Goat anti Human PSEN1 (N-terminal, aa 14-33) polyclonal antibody

Notch signaling dysregulation plays an important role in altering cancer cell behaviors; however, its role in oral squamous cell carcinoma (OSCC) remains controversial. This study aimed to investigate the role of Notch signaling related genes in human OSCC using a meta-analysis of Gene Expression Omnibus database (GEO-publicly available gene expression microarray data) and to examine the role of Notch signaling in OSCC behaviors. The meta-analysis included 13 GEO datasets and was performed by combining effect sizes in a random effect model. The results demonstrated that in OSCC dysregulated genes participated in the metabolic process and protein binding as determined by gene ontology analysis. Enriched pathway analysis demonstrated the majority of the dysregulated genes were involved in pathway categories as follow; pathway in cancers, small cell lung cancer, extracellular matrix-receptor interaction, focal adhesion, and cell cycle progression. Interestingly, the enriched pathway analysis also demonstrated that OSCC samples exhibited an upregulation of genes in Notch signaling pathway, namely JAG1, JAG2, ADAM17, NCSTN, PSEN1, NCOR2, NUMB, DVL3, HDAC1, and HDAC2. Furthermore, Notch signaling inhibition by a gamma-secretase inhibitor significantly decreased OSCC cell proliferation in vitro, corresponding with a decrease in C-FOS mRNA expression. The study demonstrated that Notch signaling is dysregulated in human OSCC and plays a role in cell proliferation.

Space radiation represents a significant health risk for astronauts. Ground-based animal studies indicate that space radiation affects neuronal functions such as excitability, synaptic transmission, and plasticity, and it may accelerate the onset of Alzheimer's disease (AD). Although protons represent the main constituent in the space radiation spectrum, their effects on AD-related pathology have not been tested. We irradiated 3 month-old APP/PSEN1 transgenic (TG) and wild type (WT) mice with protons (150 MeV; 0.1-1.0 Gy; whole body) and evaluated functional and biochemical hallmarks of AD. We performed behavioral tests in the water maze (WM) before irradiation and in the WM and Barnes maze at 3 and 6 months post-irradiation to evaluate spatial learning and memory. We also performed electrophysiological recordings in vitro in hippocampal slices prepared 6 and 9 months post irradiation to evaluate excitatory synaptic transmission and plasticity. Next, we evaluated amyloid 3 (A(3) deposition in the contralateral hippocampus and adjacent cortex using immunohistochemistry. In cortical homogenates, we analyzed the levels of the presynaptic marker synaptophysin by Western blotting and measured pro-inflammatory cytokine levels (INF alpha, IL-beta, IL-6, CXCL10 and CCL2) by bead-based multiplex assay. TG mice performed significantly worse than WT mice in the WM. Irradiation of TG mice did not affect their behavioral performance, but reduced the amplitudes of population spikes and inhibited paired-pulse facilitation in CA1 neurons. These electrophysiological alterations in the TG mice were qualitatively different from those observed in WT mice, in which irradiation increased excitability and synaptic efficacy. Irradiation increased A beta deposition in the cortex of TG mice without affecting cytokine levels and increased synaptophysin expression in WT mice (but not in the TG mice). Although irradiation with protons increased A beta deposition, the complex functional and biochemical results indicate that irradiation effects are not synergistic to AD pathology.