1-(2-Hy­droxy-3,5-dimeth­oxy­phen­yl)ethanone

In title compound, C10H12O4, all of the non-H atoms lie approximately in a plane with the largest deviation being 0.061 (2) Å. An intra­molecular O—H⋯O hydrogen bond generates an S(6) ring motif. No classical inter­molecular hydrogen bonding occurs, with only van der Waals forces stabilizing the crystal structure

ETS proto-oncogene 1 modulates PTP1B expression to participate in high glucose-mediated endothelial inflammation

Hyperglycemia-induced endothelial inflammation participates in the pathogenesis of cardiovascular complications in diabetics. Previous studies showed that protein tyrosine phosphatase 1B (PTP1B) and ETS proto-oncogene 1 (ets1) are involved in hyperglycemia-induced endothelial inflammation. In this study, we hypothesized that ets1 modulates PTP1B expression, thus playing a crucial role in hyperglycemia-induced vascular endothelial inflammation. Our results indicated that high glucose increases monocyte/endothelial adhesion, vascular cell adhesion molecule-1 (VCAM-1) expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose-mediated endothelial inflammation is reversed by PTP1B silencing. In addition, high glucose increases ets1 expression in HUVECs. Ets1 silencing reverses high glucose-mediated endothelial inflammation. Furthermore, the effect of ets1 overexpression is similar to that of high glucose treatment, which is counteracted by si-PTP1B. The results from ChIP assays indicated that ets1 occupies the PTP1B promoter region. Ets1 overexpression enhances PTP1B promoter activity, which is disappeared after specific binding site mutation. In vivo experiments demonstrated that the expressions of VCAM-1, PTP1B, and ets1, as well as the phosphorylation of p65 are augmented in the aorta of diabetic rats. In conclusion, ets1 contributes to hyperglycemia-mediated endothelial inflammation via upregulation of PTP1B expression

Ketamine attenuates high-glucose-mediated endothelial inflammation in human umbilical vein endothelial cells

Hyperglycemia mediates oxidative stress, thus inducing transcription factor nuclear factor kappa B (NF-κB) activation, increasing endothelial adhesion molecules expression and monocytes/endothelial interaction, and resulting in endothelial injury. Ketamine was reported to attenuate oxidative stress in many cases. In this research, we determined whether and how ketamine protects against high glucose-mediated augment of monocytes/endothelial interaction and endothelial adhesion molecules expression in human umbilical vein endothelial cells (HUVECs). High glucose augmented monocytes/endothelial adhesion and endothelial adhesion molecules expression. High glucose induced ROS production, augment of p-PKC βII expression and PKC activity. Moreover, high glucose inhibited inhibitory subunit of nuclear factor-κBα (IκBα) expression in cytoplasm, induced NF-κB nuclear translocation. Importantly, the effects induced by high glucose were counteracted by ketamine treatment. Further, CGP53353, a PKC βII inhibitor, inhibited high glucose-mediated NF-κB nuclear translocation, attenuated adhesion molecules expression, and reduced monocytes/endothelial interaction. Further, these effects of ketamine against high glucose-induced endothelial injury were inhibited by PMA, a PKC βII activator. In conclusion, ketamine, via reducing ROS accumulation, inhibiting PKC βII Ser660 phosphorylation, PKC and NF-κB activation, reduced high glucose-induced the expression of endothelial adhesion molecules and monocytes/endothelial interaction.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities

Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target