We have previously shown that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the "endocannabinoid-like" substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently de-orphanized receptor, which is currently being investigated as a promising anti-diabetic drug target. Thus, in the current study, we investigated the effects of OEA as well as the expression and role of GPR119 in human sebocytes. Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for transforming growth factor-β (TGF-β) signaling, and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in anti-tumor activity. Endoglin was overexpressed in angiosarcoma and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and VE cadherin phosphorylation and MMP-2 and MMP-9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-β signaling, the anti-tumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation, but on non-Smad TGF-β signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma. The 21-aminosteroid ("lazaroid") U-74389G (U74), an inhibitor of lipid peroxidation (LP), was used to protect mitochondrial function following TBI in young adult male rats. The animals received a severe (2.2 mm) controlled cortical impact-TBI. U74 was administered intravenous at 15 min and 2 h post injury (hpi) followed by intraperitoneal dose at 8 hpi at the following doses (mg/kg) 0.3 (IV) + 1 (IP), 1 + 3, 3 + 10, 10 + 30. Total cortical mitochondria were isolated at 72 hpi and respiratory rates were measured. Mitochondrial 4-HNE and acrolein were evaluated as indicators of LP-mediated oxidative damage. At 72 h post-TBI injured animals had significantly lower mitochondrial respiration rates compared to sham. Administration of U74 at the 1 mg/kg dosing paradigm significantly improved mitochondrial respiration rates for States II, III, V(II) and RCR compared to vehicle-treated animals. At 72 h post-TBI injured animals administration of U74 also reduced reactive aldehydes levels compared to vehicle-treated animals. The aim of this study was to explore the hypothesis that interrupting secondary oxidative damage via acute pharmacological inhibition of LP by U74 following a CCI-TBI would provide mitochondrial neuroprotective effects in a dose-dependent manner. We found acute administration of U74 to injured rats resulted in improved mitochondrial function and lowered the levels of reactive aldehydes in the mitochondria.  https://www.selleckchem.com/products/zebularine.html  These results establish not only the most effective dose of U74 treatment to attenuate LP-mediated oxidative damage, but also set the foundation for further studies to explore additional neuroprotective effects following TBI. OBJECTIVE The aim of the study was to evaluate electrophysiological effects of safinamide on the intrinsic and synaptic properties of striatal spiny projection neurons (SPNs) and to characterize the possible therapeutic antiparkinsonian effect of this drug in dopamine (DA) denervated rats before and during levodopa (l-DOPA) treatment. BACKGROUND Current therapeutic options in Parkinson's disease (PD) are primarily DA replacement strategies that usually cause progressive motor fluctuations and l-DOPA-induced dyskinesia (LIDs) as a consequence of SPNs glutamate-induced hyperactivity. As a reversible and use-dependent inhibitor of voltage-gated sodium channels, safinamide reduces the release of glutamate and possibly optimize the effect of l-DOPA therapy in PD. METHODS Electrophysiological effects of safinamide (1-100 μM) were investigated by patch-clamp recordings in striatal slices of naïve, 6-hydroxydopamine (6-OHDA)-lesioned DA-denervated rats and DA-denervated animals chronically treated with l-DOPA. LIDs were assessed in vivo with and without chronic safinamide treatment and measured by scoring the l-DOPA-induced abnormal involuntary movements (AIMs). Motor deficit was evaluated with the stepping test. RESULTS Safinamide reduced the SPNs firing rate and glutamatergic synaptic transmission in all groups, showing a dose-dependent effect with half maximal inhibitory concentration (IC50) values in the therapeutic range (3-5 μM). Chronic co-administration of safinamide plus l-DOPA in DA-denervated animals favored the recovery of corticostriatal long-term synaptic potentiation (LTP) and depotentiation of excitatory synaptic transmission also reducing motor deficits before the onset of LIDs. CONCLUSIONS Safinamide, at a clinically relevant dose, optimizes the effect of l-DOPA therapy in experimental PD reducing SPNs excitability and modulating synaptic transmission. Co-administration of safinamide and l-DOPA ameliorates motor deficits. Gastrin-releasing peptide (GRP) receptor-expressing (GRPR)+ neurons have a central role in the spinal transmission of itch. Because their fundamental regulatory mechanisms are not yet understood, it is important to determine how such neurons are excited and integrate itch sensation. In this study, we investigated the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH). GRPR+ neurons expressed the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) containing the GluR2 subunit. In mice, peripherally elicited histaminergic and non-histaminergic itch was prevented by intrathecal (i.t.) administration of the AMPAR antagonist NBQX, which was consistent with the fact that firing of GRPR+ neurons in SDH under histaminergic and non-histaminergic itch was completely blocked by NBQX, but not by the GRPR antagonist RC-3095. Because GRP+ neurons in SDH contain glutamate, we investigated the role of GRP+ (GRP+/Glu+) neurons in regulating itch. Chemogenetic inhibition of GRP+ neurons suppressed both histaminergic and non-histaminergic itch without affecting the mechanical pain threshold.