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1.
J Am Chem Soc ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32510205

RESUMO

Concerns about the toxicity of lead-based perovskites have aroused great interest for the development of alternative lead-free perovskite-type materials. Recently, theoretical calculations predict that Pb2+ cations can be substituted by a combination of Cu2+ and Sb3+ cations to form a vacancy-ordered layered double perovskite structure with superior optoelectronic properties. However, accessibilities to this class of perovskite-type materials remain inadequate, hindering their practical implementations in various applications. Here, we report the first colloidal synthesis of Cs4CuSb2Cl12 perovskite-type nanocrystals (NCs). The resulting NCs exhibit a layered double perovskite structure with ordered vacancies and a direct band gap of 1.79 eV. A composition-structure-property relationship has been established by investigating a series of Cs4CuxAg2-2xSb2Cl12 perovskite-type NCs (0 ≤ x ≤ 1). The composition induced crystal structure transformation, and thus, the electronic band gap evolution has been explored by experimental observations and further confirmed by theoretical calculations. Taking advantage of both the unique electronic structure and solution processability, we demonstrate that the Cs4CuSb2Cl12 NCs can be solution-processed as high-speed photodetectors with ultrafast photoresponse and narrow bandwidth. We anticipate that our study will prompt future research to design and fabricate novel and high-performance lead-free perovskite-type NCs for a range of applications.

2.
Ecotoxicol Environ Saf ; 202: 110878, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32585486

RESUMO

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) is closely associated with human health issues, especially pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. In this study, particles were characterized by scanning electron microscopy (SEM), microbeam energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). A rat model of PM2.5 exposure was established by nonsurgical intratracheal instillation, and the effects of biochanin A (BCA) treatment were examined. BCA showed a protective effect; it reduced PM2.5-induced apoptosis and the production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and the chemokine interleukin-8 (IL-8), as measured using ELISA. These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde (MDA), lactate dehydrogenase (LDH) and alkaline phosphatase (AKP). Furthermore, isobaric tag for relative and absolute quantitation (iTRAQ)-based analytical techniques and bioinformatics tools were used to identify putative biomarkers, including XRCC1, MP2K5, IGJ, and F1LQ12, and the results were verified by Western blot analysis. In conclusion, our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM2.5-associated pulmonary diseases and for the promotion of human health.

3.
Neurochem Res ; 45(7): 1614-1625, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279214

RESUMO

Glioma is a common invasive cancer with unfavorable prognosis in patients. Long non-coding RNAs (lncRNAs) exert significant functions in carcinogenesis of various cancers including glioma. Among them, long intergenic non-coding RNA 668 (LINC00668) was reported to function as oncogene in various cancers, but its molecular mechanism in glioma has not been thoroughly researched. Our current study aimed to investigate the role and molecular mechanism of LINC00668 in glioma cells. We initially found out that LINC00668 was up-regulated in glioma cells. Through a series of function assays, LINC00668 was verified to facilitate cell proliferation and inhibit apoptosis in glioma. Then, by means of online databases, RNA pull down assay and RIP assay, we verified the binding relation between LINC00668 and miR-518c-3p. Also, the next function assays exposed that miR-518c-3p was the tumor suppressor in glioma cells. Similarly, SOCS5 (suppressor of cytokine signaling 5) was found to bind with miR-518c-3p, which repressed glioma tumorigenesis by targeting SOCS5. Moreover, rescue assays manifested that LINC00668 modulated expression of SOCS5 in a miR-518c-3p-dependent way and further regulated glioma tumorigenesis. Overall, LINC00668 modulates SOCS5 expression through competitively sponging miR-518c-3p to facilitate glioma cell proliferation.

