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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]

Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely “coding” and “decoding” steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The “coding” process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N -deacetylase/ N -sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the “decoding” process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. [ABSTRACT FROM AUTHOR]

Conventional DEA models make no hypothesis concerning the internal operations in a static situation. To open the “black box” and work with dynamic assessment issues synchronously, we put forward a hybrid model for evaluating the relative efficiencies of a set of DMUs over an observed time period with a composite of network DEA and dynamic DEA. We vertically deal with intermediate products between divisions with assignable inputs in the network structure and, horizontally, we extend network structure by means of a dynamic pattern with unrelated activities between two succeeding periods. The hybrid dynamic network DEA model proposed in this paper enables us to (i) pry into the internal operations of DEA by another network structure, (ii) obtain dynamic change of period efficiency, and (iii) gain the overall dynamic efficiency of DMUs over the entire observed periods. We finally illustrate the calculation procedure of the proposed approach by a numerical example. [ABSTRACT FROM AUTHOR]

Compared to conventional progressive cavity pump (PCP), even thickness PCP has numerous advantages such as uniform thermal and swelling expansion, stable operation and high volumetric efficiency. However, adhesive failure occurs on the stator of even thickness PCP more often in actual working conditions, which limits its development and application. In this study, finite element models of conventional PCP and even thickness PCP with the same structural parameters are established and simulated to find the mechanism for adhesive failure. We primarily study the force conditions of adhesive interface which bonds the stator and cylinder sleeve. The results show that shear strain caused by hydraulic pressure difference and interference displacement is quite large around the adhesive interface of even thickness PCP. The too large shear strain around the adhesive interface is the main cause of adhesive failure. Based on this analysis, the relationship between the shear strain and design parameters, such as the rubber adhesion ratio, pressure difference, elastic modulus of stator, magnitude of interference and wall thickness, is investigated. Our results show that the shear strain increases greatly and adhesive failure tends to occur in certain conditions. Furthermore, two new techniques to enhance the adhesive performance are presented and validated with our finite element analysis. Our research can be of great significance for guiding the design and optimization of even thickness PCPs. [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]

Curdlan have been investigated for a long time. This β (1 → 3)-glucan has distinctive thermal gel-forming character and is edible, which was approved by the Food and Drug Administration (FDA) to be used in food industry. However, curdlan has poor solubility which limit its use and therefore, many researchers concentrate on curdlan modification and as a consequence diverse curdlan derivatives have been prepared. The initial modification purpose was to increase the solubility in water, while with further study, biological activities such as anti-cancer, anti-coagulation, anti-virus and immune-regulation were discovered. Thus curdlan and its derivatives have increasingly wide uses in different areas. In order to give a more comprehensive understanding for curdlan and its derivatives, we summarized recent advances of curdlan and its derivatives, as well as the existing problems need to be solved. [ABSTRACT FROM AUTHOR]

Background: We investigated the effect of the pretransplant administration of recipient''s blood to donor on rat hepatic allograft survival. Methods: Serum levels of interferon (IFN)-γ were determined after transplantation. Immunocompetent cells from the donor were identified with anti-donor class II MHC (RT1Ba) (OX-76) antibodies. The number of donor-derived CD4+ and CD8+ T cells in hepatic allografts or recipient spleen was determined. Results: LEW rats transplanted with hepatic allografts from ACI rats survived a mean of 11.1±2.1 days. Pretreatment intravenous administration of recipient LEW blood did not prolong the survival of hepatic allografts (10.5±1.7 days). In contrast, pretreatment intraportal administration of recipient LEW blood significantly increased the survival of LEW recipients with ACI livers to 31.7±7.6 days (Table 1). The ratio of ox76+CD4+ or ox76+CD8+ T cell to CD4+ or CD8+ cell was significantly greater (25.6% versus 5.7%, 26.6% versus 6.8%) in hepatic allografts pretreated with pretransplant intraportal administration of LEW recipient blood, rather than those cells in recipient spleen (46.2% versus 34.4%, 63.7% versus 71.4%). Conclusions: Pretransplant intraportal administration of recipient LEW blood to ACI donor rats prolonged the survival of hepatic allografts. This may be associated with the regional graft-versus-host reaction. [Copyright &y& Elsevier]

The core component of the fracturing and completion integral string is the setting and anchoring system, which mainly includes upper and lower permanent slips. Reasonable structural optimization design can reduce the damage of downhole string components and improve the adaptability of completion string in complex reservoir. In order to optimize the structural design of completion string and improve the reliability of anchoring setting, the influence of shape and bearing capacity on slip structure of permanent packer was considered by using nonlinear finite element numerical analysis method. On this basis, the optimized results of the permanent slips were tested by the anchoring and setting experiments of the loading pressure inside the string. The results showed that the optimized permanent slip had the advantages of low fracture strength, supplementary fracture setting performance and high reliability compared with the conventional permanent slip structure. The optimized permanent slip structure plays an important role in improving the reliability of the completion string, which is of great significance to improve the formation adaptability of the whole fracturing completion string and the effective development of tight sandstone gas reservoirs. [ABSTRACT FROM AUTHOR]

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]

