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1.
Am J Physiol Cell Physiol ; 326(6): C1721-C1734, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38646788

RESUMO

Atherosclerosis (AS) is a significant contributor to cardio-cerebrovascular ischemia diseases, resulting in high mortality rates worldwide. During AS, vascular smooth muscle cells (VSMCs) play a crucial role in plaque formation by undergoing phenotypic and osteogenic switching. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has previously been identified as a nuclear regulator that promotes tumorigenesis and metastasis, but its role in regulating VSMCs in AS remains unclear. Our study aimed to investigate the biological functions and specific mechanisms of NEAT1 in regulating VSMCs in AS. We found that NEAT1 was upregulated in the aortas of AS mouse models and dedifferentiated primary VSMCs. Silencing NEAT1 in vitro attenuated the proliferation, migration, and osteogenic differentiation of VSMCs, while NEAT1 overexpression had the opposite effect. Furthermore, NEAT1 promoted VSMC osteogenic differentiation and vascular calcification in both in vivo and in vitro vascular calcification models. We also discovered that NEAT1 directly activates enhancer of zeste homolog 2 (EZH2), an epigenetic enzyme that suppresses the expression of senescence- and antimigration-related genes, by translocating it into the nucleus. CUT&Tag assay revealed that NEAT1 guides EZH2 to the promoters of senescence-related genes (P16, P21, and TIMP3), methylating local histones to reduce their transcription. Our findings suggest that NEAT1 functions in AS by modulating the epigenetic function of EZH2, which enhances the proliferation, migration, and osteogenic differentiation of VSMCs. This study provides new insights into the molecular mechanisms underlying the pathogenesis of AS and highlights the potential of NEAT1 as a therapeutic target of AS.NEW & NOTEWORTHY Our study demonstrates that the upregulation of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes proliferation and migration during phenotypic switching of vascular smooth muscle cells in atherosclerosis. We also provide in vivo and in vitro evidence that NEAT1 accelerates vascular calcification. Our findings identified the direct interaction between enhancer of zeste homolog 2 (EZH2) and NEAT1 during atherosclerosis. NEAT1 is necessary for EZH2 to translocate from the cytoplasm to the nucleus, where EZH2 epigenetically inhibits the expression of genes related to senescence and antimigration.


Assuntos
Aterosclerose , Diferenciação Celular , Proteína Potenciadora do Homólogo 2 de Zeste , Músculo Liso Vascular , Miócitos de Músculo Liso , Osteogênese , RNA Longo não Codificante , Calcificação Vascular , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Osteogênese/genética , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Calcificação Vascular/patologia , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Proliferação de Células , Fenótipo , Células Cultivadas , Humanos , Movimento Celular
2.
BMC Ophthalmol ; 23(1): 47, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36726067

RESUMO

BACKGROUND: Morgan and Scheiman's Optometric Extension Program (OEP) expected binocular vision findings have longstanding use in optometry. With technological advances, the demands and standards of binocular function have changed. This study aimed to investigate which binocular visual functions can effectively predict visual behavior performance. METHODS: Participants aged 15-24 years were recruited from two colleges and two universities. After completing the CSMU-Visual Behavioral Performance questionnaire (CSMU-VBP, with four components: near work, visual perception, visual comfort, and whole-body balance), participants were divided into symptomatic and asymptomatic groups based on questionnaire findings (cutoff: < 12 vs. ≥ 12 symptoms). Then a 24-step binocular visual examination was undertaken. Data were analyzed with one-sample, Student's, and paired t-tests. Additionally, receiver operating characteristic analysis was used to determine the predictors of binocular visual function required for near work, visual perception, visual comfort, and body balance dimensions. RESULTS: Among 308 participants, 43 (14%) and 265 (86%) were symptomatic and asymptomatic, respectively. Among the 46 participants with abnormal binocular vision, 36 (78%) reported that they had no obvious symptoms. The commonest dysfunctions were accommodative excess and convergence excess. Most of the binocular visual findings significantly diverged from traditional normal values: amplitude of accommodation, as well as base-in prism to break and recovery points at distance were higher than traditional normal values, whereas others were lower than traditional normal values. Total CSMU-VBP scores indicated that the asymptomatic and symptomatic groups had significant differences in DBO recovery (t = 2.334, p = 0.020) and BAF (t = 1.984, p = 0.048). Receiver operating characteristic curve analysis yielded the following binocular visual functional cutoff points: near work (DBO blur < 7, DBO recovery < 5.5), visual perception (MAF < 10.5, BAF < 10.25), visual comfort (DLP < - 2.25, DBI break > 11.5, NBI blur > 15, NBI break > 17.5, NBI recovery > 13, NPC < 5.75), and body balance (NFD_H > - 0.5, gradient AC/A [minus] > 2.25, NPC < 4.75). CONCLUSIONS: The mean values of binocular visual function among young Taiwanese adults were statistically different from traditional normative values. Further research is required to confirm whether these findings reflect impaired binocular vision or stringent criteria. Assessments of binocular visual function, especially binocular accommodation sensitivity, are crucial in routine optometric examination.


