63 results about "Zonulin" patented technology

The invention provides application of polygonatum cyrtonema polysaccharide in preparation of medicines for treating ulcerative colitis or reducing blood glucose. A main chain of a sugar chain structure of the homogeneous polysaccharide PCP2 in polygonatum cyrtonema is mainly composed of-> 1)-beta-D-Fur-(2->,-> 1, 6)-beta-D-Fur-(2-> and-> 6)-alpha-D-Glcp-(1-> and beta-D-Fur-(2->), a side chain is mainly composed of beta-D-Fur-(2-> and-> 2)-beta-D-Fur-(6-> at a C-6 position of-> 1, 6)-beta-D-Fur-(2->), Fur represents furanose, Glcp represents glucopyranose, Glcp represents glucopyranose, and Glcp represents glucopyranose. The novel polysaccharide compound can relieve intestinal injury of mice, increase expression of tight nectin and mucoprotein, relieve oxidative stress reaction, promote production of short-chain fatty acid and improve composition of intestinal flora, and can be applied to the field of medicine as a medicine for treating ulcerative colitis. Meanwhile, the homogeneous polysaccharide PCP2 in polygonatum cyrtonema can significantly inhibit the activity of alpha-amylase and alpha-glucosidase, can also promote the ability of insulin resistance 3T3-L1 fat cells to uptake and consume glucose, shows a significant hypoglycemic effect, and has a good development prospect in the aspect of preparation of hypoglycemic drugs.

The present invention relates to the fields of medicine and cosmetology, and discloses a cell active peptide composition that promotes the regeneration of multi-type collagen structural proteins, its preparation method, and its application in medicine and cosmetology. The composition uses raw materials such as tripeptide-10 citrulline, hexapeptide-9, hydrolyzed sodium hyaluronate, γ-aminobutyric acid, decarboxylated carnosine hydrochloride, acetyl tetrapeptide-3, acetyl tetrapeptide-11, palmitoyl dipeptide-7, and palmitoyl pentapeptide-4. The composition can promote the coordinated expression of skin type I, type III, type IV, type VII, type XVII collagen, fibronectin, elastin, and glycosaminoglycans; prevent collagen cross-linking, maintain triple helix structure, and inhibit collagen degradation. Applied to dermatology and cosmetology, it can accelerate the regeneration of structural proteins such as skin collagen, repair skin damage, reduce wrinkles such as crow's feet, tear groove lines, nasolabial folds, and under-eye lines, solve the skin aging problem caused by the loss of structural proteins such as collagen, and improve skin elasticity and firmness.

Provided are antibodies that include amino acid sequences of SEQ ID NOs: 2, 4, and 6-12, or amino acid sequences that are about 95% identical thereto, and fragments thereof. Also provided are scFv peptides that include a VH segment having a first amino acid sequence of amino acids 4-113 of any one of SEQ ID NOs: 2 and 8-12, a VL segment having a second amino acid sequence having amino acids 113-237 of SEQ ID NOs. 2 and 8-12, or both; nucleic acids encoding the same; methods for using the same to detect and / or target conformational states of FN in samples; methods for treating diseases and / or disorders and / or for meliorating at least one symptom of consequence of a disease or disorder associated with abnormal expression of a force-induced conformational state of FN in subjects; and methods for screening for compounds having selective binding activities for conformational states of FN.

The present invention relates to a composition comprising the compound of chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of fibrotic diseases. The composition according to the present invention inhibits the expression of collagen type 1 (COL1A1) or fibronectin and thus can be advantageously used as a composition for the prevention or treatment of fibrotic diseases.

A phosphodiesterase type 5 inhibitor is used in the preparation of a medicament for resisting fibrotic diseases. Experiments in animal models of ischemia-reperfusion (UIRI)-induced renal fibrosis, unilateral ureteral obstruction (UUO)-caused kidney fibrosis and idiopathic pulmonary fibrosis show that a PDE5 inhibitor such as tadalafil, sildenafil and vardenafil can significantly inhibit the expression of multiple fibrosis iconic proteins such as fibronectin, collagen I, renal injury molecule-1, and α-skeletal muscle actin in UIRI and UUO renal fibrosis lesions, improves glomerulopathy, degree of renal tubular distension, renal interstitial collagen fiber deposition and inflammatory cell infiltration, reduces the fibrotic area within the lesion, and significantly inhibits the progression of renal fibrosis; and the PDE5 inhibitor can significantly improve smooth muscle proliferation and inflammatory cell infiltration in bronchioles and pulmonary arterioles of idiopathic pulmonary fibrosis lesion, improve damage condition of alveolar tissue, and significantly inhibit the progression of pulmonary fibrosis.

