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1.
Bioorg Med Chem Lett ; 30(9): 127097, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171616

RESUMO

A series of novel rutaecarpine derivatives were synthesized and subjected to pharmacological evaluation as PDE5 inhibitors. The structure-activity relationships were discussed and their binding conformation and simultaneous interaction mode were further clarified by the molecular docking studies. Among the 25 analogues, compound 8i exhibited most potent PDE5 inhibition with IC50 values about 0.086 µM. Moreover, it also produced good effects against scopolamine-induced cognitive impairment in vivo. These results might bring significant instruction for further development of potential PDE5 inhibitors derived from rutaecarpine as a good candidate drug for the treatment of Alzheimer's disease.

2.
Chemosphere ; 241: 125124, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683421

RESUMO

Efficient electrochemical generation of ferrate (Fe(VI)) is still challenged by the passivation of iron materials. Herein, we employed Fe(0)-plated carbon sheet as an anode to enable an efficient production of Fe(VI) with its concentration reached up to 55 mM, which was 8 times higher than that with iron sheet of the same size as an anode. The SEM results showed that the close and uniform dispersion of tapered Fe(0) particles on the surface of carbon sheet helped prevent the formation of passivated layer. The preparative process of electro-deposited Fe(0) affected the generation of Fe(VI). The increase of electroplating time to 40 min and electroplating temperature to 30 °C promoted the production of Fe(VI), and the change in the concentration of Fe2+ in electroplated solution showed little impact on Fe(VI) generation. However, the addition of additives inhibited Fe(VI) generation. As well, an effective removal of cyanide was achieved using on-line production of Fe(VI), comparable to that by NaClO and higher than that by other traditional oxidants containing H2O2, O3, and KMnO4. This study would provide an simple and promising iron anode for efficient production of Fe(VI) by electrochemical method.


Assuntos
Cianetos/isolamento & purificação , Técnicas Eletroquímicas/métodos , Ferro/química , Purificação da Água/métodos , Carbono/química , Eletrodos , Oxidantes , Oxirredução , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação
3.
Brain Res Bull ; 153: 223-231, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493542

RESUMO

Alzheimer's disease (AD), characterized by a progressive impairment of memory and cognition, is a major health problem in both developing and developed countries. Currently, no drugs can reverse the progression of AD. Phosphodiesterase 5 (PDE5) is a critical component of the cyclic guanosine monophosphate/protein kinase G (cGMP/PKG) signaling pathway in neurons, the inhibition of which has produced neuroprotective effects, and PDE5 inhibitors have recently been thought to be potential therapeutic agents for AD. In this paper, we summarized the outstanding progress that has been made in PDE5 inhibitors as anti-AD agents with encouraging results in animal studies, clinical trials and the investigations on the underlying mechanisms. The novel PDE5 inhibitors reported recently in the treatment of AD were also reviewed and discussed.

4.
Environ Sci Pollut Res Int ; 26(9): 8516-8524, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30761490

RESUMO

Most prevailing processes are incapable of removing Cr(III)-organic complexes efficiently and facing the problem of in-process formation of highly toxic Cr(VI) based on oxidation. The efficient decomplexation of Cr(III) complexes and simultaneous abatement of Cr with low Cr(VI) accumulation would be desirable in treatment of Cr(III)-complexed wastewater. Here, we found efficient degradation of Cr(III)-EDTA and simultaneous removal of Cr by forming Cr2O3 precipitate from simulated solution as well as an electroplating effluent under UV irradiation. The results showed a complete degradation of Cr(III)-EDTA after reaction time of 60 min and 70-80% of TOC mineralization within 180 min as well. About 90% of Cr(III) precipitated as Cr2O3 simultaneously, with the residual total Cr below 1.5 mg/L. The degradation of Cr(III)-EDTA was a stepwise de-acetate group process, as proven by the obvious attenuation of peaks related to carboxyl groups and C-C bond from FT-IR spectra of Cr(III)-EDTA and significant mineralization of TOC after UV irradiation. Based on negligible accumulation of Cr(VI) (less than 0.1 mg/L) under N2-sparged condition, the C-centered radicals from the ß-fragmentation of O-centered radicals formed by photo-induced ligand-to-metal charge transfer were responsible for the in situ reduction of intermediate Cr(VI), resulting in the low accumulation of Cr(VI). The addition of 20 mg/L Fe2+ was capable of removing the remaining Cr(VI) and total Cr, with Cr(VI) and total Cr less than 0.1 and 1.0 mg/L, respectively. Moreover, the photo-oxidation process combined with Fe2+ addition were efficient in removing other Cr(III) complexes, such as Cr(III)-citrate and those from a realistic electroplating effluent. We believe that this study would provide an alternative option for efficient degradation of Cr(III) complexes and simultaneous abatement of Cr from contaminated water.


