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Here, we describe highly efficient intramolecular hydroarylations mediated by Re2O7/HReO4. Styrene derivatives of different electronic properties have been activated to effect a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures. This method is characterized by mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy. The potential synthetic application of this methodology was exemplified by the efficient total synthesis of an isoCA-4 analogue.
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A novel, simple, and rapid method is demonstrated for measuring the pore size and pore size distribution of filtration membranes (FMs) used in aqueous applications with fluorescence probes. Because the selected fluorescent probes are mixable and have strong signals, combined with the operation of dead-end filtration, this method only requires small amounts of reagents; additionally, it is time-efficient by avoiding multiple rounds of filtration. This method detects the size of a FM pore throat (i.e., the narrowest position of a pore tunnel), which is more consistent with the actual filtration situation. The conditions, such as probe concentration, temperature, transmembrane pressure difference, and types of surfactants, have been optimized. The experimental results show that the fluorescence probe method has good accuracy and reproducibility for measuring the pore size and pore size distribution of both organic and inorganic FMs. The method is particularly suitable for rapid testing of the filtration performance (nominal pore size≥0.02 µm) of purchased or synthetic membranes in the laboratory.
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INTRODUCTION: This study aimed to describe the fabrication, implementation and evaluation of 3D-printed patient-specific models for unskilled students to enhance learning in immediate implant procedures and provisionalization. MATERIALS AND METHODS: The individualized simulation models were designed and processed based on CT and digital intraoral scanning of a patient. Thirty students performed simulation implant surgery and provisionalized the implant sites on the models and answered questionnaires to assess their perceptions before and after the training. The scores of the questionnaires were analysed using the Wilcoxon signed-rank test. RESULTS: Significant differences before and after training were found in the students' responses. Students reported better results in understanding of surgical procedures, knowledge in prosthetically driven implantology, understanding of minimally invasive tooth extraction, confirming the accuracy of surgical template, usage of the guide rings and usage of the surgical cassette after simulation training. The overall expenditure on the simulation training involving 30 students amounted to 342.5 USD. CONCLUSIONS: The patient-specific and cost-efficient 3D printed models are helpful for students to improve theoretical knowledge and practical skills. Such individualized simulation models have promising application prospects.
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Impressão Tridimensional , Treinamento por Simulação , Humanos , Educação em Odontologia , EstudantesRESUMO
Implant placement in close proximity with adverse angulations may result in difficulty with impression making. With the lock surface function provided by intraoral scanning software programs, severely tilted adjacent implants can be digitized one by one without interfering with the accuracy of the digital cast. This article presents a straightforward digital impression technique for severely mesiodistally tilted adjacent implants in a clinical case.
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Implantes Dentários , Técnica de Moldagem Odontológica , Desenho Assistido por Computador , Materiais para Moldagem Odontológica , Modelos DentáriosRESUMO
Atherosclerosis (AS) is the main pathological basis for ischemic cardiovascular and cerebrovascular diseases. Mesenchymal stem cell (MSC)-derived exosomes have the potential to alleviate AS, while the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism of MSC-derived exosomes in AS. The AS mouse model was prepared by feeding ApoE-/- mice with high-fat diet. AS mice were administered with MSC-derived exosomes, and the atherosclerotic plaque area was analyzed by Oil Red O staining. Mouse RAW264.7 macrophages were incubated with MSC-derived exosomes. The macrophage infiltration, macrophage proportion, and cell migration were estimated by immunohistochemistry, flow cytometry, or Transwell assay. The relationship between miR-21a-5p and kruppel-like factor 6 (KLF6) or extracellular signal-regulated protein kinases 2 (ERK2) was verified by luciferase reporter assay. We found that MSC-derived exosomes promoted M2 polarization of macrophages and reduced plaque area and macrophage infiltration in AS mice. miR-21a-5p overexpression caused an increase of M2 macrophages in RAW264.7 cells and led to a decrease in migration of RAW264.7 cells. Moreover, both KLF6 and ERK2 are the targets of miR-21a-5p. MSC-derived exosomes containing miR-21a-5p promoted M2 polarization of RAW264.7 cells by suppressing KLF6 expression. MSC-derived exosomes containing miR-21a-5p inhibited migration of RAW264.7 cells through inhibiting the ERK1/2 signaling pathway. In conclusion, MSC-derived exosomes containing miR-21a-5p promote macrophage polarization and reduce macrophage infiltration by targeting KLF6 and ERK1/2 signaling pathways, thereby attenuating the development of AS. Thus, MSC-derived exosomes may be a promising treatment for AS.
