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1.
Int J Legal Med ; 138(4): 1295-1306, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38424369

RESUMO

Methiopropamine or 1-(thiophen-2-yl)-2-methylaminopropane (MPA) is a thiophene ring-based structural analogue of methamphetamine, first synthesized in 1942 but become popular when it started to be available for purchase on websites selling 'legal highs' since 2010. While it is legally controlled in many countries, it remains readily accessible and frequently encountered in recreational settings. The growing prevalence of MPA use results in new therapeutic challenges. Relatively few studies have focused on its pharmacodynamics and pharmacokinetics, making it important to better understand its potential risks and harmful effects in humans in terms of its toxicity. This review provides a comprehensive profiling of MPA toxicological properties, including its chemical properties, analytical methods, prevalence, patterns of use, and legal status. Additionally, it discusses the drug's effects on the central nervous system, its potential for addiction, and its adverse physical and mental health effects. Improving the understanding of safety aspects of MPA and how it imposes health threats for public health will guide the development of therapeutic approach of its intoxication and guide the authorities in deciding its legal status.


Assuntos
Metanfetamina , Humanos , Metanfetamina/análogos & derivados , Metanfetamina/química , Drogas Ilícitas/química , Estimulantes do Sistema Nervoso Central/química , Psicotrópicos/química , Transtornos Relacionados ao Uso de Substâncias , Tiofenos
2.
Front Aging Neurosci ; 15: 1158001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818479

RESUMO

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions.

3.
Oxid Med Cell Longev ; 2023: 4416410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36785791

RESUMO

Aging is a complex process characterized by progressive loss of functional abilities due to the accumulation of molecular damages. Metabolomics could offer novel insights into the predictors and mechanisms of aging. This cross-sectional study is aimed at identifying age-associated plasma metabolome in a Malay population. A total of 146 (90 females) healthy participants aged 28-69 were selected for the study. Untargeted metabolomics profiling was performed using liquid chromatography-tandem mass spectrometry. Association analysis was based on the general linear model. Gender-associated metabolites were adjusted for age, while age-associated metabolites were adjusted for gender or analyzed in a gender-stratified manner. Gender-associated metabolites such as 4-hydroxyphenyllactic acid, carnitine, cortisol, and testosterone sulfate showed higher levels in males than females. Deoxycholic acid and hippuric acid were among the metabolites with a positive association with age after being adjusted for gender, while 9(E),11(E)-conjugated linoleic acid, cortisol, and nicotinamide were negatively associated with age. In gender-stratified analysis, glutamine was one of the common metabolites that showed a direct association with age in both genders, while metabolites such as 11-deoxy prostaglandin F2ß, guanosine monophosphate, and testosterone sulfate were inversely associated with age in males and females. This study reveals several age-associated metabolites in Malays that could reflect the changes in metabolisms during aging and may be used to discern the risk of geriatric syndromes and disorders later. Further studies are required to determine the interplay between these metabolites and environmental factors on the functional outcomes during aging.


Assuntos
Hidrocortisona , Metabolômica , Humanos , Masculino , Feminino , Idoso , Malásia , Estudos Transversais , Metabolômica/métodos , Testosterona
4.
Neural Regen Res ; 18(6): 1179-1185, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36453391

RESUMO

Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.

