34 results about "CTGF" patented technology

Disclosed in the present disclosure are an inhibitor against CTGF RNA, MITF RNA and SRD5A2 RNA and the use of the inhibitor. The inhibitor is a gene editing system. The gene editing system of the present disclosure is capable of knocking down CTGF RNA, MITF RNA and SRD5A2 RNA, and can be used for repairing scars, whitening skin, reducing or eliminating chloasma, preventing or treating melanoma, and / or preventing or treating androgenetic alopecia.

The invention discloses a preparation method of a growth factor gradient bionic scaffold for tendon-bone interface regeneration and repair, and belongs to the technical field of biomedical materials. The composite scaffold is constructed by adopting a coaxial electrospinning and self-assembly technology, and is compounded by a core-shell oriented nanofiber layer and a non-oriented nanofiber layer through a gelatin adhesive to respectively simulate tendon phase and bone phase structures of a tendon-bone interface; a shell layer of the tendon-phase-simulated core-shell oriented nanofiber is a PCL layer containing CTGF, a core layer of the tendon-phase-simulated core-shell oriented nanofiber is a PVA layer containing TGF-beta1, and a bone-phase-simulated non-oriented nanofiber layer is a PCL / Gel co-spun layer containing BMP-2 polylactic acid microspheres and nano-hydroxyapatite. The scaffold can realize secondary controlled release of early-stage release of CTGF, slow release of TGF-beta1 in the middle and later periods and continuous release of BMP-2, and cooperates with a fiber orientation structure to induce graded differentiation of mesenchymal stem cells and promote integrated repair of a tendon-bone interface gradient structure, so that the problems of poor healing of a tendon-bone interface and high repeated fracture rate in a traditional repair method are solved, and the scaffold has good application prospects. The important application value is realized in the field of tendon-bone injury treatment in sports medicine.

The invention discloses a three-dimensional biological printing meniscus model for simulating the mechanical heterogeneity of a natural meniscus and a preparation method of the three-dimensional biological printing meniscus model. The model comprises a structural PCL fiber frame (red region fiber circumferential arrangement and white region radial arrangement, and simulates the trend of natural collagen fiber), regional specific hydrogel (the red region contains GelMA, HAMA and SilMA, and the white region contains GelMA and HAMA), and partitioned cell components (the red region contains BMSC, HUVEC and CTGF, and the white region contains BMSC and TGF-beta3), the PCL frame and the hydrogel cooperate to form a mechanical gradient, and the compression modulus from the red region to the white region is simulated to continuously change. The preparation method comprises the following steps: designing a three-dimensional model, printing a PCL framework, preparing hydrogel and a cell suspension, preparing bio-ink, filling and printing by multiple nozzles, curing and culturing in vitro to obtain a target model. Compared with the prior art, the method has the advantages that the key problem of mechanical mismatch of an existing support is effectively solved, the model better fits a natural meniscus in mechanical property and biological function, and a more adaptive in-vitro model support is provided for individualized meniscus repair and transplantation substitution research.

The present invention provides a fusion protein composed of an anti-human CTGF antibody and the extracellular domain of the human type II TGF-β receptor, linked via a linker. This fusion protein can bind both CTGF and TGF-β. This fusion protein can be purified in a single step to obtain a 100% pure target protein. Experiments have shown that even a low dose of 1 mg / kg can significantly reduce the degree of pulmonary fibrosis in experimental animals.

The present invention belongs to the field of pulmonary vascular disease treatment, and specifically discloses a TGF-β receptor inhibitor for the treatment of pulmonary hypertension. In the rat pulmonary hypertension model induced by monocrotaline (MCT), after using the preparation, the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (Fulton index), pulmonary vascular resistance and vascular wall thickness of the rat can be reversed and reduced, and the survival rate of monocrotaline (MCT)-induced pulmonary hypertension rats can be prolonged. Compared with the modeling group, the expression of IL-17, IL-6 and GM-CSF inflammatory factors in the lung tissue of the preparation-treated group was significantly reduced, and the expression of extracellular matrix-related genes CTGF, Fn1 and Col1α1 also decreased. The preparation can significantly alleviate the pulmonary hypertension in rats induced by monocrotaline (MCT), showing good therapeutic effect and application prospects.

