Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 137
Filtrar
1.
J Sep Sci ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670445

RESUMO

High-performance liquid chromatography coupled with photodiode array detection has been extensively applied in many fields and the peaks among the analyzed samples can be shifted due to the variations of instrumental and experimental conditions. In the multivariate analysis, the retention time alignment is an important pretreatment step. Hence, the shifted peaks in High-performance liquid chromatography coupled with photodiode array detection three-dimensional spectra should be aligned for further analysis. Being motivated by this purpose, the interval correlated shifting method combined with the proposed data arrangement methods are recommended and employed on High-performance liquid chromatography coupled with photodiode array detection data as a demonstration. We validate the alignment performance of the proposed method through comparison the consistency of the retention time before and after alignment. The obtained results demonstrated that the proposed method is capable of successful aligning the employed data. Additionally, the interval correlated shifting method combined with the data arrangement modes is implemented in an easy-to-use graphical user interface environment and so can be operated easily by users not familiar with programming languages. This article is protected by copyright. All rights reserved.

2.
Viruses ; 11(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597372

RESUMO

Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a > 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (TEM) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.

3.
Viruses ; 11(10)2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31590353

RESUMO

Peste des petits ruminants is a highly contagious acute or subacute disease of small ruminants caused by the peste des petits ruminants virus (PPRV), and it is responsible for significant economic losses in animal husbandry. Vaccination represents the most effective means of controlling this disease, with virus-like particle (VLP) vaccines offering promising vaccine candidates. In this study, a PPRV VLP-based vaccine was developed using a baculovirus expression system, allowing for the simultaneous expression of the PPRV matrix (M), hemagglutinin (H), fusion (F) and nucleocapsid (N) proteins in insect cells. Immunization of mice and goats with PPRV VLPs elicited a robust neutralization response and a potent cellular immune response. Mouse studies demonstrated that VLPs induced a more robust IFN-γ response in CD4+ and CD8+ T cells than PPRV Nigeria 75/1 and recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. In addition, PPRV VLPs induced a strong Th1 class response in mice, as indicated by a high IgG2a to IgG1 ratio. Goat studies demonstrated that PPRV VLPs can induce the production of antibodies specific for F and H proteins and can also stimulate the production of virus neutralizing antibodies to the same magnitude as the PPRV Nigeria 75/1 vaccine. Higher amounts of IFN-γ in VLP-immunized animal serum suggested that VLPs also elicited a cellular immune response in goats. These results demonstrated that VLPs elicit a potent immune response against PPRV infection in small ruminants, making PPRV VLPs a potential candidate for PPRV vaccine development.

4.
Atherosclerosis ; 289: 94-100, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31487565

RESUMO

BACKGROUND AND AIMS: About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS: 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS: Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ±â€¯1.7 mm2vs. 1.9 ±â€¯1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS: Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.

5.
Viruses ; 11(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470645

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.

6.
FEBS Open Bio ; 9(11): 1869-1879, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505105

RESUMO

Cervical cancer is one of the most common gynecological malignancies globally, Unfortunately, radiotherapy and chemotherapy are not effective at treating some cases of this disease, and the 5-year survival rate is only 40-50%. Cell division cycle 25A (CDC25A) has been shown to induce radioresistance in a variety of tumor cells, but the role of CDC25A in the radioresistance of cervical cancer has not been fully elucidated. Here, we report that CDC25A is highly expressed and miR-122-5p lowly expressed in cervical cancer tissues and cells. The TargetScan database was used to predict CDC25A as a target of miR-122-5p, and the interactions between miR-122-5p and CDC25A were further confirmed by western blot, real-time PCR and dual-luciferase reporter assay. Under X-ray irradiation, up-regulation of CDC25A can promote the radiation resistance of cervical cancer cells, whereas overexpression of miR-122-5p or knockdown of CDC25A inhibits the survival and induces apoptosis of cervical cancer colonies. In conclusion, our data suggest that miR-122-5p enhances the radiosensitivity of cervical cancer cells by targeting CDC25A.

