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1.
Front Neurol ; 12: 722892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744967

RESUMO

Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD. Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA). Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = -1.68, 95% confidence interval, CI: -2.74 to -0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = -1.19, 95% CI: -2.26 to -0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = -3. 66, 95% CI: -4. 30 to -3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = -2.03, 95% CI: -3.08 to -0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = -2.48, 95% CI: -4.07 to -0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = -4. 93, 95% CI: -6.79 to -3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = -3.52, 95% CI: -5.25 to -1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith-Hamilton Pleasure Scale (MD = -0.12, 95% CI: -0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability. Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.

2.
BMC Cancer ; 21(1): 1084, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620113

RESUMO

BACKGROUND & AIMS: Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. METHODS: We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. RESULTS: Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27-1.72] and central obesity [HR 1.65, 95% CI 1.18-2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk. CONCLUSIONS: MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.


Assuntos
Neoplasias Hepáticas/etiologia , Síndrome Metabólica/complicações , Fatores Sexuais , Adulto , Idoso , Glicemia , HDL-Colesterol/sangue , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Hiperglicemia/complicações , Hipertensão/complicações , Hipertrigliceridemia/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologia , Circunferência da Cintura
3.
Front Aging Neurosci ; 13: 709878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483882

RESUMO

To review the therapeutic effects of drugs on REM sleep behavior disorder (RBD) in Parkinson's disease (PD) by searching the MEDLINE/PubMed, Embase, Cochrane, and CBM databases. According to the inclusion and exclusion criteria, studies were included after excluding duplicate data. We evaluated the safety and efficacy of pharmacological intervention to improve RBD in patients with Parkinson's disease (PD-RBD). This systematic review mainly describes the drugs that can be used to treat PD-RBD patients. The results have shown that melatonin can be used as the first-line drug for PD-RBD, and clonazepam provides significant improvement on PD-RBD, androtigotine can be used as an alternative drug. However, further large-scale clinical trial studies are still needed to provide the best guidelines for the pharmacological treatment of PD-RBD.

4.
Cancer Med ; 10(13): 4522-4531, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34114748

RESUMO

OBJECTIVE: To evaluate the association between body composition and subsequent risk of the major gynecologic malignancies. METHODS: This is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. RESULTS: We document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat-free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02-1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49-3.13) times and 1.89 (95% CI 1.31-2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat-free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07-1.31) and postmenopausal women (HR 1.13,95% CI 1.09-1.18). Meanwhile, FM/FFM distributed in the limbs present an U-shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer. CONCLUSION: FM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed.

5.
Int J Cancer ; 149(7): 1435-1447, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019699

RESUMO

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454 079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27 794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk.


Assuntos
Adiposidade , Composição Corporal , Índice de Massa Corporal , Neoplasias/classificação , Neoplasias/epidemiologia , Obesidade/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
6.
Environ Pollut ; 282: 117032, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831628

RESUMO

Among emerging organic contaminants (EOCs), triclosan (TCS) is an antibacterial agent and frequently detected in sludge. In this study, RNA sequencing (RNA-seq) was used to obtain the first transcriptomic profile of tobacco with TCS treatment in comparison with control. The results of transcriptome profiling indicated that salicylic acid (SA) signalling pathway actively participated in the tobacco's response to TCS treatment. The accumulation of endogenous SA in transgene tobacco lines transformed with a homologous gene of SA binding protein (LcSABP) was significantly enhanced. The resistance of transgenic tobacco lines to TCS was markedly enhanced revealed by morphological and physiological indexes while the total Chl level and Pn of transgenic individuals showed about 180% and 250% higher than that of WT on average, and the accumulation of H2O2 and O2- induced by TCS in SABP overexpressing tobacco was 35.3%-37.3% and 53.0%-56.0% lower than that of WT. In order to further explore the mechanism of TCS tolerance in transgenic plants, RNA-seq was then performed to obtain the second transcriptomic profile between wild type and transgenic samples with TCS exposure. The results indicated that differentially expressed genes (DEGs) were most highly enriched in MAPK signalling pathway, amino acid synthesis pathway and plant hormone transduction pathway. Especially, genes encoding key proteins such as cytochrome P450, laccase, peroxidase, glycosyl transferase, glutathione S-transferase and ATP-binding cassette were considered to be related to the increased tolerance ability of transgenic tobacco to the treatment of TCS stress. This research will likely provide novel insights into the molecular mechanism of SA-mediated amelioration of TCS stress on tobacco.


