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2.
Eur J Pharmacol ; 908: 174353, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34274339

RESUMO

The purpose of this study was to investigate the role of glycyrrhizic acid (GA) in regulating myocardial ischemia-reperfusion injury (MIRI) in rats as well as the underlying mechanism. H9c2 cells were subjected to hypoxia/re-oxygenation (H/R) to mimic the MIRI in vitro, while a rat model of ischemia-reperfusion (I/R) was constructed by occlusion of the left anterior descending coronary artery for 0.5 h followed by 2 h of reperfusion. While flow cytometry and TUNEL assay were performed to analyze apoptosis in cells and myocardial tissue, echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were conducted to evaluate cardiac function and pathological changes, respectively. The levels of serum CK, CK-MB, LDH, AST, TNF-α, and IL-6 as well as the contents of MDA and SOD in tissues were measured by ELISA, while Western blot analysis was performed to detect the expression of endoplasmic reticulum stress (ERS)-related proteins. GA treatment significantly reduced apoptosis in H9c2 cells, while it alleviated left ventricular dysfunction, fibrosis and myocardial apoptosis, down-regulated the levels of CK, CK-MB, LDH, AST, TNF-α, IL-6, and MDA, and up-regulated SOD levels in I/R rats. Moreover, GA treatment led to a decrease in the expression of CHOP, GRP78, and p-PERK in both H/R cells and I/R rats. This study demonstrates that cardioprotective role of GA in MIRI may involve the attenuation of ERS-induced apoptosis and inflammation, potentially providing an alternative strategy for intervention of MIRI.

3.
Biomed Res Int ; 2021: 6653802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860048

RESUMO

Objective: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Epigenoma , Genoma Humano , Genômica , Transcriptoma/genética , Cardiomiopatia Dilatada/sangue , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
4.
Exp Ther Med ; 20(5): 119, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33005245

RESUMO

α1-antitrypsin (AAT) is a protein released as part of the anti-inflammatory response. It regulates the activity of serine proteinases and has a crucial role in the pathogenesis of acute coronary syndrome (ACS). The present study aimed to examine its role in patients with ACS. The plasma samples of 117 patients were collected at the Cardiology Department of the Affiliated Hospital of Youjiang Medical University (Baise, China). These included 46 cases of ACS (who met the diagnostic criteria for ACS and had ≥50% luminal stenosis of any coronary vessel), 35 cases of stable angina (SA; with ≥50% luminal stenosis of any coronary vessel but in a stable condition) and 36 normal healthy controls (subjects with no luminal stenosis in their coronary arteries). Plasma AAT protein concentrations were measured by ELISA and clinical data were collected. The plasma levels of AAT protein in patients with ACS were lower than those in controls and cases of SA (P<0.05), and the levels tended to decrease with the number of coronary artery lesions involved. There were no significant associations of the expression of plasma AAT protein and the number of diseased vessels in patients or the degree of stenosis. There was no correlation between the plasma protein levels of AAT and Gensini scores of patients with ACS. In conclusion, the plasma AAT protein levels in patients with ACS may contribute to the occurrence and development of coronary artery disease.

5.
Chem Biodivers ; 17(11): e2000529, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32939944

RESUMO

In this study, bufalin was glycosylated by an efficient chemo-enzymatic strategy. Firstly, 2-chloro-4-nitrophenyl-1-O-ß-D-glucoside (sugar donors) was obtained by chemical synthesis. Then, the glycosylation of the bufalin was achieved with the synthesized sugar donor under the catalysis of two glycosyltransferases (Loki and ASP). Finally, two glycosides, i. e., bufalin-3-O-ß-D-glucopyranoside and bufalin-3-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranoside)], were obtained by preparative HPLC. Compared to our previously reported sole chemical (total yield 10 % in four steps) or enzymatic methods (30 %), our combined chemo-enzymatic strategy in this article greatly improves the yields of monoglycoside (68 %) and diglycoside (21 %) and decreased the experimental cost (90 %). Furthermore, we tested the water solubility of these glycosides and found that the water solubilities of the two glycosides were 13.1 and 53.7 times of bufalin, respectively. In addition, the inhibitory activity of these glycosides against Na+ , K+ -ATPase were evaluated. The mono-glycosylated compound showed more potent activity than bufalin, while the diglycosylated compound was less potent.


Assuntos
Bufanolídeos/metabolismo , Glicosídeos/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Bufanolídeos/química , Glicosídeos/química , Glicosilação , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Humanos , Conformação Molecular , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , ATPase Trocadora de Sódio-Potássio/metabolismo , Solubilidade , Água/química
6.
Exp Ther Med ; 18(3): 2346-2352, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452718

RESUMO

The present study attempted to determine the correlation of the degree of coronary artery stenosis and Tolllike receptor 2/4 (TLR2/4) levels in Chinese Zhuang patients with coronary heart disease (CHD). A total of 466 Chinese patients from the Zhuang Ethnic population diagnosed with CHD at the Department of Cardiology the Affiliated Hospital of Youjiang Medical University between January 2016 and August 2017, together with 102 control patients, were recruited for the present study. The patients with CHD were divided into three groups depending on the number of diseased arteries. The patients with CHD were also classified according to their Gensini scores. Blood liver and renal function parameters, as well as blood sugar and lipid levels were measured. ELISA was used for TLR2/4 measurements. There were no significant differences with gender, age and body mass index between the CHD and control groups. The levels of TLR2/4 in the peripheral blood of the control and CHD groups were 2.34±0.85/5.08±2.41 and 5.22±3.16/9.33±4.92 ng/ml, respectively, and the differences were significant (P<0.001). Analysis of the three subgroups of vessel disease indicated that the expression of TLR2/4 was progressively higher with the increase in the number of affected vessels (P<0.01). There were also significant differences between the mild, moderate and severe stenosis groups (P<0.01). A positive linear correlation between TLR2/4 and the Gensini coronary artery score was identified (r=0.508 and 0.346, respectively; P<0.0001). In conclusion, the present study determined a positive correlation between the degree of coronary artery stenosis and the expression level of TLR2/4 in the serum of Chinese Zhuang patients with CHD. Serum TLR2/4 may be used to predict the severity of CHD.

7.
Gene ; 708: 1-9, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082501

RESUMO

OBJECTIVES: Toll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. METHODS: 1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. RESULTS: There are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. CONCLUSIONS: The rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Receptor 4 Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/sangue , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Receptor 4 Toll-Like/sangue
8.
J Hazard Mater ; 333: 63-72, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28342356

RESUMO

In this work, the simple preparation of novel polymer supported polyoxometallates (POMs) catalysts has been reported. Soluble task-specific cross-linked poly (ionic liquid) (PIL) was prepared with N,​N-​dimethyl-​dodecyl-​(4-​vinylbenzyl) ammonium chloride and divinylbenzene as co-monomers. The as-prepared cationic PILs were assembled with different commercial POMs to form the interlinked mesoporous catalysts, and the formation mechanism was provided. The catalytic oxidation activities of the catalysts were closely related to the formation pathway of their corresponding peroxide active species. The catalyst with H2W12O4210- as counterion, which exhibited the best activity in the oxidation of benzothiophene (BT) and dibenzothiophene (DBT) to sulfones in model oil with hydrogen peroxide (H2O2, 30wt%) as oxidant, was characterized by different techniques and systematically studied for its sulfur removal performance. As for the oxidative desulfurization of a real diesel, it was observed that almost all of the original sulfur compounds could be completely converted, and the catalyst could be reused for at least eight cycles without noticeable changes in both catalytic activity and chemical structure. In the end, a catalytic mechanism was put forward with the assistant of Raman analysis.

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