Assuntos
Cromo/química , Ácido Edético/química , Poluentes Químicos da Água/química , Galvanoplastia , Modelos Químicos , Oxirredução , Processos Fotoquímicos , Espectroscopia de Infravermelho com Transformada de Fourier , Raios Ultravioleta , Águas Residuárias/análise
5.
Environ Sci Technol ; 53(4): 2036-2044, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30653306

RESUMO

Traditional processes usually cannot enable efficient water decontamination from toxic heavy metals complexed with organic ligands. Herein, we first reported the removal of Cu(II)-EDTA by a UV/chlorine process, where the Cu(II)-EDTA degradation obeyed autocatalytic two-stage kinetics, and Cu(II) was simultaneously removed as CuO precipitate. The scavenging experiments and EPR analysis indicated that Cl• accounted for the Cu(II)-EDTA degradation at diffusion-controlled rate (∼1010 M-1 s-1). Mechanism study with mass spectrometry evidence of 11 key intermediates revealed that the Cu(II)-EDTA degradation by UV/chlorine was an autocatalytic successive decarboxylation process mediated by the Cu(II)/Cu(I) redox cycle. Under UV irradiation, Cu(I) was generated during the photolysis of the Cl•-attacked complexed Cu(II) via ligand-to-metal charge transfer (LMCT). Both free and organic ligand-complexed Cu(I) could form binary/ternary complexes with ClO-, which were oxidized back to Cu(II) via metal-to-ligand charge transfer (MLCT) with simultaneous production of Cl•, resulting in the autocatalytic effect on Cu(II)-EDTA removal. Effects of chlorine dosage and pH were examined, and the technological practicability was validated with authentic electroplating wastewater and other Cu(II)-organic complexes. This study shed light on a new mechanism of decomplexation by Cl• and broadened the applicability of the promising UV/chlorine process in water treatment.


Assuntos
Cloro , Purificação da Água , Ácido Edético , Raios Ultravioleta , Águas Residuárias
6.
Sci Total Environ ; 651(Pt 1): 218-229, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30227292

RESUMO

Grasping the temporal-spatial characteristics of interactions and spatial scales of multiple ecosystem services is the foundation for sustainable ecosystem management. Eight ecosystem services, including crop production, freshwater supply, aquatic production, net primary production, soil conservation, water retention, flood regulation, and forest recreation were measured at the 1-km2 pixel scale in the Taihu Lake Basin (TLB) of China from 1990 to 2010. Furthermore, we quantified the trade-offs and synergies of services at different periods of urbanization and across the 1-km2 pixel scale and the county scale. We aim to find which ecosystem services interactions temporally vary and depend on spatial scale. Our results found that: 1). Tremendous amount of cultivated lands were converted to construction land, and rapidly shrank from 1990 to 2010. 2). Determined by land use, different ecosystem services had spatial heterogeneity of their strength. Ecosystem services hot spots experienced an increasing trend while cold spots showed a trend of decreasing first and then increasing from 1990 to 2010. 3). Trade-offs between provisioning services and regulating services at the 1-km2 pixel scale changed over time. There was a new synergy between freshwater supply and aquatic production at the 1-km2 pixel scale in 2010 with the human demand. 4). From 1990 to 2010, the changes of provisioning services led to trade-offs among provisioning services, regulating services and cultural services at two scales. Taking temporal variation and scale dependence into account, this research is helpful to the delineation of "Ecological Conservation Redline" and implement the project of "Grain for Green". We also provide suggestions for maintaining ecosystem services with economic growth in China's Yangtze River Economic Belt for land use policies and decision making.


