PeposX-Exhaust: A lightweight and efficient tool for identification of short peptides.

Short peptides have become the focus of recent research due to their variable bioactivities, good digestibility and wide existences in food-derived protein hydrolysates. However, due to the high complexity of the samples, identifying short peptides still remains a challenge. In this work, a tool, named PeposX-Exhaust, was developed for short peptide identification. Through validation with known peptides, PeposX-Exhaust identified all the submitted spectra and the accuracy rate reached 75.36%, and the adjusted accuracy rate further reached 98.55% when with top 5 candidates considered. Compared with other tools, the accuracy rate by PeposX-Exhaust was at least 70% higher than two database-search tools and 15% higher than the other two de novo-sequencing tools, respectively. For further application, the numbers of short peptides identified from soybean, walnut, collagen and bonito protein hydrolysates reached 1145, 628, 746 and 681, respectively. This fully demonstrated the superiority of the tool in short peptide identification.

Corrigendum: miR-766-3p targeting BCL9L suppressed tumorigenesis, epithelial-mesenchymal transition, and metastasis through the ß-catenin signaling pathway in osteosarcoma cells.

[This corrects the article DOI: 10.3389/fcell.2020.594135.].

A Novel Porous Butyryl Chitin-Animal Derived Hydroxyapatite Composite Scaffold for Cranial Bone Defect Repair.

Bone defects, a common orthopedic problem in clinical practice, are a serious threat to human health. As alternative materials to autologous bone grafts, synthetic cell-free functionalized scaffolds have been the focus of recent research in designing scaffolds for bone tissue engineering. Butyryl chitin (BC) is a derivative of chitin (CT) with improved solubility. It has good biocompatibility, but few studies have investigated its use in bone repair. In this study, BC was successfully synthesized with a degree of substitution of 2.1. BC films were prepared using the cast film method and showed strong tensile strength (47.8 ± 4.54 N) and hydrophobicity (86.4 ± 2.46°), which was favorable for mineral deposition. An in vitro cytological assay confirmed the excellent cell attachment and cytocompatibility of the BC film; meanwhile, in vivo degradation indicated the good biocompatibility of BC. Hydroxyapatite (HA), extracted from bovine cancellous bone, had good cytocompatibility and osteogenic induction activity for the mouse osteoblast cell line MC3T3-E1. With the aim of combining the advantages of BC and HA, a BC-HA composite scaffold, with a good pore structure and mechanical strength, was prepared by physical mixing. Administered into skull defects of rats, the scaffolds showed perfect bone-binding performance and effective structural support, and significantly promoted the regeneration of new bone. These results prove that the BC-HA porous scaffold is a successful bone tissue engineering scaffold and has strong potential to be further developed as a substitute for bone transplantation.

A fast stop-flow two-dimensional liquid chromatography tandem mass spectrometry and its application in food-derived protein hydrolysates.

Food-derived bioactive peptides have many outstanding features like high safety, easy absorption, etc. However, explorations of the peptides are suffering from the limited knowledge of sample composition and low efficiency of separation techniques. In this work, a fast stop-flow two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS) was designed and constructed in-house. For chromatographic system optimization, the effects of column pairs and fraction transfer volumes on separation performance were studied. The pair of Protein BEH SEC and HSS T3 columns was found of high orthogonality. The peak capacity detected by the optimized 2DLC reached 1165 (for corn protein hydrolysates), indicating high resolving power. Moreover, the number of peptides identified from corn, soybean and casein protein hydrolysates reached as high as 8330, 8925 and 7215, respectively, demonstrating the high potential of the system. This would help reveal the peptide composition and facilitate the research on exploring bioactive peptides from food-derived protein hydrolysates.

Multichannel nerve conduit based on chitosan derivates for peripheral nerve regeneration and Schwann cell survival.

In this study, a chitosan-based composite multichannel nerve conduit consisting of a warp-knitted chitosan scaffold and internally oriented N-succinyl-chitosan (NS-chitosan) fibers was applied to bridge a 10-mm nerve defect in rats. This study confirmed that an external pipeline with appropriate mechanical support was obtained by warp knitting techniques and that NS-chitosan fibers were not toxic to L-929 and PC-12 cells. These fibers degraded slowly for over 90 days and exerted sustained neuroprotective effects on peripheral nerves through their ability to drive cellular migration, promote survival, and block apoptosis of damaged Schwann cells through the Bcl-2/Bax/caspase-3 pathway. The multichannel chitosan/NS-chitosan conduit represented a histologically and functionally successful nerve reconstruction across a damaged 10-mm peripheral nerve model, showing regenerative efficacy equal to that of an autograft. The results demonstrated that the chitosan/NS-chitosan conduit with a warp-knitted tube construct and aligned inner fiber had good mechanical and bioactive properties for nerve repair.

