223 results about "Claudin" patented technology

Provided are an anti-CLDN18.2 antibody or an antigen-binding fragment thereof, a derivative comprising said antibody or antigen-binding fragment thereof, a pharmaceutical composition, and related use of said antibody or antigen-binding fragment thereof for treating, diagnosing and detecting cancers.

The invention belongs to the technical field of probiotic products, and particularly relates to lactobacillus rhamnosus JM039 as well as a composition and application thereof. The preservation number of the lactobacillus rhamnosus JM039 is GDMCC No: 64409. The lactobacillus rhamnosus JM039 is a lactobacillus rhamnosus strain. The composition is prepared from lactobacillus reuteri J1, lactobacillus gasseri JM1, lactobacillus paracasei JY062, lactobacillus paracasei with the preservation number of GDMCC.No.62990, lactobacillus plantarum JY039 and lactobacillus rhamnosus JM039, and is prepared from lactobacillus reuteri J1, lactobacillus gasseri JM1, lactobacillus paracasei JY062, lactobacillus paracasei with the preservation number of GDMCC.No.62990, lactobacillus plantarum The combined bacteria of the six probiotics can improve the levels of anti-inflammatory factors and intestinal epithelium tight junction proteins and reduce the levels of proinflammatory factors and claudin-2 mRNA, so that the intestinal microenvironment homeostasis and intestinal barrier integrity are maintained through double regulation of inflammatory factors and tight junction proteins, and necrotizing enterocolitis can be relieved.

The invention belongs to the technical field of biological medicine, and particularly relates to application of garlic polysaccharide in preparation of a product for repairing intestinal injury caused by constipation. An embodiment verifies that the garlic polysaccharide can effectively repair intestinal physical, chemical and immune barrier injuries caused by constipation, and by up-regulating expression of tight junction proteins (such as ZO-1 and Occludin) and reducing expression of Claudin-1, the garlic polysaccharide can enhance tight junction between intestinal epithelial cells and reduce intestinal permeability; besides, the garlic polysaccharide can promote secretion of intestinal mucoprotein and enhance the protection function of the intestinal mucous layer by up-regulating expression of MUC2 and MUC4 genes. The invention discloses a multi-aspect action mechanism of the garlic polysaccharide in repairing intestinal injury caused by constipation, and the garlic polysaccharide is expected to become a novel intestinal repairing agent for treating constipation and related complications thereof.

The invention belongs to the field of biological medicines, and particularly discloses application of uridine in preparation of medicines for preventing and treating ulcerative colitis, including application of uridine in preparation of medicines for preventing and treating ulcerative colitis in acute stage, application of uridine in preparation of medicines for preventing and treating ulcerative colitis in remission stage and the like. Uridine can improve the symptoms of DSS-induced acute experimental colitis model mice, has a good treatment effect, and improves the weight of the model mice; experimental results indicate that a high-dose group of uridine has a good treatment effect, the mechanism and specificity of uridine up-regulate expression and activity of colon local SIRT1 protein, further inhibit phosphorylation activation of an NF-kappa B signal channel, regulate secretion of inflammatory factors and expression of tight junction protein, repair intestinal mucosal barrier while moderately regulating immunity, and improve the immunity of a human body. The systemic inflammatory response is effectively relieved.

The invention belongs to the technical field of biological medicine, and discloses application of cornu cervi degelatinatum extract in strengthening a skin barrier. The cornu cervi degelatinatum extract disclosed by the invention can promote proliferation of HacaT cells and expression of tight junction protein Claudin-1, also has better capabilities of removing hydroxyl free radicals, DPPH free radicals and superoxide anions and an effect of promoting wound healing, and can protect a skin mechanical barrier and promote barrier injury repair. The cornu cervi degelatinatum extract has a good application prospect in preparation of drugs for promoting wound healing and products related to strengthening and toughening skin barriers, and resource development and utilization of cornu cervi degelatinatum are enriched.

Provided herein anti-human claudin 6 (CLDN6) and anti-human C5 antibodies.

The present invention relates to bispecific antibodies against claudin 18.2 and CD3, pharmaceutical compositions comprising said bispecific antibodies, and related uses in the treatment of cancer.

Provided are combination therapies that include an inhibitor of PD-1 or PD-L1 and an antibody-drug conjugate targeting claudin 18.2.

Antibodies and compositions against Claudin 6 and uses thereof are provided.

The invention discloses application of fraxinellone as a cGAS-STING signal channel inhibitor in preparation of a medicine for treating inflammatory bowel disease, and belongs to the technical field of biological medicine. Aiming at the problem that the specific action mechanism between fraxinellone and the inflammatory bowel disease is not clear, the invention researches the specific action mechanism of fraxinellone for exerting the treatment and protection effects on the inflammatory bowel disease from the in-vivo and in-vitro aspects. Results show that the FRA can significantly inhibit the increase of the ROS level of IEC-6 cells caused by LPS, improve the mitochondrial membrane potential, significantly improve the pathological characteristics of DSS-induced mouse weight loss, DAI index increase, red, swollen and shortened colon, damaged colon tissue structure and the like, and inhibit the expression level of inflammatory factors. According to the present invention, it is found that the FRA can up-regulate the TJ tight junction protein and recover the intestinal barrier function by regulating the expression of cGAS-STING signal channel related proteins such as cGAS, STING, p-TBK1, NF-kappa B and the transcriptional level of mRNA, such that the IBD treatment effect is provided, and the basic basis is provided for the development of the new IBD treatment drug or strategy.

The application discloses a use of a solute carrier family 25A33 gene in preparation of a medicament for treating presbycusis, and the use is achieved by enhancing SLC25A33 expression on an endolymphatic vascular stripe, by maintaining mitochondrial function stability of pericyte cells around the vascular stripe, by reducing active oxygen free radical (ROS) generation, and by blocking TGFbeta / SMAD pathway-mediated pericyte differentiation, so as to protect the integrity of the blood labyrinth barrier. Animal experiments show that overexpression of SLC25A33 can significantly reduce the hearing threshold of a presbycusis model mouse, protect the structure of the blood labyrinth barrier, and improve the expression of tight junction proteins, and the SLC25A33 gene has the potential to treat presbycusis.

The present application provides a nanobody targeting Claudin18.2 and a nucleic acid sequence encoding the same. The present application also provides a multispecific antibody, a chimeric antigen receptor, an antibody conjugate comprising the Claudin18.2 nanobody, a pharmaceutical composition and a kit comprising the same, and the use of the same in the diagnosis / treatment / prevention of diseases associated with Claudin18.2 expression.

The present disclosure relates to a method of treating bile duct cancer in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an anti-tight junction protein-1 antibody.

The present invention provides a method of constructing a library of binder scaffolds (library of protein scaffolds) comprising the steps a) providing an initial polypeptide, wherein said initial polypeptide comprises or consists of a polypeptide having at least 90% identity to SEQ ID NO:1, and b) introducing diversity into copies of said initial polypeptide to form the binder scaffold library (protein scaffold library).

Described herein are methods for inhibiting a solid tumor expressing claudin-6 in a human subject, comprising administering to the human subject an effective amount of a composition comprising conjugates of a CLDN6-specific antigen-binding protein covalently bound to heterologous moieties comprising structural formula (I):whereina first plurality of the conjugates are bound to four heterologous moieties comprising structural formula (I);at least about 95% of the first plurality of conjugates are structurally homogenous; andthe effective amount is in a range of about1.0 mg of conjugate / kg weight of the subject to 10 mg of conjugate / kg weight of the subject.

The invention relates to an application of a synthetic peptide targeting CLDN12 in reduction of hepatic metastasis of pancreatic cancer. Research finds that the tight junction protein Claudin12 (CLDN12) is expressed on the surface of pancreatic cancer cells and also expressed on fibroblasts, and the CLDN12 on the fibroblasts and the CLDN12 on the pancreatic cancer cells mediate an adhesion effect through homologous interaction and guide migration and invasion of the pancreatic cancer cells. The adhesion effect of CLDN12-mediated fibroblasts and pancreatic cancer cells is blocked, and the invasion of the pancreatic cancer cells dominated by the fibroblasts can be blocked, so that the invasion and metastasis of the pancreatic cancer are reduced.

The invention discloses a manganese-based nano-enzyme composite material as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) preparing Mn3O4-PVP from Mn3O4 NPs and PVP10, and then loading the Mn3O4-PVP into a ZIF-8 structure in the process that Zn < 2 + > and 2-MI react to form ZIF-8, so as to obtain Mn3O4-coated ZIF-8 NPs; (2) covering the surface of the Mn3O4 ZIF-8 with HA through ion coordination, and synthesizing MZH; and (3) carrying out clathration on MZH through ES100, and synthesizing MZH coated ES100. By inhibiting a TLR4 / NF-kappa B pathway, activating an Nfr2 / Keap1 pathway and increasing expression of intestinal tight junction protein, mouse colitis induced by DSS is resisted, and symptoms of the mouse colitis are relieved.

Provided are bispecific and multi-specific antibodies that target claudin 6 (CLDN6) and 4-1BB. These antibodies, in the absence of CLDN6-expressing cells, can bind to 4-1BB but are unable to activate 4-1BB signaling. In the presence of CLDN6-expressing cells, however, these antibodies can trigger CLDN6-dependent 4-1BB signaling, leading to potent immune response to the CLDN6-expressing tumor cells.