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Aterosclerose/tratamento farmacológico , Exossomos/genética , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células-Tronco Mesenquimais/citologia , MicroRNAs/metabolismo , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/patologia , Movimento Celular/genética , Modelos Animais de Doenças , Exossomos/metabolismo , Fator 6 Semelhante a Kruppel , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Células RAW 264.7RESUMO
During long-pulse deuterium plasma operations in the Experimental Advanced Superconducting Tokamak (EAST), a mixed radiation field is generated, which is mainly composed of fusion neutrons, gamma rays, and x-rays. More accurate and effective dose monitoring methods have been developed and established to determine the ionizing radiation intensity both for the stable operation of the device and for the radiation safety of personnel. As far as we know, there are few reports about the biological effects of radiation induced by fusion neutrons andγradiation, which are of vital importance for the assessment of radiation hazards presented by fusion devices, such as EAST, to human beings and the environment. In this study, three positions in the EAST hall were selected to detect genotoxic effects induced by nuclear fusion radiation using aVicia fabamicronucleus (MN) test for the first time. The doses of neutrons and gamma rays at these places were measured by thermoluminescence dosimeters four times between June 2019 and May 2020. The radiation doses decreased as the distances from the EAST device shell gradually increased from S1 to S3. The radiation in the EAST hall resulted in a significant induction of MN in theVicia fabaroot tip cells compared to a negative control, which was different from the MN frequency induced by fission neutrons,γ-rays and other kinds of radiation in previous studies. These results indicate the existence of potential genotoxic effects induced by radiation from EAST which is different from other radiation and suggest that personnel should not be permitted to enter the experimental hall during the discharge process, and that radiation protection measures should be taken during necessary maintenance to avoid radiation damage. These newly acquired results will certainly increase our knowledge about the biological effects induced by radiation from nuclear fusion and provide good data support for developing more effective environmental and personnel fusion radiation protection.
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Dano ao DNA , Nêutrons , Bioensaio , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Humanos , Raios XRESUMO
BACKGROUND: Assessment of the coronary microcirculation remains challenging. OBJECTIVE: we explored the feasibility of evaluating the coronary microvasculature in rats with myocardial infarction (MI) using a three-dimensional visualization technique. METHODS: Animals were divided into the sham operation group (S), MI 45 min group (M45), and MI 180 min group (M180). Opened microvessels were labelled with the fluorescent dye DiI (1, 1'-dioctadecyl-3, 3, 3'3'-tetramethylindo carbocyanine perchlorate) using a heart perfusion method. The microvascular distribution and opening status were observed under laser scanning confocal microscopy, which was adjusted to facilitate evaluation of subjects around 6 to 20 µm. RESULTS: Microvascular vessels (6-20 µm) were successfully labelled by DiI. Intact and clear three-dimensional microvascular structures were observed in myocardium of sham rats and remote non-infarct myocardial tissue of MI rats, while there was almost no microvascular structure in the infarct area of the M45 group, and only a small amount of microvascular visualization was visualized in the infarct area of the M180 group. The microvascular area and microvascular density in M45 group and M180 group in the infarct border zone were significantly lower than corresponding area in S group. CONCLUSION: Three-dimensional visualization of opened coronary microvascular vessels is feasible in DiI-labelled myocardium in this rat MI model. This novel technique might be useful for defining the underlying mechanisms of coronary microvascular diseases and observe the efficacy of various therapy strategies on coronary microvessels.
