Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mycoses ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222082

RESUMO

BACKGROUND: Causes of voriconazole-related visual adverse events (VVAE) remained controversial. OBJECTIVES: We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE. PATIENTS/METHODS: This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. RESULT: Of the 76 patients, a total of 229 steady-state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1-5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was under-presented (OR, 0.11; 95% CI, 0.01-0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14-69.02; P = .013) in patients with visual hallucination when compared with those without. CONCLUSION: Transient receptor potential melastatin 1 was genetically associated with voriconazole-related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.

2.
Int Immunopharmacol ; 82: 106316, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32088642

RESUMO

Hydroxysafflor yellow A (HSYA) is an effective therapeutic agent that alleviates myocardial ischaemia/reperfusion injury (MIRI), but the exact mechanisms remain elusive. The aim of this study was to investigate the potential protective effect of HSYA against MIRI through mechanisms related to NLRP3 inflammasome regulation. In this study, hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocytes were treated with HSYA or the AMPK inhibitor, compound C (CC). Our results showed that HSYA pretreatment improved cardiomyocyte viability, maintained mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased caspase-3 activity, and inhibited NOD-like receptor 3 (NLRP3) inflammasome activation during H/R injury. Moreover, the inhibition of AMPK activation by the CC inhibitor partially abolished the effects of HSYA treatment, including suppressing the upregulation of NLRP3 inflammasome components (NLRP3, caspase-1 and interleukin-1ß) and promoting autophagy (LC3-II/LC3-I and p62). In conclusion, the protective mechanism of HSYA in H/R-induced cardiomyocyte injury is associated with inhibiting NLRP3 inflammasome activation through the AMPK signalling pathway.

3.
Mol Med Rep ; 21(2): 842-850, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974627

RESUMO

The present study investigated the role of cytochrome P450 family 2 subfamily E polypeptide 1 (CYP2E1) in the development and progression of gastric cancer (GC). The expression levels of CYP2E1 in MGC­803 GC cells and normal GES­1 cells were investigated via western blotting, and it was identified that the expression of CYP2E1 was different between GES­1 and MGC­803 cells. CYP2E1 was overexpressed in MGC­803 cells using a lentiviral vector GV358. Cell Counting Kit­8, flow cytometry, cell migration and Matrigel invasion assays suggested that overexpression of CYP2E1 promoted the proliferation and invasion, and inhibited the apoptosis of GC cells. The relationship between CYP2E1 expression and key signaling molecules in the PI3K/Akt/mTOR signaling pathway was assessed. Reverse transcription­quantitative PCR analysis showed that mTOR mRNA expression was significantly increased after overexpression of CYP2E1 (P<0.05). Western blotting results showed that overexpression of CYP2E1 upregulated the expression of phosphorylated (p)­Akt, p­mTOR and p­p70 ribosomal protein S6 kinase (P70S6K; Ser371) proteins (P<0.05). To further investigate the relationship between CYP2E1 and the PI3K/Akt/mTOR signaling pathway in GC cells, MGC­803 cells were treated with the PI3K inhibitor LY294002, and changes in the expression levels of PI3K, AKT, mTOR, P70S6K and CYP2E1 were observed. The present results showed that LY294002 downregulated the expression of PI3K, CYP2E1, AKT, mTOR and P70S6K (P<0.05). Therefore, changes in the biological function of GC cells induced by CYP2E1 overexpression may be via the PI3K/Akt/mTOR signaling pathway.

4.
Eur J Med Chem ; 185: 111729, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655431

RESUMO

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18, was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents.