Assuntos
Ácido Salicílico , Tabaco , Triclosan/toxicidade , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Estresse Fisiológico , Tabaco/efeitos dos fármacos , Tabaco/crescimento & desenvolvimento
7.
Cancer Med ; 10(6): 2164-2174, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33624430

RESUMO

The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow-up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat-free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5-unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat-free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer.


Assuntos
Composição Corporal , Neoplasias Gástricas/etiologia , Adiposidade , Fatores Etários , Intervalos de Confiança , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Neoplasias Gástricas/diagnóstico
8.
J Biol Res (Thessalon) ; 28(1): 6, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632304

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. METHODS: We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. RESULTS: No significant cytotoxicity was observed at ART concentrations up to 40 µM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. CONCLUSION: Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

9.
Chemosphere ; 270: 129456, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33418217

RESUMO

Triclosan (TCS) is a highly effective antibacterial agent, which is widely distributed in wastewater and sludge. The application of sludge containing high concentration TCS in agriculture will cause physiological damage to plants. Nevertheless, little is known about the physiological and molecular mechanism of TCS to plants. So firstly the physiological and biochemical indexes of tobacco with treatment of different concentrations of TCS were evaluated in this study. The results showed that tobacco plants with TCS treatment exhibited lower germination rate, root development, photosynthesis efficiency, and higher ROS accumulation in comparison with control group. The transcriptome analysis of tobacco plants was then performed to reveal the molecular mechanism in the response of tobacco to TCS. There were 3, 819 differentially expressed genes (DEGs) were identified between groups with or without TCS treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these DEGs were mainly enriched in groups of the plant hormone signal transduction pathway. To further investigate the role of plant hormone, transgenic tobacco overexpressing a homologous of salicylic acid (SA) binding protein gene was used to assess the SA-mediate TCS tolerance in plant. The results showed that transgenic plants exhibited enhanced activities of antioxidant enzymes and stronger TCS resistance than wild-type ones, which verify the important role of SA signal pathway in TCS response of tobacco plants. This study could be used to better understand the key roles of plant hormones in the TCS stress response of higher plants, and find key pathways and candidate genes for phytoremediation.


Assuntos
Tabaco , Triclosan , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Ácido Salicílico , Estresse Fisiológico/genética , Tabaco/metabolismo , Transcriptoma , Triclosan/toxicidade
10.
Brain Imaging Behav ; 15(3): 1355-1363, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32748322

RESUMO

A true understanding of the distribution and functional correlates of Alzheimer's disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.9% women, 13.7% APOE*4 carriers) recruited for neuroimaging from a larger representative population-based cohort participating in an ongoing longitudinal study of aging, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT). All participants scored < 1.0 on the Clinical Dementia Rating (CDR) Scale, with 8 participants (7.8%) scoring CDR = 0.5. Participants completed a positron emission tomography scan using the tracers [C-11]Pittsburgh Compound-B (PiB) and [F-18]AV-1451 to estimate amyloid and tau deposition. PiB positivity was defined on a regional basis using established standardized uptake value ratio cutoffs (SUVR; cerebellar gray matter reference), with 39 participants (38.2%) determined to be PiB(+). Health history, lifestyle, and cognitive abilities were assessed cross-sectionally at the nearest annual parent MYHAT study visit. A series of adjusted regression analyses modeled cognitive performance as a function of global PiB SUVR and [F-18]AV-1451 SUVR in Braak associated regions 1, 3/4, and 5/6. In comparison to PiB(-) participants (n = 63), PiB(+) participants were older, less educated, and were more likely to be APOE*4 carriers. Global PiB SUVR was significantly correlated with [F-18]AV-1451 SUVR in all Braak-associated regions (r = .38-0.53, p < .05). In independent models, higher Global PiB SUVR and Braak 1 [F-18]AV-1451 SUVR were associated with worse performance on a semantic interference verbal memory test. Our findings suggest that brain amyloid is common in a community-based setting, and is associated with tau deposition, but both pathologies show few associations with concurrent cognitive performance in a dementia-free sample.