Assuntos
Convergência Ocular , Transtornos da Motilidade Ocular , Humanos , Adulto , Acomodação Ocular , Visão Binocular , Transtornos da Visão/diagnóstico
3.
J Transl Med ; 20(1): 7, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980170

RESUMO

Cardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-ß1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.


Assuntos
Insuficiência Cardíaca , MicroRNAs , RNA Longo não Codificante , Animais , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Fibrose , Insuficiência Cardíaca/genética , Humanos , Camundongos , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Smad7/genética , Proteína Smad7/metabolismo
4.
PLoS Pathog ; 16(8): e1008710, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817722

RESUMO

Rice stripe virus (RSV, genus Tenuivirus, family Phenuiviridae) is the causal agent of rice stripe disease transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a persistent propagative manner. The midgut and salivary glands of SBPH are the first and last barriers to the viral circulation and transmission processes, respectively; however, the precise mechanisms used by RSV to cross these organs and transmit to rice plants have not been fully elucidated. We obtained the full-length cDNA sequence of L. striatellus α-tubulin 2 (LsTUB) and found that RSV infection increased the level of LsTUB in vivo. Furthermore, LsTUB was shown to co-localize with RSV nonstructural protein 3 (NS3) in vivo and bound NS3 at positions 74-76 and 80-82 in vitro. Transient gene silencing of LsTUB expression caused a significant reduction in detectable RSV loads and viral NS3 expression levels, but had no effect on NS3 silencing suppressor activity and viral replication in insect cells. However, suppression of LsTUB attenuated viral spread in the bodies of SBPHs and decreased RSV transmission rates to rice plants. Electrical penetration graphs (EPG) showed that LsTUB knockdown by RNAi did not impact SBPH feeding; therefore, the reduction in RSV transmission rates was likely caused by a decrease in viral loads inside the planthopper. These findings suggest that LsTUB mediates the passage of RSV through midgut and salivary glands and leads to successful horizontal transmission.


Assuntos
Hemípteros/metabolismo , Proteínas de Insetos/metabolismo , Insetos Vetores/metabolismo , Oryza/virologia , Doenças das Plantas/virologia , Tenuivirus/fisiologia , Tubulina (Proteína)/metabolismo , Animais , Sistema Digestório/metabolismo , Sistema Digestório/virologia , Hemípteros/genética , Hemípteros/virologia , Proteínas de Insetos/genética , Insetos Vetores/genética , Insetos Vetores/virologia , Glândulas Salivares/metabolismo , Glândulas Salivares/virologia , Tubulina (Proteína)/genética
5.
Zhongguo Zhong Yao Za Zhi ; 47(11): 2955-2963, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35718517

RESUMO

In this paper, a flavonoid extract powder properties-process parameters-granule forming rate prediction model was constructed based on design space and radial basis function neural network(RBFNN) to predict the formability of flavonoid extract gra-nules. Box-Behnken experimental design was employed to explore the mathematical relationships between critical process parameters and quality attributes. The design space of critical process parameters was developed, and the accuracy of the design space was verified by Monte Carlo method(MC). Design Expert 10 was used for Box-Behnken design and mixture design. Scutellariae Radix mixed powder was prepared and its powder properties were measured. The mixed powder was then subjected to dry granulation and the granule forming rate was determined. The correlations between powder properties were analyzed by variance influence factor(VIF), and principal component analysis(PCA) was performed for the factors with strong collinearity. In this way, a prediction model of powder properties-process parameters-granule forming rate was established based on RBFNN, the accuracy of which was evaluated with examples. The results showed that the model had a good predictive effect on the granule forming rate, with the average relative error of 1.04%. The predicted value and the measured value had a high degree of fitting, which indicated that model presented a good prediction ability. The prediction model established in this study can provide reference for the establishment of quality control methods for Chinese medicinal preparations with similar physical properties.


