The blood–brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability.
Women are at increased risk of developing post-traumatic stress disorder (PTSD) following a traumatic event. Recent studies suggest that this may be mediated, in part, by circulating estrogen levels. This study evaluated the hypothesis that individual variation in response to estrogen levels contributes to fear regulation and PTSD risk in women. We evaluated DNA methylation from blood of female participants in the Grady Trauma Project and found that serum estradiol levels associates with DNA methylation across the genome. For genes expressed in blood, we examined the association between each CpG site and PTSD diagnosis using linear models that adjusted for cell proportions and age. After multiple test correction, PTSD associated with methylation of CpG sites in the HDAC4 gene, which encodes histone deacetylase 4, and is involved in long-term memory formation and behavior. DNA methylation of HDAC4 CpG sites were tagged by a nearby single nucleotide polymorphism (rs7570903), which also associated with HDAC4 expression, fear-potentiated startle and resting state functional connectivity of the amygdala in traumatized humans. Using auditory Pavlovian fear conditioning in a rodent model, we examined the regulation of Hdac4 in the amygdala of ovariectomized (OVX) female mice. Hdac4 mRNA levels were higher in the amygdala 2h after tone-shock presentations, compared to OVX-homecage control females. In naturally cycling females, tone-shock presentations increased Hdac4 expression relative to homecage controls for metestrous (low estrogen) but not the proestrous (high estrogen) group. Together, these results support an estrogenic influence of HDAC4 regulation and expression that may contribute to PTSD in women.
We present the study of a sample of seven "bare" active galactic nuclei (AGN) observed with Suzaku. We interpret the spectrum of these sources with a relativistic reflection component and we employ our model relxill nk to test the Kerr nature of their supermassive black holes. We constrain the Johannsen deformation parameters α13 and α22, in which the Kerr metric is recovered when α13 = α22 = 0. All our measurements are consistent with the hypothesis that the spacetime geometry around these supermassive objects is described by the Kerr solution. For some sources, we obtain quite strong constraints on α13 and α22 when compared to those found in our previous studies. We discuss the systematic uncertainties in our tests and the implications of our results.
The nanohybrid of electrochemically-reduced graphene oxide (ERGO) nanosheets decorated with MnO2 nanorods (MnO2 NRs) was modified on the surface of a glassy carbon electrode (GCE). Controlled potential reduction was applied for the reduction of graphene oxide (GO). The characterization was performed by scanning electron microscopy, X-ray diffraction and cyclic voltammetry. Compared with the poor electrochemical response at bare GCE, a well-defined oxidation peak of sunset yellow (SY) was observed at the MnO2 NRs-ERGO/GCE, which was attributed to the high accumulation efficiency as well as considerable electrocatalytic activity of ERGO and MnO2 NRs on the electrode surface. The experimental parameters for SY detection were optimized in detail. Under the optimized experiment conditions, the MnO2 NRs-ERGO/GCE showed good linear response to SY in concentration range of 0.01–2.0 μM, 2.0–10.0 μM and 10.0–100.0 μM with a detection limit of 2.0 nM. This developed method was applied for SY detection in soft drinks with satisfied detected results.
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