30 results about "Heparan Sulfate Proteoglycan" patented technology

The invention discloses a tissue-engineered bone cartilage composite scaffold and a preparation method thereof, belonging to the technical field of biomaterials. The scaffold is of a multilayer integrated structure and comprises a cartilage tissue scaffold layer, a cartilage tissue calcified layer, a porous cell isolation membrane and a bone tissue scaffold layer. The cartilage tissue scaffold layer is inoculated with cartilage cells, and growth factors for promoting formation of cartilage are introduced to promote growth of cartilage cells. Main raw materials like heparan sulfate proteoglycan with good biocompatibility and degradability are selected and used and the method consisting of a cross-linking reaction, freeze drying, directional pore formation, compounding of multiple layers, overall integration and the like are carried out so as to obtain the functionalized multilayer integrated tissue-engineered bone cartilage composite scaffold with good mechanical properties. According to the invention, micro-nano hydroxyapatite crystal, degradable non-stoichiometric polyethylene glycol / poly(epsilon-caprolactone) nanometer coaxial short fiber, RGD-grafted heparan sulfate proteoglycan / oxidized sodium alginate and N-succinyl chitosan are compounded together to prepare the composite scaffold; and the composite scaffold is mainly used for restoration of full-thickness defects of articular cartilage and subchondral bone.

The present invention relates to method for the preparation of glycosaminoglycan compositions, isolated glycosaminoglycan compositions obtainable therefrom, glycosaminoglycan compositions, kits and use thereof. More specifically, the present invention provides a method for isolating glycosaminoglycan compositions of the invention from human follicular fluid. The compositions, related methods and uses according to the present invention are useful in the treatment and / or prevention of thrombotic diseases, cell proliferation disorders, proteolysis and inflammation mediated cell invasion and infertility.

The present invention relates to a chimeric molecule comprising (i) a targeting moiety that binds to heparin or heparan sulfate proteoglycans, (ii) a lysosomal peptide or protein, (iii) wherein the targeting moiety is a neurotrophic growth factor and / or, wherein the targeting moiety comprises one of the following consensus sequences BBXB, BXBB, BBXXB, BXXBB, BBXXXB or BXXXBB and wherein B represents an arginine, lysine or histidine amino acid and X represents any amino acid, (iii) with the proviso that the targeting moiety is at least thirteen amino acids long.

Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and / or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets. The matrix compositions of the present invention can be used to tissue engineer transplantable innervated GI smooth muscle constructs to remedy aganglionic disorders.

The present invention relates to an in vitro method for identifying a molecule, which interferes with the interaction between a glial cell-line derived neurotrophic factor family ligand (GFL) and a heparan sulfate proteoglycan (HSPG), by screening a library of molecules against a matrix anchored complex comprising at least one immobilized glial cell-line derived neurotrophic factor family ligand (GFL) and at least one heparan sulfate proteoglycan (HSPG), wherein the interfering molecule is isolated based on its capacity to replace a glial cell-line derived neurotrophic factor family ligand (GFL) in said anchored complex. The invention also relates to a complex for identifying such a molecule. The invention also relates to methods for preventing or delaying a neurodegenerative process as well as to method for prophylactic treatment or treatment of a disorder in the nervous system.

A method of perlecan isolation (from the EHS tumor) which produces “clean” (i.e. substantially “pure”) perlecan is disclosed. Clean perlecan is thus produced in sufficient quantities for use in a number of different in vitro and in vivo assays. In addition, this isolation method exploits a newly discovered aggregating property of a ˜220 kDa heparan sulfate proteoglycan (HSPG) observed during gel filtration chromatography, which allows it to be effectively separated from non-aggregating perlecan. The method employs specific cation exchange, anion exchange, molecular sieve chromatography and immobilized GAG affinity chromatography. It is demonstrated that there are no other contaminating proteins in the perlecan and HSPG preparations, and that the perlecan core protein is intact. Improved, clean perlecan based, rodent models of fibrillar amyloid protein deposition, accumulation and / or persistence in tissues are disclosed.

