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Background: The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear. Methods: Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway. Results: Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration. Conclusion: These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes. Dm4iGs5nWD8FkGrYCfJL2M Video Abstract [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is the second most prevalent cancer worldwide and the eighth most common cause of tumor-related death in Taiwan. Helminthostachys zeylanica , a flavonoid compound, has anti-inflammatory, immunomodulatory, and anticancer effects. We examined whether an extract of H. zeylanica (E1 and E2) has potential as a treatment for GC. Methods: We investigated the effects (pro-apoptosis, pro-autophagy, and antiproliferation ability) of H. zeylanica -E2 on cell viability in healthy gastric epithelial (GES-1) and GC cells (AGS and BGC823). H. zeylanica -E2 was toxic to GC cells but had little or no toxicity to normal cells. Results: In this study, H. zeylanica -E2 induced apoptosis through caspase 3/7, Bcl-2, Bax, cyclooxygenase-2 (COX-2), and cleaved poly (ADP-ribose) polymerase pathways in GC cells. In addition, it increased autophagy by stimulating autophagy-related protein (ATG)5, ATG7, LC3-I/LC3-II, and inhibiting COX-2 activity in GC cells. We also found that H. zeylanica -E2 exhibited antiproliferation ability through cell cycle arrest in G0/G1 and G2/M and suppressed the migration of GC cells. The anticancer effects of H. zeylanica -E2 in GC cells might be mediated partly through inhibition of tumor necrosis factor-α (TNF-α)-activated proinflammatory cytosolic phospholipase A2 (cPLA2)-COX-2-prostaglandin E 2 (PGE 2 ) pathway. Conclusions: Our results suggest that H. zeylanica -E2 has potential as a novel adjunctive agent for the treatment of GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Thyroid hormone (T3) regulates growth, development and differentiation. These activities are mediated by nuclear thyroid hormone receptors (TRs), which belong to the steroid/thyroid hormone receptor superfamily of ligand-dependent transcription factors. In an effort to study the mechanism of target genes regulation and their physiological significance after T3 treatment in a TR alpha-overexpressing hepatoma cell line (HepG2-TR alpha), c-DNA microarrays were performed. The data demonstrated that approximately 149 genes represented were positively regulated by T3, including fibrinogen, transferrin, fibronectin (FN), androgen receptor (AR)-associated protein (ARA70), and dehydroepiandrosterone sulfotransferase family 1A member 2 (SULT2A1). To further confirm the microarray results, a quantitative-reverse transcription polymerase chain reaction (Q-RT-PCR) was applied. The protein synthesis inhibitor, cycloheximide was used to determine whether the regulation was direct or indirect. A promoter assay further showed that T3 regulation was largely at the level of transcription. Although those genes were isolated from a human tumor cell line, they are regulated similarly in rats and humans. These results indicate that T3 might play an important role in the process of blood coagulation, inflammation, metabolism and cell proliferation. This may help to explain the association between thyroid diseases and the mis-regulation of the inflammatory and clotting profiles evident in the circulatory systems of these patients.