Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in gastric mucosal cells and mouse stomach in vivo: AP-1 as a potential target

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E-2 to non-tumerigenic 15-keto prostaglandin E-2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma Tonga Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-jun and cFos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curaimin increased phosphorylation of ERK1/2 and JNK. and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of clun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the alpha,beta-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobater pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis. (C) 2020 Elsevier Inc. All rights reserved.

Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway

Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) α and prostaglandin E2 (PGE2) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway

Porcine Knock-in Fibroblasts Expressing hDAF on α-1,3-Galactosyltransferase (GGTA1) Gene Locus

The Galactose-α1,3-galactose (α1,3Gal) epitope is responsible for hyperacute rejection in pig-to-human xenotransplantation. Human decay-accelerating factor (hDAF) is a cell surface regulatory protein that serves as a complement inhibitor to protect self cells from complement attack. The generation of α1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a necessary step for their use as organ donors for humans. In this study, we established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was lower in the knock-in heterozygous cell line compared to the normal pig cell. Knock-in heterozygous cells afforded more effective protection against cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control cells. These cell lines may be used in the production of GGTA1 knock-out and DAF expression pigs for xenotransplantation

Cause and Management of Patients With Failed Endonasal Dacryocystorhinostomy

Objectives Endonasal dacryocystorhinostomy (DCR) is a well-established treatment method in patients with nasolacrimal duct obstruction. However, there are a few reports about the overall management of failed endonasal DCR. We investigated the causes and management strategies of failed endonasal DCR. Methods This retrospective review included 61 patients (61 eyes) who had undergone revision surgery by the same surgeon after failed endonasal DCR between January 2008 and December 2012. The appropriate revision method was determined after analysis of the etiology of failure by the fluorescein dye disappearance test, nasal endoscopy, lacrimal irrigation, and probing. The criteria for success of the revision surgery were defined by the passage of fluid without resistance upon lacrimal irrigation and normalization of the tear meniscus height. Results The mean duration between the primary endonasal DCR and revision surgery was 15.3 months. The average follow-up period after revision surgery was 12.2 months. The most common cause of endoscopic revision surgery was membranous obstruction. Endoscopic revision surgery was performed in 48 patients, while lacrimal silicone tube intubation under endoscopy was performed in 13 patients. The most common indication for lacrimal silicone tube intubation was functional epiphora. The overall success rate of the revision surgery was 89%. Conclusion The most common cause of failed endonasal DCR was membranous obstruction. When patients with failed endonasal DCR presented at the clinic, it is important to identify the cause of the failure. Revision surgery could increase the final success rate of endonasal DCR

A Photometric and Spectroscopic Study of the Short-Period Algol EW Bo\"{o}tis with a δ\delta Sct Pulsator

In this paper, we present TESS photometry and high-resolution spectra of the short-period Algol EW Boo. We obtained double-lined radial velocities (RVs) from the time-series spectra and measured the effective temperature of the primary star as $T_{\rm{eff,1}}$ = 8560 $\pm$ 118 K. For the orbital period study, we collected all times of minima available for over the last 30 years. It was found that the eclipse timing variation of the system could be represented by a periodic oscillation of 17.6 $\pm$ 0.3 years with a semi-amplitude of 0.0041 $\pm$ 0.0001 d. The orbital and physical parameters were derived by simultaneously analyzing the TESS light and RV curves using the Wilson-Devinney (WD) binary star modeling code. The component masses and radii were showed over 3% precision: $M_{1}$ = 2.67 $\pm$ 0.08 M$_{\odot}$, $M_{2}$ = 0.43 $\pm$ 0.01 M$_{\odot}$, $R_{1}$ = 2.01 $\pm$ 0.02 R$_{\odot}$, and $R_{2}$ = 1.35 $\pm$ 0.01 R$_{\odot}$. Furthermore, multiple frequency analyses were performed for the light-curve residuals from the WD model. As a result, we detected 17 pressure-mode pulsations in the region of 40.15 - 52.37 d$^{-1}$. The absolute dimensions and pulsation characteristics showed that the $\delta$ Sct pulsator was the more massive and hotter primary star of the EW Boo.Comment: 27 pages, 8 figures, Accepted for publication in A