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Vasos Coronários/diagnóstico por imagem , Imageamento Tridimensional , Microscopia Confocal , Microscopia de Fluorescência , Microvasos/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Animais , Carbocianinas/administração & dosagem , Modelos Animais de Doenças , Estudos de Viabilidade , Corantes Fluorescentes/administração & dosagem , Valor Preditivo dos Testes , Ratos Sprague-DawleyRESUMO
BACKGROUND: Previous studies have linked high myopia (HM) to brain activity, and the difference between HM and low myopia (LM) can be assessed. PURPOSE: To study the differences in functional networks of brain activity between HM and LM by the voxel-level degree centrality (DC) method. MATERIAL AND METHODS: Twenty-eight patients with HM (10 men, 18 women), 18 patients with LM (4 men, 14 women), and 59 healthy controls (27 men, 32 women) were enrolled in this study. The voxel-level DC method was used to assess spontaneous brain activity. Correlation analysis was used to explore the change of average DC value in different brain regions, in order to analyze differences in brain activity between HM and LM. RESULTS: DC values of the right cerebellum anterior lobe/brainstem, right parahippocampal gyrus, and left caudate in HM patients were significantly higher than those in LM patients (P < 0.05). In contrast, DC values of the left medial frontal gyrus, right inferior frontal gyrus, left middle frontal gyrus, and left inferior parietal lobule were significantly lower in patients with HM (P < 0.05). However, there was no correlation between behavior and average DC values in different brain regions (P < 0.05). CONCLUSION: Different changes in brain regions between HM and LM may indicate differences in neural mechanisms between HM and LM. DC values could be useful as biomarkers for differences in brain activity between patients with HM and LM. This study provides a new method to assess differences in functional networks of brain activity between patients with HM and LM.
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Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Miopia/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-IdadeRESUMO
We established a rabbit model of acute massive pulmonary embolism (PE) with associated circulatory shock using autologous blood clots. Rabbits were randomly assigned to a sham operation group (S group), model group (M group; equal volume of saline intravenously after shock), and sodium nitroprusside group (SNP group; sodium nitroprusside intravenously after shock). SNP treatment significantly decreased mean pulmonary arterial pressure and increased mean arterial pressure and arterial partial pressure of oxygen and resulted in a partial reversal of the acute circulatory failure. The shock-reversal rate was 0% in the M group and 80% in the SNP group. Moreover, pulmonary artery angiography and echocardiography examinations evidenced alleviated PE-induced changes after SNP therapy. 5-Hydroxytryptamine was significantly reduced in both PE and non-PE tissues, thromboxane A2 level was significantly reduced in PE and tended to be lower in non-PE tissues, neutrophil accumulation was significantly reduced in both PE and non-PE tissues after SNP therapy. Our study demonstrated that pulmonary vasospasm in the nonembolic region might be a major pathologic factor leading to reduced left ventricular filling and circulatory shock after massive PE. Reduction of pulmonary vasospasm in the nonembolic area after SNP might serve as a major therapeutic mechanism involved in the observed beneficial effects of SNP in this model.
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Sistema Cardiovascular/efeitos dos fármacos , Modelos Animais de Doenças , Nitroprussiato/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Choque/tratamento farmacológico , Vasodilatadores/administração & dosagem , Animais , Sistema Cardiovascular/patologia , Masculino , Embolia Pulmonar/complicações , Coelhos , Choque/complicaçõesRESUMO
BACKGROUND: We recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model. METHODS: Rabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 µg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 µg/kg/min intravenously, n = 10). RESULTS: MPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO2 in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions. CONCLUSION: Present results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.