Assuntos
Conservação dos Recursos Naturais , Tomada de Decisões , Ecossistema , Urbanização , China , Lagos , Modelos Teóricos , Estações do Ano , Análise Espacial , Desenvolvimento Sustentável
7.
Bioorg Med Chem Lett ; 29(3): 481-486, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30554955

RESUMO

Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders. Herein, based on the existing PDE2 inhibitors and their binding modes, a series of purin-6-one derivatives were designed, synthesized and evaluated for PDE2 inhibitory activities, which led to the discovery of the best compounds 6p and 6s with significant inhibitory potency (IC50: 72 and 81 nM, respectively). Docking simulation was performed to insert compound 6s into the crystal structure of PDE2 at the active site to determine the binding mode. Furthermore, compound 6s significantly protected HT-22 cells against corticosterone-induced cytotoxicity and rescued corticosterone-induced decreases in cAMP and cGMP levels. It also produced anxiolytic-like effect in the elevated plus-maze test and exhibited favorable pharmacokinetic properties in vivo. These results might bring significant instruction for further development of potent PDE2 inhibitors.


Assuntos
Ansiolíticos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Desenho de Drogas , Fármacos Neuroprotetores/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Purinonas/farmacologia , Animais , Ansiolíticos/síntese química , Ansiolíticos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Humanos , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Purinonas/síntese química , Purinonas/química , Relação Estrutura-Atividade
8.
Neuropharmacology ; 143: 176-185, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30268520

RESUMO

Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. The present study examined whether the effects of PDE2 inhibition on oxidative stress were directly involved in reduced ROS by regulating NADPH subunits gp91phox oxidase. The results suggested that the PDE2 inhibitor Bay 60-7550 reversed oxidative stress-induced behavioral signature, i.e. depression and anxiety. Pretreatment with the oxidizing agent DTNB completely blocked, while the reducing agent DTT and the NADPH oxidase inhibitor apocynin potentiated the effects of Bay 60-7550 on behavioral abnormalities, demonstrating the relationship between PDE2 and oxidative stress. Consistently, an in vitro test revealed the positive correlation between ROS and PDE2 levels. Moreover, Bay 60-7550 decreased corticosterone-induced gp91phox expression, which is the source of ROS. The subsequent study suggested that Bay 60-7550 induced decrease in ROS and increase in cAMP/cGMP, pVASP, pCREB, and the neurotrophic factor BDNF levels, which were completely blocked by CRISPR/Cas9-mediated gp91phox overexpression and potentiated by gp91phox siRNA-based antioxidant strategies. The in vivo test in stressed mice further suggested that gp91phox overexpression completely blocked the antidepressant- and anxiolytic-like effects of Bay 60-7550, while gp91phox knockdown enhanced such effects. These results provide solid evidence that the antidepressant- and anxiolytic-like effects of Bay 60-7550 against stress are causally related to down-regulation of gp91phox and activation of the cAMP/cGMP-pVASP-CREB-BDNF signaling pathway.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Transtorno Depressivo/tratamento farmacológico , Imidazóis/farmacologia , NADPH Oxidase 2/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Triazinas/farmacologia , Animais , Antioxidantes/farmacologia , Transtornos de Ansiedade/metabolismo , Linhagem Celular , Corticosterona/administração & dosagem , Corticosterona/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Transtorno Depressivo/metabolismo , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos ICR , NADPH Oxidase 2/genética , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Psicotrópicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo
9.
Chemosphere ; 210: 745-752, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30036822