Polypeptides of the neuregulin (NRG) heparin binding domain (N-HBD) and nucleic acids coding therefor are disclosed. In particular, fusion polypeptides are produced that comprise, as a targeting structure, a N-HBD polypeptide, fragment, homologue or functional derivative and a protein to be targeted. This is fused to a polypeptide or peptide being targeted (Ptrg) to cell surfaces rich in heparan sulfate proteoglycans to either activate or inhibit interactions at tyrosine kinase receptors. Such products are used to treat diseases or conditions where either agonism or antagonism at tyrosine kinase receptors has beneficial effects, including cancer and a multitude of diseases of the nervous system.

The invention discloses cross-linked hydrogel for muscle stem cell culture as well as a preparation method and application of the cross-linked hydrogel, and belongs to the technical field of biological food materials. The preparation method comprises the following steps: dissolving collagen to prepare a solution, then adding a certain amount of alginate and heparan sulfate proteoglycan, and uniformly mixing the alginate and heparan sulfate proteoglycan with the collagen solution; and adding epsilon-PL and TG enzyme into the solution, uniformly conducting stirring, and putting slurry into a mold for crosslinking to obtain the hydrogel. According to the hydrogel disclosed by the invention, collagen, polylysine and heparan sulfate proteoglycan are connected through TG enzyme to form covalent crosslinking, and a compact three-dimensional 'egg box' net structure is formed through physical electrostatic interaction between polylysine and alginate. By utilizing the hydrogel, the absorption of the muscle stem cells on nutrient substances can be enhanced, and the growth of the muscle stem cells is facilitated. The bi-crosslinked network hydrogel has the potential to be used as a scaffold for muscle stem cell growth of stem cell culture meat.

The present invention relates to an in vitro method for identifying a molecule, which interferes with the interaction between a glial cell-line derived neurotrophic factor family ligand (GFL) and a heparan sulfate proteoglycan (HSPG), by screening a library of molecules against a matrix anchored complex comprising at least one immobilized glial cell-line derived neurotrophic factor family ligand (GFL) and at least one heparan sulfate proteoglycan (HSPG), wherein the interfering molecule is isolated based on its capacity to replace a glial cell-line derived neurotrophic factor family ligand (GFL) in said anchored complex. The invention also relates to a complex for identifying such a molecule. The invention also relates to methods for preventing or delaying a neurodegenerative process as well as to method for prophylactic treatment or treatment of a disorder in the nervous system.

Provided herein are improved rAAV (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of ocular disorders or CNS disorders wherein the rAAV comprise one or more substitutions of amino acids that interact with heparan sulfate proteoglycan. The invention provides methods for improved transduction of retinal cells and methods for treating ocular diseases with improved compositions of rAAV particles. Further provided herein are improved recombinant adeno-associated virus (rAAV) (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of disorders of the CNS. The invention provides methods for delivering the rAAV to the CNS, methods for treating disorders of the CNS with improved compositions of rAAV particles, and kits for delivering the rAAV to the CNS and / or treating a CNS disorder.

The invention relates to the technical field of biopharmaceutics, in particular to a preparation method of an anti-HPV infection antibody, comprising the following steps: transforming capsid protein of subtype of HPV pathogenicity into 293TT cells, packaging pseudovirus, preparing virus-like particles and using the virus-like particles as part of antigen to immunize animals to acquire an anti-HPV infection antibody. The antibody obtained by the preparation method of the anti-HPV infection antibody is a polyclonal specific antibody of certain purity and concentration obtained by immunizing laying hens (or other bird species) with key proteins of invasion in an HPV infection course, namely HPV L-1 / L2(17-36 short peptides), furin and heparan sulfate proteoglycan and adding proper adjuvant through an antibody engineering technique, and the antibody can quickly neutralize HPV and block the HPV invasion passage to play the effect of preventing high risk type HPV infection.

The present invention is based on a finding that a hepatitis B virus antibody inhibits binding of a surface antigen (HBsAg) of hepatitis B virus to heparan sulfate proteoglycan, thereby preventing cccDNA formation of the hepatitis B virus. It is expected that utilizing the pharmaceutical composition and the method of preventing cccDNA formation of hepatitis B virus of the present invention can fundamentally treat chronic hepatitis B and also prevent a recurrence of hepatitis in a hepatitis B patient after liver transplant surgery. Further, according to the present invention, a material for preventing or treating hepatitis B can be newly identified by confirming whether cccDNA formation is inhibited or not. In addition, according to the present invention, a treatment supplement capable of being administered in combination with the hepatitis B virus antibody can be newly identified.

The present invention provides methods of increasing the half-life factor VIII. More specifically, the invention methods of increasing the half-life of factor VIII by substituting amino acids in the A2 domain or in the C2 domain of factor VIII or in both domains. It further provides factor VIII mutants produced by these methods. The invention also provides a method of using receptor-associated protein (RAP) to increase the half-life of factor VIII. The invention also provides polynucleotides encoding the mutant factor VIII, polynucleotides encoding RAP, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.

The invention relates to the field of daily chemicals and plant extracts, in particular to application of a bletilla striata(Thunb.)Rchb.f extract. The bletilla striata(Thunb.)Rchb.f extract has the ability of improving the expression of basilar membrane related genes and anti-aging related genes, and can effectively improve the expression of anti-aging effect related genes hbegf (heparin bindingEGF like growth factor), csf2 (colony stimulating factor 2) and egfr (epidermal growth factor receptor), and a basilar membrane stabilization related gene hspg2 (heparan sulfate proteoglycan) at the content of 0.01 percent. Thus, the bletilla striata(Thunb.)Rchb.f extract can be used for preparing external skin agents, and can serve as an anti-aging active component for firming a skin structure orstabilizing a dermal-epidermis junction.

The invention discloses novel application of the peptide fragment CSP I-plus of circumsporozoite protein CSP I-plus of plasmodium in treating plasmodium infection. Researches discover that the circumsporozoite protein CSP plays an important role in adhesion and hepatic cell invasion of plasmodium sporozoite, and the key point of malaria infection is that sporozoite of plasmodium invades liver cells, so that malaria infection can be prevented by stopping invasion of sporozoite. CSP I-plus is an important functional domain of CSP, can be specifically combined with a liver cell surface molecule, namely heparan sulfate proteoglycan (HSPG), and can stop combination of CSP and the liver cells. Therefore, the CSP I-plus is expected to be developed into a novel micro-molecule polypeptide medicine for treating plasmodium falciparum infection by stopping adhesion and liver cell invasion of CSP mediated plasmodium sporozoite, and the recombinant expression plasmid containing CSP I-plus coding genes is expected to be further developed into a novel anti-malarial genetic medicine, so that the circumsporozoite protein polypeptide CSP I-plus has an excellent clinical application prospect.

Polypeptides of the neuregulin (NRG) heparin binding domain (N-HBD) and nucleic acids coding therefor are disclosed. In particular, fusion polypeptides are produced that comprise, as a targeting structure, a N-HBD polypeptide, fragment, homologue or functional derivative and a protein to be targeted. This is fused to a polypeptide or peptide being targeted (P<SUB>trg< / SUB>) to cell surfaces rich in heparan sulfate proteoglycans to either activate or inhibit interactions at tyrosine kinase receptors. A preferred fusion polypeptide comprises an N-HBD, a spacer and the extracellular domain of erbB4, one of several receptors signaled by NRG, which is potent NRG antagonist. Such products are used to treat diseases or conditions where either agonism or antagonism at tyrosine kinase receptors has beneficial effects, including cancer and a multitude of diseases of the nervous system.

Provided is a gene therapy vector comprising an expression cassette encoding a mammalian apolipoprotein E having a residue other than arginine at at least one of position 112, position 136, or position 158, rather than a mammalian apolipoprotein E having R112, R136, and R158 or a mammalian apolipoprotein E having C112, R136, and C158, or encoding an antibody that binds to APOE4 or disrupts the binding of APOE to heparan sulfate proteoglycan, and methods of using the same.