5.
Int J Mol Sci ; 23(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35955464

RESUMO

Changes in mitochondrial bioenergetics are believed to take place during osteoclastogenesis. This study aims to assess changes in mitochondrial bioenergetics and reactive oxygen species (ROS) levels during polyethylene (PE)-induced osteoclastogenesis in vitro. For this purpose, RAW264.7 cells were cultured for nine days and allowed to differentiate into osteoclasts in the presence of PE and RANKL. The total TRAP-positive cells, resorption activity, expression of osteoclast marker genes, ROS level, mitochondrial bioenergetics, glycolysis, and substrate utilization were measured. The effect of tocotrienols-rich fraction (TRF) treatment (50 ng/mL) on those parameters during PE-induced osteoclastogenesis was also studied. During PE-induced osteoclastogenesis, as depicted by an increase in TRAP-positive cells and gene expression of osteoclast-related markers, higher proton leak, higher extracellular acidification rate (ECAR), as well as higher levels of ROS and NADPH oxidases (NOXs) were observed in the differentiated cells. The oxidation level of some substrates in the differentiated group was higher than in other groups. TRF treatment significantly reduced the number of TRAP-positive osteoclasts, bone resorption activity, and ROS levels, as well as modulating the gene expression of antioxidant-related genes and mitochondrial function. In conclusion, changes in mitochondrial bioenergetics and substrate utilization were observed during PE-induced osteoclastogenesis, while TRF treatment modulated these changes.


Assuntos
Osteogênese , Polietileno , Diferenciação Celular , Metabolismo Energético , Mitocôndrias/metabolismo , Osteoclastos/metabolismo , Polietileno/metabolismo , Ligante RANK/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-35682422

RESUMO

In 2020, the COVID-19 pandemic struck the globe and disrupted various aspects of psychological wellbeing, more so in frontline workers. Research on assessing the seroprevalence of COVID-19 has been scarce; in addition, there are limited studies assessing the association between the seroprevalence of COVID-19 and psychological distress. Therefore, this study aimed to determine the seroprevalence of COVID-19 and the prevalence of psychological distress and to determine whether sociodemographic variables, occupational information variables, coping styles, and psychological processes might contribute to the development of psychological distress. A cross-sectional study involving 168 Universiti Malaysia Sabah (UMS) front liners was carried out to assess these issues. The Depression, Anxiety and Stress Scale (DASS-21) was employed to assess psychological distress, together with the COVID-19 Rapid Test Kit Antibody (RTK Ab) and a series of questionnaires, including a sociodemographic and occupational information questionnaire, the Balanced Index of Psychological Mindedness (BIPM) questionnaire, the Mindfulness Attention and Awareness Scale (MAAS), the Acceptance and Action Questionnaire (AAQ-II), and the Brief COPE questionnaire. The results demonstrated a seroprevalence of COVID-19 at 8.3% (95% CI = 5.0-14.0). Non-healthcare workers (HCWs) had a higher COVID-19 prevalence. Meanwhile, the prevalence of depression, anxiety, and stress among front liners was low (3.0%, 3.6%, and 1.2%, respectively). Younger people (aged 30 years old or less) and HCWs had a higher prevalence of psychological distress; being a HCW was significantly associated with a higher level of anxiety. Dysfunctional coping and psychological inflexibility were consistently found to be predictors for higher levels of the three psychological distress variables. This study suggested some alternatives that could be explored by mental health providers to address mental health issues among front liners at universities.


Assuntos
COVID-19 , Angústia Psicológica , Adulto , Ansiedade/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Pessoal de Saúde/psicologia , Humanos , Malásia/epidemiologia , Pandemias , SARS-CoV-2 , Estudos Soroepidemiológicos
7.
Int J Cardiol Congenit Heart Dis ; 7: 100325, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35360459

RESUMO

Since the coronavirus disease 2019 (COVID-19) pandemic emerged in November 2019, various international guidelines and local protocols have been published to assist clinicians face the pandemic effectively. Medical and ventilatory strategies have evolved and researchers have come out with multiple studies and solutions within a short period of time. The patient's best interest is always the goal of the management. We present a case report of COVID-19 pneumonia in a patient with underlying Eisenmenger syndrome and the potential benefits of high-flow nasal oxygen therapy in this patient.

