Purpose Wound healing, especially of infected wounds, remains a clinical challenge in plastic surgery. This study aimed to manufacture a novel and multifunctional wound dressing by combining graphene oxide/copper nanocomposites (GO/Cu) with chitosan/hyaluronic acid, providing significant opportunities for the therapy of wound repair in wounds with a high risk of bacterial infection. Methods In this study, GO/Cu-decorated chitosan/hyaluronic acid dressings (C/H/GO/Cu) were prepared using sodium trimetaphosphate (STMP) crosslinking and the vacuum freeze-drying method, and chitosan/hyaluronic acid dressings (C/H) and GO-incorporated chitosan/hyaluronic acid dressings (C/H/GO) served as controls. The surface characterization, in vitro degradation under various pH values, antimicrobial potential, cytocompatibility and in vivo therapeutic efficacy in a bacteria-infected full-thickness skin defect model were systematically evaluated. Results Our experimental results indicated that the acidic environment facilitated the release of copper (CuNPs and Cu 2+ ) from the dressings, and prepared C/H/GO/Cu dressings exhibited significant in vitro antimicrobial activities against the two tested bacterial strains (ATCC35984 and ATCC25923). All three dressings showed satisfactory cytocompatibility with mouse fibroblasts (NIH/3T3-L1). Moreover, remarkably accelerated wound healing was found in the C/H/GO/Cu group, with controlled inflammatory infiltration and improved angiogenesis in granulation tissues. In addition, no pathological damage was noted in the tissue structures of the tested organs (heart, lung, liver and kidney) in any of the four groups. Conclusion Collectively, GO/Cu-incorporated chitosan/hyaluronic acid dressings suggested a synergistic antimicrobial efficacy and acceptable biocompatibility both in vitro and in vivo, as well as a significantly accelerated healing process of bacteria-infected wounds. Thus, the multifunctional C/H/GO/Cu composite is expected to be a potential alternative for wound dressings, especially for the management of intractable wounds caused by bacterial infection.

Currently, implant-related bone infection characterized by aggravated bone resorption and osteolysis, remains a severe challenge in plastic and orthopedic surgery. Therefore, surface modification of implants endowed with both antibacterial potential and suppression of osteoclastogenesis offers new insight into relevant therapeutic strategies. In this study, we designed magnesium (Mg)-incorporated nanotube-modified titanium implants (NT-Mg) that combine dual-functional Mg with antimicrobial properties of titania nanotubes with specific diameter. The surface characterization, in vitro degradation, antibacterial properties, cytocompatibility, and inhibitory effects on osteoclastogenesis together with the in vivo anti-infection potential and osseointegration of the implants were systematically investigated. Our results demonstrated that NT-Mg implants maintained continuous and reliable release of Mg ion from the titania nanotubes (TNTs), producing long lasting antimicrobial activity. The nanotubular structure and alkaline microenvironment during degradation were the two main reasons responsible for the antimicrobial properties of NT-Mg. In addition, NT-Mg exhibited favored osteoprogenitor cell adhesion and proliferation without obvious cytotoxicity. Moreover, Mg 2+ released in the degraded liquid suppressed osteoclastogenesis via down-regulation of NF-κB/NFATc1 signaling. Finally, we established an implant-related bone infection model to assess the in vivo anti-infection potential and osseointegration of the NT-Mg implant. As expected, NT-Mg implants significantly prevented bone infection and osteolysis, leading to improved osseointegration. Based on these promising findings, the dual-functional magnesium-incorporated titania nanotubes represent an efficient alternative to realize better osseointegration in severe implant-related bacterial infections.

The expression of hypoxia-inducible factor 1α (HIF-1α) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1α was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. In vivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1α (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1α, suggesting it may be a potential therapeutic target for melanoma treatment.

Intelligent CNC-g-P(AzoC6MA-co-DMAEMA) fluorescent nanosensors present ultraviolet light-, temperature- and pH-responsive properties.

IntroductionMelanoma is a common skin cancer that is usually associated with poor clinical outcomes. Recently, the immune checkpoint GITR has been identified as a promising target for immunotherapy of melanoma. In this study, we aimed to investigate the post-translational regulation mechanism of GITR in melanoma.MethodsWestern blotting was used to evaluate the protein expression of NEDD4, GITR and Foxp3. Real-time PCR (RT-PCR) was performed to determine expression levels of NEDD4, GITR, Foxp3 and IL-2. Cell viability was detected by MTT assay. The ubiquitination of GITR was evaluated by immunoprecipitation. NEDD4 expression data and melanoma survival data were obtained from The Cancer Genome Atlas (TCGA) and cBioPortal databases.ResultsWe demonstrate that E3 ligase NEDD4 binds to GITR and mediates ubiquitination and degradation of GITR. Overexpression of NEDD4 inhibits anti-tumor immunity mediated by T cells against melanoma cells. We also found that the expression of NEDD4 is increased in metastatic melanoma. High NEDD4 expression level is correlated with the poor prognosis of melanoma patients.DiscussionIn summary, our findings demonstrated that E3 ligase NEDD4 mediates ubiquitination and degradation of GITR and suppresses T-cell-mediated-killings on melanoma cells. Our work highlighted the E3 ligase NEDD4 as a novel prognosis biomarker and therapeutic target for melanoma.