RESUMO
Long-term trends in riverine nutrient availability have rarely been linked to both phytoplankton composition and functioning. To explore how the changing availability of N and P affects not only phytoplankton abundance and composition but also the resource use efficiency of N, P, and CO2, a 25-year time series of water quality in the lower Han River, Korea, was combined with additional measurements of riverine dissolved organic carbon (DOC) and CO2. Despite persistent eutrophication, recent decreases in P relative to N have been steep in the lowest reach, increasing the annual mean mass ratio of N to P (N/P) from 24 (1994-2015) to 65 (2016-2018). While Chl a and cyanobacterial abundance exhibited overall positive and inverse relationships with P concentrations and N/P, respectively, severe harmful algal blooms (HABs) concurred with short-term increases in P and temperature. Microcystis often dominated HABs at low N/P that usually favors N-fixing cyanobacteria such as Anabaena. In the middle and lower reaches, phytoplanktonic P use efficiency was typically lower at low N/P. V-shaped relationships between N/P and CO2 concentrations, together with longitudinal upward shifts in the inverse relationship between Chl a and CO2, implied that eutrophication-enhanced phytoplankton biomass could turn into a significant source of CO2. after passing a threshold. The combined results suggest that cyanobacterial dominance co-limited by P availability and temperature can lower planktonic P use efficiency, while enhancing riverine CO2 emissions at low N/P ratios.
Assuntos
Cianobactérias , Fitoplâncton , Dióxido de Carbono , Eutrofização , Proliferação Nociva de Algas , Lagos , NutrientesRESUMO
Although eutrophic urban rivers receiving loads of wastewater represent an important anthropogenic source of N2O, little is known as to how temperature and other environmental factors affect temporal variations in N2O emissions from wastewater treatment plants (WWTPs) and downstream rivers. Two-year monitoring at a WWTP and five river sites was complemented with available water quality data, laboratory incubations, and stable isotopes in N2O and NO3- to explore how wastewater effluents interact with seasonal changes in environmental conditions to affect downstream metabolic processes and N2O emissions from the lower Han River traversing the megacity Seoul. Water quality data from four WWTPs revealed significant inverse relationships between water temperature and the concentrations or fluxes of total N (TN) in effluents. Increased TN fluxes at low temperatures concurred with N2O surges in WWTP effluents and downstream rivers, counteracting the long-term decline in TN fluxes resulting from enhanced wastewater treatments. Incubation experiments with river water and sediment, in isolation or combined, implied the hypoxic winter sediment as a large source of N2O, whereas the anoxic summer sediment produced a smaller amount of N2O only when it was added with oxic water. For both WWTP effluents and downstream rivers, bulk isotope ratios and intramolecular distribution of 15N in N2O distinctly differed between summer and winter, indicating incomplete denitrification in the hypoxic sediment at low temperatures as a primary downstream source adding to WWTP-derived N2O. Winter surges in wastewater TN and sediment N2O release highlight temperature variability as an underappreciated control over anthropogenic N2O emissions from increasingly urbanized river systems worldwide.
Assuntos
Óxido Nitroso , Purificação da Água , Óxido Nitroso/análise , Rios , Temperatura , Águas Residuárias/análiseRESUMO
OBJECTIVES: The purpose of this study was to carry out systematic review of the literature and meta-analysis to evaluate the diagnostic utility of cerebrospinal fluid (CSF) levels of the 42 amino acid form of amyloid-beta (Aß1-42) as a biomarker for differentiating Alzheimer's disease (AD) from non-AD dementia. METHODS: Design. Systematic literature review was used to evaluate the effectiveness of the Aß for the diagnosis of AD. The Scottish Intercollegiate Guidelines Network (SIGN) tool was used to evaluate independently the quality of the studies. Data sources. The literature review covered from January 1, 2004, to October 22, 2013, and searched eight domestic databases including Korea Med and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library. Data Extraction and Synthesis. Primary criteria for inclusion were valid studies on (i) patients with mild cognitive impairment with confirmed or suspected AD and non-AD dementia, and (ii) assessment of Aß1-42 levels using appropriate comparative tests. RESULTS: A total of 17 diagnostic evaluation studies were identified in which levels of CSF Aß1-42 were assessed. Meta-analysis was performed on 11 robust studies that compared confirmed AD (n = 2211) with healthy individuals (n = 1030), 10 studies that compared AD with non-AD dementias (n = 627), and 5 studies that compared amnestic mild cognitive impairment (n = 1133) with non-amnestic type subjects (n = 1276). Overall, the CSF Aß1-42 levels were reduced in AD compared to controls or non-AD dementia. The effectiveness of test was evaluated for diagnostic accuracy (pooled sensitivity, 0.80 (95% CI 0.78-0.82); pooled specificity, 0.76 (95% CI 0.74-0.78). CONCLUSIONS: Reduced CSF Aß1-42 levels are of potential utility in the differential diagnosis of AD versus non-AD dementias and controls. Diagnostic accuracy was high in AD versus healthy controls. However, differential diagnosis for MCI or non-AD might be evaluated by other biomarkers.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Estudos de Casos e Controles , Diagnóstico Diferencial , HumanosRESUMO
Previously, we suggested that tetrahydrobiopterin (BH4), an obligatory cofactor for dopamine synthesis, as an intrinsic contributor to dopaminergic neuron vulnerability. The BH4 toxicity is observed in dopamine-producing cells, including Cath.a cells, but not in non-dopaminergic cells. Furthermore, the dopaminergic cell death induced by BH4 is apoptotic in nature and involves oxidative stress, similar to that observed in Parkinson's disease. Accordingly, various antioxidants have been found to protect dopaminergic cells from BH4. This study was undertaken to evaluate protective effects of the dopamine receptor agonist bromocriptine on BH4-induced Cath.a cell death, because bromocriptine has been reported to be an antioxidant with a neuroprotective activity. In the presence of bromocriptine, the increase in LDH activity and mitochondrial cytochrome c release induced by BH4 were significantly abolished. This cytoprotective effect was phosphatidylinositol 3-kinase (PI3K)/Akt pathway-dependent. In addition, bromocriptine was found to up-regulate the expressions of nuclear factor-E2-related factor-2 and antioxidant enzymes including NAD(P)H quinone oxidoreductase 1. Our findings show that bromocriptine stimulates antioxidant defense mechanisms in Cath.a cells and suggest a potential use of bromocriptine as a neuroprotectant.