The invention discloses a bioactive material capable of efficiently combining and stimulating bFGF activity function and application. The invention also discloses application of the bioactive materialin preparation of a product for treating myocardial infarction. The bioactive material comprises an extracellular matrix molecular material, and the extracellular matrix molecular material comprisesheparan sulfate proteoglycan. According to the bioactive material, binding of heparan sulfate proteoglycan to basic fibroblast growth factor has high efficiency, good stability, and can greatly protect the basic fibroblast growth factor from being hydrolyzed by biological enzymes, and further promote biological activity of the basic fibroblast growth factor, etc. In addition, the bioactive material is used as a carrier of basic fibroblast growth factors, can well help reduce scar accumulation after myocardial infarction, relieve ventricular hypertrophy caused by injury and provide help for cardiac function recovery, and also provides a new thought for drug loading mode change of clinical myocardial infarction treatment.

A method for enhancing chondrogenesis in a subject in need thereof comprises administering to the subject an effective amount of a pharmaceutical composition comprising a growth factor bound to hyaluronic acid (HA)-based hydrogel particles (HGPs). The hyaluronic acid (HA)-based hydrogel particles (HGPs) are conjugated with a heparan sulfate proteoglycan (HSPG). Related medicaments and methods for preparing the medicaments are provided.

The invention discloses a fusion protein of liver-targeting peptide and recombinant human endostatin, its preparation method and application. The present invention selects 19 amino acids that can be specifically combined with the receptor--heparan sulfate proteoglycan HSPG on the surface of liver cells in the conserved I region of the N-terminal of the Plasmodium circumsporozoite protein CSP, and uses genetic engineering to fuse it in The carboxy-terminus of the novel human endostatin nhES with 9 amino acid sequences (MGGSHHHHH) added to the amino-terminus, and the liver-targeting peptide and recombinant human endostatin fusion protein (ES‑CSP) were prepared. The fusion protein is easy to purify, can specifically target the liver to inhibit the formation of new blood vessels, increase the local concentration of the drug at the lesion site, reduce the systemic dosage, and reduce its toxic and side effects. It provides ideas and scientific basis for the clinical development of drugs that target angiogenesis to treat liver cancer, and has great scientific significance and practical value for further improving the treatment level of liver cancer in my country.

The invention discloses a cross-linked hydrogel used for culturing muscle stem cells, a preparation method and application thereof, and belongs to the technical field of biological food materials. In the present invention, collagen is dissolved to form a solution, and then a certain amount of alginate and heparan sulfate proteoglycan is added to mix it with the collagen solution; then ε-PL and TG enzyme are added to the solution, stirred evenly, and The slurry is placed in a mold to cross-link, resulting in a hydrogel. The hydrogel of the present invention connects collagen, polylysine and heparan sulfate proteoglycans through TG enzyme to form covalent crosslinks, and through the physical electrostatic interaction between polylysine and alginate to form Dense three-dimensional "egg carton" network structure. The use of this hydrogel can enhance the absorption of nutrients by muscle stem cells and facilitate their growth. Double-crosslinked network hydrogels have potential as scaffolds for muscle stem cell growth in stem cell culture meat.

The invention discloses a Chinese-Western compound preparation for resisting AIDS and a preparation method thereof. The preparation is prepared from main materials and auxiliary materials, wherein the main materials comprise meehania henryi, rhodiola yunnanensis, pittosporum root, cavalerie's sage, acranthera sinensis, fagopyrum cymosum, aralia chinensis root, lindera angustifolia, microsorium hymenodes, heparan sulfate proteoglycan and glucosamine, and the auxiliary materials comprise kohlrabi, podocarpus macrophyllus, cymbopogon schoenanthus, cherry leaf, roselle, hempleaf negundo chastetree leaf, murdannia bracteata, Chinese wampee leaf, soybean lecithin, fucoidan, rhein and sodium stearyl fumarate. The selected Chinese herbal medicine components are precise in components, the herbal medicines are reasonable in compatibility, complement one another, and are combined with Western medicine components to improve the immunity of the organism and achieve the purposes of removing dampness and supporting healthy energy together, so as to effectively resist the invasion of AIDS, relieve pain of a patient, improve the life quality of the patient and prolong the life of the patient. According to the Chinese-Western compound preparation, the raw materials are easy to obtain, the preparation process is simple, the cost is low, and the burden of the patient can be reduced.

