33 results about "Heparan sulfate" patented technology

Disclosed is a method of treating liver ischemia reperfusion (I / R) injury in a subject. In some aspects, the method comprises providing a subject suffering from liver I / R injury or at risk of suffering liver I / R injury; and administering to the subject one or more heparan sulfate (HS) compounds. In some aspects, the one or more HS compounds comprises about 5 to about 18 saccharide units, optionally about 12 to about 18 saccharide units. In some aspects, the one or more HS compounds comprises about 12 saccharide units.

The invention provides an application of OPO and a composition thereof in promoting intestinal development. The 1, 3-dioleoyl-2-palmitin disclosed by the invention can be used for up-regulating the transcriptional level of a coding gene gpc1 of phospholipid globulin glycan, a coding gene has1 of hyaluronic acid synthetase 1, a coding gene has2 of hyaluronic acid synthetase 2, a coding gene has3 of hyaluronic acid synthetase 3, a coding gene ext1 of exosome glycosyltransferase 1 and a coding gene ext2 of exosome glycosyltransferase 2; therefore, the development of a protein skeleton of the glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the development of the glycocalyx layer is further promoted, and the effects of improving the intestinal barrier, regulating the intestinal flora and improving the intestinal health are achieved.

The invention relates to the technical field of artificial design of enzymes, in particular to an artificial intelligence design and expression system construction method and system for lysosomal membrane protein type N-acetyltransferase with 11 transmembrane regions, and the method comprises the following steps: collecting reaction rate information of an enzyme and a substrate, associating a structure model with rate parameters, and comparing three-dimensional difference of residues, according to the method, by collecting the reaction rate correlation structure conformation, dynamic recognition of the key conformation state is achieved, the accuracy of three-dimensional space difference analysis is improved, host expression optimization factors are fused in the construction process, and the construction efficiency is improved. According to the method, the expression efficiency is improved, conformation function screening and structural stability parallel evaluation are carried out, the screening accuracy of efficient catalysis and stable expression is enhanced, three links of recognition, screening and construction are broken through, the target enzyme obtaining efficiency and expression quality are improved, and enzyme engineering is promoted to be developed towards high-throughput systematization.

This invention discloses a recombinant 2-O-sulfonyltransferase mutant and its preparation method, belonging to the field of biotechnology. The recombinant enzyme sequence is formed by fusing a truncated (E28~N356) mutant of hamster-derived 2-O-sulfonyltransferase (L119V-R188E-A240I) with an N-terminal maltose-binding protein (MBP) tag. The recombinant 2-O-sulfonyltransferase mutant exhibits higher activity, 1.9 times that of the recombinant wild type, and greater stability, retaining 86.6% of its activity after 5 days at room temperature. Furthermore, the soluble expression level of this recombinant mutant 2-O-sulfonyltransferase is increased by 5 times. This mutant, as a novel biocatalyst with high efficiency, stability, and controllable production costs, has significant application value and broad industrialization prospects in the industrial enzymatic synthesis of glycosaminoglycans such as heparin and heparan sulfate.

A major obstacle in the field of biotherapeutics is the need for platform technologies that enable high bioavailability and long-term therapeutic exposure of biotherapies in localized disease. Traditional approaches result in problematic trade-offs, such as toxicity and off-target side effects. The present disclosure provides compounds comprising follistatin domain 1 (FSD1) of follistatin (FST), which can bind to biological structures, such as the extracellular matrix, via heparan sulfate without the undesired neutralizing effects on the activity of activin A, myostatin, and GDF11, as full-length follistatin does. The present invention relates to fusion or conjugated proteins, compositions thereof, constructs or vectors encoding them, their medical uses, and methods for biotherapeutics.

The invention provides a preparation method and application of a dairy product for promoting development of an intestinal tract glycocalyx layer. Comprising a specific dose of casein phosphopeptides, and can up-regulate the transcriptional levels of a coding gene gpc1 of phospholipid globulin glycan, a coding gene has1 of hyaluronic acid synthetase 1, a coding gene has2 of hyaluronic acid synthetase 2, a coding gene has3 of hyaluronic acid synthetase 3, a coding gene ext1 of exosome glycosyltransferase 1 and a coding gene ext2 of exosome glycosyltransferase 2. Therefore, the development of a protein skeleton of the glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the development of the glycocalyx layer is further promoted, and the effects of improving the intestinal barrier, regulating the intestinal flora and improving the intestinal health are achieved.

The present invention relates to a pharmaceutical composition for preventing or treating Sanfilippo syndrome type A (MPS IIIA) comprising heparan N-sulfatase (HNS), and more particularly, to an optimal dose and period of administration of heparan N-sulfatase, which can effectively reduce the accumulation of heparan sulfate (HS) while improving the cognition of patients. According to the present invention, it can be used as enzyme replacement therapy (ERT) for treating Sanfilippo syndrome type A.

The invention discloses preparation and application of toad skin heparinoid sulfate capable of inhibiting activity of new spike protein. The preparation method comprises the following steps: crushing dried toad skin, heating in a water bath to swell, carrying out enzymolysis by using alkaline protease, and carrying out alcohol precipitation, anion exchange column purification, dialysis and freeze drying to obtain a toad skin glycosaminoglycan crude extract; crude toad skin glycosaminoglycan extracts are subjected to enzymolysis through chondroitin sulfate ABC enzyme, and the toad skin heparinoid sulfate is obtained through gel chromatographic column purification, desalination and freeze drying. The average molecular weight of the toad skin heparinoid sulfate is 11Kda, the toad skin heparinoid sulfate is composed of disaccharide units formed by connecting hexuronic acid and glucosamine through 1-4 glucosidic bonds, and the total sulfation degree of the C-2-oxygen site of hexuronic acid and the total sulfation degree of the C-6-oxygen site and the total sulfation degree of the N-site of glucosamine are 11.45%, 33.68% and 46.46% respectively. The toad skin heparinoid sulfate has competitive activity of inhibiting binding of new crown spike protein and heparin, and can prevent initial infection of new crown virus. The invention lays an important foundation for the development of new clinical application of the toad skin.

The present relates to a pharmaceutical composition for use in the treatment of ischemic stroke. The present invention has an application in particular in the therapeutic and pharmaceutical fields.

The invention relates to the field of filter materials, in particular to a melt-blown PBT non-woven fabric composite filter material and a preparation method and application thereof. The melt-blown PBT non-woven fabric composite filter material comprises a protecting net layer, a filter paper layer and a bottom layer PBT melt-blown fabric, and is characterized in that the bottom layer PBT melt-blown fabric is prepared from heparinized TPU and PBT according to the weight ratio of 1: (3-5), and a preparation method of the heparinized TPU comprises the steps that 1, TPU is dissolved to obtain a TPU solution, and the temperature is reduced to 38-42 DEG C; 2) dissolving heparan sulfate to obtain a heparan sulfate solution; the filtering material has the advantages that the heparinized TPU is obtained by compounding the TPU modified by heparan sulfate and PBT (polybutylene terephthalate), the thrombus risk in the blood filtering process is obviously reduced, and the platelet decline rate in the blood filtering process is as low as 25.4-14.9%.

Enhanced recombinant adeno-associated viruses (rAAVs) (e.g., rAAV2, rAAVrh8R, etc.) are provided herein for improved gene therapy of eye or central nervous system (CNS) disorders, wherein the rAAV comprises one or more amino acid substitutions that interact with the heparan sulfate proteoglycan. The invention provides methods for enhancing retinal cell transduction and methods for treating eye diseases with enhanced compositions of rAAV particles. Furthermore, enhanced recombinant adeno-associated viruses (rAAVs) (e.g., rAAV2, rAAVrh8R, etc.) are provided herein for improved gene therapy of CNS disorders. The invention provides methods for delivering the rAAV to the CNS, methods for treating CNS disorders with enhanced compositions of rAAV particles, and kits for delivering the rAAV to the CNS and / or treating a CNS disorder.