The present invention relates to CLAUDIN-6 conjugate dosing for cancer treatment. Described herein are methods for inhibiting a Claudin-6 expressing solid tumor in a human subject comprising administering to the human subject an effective amount of a composition comprising a CLDN6 specific antigen binding protein covalently bonded to a heterologous moiety comprising structural formula (I), wherein a first plurality of the conjugates are bonded to four heterologous moieties comprising structural formula (I); at least about 95% of the first plurality of conjugates are structurally uniform; and the effective amount is in the range of about 1.0 mg conjugate / kg body weight of the subject to 10 mg conjugate / kg body weight of the subject.

The present invention relates to a strain of Lactobacillus johnsonii N5 and its application in preventing and treating enteritis and diarrhea. Lactobacillus johnsonii N5), was deposited in the China Center for Type Culture Collection on February 10, 2023, with the deposit number CCTCC NO: M2023104. The Lactobacillus johnsonii N5 was isolated from the fecal microorganisms of piglets resistant to heat stress-induced diarrhea. This Lactobacillus johnsonii N5 has the effect of alleviating enteritis and diarrhea, which is specifically reflected in: significantly enhancing the expression of intestinal epithelial tight junction proteins and cytoprotective heat shock protein 70, improving the immune balance of animal intestinal T cells, enhancing immune tolerance, and reducing the degree of intestinal inflammation and the occurrence of diarrheal diseases in animals. Therefore, Lactobacillus johnsonii N5 has a significant effect in preventing and treating diarrhea and related intestinal inflammatory diseases.

The present invention relates to a conjugate comprising the chemotherapeutic agent monomethyl auristatin E (MMAE) and an isolated antigen-binding protein which binds claudin-6 or an antigen-binding fragment thereof, wherein the antigen-binding protein or fragment thereof comprises: (i) HC CDR1 having a sequence GFTFSNYW (SEQ ID NO: 23), (ii) HC CDR2 having a sequence IRLKSDNYAT (SEQ ID NO: 24), (iii) HC CDR3 having a sequence XDGPPSGX (SEQ ID NO: 457), wherein X at position 1 is N and X at position 8 is S, T, A, C, or Y, (iv) LC CDR1 having a sequence ENIYSY (SEQ ID NO: 20), (v) LC CDR2 having a sequence NAK (SEQ ID NO: 21), and (vi) LC CDR3 having a sequence QHHYTVPWT (SEQ ID NO: 22); wherein the antigen-binding protein or fragment thereof is linked to a chemical structure shown in Formula I that is linked to a chemical structure shown in Formula II that is linked to a chemical structure shown in Formula III that is linked to the MMAE.

The invention discloses a marker for diagnosing intestinal epithelial barrier injury induced by uremic toxin and application of the marker, and belongs to the technical field of biomedicine. Human colon cancer cells (Caco-2) are adopted to establish intestinal epithelial injury models under different urea treatment conditions, and the optimal concentration and time are screened through CCK-8 and immune blot. According to the present invention, RT-qPCR is adopted to detect the expression of lncRNANEAT1 and miR-122-5p, Westernblot and an immunofluorescence method are adopted to detect the expression of tight junction proteins Occludin, ZO-1 and Claudin-1, fluorescein sodium is adopted to detect the cell para-permeability of an intestinal epithelial injury model, and the combination of miR-122-5p with lncRNANEAT1 and Occludin is detected through bioinformatics analysis and dual-luciferase reporter gene analysis; the result shows that the lncRNANEAT1 can be used for protecting intestinal epithelial barrier injury induced by uremia toxin by regulating the miR-122-5p / Occludin axis. The discovery reveals an action mechanism of the lncRNANEAT1 in uremia toxin induced intestinal epithelial barrier injury, and provides a new thought and method for reducing complications of uremia patients and improving life quality.

The application discloses a phytosterol and phytosterol ester complex agent and application thereof, wherein the complex agent comprises phytosterol and phytosterol ester with a mass ratio of 1:10. The application aims to improve the water solubility and bioavailability of phytosterol, realize synergistic effect by compounding phytosterol and phytosterol ester, interfere with the lipid acquisition of coccidia from multiple targets, up-regulate the expression of cecal tight junction protein to repair the intestinal barrier, inhibit the release of serum and cecal pro-inflammatory factors to relieve inflammatory reaction, regulate the expression of genes related to lipid synthesis and fatty acid oxidation to remodel lipid metabolism homeostasis, and then effectively inhibit the growth and development of coccidia, and significantly improve the growth performance of broilers infected with coccidia.

Disclosed in the present invention are a CLDN18.2-targeting nanobody, and a preparation method therefor and the use thereof. Specifically disclosed are CLDN18.2-targeting nanobodies having amino acid sequences of SEQ ID NOs: 2, 4 and 20, respectively, and the uses thereof. The nanobody of the present invention has a high affinity and a good specificity, can bind to a CLDN18.2 antigen, has an anti-tumor activity, and cannot bind to other CLDN family members. The nanobody has few toxic and side effects, and thus can be prepared into a prophylactic and therapeutic drug for a Claudin 18.2 target-related disease, a diagnostic drug, a detection or in-vivo imaging product for a Claudin 18.2 protein, etc.

This barrier function enhancer, this occludin mRNA expression promoter, this claudin-1 mRNA expression promoter, this claudin-4 mRNA expression promoter, this tight junction protein-1 mRNA expression promoter, and this tight junction protein-2 mRNA expression promoter contain ganoderic acid as an active ingredient.

The present invention provides anti-claudin 18.2 nanobodies or their binding fragments. The antibody exhibits good specificity, and immune effector cells targeting claudin 18.2 prepared using the antibody show good therapeutic efficacy in treating or improving diseases with positive claudin 18.2 expression.

Provided herein are Claudin 18.2 binding agents and chimeric antigen receptors (CARs) that comprise Claudin 18.2 binding molecules that specifically bind to Claudin 18.2, and the immune cells, such as CAR-T cells, that comprise these Claudin 18.2 specific CARs.Also provided are the methods for producing and using Claudin 18.2 specific CARs and Claudin 18.2 binding agents, and the immune cells that comprise Claudin 18.2 specific CARs.

The invention discloses an application of glabridin in preparation of related drugs for inhibiting epithelial-mesenchymal transition in inflammatory bowel diseases. In the epithelial-mesenchymal transformation process, epithelial cells lose cell polarity and intercellular connection, are transformed into mesenchymal cells in function and morphology, directly participate in fibroblast activation and extracellular matrix deposition and cause intestinal fibrosis, and are one of anti-fibrosis targets. According to the application of the glabrione in preparation of the medicine related to inhibition of epithelial-mesenchymal transition in the inflammatory bowel disease, provided by the invention, the expression change of epithelial cell markers Claudin-1 and E-cadherin caused by TGF-beta 1 and interstitial cell markers Vimentin, N-cadherin, Snail and alpha-SMA can be relieved, cell migration caused by TGF-beta is improved, and the epithelial-mesenchymal transition induced by TGF-beta 1 is inhibited. The research on the mechanism of action shows that by blocking a TGF-beta1 / Smad2 / 3 signal channel and inhibiting AKT1 activation and inhibition of epithelial-mesenchymal transition, the application of the compound in inhibition of epithelial-mesenchymal transition and prevention of intestinal disease related fibrosis is prompted.

The invention discloses asterias amurensis glucan as well as a preparation method and application thereof, and belongs to the technical field of biological medicine, the asterias amurensis glucan is obtained by combining an enzymolysis method with anion exchange column chromatography and gel column chromatography purification, the main chain structure of the asterias amurensis glucan is 1, 4-linked alpha-D-glucose, and the main chain structure of the asterias amurensis glucan is 1, 4-linked alpha-D-glucose. A terminal alpha-D-glucose branch chain is arranged at the O-6 position of a main chain, and meanwhile, a small amount of mannose and galactose are contained. Moreover, it is proved for the first time that the asterias amurensis glucan can serve as an intestinal barrier protective agent, and oxidative damage, caused by H2O2, of intestinal epithelial cells is improved by up-regulating an Nrf2 signal channel and tight junction protein. Therefore, the asterias amurensis glucan prepared by the invention has a huge potential of being developed into medicines and health-care products for protecting intestinal tracts.

The invention discloses a probiotic which is derived from human milk and has the effects of resisting oxidation, resisting inflammation, protecting tissues and protecting intestinal barriers and application of the probiotic. Lactobacillus paracasei DPUMW-M14-9 is preserved in the general microbiological center of the China Committee for Culture Collection of Microorganisms, and the preservation number is CCTCC M 20252990. The strain has the characteristics of acid resistance, bile resistance, strong oxidation resistance, high surface hydrophobicity, self-aggregation capability and the like. The lactobacillus paracasei DPUMW-M14-9 can effectively adhere to epithelial cells, promote cell proliferation and regulate and control the process of a cell cycle. The bacterial strain can be used for inhibiting proinflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) induced by lipopolysaccharide (LPS) and repairing tight junction proteins (ZO-1, Occludin and Claudin-1) at the same time, so that the integrity of epithelial cells is enhanced.