4.
Ultrason Sonochem ; 66: 105072, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32229388

RESUMO

Copper (Cu) based metal oxides have high electrocatalytic ability. In this work, we are synthesized stone-like cuprous oxide particles (Cu2O SNPs) covered on acid functionalized graphene oxide (GOS) sheets using ultrasonic process (50 kHz and 100 W). Besides, the chemical structural and crystalline analyses of Cu2O SNPs@GOS composites were characterized by transmission electron microscopy, X-ray crystallography and energy-dispersive X-ray spectroscopy. The Cu2O SNPs@GOS nanomaterials were tested towards detection of 8-hydroxydeoxyguanosine (8-OHdG) in biological samples. As expected Cu2O SNPs@GOS catalyst modified electrodes performed an outstanding catalytic ability on 8-hydroxydeoxyguanosine oxidation. 8-OHdG is oxidative stress biomarker. Further, it is noted that the detection performance of Cu2O SNPs@GOS coated electrodes and it's highly enhanced due to the synergistic effect of Cu2O SNPs and GOS. Besides, the modified materials provide more electro-active faces and as well as rapid electron transport pathway and shorten diffusion. Moreover, oxidation of 8-OHdG sensor is exploring a long linear or working range of 0.02-1465 µM and high sensitivity (8.75 nM). The viability of the Cu2O SNPs@GOS proposed electrochemical methods have tested, to find out 8-OHdG concentrations in biological fluids (blood serum and urine) with a satisfying recovery ranges.

5.
Auton Neurosci ; 225: 102643, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32097879

RESUMO

BACKGROUND AND PURPOSE: Paroxysmal sympathetic hyperactivity (PSH) is a rare complication of spontaneous intracerebral hemorrhage (ICH).We aimed to evaluate the risk factors and clinical features for PSH after ICH. METHODS: From January 1, 2013 to April 1, 2018, patients with ICH were consecutively included in this observational study. Baseline characteristics were compared in patients with and without PSH. Multivariate logistic regression analysis was used to determine the risk factors associated with PSH development. Clinical features of patients with PSH were also analyzed. RESULTS: There were 548 patients with ICH included and a total of 15 (2.7%) patients were identified with PSH. In univariate analysis, PSH development was associated with the following: previous hemorrhagic stroke, pupils abnormity, admission Glasgow Coma Scale (GCS) score, hematoma volume, liver function abnormity, neutrophil count and early tracheostomy. Multivariate logistic regression analysis showed that a significantly increased risk of PSH was found in patients with previous hemorrhagic stroke (odds ratio [OR], 4.176; 95% confidence interval [CI], 1.111-15.698), admission GCS score (OR, 0.703; 95% CI, 0.548-0.902) and early tracheostomy (OR, 8.317; 95%CI, 1.755-39.412).The most common symptoms of PSH were hyperthermia (80%) and hyperhidrosis (80%).The median Intensive Care Unit stays and Glasgow Outcome Scale at discharge were 34 (19-46) and 2 (1.5-3), respectively. CONCLUSIONS: PSH is characterized by a cluster of symptoms and abnormal vital signs, which may lead to poor outcomes in ICH. The present study suggests that previous hemorrhagic stroke, admission GCS score and early tracheostomy may be the significant risk factors for PSH after ICH.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 64-66, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922600

RESUMO

OBJECTIVE: To explore the genetic basis of a child with developmental delay and intellectual disability. METHODS: Peripheral blood samples of the child and his parents were collected for routine G-band karyotyping analysis and single nucleotide polymorphism array (SNP array) assay. Amniotic fluid sample was collected during the next pregnancy for prenatal diagnosis. RESULTS: No karyotypic abnormality was found in the child and his parents. SNP array showed that the child has carried a 855.3 kb microduplication in 15q11.2. His mother carried the same duplication but had no phenotypic anomaly. No microdeletion/microduplication was found in his father. Upon prenatal diagnosis, no abnormalities was found with the chromosomal karyotype and SNP array result of the fetus. CONCLUSION: 15q11.2 microduplication may result in developmental delay and intellectual disability, for which CYFIP1 may be a candidate gene. However, the duplication may increase the risk but with a low penetrance. This should attract attention during clinical consultation.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 15 , Deficiência Intelectual , Proteínas Adaptadoras de Transdução de Sinal , Criança , Bandeamento Cromossômico , Cromossomos Humanos Par 15/genética , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-Natal
7.
Bioresour Technol ; 301: 122747, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31935643