Assuntos
Ginsenosídeos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ginsenosídeos/síntese química , Ginsenosídeos/química , Masculino , Estrutura Molecular , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Troponina I/sangue
5.
Ann Transl Med ; 7(20): 562, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807543

RESUMO

Background: Shuxuening injection (SXNI) has a good effect on cardiovascular and cerebrovascular diseases. Here, our study aims to investigate whether SXNI have the protective effect on myocardial ischemia-reperfusion injury (MIRI) and elucidate the mechanism of SXNI's cardiac protection. Methods: In this experiment, the coronary arteries of Sprague-Dawley (SD) rats were ligated for the induction of a MIRI model. TTC staining and haematoxylin-eosin (HE), as well as troponin I (TnI), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and CK-MB levels, were used to detect the protective effect of SXNI. In rat cardiac tissue, superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) activities and glucose-regulated protein 78 (GRP78), calreticulin (CRT), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression levels were detected. In rat serum, the levels of inflammatory factors, including high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, tumour necrosis factor-α, interleukin-6 (IL-6) and IL-1ß, were measured by Elisa. In the rat arterial tissue, Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) expression was measured by western blot. In the rat plasma, ELISA was used to assay the levels of coagulation and plasmin system indicators, including platelet activating factor, endothelin, tissue factor (TF), plasminogen inhibitor, thromboxane B2, plasma fibrinogen. Results: The results showed that SXNI can reduce the infarct size of myocardial tissue, decrease the myocardial enzyme and TnI levels and decrease the degree of myocardial damage compared with the model group. Additionally, SXNI can increase the activity of antioxidant enzymes, reduce the MDA level and decrease the GRP78, CRT, CHOP and caspase-12 expression levels. SXNI also decreased the levels of inflammatory cytokines in rat serum, lowered the level of procoagulant molecules in plasma and reduced the TLR4/NF-κB expression. Conclusions: SXNI has protective effect on MIRI mainly by inhibiting oxidative stress and endoplasmic reticulum stress (ERS), thereby regulating TLR4/NF-κB pathway to reduce inflammation, and lowing procoagulant-related factors levels to reduce the risk of thrombosis.

6.
Biomed Pharmacother ; 117: 109143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387189

RESUMO

Araloside C (AsC) has potential cardioprotective properties. However, the underlying mechanism of AsC-mediated cardioprotection, especially the role of mitochondrial function, remains largely unknown. Here, we used H9c2 cardiomyocytes to study the cardioprotective mechanisms of AsC through H2O2-induced oxidative stress. Cell viability, lactate dehydrogenase release, mitochondrial functions and bioenergetics were evaluated. Western blot analysis was used to measure the protein expression levels of apoptosis and the phosphorylation of AMP-activated protein kinase (AMPK). Results revealed that AsC increased cell viability, improved mitochondrial membrane potential disruption, decreased mitochondrial reactive oxygen species level, elevated cellular ATP levels and alleviated impaired mitochondrial respiration in H2O2-induced H9c2 cardiomyoblasts injury. Furthermore, AsC modulated apoptosis-associated protein expression and AMPK pathway in H9c2 cells under oxidative stress. In conclusion, AsC potentially protects H9c2 cardiomyoblasts against oxidative stress by regulating mitochondrial function and AMPK activation. AsC may be an effective therapeutic agent for the prevention of oxidative stress in cardiac injury.


Assuntos
Cardiotônicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Peróxido de Hidrogênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Int J Mol Sci ; 20(15)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349548

RESUMO

Currently, hundreds of herbal products with potential hepatotoxicity were available in the literature. A comprehensive summary and analysis focused on these potential hepatotoxic herbal products may assist in understanding herb-induced liver injury (HILI). In this work, we collected 335 hepatotoxic medicinal plants, 296 hepatotoxic ingredients, and 584 hepatoprotective ingredients through a systematic literature retrieval. Then we analyzed these data from the perspectives of phylogenetic relationship and structure-toxicity relationship. Phylogenetic analysis indicated that hepatotoxic medicinal plants tended to have a closer taxonomic relationship. By investigating the structures of the hepatotoxic ingredients, we found that alkaloids and terpenoids were the two major groups of hepatotoxicity. We also identified eight major skeletons of hepatotoxicity and reviewed their hepatotoxic mechanisms. Additionally, 15 structural alerts (SAs) for hepatotoxicity were identified based on SARpy software. These SAs will help to estimate the hepatotoxic risk of ingredients from herbs. Finally, a herb-ingredient network was constructed by integrating multiple datasets, which will assist to identify the hepatotoxic ingredients of herb/herb-formula quickly. In summary, a systemic analysis focused on HILI was conducted which will not only assist to identify the toxic molecular basis of hepatotoxic herbs but also contribute to decipher the mechanisms of HILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Preparações de Plantas/efeitos adversos , Preparações de Plantas/química , Plantas Medicinais/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Interações Medicamentosas , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estrutura Molecular , Filogenia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Preparações de Plantas/análise , Plantas Medicinais/classificação , Plantas Medicinais/genética , Relação Estrutura-Atividade
8.
Lancet ; 394(10196): 407-418, 2019 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-31230828

