Baicalin Attenuates Oxygen–Glucose Deprivation/Reoxygenation–Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron–Astrocyte Cocultures

Background: Baicalin (BCL), a candidate drug for ischemic stroke, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF). However, the cellular source of BDNF release promoted by baicalin and its detailed protective mechanism after ischemia/reperfusion remains to be studied. The aim of this study was to investigate the neuroprotective mechanisms of baicalin against oxygen–glucose deprivation/reoxygenation (OGD/R) in a neuron–astrocyte coculture system and to explore whether the BDNF-TrkB pathway is involved.Methods and Results: A neuron–astrocyte coculture system was established to elucidate the role of astrocytes in neurons under OGD/R conditions. The results demonstrated that astrocytes became reactive astrocytes and released more BDNF in the coculture system to attenuate neuronal apoptosis and injury after OGD/R. BCL maintained the characteristics of reactive astrocytes and obviously increased the expression of cyclic AMP response element-binding protein (CREB) and the levels of BDNF in the coculture system after OGD/R. To further verify whether BDNF binding to its receptor tyrosine kinase receptor B (TrkB) was required for the neuroprotective effect of baicalin, we examined the effect of ANA-12, an antagonist of TrkB, on NA system injury, including oxidative stress, inflammation, and apoptosis induced by OGD/R. The results showed that treatment of NA systems with ANA-12 significantly attenuated the neuroprotection of BCL. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways are two important downstream cascades of signaling pathways activated by BDNF binding to TrkB. We investigated the expressions of TrkB, PI3K, Akt, MAPK, and ERK. The results demonstrated that baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK.Conclusion: The neuroprotective effects of baicalin against oxidative stress, inflammation, and apoptosis were improved by astrocytes, mainly mediated by increasing the release of BDNF and its associated receptor TrkB and downstream signaling regulators PI3K/Akt and MAPK/ERK1/2

Friction Coefficient Compensation Control in Synchronizer Synchronization Process for Transmission

In the synchronization process of a synchronizer, the friction coefficient of the friction cone is changed because of friction heat. In this paper, the influence of a changing friction coefficient on shift quality was analyzed. The quantitative relationship between friction coefficient and its influencing factors was studied through a synchronizer synchronization process test bench. Based on the quantitative analysis and an optimal shift force control method, a compensation control strategy for friction coefficient was established. Moreover, the effectiveness of the compensation control was verified through simulation and experiment. The results showed that the friction coefficient was maintained near the expected value of 0.08 after the compensation control, the shifting speed difference the synchronous time was shortened by nearly 0.12 s, and the sliding friction was reduced by 4.64 J under the experimental conditions. The analysis and compensation of the friction coefficient provide a theoretical reference for improving shift quality

Altered myelination in the Niemann-Pick type C1 mutant mouse

Niemann–Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by mutation of Npc1 or Npc2 gene, resulting in various progressive pathological features. Myelin defection is a major pathological problem in Npc1 mutant mice; however, impairment of myelin proteins in the developing brain is still incompletely understood. In this study, we showed that the expression of myelin genes and proteins is strongly inhibited from postnatal day 35 onwards including reduced myelin basic protein (MBP) expression in the brain. Furthermore, myelination characterized by MBP immunohistochemistry was strongly perturbed in the forebrain, moderately in the midbrain and cerebellum, and slightly in the hindbrain. Our results demonstrate that mutation of the Npc1 gene is sufficient to cause severe and progressive defects in myelination in the mouse brain

Proinsulin-Transferrin Fusion Protein as a Novel Long-Acting Insulin Analog for the Inhibition of Hepatic Glucose Production

Diplomski rad pod nazivom Disocijacija nastao je kao reakcija i vizualizacija normativnih disocijativnih stanja koja su dio naše svakodnevice. Izveden je u obliku 12 crteža olovkom koji čine jednu cjelinu. Crteži su vizualni zapisi emocija i disocijativnih stanja u kojima sam se nalazila tijekom crtanja. Oni su ustvari vizualizacija sanjarenja i maštanja, ali ne u doslovnom smislu već metaforičkom. Glavni motiv na njima su životinje koje svojom gestikulacijom, položajem tijela i smještajem u kompoziciji prikazuju emocije, likove ili situacije u kojima sam se našla u svojim mislima

Friction Characteristics of Synchronization Process Based on Tribo-Thermodynamics

In order to improve the shift control accuracy and shift quality, the temperature and friction coefficient changing regularities of a friction cone during the synchronization process were investigated. The thermal-structural coupling model was established through tribo-thermodynamic analysis. The relevant experiment was carried out as well. The results show that the error between the experimental and simulated results is within 3%. Besides, the maximum temperature of the synchronous ring friction surface increases 1.8°C for every additional 50 N of shift force, while increases 1.1°C for every additional 200  r/min shift speed difference. Moreover, the friction coefficient declines rapidly first and then tends to be stable slowly during the synchronization process. The result of friction coefficient changing regularity lays a good theoretical basis for establishing an effective friction coefficient compensation control strategy

Simvastatin Modulates Remodeling of Kv4.3 Expression in Rat Hypertrophied Cardiomyocytes

<p><b>Objectives:</b> Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.</p><p><b>Methods: </b>Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs) underwent abdominal aortic banding (AAB) for 7 weeks and angiotensin II (AngII) treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial) in the left ventricle was measured. The transient outward potassium current (<i>I</i>_to) of NRVMs was recorded using a whole-cell patch-clamp method.</p><p><b>Results:</b> Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial) in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the <i>I</i>_to current and this effect was partially reversed by simvastatin.</p><p><b>Conclusions:</b> Simvastatin alleviated the reduction of Kv4.3 expression, <i>I</i>_to currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.</p