The high vascularization of glioma highlights the potential value of anti-angiogenic therapeutics for glioma treatment. Previously, we designed a novel vascular-targeting and blood–brain barrier (BBB)-penetrating peptide, TAT-AT7, by attaching the cell-penetrating peptide TAT to a vascular-targeting peptide AT7, and we demonstrated that TAT-AT7 could target binding to the vascular endothelial growth factor receptor 2 (VEGFR-2) and Neuropilin-1 (NRP-1), which are both highly expressed in endothelial cells. TAT-AT7 has been proven to be a good targeting peptide which could effectively deliver the secretory endostatin gene to treat glioma via the TAT-AT7-modified polyethyleneimine (PEI) nanocomplex. In the current study, we further explored the molecular binding mechanisms of TAT-AT7 to VEGFR-2 and NRP-1 and its anti-glioma effects. Accordingly, TAT-AT7 was proven to competitively bind to VEGFR-2 and NRP-1 and prevent VEGF-A165 binding to the receptors by the surface plasmon resonance (SPR) assay. TAT-AT7 inhibited endothelial cells' proliferation, migration, invasion, and tubule formation, as well as promoted endothelial cells' apoptosis in vitro. Further research revealed that TAT-AT7 inhibited the phosphorylation of VEGFR-2 and its downstream PLC-γ, ERK1/2, SRC, AKT, and FAK kinases. Additionally, TAT-AT7 significantly inhibited angiogenesis of zebrafish embryo. Moreover, TAT-AT7 had a better penetrating ability and could penetrate the BBB into glioma tissue and target glioma neovascularization in an orthotopic U87-glioma-bearing nude mice model, and exhibited the effect of inhibiting glioma growth and angiogenesis. Taken together, the binding and function mechanisms of TAT-AT7 were firstly revealed, and TAT-AT7 was proven to be an effective and promising peptide for the development of anti-angiogenic drugs for targeted treatment of glioma. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As a key component in the standard treatment of TNBC, paclitaxel (PTX) effectively inhibits the growth and proliferation of tumor cells. However, the application of PTX in clinical treatment is limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, and side effects. To counter these problems, we constructed a novel PTX conjugate based on the peptide-drug conjugates (PDCs) strategy. In this PTX conjugate, a novel fused peptide TAR consisting of a tumor-targeting peptide, A7R, and a cell-penetrating peptide, TAT, is used to modify PTX. After modification, this conjugate is named PTX-SM-TAR, which is expected to improve the specificity and penetrability of PTX at the tumor site. Depending on hydrophilic TAR peptide and hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles and improve the water solubility of PTX. In terms of linkage, the acid- and esterase-sensitive ester bond was used as the linking bond, with which PTX-SM-TAR NPs could remain stable in the physiological environment, whereas PTX-SM-TAR NPs could be broken and PTX be released at the tumor site. A cell uptake assay showed that PTX-SM-TAR NPs were receptor-targeting and could mediate endocytosis by binding to NRP-1. The vascular barrier, transcellular migration, and tumor spheroids experiments showed that PTX-SM-TAR NPs exhibit great transvascular transport and tumor penetration ability. In vivo experiments, PTX-SM-TAR NPs showed higher antitumor effects than PTX. As a result, PTX-SM-TAR NPs may overcome the shortcomings of PTX and present a new transcytosable and targeted delivery system for PTX in TNBC treatment. [ABSTRACT FROM AUTHOR]

Glycosyltransferases (GTs) play a critical role in the enzymatic and chemoenzymatic synthesis of oligosaccharides and glycoconjugates. However, the development of these synthetic approaches has been limited by a lack of sensitive screening methods for the isolation of novel natural GTs or their active variants. Herein, we describe the results of our investigation towards the soluble expression and potential application of the Saccharomyces cerevisiae apyrase YND1. By replacing the hydrophobic transmembrane domain of YND1 with three glycine-serine repeats, this protein was successfully expressed in a soluble form in Escherichia coli . This new protein was then used to develop a two-step nucleoside diphosphate (NDP)-based Leloir-GT high-throughput assay. Purified rYND1 was initially added to a GT reaction to hydrolyze NDP to nucleoside phosphate plus inorganic phosphate, which was determined using a phosphorus molybdenum blue chromogenic reaction. Purified rYND1 was shown to have a positive effect on saccharide synthesis by eliminating the potential by-product inhibition from NDP. Most of the mono-sugar donors used for Leloir-GTs are activated by uridine diphosphate and guanosine diphosphate, which can be catalyzed by rYND1. The rYND1 is amenable to screening methods and could be applied to a wide range of Leloir-GT-catalyzed reactions, therefore representing a remarkable step forward in glycotechnology. [ABSTRACT FROM AUTHOR]

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors. [Display omitted] [ABSTRACT FROM AUTHOR]