Provided herein are methods for improving glycemic control in a human patient, methods for treating, preventing or reducing overweight or obesity and related co-conditions, and methods for treating or preventing type II diabetes mellitus by administering a polypeptide to the patient, the polypeptide comprises a fibronectin type III tenth (10Fn3) domain that binds to a myostatin. In some embodiments, the polypeptides are administered according to a specific clinical dosing regimen (e.g., at a specific dose and according to a specific time interval) (or for administration according to the regimen).

The application discloses a Mycoplasma bovum adhesion protein FtsZ and application thereof. The nucleic acid sequence of the Mycoplasma bovum adhesion protein FtsZ is shown as SEQ ID NO. 1. The application also discloses a recombinant plasmid pET-30a-ftsZ and an E. coli containing the recombinant plasmid pET-30a-ftsZ. ftsZ The recombinant protein rFtsZ has the advantages of being capable of specifically combining with EBL cell membrane protein, being capable of combining with extracellular matrix components (fibronectin, fibronectin, laminin and type IV collagen), having the direct adhesion host cell effect, having good antigenicity, being capable of producing high-level antibodies, being capable of providing good immune protection effect, and providing a new target and thought for elucidating the pathogenic mechanism of the Mycoplasma bovum and developing a new vaccine and medicine.

The present invention relates to compositions and methods of GDNF fusion polypeptides, wherein the GDNF fusion polypeptides include an Fc domain, an albumin-binding peptide, a fibronectin domain, or a human serum albumin, joined to a GDNF variant either directly or by the way of a linker. The GDNF fusion polypeptides may used to treat metabolic diseases, such as obesity and Type-1 and Type-2 diabetes, and neurological diseases, such as Amyotrophic lateral sclerosis (ALS) and Parkinson's disease.

The current application describes various compositions and methods for the production of FN3-based binding proteins with improved stability properties. Aspects of the disclosure relate to polypeptides comprising a variant fibronectin type III (FN3) domain from Sulfolobus tokodaii or Pyrococcus horikoshii comprising one or more amino acid substitutions or insertions in a loop region of FN3, in a non-loop region of FN3, or in both.

The present invention relates to a composition for preventing, alleviating or treating fibrosis, the composition comprising bentonite as an active ingredient. Bentonite is highly effective in reducing a disease activity index, inhibiting shortening of colon length, regulating the expression level of a gene related to intestinal fibrosis, reducing a collagen deposition site in intestinal tissue, reducing the expression level of fibronectin and collagen proteins in intestinal tissue in an intestinal fibrosis animal model induced by dextran sulfate sodium (DSS), and reducing the expression level of ɑ-smooth muscle actin (ɑ-SMA) and collagen proteins in an intestinal fibrosis cell model induced by TGF-β, and is thus expected to be useful as a composition for preventing, alleviating, or treating intestinal fibrosis.

Provided are antibodies that include amino acid sequences of SEQ ID NOs: 2, 4, and 6-12, or amino acid sequences that are about 95% identical thereto, and fragments thereof. Also provided are scFv peptides that include a VH segment having a first amino acid sequence of amino acids 4-113 of any one of SEQ ID NOs: 2 and 8-12, a VL segment having a second amino acid sequence having amino acids 113-237 of SEQ ID NOs. 2 and 8-12, or both; nucleic acids encoding the same; methods for using the same to detect and / or target conformational states of FN in samples; methods for treating diseases and / or disorders and / or for meliorating at least one symptom of consequence of a disease or disorder associated with abnormal expression of a force-induced conformational state of FN in subjects; and methods for screening for compounds having selective binding activities for conformational states of FN.