8.
Biomolecules ; 12(3)2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35327640

RESUMO

This study aimed to determine the effect of age on CVLM C1 neuron glucoregulatory proteins in the feeding pathway. Male Sprague Dawley rats aged 3 months and 24 months old were divided into two subgroups: the treatment group with 2-deoxy-d-glucose (2DG) and the control group. Rat brains were dissected to obtain the CVLM region of the brainstem. Western blot was used to determine protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK), and neuropeptide Y Y5 receptors (NPY5R) in CVLM samples. Immunofluorescence was used to determine TH-, AMPK-, and NPY5R-like immunoreactivities among other brain coronal sections. Results obtained denote a decrease in basal TH phosphorylation levels and AMPK proteins and an increase in TH proteins among aged CVLM neurons. Increases in the basal immunoreactivity of TH+, AMPK+, NPY5R+, TH+/AMPK+, and TH+/NPY5R+ were also observed among old rats. Young treatment-group rats saw a decrease in TH phosphorylation and AMPK proteins following 2DG administration, while an increase in AMPK phosphorylation and a decrease in TH proteins were found among the old-treatment-group rats. These findings suggest the participation of CVLM C1 neurons in counter-regulatory responses among young and old rats. Altering protein changes in aged CVLM C1 neurons may attenuate responses to glucoprivation, thus explaining the decline in food intake among the elderly.


Assuntos
Glucose , Bulbo , Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento , Animais , Anorexia , Glucose/metabolismo , Masculino , Bulbo/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologia
9.
Front Pharmacol ; 13: 1035220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36686668

RESUMO

Neurodegenerative diseases (NDs) are sporadic maladies that affect patients' lives with progressive neurological disabilities and reduced quality of life. Neuroinflammation and oxidative reaction are among the pivotal factors for neurodegenerative conditions, contributing to the progression of NDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and Huntington's disease (HD). Management of NDs is still less than optimum due to its wide range of causative factors and influences, such as lifestyle, genetic variants, and environmental aspects. The neuroprotective and anti-neuroinflammatory activities of Moringa oleifera have been documented in numerous studies due to its richness of phytochemicals with antioxidant and anti-inflammatory properties. This review highlights up-to-date research findings on the anti-neuroinflammatory and neuroprotective effects of M. oleifera, including mechanisms against NDs. The information was gathered from databases, which include Scopus, Science Direct, Ovid-MEDLINE, Springer, and Elsevier. Neuroprotective effects of M. oleifera were mainly assessed by using the crude extracts in vitro and in vivo experiments. Isolated compounds from M. oleifera such as moringin, astragalin, and isoquercitrin, and identified compounds of M. oleifera such as phenolic acids and flavonoids (chlorogenic acid, gallic acid, ferulic acid, caffeic acid, kaempferol, quercetin, myricetin, (-)-epicatechin, and isoquercitrin) have been reported to have neuropharmacological activities. Therefore, these compounds may potentially contribute to the neuroprotective and anti-neuroinflammatory effects. More in-depth studies using in vivo animal models of neurological-related disorders and extensive preclinical investigations, such as pharmacokinetics, toxicity, and bioavailability studies are necessary before clinical trials can be carried out to develop M. oleifera constituents into neuroprotective agents.

10.
Front Psychiatry ; 12: 680393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819880

RESUMO

Background: Natural disasters may physically and psychologically affect individuals and their surrounding community. This study determines the prevalence of post-traumatic stress (PTS) symptoms and its association with maladaptive trauma-related cognition and resilience among adolescents post-earthquake. Materials and Methods: Data were collected, in this cross-sectional study, during an intervention program post-earthquake held in a state high school located at Lombok, Indonesia. The study sample engaged students 14-19 years of age using the purposive sampling method. The questionnaires used to measure PTS symptoms, maladaptive trauma-related cognition, and resilience were Children's Revised Impact of Event Scale-13 (CRIES-13), Child Post-Traumatic Cognitions Inventory (CPTCI), and Child and Youth Resilience Measure-Revised (CYRM-R), respectively. Results: The prevalence of PTS symptoms was 69.9%. Among the respondents, 61.37% were female and 56.48% had mothers with lower educational levels. Using multiple linear regression, the final predictors of PTS symptoms were excessive reactions (e.g., wailing loudly, miserable shrieking) of proxy during earthquake (ß = 3.283, p = 0.005), maladaptive trauma-related cognition (ß = 0.224, p = 0.002), and resilience (ß = 0.192, p < 0.001) with female gender (ß = 7.350, p < 0.001) as a control variable. Through simple linear regression, victims who witnessed injury or death during the earthquake (p = 0.003), had a proxy died during the earthquake (p = 0.01), and trapped victims or those who had difficulty escaping (p = 0.01) were identified to potentially predict the occurrence of PTS symptoms, warranting further study. Conclusion: The presence of excessive proxy reactions during the earthquake, maladaptive trauma-related cognition, and resilience in adolescents exposed to a natural disaster are worth targeting and prioritizing in future post-disaster interventions.

