The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included.
Angiogenesis is required for bone development, growth, and repair. It is influenced by the local bone environment that involves cross-talks between endothelial cells and adjacent bone cells. However, data regarding factors that directly contribute to angiogenesis by bone cells remain poorly understood. Here, we report that EGFL6, a member of the epidermal growth factor (EGF) repeat superfamily proteins, induces angiogenesis by a paracrine mechanism in which EGFL6 is expressed in osteoblastic-like cells but promotes migration and angiogenesis of endothelial cells. Co-immunoprecipitation assays revealed that EGFL6 is secreted in culture medium as a homodimer protein.Using scratch wound healing and transwell assays, we found that conditioned medium containing EGFL6 potentiates SVEC (a simian virus 40-transformed mouse microvascular endothelial cell line) endothelial cell migration. In addition, EGFL6 promotes the endothelial cell tube-like structure formation in Matrigel assays and angiogenesis in a chick embryo chorioallantoic membrane. Furthermore, we show that EGFL6 recombinant protein induces phosphorylation of ERK in SVEC endothelial cells. Inhibition of ERK impaired EGFL6-induced ERK activation and endothelial cell migration. Together, these results demonstrate, for the first time, that osteoblastic-like cells express EGFL6 that is capable of promoting endothelial cell migration and angiogenesis via ERK activation. Thus, the EGLF6 mediates a paracrine mechanism of cross-talk between vascular endothelial cells and osteoblasts and might offer an important new target for the potential treatment of bone diseases, including osteonecrosis, osteoporosis, and fracture healing.Angiogenesis plays a pivotal role in bone formation, remodeling, and healing (1). In early osteogenesis during embryonic development, vascularization is required for the replacement of the hypertrophied cartilage core with bone marrow. During adulthood, angiogenesis is closely coupled with the process of bone remodeling (2, 3). Evidence has been presented that bone remodeling takes place in specialized vascular structures, bone remodeling compartments that contain osteoblastic-like cells and a vascular structure (4, 5). Lack of bone vascularity is associated with decreased bone formation and bone mass (1, 6). Furthermore, inhibition of angiogenesis during fracture repair in animals results in the formation of fibrous tissue and atrophic nonunions, leading to impaired bone healing (7).It has been widely speculated that bone remodeling requires an intimate connection between blood vessels and bone cells. Vascular endothelial cells, bone building osteoblasts, and bone-resorbing osteoclasts contribute multiple regulatory proteins that interplay autocrine/paracrine modes of regulation for the recruitment, proliferation, differentiation function, and survival of these vascular and bone cells (1,8). For instance, endothelial cells produce many factors that influence bone cells, including M-CSF, RANKL, 2 and chemokines (1, 9). Conversely, both osteoclas...
Fruit wastes are one of the main sources of municipal waste. In order to explore the potential of fruit wastes as natural resources of bioactive compounds, the antioxidant potency and total phenolic contents (TPC) of lipophilic and hydrophilic components in wastes (peel and seed) of 50 fruits were systematically evaluated. The results showed that different fruit residues had diverse antioxidant potency and the variation was very large. Furthermore, the main bioactive compounds were identified and quantified, and catechin, cyanidin 3-glucoside, epicatechin, galangin, gallic acid, homogentisic acid, kaempferol, and chlorogenic acid were widely found in these residues. Especially, the values of ferric-reducing antioxidant power (FRAP), trolox equivalent antioxidant capacity (TEAC) and TPC in the residues were higher than in pulps. The results showed that fruit residues could be inexpensive and readily available resources of bioactive compounds for use in the food and pharmaceutical industries.
Recent advances in nanotechnology and material sciences have promoted the development of nanomedicine. Among the formulations developed, novel lipid-enveloped hybrid nanoparticles have attracted more attention because of their special structure, properties and clinical applicability. The hybrid nanoparticles are composed of a hydrophilic PEG shell, a nano-sized polymeric or inorganic core and a lipid mono- or bi-layer between the core and PEG shell. This kind of nanoparticle possesses both the characteristics of liposomes and nanoparticles which endows it with many advantages like long circulation, high drug loading efficiency, high stability and biocompatibility, controlled release properties, and drug cocktail delivery. This review describes the recent developments of lipid-enveloped hybrid nanoparticles in cancer treatment, including the fabrication methods, formulations and applications of these hybrid nanoparticles. We expect that the continuing development of lipid-based nanomedicine will greatly improve cancer treatment.
