RESUMO
The question of how the income inequality of residents affects the level of environmental regulation in the context of official corruption was the core research issue of this study. We analyzed this problem using the panel threshold regression model from 26 provinces in China from 1995 to 2017. We found that when there is no official corruption, the widening of the residents' income inequality promotes stricter environmental regulations; when the corruption problem is serious, the expansion of the residents' income inequality leads to the decline in environmental standards; that is, the impact of residents' income inequality on environmental regulation has a threshold effect due to corruption. In addition, the threshold effect due to corruption of all residents' income inequality on environmental regulation is mainly generated by the urban residents' income inequality and the urban-rural income inequality. This paper contributes to the literature that concentrates on the relationship between income inequality and environmental regulation, and shows that corruption is a key factor that can deeply influence that relationship. The research conclusion shows that increasing anti-corruption efforts can not only maintain national political stability, social fairness, and justice, but also be a powerful measure for environmental pollution governance.
Assuntos
Poluição Ambiental , Renda , China , Humanos , População Rural , Justiça Social , Fatores SocioeconômicosRESUMO
OBJECTIVE: To investigate the protective effects of dexmedetomidine (DEX) against cerebral ischemia/reperfusion (I/R) injury in mice and its relation with mitochondrial fusion and fission. METHODS: Male ICR mice were randomly divided into sham-operated group, I/R group, I/R+DEX group and I/R+DEX+dorsomorphin group. Mouse models of cerebral I/R injury were established by modified thread occlusion of the middle cerebral artery. DEX (50 µg/kg) was injected intraperitoneally at 30 min before cerebral ischemia, which lasted for 1 h followed by reperfusion for 24 h. The neurobehavioral deficits of the mice were evaluated based on Longa's scores. The volume of cerebral infarction was detected by TTC staining. The changes in mitochondrial morphology of the brain cells were observed with transmission electron microscopy. Western blotting was performed to detect the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), mitochondrial fusion protein (Mfn2) and mitochondrial fission protein (p-Drp1) in the brain tissues. RESULTS: DEX pretreatment significantly reduced the neurobehavioral score and the percent volume of cerebral infarction in mice with cerebral I/R injury. Treatment with dorsomorphin (an AMPK inhibitor) in addition to DEX significantly increased the neurobehavioral score and the percent volume of cerebral infarction in the mouse models. Transmission electron microscopy showed that DEX obviously reduced mitochondrial damage caused by cerebral I/R injury and restored mitochondrial morphology of the brain cells, and such effects were abolished by dorsomorphin treatment. Western blotting showed that DEX pretreatment significantly increased the expressions of p-AMPK and Mfn2 protein and decreased the expression of p-Drp1 protein in the brain tissue of the mice, and these changes were also reversed by dorsomorphin treatment. CONCLUSIONS: Preconditioning with DEX produces protective effects against cerebral I/R injury in mice possibly by activating AMPK signaling to regulate mitochondrial fusion and fission in the brain cells.
Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Dexmedetomidina , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dinâmica MitocondrialRESUMO
BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.
Assuntos
Demência/etiologia , Perda de Dente/psicologia , Adulto , Idoso , Demência/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Razão de Chances , Análise de Regressão , Fatores de RiscoRESUMO
As microglial activation is a key factor in the pathogenesis of Parkinson's disease (PD), drugs that target this process may help to prevent or delay the development of PD. The present study investigated the effects of dl3nbutylphthalide (NBP) on microglia in a lipopolysaccharide (LPS)-induced PD mouse model. The mice were randomly divided into a blank control group, LPS control group and NBP + LPS treatment group. Mice in the treatment group were given an intragastric infusion of 120 mg/kg NBP daily for 30 days during the establishment of the PD mouse model. At 4 and 28 weeks posttreatment, the motor behaviours of the mice in each group were observed using the rotarod test and the open field test. In addition, immunohistochemical staining was performed to determine the levels of activated microglia, tumour necrosis factorα and αsynuclein, and the number of tyrosine hydroxylase (TH)positive cells in the substantia nigra. NBP significantly improved dyskinesia, reduced microglial activation, decreased nuclear αsynuclein deposition and increased the survival of THpositive cells in the substantia nigra of LPSinduced PD model mice. These findings suggested that NBP may exert its therapeutic effect by reducing microglial activation in a mouse model of PD.
