Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial ...function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.
Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are ...incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPK
flox/flox
mice with TekCre
+
or Cadh5Cre
+
mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2
+
T-cells, CD11b
+
F4/80
+
macrophages and Ly6G
−
Ly6C
+
monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment.
Young adults are susceptible to overweight and obesity and their adverse outcomes. However, limited studies have been conducted to understand this health problem in Vietnamese youths. This study was ...conducted to examine the rate of overweight and obesity, as well as the relationship between this condition on body perception, physical activity, and respiratory function among young adults in Hanoi, Vietnam. We performed a cross-sectional survey with 367 students aged 18-25 years at the Hanoi University of Pharmacy from June 2017 to June 2018. The result showed that the rate of overweight and obesity in our sample was 16.6%. There were 55.7% of overweight/obese students having the misperception of their body image. Results of multivariate regression analysis showed that overweight/obesity increased nearly three times (OR=2.8, 95% CI: 1.5-5.0) the ability to be active. Overweight/obese students with physical activity had a better respiratory function. To conclude, this study underlined the associations between overweight and obesity with physical activity, body image, and respiratory function in our young sample. Further longitudinal studies should be warranted to examine their causal relationships.
The characteristics and evolution of the solidification microstructure of a Fe-0.7C-22Mn (wt-%) TWIP steel was experimentally analysed. The primary dendrite arm space was about 1-2 mm while the ...diameter of equiaxed grains was about 2-4 mm. Decreasing the Mn concentration was proved beneficial to grains refinement and interdendrite soundness improvement. The tensile strength and yield strength of the concerning TWIP steel were found to be higher than that of C-Mn HSLA steel under as cast conditions above 1073 K, according to the comparison of hot tensile experiment results. It is inferred the solution strengthening effect should be the main explanation for that. The hot ductility of this TWIP steel was observed to be not very favourable, since most of the reduction rates of area were lower than 40%. Obvious drop of the hot ductility within the temperature range from 1073 to 1223 K of this Fe-0.7C-22Mn TWIP steel was determined. Intragranular MnS inclusions and grain boundaries sliding at elevated temperatures should be the main reason, according to the experimental results of optical microscope (OM), scanning electron microscope (SEM) and X-ray diffraction (XRD). Besides, both strength and ductility increased linearly as logarithmic strain rate increased, attributed to the combined effect of strain hardening, dynamic strain aging and dynamic recrystallisation.
A three-dimensional finite element model has been developed with heat, flow and solute transfer behaviour coupled calculation to predict shrinkage and macrosegregation defects in an as cast steel ...ingot. Solidification evolution and carbon segregation have been verified by previous investigations of a 3·3 t steel ingot. The heat transfer coefficient (HTC) at the ingot mould interface against temperature was researched by an inverse calculation method based on thermophysical parameters from microsegregation model and experimental temperatures. Good agreements were obtained both in range and variation trend of HTC compared with experimental results in references. Macrosegregation and shrinkage porosities were observed to accompany each other at the hot top of the rectangular ingot, which should be further investigated by numerical simulation. Applications of the model were extended to steel plants. The soundness and homogeneity of rolled blooms were both satisfied.
Aim
Assessment of lymph node (LN) involvement is of crucial importance in the estimation of prognosis and choice of therapeutic options for patients with colon cancer. The relationship between the ...radiological size of LNs and prognosis in node‐negative colon cancer remains uncertain. This study aims to investigate the prognostic impact of radiologically enlarged LNs on the survival of patients with node‐negative colon cancer.
Method
This retrospective study recruited 395 patients with Stages I and II colon cancer diagnosed between January 2012 and March 2016. Preoperative computed tomography was reviewed for the maximum short‐axis diameter of regional LNs, the optimal cutoff value of which was set to 8 mm. The prognostic relevance was analysed in Kaplan–Meier and multivariable Cox proportional hazard regressions.
Results
Patients with tumour in the left colon, TNM Stage II and 12 or more retrieved LNs tended to have radiologically enlarged LNs. Our results suggest that 3‐year recurrence‐free survival (RFS) and overall survival (OS) were significantly worse in patients with enlarged LNs than those without (RFS 82.8% vs 92.4%, P = 0.026; OS 87.1% vs 95.2%, P = 0.017), which was also confirmed in multivariable analysis RFS hazard ratio (HR) = 2.192, P = 0.018; OS HR = 3.305, P = 0.010. Subgroup analysis revealed that in patients with Stage II disease or at least 12 retrieved LNs, radiologically enlarged LN remained an independent predictor of poor RFS and OS.
Conclusion
The presence of radiologically enlarged LNs in patients with node‐negative colon cancer had an adverse prognosis.
HIV testing during pregnancy facilitates timely antiretroviral treatment for HIV-positive women. This study identifies reasons for late HIV testing among pregnant women delivering at a hospital in Ho ...Chi Minh City. We conducted a case–control study in which 160 cases were women who were tested for HIV late (i.e., at labor and delivery) and 160 controls were women who were tested during antenatal care (ANC). In multivariable logistic regression analysis, six variables were associated with late HIV testing: age less than 30 years, nine or fewer years of education, working as a homemaker or worker/farmer, living 20 km or more from the hospital, having received ANC at a private clinic/hospital only, and not believing that HIV testing is important during pregnancy. We recommend that national programs should provide additional effort for HIV testing during pregnancy to young women, less educated women, homemakers, and those receiving ANC at private clinics and hospitals.
Berberine is an isoquinoline alkaloid isolated from Chinese herbs such as Coptidis Rhizome. This paper is a systematic review of the structural modifications of berberine for different biological ...activities such as antitumor, antimicrobial, anti-Alzheimer's disease, antihyperglycemic, anti-inflammatory and antimalaria. The current review would provide some useful information for further studies on structural modification of berberine for discovering new drug leads.
Surface transverse cracking, especially corner cracking, is prone to generate in continuously cast slabs of microalloyed steels. The method of surface structure control (SSC) was supposed to the best ...way to avoid the detrimental defects. However, the mechanism of improving hot ductility by SSC and the specific parameters to control the process are still unclear for the reasonable adoption in production. In the present work, the impact of cooling rate, holding temperature and holding time on austenite decomposition, and the austenite grain size before and after intense cooling were investigated by thermal simulation method. With the increase of cooling rate, it is observed that the phase is transformed from austenite → grain boundary film-like alltromorph ferrite → Widmanstätten ferrite plates (or intragranular ferrite plates) → bainite+martensite. Mostly important, the film-like ferrite can be eliminated through intense cooling and the following reheating, but the austenite grain size is not observed to be refined through the single γ → α → γ cycle. Even though, the reduction of area (RA) is improved drastically to over 70% in the third ductility trough, whereas the RA value is just < 40% for the conventional cooling. The reason can be deduced by eliminating grain boundary film-like ferrite, and carbonitrides were precipitated inside the grain, which simultaneously act as the nucleus of intragranular ferrite. Thus, the principle of SSC process was established, and based on heat transfer calculation, water flow adjustment was put forward to implement the intense secondary cooling, which is a meaningful exploration for reducing transverse cracking.
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