Assuntos
Doença de Alzheimer , Envelhecimento Saudável , Idoso , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Tomografia por Emissão de Pósitrons
11.
Alzheimer Dis Assoc Disord ; 35(1): 30-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32960854

RESUMO

INTRODUCTION: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. METHODS: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics. RESULTS: Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors. CONCLUSIONS: Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.


Assuntos
Disfunção Cognitiva/etiologia , Exercício Físico/fisiologia , Fatores de Risco de Doenças Cardíacas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos
12.
Int Psychogeriatr ; 33(8): 767-778, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32301414

RESUMO

BACKGROUND: Longitudinal studies predictably experience non-random attrition over time. Among older adults, risk factors for attrition may be similar to risk factors for outcomes such as cognitive decline and dementia, potentially biasing study results. OBJECTIVE: To characterize participants lost to follow-up which can be useful in the study design and interpretation of results. METHODS: In a longitudinal aging population study with 10 years of annual follow-up, we characterized the attrited participants (77%) compared to those who remained in the study. We used multivariable logistic regression models to identify attrition predictors. We then implemented four machine learning approaches to predict attrition status from one wave to the next and compared the results of all five approaches. RESULTS: Multivariable logistic regression identified those more likely to drop out as older, male, not living with another study participant, having lower cognitive test scores and higher clinical dementia ratings, lower functional ability, fewer subjective memory complaints, no physical activity, reported hobbies, or engagement in social activities, worse self-rated health, and leaving the house less often. The four machine learning approaches using areas under the receiver operating characteristic curves produced similar discrimination results to the multivariable logistic regression model. CONCLUSIONS: Attrition was most likely to occur in participants who were older, male, inactive, socially isolated, and cognitively impaired. Ignoring attrition would bias study results especially when the missing data might be related to the outcome (e.g. cognitive impairment or dementia). We discuss possible solutions including oversampling and other statistical modeling approaches.

13.
Neurol Sci ; 42(2): 757-763, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32780247

RESUMO

The purpose of this research is to explore the underlying genes of Charcot-Marie-Tooth (CMT). Technologies such as electrophysiological testing and gene sequencing have been applied. We identified a novel variant NEFH c.2215C>T(p.P739S)(HGNC:7737) in a heterozygous state, which was considered to be pathogenic for CMT2CC(OMIM:616924).The proband and his brothers presented with muscle atrophy of hand and calf and moderately decreased conduction velocities. By whole exome sequencing analysis, we found the novel missense pathogenic variant in the proband, his brother and mother. This report broadened current knowledge about intermediate CMT and the phenotypic spectrum of defects associated with NEFH. In addition, the proband carried other five variants {HSPD1c.695C>A (p.S232X), FLNCc.1073A>G (p.N358S), GUSBc.323C>A (p.P108Q), ACY1 c.1063-1G>A and APTX c.484-2A>T}, which have not been reported until now. The NEFH c.2215C>T (p.P739S) give us a new understanding of CMT, which might provide new therapeutic targets in the future.


Assuntos
Doença de Charcot-Marie-Tooth , Doença de Charcot-Marie-Tooth/genética , Proteínas de Ligação a DNA , Heterozigoto , Humanos , Masculino , Mutação , Mutação de Sentido Incorreto , Proteínas de Neurofilamentos , Proteínas Nucleares , Linhagem
14.
Aging (Albany NY) ; 13(1): 831-845, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33289703

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that atorvastatin could reduce the risk of PD, but the mechanism is still unclear. In this paper, Our findings showed that atorvastatin increased muscle capacity and the coordination of movement and improved anxiety and depression. Atorvastatin could decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), increase the protein expression of LC3II/I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected at midbrain with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders. NOX2 may be a potential gene target for new drug development in PD.