Assuntos
Antioxidantes/metabolismo , Biopterinas/análogos & derivados , Bromocriptina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Biopterinas/antagonistas & inibidores , Biopterinas/toxicidade , Bromocriptina/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Citocromos c/metabolismo , Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Enzimas/efeitos dos fármacos , Enzimas/metabolismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/fisiologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Parkinson's disease (PD) is a neurodegenerative disorder associated with selective loss of dopaminergic neurons in the substantia nigra. Because oxidative stress caused by dopamine oxidation to dopamine quinone is suggested as a major factor contributing to the pathogenesis of PD, the induction of the enzyme that catalyzes the reduction of quinones, NAD(P)H quinone oxidoreductase1 (NQO1), could be a desirable therapeutic strategy to protect cells from oxidative damage. The dopamine agonist bromocriptine is used clinically for PD therapy. In addition to ameliorating the motor deficit via dopamine D2 receptor activation, bromocriptine also has neuroprotective and antioxidative activity. In the present study, we show that bromocriptine upregulates the expression and activity of NQO1, attenuates the increase in the protein-bound quinone in H(2)O(2)-treated PC12 cells, and protects PC12 cells against oxidative damage. Bromocriptine increases the expression and nuclear translocation of a basic leucine zipper transcription factor, nuclear factor-E2-related factor-2 (Nrf2), which is known to be involved in the regulation of numerous antioxidant enzymes via the antioxidant response element. The Nrf2-related cytoprotective and antioxidative effects of bromocriptine are PI3K/Akt pathway-dependent, and are independent of dopamine receptor activation. The cytoprotective effect of bromocriptine in PC12 cells is not affected by the presence of dopamine D2 antagonist, and the bromocriptine-induced Nrf2-ARE activation and cytoprotection against oxidative stress are observed in both dopamine D2 receptor-expressing A7-D2 and non-expressing A7 cells. Taken together, we investigate the novel cytoprotective effect of bromocriptine involving PI3K- and Nrf2-mediated upregulation of the antioxidant enzyme NQO1.
Assuntos
Bromocriptina/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Antiparkinsonianos/farmacologia , Citoproteção/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Peróxido de Hidrogênio/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Ratos , Receptores de Dopamina D2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Sasa borealis (Poaceae) is a perennial medicinal plant which is a major source of bamboo leaves in Korea. The n-BuOH extract of S. borealis leaves exhibited significant antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and a cytoprotective effect against oxidative damage in HepG2 cells. Bioactivity-guided fractionation by column chromatography led to the isolation of two antioxidative flavonoid C-glycoside derivatives, isoorientin (2) and isoorientin 2"-O-alpha-L-rhamnoside (4) along with tricin 7-O-beta-D-glucopyranoside (1) and apigenin 6-C-beta-D-xylopyranosyl-8-C-beta-D-glucopyranoside (3). Their structures were identified on the basis of chemical and spectroscopic methods. The radical scavenging activity and cytoprotective effect against oxidative damage of all the isolated compounds were also evaluated. Isoorientin (2) and isoorientin 2-O-alpha-L-rhamnoside (4) showed potent free radical scavenging activity with IC50 values of 9.5 and 34.5 microM, respectively, and strong cytoprotective effects against t-BOOH-induced oxidative damage in HepG2 cells, at very low concentrations of 1.1 microM isoorientin and 0.8 microM isoorientin 2-O-alpha-L-rhamnoside. This is the first report of the isolation and antioxidant activity of compounds 2 and 4 from S. borealis.
Assuntos
Flavonas/farmacologia , Sequestradores de Radicais Livres/farmacologia , Glicosídeos/farmacologia , Sasa/química , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavonas/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Glicosídeos/isolamento & purificação , Humanos , Hidrazinas/química , Estrutura Molecular , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Picratos , Folhas de Planta/química , Relação Estrutura-Atividade , terc-Butil Hidroperóxido/toxicidadeRESUMO
Because oxidative stress is involved in the pathogenesis of various chronic diseases and the aging process, antioxidants that can increase the intrinsic antioxidant potency are proposed as desirable therapeutic agents to counteract oxidative stress-related diseases. NF-E2-related factor-2 (Nrf2) is a transcription factor that regulates important antioxidant and phase II detoxification genes, and therefore, the molecule that regulates nuclear translocation of Nrf2 and the induction of antioxidative proteins is thought to be a promising candidate as a cytoprotective agent for oxidative stress. In the present study, we show that isoorientin (luteolin 6-C-beta-D-glucoside) obtained from the leaves of Sasa borealis upregulates and activates Nrf2, and has protective ability against oxidative damage caused by reactive oxygen intermediates in HepG2 cells. Isoorientin induces increase in the level of antioxidant enzyme proteins, especially NQO1, and the cytoprotective and antioxidative effects of isoorientin are PI3K/Akt pathway-dependent. Together with direct radical scavenging activity, the novel effect of isoorientin on the regulation of antioxidative gene expression provides attractive strategy to prevent diseases associated with oxidative stress and attenuate the progress of the diseases.