7.
Medicine (Baltimore) ; 98(33): e16803, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415391

RESUMO

BACKGROUND: This proposed study will systematically assess the effect and safety of cognitive-behavioral therapy (CBT) for heart failure (HF). METHODS: We will search the following electronic databases for randomized controlled trials assessing the effect of CBT in patients with HF: PUBMED, EMBASE, Cochrane Library, Web of Science, Scopus, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data from their inceptions to present without any language limitations. Two authors will independently conduct the study selection, data extraction, and methodological quality assessment. The methodological quality will be evaluated by Cochrane risk of bias tool. RESULTS: This study will assess the efficacy and safety of CBT for patients with HF. The primary outcomes consist of depression and anxiety. The secondary outcomes comprise of all-cause mortality, change in body weight, urine output, change in serum sodium; and any adverse events. CONCLUSION: The results of this study will summarize the up-to-date evidence on the effect and safety of CBT for HF. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019135932.


Assuntos
Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Depressão/terapia , Insuficiência Cardíaca/psicologia , Adulto , Idoso , Ansiedade/etiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-31161381

RESUMO

The objective of this study was to increase the intracellular polysaccharide yield of Ganoderma lucidum. The accordingly optimized fermentation medium by central composite design method contains glucose 40 g L-1, yeast powder 12 g L-1, potassium dihydrogen phosphate 3 g L-1, initial pH 5.5, and inoculum size 10 mL 100 mL-1. Under this condition, the predicted value of intracellular polysaccharide yield was 2.03 g L-1. Shake flask experiments confirmed that the average intracellular polysaccharide yield was 1.98 g L-1 similar to the predicted value. The yields of intracellular polysaccharides in the 5-L and 50-L fermentors were 2.59 g L-1 and 2.65 g L-1, respectively. The molecular weight distribution of intracellular and extracellular polysaccharides obtained was determined by HPSEC-MALLS-RI. The results showed that the weight-average molecular weight of component 1 in the intracellular crude polysaccharide was 4.695 × 106 Da and the mass fraction was 58%. The weight-average molecular weight of component 2 in the extracellular polysaccharide was 5.554 × 104 Da. The mass fraction was 94.9%. The liquid submerged fermentation process of G. lucidum mycelium obtained from this study has effectively increased the yield of intracellular polysaccharides. Its intracellular and extracellular polysaccharides have good immunological activity. Conceivably, the optimized process can be applied for the large-scale production.

10.
Virus Genes ; 55(4): 550-556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161411

RESUMO

Japanese encephalitis virus SA14-14-2 (JEV SA14-14-2) is a widely used vaccine in China and other southeastern countries to prevent Japanese encephalitis in children. In this study, a stable infectious cDNA clone of JEV SA14-14-2 with a low copy number pACYC177 vector dependent on the T7 promoter and T7 terminator was developed. Two introns were inserted into the capsid gene and envelope gene of JEV cDNA for gene stability. Hepatitis delta virus ribozyme (HDVr) was engineered into the 3' UTR cDNA of JEV for authentic 3' UTR transcription. The rescued virus showed biological properties indistinguishable from those of the parent strain (JEV SA14-14-2). The establishment of a JEV SA14-14-2 reverse genetics system lays the foundation for the further development of other flavivirus vaccines and viral pathogenesis studies.

11.
Medicine (Baltimore) ; 98(18): e15374, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045783

RESUMO

There is scarce evidence regarding the association between the consumption of vegetables and fruits and depressive symptoms in Chinese population. The purpose of this study was to ascertain the influence of vegetables and fruits consumption on depressive symptoms in a middle-aged Chinese population. This study comprised 1676 Chinese adults aged between 45 and 59 years, who participated in a Health Survey at the time of periodic checkup in the city of Linyi, Shandong Province, China. Dietary intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Depressive symptoms were assessed using the Center for Epidemiological Studies Depression (CES-D) scale. Log-binomial regression analysis was used to evaluate the association between the consumption of vegetables and fruits and depressive symptoms. A total of 53 participants (3.2%) were classified as having depressive symptoms. After adjustment for confounding variables, participants in the highest quartile of the fruits consumption and vegetables consumption had lower prevalence ratio (PR) for depressive symptoms (PR = 0.76; 95% confidence interval [CI]: 0.603-0.974, P = .042; PR = 0.77; 95% CI: 0.612-0.977, P = .045) than those in the lowest quartile. Moreover, those in the highest quartile of total vegetables and fruits consumption had also a lower PR of depressive symptoms (PR = 0.67; 95% CI: 0.503-0.806, P = .037) than did those in the lowest quartile.Our findings indicate that higher consumption of vegetables and fruits is significantly associated with a lower risk of depressive symptoms. Further prospective studies are needed to confirm these findings.


