The role of surface functionalization on the pulmonary inflammogenicity and translocation into mediastinal lymph nodes of graphene nanoplatelets in rats.

Graphene, a two-dimensional monocrystalline layer of carbon atoms, has potential in many applications not only in material sciences, but also in the biomedical fields, but there is little information about the role of surface modification on the toxicity of graphene-based nanomaterials. Here, we evaluated the role of surface functionalization of the graphene nanoplatelets (GNPs) on the pulmonary inflammogenicity and translocation into mediastinal lymph nodes using a rat intratracheal instillation model. Six types of GNPs were used: All types of GNPs were based on the pristine GNPs (GNPdot), and different functional groups were conjugated onto them including a COOH (GNPCOOH), COH [Formula: see text], N-H [Formula: see text], F x (GNPF), and N=H [Formula: see text]. All types of GNPs showed very high potential for the generation of reactive oxygen species (ROS) in a dose-dependent manner when measured by a 2'7'-dichlorofluorescin diacetate assay. GNPs were instilled into the lungs of rats at 0.3 and 1 mg/rat for the evaluation of acute (24 h) inflammation and at 3 mg/rat for chronic (1 and 4 weeks) inflammation. At 24 h after instillation, all types of GNPs showed good dose-dependent increases in polymorphonuclear leukocytes with a clear dose-dependency although significant increases compared to vehicle control were found only in positively charged GNPs [Formula: see text]. While the acute inflammation in all treatment groups was returned to control levels at 1 and 4 weeks after instillation, GNPs showed similar patterns of translocation into the mediastinal lymph nodes with a higher degree over time. This study implies that the main factors of GNPs for producing lung inflammation are the potential for ROS generation and surface charge. In addition, functional groups on the GNPs might not play an important role in the extrapulmonary translocation into the mediastinal lymph nodes.

Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors.

Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-mediated synaptic transmission. We observed marked decreases in NMDA receptor-mediated synaptic currents at afferent inputs to the amygdala of neuroligin-1 knockout mice. However, the knockout mice exhibited a significant impairment in spike-timing-dependent long-term potentiation (STD-LTP) at the thalamic but not the cortical inputs to the amygdala. Subsequent electrophysiological analyses indicated that STD-LTP in the cortical pathway is largely independent of activation of postsynaptic NMDA receptors. These findings suggest that neuroligin-1 can modulate, in a pathway-specific manner, synaptic plasticity in the amygdala circuits of adult animals, likely by regulating the abundance of postsynaptic NMDA receptors.

Hyperbaric oxygen (HBO) therapy as an effective approach to the treatment of patients with severe idiopathic sudden sensorineural hearing loss.

Background: The potential etiology of idiopathic sudden sensorineural hearing loss (ISSNHL) is cochlear ischemia, therefore, hyperbaric oxygen (HBO) therapy is a promising treatment, particularly in patients with severe hearing loss (≥70 dB).Aims/objectives: To evaluate the efficacy of HBO therapy.Material and methods: The medical records of patients diagnosed with ISSNHL were retrospectively reviewed (≥70 dB). Patients received HBO therapy 14 times in addition to systemic and intratympanic steroid therapy (HBO group), or systemic and intratympanic steroid therapy only (control group).Results: Data from a total of 82 patients (83 ears) were included in the analysis; 37 (38 ears) in the HBO group and 45 (45 ears) in the control group. After 2 weeks' treatment, hearing was significantly improved in the HBO group versus controls (weighted four-frequency average 28.1 ± 26.9 dB versus 14.8 ± 13.5 dB, respectively; p < .05), particularly in the low frequency groups (0.5 kHz, 1 kHz, 2 kHz; p < .05).Conclusion and significance: These data demonstrate that HBO therapy is an effective initial treatment option for patients with ISSNHL suffering from severe hearing loss.

Neuritin attenuates cognitive function impairments in tg2576 mouse model of Alzheimer's disease.

Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.

PPARdelta agonist-mediated ROS stimulates mouse embryonic stem cell proliferation through cooperation of p38 MAPK and Wnt/beta-catenin.

PPARdelta (peroxisome proliferator-activated receptor delta) is a member of the nuclear receptor superfamily. However, its function in tissues and cells is unknown, particularly as related to stem cell biology. We therefore investigated the PPARdelta effects on DNA synthesis in mouse embryonic stem cells (ES cells) and its related signal pathways. PPARdelta increased biphasic reactive oxygen species (ROS) production at 15 min and at 120 min incubation. PPARdelta significantly increased [(3)H] thymidine incorporation levels at various concentrations (10(-8) M to 10(-6) M) and incubation times (12 to 48 hr), and this activity was blocked by antioxidants. In addition, PPARdelta increased protein kinase C (PKC), cytosolic phospholipase A(2) (cPLA(2)) and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, and Wnt/beta-catenin activation. PPARdelta increased the protein levels of cell cycle regulators, and these levels were abolished by antioxidants, bisindolymaleimide I, SB203580 and beta-catenin specific siRNA. In addition, the effect of PPARdelta on increased [(3)H] thymidine incorporation was blocked by bisindolymaleimide I, SB203580 and beta-catenin specific siRNA. In conclusion, PPARdelta agonist enhanced mouse ES cells proliferation through ROS-mediated p38 MAPK and Wnt/beta-catenin activation.