Intranasal vaccination offers crucial protection against influenza virus pandemics. However, antigens, especially subunit antigens, often fail to induce effective immune responses without the help of immune adjuvants. Our research has demonstrated that a polyelectrolyte complex, composed of curdlan sulfate/ O -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/ O -HTCC), effectively triggers both mucosal and systemic immune responses when administrated intranasal. In this study, stable nanoparticles formed by curdlan- O -HTCC conjugate (C O NP) were prepared and characterized. Furthermore, the efficacy of C O NP was evaluated as a mucosal adjuvant in an intranasal influenza H1N1 subunit vaccine. The results revealed that C O NP exhibits uniform and spherical morphology, with a size of 190.53 ± 4.22 nm, and notably, it remains stable in PBS at 4 °C for up to 6 weeks. Biological evaluation demonstrated that C O NP stimulates the activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), both in vitro and in vivo. Furthermore, intranasal administration of C O NP effectively elicits cellular and humoral immune responses, notably enhancing mucosal immunity. Thus, C O NP emerges as a promising mucosal adjuvant for influenza subunit vaccines. • Curdlan- O -HTCC conjugate nanoparticle (C O NP) was prepared and characterized. • C O NP was spherical, uniform in size and stable in PBS at 4 °C up to 6 weeks. • C O NP significantly stimulated the activation of antigen presenting cells in vitro. • C O NP induced systemic and mucosal immune responses after intranasal administration. [ABSTRACT FROM AUTHOR]

Intranasal vaccination offers crucial protection against influenza virus pandemics. However, antigens, especially subunit antigens, often fail to induce effective immune responses without the help of immune adjuvants. Our research has demonstrated that a polyelectrolyte complex, composed of curdlan sulfate/ O -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/ O -HTCC), effectively triggers both mucosal and systemic immune responses when administrated intranasal. In this study, stable nanoparticles formed by curdlan- O -HTCC conjugate (C O NP) were prepared and characterized. Furthermore, the efficacy of C O NP was evaluated as a mucosal adjuvant in an intranasal influenza H1N1 subunit vaccine. The results revealed that C O NP exhibits uniform and spherical morphology, with a size of 190.53 ± 4.22 nm, and notably, it remains stable in PBS at 4 °C for up to 6 weeks. Biological evaluation demonstrated that C O NP stimulates the activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), both in vitro and in vivo. Furthermore, intranasal administration of C O NP effectively elicits cellular and humoral immune responses, notably enhancing mucosal immunity. Thus, C O NP emerges as a promising mucosal adjuvant for influenza subunit vaccines. • Curdlan- O -HTCC conjugate nanoparticle (C O NP) was prepared and characterized. • C O NP was spherical, uniform in size and stable in PBS at 4 °C up to 6 weeks. • C O NP significantly stimulated the activation of antigen presenting cells in vitro. • C O NP induced systemic and mucosal immune responses after intranasal administration. [ABSTRACT FROM AUTHOR]

Thymus immunosuppressive pentapeptide (TIPP) is a novel anti-inflammatory peptide with high efficacy and low toxicity. This study aims to establish a selective LC-MS/MS method for analyzing the analyte TIPP in biological samples, laying the foundation for further PK and PD studies of TIPP. Protein precipitation was conducted in acetonitrile supplemented with 2% formic acid and 25 mg/mL dithiothreitol as a stabilizer, which was followed by backwashing the organic phase using dichloromethane. The chromatographic separation of TIPP was achieved on a C18 column with a gradient elution method. During positive electrospray ionization, TIPP was analyzed via multiple-reaction monitoring. The linear relationships between the concentration of TIPP and peak area in murine plasma cell lysates, supernatants, and the final cell rinse PBS were established within the ranges of 20–5000 ng/mL, 1–200 ng/mL, 10–200 μg/mL, and 0.1–20 ng/mL, respectively (r2 > 0.99). Validated according to U.S. FDA guidelines, the proposed method was proved to be acceptable. Such a method had been successfully applied to investigate the pharmacokinetics of TIPP in mice via subcutaneous injection. The plasma half-life in mice was 5.987 ± 1.824 min, suggesting that TIPP is swiftly eliminated in vivo. The amount of TIPP uptake by RBL-2H3 cells was determined using this method, which was also visually verified by confocal. Furthermore, the effective intracellular concentration of TIPP was deduced by comparing the intracellular concentration of TIPP and degrees of inflammation, enlightening further investigation on the intracellular target and mechanism of TIPP. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: O‐Mannosylation plays a vital role in the regulation of a variety range of biological processes, for instance, brain and muscle development. However, the precise function remains largely unknown due to its innate heterogeneity. In this regard, it is still welcome to develop efficient methods to access diverse structurally‐defined glycopeptides. In this study, a diversity‐oriented assembly of O‐mannosyl α‐dystroglycan (α‐DG) glycopeptides has been achieved via a chemoenzymatic strategy. This strategy features (i) gram scale divergent synthesis of core m1, core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation; (ii) efficient glycopeptide assembly via the optimized microwave‐assisted solid phase peptide synthesis (SPPS); and (iii) enzymatic elaboration of the core glycan structures to install galactosyl and sialyl‐galactosyl moieties. The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1, core m2 and core m3 mannosyl glycans, including a core m2 glycopeptide bearing a heptasaccharide for the first time. [ABSTRACT FROM AUTHOR]