The invention provides application of cheese protein zymolyte in promoting intestinal development. The casein zymolyte provided by the invention can up-regulate the transcriptional levels of a coding gene gpc1 of phospholipid globulin glycan, a coding gene has1 of hyaluronic acid synthetase 1, a coding gene has2 of hyaluronic acid synthetase 2, a coding gene has3 of hyaluronic acid synthetase 3, a coding gene ext1 of exosome glycosyltransferase 1 and a coding gene ext2 of exosome glycosyltransferase 2; therefore, the development of a protein skeleton of the glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the development of the glycocalyx layer is further promoted, and the effects of improving the intestinal barrier, regulating the intestinal flora and improving the intestinal health are achieved.

The invention provides application of casein phosphopeptides in promoting development of intestinal glycocalyx layers and preparing related products. The casein phosphopeptide provided by the invention can up-regulate the transcriptional level of a coding gene gpc1 of phospholipid globulin glycan, the transcriptional level of a coding gene has1 of hyaluronic acid synthetase 1, the transcriptional level of a coding gene has2 of hyaluronic acid synthetase 2, the transcriptional level of a coding gene has3 of hyaluronic acid synthetase 3, the transcriptional level of a coding gene ext1 of exosome glycosyltransferase 1 and the transcriptional level of a coding gene ext2 of exosome glycosyltransferase 2; therefore, the development of a protein skeleton of the glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the development of the glycocalyx layer is further promoted, and the effects of improving the intestinal barrier, regulating the intestinal flora and improving the intestinal health are achieved.

The invention belongs to the technical field of biology, and relates to nano antibody mutation design and virus infection blocking, in particular to a mutant nano antibody Mut-Nbs1 for resisting PCV2 cell surface molecule heparan sulfate (HS) and application of the mutant nano antibody Mut-Nbs1. On the basis of a nano antibody crystal structure (PDB ID:: 7TJC), the mutant nano antibody Mut-Nbs1 is obtained through molecular docking, alanine scanning and virtual saturation mutation technologies. The mutant nano antibody Mut-Nbs1 specifically bound with HS is obtained, and the mutation site of the mutant nano antibody Mut-Nbs1 is PHE47gt; aRG, ASP < 99gt >; tYR, TYR 108gt, TYR 108gt; a PRO; eLISA results show that Mut-Nbs1 can be combined with HS in a high affinity manner, has no cross reaction with small molecules of other HS structural analogues, has good affinity and specificity, has the characteristics of high efficiency, rapidness and low cost, and has a wide application prospect.

The invention provides formula milk powder as well as a preparation method and application thereof in promoting intestinal protection or repair. The formula milk powder disclosed by the invention comprises cheese protein zymolyte, and transcriptional levels of an encoding gene gpc1 capable of up-regulating phospholipid globulin glycan, an encoding gene has1 of hyaluronic acid synthetase 1, an encoding gene has2 of hyaluronic acid synthetase 2, an encoding gene has3 of hyaluronic acid synthetase 3, an encoding gene ext1 of exosome glycosyltransferase 1 and an encoding gene ext2 of exosome glycosyltransferase 2, therefore, the formation of a protein skeleton of a glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the formation of the glycocalyx layer is further promoted, and the effects of perfecting an intestinal barrier, regulating intestinal flora, improving intestinal health and promoting intestinal protection or repair are achieved.

The present invention relates to a lyophilized preparation containing, as an active ingredient, a fusion protein of an antibody and heparan N-sulfatase (SGSH), the lyophilized preparation further comprising an isotonic agent, a nonionic surfactant, and a buffering agent, wherein the nonionic surfactant contains polysorbate and poloxamer, and the buffering agent contains histidine.

The invention relates to the technical field of aquaculture, in particular to application of heparan sulfate in prevention and treatment of grass carp reovirus. The heparan sulfate is competitively combined with the grass carp reovirus, so that the virus adsorption and infection process can be effectively inhibited. In drugs, fish feed and additives, when the concentration of heparan sulfate exceeds 0.1 mu g / mL or 10mg / kg, the effect of resisting grass carp reovirus is obviously shown. Cell experiments and artificial infection challenge experiments prove that the virus infection rate can be reduced, the survival rate can be increased, and tissue damage can be reduced. As an antiviral feed additive, the heparan sulfate provided by the invention has the advantages of low cost, small dosage, high safety and the like, provides a new strategy for preventing and treating viral diseases in the aquaculture industry, and has a wide application prospect.

Provided herein include sulfated glycosaminoglycans including sulfated disaccharides, tetrasaccharides, and oligosaccharides and methods of synthesizing heparan sulfate disaccharide, tetrasaccharide, oligosaccharide library in solution-phase. Provided herein also includes a method of treating neurological diseases or disorders with sulfated glycosaminoglycans such as 4-O-sulfated chondroitin sulfate polysaccharides.

The invention discloses heparan sulfate N-deacetylation / N-sulfotransferase with improved enzyme activity and a production method of heparan sulfate N-deacetylation / N-sulfotransferase, and belongs to the technical field of biology. The human heparan sulfate N-deacetylation / N-sulfotransferase is subjected to truncation mutation, connecting peptide optimization, site-specific mutagenesis and superposition mutation, the specific enzyme activity of the obtained mutant reaches 6.7 * 10 < 3 > U / mg and is improved by 118% compared with that of an original strain, the sulfonation modification level of 1g / L of N-sulfonated heparin precursor can be improved to 80% or above, and the specific enzyme activity of the obtained mutant is greatly improved. The sulfated modification level of the intracellular synthesized N-sulfated heparin precursor can reach 90% or above, the requirement for highly sulfated modification of heparin is met, and a solid foundation is laid for large-scale production of biosynthesized heparin.

The invention provides application of lactoferrin and a composition thereof in promoting intestinal development. The lactoferrin provided by the invention can up-regulate the transcriptional level of a coding gene gpc1 of phospholipid globulin glycan, the transcriptional level of a coding gene has1 of hyaluronic acid synthetase 1, the transcriptional level of a coding gene has2 of hyaluronic acid synthetase 2, the transcriptional level of a coding gene has3 of hyaluronic acid synthetase 3, the transcriptional level of a coding gene ext1 of exosome glycosyltransferase 1 and the transcriptional level of a coding gene ext2 of exosome glycosyltransferase 2; therefore, the development of a protein skeleton of the glycocalyx layer, the synthesis of hyaluronic acid and the synthesis of heparan sulfate are promoted, the development of the glycocalyx layer is further promoted, and the effects of improving the intestinal barrier, regulating the intestinal flora and improving the intestinal health are achieved.

The present invention provides a composition for improving the epidermal junction layer and its application. It was found that the combination of a symbiotic fermentation product of Thermus thermophilus and Bacillus sp. and grape seed extract synergistically improves the expression of proteins associated with the epidermal junction layer, increasing the expression of occludin by 316%, heparan sulfate proteoglycan (HSPG) by 64%, and hyaluronic acid receptor protein (CD44) by 69%. Compared with single ingredients, this composition is more effective in improving the health of the epidermal junction layer. It can be used to prepare cosmetics to meet the urgent need for anti-aging, has good application prospects, and also provides a new approach to the development of traditional anti-aging skin care products.

Methods and compositions for diagnosing, preventing or treating a viral infection in a subject comprising administering to a subject in need thereof an effective amount of a glycosidase or a sulfatase to degrade a glycan, such as heparan sulfate, to inhibit viral infection, such as COVID-19. Methods for identifying a glycosidase, a sulfatase, or a microbe associated with increased susceptibility to viral infection in a subject.

The invention discloses a method for modifying mesenchymal stem cells with dual-response peptide fragments and application of the mesenchymal stem cells in drug delivery. The dual response type peptide fragment (MSP-Trap) is composed of three parts: a connecting sequence sensitive to matrix metalloproteinase, a binding sequence targeting heparan sulfate, and a functional group used for NHS coupling. The MSP-Trap peptide fragment can be coupled to the surface of a mesenchymal stem cell (MSC) through NHS, and can be used as a drug carrier to realize efficient delivery of drugs. According to the invention, the MSP-Trap-MSC is further combined with a drug to form a drug-MSP-Trap-MSC compound, so that the enrichment and delivery efficiency of the drug at a diseased region is enhanced, and the MSP-Trap-MSC compound is used for treating different types of diseases.