Assuntos
Depressão/epidemiologia , Frutas , Verduras , China/epidemiologia , Estudos Transversais , Dieta , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos
12.
Sci Rep ; 9(1): 8030, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142815

RESUMO

To probe into the associations between maternal personal cosmetics use during pregnancy and risk of adverse outcomes, and explore the potential dose-response relationships, we carried out a prospective cohort study involving 9710 pregnant women in Zhuzhou City and Xiangtan City in Hunan province during 2016-2017. A structured questionnaire was used to collection information for the pregnant women and their pregnancy outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by binary or multinomial logistic regressions. The study population included 4652 (47.9%) cosmetics non-users and 5058 (52.1%) cosmetics users. Cosmetics use was associated with an increased risk of small for gestational age (SGA) (aOR = 1.23, 95%CI 1.04 to 1.44), compared with cosmetics non-users. A positive dose-response relationship between frequency of cosmetics use and SGA was observed, although a borderline association was found at low use frequency (1-2 times per week; aOR = 1.18, 95%CI 0.99 to 1.40) and moderate use frequency (3-4 times per week; aOR = 1.23, 95%CI 0.92 to 1.64). High-frequency of cosmetics use (≥5 times per week) was significantly correlated with a higher risk of SGA (aOR = 1.83, 95%CI 1.25 to 2.69). No significant association between personal cosmetics use and the risk of preterm birth, low birth weight, macrosomia, or large for gestational age was observed. The present study suggests that personal cosmetics use will increase the risk of SGA, but further research is required to determine which cosmetic products may account for the higher risk of SGA.

13.
Int J Med Mushrooms ; 21(3): 207-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002605

RESUMO

To fully analyze the composition of volatile oil extracted from Tremella fuciformis, hydrodistillation (HD) and solid phase microextraction (SPME) were adopted simultaneously. In both cases, the analysis was carried out using gas chromatography-mass spectrometry and the antioxidant activity of the volatile oil was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method with rutin as a positive control. Nineteen components in HD and 68 components in SPME were identified, respectively. Moreover, the oil obtained from T. fuciformis by HD indicated that aromatic compounds were a major class (93.5%), followed by the terpenes (5.7%), alkanes (0.4%), and alcohols (0.3%). Among them, butylated hydroxytoluene was the highest concentration (92.5%) of the compounds. The compounds detected by SPME were different from those of HD, and the substances with the largest content were esters (57.7%), followed by alcohols (19.0%), acids (7.0%), and aldehydes (6.3%). Only three of the same substances were detected in both of them, namely borneol, (-)-α-terpineol, and acetic acid. In the DPPH assays, strong antioxidant activity (IC50 = 0.176 mg/mL) was evident in volatile oil from T. fuciformis. Antioxidant activity was positively correlated with the concentration of volatile oil.


Assuntos
Agaricales/química , Antioxidantes/análise , Óleos Voláteis/química , Compostos Orgânicos Voláteis/análise , Produtos Biológicos/química , Cromatografia Gasosa-Espectrometria de Massas , Microextração em Fase Sólida
14.
Eur Radiol ; 29(10): 5528-5538, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30847586

