Molecular mechanism of action of valproate acid alone or in combination with chlorpromazine in the epigenetic regulation of schizophrenia.

This study aimed to assess the molecular mechanism of the histone deacetylase inhibitor (HDACI) valproate acid (VPA) alone or in combination with the antipsychotic drug chlorpromazine in the epigenetic regulation of schizophrenia. A total of 60 perinatal CD-SD rats were divided in a control group (16 animals) and a schizophrenia model group (44 animals). For the schizophrenia model group the rats received phencyclidine (PCP) 10 mg/kg/day by intradermal injection on days 7, 9, and 11 after birth. The model was confirmed by the Morris water test in 40 rats. The control and model rats were divided into 7 groups. The Real Time PCR assay was used to detect the mRNA expression changes of GABA system gene [GABBR1 (GABA B receptor 1)], GAD1 (glutamic acid decarboxylase1), GAD2 (glutamic acid decarboxylase2), Lipase metabolic key enzyme LPL (lipoprotein lipase) gene, glutamate neurotransmitter gene GRIA2 (AMPA subtype glutamate receptors 2), inward rectifier potassium channel members KCNJ4 (potassium voltage-gated channel subfamily J member 4) and neuropeptide signal gene TAC1 (tachykinin precursor 1,TAC1) in four brain regions: the prefrontal cortex (PC), the amygdala (AM), the caudate-putamen (CPU) and the hippocampus (HIP). The platform arrival time of PMV and PMVC groups was significantly reduced compared to the PM group, the reduction being more significant in the PMV group. In the four brain regions of the epigenetic animal model of schizophrenia, the expression of GABBR1, GAD1, and GAD2 genes increased significantly. Following administration of HDACI VPA, the mRNA expression of this gene in the four brain regions decreased or approached normal levels. GABBR1 GAD1 and GAD2 are likely to be the target genes affected by the HDACI VPA.

Sleep disorders of acute thalamic stroke and its influence on plasma IL-17.

The aim of this study was to investigate the relationship between sleep disorders in acute thalamus stroke patients and plasma IL-17 levels and the mechanism through which inflammatory reactions develop in stroke. The study included two groups of patients: an experimental group consisting of 30 patients with thalamus stroke who received treatment at the Affiliated Hong Qi Hospital of Mu Dan Jiang Medical University during October 2015 to October 2016 and a control group consisting of 15 healthy volunteers. All the subjects included in the study were biochemically monitored for blood glucose, blood fats and IL-17 plasma levels. The sleep quality of all the subjects included in the study was evaluated [Epwort, Pittsburgh Sleep Quality Index (PSQI)] with 8-hour Polysonmography (PSG) monitoring. The experimental group was divided into 3 subgroups according to the part of the brain affected by stroke: anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group. The differences were analyzed between the experimental group and the control group in sleep quality scores, sleep structural changes, and plasma IL-17 levels. The differences in sleep structural scores were also analyzed according to different parts of the brain affected by stroke. The experimental group had a higher PSQI score compared with the control group, but this difference had no statistical significance (p>0.05). Compared with the control group, the N1 phase of the experimental group was longer while the N2 and N3 phases were shorter (p<0.05). There were no differences in sleep structure between the three regions of the brain affected by stroke (anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group) (p > 0.05). The plasma levels of IL-17 in the experimental group was higher compared to the control group (p<0.05). In the experimental group, the patients with hypersomnia had higher IL-17 levels than patients without hypersomnia (p<0.01). We can conclude that PSG can be used as an electrophysiology index for early detection of sleep disorders in thalamus stroke patients. Sleep disorders in patients with thalamus stroke persist a long time after the incident, therefore monitoring their sleep structure may become an important index to predict the prognosis of the disease. The increased level of IL-17 level in the experimental group shows its implication in appearance of sleep disorders of acute thalamus stroke through inflammatory mechanism.

[Biological evaluation of three-dimensional printed co-poly lactic acid/glycolic acid/tri-calcium phosphate scaffold for bone reconstruction].

Objective: To biologically evaluate the three-dimensional(3D) printed co-poly lactic acid/glycolic acid/tri-calcium phosphate(PLGA/TCP) scaffold which could be used for repairing oral and maxillofacial bone defects, and to provide experimental evidence for its further research and clinical application. Methods: PLGA/TCP scaffolds were fabricated using low temperature rapid prototyping technique. Micro-CT and scanning electron microscope(SEM) were used to characterize the surface morphology. MC3T3-E1 cells were seeded onto the scaffold and stained with the rhodamine phalloidin and calcein acetomethoxy. After that, confocal laser scanning microscope was exploited to observe the features and viability of the cells. Moreover, the cells were co-cultured with the extract of PLGA/TCP and complete medium, respectively. The proliferation capability of the cells was assessed by the cell counting kit-8 (CCK-8) on the 1st, 2nd, and 3rd day. The PLGA/TCP scaffolds incorporated with recombinant human bone morphogenetic protein-2(rhBMP-2) of 0, 30, 60 µg(i.e. blank control group, low-dose group and high-dose group) were implanted into the latissimus dorsi muscle of the rats, and 6 weeks later, the samples were harvested to estimate the volume and pattern of new bone. Results: The 3D printed PLGA/TCP scaffold possessed a regular and well-defined porous stereo-structure with porosity of (73±3)%. Micro-CT and SEM showed that pore size were (379±32) and (453±29) µm respectively, and distance between layers were (452± 24) and (415±25) µm, and cylinder diameter were (342±24) and (350±28) µm. It also exhibited excellent cell adhesion and growth ability on the exterior and inner surface through rhodamine phalloidin and calcein acetomethoxy staining. The CCK-8 test demonstrated that the absorbance value of extract group on the 1st and 2nd day(0.51±0.08 and 0.63±0.09) were significantly higher than those in the blank control group(0.39± 0.05 and 0.53±0.05)(P<0.05), while there was no significant difference between the extract group(0.67±0.06) and the blank control group(0.68±0.04)(P>0.05) on the 3rd day. For in vivo test, there was obvious ectopic new bone formation on the PLGA/TCP scaffold incorporated with rhBMP-2, and this was demonstrated using the histological examination and micro-CT. The bone formation in the low-dose group was similar to the shape of the pre-implanted 3D printed scaffold, while much diversity was revealed in the high-dose group duo to over osteogenesis which was validated by the examinations of gross observation, histology and micro-CT. Conclusions: Customized PLGA/TCP scaffolds can be manufactured by 3D printing technique. The scaffold showed an excellent biocompatibility and ectopic osteogenesis when incorporated with rhBMP-2. However, further research is needed to validate it's effect on repairment of the oral and maxillofacial bone defects.

Facile one-pot synthesis of multi-yolk-shell Bi@C nanostructures by the nanoscale Kirkendall effect.

Multi-yolk-shell Bi@C nanostructures were prepared via a facile one-pot template-free hydrothermal approach. The prepared Bi@C nanostructures can act as a solid catalyst in the thermal decomposition of cyclotrimethylenetrinitramine (RDX) and display excellent catalytic activity, which highlights their application in the field of energetic materials.