult-related cerebral palsy

Fauzi AA, Mustafah NM, Zohdi WN

J Pediatr Rehabil Med, 2013;6(3):181-4.
PMID: 24240839 DOI: 10.3233/PRM-130251

The Gross Motor Function Classification System (GMFCS) was developed to establish uniform communication between healthcare providers, patients, and the patients' families. It is also used to prognosticate the outcome of motor function. Based on previous reports, prognostication of ambulation status in cerebral palsy is based on the motor development curve, which shows a plateau at a certain known age.

Matched MeSH terms: Brain Injuries/complications*
Zeolite-iron oxide nanocomposite from fly ash formed a 'clubbell' structure: integration of cardiac biocapture macromolecules in serum on microelectrodes

Liu Z, Gopinath SCB, Wang Z, Li Y, Anbu P, Zhang W

Mikrochim Acta, 2021 05 15;188(6):187.
PMID: 33990848 DOI: 10.1007/s00604-021-04834-w

A new zeolite-iron oxide nanocomposite (ZEO-IO) was extracted from waste fly ash of a thermal power plant and utilized for capturing aptamers used to quantify the myocardial infarction (MI) biomarker N-terminal prohormone B-type natriuretic peptide (NT-ProBNP); this was used in a probe with an integrated microelectrode sensor. High-resolution microscopy revealed that ZEO-IO displayed a clubbell structure and a particle size range of 100-200 nm. Energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy confirmed the presence of Si, Al, Fe, and O in the synthesized ZEO-IO. The limit of detection for NT-ProBNP was 1-2 pg/mL (0.1-0.2 pM) when the aptamer was sandwiched with antibody and showed the doubled current response even at a low NT-ProBNP abundance. A dose-dependent interaction was identified for this sandwich with a linear plot in the concentration range 1 to 32 pg/mL (0.1-3.2 pM) with a determination coefficient R2 = 0.9884; y = 0.8425x-0.5771. Without sandwich, the detection limit was 2-4 pg/mL (0.2-0.4 pM) and the determination coefficient was R2 = 0.9854; y = 1.0996x-1.4729. Stability and nonfouling assays in the presence of bovine serum albumin, cardiac troponin I, and myoglobin revealed that the aptamer-modified surface is stable and specific for NT-Pro-BNP. Moreover, NT-ProBNP-spiked human serum exhibited selective detection. This new nanocomposite-modified surface helps in detecting NT-Pro-BNP and diagnosing MI at stages of low expression.

Matched MeSH terms: Natriuretic Peptide, Brain/blood*; Natriuretic Peptide, Brain/immunology; Natriuretic Peptide, Brain/chemistry
Fulltext Association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma: a meta-analysis

Xin Y, Hao S, Lu J, Wang Q, Zhang L

PLoS One, 2014;9(4):e95966.
PMID: 24763305 DOI: 10.1371/journal.pone.0095966

To comprehensively evaluate the association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma.

Matched MeSH terms: Brain Neoplasms/ethnology; Brain Neoplasms/genetics*
Probiotic consumption relieved human stress and anxiety symptoms possibly via modulating the neuroactive potential of the gut microbiota

Ma T, Jin H, Kwok LY, Sun Z, Liong MT, Zhang H

Neurobiol Stress, 2021 May;14:100294.
PMID: 33511258 DOI: 10.1016/j.ynstr.2021.100294

Stress has been shown to disturb the balance of human intestinal microbiota and subsequently causes mental health problems like anxiety and depression. Our previous study showed that ingesting the probiotic strain, Lactobacillus (L.) plantarum P-8, for 12 weeks could alleviate stress and anxiety of stressed adults. The current study was a follow-up work aiming to investigate the functional role of the gut metagenomes in the observed beneficial effects. The fecal metagenomes of the probiotic (n = 43) and placebo (n = 36) receivers were analyzed in depth. The gut microbiomes of the placebo group at weeks 0 and 12 showed a significantly greater Aitchison distance (P brain axis was involved in relieving stress-related symptoms. The beneficial effect relied not only on microbial diversity changes but more importantly gut metagenome modulations at the SGB and functional gene levels.

Matched MeSH terms: Brain
Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines

Lim SW, Loh HS, Ting KN, Bradshaw TD, Zeenathul NA

Biomed Pharmacother, 2014 Oct;68(8):1105-15.
PMID: 25456851 DOI: 10.1016/j.biopha.2014.10.006

