Interactions between Brain-Derived Neurotrophic Factor and Endocannabinoids at Neocortical Inhibitory Synapses

Archival abstract submitte

Relationship between Corrosion of Reinforcement and Surface Cracking Width in Concrete

The durability of structure cannot be guaranteed when a corrosion expansion crack reaches the surface of the reinforced concrete member. In this paper, firstly, based on the existing theoretical model of steel corrosion degree, the calculation process of the model and the determination of the relevant parameters in the model were analyzed and discussed. Secondly, the stiffness reduction factor of concrete in the model was calculated according to the existing experimental data, and the engineering formula of the steel corrosion degree was established, which was related to the surface crack width of reinforced concrete. Moreover, the experiments of steel bar corrosion were carried out with different components of surface crack width, in which the parameters of the bar diameter, concrete protection layer thickness, and water-cement ratio were taken into consideration. The experimental phenomena and results were further analyzed and discussed. Finally, comparing with the experimental data, the engineering formula presented in the paper was validated. The results show that the calculated values by the engineering formula are in better agreement with the experimental values than those by the existing model, which provide a theoretical basis for further study on the durability limit state of the structure

Role for Endogenous BDNF in Endocannabinoid-Mediated Long-Term Depression at Neocortical Inhibitory Synapses

The endogenous cannabinoid (endocannabinoid) system is an important regulator of synaptic function. Endocannabinoids acutely modulate inhibitory and excitatory transmission, and also mediate long-term depression at GABAergic and glutamatergic synapses. Typically, endocannabinoid synthesis and release is stimulated by depolarization-induced calcium influx and/or activation of phospholipase-C (PLC) signaling triggered by mGluR activation. Recently it has been shown that brain-derived neurotrophic factor (BDNF) can also induce endocannabinoid release. Although there is growing evidence for cross-talk between BDNF and endocannabinoid signaling, little is known about the functional relevance of these interactions. In the present studies, we examined BDNF – endocannabinoid interactions in regulating activity-dependent long-term depression at inhibitory synapses (iLTD). We found that theta burst stimulation (TBS) in layer 2/3 of mouse somatosensory cortical slices can induce a form of endocannabinoid-mediated iLTD that is independent of metabotropic glutamate receptor (mGluR) activation. This endocannabinoid-dependent iLTD, however, requires endogenous BDNF-trkB signaling, as it is blocked by a trk tyrosine kinase inhibitor and by a trkB receptor antagonist, and also requires activation of diacylglycerol lipase (DAG-lipase, DGL). In addition, endocannabinoid-mediated iLTD can be induced by combining a subthreshold concentration of exogenous BDNF with weak TBS stimulation that by itself is insufficient to induce iLTD. Taken together, our results suggest that TBS can induce the release of endogenous BDNF, which triggers DGL-dependent endocannabinoid mobilization and cannabinoid receptor-dependent iLTD at layer 2/3 cortical synapse

A Study of 358 Cases of Locally Advanced Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiation Therapy: Improving the Seventh Edition of the American Joint Committee on Cancer T-Staging System

To evaluate the rationality and limitations of the seventh edition of the American Joint Committee on Cancer (the 7th AJCC edition) T-staging system for locally advanced nasopharyngeal carcinoma (NPC). The prognosis of 358 patients with stage T3/T4 NPC treated with intensity-modulated radiotherapy (IMRT) was analyzed with the Kaplan–Meier method or the log-rank test. The 7th AJCC staging system of NPC has some limitations in that the T category is neither the significant factor in OS/LRFS nor the independent prognostic factor in OS/LRFS/DMFS/DFS (P>0.05). After adjustment by anatomic structures, univariate analysis has shown that the adjusted-T category has statistical significance between T3 and T4 for OS (86.4% and 71.3%, P=0.002), LRFS (97% and 90.9%, P=0.048), DMFS (90.9% and 77.2%, P=0.001), and DFS (86.2% and 67.5%, P=0.000), and multivariate analysis has shown that the adjusted-T category is an independent prognostic factor for OS/DMFS/DFS (with the exception of LRFS). Then, GTV-P was taken into consideration. Multivariate analysis showed that these nT categories serve as suitable independent prognostic factors for OS/DMFS/DFS (P<0.001) and LRFS (HR = 3.131; 95% CI, 1.090–8.990; P=0.043). The 7th AJCC staging system has limitations and should be improved by including the modifications suggested, such as anatomic structures and tumor volume adjustment

Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

<p>Abstract</p> <p>Background</p> <p>Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both <it>in vitro </it>and <it>in vivo</it>. Previous studies have shown that mice lacking Kal7 (Kal7^KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.</p> <p>Results</p> <p>We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a <b>NMDA receptor-independent </b>form of LTP is shown to be normal in the absence of Kal7.</p> <p>Conclusions</p> <p>These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.</p

Lactobacillus rhamnosus GG ameliorates radiation-induced lung fibrosis via lncRNASNHG17/PTBP1/NICD axis modulation

Abstract Radiation-induced pulmonary fibrosis (RIPF) is a major side effect experienced for patients with thoracic cancers after radiotherapy. RIPF is poor prognosis and limited therapeutic options available in clinic. Lactobacillus rhamnosus GG (LGG) is advantaged and widely used for health promotion. However. Whether LGG is applicable for prevention of RIPF and relative underlying mechanism is poorly understood. Here, we reported a unique comprehensive analysis of the impact of LGG and its’ derived lncRNA SNHG17 on radiation-induced epithelial–mesenchymal transition (EMT) in vitro and RIPF in vivo. As revealed by high-throughput sequencing, SNHG17 expression was decreased by LGG treatment in A549 cells post radiation and markedly attenuated the radiation-induced EMT progression (p < 0.01). SNHG17 overexpression correlated with poor overall survival in patients with lung cancer. Mechanistically, SNHG17 can stabilize PTBP1 expression through binding to its 3′UTR, whereas the activated PTBP1 can bind with the NICD part of Notch1 to upregulate Notch1 expression and aggravated EMT and lung fibrosis post radiation. However, SNHG17 knockdown inhibited PTBP1 and Notch1 expression and produced the opposite results. Notably, A549 cells treated with LGG also promoted cell apoptosis and increased cell G2/M arrest post radiation. Mice of RIPF treated with LGG decreased SNHG17 expression and attenuated lung fibrosis. Altogether, these data reveal that modulation of radiation-induced EMT and lung fibrosis by treatment with LGG associates with a decrease in SNHG17 expression and the inhibition of SNHG17/PTBP1/Nothch1 axis. Collectively, our results indicate that LGG exerts protective effects in RIPF and SNHG17 holds a potential marker of RIPF recovery in patients with thoracic cancers

High expression of PKM2 as a poor prognosis indicator is associated with radiation resistance in cervical cancer

Our study aimed to investigate the association of Pyruvate Kinase isozyme type M2 (PKM2) with radiation resistance in locally advanced cervical squamous cell carcinoma (LACSCC). We retros-pectively reviewed 132 female patients who received primary radiation therapy to treat LACSCC at Federation Internationale of Gynecologie and Obstetrigue（FIGO）stages IB-IVA. Forty-seven patients with progression free survival (PFS) of less than 36 months were regarded to have radiation resistance. Eighty-five patients with PFS no less than 36 months were regarded as radiation sensitive. Using immunohistochemistry, we found that the overexpression rate of PKM2 in radiation resistant and radiation sensitive patients was 87.2% and 57.6%, respectively, and the difference was statistically significant (p＜0.001). The 5-year progress free survival rates in patients with low and high expression of PKM2 was 80.4% and 60.5%, respectively, and the difference was statistically significant (p=0.008). Multivariate Cox regression analysis identified that high expression of PKM2 is an independent negative prognostic factor in cervical cancer patients [Hazard ratio (95% CI), 2.888 (1.347, 6.194) p=0.006]. These results demonstrate that overexpression of PKM2 contributes to radiation resistance and acts a poor prognosis indicator in patients with LACSCC

Integration and Long Distance Axonal Regeneration in the Central Nervous System from Transplanted Primitive Neural Stem Cells*

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI