alysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.BACKGROUND Tanshinone IIA (Tan IIA) and andrographolide (Andro) are natural compounds that are reported to exhibit anticancer activities against various types of cancers. The aim of this study is to evaluate the synergistic anticancer effects of the combination of Tan IIA and Andro, and to investigate the mechanisms of pharmacological effect and their potential applications as an anticancer therapy in clinics. METHODS The anticancer effects of the combination of Tan IIA and Andro on MCF7, SMMC7721, and BGC823 cells were explored. The apoptosis of the cancer cells was determined by MTT and AV-PI dual stain assays. https://www.selleckchem.com/products/A014418.html The intracellular GSH level was measured by DTNB assay, and the intracellular levels of reactive oxygen species (ROS) were examined by flow cytometry. The expression of the proteins in the apoptosis pathway was determined by immunobloting. RESULTS The combination of Tan IIA and Andro exhibited significant synergistic anticancer effects against cancer cells, especially at low concentrations. Andro reacted with the thiol group of intracellular GSH, thus disrupting the GSH redox cycle and eventually increasing the level of intracellular ROS. Tan IIA triggered p53 responses and apoptosis by binding to the DNA of cancer cells. The crosstalk between ROS and p53 exhibited a synergistic effect on the apoptosis of cancer cells. CONCLUSION The combination of Tan IIA and Andro showed significant synergistic effects on cancer cell apoptosis by promoting crosstalk between ROS and p53, providing a novel and effective combination that has the potential to be applied in clinical anticancer therapy.BACKGROUND N-methyl-D-aspartate (NMDA) receptor is a tetrameric protein complex composed of glycine-linked NR1 subunits and glutamate-linked NR2 subunits. There are four NR2 subunits (A-D) that differ in development, anatomy, and function profiles. They play various roles in normal and neuropathologic conditions. Specific agonists, antagonists, and modulators of subunits for selective NMDA receptors may be precious mediational tools and potent agents for treating diseases. The objective of this study was to determine the effect of poricoic acid A on NMDA receptor known to mediate excitatory synaptic transmission factors and cause changes in synaptic strength. Inhibitory effect of poricoic acid A on NR1a combined with NR2A, NR2B, NR2C, or NR2D receptor was evaluated. METHODS Glutamate-mediated currents for each NR1a and NR2 subunits were investigated using two-electrode voltage-clamp techniques. Molecular modeling and molecular dynamics simulation studies were carried out with Autodock Tools. Poricoic acid A and NMDA receptor protein complex were examined with Ligplot and Pymol docking program. Ligplot shows binding activity at the protein and the ligand. RESULTS The inhibitory effect of poricoic acid A on glutamate-induced inward current in a concentration-dependent manner that was reversible. Half inhibitory concentrations of glutamate on NR1a/NR2A, NR1a/NR2B, NR1a/NR2C, and NR1a/NR2D receptors were 9.6 ± 1.2, 5.7 ± 0.4, 46.1 ± 21.5, and 21.5 ± 8.2 μM, respectively. This corresponded to the order of inhibitory effect of oocyte expressing NR1a and NR2s subunit of NR1a/NR2B > NR1a/NR2A > NR1a/NR2C > NR1a/NR2D. CONCLUSIONS Taken together, these results indicate that poricoic acid A can modulate the expression of NMDA receptor. In addition, the regulation of excitatory ligand-gating ion channel by poricoic acid A may have pharmaceutical functions on excitatory synaptic transmission of neuronal system.BACKGROUND Mast cells are immune effector cells mediating allergic inflammation by the secretion of inflammatory mediators such as histamine and pro-inflammatory cytokines. Orientin is a naturally occurring bioactive flavonoid that possesses diverse biological properties, including anti-inflammation, anti-oxidative, anti-tumor, and cardio protection. The objective of this study was to rule out the effectiveness of orientin in mast cell-mediated allergic inflammation. METHODS In this study, in vitro effects of orientin were evaluated in RBL-2H3, mouse bone marrow-derived mast cells, rat peritoneal mast cells, and in vivo effects were evaluated by inducing passive cutaneous anaphylaxis (PCA) in Imprinting Control Region (ICR) mice. RESULTS Findings show that orientin suppressed the immunoglobulin E (IgE)-mediated mast cell degranulation by reducing intracellular calcium level in a concentration-dependent manner. Orientin suppressed the secretion of pro-inflammatory cytokines in mast cells. This inhibitory effects of orientin was through inhibition of FcεRI-mediated signaling proteins. In addition, oral administration of orientin suppressed the IgE-mediated PCA reactions in a dose-dependent manner, which was evidenced by reduced Evan's blue pigmentation and ear swelling. CONCLUSIONS Based on these findings, we suggest that orientin might have potential to alleviate allergic reaction and mast cell-mediated allergic disease.BACKGROUND Prostate cancer (PCa) is the most common malignancy in men and in the absence of any effective treatments available. METHODS For the development of potential anticancer agents, 24 kinds of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety were synthesized and characterized by using spectroscopic methods. Their pharmacological activities were evaluated against human PCa cell lines (PC-3 and LNCaP) and a1-adrenergic receptors (a1-ARs; α1a, α1b, and α1d-ARs). The structure-activity relationship of these designed arylpiperazine derivatives was rationally explored and discussed. RESULTS Among these derivatives, 3c, 3d, 3h, 3k, 3o, and 3s exhibited the most potent activity against the tested cancer cells, and some derivatives with potent anticancer activities exhibited better a1-AR subtype selectivity than others did (selectivity ratio > 10). CONCLUSION This work provided a potential lead compound for the further development of anticancer agents for PCa therapy.