Assuntos
Ansiedade/psicologia , Atorvastatina/farmacologia , Autofagia/efeitos dos fármacos , Depressão/psicologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Movimento/efeitos dos fármacos , NADPH Oxidase 2/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Comportamento Animal/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Camundongos , NADPH Oxidase 2/metabolismo , Neurotoxinas , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/psicologia
15.
Anal Chim Acta ; 1131: 102-108, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32928470

RESUMO

The threat of organophosphorus pesticide (OPP) residue to food safety and human health has caused widespread concern. In this paper, a sensitive fluorescence sensor for OPP detection was constructed based on the alkaline phosphatase (ALP) -triggered in situ reaction. In this method, ALP catalyses the dephosphorylation of the substrate l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAP) to generate l-ascorbic acid (AA). AA instantly combines with o-phenylenediamine (OPD) to form 3-(1,2-dihydroxyethyl)furo[3,4-b]quinoxalin-1(3H)-one (DFQ), which contains a quinoxaline core skeleton fluorophore and emits a strong fluorescence intensity at 425 nm. The existence of OPPs inhibits the activity of ALP and the production of AA and DFQ. As a result, the fluorescence intensity obviously decreases. Under optimal conditions, the fluorescence intensity linearly depends on the logarithm of chlorpyrifos concentration over a wide range of 20 pg/mL ∼1000 ng/mL with a detection limit of 15.03 pg/mL (S/N = 3), which is lower than the previously reported values. The sensor with its satisfactory accuracy and precision has been successfully applied to the detection of chlorpyrifos in leeks and celery samples with recoveries of 94.5-106.7% and an inter-assay relative standard deviation (RSD) below 11.51%. OPPs can be semiquantitatively determined by the colour changes in ultraviolet light. The superiority of the sensor is due to its visual simplicity without complex fluorescence labelling procedures and costly instruments.


Assuntos
Fosfatase Alcalina , Praguicidas , Catálise , Corantes Fluorescentes , Humanos , Espectrometria de Fluorescência
16.
Int J Cancer ; 147(12): 3384-3393, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32580250

RESUMO

Metabolic syndrome (MetS) and its components may link to pancreatic cancer risk; however, current epidemiological evidence is limited, and the potential mechanisms underlying the associations remain unclear. To investigate this, we carried out this prospective cohort study of 474 929 participants without a diagnosis of cancer based on UK Biobank dataset. MetS was defined according to the International Diabetes Federation criteria and pancreatic cancer was identified through linkage to UK cancer registries (median follow-up time: 6.6 years). We evaluated hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demography and lifestyle factors. Restricted cubic spline was performed for each MetS component to investigate their possible nonlinear associations with risk of pancreatic cancer. During 3 112 566 person-years of follow-up, 565 cases of pancreatic cancer were identified. Individuals with MetS (HR = 1.31, 95% CI, 1.09-1.56), central obesity (HR = 1.24, 95% CI, 1.02-1.50) and hyperglycemia (HR = 1.60, 95% CI, 1.31-1.97) had increased risk of pancreatic cancer. Higher waist circumference (WC) and blood glucose were independently associated with pancreatic cancer, with no evidence against nonlinearity. Although elevated CRP (≥1.00 mg/dL) showed a positive association with the risk for pancreatic cancer, the effect was substantially increased only in participants with MetS and CRP ≥1.00 mg/dL. Our study demonstrated a positive association between MetS and increased risk of pancreatic cancer, with two of the MetS components, WC and blood glucose, showing independent associations in linear manner. Our study also suggested a potential joint effect of MetS and CRP in pancreas tumorigenesis.


