The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

Scope Nobiletin (NBT) is a major citrus flavonoid with various health benefits. Herein, we investigated the colon cancer chemopreventive effects of NBT and its colonic metabolites in a colitis-associated colon carcinogenesis mouse model as well as in human colon cancer cell models. Methods and results In azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, oral administration of NBT effectively decreased both incidence and multiplicity of colonic tumors. NBT showed significant anti-proliferative, pro-apoptotic and anti-inflammatory effects in the mouse colon. HPLC analysis revealed that oral administration of NBT resulted in high levels of metabolites, i.e. 3′-demethylnobiletin (M1), 4′-demethylnobiletin (M2), and 3′, 4′-didemethylnobiletin (M3) in the colonic mucosa. In contrast, the colonic level of NBT was about 20-fold lower than the total colonic level of three metabolites. Cell culture studies demonstrated that the colonic metabolites of NBT significantly inhibited the growth of human colon cancer cells, caused cell cycle arrest, induced apoptosis, and profoundly modulated signaling proteins related with cell proliferation and cell death. All of these effects were much stronger than those produced by NBT alone. Conclusions Our results demonstrated that oral administration of NBT significantly inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly associated with its colonic metabolites.

Orthopaedic implants are recognised as important therapeutic devices in the successful clinical management of a wide range of orthopaedic conditions. However, implant-related infections remain a challenging and not uncommon issue in patients with implanted instrumentation or medical devices. Bacterial adhesion and formation of biofilm on the surface of the implant represent important processes towards progression of infection. Given the intimate association between infection and the implant surface, adequate treatment of the implant surface may help mitigate the risk of infection. This review summarises the current surface treatment technologies and their role in prevention of implant-related infection from the beginning. Translational potential of this article Despite great technological advancements, the prevalence of implant-related infections remains high. Four main challenges can be identified. (i) Insufficient mechanical stability can cause detachment of the implant surface coating, altering the antimicrobial ability of functionalized surfaces. (ii) Regarding drug-loaded coatings, a stable drug release profile is of vital importance for achieving effective bactericidal effect locally; however, burst release of the loaded antibacterial agents remains common. (iii) Although many coatings and modified surfaces provide superior antibacterial action, such functionalisation of surfaces sometimes has a detrimental effect on tissue biocompatibility, impairing the integration of the implants into the surrounding tissue. (iv) Biofilm eradication at the implant surface remains particularly challenging. This review summarised the recent progress made to address the aforementioned problems. By providing a perspective on state-of-the-art surface treatment strategies for medical implants, we hope to support the timely adoption of modern materials and techniques into clinical practice.

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These results indicated that low doses of nano-ZnOs can have beneficial effects on growth performance, intestinal morphology and microflora, and immunity in weanling pigs, which are similar to the effects of pharmacological dosages of conventional ZnO. Nano-ZnOs may reduce mineral excretion, which may reduce environmental challenges. © 2018 Society of Chemical Industry.

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Current treatments for diabetic ulcers (DUs) remain unsatisfactory due to the risk of bacterial infection and impaired angiogenesis during the healing process. The increased degradation of polyubiquitinated hypoxia‐inducible factor‐1α (HIF‐1α) compromises wound healing efficacy. Therefore, the maintenance of HIF‐1α protein stability might help treat DU. Nitric oxide (NO) is an intrinsic biological messenger that functions as a ubiquitination flow repressor and antibacterial agent; however, its clinical application in DU treatment is hindered by the difficulty in controlling NO release. Here, an intelligent near‐infrared (NIR)‐triggered NO nanogenerator (SNP@MOF‐UCNP@ssPDA‐Cy7/IR786s, abbreviated as SNP@UCM) is presented. SNP@UCM represses ubiquitination‐mediated proteasomal degradation of HIF‐1α by inhibiting its interaction with E3 ubiquitin ligases under NIR irradiation. Increased HIF‐1α expression in endothelial cells by SNP@UCM enhances angiogenesis in wound sites, promoting vascular endothelial growth factor (VEGF) secretion and cell proliferation and migration. SNP@UCM also enables early detection of wound infections and ROS‐mediated killing of bacteria. The potential clinical utility of SNP@UCM is further demonstrated in infected full‐thickness DU model under NIR irradiation. SNP@UCM is the first reported HIF‐1α‐stabilizing advanced nanomaterial, and further materials engineering might offer a facile, mechanism‐based method for clinical DU management.