Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p.

Circular RNA F-box and WD repeat domain containing 7 (circ-FBXW7) has been revealed to be involved in the tumorigenesis of colorectal cancer (CRC). Exosomes are critical mediators of intercellular communication. However, the role of exosomal circ-FBXW7 in the CRC oxaliplatin resistance remains unknown. Cell viability, apoptosis, motility, and drug efflux were measured by the cell counting kit-8 assay, flow cytometry, transwell assay, and atomic absorption spectrophotometry, respectively. The expression of circ-FBXW7 and microRNA (miR)-18b-5p was detected using the quantitative real-time polymerase chain reaction. Western blot was used to determine multidrug resistance protein 1 (MRP1), myeloid cell leukemia-1 (MCL-1), CD9, CD63, Caspase3, E-cadherin, and N-cadherin. Exosomes were isolated and captured using the ultracentrifugation method and transmission electron microscopy. The interaction between circ-FBXW7 and miR-18b-5p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were conducted using the murine xenograft model. Our results showed that circ-FBXW7 was decreased in oxaliplatin-resistant CRC patients and cells. circ-FBXW7 was secreted by circ-FBXW7-transfected FHC cells and could be transferred to resistant CRC cells through the exosome secretion. Subsequently, in vitro and in vivo studies demonstrated exosomal circ-FBXW7 led resistant cells sensitive to oxaliplatin, increased the oxaliplatin-induced apoptosis, inhibited oxaliplatin-induced epithelial-mesenchymal transition, and suppressed oxaliplatin efflux. miR-18b-5p was increased in oxaliplatin-resistant CRC patients and cells and was confirmed to be a target of circ-FBXW7. Immediately, the rescue assay showed exosome-mediated transfer of circ-FBXW7 enhanced oxaliplatin sensitivity by binding to miR-18b-5p in vitro and in vivo. To conclude, the circ-FBXW7 delivery by exosomes could ameliorate chemoresistance to oxaliplatin in CRC by directly binding to miR-128-3p, suggesting a promising therapeutic strategy for oxaliplatin-resistant CRC patients.

W/O/W emulsion-filled sodium alginate hydrogel beads for co-encapsulation of vitamins C and E: Insights into the fabrication, lipolysis, and digestion behavior.

In this study, vitamins C and E were simultaneously encapsulated in water-in-oil-in-water (W/O/W) emulsion-filled sodium alginate (SA) hydrogel beads, as well as the effects of SA concentrations (0.5%, 1.0%, 1.5%, and 2.0%) on the structures and lipolysis the of hydrogel beads were investigated. With increasing SA concentration, the beads showed larger sizes, denser structures and better textures. The droplets tightly penetrated the gel network at high SA concentrations. Digestion behavior revealed the disintegrated intramolecular structure at low SA concentrations. The beads with 0.5% SA were fragmented, losing the initial shape during digestion in the intestinal fluid. Additionally, lipid phases were released as W/O/W and O/W emulsion droplets after digestion. However, the high SA concentration-containing beads exhibited a well-preserved morphological structure after digestion, and the release profiles of lipid phase were mainly O/W emulsion droplets. Furthermore, vitamins C and E encapsulated in the beads exhibited high bioaccessibility (vitamin C: 90.20% and vitamin E: 95.19%).

Ultrasensitive triethylamine gas sensors with ZnSe nanospheres/nest-like Cr-doped MoO3.

Developing high-sensitivity TEA sensors has extremely important significance for human health. Design of three-dimensional (3D) nanostructures assembled from one-dimensional nanomaterials can effectively improve sensing performance. In this work, a nest-like structure assembled by Cr-doped MoO3 (Cr-MoO3) nanorods with relatively higher specific surface area was prepared. In order to improve the sensing performance, Cr-MoO3 skeleton was combined with ZnSe nanospheres of different mass ratios as sensing materials (ZnSe/Cr-MoO3), and the successful construction of the heterojunction structure was supported by various spectroscopies and charge density calculation. The prepared composite with an optimal moiety ratio showed very high response values of 371 and 1301 for 10 ppm and 50 ppm for TEA at 200 °C, respectively. Simultaneously, the composite sensor also exhibited a low detection limit (1.7 ppb). The improvement of the sensing performance of ZnSe/Cr-MoO3 was attributed to the formation of oxygen vacancies induced by Cr doping, the 3D nest-like structure provided an efficient network for charge transport/collection and the n-n heterojunctions between Cr-MoO3 nanorods and ZnSe nanospheres. The simulation analysis based on density functional theory (DFT) calculations indicated that the heterojunctions could effectively enhance the adsorption energy of TEA and the more charges transferring from TEA to the Cr-MoO3 nanorods.

Characterization and utilization of soy protein isolate-(-)-epigallocatechin gallate-maltose ternary conjugate as an emulsifier for nanoemulsions: Enhanced physicochemical stability of the ß-carotene nanoemulsion.