RESUMO

Temperature regulations (mesophilic/thermophilic) and digesting modes (mono-/co-digestion) play key roles in the biomethane potential of anaerobic digestion, but limited research focus on the synergetic effects on microbial interconnections of the biomethane process. In this study, the pineapple and maize residues under different operations were monitored by batch biogas assays and 16S high-throughput sequencing to explore: 1) biomethane potential regarding different operations, 2) microbial communities in different treated reactors, and 3) significant factors determine microbial distribution. Results showed that the co-digestion had higher methanogenic abundance and biomethane production (~3300 mLn) versus mono-digestion under mesophilic condition. To the thermophilic condition, the co-digestion had less methanogenic abundance but more biomethane production (~5000 mLn). Statistical evidence uncovered that the Clostridiaceae and Thermoanaerobacteraceae dominated pathways linked closely with methanogenesis which may contribute the more biomethane production in the thermophilic condition. This study demonstrated the temperature regulations drove rare taxa as major contributors for biomethane production.


Assuntos
Reatores Biológicos , Euryarchaeota , Anaerobiose , Biocombustíveis , Metano , Temperatura
8.
J Clin Pathol ; 73(5): 278-282, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31653757

RESUMO

AIMS: Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and ß-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China. METHODS: A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and ß-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers. RESULTS: Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --SEA/αα (71.47%), -α3.7/αα (17.13%) and -α4.2/αα (3.49%). 1407 (12.06%) subjects were ß-thalassemia carriers, 18 types of ß-thalassemia mutations were identified. The common five genotypes of ß-thalassemia were ßIVS-II-654/ßN (36.53%), ßCD41-42/ßN (30.28%), ßCD17/ßN (17.13%), ßCD26/ßN (5.12%) and ß-28/ßN (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and ß-thalassemia were identified. Furthermore, 9 α-thalassemia and ß-thalassemia gene mutations (CAP +40-43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), -90 (C>T), CD3 (T>C), -α6.9) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and -90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α6.9 mutations were first identified in Chinese individual. CONCLUSIONS: Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.


Assuntos
Mutação , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , China , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto Jovem , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
9.
Medicine (Baltimore) ; 98(43): e17457, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651849

RESUMO

The activity of p70S6 kinase located downstream of the mammalian target of rapamycin (mTOR) pathway is sensitive to mTOR inhibitors. However, the methods of assessing p70S6 kinase activity are still unclear. This study aimed to investigate p70S6 kinase activity in CD4-positive cells of liver transplant patients.Liver transplant patients treated with mTOR inhibitors were recruited from Beijing Chaoyang Hospital between October 2014 and October 2016. The influence of mycophenolic acid (MPA) derivatives and prednisone on p70S6 kinase phosphorylation in CD4-positive cells was examined in liver transplant patients and healthy controls (HCs). The phosphorylation of p70S6K in CD4 + CD25 regulatory T cells (Treg cells) and CD4 + CD25- T effector cells was analyzed by phospho-flow cytometry.The phospho-flow technique detected a significant loss of p70S6 kinase phosphorylation in CD4-positive cells of patients treated with mTOR inhibitors compared with HCs. MPA derivatives and prednisone did not affect p70S6 kinase phosphorylation significantly. No significant difference in p70S6 kinase phosphorylation was observed when the whole blood was stored within 3 hours at room temperature. The phosphorylation of p70S6K was significantly lower in CD4 + CD25 Treg cells than in CD4 + CD25-T effector cells in HCs. After liver transplant patients were treated with mTOR inhibitors, p70S6K phosphorylation was more reduced in CD4 + CD25-T effector cells than in CD4 + CD25 Treg cells.The presence of phosphorylation of p70S6 kinase in CD4-positive cells was reduced in liver transplant patients who were treated by mTOR inhibitors.


Assuntos
Linfócitos T CD4-Positivos/enzimologia , Inibidores Enzimáticos/farmacologia , Transplante de Fígado , Ácido Micofenólico/farmacologia , Fosforilação/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Adulto Jovem
10.
Food Funct ; 10(11): 7188-7203, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31608342