The preparation method of the HLC-CTGF fusion protein disclosed by the invention comprises the following steps: designing a target gene synthesis and enzyme cutting site, reactivating a strain, and then sequentially carrying out expression vector construction of the fusion protein HLC-CTGF, expression of the fusion protein HLC-CTGF, purification of the fusion protein HLC-CTGF and immunoblotting of the fusion protein HLC-CTGF. The rhCol-CTGF fusion protein prepared by the preparation method disclosed by the invention is non-toxic and has good cell compatibility. The collagen can be cross-linked to prepare a hydrogel scaffold, and the collagen creates a good environment for the growth of osteoblasts by providing necessary nutrition and structural support; the CTGF is slowly released by controlling the degradation of the hydrogel, so that the defect that the expression of the CTGF in vivo has time dependence is overcome, and bone tissue repair is accelerated.

The present invention relates to the field of biomedicine. Specifically, the present invention relates to an aptamer targeting a connective tissue growth factor (CTGF) protein, an aptamer conjugate targeting the CTGF protein, and a use thereof in inhibiting the activity of the CTGF protein.

The invention discloses a preparation method and application of exosome-loaded Cas13d-RNP, and belongs to the technical field of biliary atresia research. The method comprises the following steps: extracting exosomes: culturing human bile duct cells H69 in a DMEM / F12 culture medium until the cell density reaches 90%, collecting supernatant of the culture medium, and extracting the exosomes by an ultracentrifugation method; cas13d-RNP loading: the Cas13d protein and crRNA are mixed for 15 minutes at the room temperature, Cas13d-RNP is obtained, the exosome and the Cas13d-RNP are mixed, and the Cas13d-RNP is loaded into the exosome in a circulating freezing and thawing mode. According to the invention, Cas13d-RNP is accurately delivered through the exosome vector, specific targeting is carried out on bile duct cell CTGF mRNA, and expression of fibrosis-related factors in bile duct cells is significantly reduced. Compared with traditional medicine treatment, bile duct reaction and fibrosis processes can be more effectively inhibited. As a natural vector, the exosome has the advantages of low immunogenicity and high delivery efficiency, and immunoreactions possibly caused by a traditional virus vector are reduced.

The invention features compositions featuring (a) one or more of connective tissue growth factor (CTGF) and human C-terminal CTGF peptide; and (b) one or more of insulin and IGF-1; and methods of using such compositions to reduce cardiac tissue damage associated with an ischemic event or to enhance engraftment of a cell in a cardiac tissue.

The invention discloses application of neensinine in prevention and treatment of endometriosis, the neensinine is used as a traditional Chinese medicine monomer, the neensinine is used for preventing and treating the endometriosis, and the neensinine can resist fibrosis of the endometriosis so as to play a role in prevention and treatment. A mouse endometriosis model is constructed through an allotransplantation method, after four weeks of successful modeling, a modeling mouse model group, a dienogest control group and a neferine group are respectively taken for four weeks, and then laparotomy is performed to take out ectopic lesions. HE staining and masson staining methods are used for mutual evidence of fibrosis degree, immunohistochemical detection of fibrosis index a-SMA expression conditions is carried out, and Western-blot detection of fibrosis-related protein expression levels: FN, CTGF, alpha-SMA and COL-I. Therefore, the neferine can be potentially developed into drugs for treating or preventing fibrosis of endometriosis in the future.

The invention discloses an SS / CTGF composite biological material based on carboxyl chitosan as well as a preparation method and application of the SS / CTGF composite biological material. A substance containing active sericin (SS) and CTGF at the same time is extracted from genetic engineering silkworm cocoons over-expressing human connective tissue growth factors (CTGF) by utilizing an alkali extraction-acid protection method. Furthermore, the active substance, carboxyl chitosan and beta-glycerophosphate are used as raw materials, and the CH-SS / CTGF composite hydrogel biological material with the core-shell structure is prepared through thermal induction gelation. The material has the characteristics that the water content is adjustable, the mechanical property is controllable, and active protein can be quickly released. Compared with pure sericin, the active SS / CTGF substance and the composite hydrogel thereof can more remarkably promote cell proliferation and migration, and show good biocompatibility. The biological material prepared by the invention has wide application prospects in the fields of wound healing, drug delivery and regenerative medicine.