Edible macro-fungi are widely consumed as food sources for their flavors and culinary features. In order to explore the potential of macro-fungi as a natural resource of bioactive compounds, the antioxidant properties and polysaccharide contents of 49 edible macro-fungi from China were evaluated systematically. A positive correlation between antioxidant capacity and total phenolic content indicated that phenolic compounds could be main contributors of antioxidant capacities of these macro-fungi. Furthermore, many bioactive compounds such as gallic, homogentisic, protocatechuic, and p-hydroxybenzoic acid were identified and quantified. The macro-fungi species Thelephora ganbajun Zang, Boletus edulis Bull., Volvariella volvacea Sing, Boletus regius Krombh, and Suillus bovinus Kuntze displayed the highest antioxidant capacities and total phenolic contents, indicating their potential as important dietary sources of natural antioxidants.
Purpose: To investigate the expression of myeloid differentiation factor 88 (MyD88) in hepatocellular carcinoma (HCC) and its prognostic value in patients with HCC.Experimental Design: Expression of MyD88 was detected by immunohistochemistry in surgical HCC specimens (n ¼ 110). The correlation of MyD88 expression to clinicopathologic characteristics was analyzed. The involvement of MyD88 in tumor growth and invasion was investigated.Results: The expression of MyD88 was significantly higher in HCC tumors than that in adjacent nontumor tissues. Particularly, high expression of MyD88 was found in HCCs with late tumor stage (P ¼ 0.029). Patients with high MyD88 staining revealed a higher recurrence rate (65% vs. 40%; P ¼ 0.008). Kaplan-Meier analysis showed that recurrence-free survival (RFS; P ¼ 0.011) and overall survival (OS; P ¼ 0.022) were significantly worse among patients with high MyD88 staining. Univariate and multivariate analyses revealed that MyD88 was an independent predictor for OS and RFS. Ectopic expression of MyD88 promoted HCC cell proliferation and invasion in vitro. Suppression of MyD88 expression with lentivirus encoding short hairpin RNA reduced tumor growth and invasion, as well as lung metastasis. Finally, silencing of MyD88 inhibited the activation of NF-kB and AKT in HCC cells, whereas forced expression of MyD88 was able to enhance the activation of NF-kB and p38/extracellular signal-regulated kinase without Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling.Conclusion: Elevated expression of MyD88 may promote tumor growth and metastasis via both TLR/IL-1R-dependent and -independent signaling and may serve as a biomarker for prognosis of patients with HCC.
In the present study, a targetable vector was developed for the targeted delivery of anticancer agents, consisting of lipid-coated poly D,L-lactic-co-glycolic acid nanoparticles (PLGA-NP) that were modified with transferrin (TF). Doxorubicin (DOX) was used as a model drug for lung cancer therapy. The use of these NPs combined the advantages and avoided the disadvantages exhibited individually by liposomes and polymeric NPs during drug delivery. The lipid coating of the polymeric core was confirmed by transmission electron microscopy. The physicochemical characteristics of transferrin-conjugated lipid-coated NPs (TF-LP), including the particle size, zeta potential, morphology, encapsulation efficiency and in vitro DOX release, were also evaluated. The cellular uptake investigation in the present study found that TF-LP was more efficiently endocytosed by the A549 cells, than LP and PLGA-NPs. Furthermore, the anti-proliferative effect exhibited by DOX-loaded TF-LPs on A549 cells and the inhibition of tumor spheroid growth was stronger compared with the effect of DOX-loaded lipid-coated PLGA-NPs and PLGA-NPs. In the in vivo component of the present study, TF-LP demonstrated the best inhibitory effect on tumor growth in the A549 tumor-bearing mice. It was concluded that TF-LP may be an efficient targeted drug-delivery system for lung cancer therapy.
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