Assuntos
Medicamentos de Ervas Chinesas , Flavonoides , Tamanho da Partícula , Pós , Controle de Qualidade , Comprimidos
6.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638638

RESUMO

Many vector-borne viruses possess the ability to manipulate vector behaviors to facilitate their transmission. There is evidence that the mechanism of this phenomenon has been described in part as direct manipulation through regulating vector chemosensation. Rice stripe virus (RSV) is transmitted by the small brown planthopper, Laodelphax striatellus (Fallen), in a persistent, circulative-propagative manner. The effect of RSV infection on the olfactory system of L. striatellus has not been fully elucidated. Here, we employed transcriptomic sequencing to analyze gene expression profiles in antennae, legs and heads (without antennae) from L. striatellus females and males with/without RSV infection. Comparisons of the differentially expressed genes (DEGs) among antennae, legs and heads indicated that tissue-specific changes in the gene expression profile were greater than sex-specific changes. A total of 17 olfactory related genes were differentially expressed in viruliferous antennae as compared to nonviruliferous antennae, including LstrOBP4/9, LstrCSP1/2/5, LstrGR28a/43a/43a-1, LstrIR1/2/NMDA1, LstrOR67/85e/56a/94 and LstrSNMP2/2-2. There are 23 olfactory related DEGs between viruliferous and nonviruliferous legs, including LstrOBP2/3/4/12/13, LstrCSP13/5/10, LstrIR1/2/Delta2/Delta2-1/kainate2/NMDA2, LstrOR12/21/31/68 and LstrORco. A low number of olfactory related DEGs were found between viruliferous and nonviruliferous heads, including LstrCSP1, LstrOBP2, LstrOR67 and LstrSNMP2-2. Among these DEGs, the expression patterns of LstrOBP2, LstrOBP3 and LstrOBP9 in three tissues was validated by quantitative real-time PCR. The demonstration of overall changes in the genes in L. striatellus' chemoreception organs in response to RSV infection would not only improve our understanding of the effect of RSV on the olfactory related genes of insect vectors but also provide insights into developing approaches to control the plant virus transmission and spread as well as pest management in the future.


Assuntos
Células Quimiorreceptoras/fisiologia , Hemípteros/genética , Hemípteros/virologia , Oryza/genética , Oryza/virologia , Tenuivirus/genética , Transcriptoma/genética , Animais , Perfilação da Expressão Gênica/métodos , Proteínas de Insetos/genética , Insetos Vetores/genética , Insetos Vetores/virologia , Doenças das Plantas/virologia , Vírus de Plantas/genética
7.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1460-1466, 2021 Mar.
Artigo em Zh | MEDLINE | ID: mdl-33787144

RESUMO

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 µmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.


Assuntos
Ginsenosídeos , Apoptose , Ginsenosídeos/farmacologia , Heme Oxigenase-1/genética , Humanos , Hipóxia , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2/genética
8.
Int J Med Sci ; 17(15): 2328-2337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922198

RESUMO

Background: Dilated cardiomyopathy (DCM) is considered as the most common form of non-ischemic cardiomyopathy with a high mortality worldwide. Cytoskeleton protein Cypher plays an important role in maintaining cardiac function. Genetic studies in human and animal models revealed that Cypher is involved in the development of DCM. However, the underlying molecular mechanism is not fully understood. Accumulating evidences suggest that apoptosis in myocytes may contribute to DCM. Thus, the purpose of this study is to define whether lack of Cypher in cardiomyocytes can elevate apoptosis signaling and lead to DCM eventually. Methods and Results: Cypher-siRNA sufficiently inhibited Cypher expression in cardiomyocytes. TUNEL-positive cardiomyocytes were increased in both Cypher knockdown neonatal rat cardiomyocytes and Cypher knockout mice hearts, which were rare in the control group. Flow cytometry further confirmed that downregulation of Cypher significantly increased myocytes apoptosis in vitro. Cell counting kit-8 assay revealed that Cypher knockdown in H9c2 cells significantly reduced cell viability. Cypher knockdown was found to increase cleaved caspase-3 expression and suppress p21, ratio of bcl-2 to Bax. Cypher-deficiency induced apoptosis was linked to downregulation of Akt activation and elevated p-p38 MAPK accumulation. Pharmacological activation of Akt with SC79 attenuated apoptosis with enhanced phosphorylation of Akt and reduced p-p38 MAPK and Bax expression. Conclusions: Downregulation of Cypher participates in the promotion of cardiomyocytes apoptosis through inhibiting Akt dependent pathway and enhancing p38 MAPK phosphorylation. These findings may provide a new potential therapeutic strategy for the treatment of DCM.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Cardiomiopatia Dilatada/patologia , Proteínas com Domínio LIM/deficiência , Miócitos Cardíacos/patologia , Acetatos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Cardiomiopatia Dilatada/genética , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Proteínas com Domínio LIM/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Knockout , Miocárdio/citologia , Miocárdio/patologia , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 45(24): 5982-5987, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33496138