In order to solve the problem that the wellbore liquid loading of low permeability horizontal wells can't be predicted accurately in previous studies, this article establishes a new matrix - natural fracture - wellbore horizontal gas well productivity equation considering stress sensitivity, starting pressure gradient and high speed turbulence effect. The method is used to judge whether there is liquid loading in a gas reservoir, and verified by the critical liquid carrying flow method. The results show that the accuracy rate of predicting liquid loading by productivity equation method is 80%, and the accuracy rate of predicting gas well productivity is 91.55%. Meanwhile, the influence rule of natural fracture parameters on productivity is given and it is found that the stress sensitivity coefficient has little effect on productivity. At the same bottom hole pressure, the gas production gradually decreases with the increase of high-speed nonlinear coefficient and gas production gradually increases with the increase of the number and width of natural fractures. The findings of this study can help for better understanding of the relationship between wellbore liquid loading and gas well productivity, and then better grasping the timing of gas well drainage and gas recovery. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) deposition and neurotoxicity play an important role in Alzheimer's disease (AD). Notably, the nonnegligible role of endogenous heparan sulfate (HS) in the release, uptake and misfolding of Aβ sheds light on the discovery of HS as an effective drug for AD. In this work, the effects of HS from porcine mucosa (PMHS) on Aβ 1 – 42 -induced neurotoxicity were investigated both in vitro and in vivo. The in vitro AD model was established in SH-SY5Y via treatment with oligomeric Aβ 1 – 42 , and the in vivo AD model was established by intracerebroventricular injection of Aβ 1 – 42 to KM mice. The results showed that in vitro , PMHS could ameliorate the inflammation and apoptosis response of SH-SY5Y cells induced by Aβ 1 – 42 ; in vivo , PMHS could not only improve the cognitive impairment induced by Aβ 1 – 42 but also inhibit neuroinflammation and apoptosis in the brain. Furthermore, PMHS lowered the levels of Aβ 1 – 42 in the peripheral circulation and brain by improving the phagocytosis function of neutrophils. This is the first report that PMHS enhances the phagocytosis function of neutrophils to alleviate Aβ-induced neurotoxicity. Moreover, our work verified the feasibility of peripheral Aβ clearance for improving neurotoxicity. Conclusively, we believe that PMHS could be developed into neuroprotective drugs for AD. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA), a natural high molecular weight polysaccharide, is produced by Streptococcus zooepidemicus. However, Streptococcus has several drawbacks including its potential to produce exotoxins, so there is demand for an alternative HA source. Here, a recombinant HA biosynthesis operon, as well as the HA biosynthesis operon of S. zooepidemicus were introduced into L. lactis using the nisin-controlled expression system, respectively. HA was successfully synthesized by recombinant L. lactis. Furthermore, overexpression of the endogenous enzymes directing the synthesis of precursor sugars was effective at increasing HA production, and increasing the supply of UDP-activated monosaccharide donors aided synthesis of monodisperse HA polysaccharides. Besides GRAS host strain ( L. lactis) and NICE system, the selecting marker ( lacF gene) of the recombinant strain is also food grade. Therefore, HA produced by recombinant L. lactis overcomes the problems associated with Streptococcus and provides a source of food-grading HA appropriate for widespread biotechnological applications. [ABSTRACT FROM AUTHOR]

Abstract: Surface-driven progressive cavity pump (PCP) has been widely used as an effective artificial lift equipment in various oilfield productions. During the operation of PCPs, the problem of internal slip, which defines the pump performance in terms of volumetric efficiency and lifting capacity, always occurs. However, due to the complex geometrical structure and coupling interactions between the stator and the oil lifted, it is difficult to solve the volumetric efficiency analytically. In this study, we established a new finite element model of PCP, which consists of the stator, the rotor, the lifted fluid and the fluid–solid interaction. The controlling equations of solid deformation and fluid dynamics are solved using different solvers for solid domain and fluid domain respectively, and their results are exchanged through the fluid–solid interface. Partitioned solution algorithm is employed to tackle the problem of this two-way fluid–solid interaction. From our numerical simulation results, we found two leakage mechanisms: longitudinal slippage and transversal slippage. We took GLB500 PCP as a benchmark to validate our model and simulation method. Our computed volumetric efficiency of PCP with specified design parameters is consistent with experimental result of laboratory test. Furthermore, the model with fluid–structure interaction was used to compare the hydraulic characteristic curves of conventional and even-thickness PCPs and study the influence of different material and structure parameters on internal slip of PCP. The interference and stator thickness are found to be the two main factors influencing the volumetric efficiency, which can be used to optimize the design of PCP for specified purpose. [Copyright &y& Elsevier]

[Display omitted] • Different classes and assembled mechanisms of amphipathic peptides are described. • Several strategies to design and stabilize amphiphilic peptides are summarized. • Several strategies to realize functional transformation are elaborated. • Several delivery systems of amphiphilic peptides are outlined. Amphiphilic self-assembling peptides are widely used in tissue and cell engineering, antimicrobials, drug-delivery systems and other biomedical fields due to their good biocompatibility, functionality, flexibility of design and synthesis, and tremendous potential as delivery carriers for drugs. Currently, the design and study of amphipathic peptides by a bottom-up method to develop new biomedical materials have become a hot topic. However, defined rules have not been established for the design and development of self-assembled peptides. Therefore, the focus of this review is to summarize and provide several rational strategies for the design and study of amphiphilic self-assembly peptides. In addition, this paper also describes the types and general self-assembling mechanism of amphipathic peptides, and outlines their applications in the delivery of hydrophobic drugs, nucleic acid drugs, peptide drugs and vaccines. Amphiphilic self-assembled peptides are expected to exploit new functional materials for drug delivery and other applications. [ABSTRACT FROM AUTHOR]

