103 results about "Claudin" patented technology

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.

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 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.

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 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.

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.

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.

This application relates to antibody-drug conjugates and their use.

The present invention provides Claudin-6-specific immunoreceptors (T cell receptors and artificial T cell receptors (chimeric antigen receptors; CARs)) and T cell epitopes which are useful for immunotherapy.

The invention discloses recombinant lactobacillus casei for expressing sialyltransferase ST6GALNAC1, and belongs to the technical field of genetic engineering and microorganisms. The recombinant bacterium is obtained by cloning an ST6GALNAC1 gene to a pPG612 vector and electrically transforming the ST6GALNAC1 gene into lactobacillus casei ATCC393. Experiments show that the engineering bacterium can significantly enhance glycosylation modification of intestinal mucoprotein MUC2, improve expression of tight junction proteins (ZO-1, Occludin and Claudin-1), inhibit activation of a p38 / MAPK inflammation pathway and regulate an intestinal flora structure, so that intestinal injury and systemic inflammatory response caused by salmonella are effectively relieved. The invention provides a strain basis and technical support for developing a novel oral microecological preparation.

The invention belongs to the technical field of medicine and pharmacy, and particularly relates to application of an AP1B1 allosteric activator of ethyl gallate. In the invention, AP1B1 is a beta 1 subunit (AP1B1) of a linking factor associated protein complex 1 (AP-1), and is an essential component for assembling a functional AP-1B complex. The ethyl gallate is used as an allosteric activator of AP1B1 and is specifically combined with an allosteric pocket of the AP1B1 to induce the AP1B1 to generate conformational change, so that the vesicle transportation function of an AP1B complex is activated, and the substrate-side membrane protein sorting capacity is recovered. A target dependence experiment verifies that the effect of ethyl gallate on promoting tight junction protein ZO-1 expression and membrane localization in AP1B1 knocked-down Caco-2 cells is remarkably weakened, and it is prompted that the intestinal barrier protection function of ethyl gallate depends on AP1B1. The invention provides a new strategy for developing medicines for treating intestinal barrier injury related diseases.

The application discloses a nanobody targeting Claudin 18.2 and an application thereof, and belongs to the technical field of molecular biology. In view of the unique advantages of the nanobody in the prior art, the application provides a nanobody targeting Claudin 18.2, wherein the amino acid sequence of the nanobody is shown as SEQ ID NO. 1; the nanobody has strong affinity to 293T-Claudin 18.2 positive cells and can be combined with the Claudin 18.2 protein expressed on the cell surface. The nanobody targeting Claudin 18.2 provided by the application can be prepared by large-scale expression of an in-vitro engineering bacterium, can be applied to preparation of a protein detection antibody or a therapeutic antibody, can be used for in-vitro and in-vivo detection of tumor tissues expressing Claudin 18.2, and has important commercial value in clinical disease diagnosis and treatment.

A panel of monoclonal antibodies is provided that specifically bind to CLDN18.2 and do not specifically bind to CLDN18.1, and optionally have an engineered Fc region.

The present invention provides a claudin-reducing agent, a tight junction relaxant, and a cosmetic composition that contribute to the penetration of active ingredients into the skin. [Solution] The claudin-reducing agent of the present invention contains Swertia japonica extract. In this claudin-reducing agent, Swertia japonica extract is an extract obtained by extracting the whole plant of the Gentianaceae plant Swertia japonica with 1,3-butylene glycol (1,3-BG).

Antibodies that specifically bind to the human tight junction molecule CLDN18.2 and have functional properties that make them suitable for use in antibody-based immunotherapies of a disease associated with aberrant expression of CLDN18.2 are disclosed.

The present application relates to the use of claudin-3 as a small cell lung cancer treatment target, and more particularly, to a composition for preventing or treating small cell lung cancer with reduced side effects, the composition comprising an anti-claudin-3 specific antibody as an active ingredient. The composition described in the present application does not exhibit ADCC activity in normal cells compared to small cell lung cancer cells, and thus can be effectively used to develop a small cell lung cancer-specific therapeutic agent with fewer side effects.