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Neuropeptídeo Y/biossíntese , Embolia Pulmonar/metabolismo , Choque/metabolismo , Tirosina 3-Mono-Oxigenase/biossíntese , Vasodilatadores/uso terapêutico , Animais , Embolia Pulmonar/tratamento farmacológico , Coelhos , Distribuição Aleatória , Choque/tratamento farmacológico , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Vasodilatadores/farmacologiaRESUMO
We recently showed that ticagrelor reduced myocardial ischemia-reperfusion injury (IRI) and downregulated galectin-3 in the ischemic myocardium. This study tested the hypothesis that ticagrelor could reduce IRI through the NF-κB pathway. Rats were randomly divided into sham-operated group, placebo group (gastric administration of saline after IRI), ticagrelor group (gastric administration of ticagrelor after left anterior descending artery ligation), dextran sodium sulfate (DSS) group (DSS was added to drinking water 7 days before IRI), and DSS + ticagrelor group (DSS was added to drinking water 7 days before IRI and gastric administration of ticagrelor after left anterior descending artery ligation). Ticagrelor significantly reduced the infarct size and plasma cTnI at 3 and 7 days after IRI, significantly downregulated protein and mRNA expressions of NF-κB and galectin-3, and mRNA expressions of IL-6 and TNF-α in the ischemic area at 24 hours, 3 and 7 days after IRI. Ticagrelor also significantly decreased plasma high-sensitivity C-reactive protein and NT-proBNP levels at 24 hours and 3 days after IRI. Furthermore, pretreatment with DSS blocked the beneficial effects of ticagrelor. Our study indicates that the cardioprotective effect of ticagrelor might be partly mediated by inhibiting the NF-κB pathway in this rat model of IRI.
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Anti-Inflamatórios/farmacologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , NF-kappa B/metabolismo , Ticagrelor/farmacologia , Animais , Proteína C-Reativa/metabolismo , Modelos Animais de Doenças , Galectina 3/genética , Galectina 3/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , NF-kappa B/genética , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ratos Sprague-Dawley , Transdução de Sinais , Troponina I/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Neutrophil extracellular traps (NETs) play an important role in the pathological process of atherosclerosis (AS). This study aims to evaluate whether exosomes from oxidized low-density lipoprotein (ox-LDL)-treated vascular endothelial cells (VECs) aggravate AS by inducing NET formation. Exosomes from the peripheral blood of healthy donors and AS patients (namely NC-EXO and AS-EXO, respectively) and exosomes from human umbilical vein endothelial cells (HUVECs) treated without or with ox-LDL (namely normal EXO and ox-LDL-EXO, respectively) were isolated, identified, and co-cultured with neutrophils from peripheral blood of healthy donors. NET formation was evaluated by immunofluorescence staining and determining the content of cell-free DNA and myeloperoxidase-DNA complex. Dual-luciferase reporter assay, chromatin immunoprecipitation assay, quantitative reverse transcription polymerase chain reaction, and western blot analysis were performed to explore the underlying mechanisms. We found that AS-EXO and ox-LDL-EXO induced NET release from neutrophils. Mechanistically, ox-LDL treatment in HUVECs might activate the NF-κB pathway, which transcriptionally activates miR-505, and then the exosome-encapsulated high miR-505 expression targeted and inhibited SIRT3 in neutrophils, thereby inducing reactive oxygen species (ROS) level increase and NET release by neutrophils. Further in vivo experiments showed that ox-LDL-EXO accelerated AS progression in AS mice. In summary, exosome-encapsulated miR-505 from ox-LDL-treated VECs aggravates AS by inducing NET formation.
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Aterosclerose/metabolismo , Exossomos/metabolismo , Armadilhas Extracelulares/metabolismo , Lipoproteínas LDL/metabolismo , MicroRNAs/fisiologia , Idoso , Animais , Células Cultivadas , Progressão da Doença , Feminino , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Masculino , Camundongos , Camundongos Knockout para ApoE , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor V (FV) deficiency. METHODS: All of the exons, flanking sequences, and 5' and 3' untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. RESULTS: The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FV activity (FV:C) and FV antigen (FV:Ag) were reduced by 13% and 17%, respectively. The FV:C and FV:Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c.2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c.1538G to A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p.Ser923LeufsX8 variant, while his mother and son carried the heterozygous p.Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p.Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p.Ser923LeufsX8 variant, and the result has predicted a corresponding disease. CONCLUSION: A heterozygous deletional mutation c.2851delT in exon 13 of the F5 gene and a heterozygous c.1538G to A polymorphism harbored by the proband may be associated with the decreased FV level in this pedigree.