Assuntos
Síndrome Metabólica/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Neoplasias Pancreáticas/etiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reino Unido/epidemiologia , Circunferência da Cintura
17.
AAPS PharmSciTech ; 21(4): 130, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32405780

RESUMO

As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal with this critical situation. In addition to being controlled through effective isolation, we need a rapid response from the healthcare and biotechnology industries to accelerate drug treatment research. By reviewing the currently available literature published at home and abroad, we summarize the current research progress of drug treatment during the epidemic period. At present, the drugs that can be used for treatment mainly include antiviral drugs, antimalarials, glucocorticoids, plasma therapy, biological agents, and traditional Chinese medicine. The effectiveness and safety of drug therapy need to be confirmed by more clinical studies.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Fatores Biológicos/uso terapêutico , Pesquisa Biomédica/tendências , COVID-19 , Infecções por Coronavirus/terapia , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva , Medicina Tradicional Chinesa , Pandemias , SARS-CoV-2
18.
Aging (Albany NY) ; 12(9): 8107-8119, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401747

RESUMO

Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Silencing Nur77 with siRNA can aggravate intracellular LDH release, increase the expression of pro-inflammatory genes (such as tumor necrosis factor α, nuclear factor κB (p65), monocyte chemotactic protein 1, interleukin-6), and decrease cell survival, decrease expression of nuclear factor E2-related factor(Nrf2), heme oxygenase 1, NADPH quinineoxidoreductase-1. Cytosporone B (Nur77 agonist) has the opposite effect to Nur77 silencing. PDTC (NF-κB inhibitor / antioxidant) can also inhibit pro-inflammatory genes to a similar degree as Cytosporone B. Phosphorylated IκB-α can be inhibited by Cytosporone B, while silencing Nur77 can increase the protein expression level of phosphorylated IκB-α. After silencing IκB-α, both Cytosporone B and siNur77 did not affect pro-inflammatory genes and antioxidant stress. These findings reveal the first evidence that Nur77 exerts anti-inflammatory and antioxidant stress effects by inhibiting IκB-α phosphorylation expression in a Parkinson cell model. Nur77 may be a potential therapeutic target for Parkinson's disease.


Assuntos
Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Estresse Oxidativo , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Apoptose , Sobrevivência Celular , Humanos , Inflamação/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
19.
Anal Chem ; 92(10): 7200-7208, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32233451

RESUMO

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.


Assuntos
Benzopirenos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Técnicas Analíticas Microfluídicas , Nicotina/efeitos adversos , Pneumonia/induzido quimicamente , Alvéolos Pulmonares/efeitos dos fármacos , Benzopirenos/química , Células Cultivadas , Técnicas de Cocultura , Citocinas/análise , Citocinas/metabolismo , Poluentes Ambientais/química , Humanos , Microscopia Confocal , Estrutura Molecular , Nicotina/química , Pneumonia/metabolismo , Pneumonia/patologia , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo
20.
Cell Mol Neurobiol ; 40(7): 1155-1164, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32016638

RESUMO

The cognitive function impairment may be related to the inflammation of the hippocampus in Parkinson's disease. Simvastatin can play a positive role in Parkinson's disease. The purpose of this study was to investigate whether simvastatin could improve behavioral disorders, especially depression, anxiety and cognitive function in mouse PD models, and further explore the molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for 5 consecutive days. At the same time, simvastatin (10 mg/kg) was pretreated for 2 days before the Parkinson's disease model was established, and then continued for 5 days, and the control group underwent intraperitoneal injection of MK801 (dizocilpine, 0.2 mg/kg) and saline solution. Depression status was tested by a tail suspension test and a sucrose splash test, followed by an open-field test and an elevated plus maze test to determine anxiety levels. Spatial behavior and muscle status were measured with a water maze and a rotarod test. The expression of RNA and protein of N-methyl-D-aspartate receptor subtype 2B (NMDAR2B), nerve growth factor IB (Nur77), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF) α were assayed by real-time polymerase chain reaction and Western blot. Our results showed that simvastatin can improve the cognitive function, anxiety, and depression of PD mice with MPTP injury. Simvastatin reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice. This role of simvastatin was consistent with MK801 in increasing the expression of Nur77 and inhibiting NMDAR2B and cytokines in MPTP-lesioned PD mice. These findings suggest that reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice may be one of the mechanisms that simvastatin improves cognitive functions, depression, and anxiety in MPTP-lesioned mice.


Assuntos
Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Sinvastatina/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Hipocampo/metabolismo , Inflamação/patologia , Camundongos Endogâmicos C57BL , N-Metilaspartato/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo
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