Nerve Regeneration Effect of a Composite Bioactive Carboxymethyl Chitosan-Based Nerve Conduit with a Radial Texture.

Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.

Long Noncoding RNA LINC00909 Induces Epithelial-Mesenchymal Transition and Contributes to Osteosarcoma Tumorigenesis and Metastasis.

Background: Osteosarcoma (OS) is a malignant tumor that is highly metastatic with a high mortality rate. Although mounting evidence suggests that LINC00909 is strongly associated with the malignant progression of various tumors, the exact role of LINC00909 in OS remains unknown. Therefore, the current study was designed to investigate the relationship between LINC00909 and the malignant progression of OS. Methods: LINC00909 expression was measured in OS cell lines and clinical specimens using RT-qPCR assays. The effects of LINC00909 on OS proliferation, invasion, and migration were calculated both in vitro and in vivo. Apart from that, bioinformatics analyses, FISH, RIP, and luciferase reporter assays were carried out to investigate the downstream target of LINC00909. Rescue experiments were also conducted to investigate the potential mechanisms of action of competitive endogenous RNAs (ceRNAs). Results: In this study, we found that LINC00909 was highly expressed in OS cell lines and clinical specimens. In vivo and in vitro experiments demonstrated that LINC00909 induces epithelial-to-mesenchymal transition (EMT) and contributes to OS tumorigenesis and metastasis. FISH, RIP, and luciferase assays indicated that miR-875-5p is a direct target of LINC00909. Moreover, HOXD9 was validated as the downstream target of miR-875-5p in a luciferase reporter assay and western blotting experiments. Rescue experiments revealed that HOXD9 reversed the effect of LV-sh-LINC00909 on OS cells by positively regulating the PI3K/AKT/mTOR signaling pathway. Conclusion: Collectively, LINC00909 induces EMT and contributes to OS tumorigenesis and metastasis through the PI3K/AKT/mTOR pathway by binding to miR-875-5p to upregulate HOXD9 expression. Targeting the LINC00909/miR-875-5p/HOXD9 axis may have potential in treating OS.

Study on repair of abdominal wall defect rats with hernia mesh coated with chitosan-based photosensitive hydrogel.

Herein, hydroxypropyl chitosan azide (AZ-HPCTS) was synthesized and prepared as a hydrogel coating applied to a polypropylene mesh (PPM) through UV irradiation. This study confirmed the hypothesis that hydrogels with porous three-dimensional network structures exhibited excellent biocompatibility and biodegradability and adhered well to PPM. During the 180-day follow-up period, the AZ-HPCTS-coated PPM (AH-PPM) promoted wound healing by promoting the secretion of transforming growth factor-beta1 (TGF-beta1) in the acute reaction stage, which was reduced to a lower level at 30 d. The PPM exhibited a lower fibrin lysozyme activity based on the expression of tissue plasminogen activator (tPA) compared with that of AH-PPM (P < 0.05). The intraperitoneal adhesion score of AH-PPM decreased to 2.4 at 180 d in contrast with PPM (P < 0.01), which remained at a high level throughout the study. In conclusion, the AZ-HPCTS hydrogel is a potential coating for hernia patches that deserves further study in the biomaterial field.

Multifunctional effects of wound dressing based on chitosan-coordinated argentum with resistant bacterial penetration.

Third-degree scald, causing serious tissue destruction with continuous pain, easily leads to microbial infections and delayed wound healing. Therefore, a multifunctional treatment is attractive for seriously damaged tissue. Herein, carboxymethyl chitosan-coordinated argentum (Ag-CMC) was synthesized via a complexation method, and then the Ag+ release, antibacterial activity, biocompatibility, pain relief and wound healing properties of Ag-CMC were investigated in vitro and in vivo. The results revealed that Ag+ had interacted with carboxymethyl chitosan, containing approximately 1.2% of silver. The Ag-CMC (50-200 µg/mL) with Ag+ sustained release exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, drug-resistant E. coli, PA, MRSA and good biocompatibility with L929 cells. Furthermore, antibacterial and wound healing experiments demonstrated that Ag-CMC achieved an effective contraction rate of 90% after 28 days by accelerating re-epithelialization, regulating inflammation response, relieving pain and infections. Therefore, Ag-CMC is a safe multifunctional treatment for wound healing and infections.