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Deficiência do Fator V/genética , Fator V/genética , Deleção de Genes , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , FenótipoRESUMO
The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ± dP/dt and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of CD3+ and CD14+ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.
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AIMS: The full benefits of myocardial revascularization strategies applied to acute myocardial infarction patients might be reduced by myocardial ischaemia and reperfusion (I/R) injury. It is known that inflammation plays an important role in the pathogenesis of I/R injury and galectin-3, a known inflammatory factor, is actively involved in ischaemia-induced inflammation and fibrosis of various organs. Previous studies demonstrated that anti-platelets therapy with ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate myocardial I/R injury and I/R injury-related inflammatory responses. It remains unknown whether the cardioprotective effects of ticagrelor are also mediated by modulating myocardial galectin-3 expression. METHODS: We determined the ratio of infarct area (IA)/area at risk (AAR), expression of galectin-3, TNF-α and IL-6 in infarct area of rats treated with placebo (equal volume saline per gastric gavage immediately after LAD ligation, then once daily till study end) or ticagrelor (150 mg kg-1 dissolved in saline per gastric gavage immediately after LAD ligation, then once daily till study end) at 24 h, 3 and 7 days post I (45 min)/R injury. Sham-operated rats served as control. RESULTS: Our results showed that ticagrelor treatment significantly reduced IA/AAR ratio at 3 and 7 days post I/R, downregulated mRNA and protein expression of galectin-3, as well as mRNA expression of TNF-α and IL-6 in infarct area at 24 h, 3 and 7 days post I/R. CONCLUSIONS: Our results suggest that the cardioprotective effects of ticagrelor might partly be mediated by downregulating galectin-3 expression in infarct area in this rat model of myocardial I/R injury.
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Anti-Inflamatórios/farmacologia , Galectina 3/metabolismo , Mediadores da Inflamação/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Ticagrelor/farmacologia , Animais , Citoproteção , Modelos Animais de Doenças , Regulação para Baixo , Galectina 3/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: We investigated the effect of (-)-epigallocatechin-3-gallate (EGCG) on cardiac function and its mechanism, which focused on the desensitization of ß1-AR and GRK2 in heart failure (HF) rats. METHODS: HF was induced by abdominal aortic coarctation. Four weeks after HF induction, the rats were given EGCG (25, 50, 100 mg/kg/day). Cardiac function was assessed by measuring haemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. The expression of ß1-AR was detected by immunohistochemistry and immunofluorescence. The membrane expression of ß1-AR and GRK2 was detected by western blot. The expression levels of ß1-AR mRNA and GRK2 mRNA were evaluated by Q-PCR. RESULT: Compared to the control group, the left ventricular end diastolic pressure, mean blood pressure, heart weight/body weight, and posterior wall thickness in the HF group were significantly increased, whereas the left ventricular systolic pressure, maximum rate of left ventricular pressure rise (+ dP/dt max) and maximum rate of left ventricular pressure fall (- dP/dt max) were clearly decreased. EGCG could improve cardiac function by regulating these parameters. Inflammatory cell infiltration, irregularly arranged cardiomyocytes, swelling of cardiomyocytes and myocardial fibrosis were observed in HF rats' myocardial morphology, and EGCG obviously improved the morphological signs. The expression of ß1-AR was significantly decreased in the left ventricle tissue of HF rats by immunohistochemistry and immunofluorescence. The membrane expression of ß1-AR decreased, whereas GRK2 increased in vivo and in vitro by western blot. EGCG could down-regulate the membrane expression of GRK2 and up-regulate the expression of ß1-AR. There were no significant differences in the total expression of ß1-AR mRNA and GRK2 mRNA. CONCLUSIONS: EGCG has therapeutic effects on the heart function of HF rats. The mechanism might be related to the inhibition of the transfer membrane of GRK2 and to the reduction of the desensitization of ß1-AR.
