Ketamine exerts dual effects on the apoptosis of primary cultured hippocampal neurons from fetal rats in vitro.

Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 µM, 100 µM and 1000 µM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 µM, 2500 µM and 3000 µM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 µM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway.

Ultrasound-based radiomics model for predicting molecular biomarkers in breast cancer.

Background: Breast cancer (BC) is the most common cancer in women and is highly heterogeneous. BC can be classified into four molecular subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker protein Ki-67. However, they can only be obtained by biopsy or surgery, which is invasive. Radiomics can noninvasively predict molecular expression via extracting the image features. Nevertheless, there is a scarcity of data available regarding the prediction of molecular biomarker expression using ultrasound (US) images in BC. Objectives: To investigate the prediction performance of US radiomics for the assessment of molecular profiling in BC. Methods: A total of 342 patients with BC who underwent preoperative US examination between January 2013 and December 2021 were retrospectively included. They were confirmed by pathology and molecular subtype analysis of ER, PR, HER2 and Ki-67. The radiomics features were extracted and four molecular models were constructed through support vector machine (SVM). Pearson correlation coefficient heatmaps are employed to analyze the relationship between selected features and their predictive power on molecular expression. The receiver operating characteristic curve was used for the prediction performance of US radiomics in the assessment of molecular profiling. Results: 359 lesions with 129 ER- and 230 ER+, 163 PR- and 196 PR+, 265 HER2- and 94 HER2+, 114 Ki-67- and 245 Ki-67+ expression were included. 1314 features were extracted from each ultrasound image. And there was a significant difference of some specific radiomics features between the molecule positive and negative groups. Multiple features demonstrated significant association with molecular biomarkers. The area under curves (AUCs) were 0.917, 0.835, 0.771, and 0.896 in the training set, while 0.868, 0.811, 0.722, and 0.706 in the validation set to predict ER, PR, HER2, and Ki-67 expression respectively. Conclusion: Ultrasound-based radiomics provides a promising method for predicting molecular biomarker expression of ER, PR, HER2, and Ki-67 in BC.

Effects of Apelin on Left Ventricular-Arterial Coupling and Mechanical Efficiency in Rats with Ischemic Heart Failure.

Apelin plays important roles in cardiovascular homeostasis. However, its effects on the mechanoenergetics of heart failure (HF) are unavailable. We attempted to investigate the effects of apelin on the left ventricular-arterial coupling (VAC) and mechanical efficiency in rats with HF. HF was induced in rats by the ligation of the left coronary artery. The ischemic HF rats were treated with apelin or saline for 12 weeks. The sham-operated animals served as the control. The left ventricular (LV) afterload and the systolic and diastolic functions, as well as the mechanoenergetic indices were estimated from the pressure-volume loops. Myocardial fibrosis by Masson's trichrome staining, myocardial apoptosis by TUNEL, and collagen content in the aorta as well as media area in the aorta and the mesenteric arteries were determined. Our data indicated that HF rats manifested an increased arterial load (Ea), a declined systolic function (reduced ejection fraction, +dP/dtmax, end-systolic elastance, and stroke work), an abnormal diastolic function (elevated end-diastolic pressure, τ, and declined -dP/dtmax), and decreased mechanical efficiency. Apelin treatment improved those indices. Concomitantly, increased fibrosis in the LV myocardium and the aorta and enhanced apoptosis in the LV were partially restored by apelin treatment. A declined wall-to-lumen ratio in the mesenteric arteries of the untreated HF rats was further reduced in the apelin-treated group. We concluded that the rats with ischemic HF were characterized by deteriorated LV mechanoenergetics. Apelin improved mechanical efficiency, at least in part, due to the inhibiting cardiac fibrosis and apoptosis in the LV myocardium, reducing collagen deposition in the aorta and dilating the resistant artery.