RESUMO

In this study, the performance of a living machine (LM) system was evaluated for use in the treatment of black water collected from septic tanks with hydraulic retention times (HRTs) of 6, 5, and 4 days. We found that the HRT had little effect on the removal efficiency of chemical oxygen demand (COD). However, the removal rates of total nitrogen (TN) and ammonium nitrogen (NH4+-N) decreased with the reduction of HRT, whereas the removal efficiency of total phosphate (TP) was consistently low because of the long sludge retention time. The working conditions of #1 achieved the highest removal efficiency of COD (85%), NH4+-N (75%), and TN (47%), although the removal efficiency of TP (11%) was slightly lower than that of #2 (12%). The microbial communities in each tank of the LM system were characterized by high-throughput sequencing, which showed that the LM system successfully created more favorable conditions for fermentative bacteria than traditional systems, with relative abundances of 13% (#1), 13% (#2), and 15% (#3) compared to that of the anaerobic/anoxic/oxic (A2O) system (<3%). Smithella was the dominant fermentative bacteria, accounting for 9% (#1), 7% (#2), and 10% (#3) of total bacteria in the LM system. The relative abundances of ammonia oxidizing bacteria (AOB) (12%) and anaerobic ammonium oxidizing bacteria (AnAOB) (7%) in the LM system were much higher than that in the A2O system. Overall, the LM system offered a more sustainable and economical solution for treating black water.


Assuntos
Bactérias Anaeróbias/crescimento & desenvolvimento , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Purificação da Água/métodos , Água/química , Nitrogênio/química
10.
CNS Neurosci Ther ; 24(10): 889-896, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29722134

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a mental disease characterized by depressed mood, lifetime anxiety, and deficits of learning and memory. Inhibition of phosphodiesterase 9 (PDE9) has been reported to improve rodent cognitive and memory function. However, the role of PDE9 in MDD, in particular its manifestations of depression and anxiety, has not been investigated. METHODS: We examined the protective effects of WYQ-C36D (C36D), a novel PDE9 inhibitor, against corticosterone-induced cytotoxicity, pCREB/CREB and BDNF expression by cell viability, and immunoblot assays in HT-22 cells. The potential effects of C36D at doses of 0.1, 0.5, and 1 mg/kg on stress-induced depression- and anxiety-like behaviors and memory deficits were also examined in mice. RESULTS: C36D significantly protected HT-22 cells against corticosterone-induced cytotoxicity and rescued corticosterone-induced decreases in cGMP, CREB phosphorylation, and BDNF expression. All these effects were otherwise blocked by the PKG inhibitor Rp-8-Br-PET-cGMPS (Rp8). In addition, when tested in vivo in stressed mice, C36D produced antidepressant-like effects on behavior, as shown by decreased immobility time both in the forced swimming and tail suspension tests. C36D also showed anxiolytic-like and memory-enhancing effects in the elevated plus-maze and novel object recognition tests. CONCLUSION: Our results show that inhibition of PDE9 by C36D produces antidepressant- and anxiolytic-like behavioral effects and memory enhancement by activating cGMP/PKG signaling pathway. PDE9 inhibitors may have the potential as a novel class of drug to treat MDD.


Assuntos
Corticosterona/toxicidade , GMP Cíclico/metabolismo , Depressão/tratamento farmacológico , Síndromes Neurotóxicas/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Proteína de Ligação a CREB/metabolismo , Linhagem Celular Transformada , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Depressão/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Elevação dos Membros Posteriores/psicologia , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Síndromes Neurotóxicas/etiologia , Restrição Física/efeitos adversos , Natação/psicologia
11.
CNS Neurosci Ther ; 24(7): 652-660, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29704309