The pure vitamin isomer, β-tocotrienol has the least abundance among the other vitamin E isomers that are present in numerous plants. Hence, it is very scarcely studied for its bioactivity. In this study, the antiproliferative effects and primary apoptotic mechanisms of β-tocotrienol on human lung adenocarcinoma A549 and glioblastoma U87MG cells were investigated. It was evidenced that β-tocotrienol had inhibited the growth of both A549 (GI50=1.38±0.334μM) and U87MG (GI50=2.53±0.604μM) cells at rather low concentrations. Cancer cells incubated with β-tocotrienol were also found to exhibit hallmarks of apoptotic morphologies including membrane blebbing, chromatin condensation and formation of apoptotic bodies. The apoptotic properties of β-tocotrienol in both A549 and U87MG cells were the results of its capability to induce significant (P<0.05) double-strand DNA breaks (DSBs) without involving single-strand DNA breaks (SSBs). β-Tocotrienol is said to induce activation of caspase-8 in both A549 and U87MG cells guided by no activation when caspase-8 inhibitor, z-IETD-fmk was added. Besides, disruption on the mitochondrial membrane permeability of the cells in a concentration- and time-dependent manner had occurred. The induction of apoptosis by β-tocotrienol in A549 and U87MG cells was confirmed to involve both the death-receptor mediated and mitochondria-dependent apoptotic pathways. These findings could potentiate the palm oil derived β-tocotrienol to serve as a new anticancer agent for treating human lung and brain cancers.

Matched MeSH terms: Brain Neoplasms/drug therapy; Brain Neoplasms/enzymology*
Fulltext Symptomatic chronic strongyloidiasis in children following treatment for solid organ malignancies: case reports and literature review

Norsarwany M, Abdelrahman Z, Rahmah N, Ariffin N, Norsyahida A, Madihah B, et al.

Trop Biomed, 2012 Sep;29(3):479-88.
PMID: 23018511

Strongyloidiasis is an infection caused by the intestinal nematode Strongyloides stercoralis. Infected healthy individuals are usually asymptomatic, however it is potentially fatal in immunocompromised hosts due to its capacity to cause an overwhelming hyperinfection. Strongyloidiasis could be missed during routine screening because of low and intermittent larval output in stool and variable manifestations of the symptoms. We present two cases of strongyloidiasis occurring in children with solid organ malignancies suspected to have the infection based on their clinical conditions and treatment history for cancer. Both patients were diagnosed by molecular and serological tests and were successfully treated. Thus, strongyloidiasis in patients undergoing intensive treatment for malignancies should be suspected, properly investigated and treated accordingly.

Matched MeSH terms: Brain Neoplasms/complications; Brain Neoplasms/radiography; Brain Neoplasms/surgery
Feed-based vaccination regime against streptococcosis in red tilapia, Oreochromis niloticus x Oreochromis mossambicus

Ismail MS, Siti-Zahrah A, Syafiq MR, Amal MN, Firdaus-Nawi M, Zamri-Saad M

BMC Vet Res, 2016;12(1):194.
PMID: 27608936 DOI: 10.1186/s12917-016-0834-1

Streptococcosis is an important disease of tilapia throughout the world. In Malaysia, streptococcosis outbreak was commonly reported during the 3-month period of high water temperature between April and July. This study describes the duration of protection following single and double booster dose regimes against streptococcosis in tilapia using a feed-based vaccine containing formalin-killed Streptococcus agalactiae. A total of 510 tilapias of 120 ± 10 g were selected and divided into 3 groups. Fish of Group 1 were vaccinated at weeks 0 and 2 (single booster group) while fish of Group 2 were vaccinated at weeks 0, 2 and 6 (double booster group) with a feed-based vaccine against streptococcosis. Fish of Group 3 was not vaccinated. Serum samples were collected weekly to determine the antibody level while samples of eye, brain and kidney were collected for bacterial isolation. At week 10, all fish were challenged with live S. agalactiae and the survival rate was determined.

Matched MeSH terms: Brain
Associations Between Delay Discounting and Connectivity of the Valuation-control System in Healthy Young Adults

Loganathan K, Lv J, Cropley V, Ho ETW, Zalesky A

Neuroscience, 2021 01 01;452:295-310.
PMID: 33242540 DOI: 10.1016/j.neuroscience.2020.11.026

The process of valuation assists in determining if an object or course of action is rewarding. Delay discounting is the observed decay of a rewards' subjective value over time. Encoding the subjective value of rewards across a spectrum has been attributed to brain regions belonging to the valuation and executive control systems. The valuation system (VS) encodes reward value over short and long delays, influencing reinforcement learning and reward representation. The executive control system (ECS) becomes more active as choice difficulty increases, integrating contextual and mnemonic information with salience signals in the modulation of decision-making. Here, we aimed to identify resting-state functional connectivity-based patterns of the VS and ECS correlated with value-setting and delay discounting (outside-scanner paradigm) in a large (n = 992) cohort of healthy young adults from the Human Connectome Project (HCP). Results suggest the VS may be involved in value-setting of small, immediate rewards while the ECS may be involved in value-setting and delay discounting for large and small rewards over a range of delays. We observed magnitude sensitive connections involving the posterior cingulate cortex, time-sensitive connections with the ventromedial and lateral prefrontal cortex while connections involving the posterior parietal cortex appeared both magnitude- and time-sensitive. The ventromedial prefrontal cortex and posterior parietal cortex could act as "comparator" regions, weighing the value of small rewards against large rewards across various delay duration to aid in decision-making.

Matched MeSH terms: Brain

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