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BACKGROUND: Acute myocardial infarction (AMI), which commonly leads to heart failure, is among the leading causes of mortality worldwide. The aim of this study was to find potential regulatory network for miRNA-inflammation, oxidative stress and prognosis-related mRNA to uncover molecular mechanisms of AMI. METHODS: The expression profiles of miRNA and mRNA in the blood samples from AMI patients were downloaded from the Gene Expression Omnibus (GEO) dataset for differential expression analysis. Weighted gene co-expression network analysis (WGCNA) was used to further identify important mRNAs. The negatively regulatory network construction of miRNA-inflammation, oxidative stress and prognosis-related mRNAs was performed, followed by protein-protein interaction (PPI) and functional analysis of mRNAs. RESULTS: A total of three pairs of negatively regulatory network of miRNA-inflammation and prognosis-related mRNAs (hsa-miR-636/hsa-miR-491-3p/hsa-miR-188-5p/hsa-miR-188-3p-AQP9, hsa-miR-518a-3p-C5AR1 and hsa-miR-509-3-5p/hsa-miR-127-5p-PLAUR), two pairs of negatively regulatory network of miRNA-oxidative stress and prognosis-related mRNAs (hsa-miR-604-TLR4 and hsa-miR-139-5p-CXCL1) and three pairs of negatively regulatory network of miRNA-inflammation, oxidative stress and prognosis-related mRNA (hsa-miR-634/hsa-miR-591-TLR2, hsa-miR-938-NFKBIA and hsa-miR-520h/hsa-miR-450b-3p-ADM) were identified. In the KEGG analysis, some signaling pathways were identified, such as complement and coagulation cascades, pathogenic Escherichia coli infection, chemokine signaling pathway and cytokine-cytokine receptor interaction and Toll-like receptor signaling pathway. CONCLUSION: Identified negatively regulatory network of miRNA-inflammation/oxidative stress and prognosis-related mRNA may be involved in the process of AMI. Those inflammation/oxidative stress and prognosis-related mRNAs may be diagnostic and prognostic biomarkers for AMI.
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Nicotine is proved to be an important factor for cardiac hypertrophy. Autophagy is important cell recycling system involved in the regulation of cardiac hypertrophy. Cilostazol, which is often used in the management of peripheral vascular disease. However, the effects of cilostazol on nicotine induced autophagy and cardiac hypertrophy are unclear. Here, we aim to determine the role and molecular mechanism of cilostazol in alleviating nicotine-induced cardiomyocytes hypertrophy through modulating autophagy and the underlying mechanisms. Our results clarified that nicotine stimulation caused cardiomyocytes hypertrophy and autophagy flux impairment significantly in neonatal rat ventricular myocytes (NRVMs), which were evidenced by augments of LC3-II and p62 levels, and impaired autophagosomes clearance. Interestingly, cathepsin B (CTSB) activity decreased dramatically after stimulation with nicotine in NRVMs, which was crucial for substrate degradation in the late stage of autophagy process, and cilostazol could reverse this effect dramatically. Intracellular ROS levels were increased significantly after nicotine exposure. Meanwhile, p38MAPK and JNK were activated after nicotine treatment. By using ROS scavenger N-acetyl-cysteine (NAC) could reverse the effects of nicotine by down-regulation the phosphorylation of p38MAPK and JNK pathways, and pretreatment of specific inhibitors of p38MAPK and JNK could restore the autophagy impairment and cardiomyocytes hypertrophy induced by nicotine. Moreover, CTSB activity of lysosome regained after the treatment with cilostazol. Cilostazol also inhibited the ROS accumulation and the activation of p38MAPK and JNK, which providing novel connection between lysosome CTSB and ROS/p38MAPK/JNK related oxidative stress pathway. This is the first demonstration that cilostazol could alleviate nicotine induced cardiomyocytes hypertrophy through restoration of autophagy flux by activation of CTSB and inhibiting ROS/p38/JNK pathway, exhibiting a feedback loop on regulation of autophagy and cardiomyocytes hypertrophy.
Assuntos
Catepsina B/metabolismo , Cilostazol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Nicotina/toxicidade , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Broncodilatadores/farmacologia , Catepsina B/genética , Regulação da Expressão Gênica/efeitos dos fármacos , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Agonistas Nicotínicos/toxicidade , Proteínas Proto-Oncogênicas/genética , Ratos , Receptores Proteína Tirosina Quinases/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Intracoronary application of nicorandil can effectively reduce the myocardial no-reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro-inflammatory cytokines was significantly increased, while the anti-inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.
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Inflamação/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Nicorandil/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Proteômica , Idoso , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
Polyethylene (PE), polypropylene (PP), polyamide (PA), and polyethylene terephthalate (PET) surfaces and particles were employed to study effects of polymer materials on linseed oil, peanut oil, rapeseed oil and sunflower seed oil oxidation. The surface types of the materials, hydroperoxide content and volatile in oils were determined by contact angle, Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry. Oils on PP surfaces underwent a more rapid oxidation, followed by PA, PE and PET. Except PP sets, this order was consistent with surface hydrophilicity of polymers. Further study using polymer particles avoiding packaging barrier suggested this was probably due to barrier factors. Although PE surfaces allowed oil to have lower content of hydroperoxides, it can promote oil hydroperoxide decomposition into volatile products. Surface types of polymer materials are correlated with oxidation of contacted oil, and these surfaces can also affect the oil secondary oxidation and the degradation of oxidation products.