Assuntos
Benzofuranos/farmacologia , Discinesias/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Animais , Modelos Animais de Doenças , Discinesias/etiologia , Discinesias/genética , Discinesias/fisiopatologia , Regulação da Expressão Gênica , Imuno-Histoquímica , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/antagonistas & inibidores , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Atividade Motora/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/fisiopatologia , Teste de Desempenho do Rota-Rod , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
DL3nbutylphthalide (NBP) is extracted from rapeseed and exhibits multiple neuroprotective effects, exerted by inhibiting the inflammatory process, including reducing oxidative stress, improving mitochondrial function and reducing neuronal apoptosis. The present study aimed to investigate the neuroprotective effects of NBP in a lipopolysaccharide (LPS)induced mouse model of Parkinson's disease (PD). The behavior of mice was assessed using the rotarod test and openfield test, the amount of tyrosine hydroxylase in the substantia nigra pars compacta was evaluated by immunohistochemistry, and the levels of phosphorylated cJun Nterminal kinase (JNK), mitogenactivated protein kinase 14 (p38) and extracellular signalregulated kinase 1 were determined by western blotting. It was demonstrated that the LPSinduced behavioral deficits were significantly improved. LPSinduced dopaminergic neurodegeneration was relieved following treatment with NBP, as determined from tyrosine hydroxylasepositive cells. Phosphorylation of JNK and p38 was significantly inhibited following treatment with NBP. Therefore in the present study, a role for NBP has been established in the treatment of a PD murine model, laying the experimental basis for the treatment of PD with this agent.
Assuntos
Benzofuranos/farmacologia , Lipopolissacarídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Teste de Desempenho do Rota-Rod/métodos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Dual specificity phosphatase 6 (DUSP6), a member of the dual specificity protein phosphatase subfamily, can inactivate ERK1/2. However, its possible role in glutamate-induced oxidative cytotoxicity effects is not clear.Here, we aimed to investigate whether DUSP6 was neuroprotective against glutamate-induced cytotoxicity in HT22 mouse hippocampal cells and primary cultured hippocampal neurons (pc-HNeu). HT22 and pc-HNeu cells were treated with varying concentrations of glutamate (from 0.05mM to 5.0mM) and DUSP6 protein expression were detected by western blotting. DUSP6-overexpressing HT22 and pc-HNeu cells were generated by transfection with DUSP6-overexpressing plasmid. The effects of DUSP6 overexpression on glutamate-induced cytotoxicity, cell death, cell apoptosis, and cell autophagy were determined by cell proliferation assays, flow cytometry, transmission electron microscopy, and western blotting. Glutamate treatment from 0.5mM to 5.0mM downregulated DUSP6 protein expression in both HT22 and pc-HNeu cells. DUSP6 overexpression ameliorated glutamate-induced cell death, apoptosis, and autophagy in both HT22 and pc-HNeu cells. Furthermore, ERK1/2 phosphorylation was decreased by DUSP6 overexpression. In conclusion, DUSP6 has neuroprotective effects against glutamate-induced cytotoxicity in HT22 and pc-HNeu cells. Targeting DUSP6 may be a useful strategy to prevent neuronal death in neurodegenerative diseases including AD.
Assuntos
Apoptose/efeitos dos fármacos , Fosfatase 6 de Especificidade Dupla/metabolismo , Ácido Glutâmico/toxicidade , Hipocampo/patologia , Neurônios/patologia , Fármacos Neuroprotetores/metabolismo , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/ultraestrutura , Fosforilação/efeitos dos fármacosRESUMO
This study aimed to explore the influence of magnesium elevation on fate determination of adult neural progenitor cells (aNPCs) and the underlying mechanism in vitro. Adult neurogenesis, which is the generation of functional neurons from neural precursors, occurs throughout life in restricted anatomical regions in mammals. Magnesium is the fourth most abundant ion in mammals, and its elevation in the brain has been shown to enhance memory and synaptic plasticity in vivo. However, the effects of magnesium on fate determination of aNPCs, which are vital processes in neurogenesis, remain unknown. NPCs isolated from the dentate gyrus of adult C57/BL6 mice were induced to differentiate in a medium with varying magnesium concentrations (0.6, 0.8, and 1.0 mM) and extracellular signal-regulated kinase (ERK) inhibitor PD0325901. The proportion of cells that differentiated into neurons and glial cells was evaluated using immunofluorescence. Quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of ß-III tubulin (Tuj1) and glial fibrillary acidic protein (GFAP). The activation of ERK and cAMP response element-binding protein (CREB) was examined by Western blot to reveal the underlying mechanism. Magnesium elevation increased the proportion of Tju1-positive cells and decreased the proportion of GFAP-positive cells. Also, the expression of Tuj1 was upregulated, whereas the expression of GFAP was downregulated. Moreover, magnesium elevation enhanced the activation of both ERK and CREB. Treatment with PD0325901 reversed these effects in a dose-dependent manner. Magnesium elevation promoted neural differentiation while suppressing glial cell differentiation, possibly via ERK-induced CREB activation.