11.
Cells ; 10(7)2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199148

RESUMO

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult's susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.


Assuntos
Envelhecimento/genética , Cognição/fisiologia , Transcriptoma/genética , Adulto , Idoso , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Malásia , Pessoa de Meia-Idade , Análise de Componente Principal , Reprodutibilidade dos Testes
12.
Antioxidants (Basel) ; 9(10)2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092139

RESUMO

Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.

13.
Exp Gerontol ; 129: 110779, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705967

RESUMO

BACKGROUND: Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function. OBJECTIVE: This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response. METHOD: Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR. RESULTS: This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased. CONCLUSION: These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.


Assuntos
Desoxiglucose/metabolismo , Ingestão de Energia/fisiologia , Neurônios/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/metabolismo , Colecistocinina/metabolismo , Desoxiglucose/farmacologia , Masculino , Bulbo/metabolismo , Neuropeptídeo Y , Fosforilação , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo
14.
J Imaging ; 6(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460528

RESUMO

The recent developments of deep learning support the identification and classification of lung diseases in medical images. Hence, numerous work on the detection of lung disease using deep learning can be found in the literature. This paper presents a survey of deep learning for lung disease detection in medical images. There has only been one survey paper published in the last five years regarding deep learning directed at lung diseases detection. However, their survey is lacking in the presentation of taxonomy and analysis of the trend of recent work. The objectives of this paper are to present a taxonomy of the state-of-the-art deep learning based lung disease detection systems, visualise the trends of recent work on the domain and identify the remaining issues and potential future directions in this domain. Ninety-eight articles published from 2016 to 2020 were considered in this survey. The taxonomy consists of seven attributes that are common in the surveyed articles: image types, features, data augmentation, types of deep learning algorithms, transfer learning, the ensemble of classifiers and types of lung diseases. The presented taxonomy could be used by other researchers to plan their research contributions and activities. The potential future direction suggested could further improve the efficiency and increase the number of deep learning aided lung disease detection applications.

15.
J Alzheimers Dis ; 72(1): 229-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31594216

RESUMO

Tocotrienol-rich fraction (TRF) is a mixture of vitamin E analogs derived from palm oil. We previously demonstrated that supplementation with TRF improved cognitive function and modulated amyloid pathology in AßPP/PS1 mice brains. The current study was designed to examine proteomic profiles underlying the therapeutic effect of TRF in the brain. Proteomic analyses were performed on samples of hippocampus, medial prefrontal cortex (mPFC), and striatum using liquid chromatography coupled to Q Exactive HF Orbitrap mass spectrometry. From these analyses, we profiled a total of 5,847 proteins of which 155 proteins were differentially expressed between AßPP/PS1 and wild-type mice. TRF supplementation of these mice altered the expression of 255 proteins in the hippocampus, mPFC, and striatum. TRF also negatively modulated the expression of amyloid beta A4 protein and receptor-type tyrosine-protein phosphatase alpha protein in the hippocampus. The expression of proteins in metabolic pathways, oxidative phosphorylation, and those involved in Alzheimer's disease were altered in the brains of AßPP/PS1 mice that received TRF supplementation.


