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This study investigated the potential effect of n-6/n-3 polyunsaturated fatty acids (PUFA) on inflammation and myocardial ischemic reperfusion injury (MIRI) in rats, together with the underlying protective mechanisms, and screen out most effective ratio of n-6/n-3 within limits. The rats with pre-infarct treatment were distributed among 5 groups according to the n-6/n-3 ratio (36:1; 1:1, 5:1, 10:1, 50:1); for the post-infarct treatment, the rats were distributed among 6 groups, including the control group (36:1) which was subjected to a sham procedure; the model group (36:1); and 4 test groups (n-6/n-3 ratio: 1:1, 5:1, 10:1, 50:1). All of the rats were fed a purple perilla seed oil and safflower oil-based fatty emulsion. The serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were determined using enzyme-linked immunosorbent assay. Staining with triphenyl tetrazolium chloride, hematoxylin and eosin, or Masson's trichrome was performed for histological examination. Cardiomyocyte apoptosis was examined by TUNEL assay. Western blotting was performed to examine the expression levels of apoptosis-related proteins and signaling pathway proteins. Our data indicate that in both the pre-infarct treatment and post-infarct treatment, low ratios of n-6/n-3 PUFAs significantly inhibited the levels of serum inflammatory factors, the infarct size of MIRI rats, number of cardiomyocytes undergoing apoptosis, and the expression levels of caspase-3, Bcl-2, and Bax in the MIRI group. Thus a low ratio of n-6/n-3 PUFAs ameliorates inflammation and myocardial ischemic reperfusion injury.
Assuntos
Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Inflamação/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Scavenger receptor A (SRA) can regulate immune response and is involved in pathophysiological processes of acute brain injury. We analyzed the prognostic role of serum soluble SRA in intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study of 110 healthy controls and 110 patients with acute basal ganglia hemorrhage, serum soluble SRA concentrations were detected. Univariate analyses, followed by multivariate logistic regression analyses, were utilized to explore the relationship between serum soluble SRA concentrations and early neurologic deterioration (END) plus post-stroke 3-month poor prognosis (modified Rankin Scale scores of 3-6). RESULTS: Serum soluble SRA concentrations of patients were significantly higher than those of controls (median, 3.6 vs 0.9 ng/ml; P < 0.001). Serum soluble SRA concentrations of patients were independently correlated with hematoma volume (ß, 0.201; 95 % confidence interval (CI), 0.093-0.309; P = 0.001), National Institutes of Health Stroke Scale (NIHSS) scores (ß, 0.118; 95 % CI, 0.024-0.213; P = 0.024), and 3-month modified Rankin Scale scores (ß, 0.148; 95 % CI, 0.063-0.232; P = 0.001). Serum soluble SRA concentrations independently predicted END and poor 3-month prognosis with odds ratio values of 1.394 (95 % CI, 1.024-1.899; P = 0.035) and 1.441 (95 % CI, 1.016-2.044; P = 0.040) respectively. Serum soluble SRA concentrations were efficiently predictive of the development of END (ROC AUC 0.746; 95 % CI, 0.631-0.861) and poor 3-month prognosis (AUC, 0.773; 95 % CI, 0.685-0.861). Serum soluble SRA concentrations significantly improved AUCs of NIHSS score and hematoma volume to 0.889 (95 % CI, 0.829-0.948; P = 0.035) and 0.873 (95 % CI, 0.811-0.936; P = 0.036) for prognostic prediction. The END predictive ability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.900; 95 % CI, 0.835-0.965) was significantly superior to those of NIHSS score (P = 0.020) and hematoma volume (P = 0.022). The prognostic predictive capability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.907; 95 % CI, 0.852-0.962) substantially exceeded those of NIHSS score (P = 0.009) and hematoma volume (P = 0.005). CONCLUSIONS: Serum soluble SRA concentrations may reflect illness severity and neurologic function after ICH, indicating serum soluble SRA may serve as a promising prognostic biochemical marker of ICH.
Assuntos
Hemorragia dos Gânglios da Base , Humanos , Prognóstico , Estudos Prospectivos , Hemorragia dos Gânglios da Base/diagnóstico , Hemorragia Cerebral , HematomaRESUMO
A palladium-catalyzed dearomative reaction of indoles has been developed through a domino Heck/gem-difluorovinylation sequence. By taking advantage of a difluorocarbene precursor (ClCF2COONa), the palladium difluorocarbene ([Pd][double bond, length as m-dash]CF2) species was formed smoothly. Then, a migratory insertion/ß-H elimination process enabled access to polycyclic indolines containing 1,1-difluoroethylene units in acceptable yields with a broad substrate scope, which also showed dearomative gem-difluorovinylation for the first time. Remarkably, the superb diversified transformations allowed the product to install various functional groups.
