Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, accumulating evidence indicates that ROS also serve as critical signaling molecules in cell proliferation and survival. While there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the “oxidative interface.” Cellular ROS sensing and metabolism are tightly regulated by a variety of proteins involved in the redox (reduction/oxidation) mechanism. This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases, PI3 kinase, PTEN, and protein tyrosine phosphatases), ROS homeostasis and antioxidant gene regulation (thioredoxin, peroxiredoxin, Ref-1, and Nrf-2), mitochondrial oxidative stress, apoptosis, and aging (p66Shc), iron homeostasis through iron–sulfur cluster proteins (IRE–IRP), and ATM-regulated DNA damage response.

Background Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC). Methods Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice. In silico analysis was conducted to predict differentially expressed genes and regulatory miRNAs related to PDAC treated with macrophages, which determined miR-501-3p and TGFBR3 for subsequent experiments. Next, gain- and loss-of-function experiments were performed to examine their role in PDAC progression with the involvement of the TGF-β signaling pathway. Results TAM recruitment in PDAC tissues was associated with metastasis. Highly expressed miR-501-3p was observed in PDAC tissues and TAM-derived exosomes. Both M2 macrophage-derived exosomes and miR-501-3p promoted PDAC cell migration and invasion, as well as tumor formation and metastasis in nude mice. MiR-501-3p was verified to target TGFBR3. PDAC cells presented with down-regulated TGFBR3, which was further decreased in response to M2 macrophage treatment. TGF-β signaling pathway activation was implicated in the promotion of miR-501-3p in PDAC development. The suppression of macrophage-derived exosomal miR-501-3p resulted in the inhibition of tumor formation and metastasis in vivo. Conclusion M2 macrophage-derived exosomal miR-501-3p inhibits tumor suppressor TGFBR3 gene and facilitates the development of PDAC by activating the TGF-β signaling pathway, which provides novel targets for the molecular treatment of PDAC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1313-x) contains supplementary material, which is available to authorized users.

The cellulose fiber was extracted from the abandoned crop sugarcane bagasse (SCB) by means of chemical treatment methods. Poly(lactic acid) (PLA) bio‐based composites with SCB were prepared through fused deposition modeling (FDM) 3D‐printing technology, and the morphologies, mechanical properties, crystallization properties, and thermal stability of 3D‐printed composites were investigated. Compared with the neat PLA, the incorporation of SCB into PLA reduces the tensile strength and flexural strength of 3D‐printed samples but increases the flexural modulus. The difference in tensile performance and bending performance is that the tensile strength of 3D‐printed samples is best when the SCB content is 6 wt%, while the flexural modulus continuously decreases as the SCB content increases. Furthermore, the effects of various printing methods on the tensile performance of 3D‐printed samples were explored via modifying G‐code of 3D models. The results indicate that the optimum SCB fiber content is identical for all printing methods except method “vertical.” Due to the fibers and molecular chains are oriented to varying degrees with altering raster angle in 3D‐printed samples, the fully oriented sample printed by method “parallel” has a better tensile strength. Besides, SCB exhibits enough high thermal decomposition temperature to meet requirements for melt extrusion processing of PLA composites, and SCB fiber is capable of promoting the crystallization of PLA.

No abstract