The present application relates to the use of vascular BACE1 as a therapeutic target for diseases related to cerebral small vessel injury. Specifically, it relates to the use of a substance that reduces the expression level of the beta-secretase (BACE1) gene and / or an inhibitor of the enzymatic activity of BACE1 protein in the preparation of a drug for treating or alleviating cerebrovascular disease, wherein the disease related to cerebral small vessel injury is preferably Alzheimer's disease, amyloid cerebral small vessel disease, and vascular dementia. The inventors have found that an increase in the content of BACE1 can cleave the tight junction protein Occludin, resulting in the degradation and loss of tight junction proteins between vascular endothelial cells, causing the structure and function of the blood-brain barrier to be damaged, ultimately leading to cerebral microbleeds and cognitive dysfunction and other pathological phenotypes of diseases related to cerebral small vessel injury; inhibition of the enzymatic activity of BACE1 can improve these pathological phenotypes of diseases related to cerebral small vessel injury.

The invention discloses lactobacillus helveticus capable of relieving rheumatoid arthritis and application of the lactobacillus helveticus, and belongs to the technical field of microorganisms. A strain of lactobacillus helveticus CCFM1501 is screened out, the lactobacillus helveticus CCFM1501 can produce cell wall protease, amino-peptidase and aromatic transaminase at high yield, and has the effect of relieving rheumatoid arthritis, and the specific effects are that the thickness of a posterior claw of a rat with rheumatoid arthritis is reduced, and knee joint injury is improved; the content of proinflammatory cytokines in the serum of rheumatoid arthritis rats is reduced, the content of anti-inflammatory cytokines IL-10 in the serum of the rheumatoid arthritis rats is increased, the content of arthritis specific antibodies in the serum of the rheumatoid arthritis rats is reduced, the mRNA relative expression quantity of colonic tight junction proteins ZO-1 and Occludin in the rheumatoid arthritis rats is increased, and the anti-inflammatory activity of the rheumatoid arthritis rats is improved. The content of acetic acid and butyric acid in excrement of rats with rheumatoid arthritis is increased.

A panel of monoclonal antibodies is provided that specifically bind to CLDN18.2 and do not specifically bind to CLDN18.1, and optionally have an engineered Fc region.

To provide antigen-binding proteins which bind to Claudin-6 (CLDN6).SOLUTION: Antigen-binding proteins which bind to Claudin-6 (CLDN6) bind to Extracellular Loop 2 (EL2) of the extracellular domain of CLDN6. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are also provided. Kits and pharmaceutical compositions comprising such entities are further provided. Also provided are methods of making antigen-binding proteins and methods of treating subjects having cancer.SELECTED DRAWING: Figure 1

The invention belongs to the technical field of biological medicine, and particularly relates to a preparation method of a probiotic hydrogel material and application of the probiotic hydrogel material in treatment of acute radioactive intestinal injury. In order to solve the clinical key problem of radioactive intestinal injury, a novel biological material TG-CCS-coated DY802 of thiolated synchronously modified chitosan hydrogel TG-CCS loaded with'localized high-response 'lactobacillus salivarius DY802 is constructed. The synthesis process of the material is synergistic and time-saving, has excellent biological safety and tumor inhibition experiment performance, and can comprehensively repair four barriers of the intestinal tract: ROS is removed, and tight junction protein is protected to repair the physical barrier; forming a hydrogel protective layer to reinforce the chemical barrier; the flora diversity is improved, and the prebiotic effect is exerted to repair the biological barrier; the sphingomyelin metabolism and ceramide abundance are regulated and controlled, the abnormal infiltration of NK cells is inhibited, and the immune barrier is remodeled. Therefore, the probiotic hydrogel material disclosed by the invention is clear in treatment mechanism and remarkable in clinical transformation potential and application value.

Provided are bispecific and multi-specific antibodies that target both claudin 18.2 (CLDN18.2) and 4-1BB. These antibodies, in the absence of CLDN18.2-expressing cells, can bind to 4-1BB but are unable to activate 4-1BB signaling. In the presence of CLDN18.2-expressing cells, however, these antibodies can trigger CLDN18.2-dependent 4-1BB signaling, leading to potent immune response to the CLDN18.2-expressing tumor cells.

