Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B-/- mouse model of ASD. Male and female Shank3B-/- mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions

Molecular Response and Cooperative Behavior during the Interactions of Melittin with a Membrane: Dissipative Quartz Crystal Microbalance Experiments and Simulations

The molecular-level interactions of an antimicrobial peptide melittin with supported membrane were studied by the combination of dissipative quartz crystal microbalance (QCM-D) experiments and computer simulations. We found the response behavior of lipids upon peptide adsorption greatly influence their interactions. The perturbance and reorientation of the lipid in liquid phase facilitate the insertion of melittin in a trans-membrane way, but in solid phase, asymmetrical membrane disruption happens. Apart from the lipid state, the local peptide-to-lipid ratio also affects the insertion capacity of melittin. When the local peptide number density is high, adjacent peptides can cooperatively penetrate into the membrane. This observation explains the occurrence of the conventional “carpet” mechanism

Therapeutic Efficiency of Nasal Mucosa-Derived Ectodermal Mesenchymal Stem Cells in Rats with Acute Hepatic Failure

Background. Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods. EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl4-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results. EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver’s microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions. These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering

Tunable dual-stimuli response of a microgel composite consisting of reduced graphene oxide nanoparticles and poly(N-isopropylacrylamide) hydrogel microspheres

A type of photo- and thermo-responsive composite microsphere composed of reduced graphene oxide nanoparticles and poly(N-isopropylacrylamide) (rGO@pNIPAM) is successfully fabricated by a facile solution mixing method. Due to the high optical absorbance and thermal conduction of rGO, the composite microspheres are endowed with the new property of photo-response, in addition to the intrinsic thermally sensitive property of pNIPAM. This new ability undoubtedly enlarges the scope of applications of the microgel spheres. Furthermore, through controlling the rGO content in the composite, the photo- and thermo-sensitivity of the composite can be effectively modulated. That is, with a lower rGO content (≤32% by weight), the composite microspheres perform only thermally induced changes, such as volume contraction (by ∼45% in diameter) and drug release, when crossing the lower critical solution temperature of pNIPAM. With a higher rGO content (∼47.5%), both temperature and light irradiation can trigger changes in the composite. However, when the rGO content is increased to around 64.5%, the thermo-responsivity of the composite disappears, and the spheres exhibit only photo-induced drug release. With a further increase in rGO content, the environmentally responsive ability of the microspheres vanishes. This journal is © the Partner Organisations 2014

Preventive Effect of <i>Arctium lappa</i> Polysaccharides on Acute Lung Injury through Anti-Inflammatory and Antioxidant Activities

The objective of this study was to investigate the preventive effects of polysaccharides extracted from the roots of Arctium lappa (ALP) against acute lung injury (ALI) models induced by lipopolysaccharide (LPS). The polysaccharides were extracted and characterized, and their anti-inflammatory and antioxidant capacities were assessed. The findings demonstrated that ALP could mitigate the infiltration of inflammatory cells and reduce alveolar collapse in LPS-induced ALI in mice. The expression levels of the pro-inflammatory factor TNF-α decreased, while the anti-inflammatory factor IL-10 increased. Furthermore, the administration of ALP improved the activities of lung antioxidant enzymes, including SOD, GSH, and CAT, and lowered MDA levels. These results suggest that ALP exhibits a preventive effect on ALI and has potential as an alternative treatment for lung injury