This disclosure relates to treating a connective tissue injury. The treatment involves injecting, or otherwise administering, a therapeutic composition into an animal, such as a human being, in need thereof. The therapeutic composition may contain transforming growth factor beta 1 (TGF-β1) and / or transforming growth factor β2 (TGF-β2), connective tissue growth factor (CTGF), and a pharmaceutically acceptable excipient or a secondary agent.

The invention discloses application of hyperoside to treatment of endometriosis, and aims to evaluate whether hyperoside has an anti-fibrosis effect when applied to a rat endometriosis model by taking fibrosis as a treatment target. The method comprises the following steps: constructing a rat endometriosis model through an autotransplantation method, dividing molded rats into a low-dose group, a medium-dose group, a high-dose group, a model group and a western medicine control group 4 weeks after successful modeling, and laparotomizing and taking out ectopic lesions after respectively taking medicines for 4 weeks. HE staining and masson staining methods are used for mutually proving the fibrosis degree, the expression conditions of fibrosis indexes a-SMA, Co-1, CTGF and Fn are detected in an immunohistochemical mode, and the anti-fibrosis effect of hyperoside is evaluated. As a result, hyperoside can prevent the development of fibrosis in endometriosis, and thus hyperoside can be used as a drug for treating or preventing fibrosis in endometriosis.

The application discloses application of an E3 ubiquitin ligase SIAH2 inhibitor in preparation of a lupus nephritis kidney protection drug. Researches of the application show that the SIAH2-LATS2 axis participates in the pathogenic process of kidney fibrosis of lupus nephritis, and it is confirmed that LATS2 can be used as a target point for preventing fibrosis progression in lupus nephritis. It is shown that LATS2 is abnormally down-regulated in lupus nephritis, and the use of an E3 ubiquitin ligase SIAH2 inhibitor can restore the LATS2 level, reduce the production of a LATS2 downstream gene CTGF, reduce the occurrence of interstitial fibrosis, reduce the proteinuria effect of lupus nephritis, thereby protecting the kidney function and delaying the progression of lupus nephritis. The application uses the SIAH2 inhibitor vitamin K3, which can prevent the conversion of lupus nephritis to ESRD, and can be used as an effective drug for treating and preventing kidney fibrosis, and provides a new selection for lupus nephritis treatment drugs and fibrosis prevention and treatment drugs.

The present invention addresses the problem of providing technology that is for preventing or treating the progression of liver conditions leading to liver cancer and targets a phenomenon other than hepatocyte death. This problem is solved by a prophylactic or therapeutic agent that is for at least one disease selected from the group consisting of liver fibrosis, cirrhosis, and liver cancer, contains at least one substance selected from the group consisting of CTGF inhibitors and integrin αV inhibitors, and is for patients suspected of having increased intrasinusoidal pressure.

The invention belongs to the technical field of organoid culture, and particularly relates to a culture medium for gastrointestinal stromal tumor organoids and a culture method of the culture medium. The invention focuses on the tumor microenvironment, and systematically screens the growth factor and the corresponding receptor which are highly expressed in the tumor cells and the microenvironment thereof through deep analysis of GIST single cell sequencing data. Through rigorous screening and identification processes, it is finally determined that four growth factors of CTGF, IGF2, PDGF-BB and SCF and corresponding receptors of the four growth factors show significant high expression in GIST tumors. Experiments prove that when four key growth factors, namely CTGF, IGF2, PDGF-BB and SCF, are simultaneously added into a GIST organoid culture system, a remarkable synergistic effect exists among the growth factors, and the growth activity of GIST tumor cells is remarkably improved, so that in-vitro continuous proliferation of the GIST tumor cells is promoted, and the culture success rate of the GIST organoid is remarkably improved.

