Copper is an indispensable trace metal element in the human body, which is mainly absorbed in the stomach and small intestine and excreted into the bile. Copper is an important component and catalytic agent of many enzymes and proteins in the body, so it can influence human health through multiple mechanisms. Based on the biological functions and benefits of copper, an increasing number of researchers in the field of biomaterials have focused on developing novel copper-containing biomaterials, which exhibit unique properties in protecting the cardiovascular system, promoting bone fracture healing, and exerting antibacterial effects. Copper can also be used in promoting incisional wounds healing, killing cancer cells, Positron Emission Tomography (PET) imaging, radioimmunological tracing and radiotherapy of cancer. In the present review, the biological functions of copper in the human body are presented, along with an overview of recent progress in our understanding of the biological applications and development of copper-containing materials. Furthermore, this review also provides the prospective on the challenges of those novel biomaterials for future clinical applications.

The potent pleiotropic lipid mediator sphingosine-1-phosphate (S1P) participates in numerous cellular processes, including angiogenesis and cell survival, proliferation, and migration. It is formed by one of two sphingosine kinases (SphKs), SphK1 and SphK2. These enzymes largely exert their various biological and pathophysiological actions through one of five G protein-coupled receptors (S1PR1–5), with receptor activation setting in motion various signaling cascades. Considerable evidence has been accumulated on S1P signaling and its pathogenic roles in diseases, as well as on novel modulators of S1P signaling, such as SphK inhibitors and S1P agonists and antagonists. S1P and ceramide, composed of sphingosine and a fatty acid, are reciprocal cell fate regulators, and S1P signaling plays essential roles in several diseases, including inflammation, cancer, and autoimmune disorders. Thus, targeting of S1P signaling may be one way to block the pathogenesis and may be a therapeutic target in these conditions. Increasingly strong evidence indicates a role for the S1P signaling pathway in the progression of cancer and its effects. In the present review, we discuss recent progress in our understanding of S1P and its related proteins in cancer progression. Also described is the therapeutic potential of S1P receptors and their downstream signaling cascades as targets for cancer treatment.

Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10 expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.

For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN–Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN–Fe wires were 1023.2 MPa and 51.0 %, respectively, which was much higher than those of other biodegradable wires. The degradation rate in vitro of HN–Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN–Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN–Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN–Fe staples was observed and no fracture occurred. The degradation rate of HN–Fe staples in vivo was significantly higher than that in vitro, and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN–Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN–Fe staples. Thereby, the favorable performance makes the HN–Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.

In-stent restenosis can be caused by the activation, proliferation and migration of vascular smooth muscle cells (VSMCs), which affects long-term efficacy of interventional therapy. Copper (Cu) has been proved to accelerate the endothelialization and reduce thrombosis formation, but little is known about its inhibition effect on the excessive proliferation of VSMCs. In this study, 316L-Cu stainless steel and L605-Cu cobalt-based alloy with varying Cu content were fabricated and their effects on surface property, blood compatibility and VSMCs were studied in vitro and in vivo. CCK-8 assay and EdU assay indicated that the Cu-bearing metals had obvious inhibitory effect on proliferation of VSMCs. Blood clotting and hemolysis tests showed that the Cu-bearing metals had good blood compatibility. The inhibition effect of the Cu-bearing metals on migration of cells was detected by Transwell assay. Further studies showed that Cu-bearing metals significantly decreased the mRNA expressions of bFGF, PDGF-B, HGF, Nrf2, GCLC, GCLM, NQO1 and HO1. The phosphorylation of AKT and Nrf2 protein expressions in VSMCs were significantly decreased by Cu-bearing metals. Furthermore, it was also found that SC79 and TBHQ treatments could recover the protein expressions of phospho-AKT and Nrf2, and their downstream proteins as well. Moreover, 316L-Cu stent proved its inhibitory action on the proliferation of VSMCs in vivo. In sum, the results demonstrated that the Cu-bearing metals possessed apparent inhibitory effect on proliferation and migration of VSMCs via regulating the AKT/Nrf2/ARE pathway, showing the Cu-bearing metals as promising stent materials for long-term efficacy of implantation.

Backgroud: Oxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer.Methods: Gene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer.Results: A total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including LRT2, ATP6V0E2, ODC1, SEL1L3 and VDR was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways.Conclusions: We developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer