Activation of the immune system in the central nervous system and oxidative stress play important roles in traumatic brain injury (TBI)-induced cognitive impairment. Rhamnetin possesses anti-inflammatory and anti-oxidative properties. This study aimed to detect the possible effects of rhamnetin on cognitive deficit, hippocampal inflammatory factors, and oxidative stress in rats with TBI. In this study, we established the traumatic brain injury model in rats. Rats respectively received vehicle saline or rhamnetin for 21 days. Cognitive functions were evaluated by assessing the acquisition of spatial learning and memory retention in Morris Water Maze test from day 15 to 19 post TBI. Levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor a (TNF-a), IL-10, and nuclear factor κB (NF-κB) in hippocampal homogenate were measured using ELISA. Oxidative stress was analysed by investigating the activities of MDA, H2O2, SOD, and GSH-Px. We found that rhamnetin significantly improved cognitive impairment in rats with TBI, and inhibited the inflammatory response and oxidative stress in the hippocampus. The results suggested that rhamnetin could enhance the recovery of cognitive deficits induced by TBI, and that its mechanism might be associated with the inhibition of inflammation and oxidative stress in the hippocampus.

A partially converted, biodegradable coralline hydroxyapatite/calcium carbonate (CHACC) composite comprising a coral calcium carbonate scaffold enveloped by a thin layer of hydroxyapatite was used in the present study. The CHACC was characterized using powder x-ray diffraction, scanning electron microscopy and energy dispersive x-ray spectroscopy. The ability of the CHACC to promote conductive osteogenesis was assessed in vitro using human mesenchymal stem cells (hMSCs) and in vivo using an immunodeficient mouse model. The clinical performance of CHACC as a bone substitute to fill voids caused by excision of bone tumours was also observed in 16 patients. The CHACC was found to consist of two overlapping layers both morphologically and chemically. Hydroxyapatite formed a thin layer of nanocrystals on the surface and a thick rough crystal layer of around 30 µm in thickness enveloping the rock-like core calcium carbonate exoskeletal architecture. hMSCs cultured on CHACC in osteogenic medium demonstrated significant osteogenic differentiation. After subcutaneous implantation of CHACC incorporating osteogenically differentiated hMSCs and an anti-resorptive agent, risedronate, into an immunodeficient mouse model, bone formation was observed on the surface of the implants. Clinical application of CHACC alone in 16 patients for bone augmentation after tumour removal showed that after implantation, visible callus formation was observed at one month and clinical bone healing achieved at four months. The majority of the implanted CHACC was degraded in 18-24 months. In conclusion, CHACC appears to be an excellent biodegradable bone graft material. It biointegrates with the host, is osteoconductive, biodegradable and can be an attractive alternative to autogenous grafts.

These data demonstrate FGF21 attenuates VSMC calcification in vitro via an FGF21/FGFR1/3/β-klotho/P38MAPK/RUNX-2 signalling pathway.

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