RESUMO

Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5) is associated with an increased risk for cardiopulmonary diseases. The MEK5/ERK5 and NF-κB signaling pathways are closely related to the regulation of acute pulmonary cell injury (APCI) and may play an important role in the underlying pathophysiological mechanisms. Related studies have shown that Biochanin A (BCA) effectively interferes with APCI, but the underlying mechanism through which this occurs is not fully understood. Previously, based on proteomic and bioinformatic research, we found the indispensable role of MEK5 in mediating remission effects of BCA against PM2.5-induced lung toxicity. Therefore, using A549 adenocarcinoma human alveolar basal epithelial cells (A549 cells), we combined western blot and qRT-PCR to study the protective signaling pathways induced by BCA, indicating that MEK5/ERK5 and NF-κB are both involved in mediating APCI in response to PM2.5, and MEK5/ERK5 positively activated NF-κB and its downstream cellular regulatory factors. BCA significantly suppressed PM2.5-induced upregulation of MEK5/ERK5 expression and phosphorylation and activation of NF-κB. Furthermore, due to the specificity of the MEK5/ERK5 protein structure, the binding sites and binding patterns of BCA and MEK5 were analyzed using molecular docking correlation techniques, which showed that there are stable hydrogen bonds between BCA and the PB1 domain of MEK5 as well as its kinase domain. BCA forms a stable complex with MEK5, which has potential effects on MEKK2/3-MEK5-ERK5 ternary interactions, p62/αPKC-mediated NF-κB regulation, and inhibition of MEK5 target protein phosphorylation. Therefore, our study suggests that MEK5 is an important regulator of intracellular signaling of APCI in response to PM2.5 exposure. BCA may exert anti-APCI activity by targeting MEK5 to inhibit activation of the MEK5/ERK5/NF-κB signaling pathway.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Genisteína/farmacologia , MAP Quinase Quinase 5/metabolismo , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Células A549 , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Genisteína/química , Humanos , MAP Quinase Quinase 5/química , MAP Quinase Quinase 5/genética , Simulação de Acoplamento Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Substâncias Protetoras/química , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos
11.
Braz J Med Biol Res ; 52(10): e8380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531524

RESUMO

The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3-L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.


Assuntos
MicroRNAs/genética , Neuralgia/genética , Análise de Sequência de RNA , Animais , Sequência de Bases , Modelos Animais de Doenças , Masculino , MicroRNAs/metabolismo , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 938-941, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537215

RESUMO

OBJECTIVE: To investigate the assessment values of procalcitonin (PCT), lactic acid (LAC), sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score in patients with sepsis. METHODS: 140 patients with suspicious bacterial infection admitted to emergency department of Beijing Chaoyang Hospital of the Capital Medical University from August 2017 to June 2018 were enrolled. They were divided into three groups according to diagnostic criteria of Sepsis-3: non-sepsis group (n = 58), sepsis group (n = 66) and septic shock group (n = 16). The PCT, LAC, SOFA score, APACHE II score, 28-day prognosis, and positive detection rate of PCT and LAC were compared among three groups. Independent predictors of 28-day mortality were analyzed by Logistic regression; predictive values of PCT, LAC, SOFA score and APACHE II score for 28-day mortality in sepsis patients were analyzed by receiver operating characteristic (ROC) curve. RESULTS: PCT, LAC, SOFA score, APACHE II score at admission, and 28-day mortality in sepsis group and septic shock group were significantly higher than those in non-sepsis group, and PCT, LAC, APACHE II score, and 28-day mortality in sepsis shock group were further higher than those in sepsis group [PCT (µg/L): 38.1±12.6 vs. 4.6±2.3, LAC (mmol/L): 3.3±2.1 vs. 2.4±2.1, APACHE II score: 14.9±2.4 vs. 9.5±4.3, 28-day mortality: 75.0% vs. 24.2%, all P < 0.05]. The positive detection rate of PCT and LAC in sepsis group and septic shock group were higher than those in non-sepsis group (positive detection rate of PCT: 56.1%, 81.3% vs. 32.8%; positive detection rate of LAC: 42.4%, 62.5% vs. 13.7%; all P < 0.01). Logistic regression analysis showed that PCT, LAC, SOFA score and APACHE II score were independent predictors of 28-day mortality [PCT: odds ratio (OR) = 0.933, 95% confidence interval (95%CI) = 0.878-0.991; LAC: OR = 0.539, 95%CI = 0.347-0.838; SOFA score: OR = 0.291, 95%CI = 0.514-0.741; APACHE II score: OR = 0.808, 95%CI = 0.669-0.976; all P < 0.05]. ROC curve analysis showed that the area under ROC curve (AUC) of PCT, LAC, SOFA score and APACHE II score predicting 28-day mortality was 0.76, 0.86, 0.81 and 0.87, respectively. The assessment values of APACHE II score and LAC were higher than PCT in predicting 28-day mortality (Z1 = 2.56, Z2 = 2.45, both P < 0.01), and the performance of SOFA score was similar to PCT. CONCLUSIONS: PCT, LAC, SOFA score and APACHE II score were reliable indexes to evaluate disease severity for patients diagnosed with infection. The assessment values of APACHE II score and LAC in 28-day mortality were superior to SOFA score and PCT.