The application discloses a recombinant humanized collagen composition for resisting HPV infection and a preparation method thereof. The composition comprises the following components in percentage by mass: 30-45% of a recombinant humanized collagen fusion protein, 30-40% of probiotics and 20-35% of glycogen. The recombinant humanized collagen fusion protein comprises, from N-terminal to C-terminal, a recombinant humanized collagen fragment and a human fibronectin fragment connected in sequence. The recombinant humanized collagen fragment and the human fibronectin fragment are connected by a linker. The recombinant humanized collagen fusion protein in the composition can promote the adhesion and colonization of the probiotic composition to the vaginal epithelial cells, rapidly improve the microbial environment of the vagina and effectively enhance the resistance of the vagina to harmful bacteria and viruses.

The present invention discloses a recombinant type VII collagen protein, Pro.C7, whose amino acid sequence is shown in any one of SEQ ID NOs. 1-8. Also disclosed are its encoding gene, expression vector, host bacteria, preparation method, and application. The present invention designs recombinant human type VII collagen based on a partial sequence of human type VII collagen. The protein is expressed in prokaryotes, and the expression system is mature. The purified protein has been experimentally verified to be non-cytotoxic. By organizing laminin, it promotes fibroblast migration and cytokine secretion, participates in skin damage and repair, and can be used as a biomaterial in cosmetic products, among other applications.

The invention relates to bacillus subtilis as well as a construction method and application thereof, and the bacillus subtilis is a gram-positive bacterium from soil, also belongs to one kind of probiotics, and has multiple benefits to a human body. The Irisin is a novel muscle factor which is generated by shearing a transmembrane fibronectin type III domain protein 5 (fibronectin type III domain-conforming protein 5, FNDC5) through a proteolytic enzyme, and has the effects of alleviating obesity, improving insulin resistance, resisting inflammation and the like. According to the invention, a strain of bacillus subtilis capable of expressing human active irisin is constructed, and meanwhile, a probiotic oral embedding method is provided, so that the in-vivo activity and effect of the bacillus subtilis are improved. The expression strain not only can express and produce the tectoridin protein with activity and without endotoxin, but also can exert the activity of probiotics through oral administration after embedding.

The invention belongs to the technical field of application of biomarker detection kits, and particularly relates to application of a kit for detecting fibronectin in evaluating the intestinal injury state, and the kit comprises an antibody specifically binding to fibronectin; the kit is used for detecting the fibronectin content in an excrement sample, and the intestinal injury state is evaluated based on the fibronectin content. In conclusion, the invention provides the application of the kit for detecting fibronectin, which is based on the excrement sample, is accurate in early stage and is superior to the existing marker, in evaluating the intestinal injury state.

Compositions and methods use one or more feline circulating proteins as markers for early chronic kidney disease (CKD) to diagnose and / or treat CKD. A method of diagnosing chronic kidney disease (CKD) in a feline can include measuring an amount of each of at least one circulating protein from the feline. The at least one circulating protein is one or more of adiponectin (ADIPOQ), antibacterial peptide (CAMP), kinetin-like protein (KIF12), plasma retinol binding protein (RBP4), Ig-like domain containing protein (ZKSCAN1), blood coagulation factor X (F10), fibronectin (FN1), and mixtures thereof. The method further comprises comparing the amount of each of the at least one circulating protein from the feline to a respective predetermined value or a respective predetermined range. The method further comprises diagnosing the feline as having or not having early CKD based on the comparison.

The invention belongs to the technical field of biology, and discloses a composition for promoting proliferation of human immortalized keratinocytes and application of the composition. The inventor finds that the collagen, the fibronectin, the allantoin and the kava pepper leaf / root / stem extract have a good synergistic effect, proliferation of HaCaT cells can be remarkably promoted, and the composition can accelerate repair of damaged skin barriers. Therefore, the invention has a good application prospect in skin care products.

This invention belongs to the field of biomedicine, specifically relating to the application of APOL2 (Apolipoprotein L2) inhibitors in the preparation of products for treating liver fibrosis. The inventors isolated a series of natural tetrodopane-type diterpenes from *Euphorbia pekinensis*, a plant in the Euphorbiaceae family. Anti-liver fibrosis-related activity tests on this series of diterpenes revealed that they significantly inhibited the expression of fibronectin, type I collagen, and α-smooth muscle actin in LX-2 cells. In animal studies, their therapeutic effect was superior to that of pirfenidone, a phase II clinical trial drug for treating liver fibrosis, and they showed no significant toxicity. Mechanistic studies showed that TD1 is an APOL2 inhibitor, and knocking out APOL2 protein in vivo can alleviate the progression of liver fibrosis. In summary, this series of tetrodopane-type diterpenes, especially TD1, shows promise as a candidate drug for treating liver fibrosis and provides a new target for researching novel drugs for treating liver fibrosis.

The application discloses a lignan compound and a preparation method and application thereof, and relates to the technical field of medicines. The application specifically relates to four lignan small-molecule compounds with the same planar structure, which are separated from amber, and include two pairs of enantiomers (+)-6 / (-)-6 and (+)-7 / (-)-7. The compound structures are as follows: In a renal fibrosis model experiment, the lignan compound provided by the application can inhibit the expression of proteins related to renal fibrosis, such as alphaSMA protein, type I collagen protein and fibronectin, in NRK-52E cells induced by transforming growth factor beta 1, which indicates that the lignan compound provided by the application has the use of preparing medicines for preventing and treating renal fibrosis.

Provided is a polypeptide that binds specifically to an artificial low molecular weight ligand. This polypeptide, in which a BC loop of a fibronectin type III domain scaffold contains an amino acid sequence represented by the following formula (1): X1aX1bX1cX1dX1eDX1fX1gD (wherein X1a is A, S, or R, X1b and X1c are each independently an arbitrary amino acid, X1d is N, H, W, or Y, and X1e to X1g are each independently an arbitrary amino acid), and an FG loop contains an amino acid sequence represented by the following formula (2): X2aX2bX2cX2dX2eKX2fX2gX2hX2i (wherein X2a and X2b are each independently an arbitrary amino acid, X2c is G, M, N, Y, or W, X2d is an arbitrary amino acid, X2e is Y, F, P, W, V, or A, X2f is W, Y, V, F, or S, X2g is W, L, V, or M, X2g if V, C, G, or A, and X2i is an arbitrary amino acid), binds specifically to an artificial low molecular weight ligand such as 1-(4-hydroxyphenyl)-3-phenylurea (HPPU) or a derivative thereof.

A method for preparing a bionic injectable polypeptide hydrogel is provided. The hydrogel is formed using a brain extracellular matrix laminin-derived peptide DDIKVAV modified with 9-fluorenylmethoxycarbonyl (Fmoc) (Fmoc-DDIKVAV) and an immunostimulatory peptide FTKPRF modified with Fmoc (Fmoc-FTKPRF) as hydrogel monomers. These monomers further utilize non-covalent bond forces such as hydrogen bonds, hydrophobic interactions, and x-x stacking to co-assemble into a hydrogel within a short time at 37° C. The bionic hybrid polypeptide hydrogel is injectable and can serve as a drug reservoir implanted into cavities formed after tumor surgery. The drugs loaded in the hydrogel are slowly released at a stable and controlled rate and appropriate concentration within the post-surgical cavity, thereby effectively killing residual tumor cells while avoiding the toxic side effects of systemic drug administration.

The invention provides application of circulating protein FGF23 in predicting sudden cardiac death risk of chronic kidney disease patients and model construction, and belongs to the technical field of medicines. The biomarkers comprise NTproBNP (N-terminal B-type natriuretic peptide), DTNB (heteronectin beta), ANGPT2 (angiopoietin 2), FGF23 (fibroblast growth factor 23) and SEPTIN8 (cytokinin 8), wherein the circulating protein FGF23 has the best prediction effect after the risk ratio and AUC evaluation are combined. The FGF23 marker is provided for early prediction of sudden cardiac death after chronic kidney disease, and a technical means is provided for prognosis evaluation of chronic kidney disease treatment.

The invention discloses a recombinant VII type collagen Pro.C7. The amino acid sequence of the recombinant VII type collagen Pro.C7 is shown as any one of SEQ ID NO.1-8. The invention also discloses a coding gene, an expression vector, host bacteria, a preparation method and application of the gene. The recombinant human VII type collagen is designed on the basis of a part of sequences in the human VII type collagen, prokaryote expression, mature expression system and purified protein have no cytotoxicity through experimental verification, fibrocyte migration and cytokine secretion are promoted through tissue laminin, and the human VII type collagen participates in skin injury and repair, so that the human VII type collagen can be used for repairing skin. The material can be applied to beauty products and the like as a biological material.

This invention relates to the field of pharmaceutical technology, specifically to the application of morin A in the preparation of drugs for the prevention and treatment of pulmonary fibrosis. This invention discovers a novel use for morin A, a monomeric component of traditional Chinese medicine, which can be applied to the prevention and treatment of pulmonary fibrosis. By reducing the transcriptional and protein expression levels of fibronectin, α-actin, and type I collagen in fibroblasts, it inhibits the differentiation of fibroblasts into myofibroblasts, thereby slowing the progression of pulmonary fibrosis and providing a new treatment strategy for pulmonary fibrosis. Experimental results show that lung injury and fibrosis were significantly reduced in mice treated with intraperitoneal injections of 10 mg / kg and 20 mg / kg morin A. Furthermore, experiments on human primary fibroblasts also demonstrate that morin A can significantly reduce the protein expression levels of type I collagen, fibronectin, and α-actin in TGF-β1-stimulated human primary fibroblasts.

A method for diagnosing facioscapulohumeral muscular dystrophy (FSHD) using one or more biomarkers is provided. More particularly, provided is a method for diagnosing FSHD in a subject, the method comprising detecting the presence of a biomarker or change in level of a biomarker in a biological sample from the subject, wherein the biomarker is wherein the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), lumican (LUM), phosphatidylinositol-glycan-specific phospholipase D (GPLD1 ), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, LUM, GPLD1, C4BPB, CNDP1, or IGKV2-30. In some aspects, when the change in level of the biomarker is an increase in the level of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, and / or LUM, or a combination of any thereof, the subject is diagnosed as having FSHD. In some aspects, when the change in level of the biomarker is a decrease in the level of GPLD1, C4BPB, CNDP1, and / or IGKV2-30, or a combination of any thereof, the subject is diagnosed as having FSHD. Also provided is a method for determining efficacy of a therapeutic treatment for FSHD in a subject, the method comprising measuring the level of a biomarker in a biological sample from the subject before and after the treatment, and determining that the treatment is effective in treating FSHD if the level of the biomarker is decreased or increased relative to a reference level or to the level of the biomarker in the sample from the subject before treatment, wherein when the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), or lumican (LUM), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, or LUM, the treatment is effective when the level of the biomarker decreases, or wherein when the biomarker is phosphatidylinositol-glycan-specific phospholipase D (GPLD1), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of GPLD1, C4BPB, CNDP1, or IGKV2-30, the treatment is effective when the level of the biomarker increases. In various aspects, the method further comprises treating the subject diagnosed with FSHD.

This application relates to particles with antibodies bound to their surfaces. Specifically, this application relates to a particle with an antibody bound to its surface, and the structure of the particle is shown by the following formula: antibody - bridging protein - particle. This structure is beneficial to maintaining the activity of the antibody, and at the same time, the long arms formed by the bridging protein help to reduce the steric hindrance effect of the antibody and facilitate the binding to the antigen. The particles and reagents prepared in this application have improved accuracy and sensitivity.

The present invention provides, among other things, an integrin α5β1 antibodies and therapeutic uses of such antibodies in effectively treating diseases or disorders associated with integrin α5β1, such as pulmonary arterial hypertension (PAH). The human integrin α5β1 antibodies disclosed herein are characterized with a high affinity to α5β1 integrin, ability to specifically inhibit interaction with fibronectin, and / or binding to α5 β-propeller domain.

The present invention provides novel fibronectin type III domains that bind serum albumin, and specifically relates to polypeptides comprising the tenth fibronectin type III domain (<supgt;10< / supgt;Fn3) with Antarctic loop substitutions, which polypeptides bind to serum albumin. The present invention further relates to fusion molecules comprising <supgt;10< / supgt;Fn3 that binds serum albumin linked to a heterologous protein for use in diagnostic or therapeutic applications.

The present invention provides a protein, and the protein includes a 10th human fibronectin type III domain and has a first mutation at an amino acid residue with a cysteine residue and a second mutation at another amino acid residue with another cysteine residue, wherein the first mutation and the second mutation take place at a region of the 10th human fibronectin type III domain other than a loop FG so that a disulfide bond is formed between the cysteine residue formed by the first mutation and the cysteine residue formed by the second mutation.