RESUMO

BACKGROUND: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population. METHODS: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 µg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma. FINDINGS: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45·7 million Chinese adults. The prevalence of asthma with airflow limitation was 1·1% (0·9-1·4), representing 13·1 million adults. Cigarette smoking (odds ratio [OR] 1·89, 95% CI 1·26-2·84; p=0·004), allergic rhinitis (3·06, 2·26-4·15; p<0·0001), childhood pneumonia or bronchitis (2·43, 1·44-4·10; p=0·002), parental history of respiratory disease (1·44, 1·02-2·04; p=0·040), and low education attainment (p=0·045) were associated with prevalent asthma. In 2032 people with asthma, only 28·8% (95% CI 19·7-40·0) reported ever being diagnosed by a physician, 23·4% (13·9-36·6) had a previous pulmonary function test, and 5·6% (3·1-9·9) had been treated with inhaled corticosteroids. Furthermore, 15·5% (11·4-20·8) people with asthma reported at least one emergency room visit and 7·2% (4·9-10·5) at least one hospital admission due to exacerbation of respiratory symptoms within the preceding year. INTERPRETATION: Asthma is prevalent but largely undiagnosed and undertreated in China. It is crucial to increase the awareness of asthma and disseminate standardised treatment in clinical settings to reduce the disease burden. FUNDING: National Key R&D Program of China, Ministry of Science and Technology of China; the Special Research Foundation for Public Welfare of Health, Ministry of Health of China; the Chinese National Research Program for Key Issues in Air Pollution Control; and the National Natural Science Foundation of China.


Assuntos
Asma/tratamento farmacológico , Asma/epidemiologia , Bronquite/epidemiologia , Fumar Cigarros/epidemiologia , Pneumonia/epidemiologia , Rinite Alérgica/epidemiologia , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Asma/etiologia , Bronquite/complicações , China/epidemiologia , Fumar Cigarros/efeitos adversos , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Prevalência , Rinite Alérgica/complicações , Fatores de Risco , Inquéritos e Questionários
9.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999595

RESUMO

As one of the leading causes of drug failure in clinical trials, drug-induced liver injury (DILI) seriously impeded the development of new drugs. Assessing the DILI risk of drug candidates in advance has been considered as an effective strategy to decrease the rate of attrition in drug discovery. Recently, there have been continuous attempts in the prediction of DILI. However, it indeed remains a huge challenge to predict DILI successfully. There is an urgent need to develop a quantitative structure-activity relationship (QSAR) model for predicting DILI with satisfactory performance. In this work, we reported a high-quality QSAR model for predicting the DILI risk of xenobiotics by incorporating the use of eight effective classifiers and molecular descriptors provided by Marvin. In model development, a large-scale and diverse dataset consisting of 1254 compounds for DILI was built through a comprehensive literature retrieval. The optimal model was attained by an ensemble method, averaging the probabilities from eight classifiers, with accuracy (ACC) of 0.783, sensitivity (SE) of 0.818, specificity (SP) of 0.748, and area under the receiver operating characteristic curve (AUC) of 0.859. For further validation, three external test sets and a large negative dataset were utilized. Consequently, both the internal and external validation indicated that our model outperformed prior studies significantly. Data provided by the current study will also be a valuable source for modeling/data mining in the future.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Simulação por Computador , Modelos Biológicos , Relação Quantitativa Estrutura-Atividade , Xenobióticos/química , Xenobióticos/toxicidade , Animais , Descoberta de Drogas/métodos , Humanos , Aprendizado de Máquina , Curva ROC
10.
Int J Mol Med ; 43(5): 2133-2143, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864694

