Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis.

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design of a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded with azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN with a size of 268 nm are stable under physiological conditions, can be specifically taken up by macrophages through the FN-mediated targeting, and can be dissociated in the oxidative inflammatory microenvironment. The G4-TBP NPs-FN loaded with G4-TBP dendrimer having intrinsic anti-inflammatory property and FN having both anti-inflammatory and antioxidative properties display integrated functions of ROS scavenging, hypoxia attenuation, and macrophage M2 polarization, thus protecting macrophages from apoptosis and creating designed bone immune microenvironment for stem cell osteogenic differentiation. These characteristics of the G4-TBP NPs-FN lead to their effective treatment of an OA model in vivo to reduce pathological changes of joints including synovitis inhibition and cartilage matrix degradation and simultaneously promote osteogenic differentiation for bone repair. The developed nanomedicine formulation combining the advantages of both bioactive phosphorus dendrimers and FN to treat OA may be developed for immunomodulatory therapy of different inflammatory diseases.

Association between green tea intake and risk of gastric cancer: a systematic review and dose-response meta-analysis of observational studies.

OBJECTIVE: To examine and quantify the potential dose-response relationship between green tea intake and the risk of gastric cancer. DESIGN: We searched PubMed, EMBASE, Web of Science, CBM, CNKI and VIP up to December 2015 without language restrictions. SETTING: A systematic review and dose-response meta-analysis of observational studies. SUBJECTS: Five cohort studies and eight case-control studies. RESULTS: Compared with the lowest level of green tea intake, the pooled relative risk (95 % CI) of gastric cancer was 1·05 (0·90, 1·21, I 2=20·3 %) for the cohort studies and the pooled OR (95 % CI) was 0·84 (0·74, 0·95, I 2=48·3 %) for the case-control studies. The pooled relative risk of gastric cancer was 0·79 (0·63, 0·97, I 2=63·8 %) for intake of 6 cups green tea/d, 0·59 (0·42, 0·82, I 2=1·0 %) for 25 years of green tea intake and 7·60 (1·67, 34·60, I 2=86·5 %) for drinking very hot green tea. CONCLUSIONS: Drinking green tea has a certain preventive effect on reducing the risk of gastric cancer, particularly for long-term and high-dose consumption. Drinking too high-temperature green tea may increase the risk of gastric cancer, but it is still unclear whether high-temperature green tea is a risk factor for gastric cancer. Further studies should be performed to obtain more detailed results, including other gastric cancer risk factors such as smoking and alcohol consumption and the dose of the effective components in green tea, to provide more reliable evidence-based medical references for the relationship between green tea and gastric cancer.