Anti-Human CLINT1 (C-terminal) Polyclonal antibody

Angular-type pyranocoumarins (APs) show attractive prospects in anti- hypertension, chemotherapy and anti-HIV treatment. Previous studies revealed extensive hepatic metabolisms of several APs following similar pathways. This study investigated the enzyme kinetics and the main CYP450 isozyme(s) involved in metabolism of (+)-praeruptorin A (dPA), an AP with significant cardio-protective activities, in human liver microsomes (HLMs) using ultra high-performance liquid chromatography coupled with a hybrid quadrupole-linear ion trap mass spectrometry (UHPLC-QT-MS/MS). dPA produced 6 metabolites via hydrolysis (M1-M3), oxidation (M4-M6), and hydrolysis followed by acyl migration (M2 or M3). Oxidation at the C-3' side chain instead of the coumarin ring was consolidated with the aromatic proton signal in NMR spectra. The major metabolite (-)-cis-khellactone (M1) followed biphasic kinetics in HLMs with high affinity (K-m1 0.02 mu M) and intrinsic clearance (CLint1, (in vitro) 1.29 mL/min/mg protein), whereas other metabolites (M2-M6) fitted typical Michaelis-Menten kinetics with lower affinity (K-m 3.85-39.13 mu M). Recombinant human CYP3A4 showed the highest activity toward M1 and M4 formation, while it was CYP2C19 for M2/M3 and M5 and CYP2B6 for M6. Principal component analysis of the metabolite formation profile of dPA also revealed the highest similarity between CYP3A4 and HLMs. Both quercetin (CYP2C8 inhibitor) and ketoconazole (CYP3A4 inhibitor) showed 60-100% inhibition of M1-M4 and M6 formations in HLMs, while M5 formation was mainly inhibited by alpha-naphthoflavone (CYP1A2 inhibitor, 70-80%) and quercetin (90%). Moreover, formations of all metabolites were predominantly inhibited by CYP3A4 antibody (37-68%). These findings shed a light on main involvement of CYP3A4 in human hepatic elimination of APs, indicating potential drug interactions. (c) 2013 Elsevier B.V. All rights reserved.

Background. Colon cancer is a heterogeneous disease, differing in clinical symptoms, epigenetics, and prognosis for each individual patient. Identifying the core genes is important for early diagnoses and it provides a more precise method for treating colon cancer. Materials and Methods. In this study, we wanted to pinpoint these core genes so we obtained GSE101502 microRNA profiles from the GEO database, which resulted in 17 differential expressed microRNAs that were identified by GEO2R analysis. Then, 875 upregulated and 2920 downregulated target genes were predicted by FunRich. GO and KEGG pathway were used to do enrich analysis. Results. GO analysis indicated that upregulated genes were significantly enriched in the regulation of cell communication and signaling and in nervous system development, while the downregulated genes were significantly enriched in nervous system development and regulation of transcription from the RNA polymerase II promoter. KEGG pathway analysis suggested that the upregulated genes were enriched in axon guidance, MAPK signaling pathway, and endocytosis, while the downregulated genes existed in pathways in cancer, focal adhesion, and PI3K-Akt signaling pathway. The top four molecules including 82 hub genes were identified from the PPI network and involved in endocytosis, spliceosome, TGF-beta signaling pathway, and lysosome. Finally, NUDT21, GNB1, CLINT1, and COL1A2 core gene were selected due to their correlation with the prognosis of IIA stage colon cancer. Conclusion. this study suggested that NUDT21, GNB1, CLINT1, and COL1A2 might be the core genes for colon cancer that play an important role in the development and prognosis of IIA stage colon cancer.