The application discloses a lactobacillus taiwanensis with enhanced intestinal barrier function and application thereof, and belongs to the technical field of microorganisms and medicine. The lactobacillus taiwanensis is preserved in the Guangdong Microbial Culture Collection Center, and the preservation number is GDMCC No.63714. The intestinal barrier enhancement and protection of the lactobacillus taiwanensis CCFM1318 are embodied in the following aspects: (1) the lactobacillus taiwanensis CCFM1318 has good in-vitro gastrointestinal tolerance, strong adhesion to intestinal epithelial cells and strong colonization in the gastrointestinal tract; (2) the lactobacillus taiwanensis CCFM1318 significantly up-regulates the expression level of tight junction protein related genes in Caco-2 cells after DSS stimulation; (3) the bacterial-free culture medium supernatant of the lactobacillus taiwanensis CCFM1318 can promote the expression and secretion of MUC2 of the LS 174T goblet cell line, and can improve the expression of MUC2 after endoplasmic reticulum stress, thereby enhancing and protecting the intestinal barrier. The lactobacillus taiwanensis CCFM1318 has great application prospect in products (such as food or medicine) for enhancing and protecting the intestinal barrier.

In alternative embodiments, an immunohistochemical (IHC) method is provided for reproducibly determining and scoring the degree of expression of protein sealant protein 18.2 in a tissue sample. In alternative embodiments, methods are provided for diagnosing, treating or ameliorating or assessing the risk of recurrence of cancer or tumors using the IHC methods as provided herein. In alternative embodiments, kits comprising components and instructions for practicing the methods as provided herein are provided. Described herein are methods for scoring sealin 18.2 expression and using the score as a companion or supplemental diagnosis or treatment or amelioration of cancer or tumor.

The application provides a Claudin 6 antibody containing a non-natural amino acid modification and a preparation method and application thereof, the sequence of the antibody is obtained by replacing original amino acids with non-natural amino acids on the basis of SEQ ID NO: 1 and 6; the replacement site of the non-natural amino acid is selected from any one or a combination of at least two of the following: heavy chain: S114, T115, P148, G156, A157, T159, Q191, V149, L158 or G161; or light chain: T109, A112, K169, S202, S203, L154 or S156. The application introduces non-natural amino acids into specific sites of the antibody and expresses the antibody by using a cell expression system, evaluates the influence of non-natural amino acid insertion at different sites on the expression level, structural stability and binding capacity of the antibody, and provides a new idea for rational design and functional optimization of the antibody.

The invention discloses application of electroshock therapy in improvement of depression by regulating blood brain barrier and inflammatory factors, and relates to the technical field of nerve regulation. The invention discloses application of an electroshock treatment device in preparation of a medicine or a medical preparation for improving depression. The medicine or the medical preparation is used for improving depression by adjusting blood-brain barrier permeability of a subject. The regulation of the permeability of the blood-brain barrier comprises a close connection structure for repairing the blood-brain barrier; the repair is realized by up-regulating the expression of a tight junction protein, and the tight junction protein is selected from at least one of ZO-1, occuldin or claudin-5. The invention systematically discloses a brand new mechanism for treating and improving depression by electroshock, namely, a continuous path for reversing peripheral immune activation, repairing blood-brain barrier injury and relieving central nervous inflammation plays a role; the mechanism chain is clear, and innovative explanation is provided for the curative effect of ECT.

The invention discloses a polypeptide targeting CLDN6 protein as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The invention relates to a polypeptide targeting CLDN6 protein. The structural general formula of the amino acid sequence of the polypeptide is X1IX2PYX3, wherein X1-X3 represents a sequence with the length of 1-7 amino acid residues, and the amino acid is any one of 21 natural amino acids and non-natural amino acids; the amino acid sequence of the polypeptide is as shown in SEQ ID NO. 5, SEQ ID NO. 6 or SEQ ID NO. 7. The polypeptide can specifically target CLDN6 positive cells, is high in selectivity, and can be used as a drug delivery carrier or coupled with known components to form a drug combination, so that a better treatment effect is obtained.