RESUMO

Myrica rubra is well known for its delicious taste and high nutritional value. The present study investigated the potential protective effects and mechanisms of M. rubra flavonoids (MRF) extract on isoproterenol (ISO)­induced myocardial injury in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. An in vivo study revealed that MRF decreased serum cardiac enzyme levels, ameliorated pathological heart alterations and increased the antioxidant potential. The in vitro investigation demonstrated that MRF inhibited cell death, reactive oxygen species (ROS) accumulation, mitochondrial membrane depolarization, apoptosis rate and caspase­3 activation and enhanced the Bcl­2/Bax ratio during H/R injury. These effects were accompanied by the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase (GSK)­3ß. Further mechanism studies demonstrated that LY294002, a specific inhibitor of phosphoinositide 3­kinase (PI3K), abolished the MRF­mediated cardioprotection against H/R­induced apoptosis and ROS overproduction. Collectively, these results suggested that MRF exerts cardioprotective effects by attenuating oxidative damage and cardiomyocyte apoptosis most likely via a PI3K/Akt/GSK3ß­dependent mechanism.


Assuntos
Cardiotônicos/farmacologia , Flavonoides/farmacologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Myrica/química , Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Cromonas/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Isoproterenol , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Morfolinas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
11.
Molecules ; 24(3)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717322

RESUMO

Arsenic trioxide (ATO) has been verified as a breakthrough with respect to the management of acute promyelocytic leukemia (APL) in recent decades but associated with some serious adverse phenomena, particularly cardiac functional abnormalities. Salvianolic acid A (Sal A) is a major effective component in treating ATO-induced cardiotoxicity. Therefore, the objective of our study was to assess whether Sal A had protective effects by the regulation of calcium homeostasis and endoplasmic reticulum (ER) stress. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A via daily tail vein injections for two weeks. For the in vitro study, we detected the effects of ATO and/or Sal A in real time using adult rat ventricular myocytes (ARVMs) and an IonOptix MyoCam system. Our results showed that Sal A pretreatment alleviated cardiac dysfunction and Ca2+ overload induced by ATO in vivo and vitro. Moreover, Sal A increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity and expression, alleviated [Ca2+]ER depletion, and decreased ER stress-related protein expression. Sal A protects the heart from ATO-induced injury and its administration correlates with the modulation of SERCA, the recovery of Ca2+ homeostasis, and the down-regulation of ER stress-mediated apoptosis.


Assuntos
Trióxido de Arsênio/efeitos adversos , Ácidos Cafeicos/administração & dosagem , Cardiotoxicidade/tratamento farmacológico , Lactatos/administração & dosagem , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Animais , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/administração & dosagem , Cálcio/metabolismo , Cardiotoxicidade/etiologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Ratos , Retículo Sarcoplasmático/efeitos dos fármacos
12.
Stem Cell Res Ther ; 10(1): 20, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635051

RESUMO

BACKGROUND: Cardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components. METHODS: In this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 µM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment. RESULTS: The results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes. CONCLUSIONS: This finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates.

13.
ACS Appl Mater Interfaces ; 11(6): 6431-6441, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30640425

RESUMO

Development of a Pd-based catalyst with highly active and durable properties for formic acid oxidation reaction at the anode remains an important matter of interest in the research community. Herein, we have designed novel coal-based carbon fibers (Coal-CFs) with dicyandiamide (DCD) as nitrogen (N) source, triphenylphosphine (TPP) as phosphorus (P) source dual-doped to support Pd catalysts (Pd/NP-Coal-CFs(DCD/TPP)), which exhibit superior catalytic performance toward formic acid oxidation reaction. Mass activity of formic acid oxidation of Pd/NP-Coal-CFs(DCD/TPP) catalyst is 536.6 mA·mg-1Pd, which is 2.5 times higher than that of Pd/Coal-CFs catalyst. The higher specific surface areas, exclusive electron transport path, and the high synergistic interaction of N and P are the favorable phenomena for catalytic performance. The addition of coal not only increases the abundant defects sites but also makes the utilization of coal with high added value. This N and P dual-doped catalyst inspires an idea for promoting applications in practical fuel cells.