The present invention relates to heparan sulfate sugar mimetic compounds as heparan sulfate mimetics, and the use of these compounds as medicaments, cosmeceuticals and as molecular probes. The invention also relates to intermediate compounds useful in the preparation of various sugar mimetic compounds. The invention is particularly suitable for treating or preventing diseases such as cancer, inflammation, diabetic nephropathy, neurodegenerative diseases, for bone healing or wound healing, for cosmeceutical use, and as molecular probes comprising imaging agents.

The invention discloses a composite collagen dressing and a preparation method thereof, and relates to the technical field of composite collagen, the dressing comprises a body formed by a double-layer composite structure, and the double-layer composite structure comprises a chitosan fiber non-woven fabric layer and a functional layer. According to the invention, through compounding of collagen and regenerated cellulose, active crosslinking of heparan sulfate, and multiple technological innovations of a PCL drug-loaded microsphere and adhesive-free double-layer structure, the composite dressing which has excellent mechanical properties, an active repair function, long-acting drug sustained release and good biocompatibility is cooperatively constructed.

Provided herein are small molecule compounds, including non-anticoagulant heparan sulfate oligosaccharide molecules, having anti-inflammatory properties and capable of interacting with high mobility group box 1 (HMGB1) proteins in a manner sufficient to affect an interaction between the HMGB1 protein and a receptor for advanced glycation end products (RAGE). Also provided herein are methods of treating Paracetamol (APAP) overdose in subjects.

In the field of biotherapy, a major disorder is the need for a platform technology that enables high bioavailability and long-term treatment exposure of biotherapy in the context of localized disease. Conventional methods have some troublesome tradeoff problems, such as toxic and off-target side effects. The present disclosure provides compounds comprising the follistatin domain 1 (FSD1) of a follistatin (FST) that are capable of binding to a biological structure, such as an extracellular matrix, by heparan sulfate without poorly neutralizing activin A, myostatin, and GDF11 activity, such as full-length follistatin. The present invention relates to fusion proteins or binding proteins and compositions thereof, constructs or vectors encoding the same, medical uses thereof and biotherapeutic methods.

The application provides application of lactoferrin and a composition thereof in promoting intestinal development. The lactoferrin of the application can up-regulate the transcription level of a phospholipid globulin polysaccharide coding gene gpc1, a hyaluronic acid synthase 1 coding gene has1, a hyaluronic acid synthase 2 coding gene has2, a hyaluronic acid synthase 3 coding gene has3, an exosin glycosyltransferase 1 coding gene ext1 and an exosin glycosyltransferase 2 coding gene ext2, thereby promoting development of a protein skeleton of a glycocalyx layer, synthesis of hyaluronic acid, synthesis of heparan sulfate, further promoting development of the glycocalyx layer, and achieving the effects of perfecting an intestinal barrier, regulating intestinal flora and improving intestinal health.

It is provided a bioadhesive comprising an isolated extracellular matrix (ECM) from a decellularized organ with preserved (ultra) structure comprising laminins, collagen 4, collagen-6, collagen-1, fibronectin, elastin, fibrillin, ECM protein 1, proteoglycans, glycoproteins, biglycan, histidine rich glycoprotein, tenascin, and heparan sulfate proteoglycan 2. The bioadhesive described herein and provided composition can be used to seal intra-operative pulmonary air leaks after lung surgery.

The invention provides a method for producing a sulfated polysaccharide by generating a sulfated polysaccharide by incorporating, in a reaction solution in the presence of ATP or an ATP source, a sulfate ion source, and N-sulfoheparosan, a transformant (a) of a bacterium of the genus Corynebacterium, comprising at least a gene encoding an ATP sulfurylase and a gene encoding an APS kinase, and at least one selected from a transformant (b) of a microorganism belonging to prokaryotes, comprising at least a gene encoding a C5-epimerase, a transformant (c) of a microorganism belonging to prokaryotes, comprising at least a gene encoding a 2-O-sulfotransferase, a transformant (d) of a microorganism belonging to prokaryotes, comprising at least a gene encoding a 6-O-sulfotransferase, and a transformant (e) of a microorganism belonging to prokaryotes, comprising at least a gene encoding a 3-O-sulfotransferase.