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Embalagem de Alimentos , Nylons/química , Óleos de Plantas/química , Polietileno/química , Polipropilenos/química , Verduras/química , Cromatografia Gasosa-Espectrometria de Massas , Oxirredução , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Eucommia ulmoides is a traditional Chinese herb whose seeds can be used to produce edible oils. Fourier transform infrared (FTIR) and synchronous fluorescence spectroscopic (SyFS) spectra of Eucommia ulmoides seed oil (EUSO) are lacking. The relevant functional and fluorescent groups were determined by FTIR and SyFS techniques for discriminating adulteration of EUSO, respectively. FTIR and SyFS spectra of EUSO and six common-used vegetable oils were recorded from 4000-400 cm-1 and 250-700 nm at wavelength interval of 60 nm, respectively. Principal component analysis (PCA), linear discriminant analysis (LDA), cluster analysis (CA) and partial least square (PLS) regression was used for qualitative and quantitative calibration of EUSO adulteration. The FTIR spectral regions of 1429-1377 cm-1 and 1128-1110 cm-1 based on PCA, LDA, and CA, and the PCA of SyFS spectral regions of 600-700 nm and 300-500 nm were evaluated for qualitative differentiation of EUSO adulteration. The recognition rate of PCA validation was found to be 100% by FTIR regions. PLS calibration was optimal by the spectral normalization vector treatment in the two FTIR spectral regions and SyFS spectra were combined with characteristic absorption peak area, which can achieve quantitative detection of EUSO adulteration. The two techniques are useful for EUSO adulteration detection at levels down to 1% and 0.48% (w/w), respectively. The results indicated that spectral information obtained by FTIR and SyFS of EUSO can be used for qualitative and quantitative analysis of EUSO adulteration with the advantages of high sensitivity, simplicity, and rapidness.
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Gorduras Insaturadas na Dieta/análise , Eucommiaceae/química , Contaminação de Alimentos/prevenção & controle , Qualidade dos Alimentos , Óleos de Plantas/química , Sementes/química , Espectrometria de Fluorescência/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Calibragem , Sensibilidade e EspecificidadeRESUMO
A Fourier transform infrared (FTIR) spectroscopy with infrared quartz cuvette (IQC) as spectral accessory method was developed to determine acid value (AV) of edible oils. The absorption peak at 5680 cm-1/5487 cm-1 ascribed to the C-H stretching band was a substitute for the peak of an internal standard. Partial least square (PLS) regression was used for AV calibration, and samples were validated by titrated method. Results showed dilution calibration was feasible for randomly dilution among 6-13:1 (CCl4: oils, v/v). PLS calibration was optimal by a spectral wavenumber (3603 cm-1-3250 cm-1) as the first derivative treatment. Correlation coefficient and root mean square error of calibration were 0.9967 and 0.135, respectively. Calibrated validation, blind sample validation and precision analysis presented a good correlation between IQC-FTIR and titrated methods. Based on the dilution calibration, randomly diluted oil samples can be employed by IQC-FTIR.
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Óleos de Plantas/química , Quartzo/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Calibragem , Magnoliopsida/química , Oxirredução , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentaçãoRESUMO
OBJECTIVE: To evaluate the therapeutic effect of Compound Xuanju Capsule on type III prostatitis. METHODS: A total of 242 patients with type III prostatitis diagnosed by the NIH criteria were randomly divided into an experimental and a control group of equal number, the former treated with Compound Xuanju Capsule + Tamsulosin Hydrochloride, and the latter with Quinolinone antibiotics + Tamsulosin and Hydrochloride, both for 6 months. After treatment, we assessed the therapeutic effects based on the NIH-CPSI scores and the improvement of relevant complications. RESULTS: All the 242 patients completed the treatment. The total effectiveness rate was 77.69% (94/121) in the experimental group, 71.56% (78/109) in those with complications. In comparison, it was only 47.10% (57/121) in the control group, 31.78% (34/107) in those with complications. Both the NIH-CPSI scores and the improvement of complications were significantly higher in the experimental than in the control group (P < 0.05). CONCLUSION: Compound Xuanju Capsule has a good therapeutic effect on type III prostatitis.
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Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Prostatite/tratamento farmacológico , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To assess a novel hormone replacement therapy (HRT) paradigm using raloxifene, aspirin combined with estrogen in rabbit model of menopause. METHODS: Female New Zealand white rabbits were ovariectomized or sham-operated. The ovariectomized rabbits were divided into 7 groups: estradiol valerate (E(2)), raloxifene, aspirin, E(2) /raloxifene, E(2)/aspirin, E(2) /raloxifene/aspirin and vehicle. Two weeks after the operation, the rabbits were administered the above drugs for 12 weeks. Then, the mammary glands were examined histologically, uterus was weighted, and blood sample was collected for analyzing the levels of estrogen, serum lipids and monocyte chemoattractant protein (MCP)-1, and platelet aggregation. The aortic tissue was examined morphometrically. RESULTS: Compared with E(2) 0.1 mg·kg(-1)·d(-1) treatment alone, the pairing of raloxifene 10 mg·kg(-1)·d(-1) with E(2) significantly decreased the extent of mammary gland branches and ducts (5.53%±1.23% vs 15.4%±2.17%, P<0.01), as well as the uterine weight (2.16±0.35 g vs 4.91±0.75 g, P<0.01). However, E(2)/raloxifene or E(2) alone treatment significantly stimulated platelet aggregation relative to vehicle group. Addition of aspirin 5 mg·kg(-1)·d(-1) reduced platelet aggregation to almost the same level as the vehicle group. E(2) treatment exerted a positive effect on serum lipids and MCP-1, and a regression in aortic intimal plaque size compared to the vehicle. Raloxifene reinforced the positive effects of E(2). CONCLUSION: The combination of raloxifene, aspirin and E(2) exhibits positive lipid, MCP-1 and atherosclerotic responses with minimal stimulation of breast and uterine tissues as well as platelet aggregation in a rabbit model of the menopause.