Abstract: Heparin and heparosan have been confirmed to be effective blockers in inhibiting adhesion of pathogens in vitro. However, their effects on gut microbiota in vivo remain unknown. Here we have studied the effects of oral administration of heparin or heparosan on gut microbiota in rats by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Results showed that the predominant bacterial communities in the feces of heparin- or heparosan-treated animals were different from those of the saline-treated animals, with increased Lactobacillus spp. and decreased Enterococcus sp. Different DGGE banding patterns were also observed for the subpopulations of Lactobacillus and Bacteroides groups. In conclusion, heparin or heparosan may be used as an effective gut microbiota modulator by increasing the subpopulation of Lactobacillus. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: The object of this study was to explore the feasibility of support vector machine (SVM) to identify the origin of chondroitin sulfate (CS) by near infrared spectroscopy. 96 batches CS from three different origins were collected in this research, 66 batches of which were chosen for training set by Kennard–Stone (KS) method and the rest were used for testing. Through the comparison of pretreatment methods of standard normal variate transformation (SNV), multiplicative scatter correction (MSC), Savitzky-Golay (SG) smoothing and derivative with SG smoothing, a SVM discrimination model was constructed, of which the prediction result is 100% accurate with the pretreatment of first derivative and SG smoothing with 15 points. The result indicated that it had great potential using SVM to identify the origin of CS. [Copyright &y& Elsevier]

Abstract: In this study, the effects of heparin–superoxide dismutase conjugate (heparin–SOD) on bleomycin-induced pulmonary fibrosis in vivo and on inflammatory cytokine expression in vitro were evaluated. To investigate the effects of heparin–SOD on pulmonary fibrosis, heparin–SOD was administered to bleomycin (BLM)-treated mice by intraperitoneal injection once a day and the hydroxyproline content in lung was determined per 7days. The degree of fibrosis was assessed quantitatively using histopathologic features. The results showed that heparin–SOD inhibited BLM-induced lung fibrotic lesions as reflected by the decrease of lung hydroxyproline content and lung fibrosis grade 28days after BLM instillation. The in vitro effects on the cytokine level expressed by irradiated 3T3 fibroblasts showed that heparin–SOD significantly lowered the levels of transforming growth factor-β1 and interleukin-1β. These results strongly demonstrated that heparin–SOD might be useful in the prevention and treatment of pulmonary fibrosis. [Copyright &y& Elsevier]

Abstract: 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 (0.8–500μg/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 24h 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. [Copyright &y& Elsevier]

Sweroside, as one of the main components of Swertia L. in Gentianaceae, has the effect of clearing heat and detoxifying. In previous studies, sweroside has been reported to have anti-inflammatory effect on LPS-induced inflammation by alleviating NF-κB signaling pathway. In this paper, we investigate the anti-inflammatory effects of sweroside by establishing LPS-induced acute lung injury (ALI) model in mice. Experimental results showed that sweroside could reduce the wet-to-dry ratio of the lung and inhibit MPO activity. In addition, it turned out that sweroside reduced pathological changes in lung tissue and the numbers of inflammatory cells. Moreover, sweroside significantly reduced the levels of inflammatory cytokines and down-regulated the NF-κB signaling pathway. And the results demonstrated that sweroside could increase the expression of SIRT1, and the protective effects of sweroside on LPS-induced ALI were reversed by SIRT1 inhibitor EX-527. In conclusion, sweroside can protect LPS-induced ALI mice through inhibiting inflammation. [ABSTRACT FROM AUTHOR]

The content of pullulan and melanin in 500 mutants of Aureobasidum pullulans obtained by ultraviolet mutagenesis were examined and statistically analyzed, and a strong positive correlation was found between them. The result was further confirmed by culturing wild type strain As3.3984 in different media. Then we constructed melanin-deletion mutant As- Δalb1 and pullulan-deletion mutant As- Δpul. As- Δalb1 was a melanin-free strain with the yield of pullulan decreased by 41.01%. The supplementation of melanin in the culture of As- Δalb1 increased the production of pullulan. As- Δpul synthesized neither pullulan nor melanin and recovered melanin synthesis by adding pullulan to the medium. The results suggested that high concentration- of pullulan induced morphological transformation and synthesis of melanin, and melanin promoted the synthesis of pullulan. The pullulan biosynthetic genes, upt , pgm , ugp , and pul , were down-regulated, while the negative regulatory gene of pullulan synthesis, creA , was up-regulated by melanin deficiency. • The synergistic correlation exists between the synthesis of pullulan and melanin. • High concentrations of pullulan induced the synthesis of melanin. • Melanin promotes the synthesis of pullulan. [ABSTRACT FROM AUTHOR]