Assuntos
Corpo Estriado/metabolismo , Hipocampo/metabolismo , Óleo de Palmeira/farmacologia , Córtex Pré-Frontal/metabolismo , Proteoma/metabolismo , Tocotrienóis/farmacologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Antioxidantes/farmacologia , Corpo Estriado/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Córtex Pré-Frontal/efeitos dos fármacos , Presenilina-1/genética , Presenilina-1/metabolismo , Proteoma/genética , Proteômica/métodos
16.
J Alzheimers Dis ; 70(s1): S43-S62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30594926

RESUMO

BACKGROUND: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population. OBJECTIVE: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency. METHODS: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output. RESULTS: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays' cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation. CONCLUSION: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function.


Assuntos
Envelhecimento/psicologia , Cognição/fisiologia , Proteoma , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Estudos Transversais , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Proteômica , Espectrometria de Massas em Tandem
17.
J Alzheimers Dis ; 70(s1): S239-S254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30507571

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-ß (Aß) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aß deposition in the hippocampus of an AD mouse model. In the present study, we investigate the effect of 6 months of TRF supplementation on transcriptome profile in the hippocampus of APPswe/PS1dE9 double transgenic mice. TRF supplementation can alleviate AD conditions by modulating several important genes in AD. Moreover, TRF supplementation attenuated the affected biological process and pathways that were upregulated in the AD mouse model. Our findings indicate that TRF supplementation can modulate hippocampal gene expression as well as biological processes that can potentially delay the progression of AD.


Assuntos
Doença de Alzheimer/metabolismo , Hipocampo/efeitos dos fármacos , Tocotrienóis/administração & dosagem , Transcriptoma/efeitos dos fármacos , Doença de Alzheimer/genética , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Camundongos , Camundongos Transgênicos
18.
Exp Gerontol ; 111: 53-64, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29981398

RESUMO

Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.


Assuntos
Envelhecimento/metabolismo , Corpo Estriado/metabolismo , Hipocampo/metabolismo , Córtex Pré-Frontal/metabolismo , Proteoma/metabolismo , Animais , Atrofia , Cromatografia Líquida , Masculino , Proteoma/genética , Proteômica , Ratos , Ratos Sprague-Dawley
19.
J Alzheimers Dis ; 64(1): 249-267, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29889072

RESUMO

We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AßPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aß interaction or independent of Aß interaction.


Assuntos
Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Transtornos Mentais/tratamento farmacológico , Redes e Vias Metabólicas/efeitos dos fármacos , Óleo de Palmeira/química , Tocotrienóis/uso terapêutico , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Sinais (Psicologia) , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos Mentais/etiologia , Redes e Vias Metabólicas/fisiologia , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/genética , Presenilina-1/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Navegação Espacial/efeitos dos fármacos , Estatísticas não Paramétricas , Fatores de Tempo
20.
Pest Manag Sci ; 74(1): 240-245, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28834586

RESUMO

BACKGROUND: Pest control in post-harvest food storage represents a great challenge in the sustainable prevention of food losses, and insecticide-treated netting may represent a valid alternative to traditional practices such as the direct application of insecticides. In our work, the efficacy of a permethrin-incorporated net, in combination with polypropylene or jute sacking, was tested for the control of Sitophilus oryzae. Contamination of maize grain by permethrin from the treated netting was also evaluated. RESULTS: A 98% control of S. oryzae was achieved using permethrin-treated netting. Both jute and polypropylene acted as additional barriers, increasing efficacy to 100%. The results also showed the contamination of maize kernel by permethrin released from the treated netting. The concentration of residues in maize kernels increased with increasing temperature; however, use of jute or polypropylene significantly reduced (by 87% to 97%) the concentration of residues transferred to maize kernels. CONCLUSIONS: Permethrin-treated netting provided a high level of efficacy in the post-harvest protection of maize. Several factors influenced permethrin residue concentrations in grains when treated nets are used. Therefore, solutions should be found to prevent contamination of food stored in the bags that are treated with insecticides. © 2017 Society of Chemical Industry.


Assuntos
Controle de Insetos , Inseticidas , Permetrina , Gorgulhos , Zea mays , Animais , Grão Comestível , Feminino , Masculino
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