RESUMO

This paper aims to construct a Bayesian(BN) fault diagnosis model of traditional Chinese medicine dry granulation based on the failure model and effect analysis(FMEA), effectively control risk factors and ensure the quality of granules.Firstly, the risk ana-lysis of dry granulation process was carried out with FMEA, and the selected medium and high risk factors were taken as node variables to establish corresponding BN network with causality.According to the mathematical reasoning method of probability theory, the model was accurately inferred and verified by Netica, and the granule nonconformance was used as the evidence for reversed reasoning to determine the most likely cause of the failure that affected the granule quality.The BN fault diagnosis model of traditional Chinese medicine dry gra-nulation was established based on the medium and high risk factors of process, prescription and equipment screened out by FMEA, such as roller pressure, raw material viscosity, clearance between rollers in the paper.The fault diagnosis of traditional Chinese medicine dry granulation process was then carried out according to the model, and the posterior probability of each node under the premise of nonconforming granule quality was obtained.This method could provide strong support for operators to quickly eliminate faults and make decisions, so as to improve the efficiency and accuracy for fault diagnosis and prediction, with innovation in its application.


Assuntos
Medicina Tradicional Chinesa , Teorema de Bayes , Probabilidade
10.
Int J Mol Sci ; 20(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052553

RESUMO

Small nucleolar RNAs (snoRNAs) are a new type of functional small RNAs involved in the chemical modifications of rRNAs, tRNAs, and small nuclear RNAs. It is reported that they play important roles in tumorigenesis via various regulatory modes. snoRNAs can both participate in the regulation of methylation and pseudouridylation and regulate the expression pattern of their host genes. This research investigated the expression pattern of snoRNAs in eight major cancer types in TCGA via several machine learning algorithms. The expression levels of snoRNAs were first analyzed by a powerful feature selection method, Monte Carlo feature selection (MCFS). A feature list and some informative features were accessed. Then, the incremental feature selection (IFS) was applied to the feature list to extract optimal features/snoRNAs, which can make the support vector machine (SVM) yield best performance. The discriminative snoRNAs included HBII-52-14, HBII-336, SNORD123, HBII-85-29, HBII-420, U3, HBI-43, SNORD116, SNORA73B, SCARNA4, HBII-85-20, etc., on which the SVM can provide a Matthew's correlation coefficient (MCC) of 0.881 for predicting these eight cancer types. On the other hand, the informative features were fed into the Johnson reducer and repeated incremental pruning to produce error reduction (RIPPER) algorithms to generate classification rules, which can clearly show different snoRNAs expression patterns in different cancer types. The analysis results indicated that extracted discriminative snoRNAs can be important for identifying cancer samples in different types and the expression pattern of snoRNAs in different cancer types can be partly uncovered by quantitative recognition rules.


Assuntos
Regulação Neoplásica da Expressão Gênica , Aprendizado de Máquina , Neoplasias/genética , RNA Nucleolar Pequeno/genética , Algoritmos , Humanos , Método de Monte Carlo , Máquina de Vetores de Suporte
11.
Zhongguo Zhong Yao Za Zhi ; 44(24): 5390-5397, 2019 Dec.
Artigo em Zh | MEDLINE | ID: mdl-32237385

RESUMO

This paper constructs a prediction model of material attribute-tensile strength based on principal component analysis-radial basis neural network( PCA-RBF),in order to predict the formability of traditional Chinese medicine tablets. Firstly,design Expert8. 0 software was used to design the dosage of different types of extracts,the mixture of traditional Chinese medicine with different physical properties was obtained,the powder properties of each extract and the tensile strength of tablets were determined,the correlation of the original input layer data was eliminated by PCA,the new variables unrelated to each other were trained as the input data of RBF neural network,and the tensile strength of the tablets was predicted. The experimental results showed that the PCA-RBF model had a good predictive effect on the tensile strength of the tablet,the minimum relative error was 0. 25%,the maximum relative error was2. 21%,and the average error was 1. 35%,which had a high fitting degree and better network prediction accuracy. This study initially constructed a prediction model of material properties-tensile strength of Chinese herbal tablets based on PCA-RBF,which provided a reference for the establishment of effective quality control methods for traditional Chinese medicine preparations.