RESUMO

AIMS: Depression is currently the most common mood disorder. Regulation of intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) signaling by phosphodiesterase (PDE) inhibition has been paid much attention for treatment of depression. This study aimed to investigate the neuroprotective effects of Hcyb1, a novel PDE2 inhibitor, in HT-22 cells and antidepressant-like effects in mouse models of depression. METHODS: Hcyb1 was synthesized and its selectivity upon PDE2 was tested. Moreover, HT-22 hippocampal cells were used to determine the effects of Hcyb1 on cell viability, cyclic nucleotide levels, and the downstream molecules related to cAMP/cGMP signaling by neurochemical, enzyme-linked immunosorbent, and immunoblot assays in vitro. The antidepressant-like effects of Hcyb1 were also determined in the forced swimming and tail suspension tests in mice. RESULTS: Hcyb1 had a highly selective inhibition of PDE2A (IC50  = 0.57 ± 0.03 µmol/L) and over 250-fold selectivity against other recombinant PDE family members. Hcyb1 at concentrations of 10-10 and 10-9  mol/L significantly increased cell viability after treatment for 24 hours. At concentrations of 10-9 ~10-7  mol/L, Hcyb1 also increased cGMP levels by 1.7~2.3 folds after 10-minute treatment. Furthermore, Hcyb1 at the concentrations of 10-9  mol/L increased both cGMP and cAMP levels 24 hours after treatment. The levels of phosphorylation of CREB and BDNF were also increased by Hcyb1 treatment in HT-22 cells for 24 hours. Finally, in the in vivo tests, Hcyb1 (0.5, 1, and 2 mg/kg, i.g.) decreased the immobility time in both forced swimming and tail suspension tests, without altering locomotor activity. CONCLUSION: These results suggest that the novel PDE2 inhibitor Hcyb1 produced neuroprotective and antidepressant-like effects most likely mediated by cAMP/cGMP-CREB-BDNF signaling.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Linhagem Celular Transformada , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Elevação dos Membros Posteriores/métodos , Concentração Inibidora 50 , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , N-Metilaspartato/toxicidade , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia , Natação
12.
Front Pharmacol ; 9: 199, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670521

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aß accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3ß pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.

13.
Bioresour Technol ; 249: 175-181, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29040852

RESUMO

This study assesses the use of vertical greening for blackwater treatment. The effects of hydraulic retention time (HRT) and drip frequency on treatment performance were systematically studied. Additionally, microbial communities in the vertical greening system were characterized. The results show that the removal efficiencies of NH4+-N and total phosphate (TP) increased with an increase in HRT, and the drip frequency had a significant effect on TP. High-throughput sequencing revealed that the diversity of the microbial community did not change significantly along vertical and horizontal directions, but the dominant species shifted. Heterotrophic nitrifying and denitrifying bacteria decreased significantly while autotrophic nitrifying bacteria, especially ammonia oxidizing bacteria, proliferated in a vertical direction. Therefore, it is concluded that vertical greening systems can effectively treat blackwater and lower NH+-N levels.


Assuntos
Reatores Biológicos , Processos Autotróficos , Bactérias
14.
Sci Rep ; 7(1): 12044, 2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28935920

RESUMO

Beta amyloid peptides (Aß) are known risk factors involved in cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP and/or cGMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and neuroinflammatory events, as well as cognitive performance in AD are related to cAMP/cGMP-dependent pathways. The present study investigated how the selective PDE2 inhibitor BAY60-7550 (BAY) affected Aß-induced learning and memory impairment in two classic rodent models. IL-22 and IL-17, Bax and Bcl-2, PKA/PKG and the brain derived neurotropic factor (BDNF) levels in hippocampus and cortex were detected with immunoblotting assay. The results showed that BAY reversed Aß-induced cognitive impairment as shown in the water maze test and step-down test. Moreover, BAY treatment reversed the Aß-induced changes in IL-22 and IL-17 and the ratio of Bax/Bcl-2. Changes in cAMP/cGMP levels, PKA/PKG and BDNF expression were also prevented by BAY. These effects of BAY on memory performance and related neurochemical changes were partially blocked by the PKG inhibitor KT 5823. These findings indicated that the protective effects of BAY against Aß-induced memory deficits might involve the regulation of neuroinflammation and neuronal apoptotic events.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Imidazóis/farmacologia , Transtornos da Memória , Triazinas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Aprendizagem/efeitos dos fármacos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/enzimologia , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos
15.
J Environ Sci (China) ; 54: 231-238, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28391934