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Catequina/análogos & derivados , Quinase 2 de Receptor Acoplado a Proteína G/genética , Insuficiência Cardíaca/tratamento farmacológico , Receptores Adrenérgicos beta 1/genética , Animais , Western Blotting , Catequina/administração & dosagem , Catequina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Imuno-Histoquímica , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Chá/químicaRESUMO
Based on the strategy of the development of phosphine-free palladium-catalyzed direct C-H arylation, a series of camphyl-based α-diimine palladium complexes bearing sterically bulky substituents were synthesized and characterized. The palladium complexes were applied for the cross-coupling of thiazole derivatives with aryl bromides. The effect of the sterically bulky substituent on the N-aryl moiety as well as the reaction conditions was screened. Under the optimal protocols, a wide range of aryl bromides can be smoothly coupled with thiazoles in good to excellent yields in the presence of a low palladium loading of 0.2 mol% under open-air conditions.
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Divertor impurity injection on Tokamak is the most important means to achieve divertor impurity screening efficiency. In this paper, a fast-response extreme-ultraviolet (EUV) spectrometer is used to monitor the Ar emission lines during the EAST(Experimental Advanced Superconducting Tokamak)divertor Ar injection experiment. Based on the NIST(National Institute of Standards and Technology)atomic spectrum database, the emission lines from different ionized Ar ions in 2ï½50 nm wavelength range, e.g. Ar â £, Ar â £-â ª and Ar â ©â £-â ©â ¥, are being identified. Ar â ©â ¥ 35.39 nm and Ar â £ 44.22 nm with the ionization energy of 918.4 and 59.6 eV respectively are being monitored during the experiment with Ar puffing to observe the behavior of Ar impurities in different regions in plasmasimultaneously. The preliminary analysis on divertor impurity screening efficiency is carried outwith the time evolution of intensities of two Ar emission lines. The results of experiment puffing from the same gas puffing inlet (e. g. from lower outer target inlet) and withdifferent plasma configurations (e. g. lower single null, upper single null) show that the screening effect on the impurity injected from the divertor region is better thanfrom the main plasma region; the screening effect of lower divertor and particle pumping by internal cryopump installed in lower divertor is stronger than upper divertor.
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OBJECTIVE: Disequilibrium of the cytokine network was reported to play an important role in the progression of chronic heart failure (CHF). Catechin exerts cardioprotection through treating many kinds of angiocardiopathy. However, the effects of catechin on CHF are currently unclear. Therefore, the main aim of this study was to investigate the efficacy of catechin on CHF rats as well as its relationship to immunoregulation. METHODS: CHF was induced in rats by ligation of the abdominal aorta. Myocardial function was evaluated by left ventricular systolic pressure and left ventricular end-diastolic pressure. The cytokine level was measured by enzyme-linked immunosorbent assay. Th17 and Treg levels in peripheral blood and spleen were analyzed by flow cytometry. RESULTS: The results showed that catechin treatment (50, 100 mg/kg/day) markedly improved myocardial function in rats treated with abdominal aortic coarctation. Severity of myocardial dysfunction in CHF rats significantly correlated with serum values of interleukin-17 (IL-17)/IL-10. Further results indicated catechin obviously inhibited immune activation, regulated unbalanced levels of IL-17/IL-10, and reversed abnormal polarization of TH17 as well as Treg in peripheral blood and spleen. CONCLUSIONS: Taken together, oral administration of catechin effectively suppressed abdominal aorta ligation-induced CHF in rats, which was closely associated with its modulation on Th17 and Treg.
Assuntos
Cardiotônicos/uso terapêutico , Catequina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Animais , Aorta Abdominal/cirurgia , Cardiotônicos/farmacologia , Catequina/farmacologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/fisiopatologia , Imunomodulação/efeitos dos fármacos , Interleucina-10/sangue , Interleucina-17/sangue , Ligadura , Masculino , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologia , Linfócitos T Reguladores/fisiologia , Células Th17/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
In this paper, we describe a Re2O7-mediated ring-opening arylation of unactivated arylcyclopropane because of its functionalization with various arenes via Friedel-Crafts-type reactivity. This protocol allows facile access to functionalized 1,1-diaryl alkanes and is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. Both density functional theory calculations and deuterium labeling experiments were carried out to justify the indispensable role of HFIP in this transformation and pointed to Re2O7-mediated ring opening being the rate-determining step.