In this study, a ternary conjugate was prepared by covalent bonding of protein, polysaccharide, and polyphenol via ultrasound and the Maillard reaction. Subsequently, the ß-carotene nanoemulsion was prepared with the soy protein isolate-(-)-epigallocatechin gallate-maltose (SPI-EGCG-maltose) conjugate as the emulsifiers via ultrasound. The SPI-EGCG-maltose conjugate showed superior solubility, emulsification and foaming properties at 4 h reaction time. Meanwhile, the retention rates of ß-carotene in the nanoemulsion after 30 d of storage, 8 h of light, and 55 °C of heat were >60%, >75%, and >60%, respectively. Furthermore, ultrasound treatment at 500 W for 10 min produced an inhibitory effect on the degradation of ß-carotene. This study indicates that the nanoemulsion based on the ternary conjugate can effectively inhibit the ß-carotene degradation by the external environment and prevent the oxidation and degradation of ß-carotene in the nanoemulsion.

The essential effect of mTORC1-dependent lipophagy in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease with increasing prevalence. Lipophagy is a type of programmed cell death that plays an essential role in maintaining the body's balance of fatty acid metabolism. However, the livers of NAFLD patients are abnormally dysregulated in lipophagy. mTORC1 is a critical negative regulator of lipophagy, which has been confirmed to participate in the process of lipophagy through various complex mechanisms. Therefore, targeting mTORC1 to restore failed autophagy may be an effective therapeutic strategy for NAFLD. This article reviews the main pathways through which mTORC1 participates in the formation of lipophagy and the intervention effect of mTORC1-regulated lipophagy in NAFLD, providing new therapeutic strategies for the prevention and treatment of NAFLD in the future.

Encapsulating vitamins C and E using food-grade soy protein isolate and pectin particles as carrier: Insights on the vitamin additive antioxidant effects.

Functional factors show additive effects in the same nutraceutical food. In this study, a core-shell structure based on soy protein isolate (SPI) and pectin was constructed as a delivery system for vitamins C and E under neutral (pH 7.0) and acidic environment (pH 4.0). The SPI-vitamin-pectin complex formed at pH 4.0 showed larger particle size, higher turbidity, lower fluorescence intensity, and higher vitamin E encapsulation efficiency than those formed at pH 7.0. Also, the addition of vitamin C significantly enhanced the vitamin E encapsulation efficiency in the particles. Furthermore, the antioxidant properties of DPPH, ABTS, and hydroxyl radicals were increased by the addition of vitamin C, maximum values of 77%, 82%, and 65%, suggesting that vitamins C and E have additive antioxidant effects. These findings proposed a simple, structured protein-polysaccharide-based food-grade delivery system, which could serve as the basis for the design of products having multiple functional factors.

Caffeine Ameliorates AKT-Driven Nonalcoholic Steatohepatitis by Suppressing De Novo Lipogenesis and MyD88 Palmitoylation.

Dysregulated hepatic lipogenesis represents a promising druggable target for treating nonalcoholic steatohepatitis (NASH). This work aims to evaluate the therapeutic efficacy of caffeine in a NASH mouse model displaying increased hepatic lipogenesis driven by constitutive hepatic overexpression of the active v-akt murine thymoma viral oncogene homolog (AKT). Caffeine was administered in the AKT mice to study the efficacy in vivo. AKT-transfected and insulin-stimulated human hepatoma cells were used for in vitro experiments. The results demonstrated that caffeine ameliorated hepatic steatosis and inflammatory injury in vivo. Mechanistically, caffeine repressed the AKT/mTORC1 and SREBP-1/ACC/FASN signaling in mice and in vitro. Furthermore, caffeine impaired NF-κB activation by stabilizing IκBα, resulting in a reduction of proinflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Notably, caffeine abolished mTORC1/FASN-dependent MyD88 palmitoylation, which could be essential for its anti-inflammatory potential. Collectively, these results suggest that caffeine consumption could be advantageous in the prevention and therapy of NASH, especially in the subset accompanied by increased de novo lipogenesis.

Tumor suppressive effect of scavenger receptor class A member 5 overexpression in colorectal cancer by regulating PI3K/AKT/mTOR pathway.

BACKGROUND: Colorectal cancer (CRC) exhibits high risks of morbidity and mortality. OBJECTIVE: To investigate the effect of scavenger receptor class A member 5 (SCRAR5) on CRC and its mechanism on modulation of cancer development. METHODS: The SCRAR5 expression in four kinds of CRC cell lines (SW620, SW480, HT29, and HCT116) was measured by quantitative PCR and western blotting, respectively. The effects of SCRAR5 abnormal expression on cell proliferation, apoptosis, and migration were analyzed by CCK-8 assay, EdU assay, colony-forming assay, flow cytometry assay, Transwell assay and wound healing assay, respectively. Meanwhile, the involvements of PI3K/AKT/mTOR pathway with the role of SCRAR5 were investigated by western blotting. Afterwards, the in vivo effects of SCRAR5 abnormal expression on CRC xenograft mice were finally investigated by evaluating tumor volume, apoptosis and Ki67 expression. RESULTS: SCRAR5 was lowly expressed in CRC cell lines, especially SW480 cells. Up-regulation of SCRAR5 significantly promoted cell apoptosis, reduced cell proliferation and migration in SW480 cells. Notably, SCRAR5 overexpression obviously inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Reversely, SCRAR5 silence exhibited promoting effects on HT29 cells. Consistently, in vivo experiments also revealed that SCRAR5 overexpression remarkably suppressed tumor volume and Ki67 expression, as well as promoted cell apoptosis. CONCLUSIONS: Overall, up-regulating of SCRAR5 obviously inhibited CRC tumor growth in vitro and in vivo, which might be related to PI3K/AKT/mTOR pathway.