A model is proposed here to explain how the chemical features of metal oxide varistors can alter their nonohmic physical behavior, based on nonohmic similarities in the electrical properties of ZnO- and SnO2-based varistors. The proposed model explains the electrical properties of ZnO- and SnO2-based varistors before and after thermal treatments in oxygen- and nitrogen-rich atmospheres, which cause similar changes in the nonohmic feature of these polycrystalline ceramics with greatly differing chemical compositions and microstructures. The model is based on the key role that oxygen plays in varistor grain boundaries, independently of the type of ceramic system (ZnO-, SnO2- or even SrTiO3-based varistors) involved.
Findings reveal a novel basis for protecting CNS neurons against Aβ oligomers (AβOs), neurotoxins believed to instigate neural damage leading to Alzheimer’s dementia. Results with spatially separated cocultures of astrocytes and hippocampal neurons show an exosome-like mechanism by which insulin/IGF1 from astrocytes clear bound AβOs from neuronal surfaces.
This article describes the admittance-frequency feature of a class of SnO 2 •CoO-based polycrystalline ceramics with high nonlinear current-voltage characteristics ͑nonlinear coefficients above 50͒. Broad relaxation peaks caused by the presence of deep trap states were characterized based on the admittance response of different systems doped with La 2 O 3 , Pr 2 O 3 , and CeO 2. The calculation of the energy of this deep trap level revealed not only that all the compositions share the same value but also that this value could be attributed to an oxygen vacancy or to Co Sn like defects. The values of barrier height and density of states obtained from a capacitance-voltage analysis are in good agreement with the nonlinear coefficients. The highest nonlinear coefficients are found in compositions with greater barrier height values and higher density of deep trap states at the grain boundary interface.
Graphical Abstract Highlights d CSF palmitate is increased in overweight or obese humans with cognitive impairment d CSF palmitate inversely correlates with cognitive performance in overweight humans d Palmitate impairs synaptic plasticity and memory in mice d Activated microglia and TNF-a mediate palmitate-induced impairments in memory In Brief Obesity has been associated with cognitive decline. Melo et al. show that palmitate levels are increased in the CSF of overweight and obese humans. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Microglial-derived TNF-a mediates the deleterious actions of palmitate in the brain.
Cardiovascular diseases are the number one cause of death globally and are projected to remain the single leading cause of death. Treatment options abounds, although efficacy is limited. Recent studies attribute discrete and ephemeral benefits to adult stem cell therapies, indicating the urge to improve stem cell based–therapy. In this study, we show that priming mesenchymal stem cells (MSC) towards cardiomyogenic lineage enhances their beneficial effects in vivo as treatment option for acute phase myocardial infarction. MSC were primed using cardiomyogenic media for 4 days, after which peak expression of key cardiomyogenic genes are reached and protein expression of Cx-43 and sarcomeric α-actinin are observed. MSC and primed MSC (pMSC) were characterized in vitro and used to treat infarcted rats immediately after left anterior descending (LAD) occlusion. Echocardiography analysis indicated that MSC-treated myocardium presented discrete improvement in function, but it also showed that pMSC treatment lead to superior beneficial results, compared with undifferentiated MSC. Seven days after cell injection, MSC and pMSC could still be detected in the myocardium. Connexin-43 expression was quantified through immunoblotting, and was superior in pMSC, indicating that this could be a possible explanation for the superior performance of pMSC therapy.
Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues (bone marrow, adipose tissue, and placenta) are potentially sources of stem cells. Placenta-derived stem cells (p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture (mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations (after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice.
Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investigated to improve heart function in toxic cardiomyopathy. This work aimed to assess early cardiac function improvement after treatments with either flavonoid extract from Camellia sinensis or mesenchymal stem cells in Dox cardiotoxicity using strain echocardiography. Twenty Wistar rats were randomly assigned to four groups. They received water (control, Dox, Dox + stem cells) or 100 mg/kg C. sinensis extract (Dox + C. sinensis) via gavage, daily, for four weeks. Animals also received saline (control) or 5 mg/kg doxorubicin (Dox, Dox + C. sinensis, Dox + stem cells) via intraperitoneal injection, weekly, for four weeks. Stem cells were injected (3 × 106 cells) through tail vein prior the beginning of the experiment (Dox + stem cells). Animals were evaluated by hematological, electrocardiography, echocardiography, and histopathological examinations. Dox cardiotoxicity was only diagnosed with strain echocardiography, detecting a decrease in ventricular function. C. sinensis extract did not prevent ventricular dysfunction induced by Dox. However, strain echocardiography examination revealed that Dox cardiotoxicity was significantly suppressed in rats treated with stem cells. In conclusion, strain echocardiography was able to detect precocity signs of heart failure and stem cell therapy showed cardioprotection effect against Dox cardiotoxicity.
In the search for new therapeutic agents for Chagas' disease, we screened extracts obtained from the Brazilian plant Pterodon pubescens found commercially in the medicinal flora market. We investigated the potential trypanocidal effect of the oleaginous ethanolic extract of P. pubescens seeds and its fractions (PF1, PF1.1, PF1.2, and PF1.3) and of geranylgeraniol (GG-OH), the sole component of the hexane fraction (PF1.2). In experiments with bloodstream trypomastigotes of Trypanosoma cruzi, performed at 37 degrees C in culture medium, PF1.2 and GG-OH showed similar potency, while the oleaginous extract from P. pubescens seeds and the other fractions were about three times less active. GG-OH inhibited the proliferation of intracellular amastigotes, at concentrations which do not affect the mammalian host cell. Transmission electron microscopy and flow cytometry analysis indicate the mitochondrion, an organelle that plays a central role in apoptosis, of both epimastigotes and of trypomastigotes as the major target of GG-OH. On the other hand, the ultrastructural images of the endoplasmic reticulum profiles, myelin-like figures, and concentric membranous arrangements inside damaged mitochondrion are suggestive of an autophagic pathway leading to parasite death. Because the different forms of cell death share some morphological features such as mitochondrial collapse, further studies are needed to disclose the trypanocidal action of GG-OH.
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