SCGB-based preparations and methods to use these preparations to protect the glycocalyx in medical, veterinary, and cosmetic applications are provided. The secretoglobins (SCGBs) are a family of small secreted globular proteins present in all mammals and sharing conserved structure and thought to share similar immunomodulatory functions. Heparan sulfate proteoglycan proteins (HSPGs) are expressed on the outer membranes of cells and have carbohydrate side chains that, together, make up the glycocalyx. The glycocalyx is a protective layer surrounding all cells, acting as a filter regulating the passage of nutrients into the cell and modifying cell signaling by external factors. There are two major families of HSPGs including syndecans and glypicans, plus several other HSPGs in all mammals. SCGBs bind to, and interact with, HSPGs to further modulate cell signaling and cellular responses to external factors.

Provided is a method for inducing pluripotent stem cells to differentiate into somatic cells in a culture medium containing a heparin binding growth factor, the method comprising bringing cells into contact with a conjugate of a laminin E8 fragment and a growth factor binding domain-containing fragment of a heparan sulfate proteoglycan. According to the present invention, pluripotent stem cells can be induced to differentiate into any desired somatic cells in a highly efficient manner.

A method for enhancing chondrogenesis in a subject in need thereof comprises administering to the subject an effective amount of a pharmaceutical composition comprising a growth factor bound to hyaluronic acid (HA)-based hydrogel particles (HGPs). The hyaluronic acid (HA)-based hydrogel particles (HGPs) are conjugated with a heparan sulfate proteoglycan (HSPG). Related medicaments and methods for preparing the medicaments are provided.

The invention discloses a transmembrane heparan sulfate proteoglycan 1 immune agonist polypeptide, belongs to the field of anti-cancer vaccines, and particularly relates to an optimized transmembrane heparan sulfate proteoglycan 1 immune agonist polypeptide used as an anti-cancer vaccine to enhance T cell immune responses. The amino acid sequence is a brand new sequence. The polypeptide is applied to preparing medicine for treating tumors, particularly to preparing medicine for tumor immune cells and T cell immune response enhancing and preparing medicine for CAR-T cell immune treatment. The polypeptide has the advantages that the sequence is brand new, the polypeptide can be used in an immune agonist in the tumor immune cell technology, promote T cell proliferation, promote CD8+ immune response, promote combination of T cells and tumor cells and increase the survival rate in mice bearing neoplasm, and serves as a target molecule of cell therapies to be applied to CAR-T and other cell therapies.

The invention discloses a tissue engineering osteochondral composite support and a preparation method thereof, belonging to the technical field of biomaterials. The support is a multi-layer integrated structure, which is composed of a cartilage tissue support layer, a cartilage tissue calcification layer, a porous cell separation membrane and a bone tissue support layer. The cartilage tissue scaffold layer is inoculated with chondrocytes and introduced growth factors that promote chondrocyte formation to promote the growth of chondrocytes; the main raw materials such as heparan sulfate proteoglycan with good biocompatibility and degradability are selected, and cross-linking reaction, freeze-drying, and directional Pore-forming, multi-layer composite, complete integration and other methods to obtain functional multi-layer integrated tissue engineering osteochondral composite scaffold with good mechanical properties. The invention adopts micro-nano hydroxyapatite crystals and degradable non-stoichiometric polyethylene glycol / polyε-caprolactone nano-coaxial short fibers and heparan sulfate proteoglycan / oxidized sodium alginate grafted with RGD Compounded with N-succinyl chitosan, it is mainly used for repairing full-thickness defects of articular cartilage and subchondral bone.