[IL-17 regulates the expression of RANKL and OPG in human periodontal ligament fibroblasts by activating p38MAPK signaling pathway].

Objective To illuminate whether IL-17 regulates receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) expression in human periodontal ligament fibroblasts (HPDLFs) via p38MAPK signaling pathway. Methods HPDLFs were incubated in the presence of 20 ng/mL IL-17 for 0, 20, 40, 60 and 80 minutes. HPDLFs were divided randomly into 6 groups: control group, dimethyl sulfoxide (DMSO) group, p38MAPK pathway inhibitor SB203580 group, IL-17 group, IL-17 combined with DMSO group and IL-17 combined with SB203580 group. SB203580 (10 µmol/L) and IL-17 (20 ng/mL) were added to the corresponding groups. Real-time quantitative PCR was used to detect the expression of RANKL and OPG mRNAs in HPDLFs. The levels of phospho-p38MAPK (p-p38MAPK) and RANKL protein were measured using Western blot analysis. The protein level of OPG was detected by ELISA. Results After IL-17 stimulation, the expression level of p-p38MAPK protein gradually increased starting from 0 minute and reached its highest level at 60 minutes. It started to decline at 80 minutes. Stimulation with IL-17 could increase the mRNA and protein expression level of RANKL but decrease the mRNA and protein expression level of OPG. Nevertheless, unlike the IL-17 group, IL-17 combined with inhibitor SB203580 decreased the expression of RANKL mRNA and protein and increased OPG mRNA. Conclusion IL-17 can enhance the expression of RANKL in human periodontal fibroblasts and inhibit the expression of OPG mRNA through the p38MAPK signal transduction pathways.

Synthesis, characterization, photoluminescence, anti-tumor activity, DFT calculations and molecular docking with proteins of zinc(ii) halogen substituted terpyridine compounds.

Reactions between halogen substituted terpyridine ligands F- (L1), Cl- (L2), Br- (L3) and I-4'-phenyl-terpyridine (L4) and ZnBr2 or ZnI2 led to the formation of complexes [Zn(Br)2L1] (1), [Zn(i)2L1] (2), [Zn(Br)2L2] (3), [Zn(i)2L2] (4), [Zn(Br)2L3] (5), [Zn(i)2L3] (6), [Zn(Br)2L4] (7), and [Zn(i)2L4] (8), respectively, which were characterized by elemental analysis, 1H NMR, IR and single crystal X-ray diffraction. Their photoluminescence properties, solution stabilities, hydrophilicity/lipophilicity properties and anti-proliferative activity against three cancer cell lines as well as structure-function relationships are analyzed. All the complexes, which show high solution stabilities and lipophilicity under determination conditions, reveal much higher antiproliferative activities than cisplatin against the human lung carcinoma cell line (A549), human hepatocellular carcinoma cell line (Bel-7042) and human breast cancer cell line (MCF-7) in vitro. Fluorescence spectroscopy and circular dichroic analysis reveal that the compounds have strong affinity binding with ctDNA and stack onto the base pairs of the ctDNA. The results obtained are further explained in terms of the electronic properties of the compounds by density functional theory (DFT) calculations, and it is found that the halogen anions play critical roles in the antitumor activity of these compounds. Their affinities to HSP90 proteins, ALK, EGFR and HER2 kinases and the binding sites on these proteins have been determined by computational docking analysis, and the results indicate that the only form of their binding is van der Waals forces.