Induction of thoracic aortic dissection: a mini-review of ß-aminopropionitrile-related mouse models.

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using ß-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.

Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis.

OBJECTIVE: The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients. METHODS: Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality. RESULTS: Our statistics revealed that only h-FABP independently predicted SIMD (P<0.05). The addition of MPO and cTnI to h-FABP for SIMD prediction provided an NRI of 18.7% (P=0.025) and IDI of 3.3% (P=0.033). However, the addition of MPO or cTnI to h-FABP did not significantly improve the predictive ability of h-FABP to SIMD, as evidenced by the area under the curve (AUC), NRI, and IDI (all P>0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P<0.05). The addition of PAPP-A and h-FABP to MPO resulted in a mortality prediction with NRI of 25.5% (P=0.013) and IDI of 2.9% (P=0.045). However, this study revealed that the addition of h-FABP or PAPP-A to MPO did not significantly improve the ability to predict mortality, as evidenced by the AUC, NRI, and IDI (all P>0.05). CONCLUSIONS: The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.

Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis.

Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT+/+) and hepatocyte-specific AGT-deficient mice (hepAGT-/-) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT+/+ mice, Western diet-fed hepAGT-/- mice gained less body weight with improved insulin sensitivity. The attenuated severity of liver steatosis in hepAGT-/- mice was evidenced by histologic changes and reduced intrahepatic triglycerides. The abundance of SREBP1 and its downstream molecules, acetyl-CoA carboxylase and FASN, was suppressed in hepAGT-/- mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by protein kinase B (Akt)/mammalian target of rapamycin (mTOR) inhibition in vitro. Administration of losartan did not affect diet-induced body weight gain, liver steatosis severity, and hepatic p-Akt, p-mTOR, and SREBP1 protein abundance in hepAGT+/+ mice. These data suggest that attenuation of Western diet-induced liver steatosis in hepAGT-/- mice is associated with the alternation of the Akt/mTOR/SREBP-1c pathway.

Attitude and Intention Regarding Pain Management among Chinese Nursing Students: A Cross-Sectional Questionnaire Survey.

Optimal pain management is a priority in effective nursing care. Lack of sufficient pain knowledge associated with inadequate pain management has been proved. However, the intention, defined as the predictor of behavior, regarding pain management remains unknown. Therefore, the study was to determine the attitude and intention regarding pain management among Chinese nursing students and investigate the underlying determinants and their interactions in terms of intention toward pain management. The Pain Management Survey Questionnaire, comprising the key determinants of the theory of planned behavior-that is, direct attitude, belief-based intention, subjective norm, direct control, and indirect control-was used to collect data from 512 nursing students who undertook clinical rotation in an affiliated hospital of a medical college in China. Data were analyzed using descriptive statistics, independent sample t test, Pearson correlation analysis, or structural equation modeling analysis. Chinese nursing students reported negative attitudes and behavioral intentions toward pain management. Direct control, subjective norm, belief-based attitude, and indirect control independently predicted nursing students' intention to treat patients with pain. Direct control was the strongest predictor. Structural equation modeling analysis further revealed 39.84% of the variance associated with intention that could be explained by determinants of the theory of planned behavior. Additionally, educational school level and previous pain management training had great effects on pain management intention. Overall, this study identified intention as an important factor in effective pain treatment. Chinese nursing students have negative attitudes and insufficient intention to pain management. Therefore, hospitals and universities in China should manage these factors to improve nursing students' practice regarding pain management.

Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation.

OBJECTIVE: Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation. METHODS: MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson's trichrome staining, respectively. RESULTS: Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group. CONCLUSIONS: Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.