Peptide P11 suppresses the growth of human thyroid carcinoma by inhibiting the PI3K/AKT/mTOR signaling pathway.

Thyroid carcinoma is the most common endocrine malignancy, and the incidence of thyroid carcinoma is increasing in recent decades. CYYGQSKYC (P6), a nonapeptide with anti-lymphangiogenic effect by its binding to VEGFR-3 and selectively inhibiting VEGF-C binding to VEGFR-3, could suppress the migration and invasion of cancer cells. LSPPRYP (P9) acts as an effective bFGF/FGFR antagonist and inhibits the growth of the murine melanoma B16-F10 cells. In order to increase the anti-tumor effects of P6 and P9, we connected P6 with P9 via a flexible linker Gly-Gly-Gly (GGG) to reconstruct a novel peptide P11, CYYGQSKYCGGGLSPPRYP. In the present study, the mechanism of action of peptide P11 on the growth of human thyroid carcinoma cells both in vitro and in vivo was determined. Our results showed that peptide P11 inhibited the proliferation, viability, migration, and invasion of human thyroid carcinoma cells. Peptide P11 increased the apoptosis and decreased the protein levels of p-PI3K, p-AKT, and p-mTOR in human thyroid carcinoma cells. In addition, P11 could effectively inhibit the growth of human thyroid carcinoma xenograft tumors in nude mice. In conclusion, peptide P11 could inhibit the growth of human thyroid carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway. Novel peptides can be designed and applied for the treatment of various types of cancer.

Anti-inflammatory and retinal protective effects of capsaicin on ischaemia-induced injuries through the release of endogenous somatostatin.

The mechanisms regarding the retinal protective and anti-inflammatory effects of capsaicin (CAP) remain unclear. Somatostatin is contained in CAP-sensitive sensory neurons, including nerve terminals, from which it can be released by capsaicin. The present study provides a novel neurohumoral regulatory mechanism for CAP-induced-endogenous somatostatin in a retinal ischaemia-reperfusion (I/R) mouse model. CAP (0.5 mg/kg) was injected subcutaneously 5 minutes after I/R. A selective somatostatin-depleting agent, cysteamine, was applied subcutaneously 4 hours before the experiment to examine the effects of endogenous somatostatin. Ischaemia and oxidative stress-induced inflammatory factors (CXCL10, CXCR3 and NF-κB p65) were also examined in the present study. The morphometric evaluation showed that the retinal thickness was increased 24 hours after I/R injury and attenuated 7 days after I/R injury. The number of ganglion cells was reduced 7 days after I/R injury. The application of CAP significantly prevented retinal I/R damage. Cysteamine pretreatment reversed the effects of CAP. Inhibition of CXCL10/CXCR3 and NF-κB (especially in astrocytes and microglia/macrophage) was involved in capsaicin-induced retinal protection through endogenous somatostatin. CAP has anti-inflammatory and neuroprotective effects in ischaemia-induced retinal injuries through endogenous somatostatin. Novel therapeutic remedies for inflammation or neuronal injuries were developed based on the systemic humoral effects related to CAP.

Chitosan/oxidized Konjac Glucomannan films incorporated with Zanthoxylum Bungeanum essential oil: A novel approach for extending the shelf life of meat.

In this study, a novel edible composite film was prepared by chitosan, konjac glucomannan oxidized with ozone for 60 min (OKGM), and Zanthoxylum Bungeanum essential oil (ZEO). The chitosan/OKGM film was fortified with ZEO to assess the physical properties, structure, antioxidant and antibacterial abilities, and pork preservation systematically. Compared to the control group, the addition of 1 % ZEO increased tensile strength by 18.92 % and decreased water solubility, water vapor permeability, and moisture content by 10.05 %, 6.60 %, and 1.03 %, respectively. However, the treatment with ZEO (1.5 % and 2 %) decreased mechanical properties and increased the water vapor permeability. The ultraviolet barrier, antioxidant, and antibacterial abilities of composite films were enhanced by increasing the ZEO addition. Moreover, the COZ-1 film was used to protect the freshness of pork with slow-release behavior of ZEO. The results showed that addition of ZEO significantly decreased the pH value, total viable count, redness, total volatile basic nitrogen, and thiobarbituric acid and increased the hardness of pork after preservation for 10 days. Therefore, the chitosan/OKGM loaded with ZEO film can potentially be used as food packaging, providing new ideas for the research on active packaging materials.

Exogenous Hydrogen Sulfide Regulates the Growth of Human Thyroid Carcinoma Cells.

Hydrogen sulfide (H2S) is involved in the development and progression of many types of cancer. However, the effect and mechanism of H2S on the growth of human thyroid carcinoma cells remain unknown. In the present study, we found that the proliferation, viability, migration, and invasion of human thyroid carcinoma cells were enhanced by 25-50 µM NaHS (an H2S donor) and inhibited by 200 µM NaHS. However, H2S showed no obvious effects on the proliferation, viability, and migration of human normal thyroid cells. Administration of 50 µM NaHS increased the expression levels of CBS, SQR, and TST, while 200 µM NaHS showed reverse effects in human thyroid carcinoma cells. After treatment with 25-50 µM NaHS, the ROS levels were decreased and the protein levels of p-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK1/2, and p-ERK1/2 were increased, whereas 200 µM NaHS exerted opposite effects in human thyroid carcinoma cells. Furthermore, 1.4-2.8 mg/kg/day NaHS promoted the tumor growth and blood vessel formation in human thyroid carcinoma xenograft tumors, while 11.2 mg/kg/day NaHS inhibited the tumor growth and angiogenesis. In conclusion, our results demonstrate that exogenous H2S regulates the growth of human thyroid carcinoma cells through ROS/PI3K/Akt/mTOR and RAS/RAF/MEK/ERK signaling pathways. Novel H2S-releasing donors/drugs can be designed and applied for the treatment of thyroid cancer.

Peptide V3 Inhibits the Growth of Human Hepatocellular Carcinoma by Inhibiting the Ras/Raf/MEK/ERK Signaling Pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. Peptide V3 has shown anti-angiogenic and anti-tumor effects on S180 and H22 xenografts in nude mice. However, the detailed mechanism of action of peptide V3 has not yet been fully elucidated. In the present study, the effects of peptide V3 on the growth of human HCC cells were examined both in vitro and in vivo. Our results showed that peptide V3 inhibited the proliferation, viability, migration, and invasion of human HCC cells. However, no obvious effect was observed in HL-7702 cells. Peptide V3 increased the apoptosis and decreased the protein levels of H-RAS, phospho (p)-RAF, p-MEK, and p-extracellular signal-regulated protein kinase (ERK) in human HCC cells. Peptide V3 suppressed the growth of human HCC xenografts by down-regulating angiogenesis and up-regulating apoptosis. In conclusion, peptide V3 could inhibit the growth of human HCC by inhibiting the Ras/Raf/MEK/ERK signaling pathway. Novel peptides and modification strategies could be designed and applied for the treatment of different types of cancer.

Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways.

Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10-100 µM NaHS and dose-dependently inhibited by 600-1000 µM NaHS. The apoptotic levels were reduced by 25-100 µM NaHS but increased by 400-1000 µM NaHS in HCC cells. After treatment with 25-50 µM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800-1000 µM NaHS showed opposite effects on these protein levels in HCC cells. However, H2S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25-100 µM NaHS promoted HCC tumor growth and blood vessel formation, while 800-1000 µM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H2S donors could be designed and applied for further antitumor research.