Assuntos
Medicina Tradicional Chinesa , Redes Neurais de Computação , Comprimidos , Resistência à Tração , Pós , Tecnologia Farmacêutica
12.
Biomed Environ Sci ; 31(6): 483-488, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30025564

RESUMO

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr.


Assuntos
Óxido Ferroso-Férrico/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Estrôncio/análise , Poluentes Radioativos da Água/análise , Adsorção , Concentração de Íons de Hidrogênio , Modelos Teóricos , Nanopartículas/química , Propriedades de Superfície , Purificação da Água/métodos
14.
Cell Physiol Biochem ; 44(1): 21-37, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29130959

RESUMO

BACKGROUND/AIMS: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. METHODS: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. RESULTS: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). CONCLUSION: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.


Assuntos
Hipóxia Celular , Ginsenosídeos/farmacologia , Heme Oxigenase-1/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Substâncias Protetoras/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Protoporfirinas/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
15.
Cell Physiol Biochem ; 42(1): 357-372, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28535533

RESUMO

BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-ß1). METHODS: Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFß receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. RESULTS: We found that EndMT of EPCs induced by TGF-ß1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-ß1-induced EndMT by directly targeting TGFBR2 and SMAD3. CONCLUSIONS: MALAT1 modulates TGF-ß1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-ß1-induced EndMT.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Sequência de Bases , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Células Progenitoras Endoteliais/citologia , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/química , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Proteína Smad3/química , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
J Cardiovasc Electrophysiol ; 28(9): 994-1005, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28569422

RESUMO

INTRODUCTION: CF-sensing catheter emerged as a novel ablation technology and was increasingly used in clinical practice. Nonetheless, available evidence of efficacy and safety comparison between CF-guided RF catheter ablation and non-CF-guided ablation for treatment of AF was still lacking. METHODS AND RESULTS: Twenty-two eligible studies were included after systematic review through the MEDLINE, Google Scholar, the Cochrane Library and PubMed databases. AF/atrial tachycardia-free survival was markedly improved in CF-guided catheter ablation compared with non-CF-guided ablation at a median 12-month follow-up (RR: 1.12, 95% CI: 1.06-1.19, P = 0.000, fixed). Notably, CF-guided catheter ablation presented a robust survival benefit for treatment of paroxysmal AF (RR: 1.10, 95% CI: 1.03-1.18, P = 0.005, fixed), but not persistent AF (RR: 1.07, 95% CI: 0.89-1.28, P = 0.466, fixed). Moreover, procedure time (WMD: -23.87, 95% CI: -33.83 to -13.91, P = 0.000, random), fluoroscopy time (WMD: -7.78, 95% CI: -13.93 to -1.63, P = 0.013, random) and RF time (WMD: -3.98, 95% CI: -7.78 to -0.17, P = 0.040, random) were significantly reduced in CF-guided catheter ablation. The incidence of procedure-related complications did not differ between these two technologies (RR: 0.83, 95% CI: 0.59 to 1.16, P = 0.271, fixed). CONCLUSION: CF-guided RF catheter ablation was associated with a significant AF/atrial tachycardia-free survival benefit compared with non-CF-guided ablation in patients with paroxysmal AF rather than persistent AF. In addition, CF-guided ablation strategy also reduced the procedure time, fluoroscopy time, as well as RF time despite no distinct effect on the alleviation of procedure-related complications.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/instrumentação , Catéteres , Sistema de Condução Cardíaco/fisiopatologia , Cirurgia Assistida por Computador/métodos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Desenho de Equipamento , Fluoroscopia , Sistema de Condução Cardíaco/cirurgia , Humanos
17.
Europace ; 19(5): 784-794, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28065886