Functional thermosensitive hydrogels based on chitin as RIN-m5F cell carrier for the treatment of diabetes.

Herein, the thermosensitive hydroxypropyl chitin (HPCT) hydrogel was prepared and the chemical structures, microstructures, rheological properties and degradation in vitro were investigated. The HPCT hydrogel possessed satisfactory biocompatibility in mouse fibroblast cells and Sprague Dawley rats. On the other hand, N-acetylglucosamine (NAG) and carboxymethyl chitosan (CMCS) provided favorable capacity for promoting cell proliferation, delaying cell apoptosis, and facilitating the insulin secretion of rat pancreatic beta cells (RIN-m5F) in three-dimensional culture. Most importantly, the effects of HPCT/NAG and HPCT/CMCS thermosensitive hydrogels as RIN-m5F cells carriers were evaluated via injection into different areas of diabetic rats. Our results demonstrated that HPCT/NAG and HPCT/CMCS hydrogels loaded RIN-m5F cells could keep cells survival, maintain insulin secretion and reduce blood glucose for one week. Overall, the functional thermosensitive hydrogels based on HPCT were effective cell carriers for RIN-m5F cells and might provide novel strategy for the treatment of diabetes via cell engineering.

Injectable self-crosslinking hydrogels based on hyaluronic acid as vitreous substitutes.

After vitrectomy, the ideal vitreous substitute should be implanted to maintain the normal function of the eye. However, the existing materials (such as silicone oil, air, perfluorocarbons, etc.) still have some shortcomings and cannot fully meet the clinical needs. In this study, thiolated hyaluronic acid (SH-HA) was prepared based on hyaluronic acid. The SH-HA hydrogel was formed by a simple transformation of the sulfhydryl group to the disulfide bond, which had high transparency, controllable swelling property, suitable mechanical strength, excellent biocompatibility and similar physical and chemical properties to natural vitreous. SH-HA hydrogel was filled into the eyes of experimental rabbits to replace their own vitreous after vitrectomy. During the 90 days follow-up period, SH-HA hydrogel showed excellent intraocular compatibility, maintained normal intraocular pressure (IOP), and no cataract, endophthalmitis, retinal detachment and other complications were observed. In general, SH-HA hydrogel has great potential as a vitreous substitute.

Novel dopamine-modified oxidized sodium alginate hydrogels promote angiogenesis and accelerate healing of chronic diabetic wounds.

Herein, the dopamine (DA) was grafted with oxidized sodium alginate (OSA) via Schiff base reduction reaction, aiming to fabricate novel DA-grafted OSA (OSA-DA) hydrogels with enhanced biocompatibility and suitable adhesion for clinical applications. The chemical structures of OSA-DA were characterized via UV-Vis, FTIR and 1H NMR spectroscopy analysis. The hydrogel characteristics, biocompatibility, as well as the chronic diabetic wound healing efficacy were investigated. Our results demonstrated that DA was grafted with OSA successfully with highest grafting rate of 7.50%. Besides, OSA-DA hydrogels possessed suitable swelling ratio and appropriate adhesion characteristics. Additionally, OSA-DA exhibited satisfactory cytocompatibility and cell affinity in L-929 cells, and superior biocompatibility in SD rats. Moreover, OSA-DA exerted remarkable promoting effects on migration and tube formation of human umbilical vein endothelial cells (HUVECs). Studies on full-thickness excision chronic diabetic wounds further revealed that OSA-DA hydrogels could accelerate healing via promoting angiogenesis, reducing inflammation response, and stimulating collagen deposition. Overall, our studies would provide basis for SA-based hydrogels as clinical wound dressings.

Preparation, biocompatibility, and wound healing effects of O-carboxymethyl chitosan nonwoven fabrics in partial-thickness burn model.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm2, and water vapor transmission rate about 2600 g/m2∙24 h. Moreover, CM-CTS fabrics could effectively promote the mouse L-929 migration in vitro. CM-CTS fabrics yielded satisfactory results in angiogenesis, collagen deposition, interleukin-6 content, transforming growth factor level and healing rate, which were superior to the positive control and model groups after rats suffering with partial-thickness burn. In conclusion, CM-CTS fabrics possessed proper mechanical properties, air permeability, favorable biocompatibility, acceleration on fibroblasts migration and healing capacity for partial-thickness burn injury, and owned good potential as high-quality wound dressing.

Preparation, Characterization, and Biological Evaluation of Transparent Thin Carboxymethyl-Chitosan/Oxidized Carboxymethyl Cellulose Films as New Wound Dressings.

Full thickness burns in which the damage penetrates deep into the skin layers and reaches underneath the muscle, compel the need for more effective cure. Herein, cross-linked carboxymethyl-chitosan (CM-chitosan) films, prepared by Schiff base association with oxidized carboxymethyl cellulose (OCMC), are investigated regarding the wound healing capacity on full thickness burn injuries in vivo. Transparent thin CM-chitosan/OCMC films are obtained with tensile strength reaching 6.11 MPa, elongation at break above 27%, and water absorption more than 800%, which operates in favor of absorbing excess exudate and monitoring the wound status. Furthermore, the nonadherent CM-chitosan/OCMC films, with satisfactory biodegradability, cell, and tissue compatibility, are readily used to the wound sites and easily removed following therapy on scalded tissue so as to alleviate the suffering from burn. The films efficiently promote epithelial and dermal regeneration compared to the control, achieving 75.9% and 94.4% wound closure, respectively, after 14 and 27 days. More importantly, CM-chitosan/OCMC films accelerate wound healing with natural mechanisms which include controlling inflammatory response, reducing apoptosis, promoting fibroblast cell proliferation, and collagen formation. In conclusion, the CM-chitosan/OCMC films elevate the repair ratio of burn injuries and have great potential for facilitating the healing process on full-thickness exuding wounds.

1,25-Dihydroxyvitamin D Inhibits Osteoarthritis by Modulating Interaction Between Vitamin D Receptor and NLRP3 in Macrophages.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease globally. Loss of extracellular matrix (ECM) by chondrocytes is a classic feature of OA. Inflammatory cytokines, such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), secreted mainly by macrophages, promote expression of matrix degrading proteins and further aggravate progression of OA. 1,25-dihydroxyvitamin D (1,25VD) modulates inflammation thus exerting protective effects on cartilage tissue. However, the underlying mechanisms of 1,25VD activity have not been fully elucidated. METHODS: The destabilization of the medial meniscus (DMM)-induced mice model of OA was established to investigate the protective effects of 1,25VD by micro-CT and Safranin-O and Fast Green staining. And the co-culture system between THP-1 cells and primary chondrocytes was constructed to explore the effects of vitamin D receptor (VDR) and 1,25VD on chondrogenic proliferation, apoptosis, and migration. The immunofluorescence staining and Western blot analysis were used to detect the expressions of ECM proteins and matrix degradation-associated proteases. Enzyme-linked immunosorbent assay (ELISA) was used to examine the expression levels of inflammatory cytokines. RESULTS: The findings of the study showed that 1,25VD prevented cartilage degeneration and osteophyte formation by inhibiting secretion of inflammatory cytokines in OA mice model. These protective effects were exerted through the vitamin D receptor (VDR). Further studies showed that 1,25VD increased ubiquitination level of NLRP3 by binding to VDR, resulting in decrease in IL-1ß and IL-18 secretion. These findings indicate that 1,25VD binds to VDR thus preventing chondrogenic ECM degradation by modulating macrophage NLRP3 activation and secretion of inflammatory cytokines, thus alleviating OA progression. CONCLUSION: Here, our study suggests that 1,25VD, targeting to VDR, prevents chondrogenic ECM degradation through regulating macrophage NLRP3 activation and inflammatory cytokines secretion, thereby alleviating OA. These findings provide information on a novel molecular mechanism for application of 1,25VD as OA therapy.

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma.

INTRODUCTION: Osteosarcoma (OSA) is characterized by its relatively high morbidity in children and adolescents. Patients usually have advanced disease at the time of diagnosis, resulting in poor outcomes. This study focused on building a circular RNA-based ceRNA network to develop a reliable model for OSA risk prediction. METHODS: We used the Gene Expression Omnibus (GEO) datasets to explore the expression patterns of circRNA, miRNA, and mRNA in OSA. The prognostic value of circRNA host genes was assessed with data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database using Kaplan-Meier survival analysis. We established a circRNA-related ceRNA network and annotated its biological functions. Next, we developed a prognostic risk signature based on mRNAs extracted from the ceRNA network. We also developed a prognostic model and constructed a nomogram to enhance the prediction of OSA prognosis. RESULTS: We identified 166 DEcircRNAs, 233 DEmiRNAs, and 1317 DEmRNAs and used them to create a circRNA-related ceRNA network. We then established a prognostic risk model consisting of four genes (MLLT11, TNFRSF11B, SLC7A7, and PARVA). Moreover, we found that inhibition of MLLT11 and SLC7A7 blocked OSA cell proliferation and migration in in vitro experiments. CONCLUSION: Our study identifies crucial prognostic genes and provides a circRNA-related ceRNA network for OSA, which will contribute to the elucidation of the molecular mechanisms underlying the oncogenesis and development of OSA.

Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16.

BACKGROUND: Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action. METHODS: miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells. RESULTS: We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes. CONCLUSIONS: In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.

Hemostatic performance of chitosan-based hydrogel and its study on biodistribution and biodegradability in rats.

Hemostasis is of great significance regardless of the smooth operation or postoperative recovery. Therefore, it is urgent to develop a hemostatic material with excellent biodegradability and biocompatibility. It is well known that both carboxymethyl chitosan and hyaluronic acid with biodegradability and biocompatibility have wound healing promoting property. Here, a degradable chitosan-based hydrogel was prepared based on carboxymethyl chitosan and cross-linked by oxidized hyaluronic acid. The hemostatic performance of the hydrogel in rat liver resection injury was evaluated which results showed that the hydrogel exhibited comparable hemostatic properties compared with Fibrin Sealant. In addition, the hydrogel proved to be rapidly absorbed by the body without significant accumulation in vivo, demonstrating good biodegradability and biocompatibility. The overall results suggested the hydrogel will be a promising hemostatic hydrogel for controlling bleeding.

A self-healing and injectable hydrogel based on water-soluble chitosan and hyaluronic acid for vitreous substitute.

Vitreous, an essential dioptric medium for the human eyes, must be filled with artificial materials once damaged. Carboxymethyl chitosan (CMCTS) is one of the most important water-soluble chitosan derivatives with improved biocompatibility and biodegradability. In this study, oxidized hyaluronic acid (OHA) was prepared as crosslinking reagent. CMCTS and OHA were used to develop a biocompatible, self-repairing and in-situ injectable hydrogel for vitreous substitutes. Results showed the hydrogel with controllable swelling properties, high transparency, acceptable cytocompatibility on mouse fibroblast L929 and histocompatibility in vivo. Furthermore, hydrogel was injected in-situ into the vitreous cavity after vitrectomy on New Zealand Rabbits, no significant and persistent adverse effects were observed during the 90-day follow-up period. In addition, the hydrogel maintained intraocular pressure of the operated eyes and the inherent position of the retina. Collectively, this injectable, biodegradable, nontoxic hydrogel possessed enormous potential to become a vitreous substitute material.

Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth.

Selenium (Se) is a potential chemopreventive or chemotherapeutic agent against malignant tumor. Selenium-oligosaccharides are important selenium source of dietary supplementation. Due to the insufficient natural production, it is therefore urgent to develop selenium-oligosaccharides by artificial synthesis. Chitosan, the N-deacetylated derivative of chitin, has been applied widely in biomedical field, owing to its nontoxicity, hydrophilicity, biocompatibility, and biodegradation. While chitosan is water insoluble at neutral pH, limiting its application in physiological conditions. Chitosan oligosaccharide (COS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the D-glucosamine units. This study was aimed at preparing COS-conjugated selenium (COS-Se) and examining the toxicity and ability on improving immune function and blocking gastric cancer growth. Our results demonstrated that COS-Se displayed directly co-mitogenic and mitogenic actions on mouse splenocytes proliferation in vitro. Besides, COS-Se treatment could effectively elevate phagocytosis and increase the secretion of anti-inflammatory cytokine in mouse peritoneal macrophages. Further in vivo experiments showed that COS-Se exhibited immuno-enhancing effects through promoting the phagocytic index, spleen index and thymus index with no obvious toxicity to Kunming mice. Moreover, COS-Se inhibited proliferation and metastasis of human gastric cancer cells, with non-toxic effects on the normal fibroblast cells in vitro. COS-Se supplementation could significantly repress the growth of gastric adenocarcinoma through reducing levels of CD34, vascular endothelial growth factor and matrix metalloproteinase-9 of nude mice. In conclusion, COS-Se was non-toxic and showed great potential as a functional food ingredient in cancer prevention.