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OBJECTIVE: Intracerebral hemorrhage (ICH) triggers an inflammatory cascade that damages brain tissues and worsens functional outcome. S100A12 functions to promote brain inflammation. We aimed to investigate the relationship between serum S100A12 levels and functional outcome in ICH patients. METHODS: Serum S100A12 levels were measured in 101 ICH patients hospitalized within 24 h after symptom onset. Poor functional outcome was defined as a modified Rankin scale of 3 or greater at 3 months after stroke. Early neurologic deterioration was defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score or death at 24 hours from symptoms onset. RESULTS: High serum S100A12 levels were independently correlated with NIHSS score (t = 5.384, P < 0.001), hematoma volume (t = 4.221, P < 0.001) and serum C-reactive protein levels (t = 5.068, P < 0.001). Serum S100A12 levels were substantially higher in patients with a poor outcome (median, 66.5 versus 37.7 ng/mL; P < 0.001) or early neurological deterioration (median, 76.5 versus 40.1 ng/mL; P < 0.001) than in the other remainders, independently predicted a poor outcome (odds ratio, 1.035; 95% confidence interval, 1.007-1.064; P = 0.015) and early neurologic deterioration (odds ratio,1.032; 95% confidence interval, 1.003-1.060; P = 0.027), and significantly discriminated a poor outcome (area under curve, 0.794; 95% confidence interval, 0.702-0.868) and early neurologic deterioration (area under curve, 0.760; 95% confidence interval, 0.664-0.839) under receiver operating characteristic curve. CONCLUSION: High serum S100A12 levels at admission are highly associated with the extent of inflammatory response, severity, a poor functional outcome and early neurologic deterioration in ICH patients, substantializing serum S100A12 as a promising prognostic biomarker for ICH.
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OBJECTIVE: To determine the quantitive and functional changes of circulating endothelial progenitor cells (EPCs) in dogs with dehydromonocrotaline-induced pulmonary artery hypertension (PAH). METHODS: Dehydromonocrotaline was injected into the canine right ventricle to induce pulmonary hypertension. Circulating EPCs were enumerated as AC+(113), KDR+ cells by fluorescence-activated cell sorter using counting beads, and the number and activity of EPCs after in vitro expansion were determined by acLDL uptake/lectin staining assay and in vitro tubule forming assay. RESULTS: Nine of the 10 beagles survived after dehydromonocrotaline injection. Six weeks later, mean pulmonary artery pressure increased from (11.3 +/- 2.0) mm Hg (1 mm Hg = 0.133 kPa) to (20.2 +/- 1.6) mm Hg (t =10.307, P < 0.01), and the AC+(133) and KDR+ cells decreased from (632.8 +/- 42.8) cells/ml to (206.1 +/- 26.8) cells/ml (t = 25.361, P < 0.01). UEA- I and DiLDL positive cells deceased from (41 +/- 6) EPCs/ x 200 field to (22 +/- 6) EPCs/ x 200 field (t = 6.510, P < 0.01). In addition, in vasculogenesis assay, PAH EPCs formed less quantitative (11.2 +/- 2.8 vs 21.1 +/- 2.8 tubules/ x 200 field, respectively, t = 7. 583, P <0. 01) and less qualitive tubules than baseline EPCs. CONCLUSION: The number and vessel forming ability of EPCs are impaired in this canine model of dehydromonocrotaline-induced pulmonary hypertension.
Assuntos
Células Endoteliais/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Monocrotalina/análogos & derivados , Células-Tronco/efeitos dos fármacos , Animais , Contagem de Células , Células Cultivadas , Modelos Animais de Doenças , Cães , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Monocrotalina/efeitos adversos , Circulação PulmonarRESUMO
The aim of the present study was to construct a mathematical model to predict the changing trends of cardiac hypertrophy at gene level. Microarray data were downloaded from Gene Expression Omnibus database (accession, GSE21600), which included 35 samples harvested from the heart of Wistar rats on postoperative days 1 (D1 group), 6 (D6 group) and 42 (D42 group) following aorta ligation and sham operated Wistar rats, respectively. Each group contained six samples, with the exception of the samples harvested from the aorta ligated group after 6 days, where n=5. Differentially expressed genes (DEGs) were identified using a Limma package in R. Hierarchical clustering analysis was performed on common DEGs in order to construct a linear equation between the D1 and D42 groups, using linear discriminant analysis. Subsequent verification was performed using receiver operating characteristic (ROC) curve and the measurement data at day 42. A total of 319, 44 and 57 DEGs were detected in D1, D6 and D42 sample groups, respectively. AKIP1, ANKRD23, LTBP2, TGF-ß2 and TNFRSF12A were identified as common DEGs in all groups. The predicted linear equation between D1 and D42 group was calculated to be y=1.526×-186.671. Assessment of the ROC curve demonstrated that the area under the curve was 0.831, with a specificity and sensitivity of 0.8. As compared with the predictive and measurement data at day 42, the consistency of the two sets of data was 76.5%. In conclusion, the present model may contribute to the early prediction of changing trends in cardiac hypertrophy disease at gene level.