Assuntos
Ácido Láctico/metabolismo , Pró-Calcitonina/metabolismo , Sepse/metabolismo , APACHE , Humanos , Escores de Disfunção Orgânica , Prognóstico , Curva ROC
13.
Anal Chim Acta ; 1069: 1-27, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31084735

RESUMO

Aflatoxin B1(AFB1) is one of the most toxic mycotoxins produced by fungi and results in inevitable contamination of food and feed at very low concentrations. Therefore, there is an urgent need to implement selective, sensitive and highly convenient methods for the determination of aflatoxin B1. Among these methods, the progress of nanomaterials, owing to their high performances and versatile properties, offers great prospects for realizing highly sensitive, selective and simple detection of AFB1, overcoming the restrictions of traditional methods such as process-complicated, time-consuming, labor-intensive and instruments-expensive. Many nanomaterials have been used for the immobilization of biomolecules as signal generators or fluorescent quenchers or for signal amplification in AFB1 detection. This review highlights recent progress that has been made in the development of nanoparticle-based assays and focuses on the analytical potential of nanomaterials, such as Au/Ag nanoparticles (Au/Ag NPs), carbon-based nanoparticles (CBNs), magnetic nanoparticles (MNPs), Quantum dots (QDs) and novel nanomaterials, including up-conversion nanoparticles (UCNPs), metal-organic frameworks (MOFs) and nanomaterial-functional DNA intelligent hydrogels, as well as hybrid nanostructures. The determination of AFB1 is divided into three aspects: sample pretreatment prior to AFB1 detection, immunoassays and biosensors. The details of the detection methods and their application principles are described, and the challenges and opportunities in the field of food analysis are described.


Assuntos
Aflatoxina B1/análise , Contaminação de Alimentos/análise , Nanoestruturas/química , Nanotecnologia , Animais , Técnicas Biossensoriais , Humanos , Imunoensaio
14.
Biomed Res Int ; 2019: 4015969, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032345

RESUMO

Purpose: Different microRNAs (miRs) have been demonstrated to relate with the outcome of glioma patients, while the conclusions are inconsistent. We perform a meta-analysis to clarify the relationship between different miRs and prognosis of glioma. Methods: Related studies were retrieved from PubMed, Embase, and Cochrane Library. Pooled hazard ratios (HRs) of different miRs expression for survival and 95% confidence intervals (CIs) were calculated using random-effects model. Results: A total of 15 miRs with 4708 glioma patients were ultimately included. Increased expression of miR-15b (HR, 1.584; 95% CI, 1.199-2.092), 21 (HR, 1.591; 95% CI, 1.278-1.981), 148a (HR, 1.122; 95% CI, 1.023-1.231), 196 (HR, 1.877; 95% CI, 1.033-3.411), 210 (HR, 1.251; 95% CI, 1.010-1.550), and 221 (HR, 1.269; 95% CI, 1.054-1.527) or decreased expression of miR-106a (HR, 0.809; 95% CI, 0.655-0.998) and 124 (HR, 0.833; 95% CI, 0.729-0.952) was correlated with poor outcome of glioma patients. Conclusions: miR-15b, 21, 148a, 196, 210, 221, 106a, and 124 are valuable biomarkers for the prognosis of glioma which might be used in clinical settings.