RESUMO

OBJECTIVES: To construct a radiomics nomogram for the individualized estimation of the survival stratification in glioblastoma (GBM) patients using the multiregional information extracted from multiparametric MRI, which could facilitate the clinical decision-making for GBM patients. MATERIALS AND METHODS: A total of 105 eligible GBM patients (57 in the long-term and 48 in the short-term survival groups, separated by an overall survival of 12 months) were selected from the Cancer Genome Atlas. These patients were divided into a training set (n = 70) and a validation set (n = 35). Radiomics features (n = 4000) were extracted from multiple regions of the GBM using multiparametric MRI. Then, a radiomics signature was constructed using least absolute shrinkage and selection operator regression for each patient in the training set. Combined with clinical risk factors, a radiomics nomogram was constructed based on a multivariate logistic regression model. The performance of this radiomics nomogram was assessed by calibration, discrimination, and clinical usefulness. RESULTS: The radiomics signature consisted of 25 selected features and performed better than clinical risk factors (i.e., age, Karnofsky performance status, and treatment strategy) in survival stratification. When the radiomics signature and clinical risk factors were combined, the radiomics nomogram exhibited promising discrimination in the training (C-index, 0.971) and validation (C-index, 0.974) sets. The favorable calibration and decision curve analysis indicated the clinical usefulness of the radiomics nomogram. CONCLUSIONS: The presented radiomics nomogram, as a non-invasive prediction tool, could exhibit a favorable predictive accuracy and provide individualized probabilities of survival stratification for GBM patients. KEY POINTS: • Non-invasive survival stratification of GBM patients can be obtained with a radiomics nomogram. • The proposed nomogram constructed by radiomics signature selected from 4000 radiomics features, combined with independent clinical risk factors such as age, Karnofsky performance status, and treatment strategy. • The proposed radiomics nomogram exhibited good calibration and discrimination for survival stratification of GBM patients in both training (C-index, 0.971) and validation (C-index, 0.974) sets.

15.
Angew Chem Int Ed Engl ; 58(20): 6747-6751, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-30912227

RESUMO

A palladium-catalyzed enantioselective intramolecular σ-bond cross-exchange between C-I and C-C bonds is realized, providing chiral indanones bearing an alkyl iodide group and an all-carbon quaternary stereocenter. Pd/TADDOL-derived phosphoramidite is found to be an efficient catalytic system for both C-C bond cleavage and alkyl iodide reductive elimination. In addition to aryl iodides, aryl bromides can also be used for this transformation in the presence of KI. Density-functional theory (DFT) calculation studies support the ring-opening of cyclobutanones occuring through an oxidative addition/reductive elimination process involving PdIV species.

16.
Lipids Health Dis ; 18(1): 52, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764838

RESUMO

BACKGROUND: This study was designed to test the hypothesis that κ-opioid receptor (κ-OR) stimulation reduces palmitate-induced HUVECs apoptosis and to investigate its mechanisms. METHODS: HUVECs were subjected to sodium palmitate, apoptosis and cell viability were determined, HUVECs were treated with specific inhibitors to PI3K, Akt, eNOS and siRNAs targeting κ-OR and Akt. Groups were divided as follows: the control group, the sodium palmitate group, the sodium palmitate+U50,488H (a selective κ-OR agonist) group and the sodium palmitate+U50,488H + nor-BNI (a selective κ-OR antagonist) group. RESULTS: Treatment with sodium palmitate significantly reduced cell viability and increased apoptosis rate which were significantly alleviated by pretreatment with U50,488H, the effect of U50,488H was abolished by nor-BNI. Phosphorylation of Akt and eNOS, as well as NO production were attenuated and accompanied by an increased expression of caspase 3 when HUVECs were subjected to sodium palmitate, and all these changes were restored by pretreatment with U50,488H, the effects of U50,488H were abolished by nor-BNI, and specific inhibitors to PI3K, Akt, eNOS, respectively. SiRNAs targeting κ-OR or Akt abolished the effects of U50,488H on phosphorylation of Akt and eNOS as well as the expressions of caspase 3, Bax and Bcl-2. SiRNAs targeting Akt elicited no effect on the expression of κ-OR. CONCLUSION: This study provides the evidence for the first time that κ-OR stimulation possesses anti-palmitate-induced apoptosis effect, which is mediated by PI3K/Akt/eNOS signaling pathway.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Opioides kappa/genética , Analgésicos Opioides/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Ácido Palmítico/antagonistas & inibidores , Ácido Palmítico/farmacologia , Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/antagonistas & inibidores , Receptores Opioides kappa/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-30456924

RESUMO

A palladium-catalyzed enantioselective sequential ring-opening/cross-coupling of cyclobutanones is disclosed, providing chiral indanones bearing C3-quaternary stereocenters. The reaction process involves palladium-catalyzed nucleophilic addition of cyclobutanones and aryl halides, enantioselective ß-carbon elimination and intermolecular trapping of a transient σ-alkylpalladium complex with boronic acids. Alternatively, an intramolecular cyclopropanation is realized via C-H bond functionalization in the absence of external coupling reagents, affording chiral cyclopropane-fused-indanones in good yields and enantioselectivity.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30422891

