AL-209

By establishing a mouse model of hepatic ischemia-reperfusion injury (HIRI), to investigate the effects of cyclooxygenase-2 (COX-2) and endoplasmic reticulum stress (ERS) on HIRI and their interaction in HIRI.

C57BL/6J male mice were divided into four groups: Sham operation group (Sham group), hepatic ischemia-reperfusion (HIR) group, hepatic ischemia-reperfusion + Salubrinal (ER stress inhibitor) pretreatment group (HIR + Sal group), hepatic ischemia-reperfusion + NS398 (inhibitor of COX-2) pretreatment group (HIR + NS398 group). The levels of Aspartate transaminase (AST) and Alanine transaminase (ALT) in serum, the activity of Super Oxide Dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissue were detected. The mRNA and protein expression of Glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) and COX-2/PTGS (Prostaglandin-endoperoxide synthase) in liver tissue were detected. The morphological changes and apoptosis of liver tissue were observed.

Compared with the Sham group, the serum ALT and AST levels of the HIR group were increased, the SOD activity in the liver tissue was decreased, the MDA content and the expression of COX-2, p-eIF2α, GRP78 and CHOP protein were increased, and the staining results showed that hepatic sinusoidal congestion, a large number of hepatocyte death, inflammatory cell infiltration and apoptotic cells were significantly increased. The levels of ALT and AST decreased after Sal or NS398 pretreatment. SOD activity was increased, MDA content, COX-2, GRP78, CHOP mRNA and protein were decreased in liver tissue, and staining showed that liver tissue injury was improved.

In mice with HIR, COX-2 interacts with ERS to cause liver injury by regulating oxidative stress and apoptosis.

Titanium (Ti) and Ti alloy are the most widely used implant metals, but the limited bioactivity hinders the further clinical application. Aiming to enhance their osteogenesis, dual biomimetic strategies were utilized to decorate the surface of Ti by topological and biochemical cues. Firstly, a series of concentric circles with TiO₂ nanotubes on Ti were fabricated by photolithography and anodic oxidation. Furthermore, hydrothermal deposition and vacuum adsorption were adopted to introduce CaP and then assemble natural product of salidroside (Sal) on TiO₂ nanotubes (Sal/CaP/BTNT). Sal/CaP/BTNT was not only bio-mimicked the features of Haversian osteon in size and composition, but also slowed the release of Sal simultaneously. This biomimetic Haversian osteon induced bone marrow mesenchymal stem cells (BMSCs) to grow along the concentric circles, and was involved in BMP, Wnt/β-catenin, Notch and mechanical signaling pathways. Particularly, the expressions of related genes were up-regulated nearly to 200 % in mechanical signaling pathway compared to that of pure BMSCs. Additional, Sal enhanced osteogenic differentiation of BMSCs via BMP signaling pathway. The dual biomimetic Haversian osteon could promote the proliferation, differentiation and mineralization of BMSCs compared to that of pure BMSCs. In vivo studies showed that the CaP/BTNT and Sal/CaP/BTNT both promoted more new-bone formation than that of the control groups, indicating of their accelerated osseointegration due to the dual biomimetic Haversian osteon. The dual biomimetic strategies endowed Ti the excellent osteogenesis, which provided a promising surface modification strategy of Ti and Ti alloy to accelerate osteogenesis in clinic.