RESUMO

Halogenated aromatic compounds have attracted increasing concerns due to their toxicity and persistency in the environment, and dehalogenation is one of the promising treatment and detoxification methods. Herein, we systematically studied the debromination efficiency and mechanism of para-bromophenol (4-BP) by a recently developed UV/sulfite process. 4-BP underwent rapid degradation with the kinetics accelerated with the increasing sulfite concentration, pH (6.1-10) and temperature, whereas inhibited by dissolved oxygen and organic solvents. The apparent activation energy was estimated to be 27.8kJ/mol. The degradation mechanism and pathways of 4-BP were explored by employing N2O and nitrate as the electron scavengers and liquid chromatography/mass spectrometry to identify the intermediates. 4-BP degradation proceeded via at least two pathways including direct photolysis and hydrated electron-induced debromination. The contributions of both pathways were distinguished by quantifying the quantum yields of 4-BP via direct photolysis and hydrated electron production in the system. 4-BP could be readily completely debrominated with all the substituted Br released as Br-, and the degradation pathways were also proposed. This study would shed new light on the efficient dehalogenation of brominated aromatics by using the UV/sulfite process.


Assuntos
Retardadores de Chama , Modelos Químicos , Fenóis/química , Raios Ultravioleta , Halogenação , Cinética , Sulfitos/química
16.
Oncotarget ; 7(15): 20455-68, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-26967251

RESUMO

Neuropathic pain can be considered as a form of chronic stress that may share common neuropathological mechanism between pain and stress-related depression and respond to similar treatment. Ferulic acid (FA) is a major active component of angelica sinensis and has been reported to exert antidepressant-like effects; however, it remains unknown whether FA ameliorate chronic constriction injury (CCI)-induced neuropathic pain and the involvement of descending monoaminergic system and opioid receptors. Chronic treatment with FA (20, 40 and 80 mg/kg) ameliorated mechanical allodynia and thermal hyperalgesia in von Frey hair and hot plate tasks, accompanied by increasing spinal noradrenaline (NA) and serotonin (5-HT) levels. Subsequent study suggested that treatment of CCI animals with 40 and 80 mg/kg FA also inhibited spinal MAO-A levels. FA's effects on mechanical allodynia or thermal hyperalgesiawas blocked by 6-hydroxydopamine (6-OHDA) or p-chlorophenylalanine (PCPA) via pharmacological depletion of spinal noradrenaline or serotonin. Moreover, the anti-allodynic action of FA on mechanical stimuli was prevented by pre-treatment with beta2-adrenoceptor antagonist ICI 118,551, or by the delta-opioid receptor antagonist naltrindole. While the anti-hyperalgesia on thermal stimuli induced by FA was blocked by pre-treatment with 5-HT1A receptor antagonist WAY-100635, or with the irreversible mu-opioid receptor antagonist beta-funaltrexamine. These results suggest that the effect of FA on neuropathic pain is potentially mediated via amelioration of the descending monoaminergic system that coupled with spinal beta2- and 5-HT1A receptors and the downstream delta- and mu-opioid receptors differentially.


Assuntos
Analgésicos/farmacologia , Ácidos Cumáricos/farmacologia , Neuralgia/tratamento farmacológico , Receptor 5-HT1A de Serotonina/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Receptores Opioides/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monoaminoxidase/metabolismo , Neuralgia/metabolismo , Serotonina/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-26208624

RESUMO

The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or isophthalic acid (H2ip) leads to novel binary and ternary salts via hydrogen-bonding recognition. X-ray single-crystal diffraction analyses show that zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular array in either binary salts or ternary salt co-crystals, formulated as [HLf]·[Hip]·H2O (1), [HLf]·[BA]·[HBA]·H2O (2) and [HLf]·[BA]·[H2ip]·CH3OH·H2O (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding networks between HLf cations and acidic coformers with the lattice capturing water molecules. Structural comparison of (2) and (3) indicated that a delicate balance of geometries and hydrogen-bonding partners is required for stacking to favor the formation of ternary salt co-crystals. Cocrystallization was able to overcome the water insolubility of lomefloxacin. Both the salt co-crystals display enhanced solubility and better pharmaceutical applicability.


