Fabrication and characterization of anchovy protein hydrolysates-polyphenol conjugates with stabilizing effects on fish oil emulsion.

Conjugation between peptides and polyphenols could improve their bioactive and functional properties. The improvement effects of anchovy protein hydrolysates (APH) -polyphenol (catechin (CA), gallic acid (GA), tannic acid (TA)) conjugates were investigated. The content of protein and polyphenols and ratio of polyphenols/peptides in conjugates increased as the number of OH group increased with TA > CA > GA. Results showed that APH-CA and APH-GA exhibited the highest ORAC and ABTS+ scavenging capacity, respectively. Mass spectrometry analysis suggested the highest number of bioactive peptides were identified in APH-CA 5:1 (APH/polyphenols). The physical stability of fish oil emulsions during storage was significantly enhanced by TA 5:1 conjugate followed by CA 5:1 conjugate. The oxidative stability was remarkably elevated by APH-GA 10:1. This was due to the antioxidant capacity and the peptides adsorbed at the interfacial. This study demonstrated that APH-polyphenol conjugates could bring the possibility of utilizing peptides-polyphenols in the nutraceutical and functional food ingredient fields.

MicroRNA-29-3p Regulates Hepatocellular Carcinoma Progression Through NF-κB Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for over 90% of all primary liver cancers. Increasing evidence suggests that microRNAs (miRNAs) mediate signaling pathways by gene expression regulation. METHODS: In this study, we evaluated the role of miR-29a-3p in HCC progression. MiR-29a-3p was found significantly down-regulated in HCC tissues compared to adjacent non-tumor tissues. Meantime, PTEN expression was up-regulated in HCC tissues. Moreover, NF-κB activity was decreased following PTEN up-regulation. RESULTS: In vitro assays in the HCC cell line BEL7402 demonstrated that miR-29a-3p suppresses cell proliferation. CONCLUSIONS: miR-29a-3p participates in the HCC progression by regulation of NF-κB pathway via targeting PTEN.

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3ß Signaling Pathway in Human Hepatocellular Carcinoma.

BACKGROUND/AIMS: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3ß signaling pathway and highlights the applicability of erinacine in HCC treatments. METHODS: HCC and paracancerous tissues were obtained from 85 HCC patients who've undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3ß. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3ß signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3ß, CyclinD1, Vimentin, ß-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). RESULTS: The results revealed that PI3K, Akt, and GSK-3ß were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3ß, CyclinD1, Vimentin, ß-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 µM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. CONCLUSION: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3ß signaling pathway, preventing the progression of HCC.

Let-7b contributes to hepatocellular cancer progression through Wnt/ß-catenin signaling.

Elevated evidences show that microRNAs (miRNAs) play vital roles in tumor progression regulation. However, the functional role of let-7b in hepatocellular carcinoma (HCC) is still largely unknown. In this study, we try to investigate the biological activity of let-7b in human HCC cells and try to find the potential regulatory signaling pathway. Our results indicate that let- 7b was remarkably down-regulated in human HCC tissues by qRT-PCR. In addition, let-7b overexpression decreased the expression of ß-catenin and c-Myc, while upregulated E-cadherin expression in HCC cells which was verified by quantitative real-time PCR (qRT-PCR) and western blotting. Furthermore, Wnt/ß-catenin was involved in let-7b biological activity which was revealed by luciferase assay. Moreover, Wnt/ß-catenin signaling inhibitor blocks HCC cell proliferation which is as the same pattern as let-7b overexpression inhibits in HCC cells proliferation. In conclusion, down-regulated let-7b promotes HCC cell proliferation through Wnt/ß-catenin signaling in HCC cells. These results suggested that appropriate manipulation of let-7b might be a new treatment of human HCC in the future.