In the present study, we studied anti-Alzheimer′s disease (AD) activities of chondroitin sulfate (CS) oligosaccharides with different molecular weights. CS from shark cartilage was degraded by a recombinant CS endolyase, chondroitinase ABC I (CHSase ABC I), and CS disaccharide (DP2), tetrasaccharide (DP4), hexasaccharide (DP6), octasaccharide (DP8), decasaccharide (DP10) and dodecasaccharide (DP12) were obtained by separation with gel filtration. Anti-AD activities of CS oligosaccharides were assessed using Aβ-injured SH-SY5Y cells and BV2 cells. It was shown that CS oligosaccharides could block Aβ-induced oxidative stress, mitochondrial dysfunction and activation of intrinsic apoptotic pathway for SH-SY5Y cells. Furthermore, these activities increased with the increase of molecular weights. For Aβ-injured BV2 cells, CS oligosaccharides inhibited oxidative stress, the production of proinflammatory cytokines and the activation of toll-like receptor pathway, and CS DP2 had the best activity among them. In conclusion, CS oligosaccharides suppressed Aβ-induced oxidative stress and relevant injury in vitro, and these effects had different relationships with the molecular weights of CS oligosaccharides for different cell lines, which might be caused by different mechanisms. [ABSTRACT FROM AUTHOR]

Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro. Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC) vaccine immunotherapy applies tumor antigens or tumor cell lysate (TCL)-pulsed DCs to induce an antigen-specific immune response to attack cancer cells. However, tumor antigen alone has limited immunostimulatory effects, and so immunostimulants are needed to prepare mature DCs. In our previous study, curdlan sulfate (CS) showed potent adjuvant properties with the HBV vaccine; therefore, we attempted to use CS to mature TCL-pulsed DCs. We first prepared four CSs (CS1-CS4) with different sulfation (S) degrees and molecular weights (MWs), then studied the structure-activity relationship of CS in vitro and finally screened CS3 (14.316% S content and 30.66 kDa MW) as the DC vaccine adjuvant. An in vivo study showed that a DC vaccine adjuvanted with CS3 significantly prolonged the survival of tumor-bearing mice, reduced tumor burden and inhibited tumor growth. The CS3-adjuvanted DC vaccine increased CD80, MHC-I and MHC-II expression, promoted CD8+ T cell infiltration, upregulated TNF-α and IFN-γ transcription, and downregulated TGF-β transcription in tumor tissues. A preliminary mechanism study showed that CS activated DCs mainly via the TLR4 and TLR2 signalling pathways. Based on these results, we concluded that CS3 is a potential adjuvant for DC vaccines and is worth studying for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

We have recently derived a β-N-acetylhexosaminidase, BbhI, from Bifidobacterium bifidum JCM 1254, which could regioselectively synthesize GlcNAcβ1-3Galβ1-4Glc with a yield of 44.9%. Here, directed evolution of BbhI by domain-targeted mutagenesis was carried out. Firstly, the GH20 domain was selected for random mutagenesis using MEGAWHOP method and a small library of 1300 clones was created. A total of 734 colonies with reduced hydrolytic activity were isolated, and three mutants with elevated transglycosylation yields, GlcNAcβ1-3Galβ1-4Glc yields of 68.5%, 74.7%, and 81.1%, respectively, were obtained. Subsequently, nineteen independent mutants were constructed according to all the mutation sites in these three mutants. After transglycosylation analysis, Asp714 and Trp773 were identified as key residues for improvement in transglycosylation ability and were chosen for the second round of directed evolution by site-saturation mutagenesis. Two most efficient mutants D714T and W773R that acted as trans-β-N-acetylhexosaminidase were finally achieved. D714T with the substitution at the putative nucleophile assistant residue Asp714 by threonine showed high yield of 84.7% with unobserved hydrolysis towards transglycosylation product. W773R with arginine substitution at Trp773 residue locating at the entrance of catalytic cavity led to the yield up to 81.8%. The kcat/Km values of D714T and W773R for hydrolysis of pNP-β-GlcNAc displayed drastic decreases. NMR investigation of protein–substrate interaction revealed an invariable mode of the catalytic cavity of D714T, W773R, and WT BbhI. The collective motions of protein model showed the mutations Thr714 and Arg773 exerted little effect on the dynamics of the inside but a large effect on the dynamics of the outside of catalytic cavity. [ABSTRACT FROM AUTHOR]

As the core component of the fracturing tool, the packer cartridge plays a vital role in a horizontal well stimulation and transformation process (Sun and Bai in Pet Explor Dev 44:1022–1029, 2017). Influenced by many factors such as formation workflow, borehole structure and construction conditions, the mechanical response of the packer rubber cylinder in sealing is complex and changeable (Jun et al. in J Pet Sci Eng 171:495–506, 2018; Tong et al. J Pet Sci Eng 172:964–975, 2019; Zhu et al. J Pet Sci Eng 151:311–317, 2017b). In order to study the mechanical response mechanism of the packer tool under complex working conditions, tensile tests of rubber under the corrosion environment of carbon dioxide formation fluid were carried out and the constitutive material parameters of Yeoh model after corrosion were obtained. The results showed that the tensile strength of hydrogenated nitrile butadiene rubber (HNBR) decreased by 7.86–17.01% after corrosion in simulated formation fluid, and the elongation at break increased by 2.09–19.74%. Compared with AFLAS (tetrapropyl fluoro elastomer), HNBR rubber had better stability and can be used as the preferred material for the service environment of permanent packers. Based on the mechanical properties of numerical calculation results before and after corrosion, it was found that the contact pressure and compression distance of the whole HNBR packer changed slightly, which met the requirements of field construction. On the basis of optimum selection of rubber material, the sealing performance of packer in borehole casing with enlargement/reduction caused by formation is analyzed. The results show that the casing with expansion deformation will lead to setting lag or lax, and the shrinkage casing will lead to setting advance or even stress failure. The analysis results provide theoretical support for the improvement in permanent packer string and its adaptation to complex formation. [ABSTRACT FROM AUTHOR]

Highlights • Nanoparticles enter macrophages and escape from lysosomes effectively. • Nanoparticles upregulate phenotypic and functional maturation of dendritic cells. • Nanoparticles induce activation of type Ⅰ interferons in dendritic cells. • Nanoparticles promote production of cytokines in immunocytes. • Nanoparticles induce lymphocytes proliferation. Abstract Nasal immunization to prevent and treat diseases caused by infection through the respiratory tract cannot be actualized because of the lack of effective adjuvants. We have proven that compared with antigens loaded on CS or O -HTCC alone in nasal vaccination, antigens loaded on the nanoparticles of curdlan sulfate/ O -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/ O -HTCC) can induce stronger systemic and mucosal immune responses. In this study, we evaluated the immunostimulatory activity and mechanisms of CS/ O -HTCC nanoparticles. The results showed that CS/ O -HTCC nanoparticles can improve the activation of antigen-presenting cells, upregulate the production of inflammatory factors and cytokines, induce cross-presentation, and simultaneously activate type I interferon-related genes. CS/ O -HTCC nanoparticles also activated the PI3K/AKT and MAPK pathways and significantly promoted IL-2 transcription to induce the proliferation of lymphocytes. The results revealed that CS/ O- HTCC nanoparticles as a type of multifunctional adjuvant can improve multiple arms of immune responses. [ABSTRACT FROM AUTHOR]

Highlights • HTCOSC-ES2 displayed improved anti-angiogenesis activity and prolonged halflife. • HTCOSC-ES2 displayed significant anti-tumor activity in B16-tumor bearing C57 mice. • HTCOSC-ES2 has good potential in angiogenesis related tumor treatment. Abstract Most solid tumors require neovascularization during their growth. In our previous study, ES2 (IVRRADRAAVP) was covalently conjugated to soluble chitooligosaccharide chloride (HTCOSC) to form one novel HTCOSC-ES2 conjugate, which displayed better anti-angiogenic activity. In this work, the intracellular distribution and endocytosis of the conjugate in endothelial cells, as well effects on endothelial cell cycle and apoptosis were investigated. In addition, pharmacokinetic and antitumor studies were conducted. HTCOSC-ES2 entered the cell via clathrin and lipid valve pathway and was transported to the nucleus via lysosomal transport mechanism. Unlike ES2, HTCOSC-ES2 effectively inhibited the growth of endothelial cells and promoted apoptosis; thus, it could inhibit tumor angiogenesis, resulting in strong anti-tumor activity in vivo. The half-life of HTCOSC-ES2 was also prolonged, and its clearance was delayed. Immunohistochemistry assays showed that HTCOSC-ES2 obviously reduced the microvessel density, decreased the expression of VEGF, and increased the expression of caspase-3. [ABSTRACT FROM AUTHOR]

Highlights • The carboxyl group of the GSHP was linked to the amino group of the ES2 C-terminal. • The GSHP-ES2 displayed no significant anticoagulant activity. • Improved heat stability and higher P-selectin affinity was obtained through the conjugation of GSHP to ES2. • Better bioactivities of GSHP-ES2 were obtained both in vitro and in vivo. • GSHP has good potential as protein/peptide modifier. Abstract Endostatin (ES) has attracted considerable attention for the treatment of anti-angiogenesis-related disorders. An 11-amino-acid peptide (ES2, IVRRADRAAVP) from the amino terminal of ES is of interest because it is the main active fragment of ES. However, both ES and ES2 have a poor stability and a short half-life, and other disadvantages need to be further resolved. Thus, we conjugated ES2 to glycol-split heparin derivatives (GSHPs) to yield the polymer-peptide conjugate, GSHP-ES2. This study showed that GSHP-ES2 exhibited increased stability, a wider pH activity range, better inhibition of endothelial cell proliferation, migration and tube formation in vitro, better anti-angiogenic activity and a longer half-life in vivo compared with ES2. These results also indicate that GSHP-ES2 has good potential for the treatment of angiogenesis-related diseases, either alone or in combination with other chemicals. [ABSTRACT FROM AUTHOR]

Abstract Anti-flt1 peptide (GNQWFI, AF) specifically binds to Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), thereby inhibiting the interaction of VEGFR1 with a series of ligands. ES2 (IVRRADRAAVP) can effectively inhibit the proliferation and invasion of endothelial cells and play a key role in anti-angiogenesis. AF and ES2 peptides differ in their activity. To better exploit the advantages of both, we designed a new peptide called ES2-AF (IVRRADRAAVPGGGGGGNQWFI). Hyaluronic acid (HA) is widely used in the pharmaceutical industry because of its biodegradable and high load performance. The HA-specific cell surface receptor CD44 was highly expressed in the tumour site during the anti-tumour study. Therefore, we used HA as a modifier to chemically modify ES2-AF; it was expected that the modified compound would have preferable solubility, stronger targeting, longer half-life, and better anti-angiogenesis effects in vivo. In this study, the anti-proliferative, anti-migration and targeting activities of HA-ES2-AF in vitro were studied by MTT, ELISA, transwell and SPR assays. Meanwhile, the anti-neovascularization activity of HA-ES2-AF in vivo was studied by CAM assay, and the targeting of HA-ES2-AF to tumour tissue was studied by bioimaging techniques. Finally, we also studied the half-life of HA-ES2-AF in vivo. In short, the bioactivity of the new peptide ES2-AF was enhanced to a certain extent, and ES2-AF modified by HA had higher anti-neovascularization activity in vitro and in vivo , had stronger targeting to tumour tissue, and had a significantly prolonged half-life in vivo. These results laid the foundation for its further development into targeting anti-tumour drugs. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

