The wound healing potential of collagen peptides derived from the jellyfish Rhopilema esculentum

Purpose: Wound represents a major health challenge as they consume a large amount of healthcare resources to improve patient's quality of life. Many scientific studies have been conducted in search of ideal biomaterials with wound-healing activity for clinical use and collagen has been proven to be a suitable can didate biomaterial. This study in tended to investigate the wound healing activity of collagen peptides derived from jellyfish following oral administration. Methods: In this study, collagen was extracted from the jellyfish-Rhopilema esculentum using 1% pepsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fourier transform infrared (FTIR) were used to identify and determine the molecular weight of the jellyfish collagen. Collagenase II, papain and alkaline proteinase were used to breakdown jellyfish collagen into collagen peptides. Wound scratch assay (in vitro) was done to determine migration potential of human umbilical vein endothelial cells (HUVEC) covering the artificial wound created on the cell monolayer following treatment with collagen peptides. In vivo studies were con ducted to determine the effects of collagen peptides on wound healing by examining wound contraction, re-epithelialization, tissue regeneration and collagen deposition on the wounded skin of mice. Confidence level (p < 0.05) was considered significant using GraphPad Prism software. Results: The yield of collagen was 4.31%. The SDS-PAGE and FTIR showed that extracted collagen from jellyfish was type I. Enzymatic hydrolysis of this collagen using collagenase II produced collagen peptides (CPi) and hydrolysis with alkaline proteinase/papain resulted into collagen peptides (CP2). Tricine SDSPAGE revealed that collagen peptides consisted of protein fragments with molecular weight <25 kDa. Wound scratch assay showed that there were significant effects on the scratch closure on cells treated with collagen peptides at a concentration of 6.25 μg/mL for 48 h as compared to the vehicle treated cells. Overall treatment with collagen peptide on mice with full thickness excised wounds had a positive result in wound contraction as compared with the control. Histological assessment of peptides treated mice models showed remarkable sign of re-epithelialization, tissue regeneration and increased collagen deposition. Immunohistochemistry of the skin sections showed a significant increase in β-fibroblast growth factor (β-FGF) and the transforming growth factor-βi (TGF-βi) expression on collagen peptides treated group. Conclusion: Collagen peptides derived from the jellyfish-Rhopilema esculentum can accelerate the wound healing process thus could be a therapeutic potential product that may be beneficial in wound clinics in the future.

Optimized functional and structural design of dual-target LMRAP,a bifunctional fusion protein with a 25-amino-acid antitumor peptide and GnRH Fc fragment

To develop fusion protein of a GnRH Fc fragment and the integrin targeting AP25 antitumor peptide for GnRH receptor-expressing cancer therapy.The LMRAP fusion protein was constructed.A transwell invasion assay was performed.The gene mRNA and protein levels of GnRHR-I,α5β1,andαvβ3 in different cancer cell lines were assessed.Cell proliferation was measured using a cell counting kit-8.An antagonist assay was performed on GnRH receptors.Anti-tumor activity was evaluated with a mouse xenograft tumor model.Immunohistochemistry(IHC)was applied to detect CD31 and CD34 expressions.Pharmacokinetic characteristics were determined with an indirect competition ELISA.The developed bifunctional fusion protein LMRAP not only inhibited HUVEC invasion,but also inhibited proliferation of GnRHR-I,α5β1,and high expression cancer cells.The IC50 for LMRAP in the GnRH receptor was 6.235 x 10-4 mol/L.LMRAP significantly inhibited human prostate cancer cell line22 RV1 proliferation in vivo and in vitro.LMRAP significantly inhibited CD31 and CD34 expressions.The elimination half-life of the fusion protein LMRAP was 33 h in rats.The fusion protein made of a GnRH Fc fragment and the integrin targeting AP25 peptide retained the bifunctional biological activity of GnRHR blocking,angiogenesis inhibition,prolonged half-life and good tolerance.

New arbutin derivatives from the leaves of Heliciopsis lobata with cytotoxicity

Heliciopsis lobata is a medicinal plant, which is exclusively used to treat tumor in Li folk region. Two new arbutin derivatives, 6'-((E)2-methoxy-5-hydroxycinnamoyl) arbutin(1) and 2'-((E)2, 5-dihydroxycinnamoyl) arbutin(2) along with five known compounds(3–7), were isolated from the leaves of Heliciopsis lobata. Their structures were elucidated on the basis of extensive spectroscopic interpretations. They were evaluated for their potential anticancer activity. Compounds 6 and 7 exhibited cytotoxicity against MGC-803 cells with IC_(50) values being 44.1 and 11.3 μg·m L^(–1), respectively. Additionally, compounds 1, 2 and 5–7 exhibited a moderate inhibition of MGC-803 cells invasion; compound 2 at 20 μg·m L^(–1) inhibited the invasion of MGC-803 cells by 43.0%, compared with the controls..

Integrins as attractive targets for cancer therapeutics

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes.These molecules facilitate cell-extracellular matrix and cell-cell interactions,and they have been implicated in fibrosis,inflammation,thrombosis,and tumor metastasis.The role of integrins in tumor progression makes them promising targets for cancer treatment,and certain integrin antagonists,such as antibodies and synthetic peptides,have been effectively utilized in the clinic for cancer therapy.Here,we discuss the evidence and knowledge on the contribution of integrins to cancer biology.Furthermore,we summarize the clinical attempts targeting this family in anti-cancer therapy development.

Centranthera grandiflore alleviates alcohol-induced oxidative stress and cell apoptosis

Alcohol liver disease(ALD)has become a global threat to human health.It is associated with a wide range of liver diseases including alcohol fatty liver,steatosis,fibrosis and cirrhosis,and finally leads to liver cancer and even death.Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD,but no research about its mechanism is available.This study evaluated the hepatoprotective effect and mechanism of C.grandiflora against alcohol-induced liver injury in mice.We found that the ethanol extracts of C.grandiflora(CgW)alleviated the alcohol-induced liver injury,enhanced the levels of antioxidant enzymes,and reduced the amount of lipid peroxides.CgW also affected cell apoptosis by inhibiting the activity of Bax,cleaved-caspase 3 and cleaved-caspase 9,and increasing the activity of Bcl-2.In conclusion,the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time.This study suggested that C.grandiflora is a promising herbal medicine for ALD treatment.