The present disclosure generally relates to anti-CTGF (connective tissue growth factor) antibodies or antigen-binding fragments thereof. Exemplary anti-CTGF antibodies disclosed herein address the need for treatments of conditions modulated by CTGF signaling. In some aspects, the anti-CTGF antibodies or antigen-binding fragments thereof are for diagnostic and / or therapeutic use, for example in a subject in need thereof, such as a human.

The application of CTGF monoclonal antibody combined with CSF1R inhibitor and PD-1 monoclonal antibody in the preparation of a drug for treating colorectal cancer and a pharmaceutical composition, relates to the technical field of tumor treatment, and aims to solve the problem that the effect of the existing CSF1R inhibitor combined with immunotherapy is poor.The application provides the application of CTGF monoclonal antibody combined with CSF1R inhibitor and PD-1 monoclonal antibody in the preparation of a drug for treating colorectal cancer.The application also provides an anti-colorectal cancer pharmaceutical composition, which comprises CTGF monoclonal antibody, CSF1R inhibitor and PD-1 monoclonal antibody.The combination of CTGF monoclonal antibody and CSF1R inhibitor significantly improves the effect of PD-1 monoclonal antibody immunotherapy, and the combination of the three drugs significantly promotes the infiltration of CD8+ T cells and CTL in tumor tissues and enhances the anti-tumor activity.The application is used for treating MSS type colorectal cancer.

This disclosure relates to treating a connective tissue injury. The treatment involves injecting, or otherwise administering, a therapeutic composition into an animal, such as a human being, in need thereof. The therapeutic composition may contain transforming growth factor beta 1 (TGF-β1) and / or transforming growth factor β 2 (TGF-β2), connective tissue growth factor (CTGF), and a pharmaceutically acceptable excipient or a secondary agent.

The invention provides an inhibitor of CTGF RNA, MITF RNA and SRD5A2RNA and application of the inhibitor. The inhibitor is a gene editing system. The gene editing system can knock down CTGF RNA, MITF RNA or SRD5A2RNA, and can be used for repairing scars, whitening skin, reducing or eliminating chloasma, preventing or treating melanoma, and / or preventing or treating androgenetic alopecia. The invention further provides a gene editing system, the gene editing system targets the AR RNA coded by the androgen receptor gene, and the gene editing system can be used for treating androgenetic alopecia and other diseases.

An siRNA for inhibiting CTGF gene expression, which consists of a sense strand and an antisense strand thereof, wherein the sense strand is a 5'-3' nucleotide sequence, the antisense strand is a 5'-3' nucleotide sequence, and each nucleotide in the siRNA is an independently modified or unmodified nucleotide; the nucleotide sequence contained in the sense strand is selected from SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39; the nucleotide sequence contained in the antisense strand is selected from SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40; and the sense strand nucleotide sequence and the antisense strand nucleotide sequence are at least partially reverse complementary to form a double-stranded region.

The present invention relates to a double-stranded oligonucleotide capable of inhibiting CTGF expression with extremely high specificity and high efficiency, a double-stranded oligonucleotide structure and a nanoparticle comprising the same, and use thereof in preventing or treating fibrosis or respiratory diseases.

This disclosure relates to treating a connective tissue injury. The treatment involves injecting, or otherwise administering, a therapeutic composition into an animal, such as a human being, in need thereof. The therapeutic composition may contain transforming growth factor beta 1 (TGF-β1) and / or transforming growth factor β 2 (TGF-β2), connective tissue growth factor (CTGF), and a pharmaceutically acceptable excipient or a secondary agent.

Provided herein are soluble interleukin-6 receptor (sIL-6R) and CTGF binding proteins, multispecific binding proteins thereof, conjugates thereof, pharmaceutical compositions thereof, and methods of use thereof. The specific binding proteins can be single heavy chain antibodies (VHH), and the multispecific binding protein can include two variable heavy chain (VHH) immunoglobulin domains targeting sIL-6R and CTGF. The conjugates can include a binding protein or multispecific binding protein, conjugated with an anti-transferrin receptor antibody. The pharmaceutical compositions can include one or more binding proteins and / or multispecific binding proteins. The methods of use include the administration of binding proteins and / or multispecific binding protein for the treatment of neurological diseases.