We have previously reported an application of lower range of molecular weight of xanthan gum (LRWXG) for inhibiting cartilage matrix destruction and preventing mitochondrial damage in rabbit osteoarthritis (OA) model. However, whether LRWXG exerts its anti-OA activity through intrinsic bax-mitochondria cytochrome c-caspase signaling pathway in OA still requires further study. To address this problem, the OA model was induced by anterior cruciate ligament transection (ACLT) in rabbit and then treated with LRWXG. The results showed that LRWXG could inhibit the loss of collagen in cartilage matrix, protect trabecular bone in subchondral, decrease the apoptosis of chondrocytes, down-regulate the expressions of active caspase-9, active caspase-3 and bax, and up-regulate the expression of bcl-2. In addition, LRWXG could up-regulate the expression of cyt-c in mitochondria, while down-regulate the expression of cyt-c in cytoplasm. These findings show that LRWXG inhibits cartilage degradation via an intrinsic bax-mitochondria cytochrome c-caspase pathway in OA. [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]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An insightful investigation into specificity of bacterial heparinase III has been intriguingly difficult due to heterogeneity of polymeric substrates. Herein, we chemoenzymatically synthesized a tailored library of HS oligosaccharides as substrates. A ∼15-fold reactivity difference to heparinase III was found between trisaccharides bearing different primary cleavage sites. Variable glucosamine modification decreased reactivity of trisaccharides by >20-fold compared with their counterpart primary substrates, while iduronate-containing secondary linkage showed slightly less sensitivity. The 2-sulfated iduronate residue extremely reduced reactivity to its adjacent primary site at reducing end of oligosaccharides, but showed marginal influence on the non-reducing site. Moreover, oligosaccharide susceptibility to digestion was size-dependent and had an obvious preference for the internal linkages over those near to non-reducing/reducing ends. Surface plasmon resonance revealed cleavage promiscuity attributed to different affinities or incorrect binding of substrates to the enzyme. The attractive information on heparinase III will be valuable in characterizing heparin and HS. [ABSTRACT FROM AUTHOR]

We have previously reported the application of low molecular weight XG(LM-XG), with molecular weights ranging from 1 × 10 6 Da to 1.5 × 10 6 Da for treating osteoarthritis. In this study, we investigated the anti-apoptotic activity of LM-XG under oxidative stress conditions, activated by hydrogen peroxide (H 2 O 2 )-treated chondrocytes in vitro . Chondrocytes were pretreated with various doses of LM-XG (0, 10, 100, 500, or 1000 μg/mL) or 1000 μg/mL sodium hyaluronate for 12 h, and then exposed to 0.5 mmol/L H 2 O 2 for another 12 h. After treatment, chondrocyte viability was evaluated using a cell counting kit-8; DNA fragmentation was detected using Hoechst33258 staining; the percentage of DNA fragmentation was evaluated using the diphenylamine DNA assay kit; the apoptosis rate was evaluated using flow cytometry; chondrocyte ultra-microscopic morphology was observed using transmission electron microscopy; intracellular reactive oxygen species levels were observed and quantified using 2,7-dichlorofuorescin diacetate, mitochondrial permeability transition analysis was performed using MitoTracker Red CMXRos and 4′,6-diamidino-2-phenylindole staining; and finally, caspase-3 activity was detected by western blot. The results showed that, compared with H 2 O 2 -treated chondrocytes, LM-XG improved cell viability, decreased the percentage of DNA fragmentation, reduced the apoptosis rate, decreased the levels of intracellular reactive oxygen species and mitochondrial permeability transition, reverted the morphological damage, and downregulated cleaved caspase-3 levels. These results demonstrate that LM-XG has anti-apoptotic activity in H 2 O 2 -treated chondrocytes. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the immunomodulatory effects of xanthan gum (XG) in RAW264.7 macrophages and the underlying molecular mechanisms. We used scanning electron microscopy (SEM) to analyze the morphology of XG-treated RAW264.7 cells with and without lipopolysaccharide (LPS) stimulation and investigated the subsequent effects on nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) levels in LPS-activated mouse RAW264.7 macrophages. We also analyzed the binding affinity of XG to Toll-like receptor 4 (TLR4) with surface plasmon resonance (SPR) analysis and observed that XG decreased NO, IL-6 and TNF-α secretion into the culture medium and iNOS and COX-2 protein levels induced by LPS. This study reveals a two-way immunomodulatory effect of XG on inflammatory mediators in RAW264.7 macrophages that may involve the TLR4 signal pathway, providing a pharmacological basis for the use of XG in the control of inflammatory disorders. [ABSTRACT FROM AUTHOR]