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Curcumin (CCM) has many potential uses in anticancer chemotherapy, but its low water solubility poses a major problem, preventing its translation into clinical use. TPGS is a water-soluble derivative of vitamin E that acts as a surfactant with the ability to form micellar nanoparticles in water. More importantly, TPGS acts as a potent antioxidant that can neutralize intracellular reactive oxygen species (ROS). In this study, we solubilized CCM with TPGS using thin-film rehydration to prepare aqueous formulations containing CCM at clinically relevant concentrations. We found that the minimal TPGS:CCM ratio for producing nanoparticles was 5:1 (w/w): at or above this ratio, stable nanoparticles formed with an average particle diameter of 12 nm. CCM was released from TPGS/CCM micelles in simulated colonic and gastric fluids. These TPGS/CCM nanoparticles were shown to decrease intracellular ROS levels and apoptosis and inhibited migration of HT-29 human colon cancer cells more potently than free CCM. Pharmacokinetic analysis showed TPGS/CCM to be more bioavailable than free CCM after oral administration to rats. Our results suggest that TPGS/CCM may increase therapeutic efficacy of CCM against colon cancer and merits further investigation in a clinical setting.

Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla of Heph/Cp KO mice was significantly increased. Perls’ Prussian blue staining showed iron accumulation on the apical side of renal tubular cells in Heph/Cp KO mice. A significant increase in ferritin protein expression was also observed in the renal medulla and cortex of Heph/Cp KO mice. Both DMT1 and TfR1 protein expression were significantly decreased in the renal medulla of Heph/Cp KO mice, while the expression of DMT1 protein was significantly increased in the renal cortex of these animals. Significant increase in proteinuria and total urinary iron was observed in the double knockout mice, and this was associated with compromised structural integrity. These results suggest that KO of both the HEPH and CP genes leads to kidney iron deposition and toxicity, MCFs could protect kidney against a damage from iron excess.

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Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin ( Heph ) and ceruloplasmin ( Cp ) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph , Cp , and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.

Design an implant similar to the human bone is one of the critical problems in bone tissue engineering. Metal porous scaffolds have good prospects in bone tissue replacement due to their matching elastic modulus, better strength, and biocompatibility. However, traditional processing methods are challenging to fabricate scaffolds with a porous structure, limiting the development of porous scaffolds. With the advancement of additive manufacturing (AM) and computer-aided technologies, the development of porous metal scaffolds also ushers in unprecedented opportunities. In recent years, many new metal materials and innovative design methods are used to fabricate porous scaffolds with excellent mechanical properties and biocompatibility. This article reviews the research progress of porous metal scaffolds, and introduces the AM technologies used in porous metal scaffolds. Then the applications of different metal materials in bone scaffolds are summarized, and the advantages and limitations of various scaffold design methods are discussed. Finally, we look forward to the development prospects of AM in porous metal scaffolds.

In recent years, high-fat diet (HFD) has been widely applied in aquaculture, which reduces the intestinal health of cultured fish. The current study evaluated the protective effects of nano-selenium (nano-Se) on intestinal health of juvenile grass carp ( Ctenopharyngodon idella ) fed with HFD. A total of 135 experimental fish were fed with a regular diet (Con), a HFD (HFD) and a HFD containing nano-Se at 0.6 mg/kg (HSe) for 10 weeks. The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp ( P < 0.05). Also, nano-Se (0.6 mg/kg) supplement alleviated intestinal damage caused by the HFD, thus maintaining the integrity of the intestine. Moreover, it significantly up-regulated the expression of genes related to tight junction ( ZO-1 , c laudin-3 and o ccludin ), anti-oxidization ( GPx4a and GPx4b ), and the protein of ZO-1 in the intestine of juvenile grass carp, which were depressed by the HFD ( P < 0.05). Furthermore, nano-Se supplementation significantly suppressed the expressions of genes related to the inflammation, including inflammatory cytokines ( IL-8 , IL-1β , IFN-γ , TNF-α and IL-6 ), signaling molecules ( TLR4 , p38 MAPK and NF-κB p65 ), and protein expression of NF-κB p65 and TNF-α in the intestine of juvenile grass carp which were induced by the HFD ( P < 0.05). Besides, dietary nano-Se normalized the intestinal microbiota imbalance of juvenile grass carp caused by the HFD through increasing the abundance of the beneficial bacteria, e.g., Fusobacteria. Finally, dietary nano-Se increased the production of short chain fatty acids (SCFA) in the intestine, especially for butyric acid and caproic acid, which were negatively related to the increase of intestinal permeability and inflammation. In summary, supply of nano-Se (0.6 mg/kg) in HFD could effectively alleviate intestinal injury of juvenile grass carp by improving intestinal barrier function and reducing intestinal inflammation and oxidative stress. These positive effects may be due to the regulation of nano-Se on intestinal microbiota and the subsequently increased beneficial SCFA levels.

Little is known about the iron efflux mechanism in adipocytes. Here, we used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout (KO) mice and Heph/Cp double-KO mice to investigate the roles of multicopper ferroxidases (MCFs) in this process. We show that both HEPH and CP are expressed in subcutaneous adipose tissue. Ablation of either MCF leads to a compensatory increase in the other, which contributes to the balance of iron status. However, ablation of both MCFs together induces severe iron deposition in adipocytes which is associated with decreased adiponectin and leptin mRNA expression. Furthermore, Heph/Cp KO mice display disordered carbohydrate metabolism characterized as type 2 diabetes. Together, these results demonstrate the protective roles of HEPH and CP in preventing iron overload in adipocytes.