14.
Int J Mol Sci ; 20(1)2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30577658

RESUMO

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of Aralia elata (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya Aralia chinensis L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process.


Assuntos
Aralia/química , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Saponinas/química , Fator de Necrose Tumoral alfa/farmacologia
15.
Front Pharmacol ; 9: 1346, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524286

RESUMO

Patients with diabetes mellitus (DM) are at high risk for cognitive dysfunction. Endoplasmic reticulum stress (ERS) and inflammation play crucial roles in DM. Gastrodin (Gas), the main component of Gastrodia elata, possesses anti-oxidative stress, anti-inflammatory, and neuroprotective effects. This present study aims to investigate whether Gas could ameliorate cognitive dysfunction in DM and to explore its underlying mechanisms. Rats with streptozotocin-induced type 2 DM were used in this study. After administration of Gas for 5 weeks, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum, TNF-α, IL-1ß, MDA and SOD in the hippocampus were measured. Morris water maze, hematoxylin and eosin (HE) and Nissl staining were performed to assess the effects of Gas on cognitive function and hippocampal neuronal apoptosis. Protein levels of GLUT3, brain derived neurotrophic factor (BDNF), GRP78, PERK, P-PERK, TXNIP, ASC, NLRP3, CHOP, Bcl-2 and Bax were measured by using Western blot. The results showed that Gas could improve hyperglycemia and dyslipidemia in DM rats, as the levels of TC, TG LDL-C in serum were decreased. TNF-α, IL-1ß, MDA contents in the hippocampus were decreased, and SOD contents was increased in the hippocampus of DM rats. Inflammation, oxidative stress, ERS, and apoptosis were observed in the hippocampus of DM rats, accompanied with decreased expression of BDNF and GLUT3. Gas improved the cognitive deficits caused by diabetes and inhibited inflammation, oxidative stress, ERS, and apoptosis in the hippocampus. Furthermore, Gas substantially increased the expression of GLUT3, and inhibited hippocampal ERS and ERS-mediated apoptosis. Additionally, Gas increased the expression of BDNF and decreased the activation of NLRP3 inflammasome. These results suggested that by inhibiting ERS and NLRP3 inflammasome activation and increasing the expression of BDNF and GLUT3, Gas exhibits neuroprotective effects against cognitive dysfunction in DM.

16.
Int J Mol Sci ; 19(12)2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30544722

RESUMO

Patients with diabetes mellitus (DM) suffer more risks from diabetic encephalopathy such as cognitive dysfunction and depressive-like behaviors. Numerous studies show that ER (endoplasmic reticulum) stress and inflammation play important roles in the development of diabetic encephalopathy. Gastrodin (Gas), one major component of Gastrodia elata, is traditionally used in central nervous system disorders and is believed to possess anti-inflammatory, anti-apoptotic, and other neuroprotective effects. This present study aims to explore the protective effects of Gas on diabetic encephalopathy. Gas was administrated daily (70 and 140 mg/Kg) for 12 weeks. Meanwhile, the fasting blood glucose and body weight of db/db mice were measured every two weeks. After Gas treatment, the Morris water maze (MWM) test and novel object recognition (NOR) test were performed to assess the learning and memory functions of db/db mice, and the forced swim test was performed to evaluate depressive-like behaviors of db/db mice. Additionally, the expression of ER stress and Nucleotide binding and oligomerization domain-like (Nod) receptor family pyrin domain-containing 3 (NLRP3) inflammasome related proteins were evaluated by using Western blot. Our study suggested that Gas attenuated blood glucose levels and dyslipidemia of db/db mice. It has been shown that Gas could improve learning and memory function and depressive-like behaviors of db/db mice. Moreover, Gas inhibited ER stress and NLRP3 inflammasome activation in the hippocampus. Taken together, this study demonstrates that Gas attenuates the diabetic encephalopathy by inhibiting ER stress and NLRP3 inflammasome activation.


Assuntos
Comportamento Animal , Álcoois Benzílicos/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Depressão/tratamento farmacológico , Estresse do Retículo Endoplasmático , Glucosídeos/uso terapêutico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Álcoois Benzílicos/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/complicações , Depressão/sangue , Depressão/complicações , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucosídeos/farmacologia , Resistência à Insulina , Masculino , Memória/efeitos dos fármacos , Camundongos , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
17.
BMC Infect Dis ; 18(1): 643, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541454

RESUMO

BACKGROUND: The 2010 Infectious Diseases Society of America (IDSA) guidelines for management of cryptococcal diseases recommend high dose fluconazole (≥ 800 mg/day), either alone or with other antifungal drugs, as alternative anticryptococcal choices. But evidence for its use in the treatment of HIV-uninfected cryptococcal meningitis (CM) remains sparse. METHODS: A retrospective analysis of HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy from January 2011 to December 2016 at Huashan Hospital, Shanghai, China was performed. Efficacy and safety were assessed, and mortality and prognostic factors evaluated. RESULTS: A total of 44 patients were studied including 19 refractory to amphotericin B induction therapy, 8 refractory to fluconazole consolidation therapy (400 mg/d), and 17 intolerant of antifungal drugs. For salvage, 11 patients received triple therapy of high dose fluconazole, amphotericin B and flucytosine, 20 received dual therapy of high dose fluconazole and flucytosine, 13 received monotherapy of high dose fluconazole. Median duration of high dose fluconazole in salvage regimens was 136.5 days (range, 1-667 days). Clinical response rates were 72.1% (31/43) and 83.7% (36/43) when assessed at 2 weeks and the end of salvage therapy, respectively. Adverse events possibly related to high dose fluconazole occurred in 54.5% (24/44) of the patients, and all were mild or moderate. From the initiation of salvage therapy, 1-year all-cause mortality was 13.6% (6 of 44 patients) among the study population with no significant difference in refractory or intolerant patients. CONCLUSIONS: Adherence to guideline recommendations of high dose fluconazole, alone or in combination with other antifungals, was safe and often effective for salvage therapy of HIV-uninfected CM patients.


Assuntos
Antifúngicos/administração & dosagem , Fluconazol/administração & dosagem , Meningite Criptocócica/tratamento farmacológico , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , China/epidemiologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Fluconazol/efeitos adversos , Flucitosina/administração & dosagem , Flucitosina/efeitos adversos , Humanos , Masculino , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem
18.
Molecules ; 23(11)2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30413028

RESUMO

Inflammation is a major contributing factor to the progression of atherosclerosis. Ginsenoside Rb1 (Rb1), an active saponin of Panax notoginseng, has been found to exert beneficial effects on inflammation and oxidative stress. This study investigated the ability of Rb1 to inhibit the formation of atherosclerotic plaques and the potential mechanisms. In this study, the effects of Rb1 on the development of atherosclerosis were investigated in ApoE-/- deficient mice fed with a western diet. Mice were intragastrically administrated with Rb1 (10 mg/kg) for 8 weeks. This study is that ginsenoside Rb1 exerted an inhibitory effect on early atherosclerosis in ApoE-/- mice via decreasing body weight and food intake daily, upregulating the lipid levels of serum plasma, including those of TC, TG and LDL-C and HDL-C and reducing the atherosclerotic plaque area, suppressing inflammatory cytokines (levels of IL-1ß, IL-6 and TNF-α) in the serum of ApoE-/- mice, changing the expression levels of BCL-2, BAX, cleaved caspase-3 and cleaved caspase-9 and weakening apoptosis associated with anti-inflammatory activity. Hence, all these effects against atherosclerosis were tightly associated with regulation of necrosis or apoptosis associated with anti-inflammatory activity. Additionally, the results found that ginsenoside Rb1 increased autophagy flux to inhibit apoptosis via acceleration of autophagy by promoting transformation of LC3 from type I to type II in high-fat diet-induced atherosclerosis in ApoE-/- mice. This finding, along with those of the previous study, provides evidence that Rb1 promotes the process of autophagy to protect against atherosclerosis via regulating BCL-2 family-related apoptosis. These results indicate that Rb1 exhibits therapeutic effects in atherosclerosis by reversing the imbalance between apoptosis and autophagy.