Assuntos
Antibacterianos/química , Antibacterianos/farmacocinética , Fluoroquinolonas/química , Fluoroquinolonas/farmacocinética , Animais , Antibacterianos/sangue , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Fluoroquinolonas/sangue , Modelos Moleculares , Estrutura Molecular , Ratos , Sais/sangue , Sais/química , Sais/farmacocinética , Solubilidade , Espectrometria de Massas em Tandem
18.
Int Immunopharmacol ; 26(1): 265-71, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25863235

RESUMO

Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Eugenol/uso terapêutico , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/metabolismo , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Eugenol/administração & dosagem , Feminino , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Oxirredução
19.
Water Res ; 73: 9-16, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25635752

RESUMO

Ozonation of recalcitrant contaminants under acidic conditions is inefficient due to the lack of initiator (e.g., OH(-)) for ozone to produce hydroxyl radicals (HO). In this study, we reported that benzoic acid (BA), which is inert to ozone attack, underwent efficient degradation by ozone at acidic pH (2.3). The kinetics of BA degradation and ozone decomposition were both enhanced by increasing BA concentrations. Essentially, it is a HO-mediated reaction. Based on the exclusion of possible contributions of H2O2 and phenol-like intermediates for HO production, the reaction mechanism involved the formation of ozone ion ( [Formula: see text] ), which is an effective precursor of HO, was thus proposed. The hydroxycyclohexadienyl-type radicals generated during the attack of BA by HO may lead to the formation of [Formula: see text] . Meanwhile, [Formula: see text] could also be possibly formed from the reaction between ozone and organic (e.g., ROO∙) or inorganic peroxyl radicals (e.g., HO2). In addition, the hydroxylated products like phenol-like intermediates also played a positive role in HO production. Consequently, HO was produced efficiently under acidic conditions, resulting in rapid degradation of BA. This study provides a new approach for ozone activation even at acidic pHs, and broadens the knowledge of ozonation in removal of micropollutants from water.


Assuntos
Ácido Benzoico/química , Ozônio/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Purificação da Água/métodos , Espectroscopia de Ressonância de Spin Eletrônica , Concentração de Íons de Hidrogênio , Radical Hidroxila/análise
20.
Int J Clin Exp Pathol ; 7(10): 7142-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25400810

RESUMO

Osteoporosis is a complex disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics and environmental factors. Collagen type alpha 1 (COL1A) and JAGGED (JAG1) genes have been implicated in relation to BMD. The aim of this study was to investigate possible association among BMD and rs2273061 of JAG1, rs1107946 and rs1800012 of Col1A1 polymorphisms, as well as their haplotypes with BMD in postmenopausal Chinese women. A structured questionnaire for risk factors was recorded and BMD in lumbar spine and total hip was measured by dual-energy X-ray absorptiomety. Genomic DNA was obtained from 367 postmenopausal Chinese women. Genomic DNA was extracted from EDTA-preserved peripheral venous blood by phenol-chloroform extraction method and analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). As a result, the rs1800012 polymorphism of COL1A1 showed an association with BMD of the lumbar spine under a dominant model. Besides, haplotype analysis of COL1A1 gene showed that G-G haplotype presented higher BMD in lumbar spine. No significant association between genotypes and alleles distributions of the rs1107946 polymorphism of COL1A1 and rs2273061 polymorphism of the JAG1 was found. In conclusion, our results suggest that the rs1800012 polymorphism of the COL1A1 and one haplotype were significantly associated with lumbar spine BMD variations in Chinese postmenopausal women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Densidade Óssea/genética , Proteínas de Ligação ao Cálcio/genética , Colágeno Tipo I/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Vértebras Lombares/fisiopatologia , Proteínas de Membrana/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo Genético , Pós-Menopausa/genética , Absorciometria de Fóton , Fatores Etários , Idoso , China/epidemiologia , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Proteína Jagged-1 , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/etnologia , Osteoporose Pós-Menopausa/fisiopatologia , Fenótipo , Pós-Menopausa/etnologia , Proteínas Serrate-Jagged , Fatores Sexuais
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