No abstract

The overexpression of hepatocyte nuclear factor-1 beta (HNF1β) in endometriotic lesion has been demonstrated. However, the role of HNF1β in endometriosis remains largely unknown. Human endometriotic 12Z cells showed higher level of HNF1β when compared with normal endometrial HES cells. In human endometriotic 12Z cells, HNF1β knockdown increased susceptibility to apoptotic cell death by oxidative stress, while HNF1β overexpression suppressed apoptosis. In addition, HNF1β knockdown and overexpression significantly decreased and increased, respectively, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent antiapoptotic genes. Knockdown of the antiapoptotic genes significantly reduced the HNF1β-induced resistance against oxidative stress in 12Z cells. Furthermore, HNF1β regulated the transcriptional activity of NF-κB, and an NF-κB inhibitor suppressed the HNF1β-enhanced NF-κB-dependent antiapoptotic gene expression and the resistance of the 12Z cells against cell death. Taken together, these data suggest that HNF1β overexpression may protect endometriotic cells against oxidative damage by augmenting antiapoptotic gene expression.

2‐Amino‐substituted‐1,4‐naphthoquinone derivatives (10–17) were synthesized from coupling reaction between 1,4‐dihydroxynaphthalene and amines in the presence of catalyst CeCl3.7H2O. Their anticancer activity was evaluated by using three ovarian cancer cells (A2780, SKOV3, and OVCAR3). Among the eight compounds, compound 13 containing metal chelating moiety had a relatively potent cytotoxic activity (IC50 < 10 μM) on all three ovarian cancer cells.

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

Honokiol-triazole derivatives (4-17) were synthesized via click reactions between 2-or 4 0 -propargylated honokiol and azide compounds. Their anticancer activities were evaluated by using two ovarian cancer cells (A2780 and OVCAR3). Among the 14 compounds, compound 5 coupled with 4 0 -propargylated honokiol and benzyl azide exhibited relatively potent cytotoxic activity (IC 50 = 5.5 AE 0.5 μM for A2780 and IC 50 = 3.97 AE 0.6 μM for OVCAR3) but was less toxic to normal cells (IC 50 = 18.90 AE 0.9 μM for IOSE80PC). The cytotoxic effect of compound 5 is associated with caspase-dependent apoptotic cell death via induction of intracellular reactive oxygen species. 1 H NMR (400 MHz, CDCl 3 ): δ 3.34 (d, J = 6.8 Hz, 2H), 3.39 (d, J = 6.8 Hz, 2H), 4.97-5.18 (m, 4H), 5.13 (s, 1H), 5.25 (s, 2H), 5.56 (s, 2H), 5.88-6.00 (m, 2H), 6.89 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 7.06 (d,