Assuntos
Anti-Inflamatórios/administração & dosagem , Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Dieta Ocidental/efeitos adversos , Ginsenosídeos/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Aterosclerose/sangue , Aterosclerose/genética , Autofagia , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Humanos , Lipídeos/sangue , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
19.
EBioMedicine ; 37: 401-409, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30366814

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is a significant source of mortality, the pathogenesis of which has not been fully understood, especially in non-HIV infected populations. We aimed to explore the potential genetic influence of Toll-like receptor (TLR) on non-HIV CM. METHODS: This observational cohort study was done in two stages: a discovery stage and a validation stage. A case-control genetic association study was conducted between 159 non-HIV CM patients and 468 healthy controls. TLR SNPs significantly related to susceptibility went further validation in a second cohort of 583 subjects from a certain district. Associations among TLR SNPs, cerebrospinal fluid (CSF) cytokine concentrations, and clinical severity were explored in a third cohort of 99 previously untreated non-HIV CM patients. Logistic regression model was used to determine the independent predictors for disease severity. FINDINGS: In the discovery stage, eight TLR SNPs exhibited significant genetic susceptibility to non-HIV CM, one of which was validated in a population validation of HIV-infected cases while none survived in non-HIV cases. CSF cytokine detections showed that 18 cytokines were significantly over-expressed in severely ill patients. Two of the 8 SNPs (rs5743604 and rs3804099) were also significantly associated with disease severity. Specifically, the rs3804099 C/T genotype was further found to be correlated to 12 of the 18 up-regulated cytokines in severe patients. In addition, high levels of interleukin (IL)-10 in CSF (OR 2·97, 95% CI 1·49-5·90; p = 0·002) was suggested as an independent predictor for severity after adjusted for possible confounders. INTERPRETATION: TLR participates in both the occurrence and the pathogenesis of non-HIV CM. The in situ immune responses of CM were under genetic influence of TLR and contributed to disease severity. FUND: National Natural Science Foundation of China and National Key Basic Research Program of China (973 Program).


Assuntos
Meningite Criptocócica/genética , Polimorfismo de Nucleotídeo Único , Receptores Toll-Like/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Infecções por HIV , Humanos , Interleucina-10/sangue , Masculino , Meningite Criptocócica/sangue , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Receptores Toll-Like/sangue
20.
Open Forum Infect Dis ; 5(10): ofy228, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30302354

RESUMO

Background: Chronic and granulomatous invasive fungal rhinosinusitis are important causes of blindness and craniocerebral complications. However, the classification of these 2 diseases remains controversial. Methods: We retrospectively analyzed patients with chronic and granulomatous invasive fungal rhinosinusitus in a Chinese tertiary hospital from 2009 to 2017, with a focus on classification and comparisons. Results: Among 55 patients enrolled in our study, 11 (11/55, 20%) had granulomatous invasive fungal rhinosinusitis (GIFRS) and 44 (44/55, 80%) had chronic invasive fungal rhinosinusitis (CIFRS). Aspergillus fumigatus and Dematiaceous hyphomycetes were identified in 2 patients with GIFRS. Compared with granulomatous type, CIFRS was more frequently encountered in immunocompromised patients (P = .022), and the time from onset to diagnosis was much shorter (P = .001). Proptosis and orbital apex syndrome showed no significant difference between granulomatous and CIFRS in our study. The treatment options and prognosis of both diseases also showed no significant difference. Conclusions: Despite the consensus on histopathology, the classification of the chronic and granulomatous types may need further evaluation in clinical considerations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA