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O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.

A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described. These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs). Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.

O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of α-dystroglycan, which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 core M1 and core M2 O-mannose glycans. This chemoenzymatic strategy features the gram-scale chemical synthesis of five judiciously designed core structures, and the diversity-oriented modification of the core structures with three enzyme modules to provide 58 complex O-mannose glycans in a linear sequence that does not exceed four steps. The binding profiles of synthetic O-mannose glycans with a panel of lectins, antibodies, and brain proteins were also explored by using a printed O-mannose glycan array., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous studies demonstrated that SIP-SII, a sulfated derivative of SIP that is isolated from the ink of Sepiella maindroni, showed significant inhibition of tumor growth and metastasis. In this study, the effects of SIP-SII on the migration, invasion and molecular mechanism in ovarian cancer cell line, SKOV-3 cells, were investigated. The flow cytometry, confocal microscope observation, western blot and RT-PCR results indicated that SIP-SII located on cell membrane and inhibited the expression and activation of epidermal growth factor receptor (EGFR). Moreover, the binding capacity of SIP-SII with EGFR was confirmed by surface plasmon resonance (SPR) analysis and co-localization of EGFR and SIP-SII. Accordingly, SIP-SII was proved to attenuate the EGF-induced EGFR phosphorylation and migration by western blot and wound healing assay, respectively. Additionally, SIP-SII inhibited p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells significantly. What is more, SIP-SII showed amplified inhibitory activity on migration, invasion, and MMP-2 expression in combination with p38-specific inhibitor, PI3K-specific inhibitor or mTOR-specific inhibitor in SKOV-3 cells. Therefore, the mechanism that SIP-SII suppressed EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways to inhibit migration and invasion of SKOV-3 cells was demonstrated. These findings suggested that SIP-SII might be used as a potential inhibitor against tumor metastasis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

SIP-SII, the sulfated Sepiella maindroni ink polysaccharide (SIP), has been manifested to possess anti-tumor and anti-metastasis activity in vivo and in vitro. In the present study, we evaluated its inhibitory effect on the epidermal growth factor (EGF)-induced migration and invasion of human epidermoid carcinoma cell (KB cell line) as well as the related signaling pathways. The results of MTT assay indicated that SIP-SII inhibited the proliferation of KB cells in a concentration and time dependent manner. Notably, the attenuation of cell growth by SIP-SII was enlarged in the presence of EGF. The wound healing assay and transwell invasion assay were used to evaluate the effect of SIP-SII on the EGF-induced migration and invasion of KB cells and the results showed that SIP-SII markedly attenuated the EGF-induced migration and invasion. Besides, the EGF-induced matrix metalloproteinase-2 (MMP-2) expression was also suppressed by SIP-SII. However, SIP-SII showed no significant inhibition of the EGF-induced matrix metalloproteinase-9 (MMP-9) expression. Further research revealed that SIP-SII decreased the EGF-induced phosphorylation of epidermal growth factor receptor (EGFR), Akt and p38, but no significant suppression on EGF-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2) and c-Jun N-terminal kinases (JNK) by SIP-SII treatment was observed. The involvement of EGFR/Akt/p38 pathway was confirmed by evidence that SIP-SII would enlarge the inhibitory effect of the specific signal pathway inhibitors. These results indicate that SIP-SII has the potential to be used as the inhibitor of tumor metastasis especially for cancers characterized by over-activation of EGF/EGFR signaling., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The polysaccharides used in the treatment of osteoarthritis (OA) mainly include sodium hyaluronate, chondroitin sulfate, chitosan, xanthan gum, Low molecular weight heparin, alginate and other polysaccharides. This review summarizes the recent advances in the chemistry and biological activities of polysaccharides for the treatment of OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Our previous studies demonstrated that SIP-S had anti-metastatic activity and inhibited the growth of metastatic foci. Here we report the anti-tumor and immunoregulatory potential of SIP-S. SIP-S could significantly inhibit tumor growth in S180-bearing mice, and the inhibition rates was 43.7% at 30 mg/kg d. Besides, SIP-S could improve the thymus and spleen indices of S180-bearing mice and the mice treated with CTX. The combination of SIP-S (15 mg/kg d) with CTX (12.5 mg/kg d) showed higher anti-tumor potency than CTX (25 mg/kg d) alone. These results indicated that SIP-S had immunoenhancing and anticancer activity, and the immunoenhancing activity might be one mechanism for its anti-tumor activity. Flow cytometry results showed that SIP-S could induce tumor cells apoptosis. Western blot analysis indicated that SIP-S could upregulate the expression of pro-apoptotic proteins, caspase-3, -8, -9 and Bax, and downregulate the expression of anti-apoptotic protein PARP-1 in tumor cells in a dose-dependent manner. In summary, SIP-S has anti-tumor activity, which may be associated with its immunostimulating and pro-apoptotic activity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The diversity-oriented chemoenzymatic synthesis of α-dystroglycan (α-DG) core M1 O-mannose glycans has been achieved via a three-step sequential one-pot multienzyme (OPME) glycosylation of a chemically prepared disaccharyl serine intermediate. The high flexibility and efficiency of this chemoenzymatic strategy was demonstrated for the synthesis of three more complex core M1 O-mannose glycans for the first time along with three previously reported core M1 structures.

Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years.

A previous study demonstrated that SIP-SII, a sulfated Sepiella maindroni ink polysaccharide, suppressed the invasion and migration of cancer cells via the inhibition of the proteolytic activity of matrix metalloproteinase-2 (MMP-2). Therefore, this study investigated the anti-metastatic effect of SIP-SII in vivo. SIP-SII (15 and 30 mg/kg d) markedly decreased B16F10 pulmonary metastasis in mice models by 85.9% and 88.0%, respectively. Immunohistochemistry showed that SIP-SII decreased the expression of the intercellular adhesion molecule 1 (ICAM-1) and basic fibroblast growth factor (bFGF) in lung metastasis nodules. In addition, SIP-SII inhibited neovascularization in chick chorioallantoic membrane assay at 0.08-2 mg/mL. In the in vitro experiments, SIP-SII (0.8-500 μg/mL) significantly decreased the protein and mRNA expression of ICAM-1 and bFGF in SKOV3 and EA.hy926 cells, respectively. These results suggested that SIP-SII might suppress melanoma metastasis via the inhibition of the tumor adhesion mediated by ICAM-1 and the angiogenesis mediated by bFGF, as well as resulting in depression of the invasion and migration of carcinoma cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all of the chemotherapy drugs currently on the market cause serious side effects. Fortunately, several previous studies have shown that some non-toxic biological macromolecules, including polysaccharides and polysaccharide-protein complexes, possess anti-cancer activities or can increase the efficacy of conventional chemotherapy drugs. Based on these encouraging observations, a great deal of effort has been focused on discovering anti-cancer polysaccharides and complexes for the development of effective therapeutics for various human cancers. This review focuses on the advancements in the anti-cancer efficacy of various natural polysaccharides and polysaccharide complexes in the past 5 years. Most polysaccharides were tested using model systems, while several involved clinical trials., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A strain of Bacillus licheniformis 8-37-0-1 with high exopolysaccharide (EPS) production ability was isolated and identified based on morphological and physiological characteristics and phylogenetic analysis of 16S rDNA sequences. A new type of EPS was isolated from the strain fermentation broth by enzymolysis, isopropanol precipitation, anion-exchange, and gel-filtration chromatography. The new EPS was determined as homogeneous, with a molecular weight of 2.826 x 10(4), as determined by High-Performance Size-Exclusion Chromatography Multi-Angle Laser Light Scattering analysis. Its structural characteristics were investigated and elucidated by methylation analysis, partial acid hydrolysis, gas-liquid chromatography mass spectrometry, Fourier transform infrared, and nuclear magnetic resonance spectroscopy. Based on obtained data, the EPS was found to be a levan containing a (2-->6)-linked backbone with a single beta-d-fructose at the C-1 position every seven residue, on average, along the main chain. Preliminary in vitro tests revealed that EPS could significantly stimulate the proliferation of spleen lymphocyte., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Our previous work showed that SEP, a novel glucan isolated from the eggs of sea urchins, Strongylocentrotus nudus, had remarkable anti-tumor activity. To elucidate the mechanism of the anti-tumor activity, the immunomodulatory activity of SEP was investigated. The in vivo experiment results showed that SEP remarkably enhanced spleen and thymus index in S180-bearing mice, and also stimulated ConA-induced splenocyte proliferation. Immunomodulatory activity assay in vitro indicated SEP could significantly enhance the mouse splenocyte proliferation in a dose-dependent manner. According to comitogenic activity tests, SEP showed significant comitogenic activities and adjuvant properties. We also demonstrated that SEP had a unique mode of immunostimulation with regard to its cell-type specificity. In other words, SEP markedly stimulated B and T cell proliferation, however the influence on B cells was greatly weaker than that on T cells. IL-2, TNF-alpha, and IFN-gamma mRNA expression was upregulated after the mouse splenocytes were treated by SEP, indicating that Th1 cell was the primary cellular target affected by SEP on T lymphocyte. SEP enhanced production of nitric oxide (NO), upregulated mRNA expression of inducible nitric oxide synthase (iNOS) in peritoneal macrophages in a dose-dependent manner. In addition, SEP did not show direct toxicity to tumor cells. Consequently, the anti-tumor effect of SEP was related to stimulating host immunity/enhancing the immune system functions, which may mainly result from SEP activating lymphocytes and macrophages and stimulating secretion of some cytokines.

SIP-SII is the sulfated S. maindroni ink polysaccharide (SIP) isolated from cuttlefish Sepiella maindroni. SIP-SII weakly inhibited tumor cell growth without cytotoxicity in vitro assay. Herein, we examined the effects of SIP-SII on the expression of matrix metalloproteinase MMP-2 and MMP-9 as well as tumor cell invasion and migration. SIP-SII (0.8-500 microg/ml) significantly decreased the expression of MMP-2 activity in human ovarian carcinoma cells SKOV3 as evidenced by the gelatin zymography analysis. No significant decrease of MMP-9 was detected in the cell line after SIP-SII treatment. The expression of MMP-2 was also evaluated using Western blot analysis. The results showed that SIP-SII inhibited the expression of MMP-2 in SKOV3 and human umbilical vein vascular endothelial cells ECV304 after 24 h incubation. Furthermore, the activity of invasion and migration of SKOV3 and ECV304 cells were measured. SIP-SII displayed an inhibitory effect on the penetration of SKOV3 cells through Matrigel-coated membrane in transwell chamber. A significant inhibition of ECV304 cell migration was observed in the presence of SIP-SII. These results suggest that SIP-SII might suppress invasion and migration of carcinoma cells via inhibition of MMP-2 proteolytic activity.

It has been 30 years since the discovery of the anti-tumour property of paclitaxel (PTX), which has been successfully applied in clinic for the treatment of carcinomas of the lungs, breast and ovarian. However, PTX is poorly soluble in water and has no targeting and selectivity to tumour tissue. Recent advances in active tumour targeting of PTX delivery vehicles have addressed some of the issues related to lack of solubility in water and non-specific toxicities associated with PTX. These PTX delivery vehicles are designed for active targeting to specific cancer cells by the addition of ligands for recognition by specific receptors/antigens on cancer cells. This article will focus on various ligands and related targeting strategies serving as potential tools for active targeting of PTX to tumour tissues, illustrating their use in different tumour models. This review also highlights the need of further studies on the discovery of receptors in different cells of specific organ and ligands with binding efficiency to these specific receptors. [ABSTRACT FROM AUTHOR]

To improve the ability of superoxide dismutase (SOD) to suppress reactive oxygen species (ROS)-mediated injury, chemically modified derivatives of SOD with N, N, N-trimethyl chitosan chloride (TMC) and heparin, cationized SOD (TMC-SOD), and anionized SOD (heparin-SOD) were designed and prepared. In this study, the inhibitory effect of TMC-SOD and heparin-SOD on superoxide anion release from macrophages was studied in vitro. Both TMC-SOD and heparin-SOD exhibited excellent inhibitory effects on superoxide anion release from macrophages, and the effects of TMC-SOD surpassed those of native SOD and heparin-SOD. The effects of TMC-SOD and heparin-SOD on inflammatory cytokine expression in vitro were also evaluated. The results showed that both TMC-SOD and heparin-SOD could significantly lower the levels of transforming growth factor-β1 (TGF-β1) and interleukine-1β (IL-1β) expressed by irradiated 3T3 fibroblasts. These results demonstrated that cationic polysaccharide or anionic polysaccharide SOD derivatives might be useful in the prevention and treatment of ROS-mediated inflammatory diseases. This study also demonstrated that chemical modification of SOD, especially cationization, greatly enhanced SOD’s intracellular delivery and, consequently, produced a significant protective effect against ROS-mediated injury. [ABSTRACT FROM AUTHOR]

A water-soluble polysaccharide named as PRP was isolated from the fruiting bodies of Phellinus ribis by hot water extraction, DEAE-cellulose and Superdex 30 column chromatography. Its structural characteristics were investigated by FT-IR, NMR spectroscopy, GLC-MS, methylation analysis, periodate oxidation and Smith degradation. Based on the data obtained, PRP was found to be a β-d-glucan containing a (1→4), (1→6)-linked backbone, with a single β-d-glucose at the C-3 position of (1→6)-linked glucosyl residue every eight residues, along the main chain. The glucan has a weight-average molecular weight of about 8.59kDa by HPGPC determination using dextran samples as the standards. Preliminary activity tests in vitro revealed that PRP could stimulate the proliferation of spleen lymphocyte. [Copyright &y& Elsevier]

β-glucans, a group of polysaccharides exist in many organism species such as mushrooms, yeasts, oats, barley, seaweed, but not mammalians, have a variety of biological activities and applications in drugs and other healthcare products. In recent years, β-glucans have been studied as adjuvants in anti-infection vaccines as well as immunomodulators in anti-cancer immunotherapy. β-glucans can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines. When β-glucans act as immunostimulants or adjuvants, a set of receptors have been revealed to recognize β-glucans, including dectin-1, complement receptor 3 (CR3), CD5, lactosylceramide, and so on. Therefore, this review is mainly focused on the application of β-glucans as immune adjuvants, the receptors of β-glucans, as well as their structure and activity relationship which will benefit future research of β-glucans. [ABSTRACT FROM AUTHOR]

Sepiella maindroni ink polysaccharide (SIP) from the ink of cuttlefish Sepiella maindroni and its sulfated derivative (SIP-SII) have been demonstrated to possess diverse biological activities. But little is known about low molecular weight squid ink polysaccharides (LMWSIPs). In this study, LMWSIPs were prepared by acidolysis, and the fragments with molecular weight (M w) distribution in the ranges of 7 kDa to 9 kDa, 5 kDa to 7 kDa and 3 kDa to 5 kDa were grouped and named as LMWSIP-1, LMWSIP-2 and LMWSIP-3, respectively. The structural features of LMWSIPs were elucidated, and their anti-tumor, antioxidant and immunomodulatory activities were also studied. The results showed that with the exception of LMWSIP-3, the main structures of LMWSIP-1 and LMWSIP-2 did not change compared with SIP. Though there were no significant differences in the antioxidant capacity between LMWSIPs and SIP, the anti-tumor and immunomodulatory activities of SIP were enhanced to a certain extent after degradation. It is particularly noteworthy that the activities of LMWSIP-2 in anti-proliferation, promoting apoptosis and inhibiting migration of tumor cells as well as promoting the proliferation of spleen lymphocytes were significantly higher than those of SIP and the other degradation products, which is promising in the anti-tumor pharmaceutical field. • Sepiella maindroni ink polysaccharide (SIP) was degraded by acidolysis to prepare low molecular weight SIPs (LMWSIPs). • The main structures of LMWSIP-1 and LMWSIP-2, except for LMWSIP-3, were not changed compared with SIP. • Compared with SIP and other derivatives, LMWSIP-2 showed the strongest anti-tumor and immunomodulatory activities. • The antioxidant activity of SIP was not altered after degradation. [ABSTRACT FROM AUTHOR]

Chitin is a natural polymeric polysaccharide extracted from marine crustaceans, and chitosan is obtained by removing part of the acetyl group (usually more than 60 %) in chitin's structure. Chitosan has attracted wide attention from researchers worldwide due to its good biodegradability, biocompatibility, hypoallergenic and biological activities (antibacterial, immune and antitumor activities). However, research has shown that chitosan does not melt or dissolve in water, alkaline solutions and general organic solvents, which greatly limits its application range. Therefore, researchers have carried out extensive and in-depth chemical modification of chitosan and prepared a variety of chitosan derivatives, which have expanded the application field of chitosan. Among them, the most extensive research has been conducted in the pharmaceutical field. This paper summarizes the application of chitosan and chitosan derivatives in medical materials over the past five years. [Display omitted] [ABSTRACT FROM AUTHOR]

A new polysaccharide named PRG was isolated from the fruiting bodies of Phellinus ribis by hot water extraction, ethanol precipitation, anion-exchange and gel-filtration chromatography. PRG was homogeneous, with a molecular weight of 5.16 × 10 3 Da, as determined by high-performance size-exclusion chromatography–multiangle laser light scattering analysis. Its structural characteristics were investigated and elucidated by methylation analysis, partial acid hydrolysis, gas–liquid chromatography mass spectrometry, Fourier transform infrared and nuclear magnetic resonance spectroscopy. Based on obtained data, PRG was found to be a β- d -glucan containing a (1 → 3)-linked backbone, with a branch of two (1 → 6)-linked and one terminal glucoses substituting at the C-6 position every three residues, along the main chain. PRG exhibited neurotrophic activity, which significantly promoted the neurite outgrowth of the nerve growth factor-stimulated PC12 cells, suggesting that it might be a potential candidate for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract: The paper reports the preparation, characterization and potential biological activities of a chemically sulfated polysaccharide isolated from Phellinus ribis. Four sulfated derivatives (PRP-SI–IV) with variable degrees of substitution were obtained by the chlorosulfonic acid method, without degradation of the polysaccharide (PRP). The sulfate groups were not regularly distributed along the polysaccharide chain with a multiple substitution pattern as determined by 13C NMR. The sulfated derivatives except for PRP-SI showed significant inhibition effects on HepG2 cells in comparison with the native non-sulfated polysaccharide (PRP). All sulfated derivatives could block new angiogenic vessel formation in zebrafish assay, however, the effects were less than PRP. [Copyright &y& Elsevier]