RESUMO

AIMS: Cryoablation is a promising alternative technique to RF ablation for treating paroxysmal AF with encouraging results. However, data about the efficacy and safety comparison between cryoablation and RF ablation is still lacking. METHODS AND RESULTS: We systematically search the PubMed, the Cochrane Library, MEDLINE and Google Scholar databases, and finally identify 16 eligible studies including 7195 patients (2863 for cryoablation; 4332 for RF ablation). Freedom from AF/atrial tachycardial replase is slightly higher in cryoablation than RF ablation during a median 12 months of follow-up, with no statistical significant (RR: 1.05, 95% CI: 0.98-1.13, P = 0.159). In cryoablation, the procedure time is substantially shortened (WMD: -27.66, 95% CI: -45.24 to - 10.08, P = 0.002), whereas the fluoroscopy time is identical to RF ablation (WMD: -0.37, 95% CI: -2.78 to 2.04, P = 0.763). Procedure-related adverse events in cryoablation are parallel with that in RF ablation (RR: 1.08, 95% CI: 0.86-1.35, P = 0.159). CONCLUSIONS: Compared with RF ablation, cryoablation present a comparable long-term AF/atrial tachycardial-free survival and procedure-related adverse events. Meanwhile, cryoablation markedly shorten the procedure time, nonetheless, with negligible impact on the fluoroscopy time.


Assuntos
Fibrilação Atrial/mortalidade , Fibrilação Atrial/cirurgia , Ablação por Cateter/mortalidade , Ablação por Cateter/estatística & dados numéricos , Criocirurgia/mortalidade , Criocirurgia/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Causalidade , Comorbidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Fatores de Risco , Taxa de Sobrevida
18.
Biomed Environ Sci ; 28(6): 449-54, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26177906

RESUMO

Nuts have received increased attention from the public in recent years as important sources of some essential elements, and information on the levels of elements in edible nuts is useful to consumers. Determination of the elemental distributions in nuts is not only necessary in evaluating the total dietary intake of the essential elements, but also useful in detecting heavy metal contamination in food. The aim of this study was to determine the mineral contents in edible nuts, and to assess the food safety of nuts in the Beijing market. Levels of Li, Cr, Mn, Co, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Cs, Ba, Pb, Th, and U in 11 types of edible nuts and seeds (macadamia nuts, lotus nuts, pistachios, sunflower seeds, pine nuts, almonds, walnuts, chestnuts, hazelnuts, cashews, and ginkgo nuts) as well as raisins were determined by inductively coupled plasma mass spectrometry (ICP-MS). The accuracy of the method was validated using standard reference materials GBW10014 (cabbage) and GBW10016 (tea). Our results provide useful information for evaluating the levels of trace elements in edible nuts in the Beijing market, will be helpful for improving food safety, and will aid in better protecting consumer interests.


Assuntos
Análise de Alimentos/métodos , Espectrometria de Massas , Nozes/química , Oligoelementos/análise , China , Inocuidade dos Alimentos
19.
Org Biomol Chem ; 12(22): 3686-700, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24769843

RESUMO

The first enantioselective total synthesis of epiplakinic acid F (1) was achieved through a pivotal step involving a radical-mediated asymmetric peroxidation of vinylcyclopropanes with molecular oxygen to construct highly substituted 1,2-dioxolanes. Subsequent conversions of the chiral 1,2-dioxolanes led to total synthesis of epiplakinic acid F (1) and the confirmation of its absolute configuration. The enantiomer of epiplakinic acid F methyl ester (2) was also prepared.


Assuntos
Química Orgânica/métodos , Dioxolanos/síntese química , Peróxidos/síntese química , Dioxolanos/química , Ésteres/síntese química , Ésteres/química , Peróxidos/química
20.
J Assist Reprod Genet ; 31(5): 589-94, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24497298

RESUMO

PURPOSE: We investigated the disagreement between the positive cell-free fetal DNA test for trisomy 13 and the standard cytogenetic diagnosis of one case. METHODS: Cell-free fetal DNA testing was performed by massively parallel sequencing. We used conventional cytogenetic analysis to confirm the commercial cell-free fetal DNA testing. Additionally, postnatal fluorescent in situ hybridization (FISH) testing was performed on placental tissues. RESULTS: The cell-free fetal DNA testing result was positive for trisomy 13. G-banded analysis of amniotic fluid was normal, 46, XY. FISH testing of tissues from four quadrants of the placenta demonstrated mosaicism for trisomy 13. CONCLUSIONS: A positive cell-free fetal DNA testing result may not be representative of the fetal karyotype because of placental mosaicism. Cytogenetic analysis should be performed when abnormal cell-free fetal DNA test results are obtained.


Assuntos
Transtornos Cromossômicos/genética , Testes Genéticos/métodos , Mosaicismo , Placenta , Diagnóstico Pré-Natal/métodos , Trissomia/genética , Adulto , Líquido Amniótico , Aneuploidia , Cromossomos Humanos Par 13/genética , Análise Citogenética/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Cariótipo , Gravidez , Síndrome da Trissomia do Cromossomo 13
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