The invention discloses a bispecific antibody targeting CTGF (cytotoxic T growth factor) and PD-1 (programmed death-1) and application of the bispecific antibody. The bispecific antibody comprises two identical fusion light chains and two identical fusion heavy chains, cTGF molecules of CAFs and PD-1 molecules on the surfaces of T cells can be simultaneously and specifically combined. The bispecific antibody has a good pancreatic tumor resisting effect and can be used for preparing drugs for preventing or treating pancreatic cancer.

The preparation method of the HLC-CTGF fusion protein disclosed in the application comprises the following steps: designing a target gene and synthesizing and enzyme cutting sites, then reactivating a bacterial strain, and then sequentially performing expression vector construction of the fusion protein HLC-CTGF, expression of the fusion protein HLC-CTGF, purification of the fusion protein HLC-CTGF, and Western blotting of the fusion protein HLC-CTGF. The rhCol-CTGF fusion protein prepared in the application is non-toxic and has good cell compatibility. The fusion protein can be cross-linked to prepare a hydrogel scaffold, collagen provides necessary nutrition and structural support, and creates a good environment for the growth of osteoblasts; the degradation of the hydrogel is controlled to release CTGF, the time-dependent disadvantage of the expression of CTGF in the body is overcome, and the bone tissue repair is accelerated.

The present invention provides an siRNA for inhibiting the expression of the CTGF gene, and the siRNA comprises a sense strand and an antisense strand. The siRNA provided by the present invention has good stability, excellent inhibitory activity against the CTGF gene, and negligible cytotoxicity and immunostimulatory capacity, and can significantly reduce the CTGF protein level at the animal level. The present invention has important clinical value for the treatment of diseases or conditions benefiting from CTGF level reduction or expression inhibition.

The invention discloses a meniscus organ construction method based on voxelization variable wire diameter printing and an obtained product. The method comprises the following steps: acquiring target meniscus medical image data and establishing a voxelization model; printing parameters are mapped according to mechanical distribution; the PCL stent is constructed by adopting a variable-wire-diameter melt extrusion technology, fibers are laid in a 0-degree / 60-degree / 120-degree three-axis staggered manner, the wire diameter is continuously adjustable in a range of 150-350 microns, and the porosity is from 80% to 10% in an inner region to 10% in an outer region; tGF-beta functional NorCol ink is injected into the inner area through a multi-nozzle system, and CTGF functional NorCol ink is injected into the outer area; packaging the hUC-MSCs at the density of 2 * 10 < 6 > cells / mL, performing cartilage differentiation culture for 28 days after 405nm light in-situ crosslinking, and applying periodic mechanical loading during the period. The invention also relates to the prepared meniscus organ and application of the meniscus organ in preparation of a graft. According to the scheme, continuous mechanical gradient reconstruction and regional biochemical microenvironment construction are realized, and the problems of insufficient mechanical bionics and limited regional induction in the prior art are solved.

This disclosure discloses inhibitors of CTGF RNA, MITF RNA, and SRD5A2 RNA and their applications, wherein the inhibitors are gene editing systems. The gene editing systems disclosed herein can knock down CTGF RNA, MITF RNA, or SRD5A2 RNA, and can be used to repair scars, whiten skin, reduce or eliminate melasma, prevent or treat melanoma, and / or prevent or treat androgenetic alopecia. This disclosure also discloses a gene editing system that targets AR RNA encoded by the androgen receptor gene, which can be used to treat androgenetic alopecia and other diseases.

The invention provides an anti-CTGF antibody containing a light chain variable region and a heavy chain variable region and application of the anti-CTGF antibody as a medicine, the antibody can be used for preparing a medicine antibody for treating CTGF related diseases or symptoms, and the antibody is obtained by screening through the following method: immunogen preparation, animal immunization, positive hybridoma cell screening and strain establishment, ascites preparation and antibody purification. Carrying out specificity and affinity screening on 39 antibodies obtained by purification to obtain 3 antibodies with strong specificity and high affinity; and the neutralizing activity of the three antibodies is detected to finally obtain the antibody capable of inhibiting cancer cell migration in vitro.