Assuntos
Biomarcadores Tumorais/genética , Glioma/genética , MicroRNAs/genética , Prognóstico , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Análise de Sobrevida
15.
Life Sci ; 223: 174-184, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30890405

RESUMO

AIM: Atherosclerosis (AS) is a chronic condition of the arterial vessels and a risk factor for myocardial infarction and stroke. Euxanthone is a xanthone compound extracted from Polygala caudata, and shows vasodilatory action. The aim of this study was to determine the potential pharmacological effects of euxanthone against oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury. MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL, following pre-treatment with different concentrations of euxanthone. Viability, apoptosis and DNA fragmentation were respectively assessed by CCK-8 assay, Annexin-V/PI staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The cellular levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were analyzed by enzyme linked immune-sorbent assays (ELISA), and reactive oxygen species (ROS) levels using dichlorodihydrofluorescin diacetate (DCFH) staining. Quantitative RT-PCR and Western blotting were respectively used to analyze the expression levels of specific mRNAs and proteins. HUVECs were transfected with Nrf2 siRNA to induce knockdown of the latter. KEY FINDINGS: Euxanthone pre-treatment rescued the HUVECs from ox-LDL-induced cytotoxicity, apoptosis and DNA fragmentation in a dose-dependent manner. In addition, euxanthone also significantly reversed ox-LDL-triggered loss of mitochondrial membrane potential (MMP), cytochrome C release from mitochondria to cytosol, cleavage of caspase-3 and PARP, and increase in Bax/Bcl-2 ratio. Pre-treatment with euxanthone markedly suppressed ox-LDL-induced ROS generation and inhibition of antioxidant enzymes, as well as the up-regulation of pro-inflammatory factors like MCP-1, IL-1ß and TNF-α in the HUVECs. Euxanthone up-regulated and activated Nrf2 by repressing Keap1, and increased the expression of its downstream genes HO-1 and NQO-1. Nrf2 knockdown abrogated the cyto-protective, anti-apoptotic, anti-oxidant and anti-inflammatory effects of euxanthone in ox-LDL-treated HUVECs. Finally, euxanthone activated Nrf2 via the MAPK pathway and blocking the latter likewise negated the protective effects of euxanthone against cell ox-LDL. SIGNIFICANCE: Euxanthone protected HUVECs against the oxidative and inflammatory damage induced by ox-LDL, indicating its potential as a novel therapeutic agent for AS.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Lipoproteínas LDL/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Xantonas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/metabolismo , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana , Humanos , Marcação In Situ das Extremidades Cortadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Polygala/química , Xantonas/isolamento & purificação
16.
World Neurosurg ; 126: e1069-e1074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878755

RESUMO

BACKGROUND: Inferior petrosal sinus (IPS) has been commonly adopted as a route for embolizing cavernous dural arteriovenous fistula (cDAVF). According to previous anatomical studies, >90% of persons have an IPS. Because the exact confluence position of the IPS with an internal jugular vein can be difficult to obtain using preoperative digital subtraction angiography (DSA), catheterizing into the IPS during endovascular treatment can sometimes be very difficult. Because the anatomical information has not been attainable, this route has not been as widely used. Thus, methods remain to be developed to allow the IPS to play its due role in the embolization of cDAVF. METHODS: Seven cases of cDAVF were diagnosed by DSA. The 7 patients also underwent preoperative computed tomography angiography (CTA) and were treated by transvenous embolization. RESULTS: Compared with DSA, the confluence position of the IPS with the internal jugular vein was easier to find using preoperative CTA in 6 cases. Based on this anatomical information, 6 cases were successfully embolized via the IPS route and 1 via the superior ophthalmic vein route. CONCLUSIONS: Detailed anatomical information of the IPS can be obtained from preoperative CTA images. Thus, CTA can help localize the IPS and allow for embolization of cDAVF via the IPS route.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Cavidades Cranianas/diagnóstico por imagem , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Naunyn Schmiedebergs Arch Pharmacol ; 392(5): 551-563, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30607469

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of human malignancies of the urological system. Soyasapogenol B (Soy B), an ingredient of soybean, has been found to exert anti-proliferative activities in vitro in human breast cancer cells. Our current study aimed to evaluate the effectiveness of Soy B against ccRCC. The effect of Soy B on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The effect of Soy B on cell proliferation was determined by colony formation assay. Apoptotic percentage was determined by flow cytometry following annexin V-FITC/propidium iodide (PI) double staining. JC-1 staining was performed to examine the change in mitochondrial membrane potential. Western blotting was used to determine the level of relevant proteins. Isobaric tags for relative and absolute quantification (iTRAQ) was then performed to identify the potential targets of Soy B. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA level of sphingosine kinase 1 (SphK1). The SphK1 expression in ccRCC tissue from patients was examined by immunohistochemistry (IHC) assay. To validate the role of SphK1 involved in the pro-apoptotic activities of Soy B, overexpressed SphK1 vectors and shRNA targeting of SphK1 were utilized to transfected ccRCC cells. Moreover, a ccRCC xenograft murine model was used to analyze the therapeutic efficacy of Soy B in vivo. Soy B incubation led to a decrease in the number of viable cells in ccRCC cell lines and primary ccRCC cells. Soy B also suppressed the proliferation of two model ccRCC cell lines. Soy B promoted apoptotic cell death in a caspase-dependent manner. Moreover, our results showed that both extrinsic and intrinsic apoptotic signaling pathways were involved in Soy B-induced apoptosis. ITRAQ analysis identified SphK1 as most profoundly altered after the treatment of Soy B in ACHN cells. The mediatory role of SphK1 was validated when the pro-apoptotic activity of Soy B was significantly blocked by SphK1 overexpression, while SphK1 knockdown sensitized the ccRCC cells to Soy B. Moreover, in vivo studies also showed that Soy B could exhibit anti-cancer activities against ccRCC. Soy B triggers apoptotic cell death in vitro and in vivo in ccRCC by down-regulating SphK1. Our results highlight the possibility of using Soy B as a chemotherapeutic agent in the prevention and treatment of ccRCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Renais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Saponinas/farmacologia , Células Tumorais Cultivadas
18.
Braz. j. med. biol. res ; 52(10): e8380, 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1039249

RESUMO

The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3-L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.

19.
Cell Physiol Biochem ; 51(6): 2496-2508, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562739

RESUMO

BACKGROUND/AIMS: Cyclin D1 (CCND1) is frequently overexpressed in malignant gliomas. We have previously shown ectopic overexpression of CCND1 in human malignant gliomas cell lines. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blot (WB) was performed to investigate the expression of CCND1 in glioma tissues and cell lines. The biological function of CCND1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. RESULTS: Here we reported that CCND1 expression was positively associated with the pathological grade and proliferative activity of astrocytomas, as the lowest expression was found in normal brain tissue (N = 3) whereas the highest expression was in high-grade glioma tissue (N = 25). Additionally, we found that the expression level of CCND1 was associated with IC50 values in malignant glioma cell lines. Forced inhibition of CCND1 increased temozolomide efficacy in U251 and SHG-44 cells. After CCND1 overexpression, the temozolomide efficacy decreased in U251 and SHG-44 cells. Colony survival assay and apoptosis analysis confirmed that CCND1 inhibition renders cells more sensitive to temozolomide treatment and temozolomide-induced apoptosis in U251 and SHG-44 cells. Inhibition of P-gp (MDR1) by Tariquidar overcomes the effects of CCND1 overexpression on inhibiting temozolomide-induced apoptosis. Inhibition of CCND1 inhibited cell growth in vitro and in vivo significantly more effectively after temozolomide treatments than single temozolomide treatments. Finally, inhibition of CCND1 in glioma cells reduced tumor volume in a murine model. CONCLUSION: Taken together, these data indicate that CCND1 overexpression upregulate P-gp and induces chemoresistance in human malignant gliomas cells and that inhibition of CCND1 may be an effective means of overcoming CCND1 associated chemoresistance in human malignant glioma cells.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Ciclina D1/genética , Glioblastoma/tratamento farmacológico , Temozolomida/uso terapêutico , Adulto , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida/farmacologia
20.
Biochem Biophys Res Commun ; 505(4): 1211-1215, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30322616

RESUMO

microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague-Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified Klf5 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.


Assuntos
Aneurisma Intracraniano/genética , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/metabolismo , Animais , Células Cultivadas , Regulação da Expressão Gênica , Células HEK293 , Humanos , Aneurisma Intracraniano/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/fisiologia , Masculino , Ratos Sprague-Dawley
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