Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.

Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property Facilitates/promotes growth plate injury repair

Growth plate cartilage has limited self-repair ability,leading to poor bone bridge formation post-injury and ultimately limb growth defects in children.The current corrective surgeries are highly invasive,and outcomes can be unpredictable.Following growth plate injury,the direct loss of extracellular matrix(ECM)coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration.We designed an exosome(Exo)derived from bone marrow mesenchymal stem cells(BMSCs)loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties.Aldehyde-functionalized chondroitin sulfate(OCS)was introduced into gelatin methacryloyl(GM)to form GMOCS hydrogel.Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS.In addition,the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.

Polyphenol-based hydrogels: Pyramid evolution from crosslinked structures to biomedical applications and the reverse design

As a kind of nature-derived bioactive materials, polyphenol-based hydrogels possess many unique and outstanding properties such as adhesion, toughness, and self-healing due to their specific crosslinking structures, which have been widely used in biomedical fields including wound healing, antitumor, treatment of motor system injury, digestive system disease, oculopathy, and bioelectronics. In this review, starting with the classi-fication of common polyphenol-based hydrogels, the pyramid evolution process of polyphenol-based hydrogels from crosslinking structures to derived properties and then to biomedical applications is elaborated, as well as the efficient reverse design considerations of polyphenol-based hydrogel systems are proposed. Finally, the existing problems and development prospects of these hydrogel materials are discussed. It is hoped that the unique perspective of the review can promote further innovation and breakthroughs of polyphenol-based hydrogels in the future.