No abstract

Caffeic acid phenethyl ester (CAPE), extracted from propolis, was proven to inhibit colon cancer. Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2), a derivative of CAPE, was determined to be an anti-platelet agent and a protector of myocardial ischaemia with more potent effects. In the present study, CAPE-pNO2 showed stronger cytotoxic activity than CAPE. We revealed interactions between CAPE-pNO2 and experimental cells. CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. In xenograft studies, CAPE-pNO2 remarkably suppressed tumour growth dose dependently and decreased the expression of VEGF (vascular endothelial growth factor) in tumour tissue. Moreover, HE staining showed that no observable toxicity was found in the heart, liver, kidney and spleen. In addition, metabolites of CAPE-pNO2 in HT-29 cells and organs were detected. In conclusion, para-nitro may enhance the anticancer effect of CAPE by inhibiting colon cancer cell viability, inducing apoptosis and cell cycle arrest via the P53 pathway and inhibiting tumour growth and reducing tumour invasion by decreasing the expression of VEGF; additionally, metabolites of CAPE-pNO2 showed differences in cells and organs.

Background: This meta-analysis aimed to compare the clinical outcomes and complications of minimally invasive plate osteosynthesis (MIPO) and open reduction-internal fixation (ORIF) in patients with proximal humeral fractures. Methods: We searched PubMed, EMBASE, Ovid, and the Cochrane Library to identify all relevant studies from inception to April 2019. Cochrane Collaboration's Review Manage 5.3 was used for meta-analysis. Results: Sixteen studies involving 1050 patients (464 patients in the MIPO group and 586 patients in the ORIF group) were finally included. According to the meta-analysis, MIPO was superior to ORIF in operation time, blood loss, postoperative pain, fracture union time, and constant score. However, MIPO was associated with more exposure to radiation and axillary nerve injury. No significant differences were found in length of hospital stays and complication except for axillary nerve injury. Conclusion: The present evidence indicates that compared to ORIF, MIPO had advantages in functional outcomes, operation time, blood loss, postoperative pain, and fracture union time for the treatment of PHFs. However, the MIPO technique had a higher rate of axillary nerve injury and longer radiation time compared to ORIF.

No abstract

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.