Determination of submaximal exercise tolerance in athletes using a method to predict cardiac patient conditions during rehabilitation.

Many professional athletes, after the end of their careers, cannot fully carry out daily social activities due to problems with health. The main problem is a significant rate of cardiovascular diseases. Therefore, the choice of rehabilitation techniques for former athletes is of primary importance. The aim of the paper is to create a model that increases the ability to predict both relapses and remissions during rehabilitation in cardiovascular diseases. The model takes into account the features of the cardiovascular function in athletes and their recovery. The article shows that the reliability of the implemented model can predict both necessary rehabilitation duration and time to complete recovery of an athlete's functional condition. The novelty of this study is that rehabilitation is based on the approximation of exercise load to the optimal levels during disease monitoring. The practical significance of the study is that during the rehabilitation of athletes, the obtained model to predict the course of the disease is aimed at the minimization of negative consequences for the athlete's cardiovascular system following professional activities. This model is recommended for use in medical prediction.

[Erythropoietin accelerates the proliferation of glioma cells via activating Akt pathway].

OBJECTIVE: To determine whether erythropoietin (EPO) promotes rapid proliferation of glioma through Akt pathway. METHODS: We detected the expression of EPO in human glioma tissues using immunohistochemistry. A nude mouse model bearing human glioma U87 cell xenograft was established and given intraperitoneal injection of EPO or saline every other day, and the tumor growth was observed. In the in vitro experiment, U87 cells were treated with PBS (control), EPO, or EPO with Akt inhibitor, and the expression of p-Akt and cyclin D1 was detected using Western blotting; the cell proliferation rate was determined using cell counting kit-8 and clone formation assay, and the cell cycle changes were analyzed with flow cytometry. RESULTS: Compared with low-grade glioma tissues, high-grade glioma tissues exhibited a significantly increased EPO expression (P=0.0002). In the tumor-bearing mice, EPO treatment significantly increased the expression of EPO (P=0.0006) and p-Akt (P=0.0003) in the tumor and obviously increased the tumor volume (P<0.0001) and weight (P=0.0003). In U87 cells cultured in vitro, EPO treatment obviously accelerated the cell proliferation (P=0.020 on day 3 and 0.028 on day 5), promoted clone formation (P=0.0010), and increased proliferation index (P=0.0028); EPO significantly enhanced the protein expression of p-Akt (P=0.0020) and cyclin D1 (P=0.0022). The application of Akt inhibitor significantly suppressed the effect of EPO in enhancing cyclin D1 and p-Akt expression (both P<0.0001) and promoting cell proliferation. CONCLUSION: EPO can significantly accelerate the proliferation of glioma through Akt pathway.

Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.

DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients. Overexpression of DACT2 in glioma cells inhibited proliferation, cell cycle and enhanced apoptosis, sensitivity to temozolomide in vitro and suppressed tumor growth in vivo. Whereas knockdown of DACT2 induce opposite reaction. Mechanistically, overexpression of DACT2 resulted in upregulation of important signaling molecules such as p-YAP and p-ß-catenin, and prevent YAP translocating into nucleus and sequestering in the cytoplasm to degrade. The study further proved that DACT2 can suppress YAP through Wnt/ß-catenin signaling pathway. Collectively, these data indicate that DACT2 has a tumor suppressor function via inactivation of YAP pathway, providing a promising target for the treatment of gliomas.

Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability.

Abnormally synchronized synaptic transmission in the brain leads to epilepsy. Neuroligin-1 (NL1) is a synaptic cell adhesion molecule localized at excitatory synapses. NL1 modulates synaptic transmission and determines the properties of neuronal networks in the mammalian central nervous system. We showed that the expression of NL1 and its binding partner neurexin-1ß was increased in temporal lobe epileptic foci in patients and lithium-pilocarpine-treated epileptic rats. We investigated electrophysiological and behavioral changes in epileptic rats after lentivirally mediated NL1 knockdown in the hippocampus to determine whether NL1 suppression prevented seizures and, if so, to explore the probable underlying mechanisms. Our behavioral studies revealed that NL1 knockdown in epileptic rats reduced seizure severity and increased seizure latency. Whole-cell patch-clamp recordings of CA1 pyramidal neurons in hippocampal slices from NL1 knockdown epileptic rats revealed a decrease in spontaneous action potential frequency and a decrease in miniature excitatory postsynaptic current (mEPSC) frequency but not amplitude. The amplitude of N-methyl-D-aspartate receptor (NMDAR)-dependent EPSCs was also selectively decreased. Notably, NL1 knockdown reduced total NMDAR1 expression and the surface/total ratio in the hippocampus of epileptic rats. Taken together, these data indicate that NL1 knockdown in epileptic rats may reduce the frequency and severity of seizures and suppress neuronal hyperexcitability via changes in postsynaptic NMDARs.