RESUMO

Previous studies have shown that κ-opioid receptor activation possesses cardioprotection against myocardial ischemia and reperfusion (MI/R) injury. The current study was designed to investigate whether mitochondrial dysfunction following MI/R is regulated by the κ-opioid receptor and to further explore the underlying mechanisms involved. MI/R rat model was established in vivo, and a hypoxia and reoxygenation cardiomyocytes model was utilized in vitro. Mitochondrial morphology and function, as well as myocardial apoptosis were determined. Our data indicated that treatment with U50,488H (a selective κ-opioid receptor agonist) not only reduced apoptosis but also significantly improved mitochondrial morphology and function. These effects were blocked by nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), Compound C (an AMPK inhibitor), and AR-A014418 (a GSK3ß inhibitor). Moreover, in cardiomyocytes, treatment with U50,488H significantly increased the expression in phosphorylation of AMPK and the phosphorylation of GSK3ß. Treatment of cardiomyocytes with AMPKα siRNA decreased the phosphorylation of AMPK and GSK3ß. Moreover, AMPK activation resulted in the phosphorylation of GSK3ß. Our findings suggested that U50,488H exerted cardioprotective effects by improving mitochondrial morphology and function against MI/R injury through activation of the κ-opioid receptor-mediated AMPK/GSK3ß pathway.

19.
J Cell Physiol ; 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30317577

RESUMO

As one major diabetic complication, diabetic nephropathy (DN) has been reported to be associated with various kinds of microRNA (miRNA). Thus, we conducted this study to explore the potential of miR-370 in a rat model of DN through investigation of mesangial cell proliferation and extracellular matrix (ECM). A total of 40 healthy adult male Sprague-Dawley rats were enrolled and assigned into normal (n = 10) and DN ( n = 30, DN rat model) groups. Dual-luciferase reporter assay was performed for the targeting relationship between miR-370 and canopy 1 (CNPY1). Mesangial cells were collected and transfected with prepared mimic, inhibitor or small interfering RNA (siRNA) for analyzing the effect of miR-370 on DN mice with the help of expression and cell biological processes detection. CNPY1 was confirmed as a target gene of miR-370. DN mice had increased expression of miR-370, fibronectin, type I collagen (Col I), type IV collagen (Col IV), and plasminogen activator inhibitor-1 (PAI-1) but reduced CNPY1 expression. Cells transfected with miR-370 mimic and siRNA-CNPY1 had increased expression of fibronectin, Col I, Col IV, and PAI-1 but decreased CNPY1 expression. The miR-370 mimic and siRNA-CNPY1 groups showed increased cell proliferation, as well as elevated ECM accumulation and declined cell apoptosis rate as compared with the blank and negative control groups, with reverse trends observed in the miR-370 inhibitor group. Our study concludes that overexpression of miR-370 promotes mesangial cell proliferation and ECM accumulation by suppressing CNPY1 in a rat model of DN.

20.
NPJ Parkinsons Dis ; 4: 28, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30211310

RESUMO

Parkinson disease (PD) is a progressive neurodegenerative disease with motor symptoms that result from degeneration of midbrain dopaminergic neurons. Biomarker research seeks to identify the disease during the pre-symptomatic phase, which is a time when therapeutic intervention will be most helpful. Previously, we screened a combinatorial peptoid library to search for antibodies that are present at much higher levels in the serum of PD patients than in control subjects. One such compound, called the PD2 peptoid, was 84% accurate for the identification of de novo PD when employed as the capture agent in an enzyme-linked immunosorbent assay. This peptoid recognized an IgG3 antibody, and IgG3 levels were also found to be significantly higher in PD vs. control serum. In that study we used samples from the NINDS Parkinson's Disease Biomarker Program. The current study sought to validate that finding using serum samples from de novo and control subjects in the Parkinson's Progression Markers Initiative study. We found no difference in levels of antibodies captured by the PD2 peptoid in the de novo PD vs. control subjects, and no difference in IgG3 serum levels in the two groups. The failure to replicate our previous study appears to be due to the lack of difference in serum IgG3 levels between the PD and control subjects in the current study.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA