38 results about "Transforming growth factor beta" patented technology

The application discloses an electrochemical sensor for detecting IBD protein markers and a preparation method thereof. The electrochemical sensor is composed of a CNT-embedded semi-cured PDMS flexible substrate, deposited gold nanoparticles and a nucleic acid sensing layer. The nucleic acid sensing layer comprises a tumor necrosis factor-alpha sensor, an interleukin 6 sensor, an interleukin 8 sensor, a transforming growth factor beta 1 sensor, a reference electrode and a counter electrode. The tumor necrosis factor-alpha sensor, the interleukin 6 sensor, the interleukin 8 sensor and the transforming growth factor beta 1 sensor all adopt single-stranded aptamers modified by a signal molecule methylene blue, and the nucleotide sequences corresponding to the single-stranded aptamers are SEQ ID NO. 1-4. The application can improve the modulus matching of the sensor and human tissue and excellent biocompatibility, realize accurate detection of low-concentration biomarkers and stable signal output of the sensor under a strain working condition.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and / or or neurodegeneration.

This invention relates to pharmaceutical compositions and methods for treatment of ophthalmic or ocular diseases and conditions. The compositions contain targeting molecules that are made up of a bifunctional hepatoma-derived growth factor-specific antibody covalently attached to a trapper that specifically binds vascular endothelial growth factor and / or transforming growth factor beta. Specific eye conditions that can be beneficially affected by the compositions and methods of the invention include age-related macular degeneration, diabetic retinopathy, peripheral vitreoretinopathy, and retinal vein occlusion.

Certain emboidments provide a method of promoting regeneration of one or more intestinal stem cells in a mammalian organoid culture, the method comprising treating the organoid culture with an effective amount of transforming growth factor beta (TGFB). Certain embodiments also provide a method for preparing an organoid culture comprising intestinal stem cells and a method of treating a subject with damaged or defective intestinal tissue comprising engrafting an organoid into the subject.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. 5 The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and / or or neurodegeneration. 20 26 21 41 00 10 A ug 2 02 6 1 0 A u g 2 0 2 6 2 0 2 6 2 1 4 1 0 0

To provide polypeptides capable of not only neutralizing TGF-β but also specifically triggering T cell activation in the presence of TGF-β when expressed in a cell.SOLUTION: The disclosure provides such a peptide comprising a signal peptide, an antigen binding domain comprising a heavy chain variable (VH) region and a light chain variable (VL) region, a peptide spacer, a transmembrane domain and an endodomain, where the antigen binding domain specifically binds to TGF-β. T-cell activation spurs the immune cell to produce immunostimulatory cytokines and proliferate, thus turning TGF-β from an immunosuppressive signal to an activating stimulus.SELECTED DRAWING: None

To provide Transforming Growth Factor Beta (TGF-β) polypeptide constructs and complexes that find use in therapeutic treatment of diseases including autoimmune diseases, nucleic acids that encode the constructs and the complexes, and methods for preparing the constructs and complexes in cell-based expression systems.SOLUTION: A "masked TGF-β construct" includes: (i) a scaffold polypeptide sequence; (ii) a TGF-β polypeptide sequence; (iii) a masking polypeptide sequence optionally including a TGF-β receptor polypeptide sequence or an anti-TGF-β polypeptide sequence; (iv) optionally, one or more independently selected MOD polypeptide sequences; and (v) optionally, one or more independently selected linker polypeptide sequences, as a first polypeptide, wherein the masking polypeptide sequence and the TGF-β polypeptide sequence bond with each other.SELECTED DRAWING: Figure 1

A method and system are disclosed for differentiating non-human primate induced pluripotent stem cells (NHP iPSCs) into hepatocyte-like cells through a defined, multi-stage protocol. The method includes sequentially exposing NHP iPSCs to six distinct cell differentiation media over an approximate eighteen-day period. Each medium comprises defined combinations of growth factors, small molecules, and inhibitors that direct progressive lineage specification through anterior primitive streak, definitive endoderm, posterior foregut, liver bud progenitors, hepatoblasts, and hepatocyte-like cells. Concentration ranges and exposure durations are provided for each stage, ensuring reproducibility and reducing heterogeneity across cell populations. In some embodiments, treatment with a transforming growth factor beta (TGF-β ) receptor I inhibitor during early hepatoblast specification enhances lineage fidelity. The resulting hepatocyte-like cells are validated by immunostaining and western blotting for hepatic markers. Applications include preclinical drug metabolism, hepatotoxicity assessment, and in vitro disease modeling using non-human primate–derived systems.

The invention discloses an intervertebral disc annulus fibrosus repairing material, a scaffold and application of the intervertebral disc annulus fibrosus repairing material and the scaffold. The intervertebral disc annulus fibrosus repairing material comprises magnesium-silicon nanofibers, tannic acid (TA) and transforming growth factor beta (TGF-beta), and the magnesium-silicon nanofibers comprise self-assembled magnesium-silicon-oxygen nanosheets; the magnesium-silicon-oxygen nanosheet is wrapped by tannic acid; the TGF-beta is connected to the tannic acid through a reversible chemical bond. According to the present invention, the immune microenvironment is adjusted so as to enhance the extracellular matrix (ECM) expression of fibrous ring stem cells (AFSCs);

The invention relates to the technical field of biological pharmacy, and discloses a mesenchymal stem cell exosome enhancer and a preparation method thereof, the enhancer is composed of purified mesenchymal stem cell exosome, a functional lipid complex, cytokine sustained release microspheres, a targeting modifier, a stabilizer and a penetration enhancer according to specific parts by weight. The preparation method comprises the following steps: obtaining a high-activity exosome by combining ultracentrifugation with size exclusion chromatography purification; preparing a functional lipid complex composed of cholesterol, sphingomyelin and phosphatidylserine to promote membrane fusion; preparing a sodium alginate-chitosan sustained release microsphere loaded with a basic fibroblast growth factor and a transforming growth factor-beta1; synthesizing an RGD peptide modified hyaluronic acid targeting modifier; and finally, mixing the components, filtering and sub-packaging. The quality fluctuation risk of subsequent preparation preparation is reduced, and it is guaranteed that the final reinforcing agent product has a highly uniform structure.

Recombinant proteins that specifically bind TGFβ are disclosed. The recombinant proteins include a transforming growth factor beta (TGFβ) binding domain and an antibody Fc fragment. Also disclosed are compositions that include the disclosed recombinant protein, and methods of using such compositions for detecting TGFβ in a subject.

A 5 / 6-5 / 6 diaryl compound that inhibits transforming growth factor beta-activated kinase (TAK1); compositions comprising the same compounds; and their use in the treatment of cancer and inflammatory diseases.

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.

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.

A method for expanding a population of gamma delta T-cells is provided, wherein isolated activated peripheral blood mononuclear cells (PBMCs) are cultured in a medium comprising transforming growth factor beta (TGF-beta) under conditions favoring the production of effector gamma delta T-cells having therapeutic activity against a malignant disease. The use of TGF-beta in the production of effector cells, in particular Vgamma9Vdelta2 T-cells, is also described and claimed.

The invention belongs to the technical field of chemical material engineering, and particularly relates to a hydrogel coating capable of promoting tissue repair and regeneration, which is characterized by being mainly prepared from the following materials: biomolecules mixed in a hydrogel material, and a water-retaining agent, the biomolecules comprise a combination of more than one of the following components: bone morphogenetic protein 7, hepatocyte growth factors, transforming growth factors-beta and retinoic acid. The hydrogel is combined with the carboxylated chitosan hydrogel coating, the bone morphogenetic protein 7 (BMP7), the hepatocyte growth factor (HGF), the transforming growth factor beta (TGF-beta) and the retinoic acid, so that the hydrogel has a synergistic effect of promoting the regeneration and repair of postoperative tissues, and can be applied to the drainage tube to improve the mechanical property and the structural stability and improve the treatment effect.

The invention discloses an electrochemical sensor for IBD protein marker detection as well as a preparation method and application of the electrochemical sensor. The electrochemical sensor is composed of a semi-cured PDMS flexible substrate in which CNT is embedded, deposited gold nanoparticles and a nucleic acid sensing layer, the nucleic acid sensing layer comprises a tumor necrosis factor-alpha sensor, an interleukin 6 sensor, an interleukin 8 sensor, a transforming growth factor beta1 sensor, a reference electrode and a counter electrode; the tumor necrosis factor-alpha sensor, the interleukin 6 sensor, the interleukin 8 sensor and the transforming growth factor beta1 sensor all adopt aptamer single chains modified by signal molecule methylene blue, and correspondingly adopt nucleotide sequences shown in SEQ ID NO.1-4. Matching and excellent biocompatibility of the sensor and human tissue modulus can be improved, and accurate detection of low-concentration biomarkers and stable signal output of the sensor under the strain working condition are achieved.

This invention relates to a fusion protein that specifically binds to the extradomain B of fibronectin (EDB-FN) and transforming growth factor β (TGFβ), and its uses. More specifically, it relates to a fusion protein comprising a polypeptide that specifically binds to EDB-FN and a polypeptide that specifically binds to TGFβ, and its uses. The fusion protein of this invention achieves direct localization of TGFβ inhibition within the tumor microenvironment by immobilizing TGFβ, which is important for anti-tumor immune responses, in the extracellular matrix, ensuring local rather than systemic action. It not only exhibits excellent anti-tumor effects in various cancer types, but also, due to the rigidity of the extracellular matrix, demonstrates excellent anti-tumor effects in pancreatic cancer, where traditional TGFβ inhibitors are ineffective. Therefore, it can be usefully applied to the prevention or treatment of cancer.

The present invention relates to compositions, systems, and methods for treating a subject with an eye condition (e.g., topically) using a composition comprising an ACE-2 receptor antagonist (also known as Angiotensin II Receptor Blocker or “ARB”) (e.g., losartan, telmisartan, valsartan, olmesartan, candesartan, irbesartan, eprosartan, azilsartan, or losartan metabolite EXP3174). In certain embodiments, the eye condition is selected from: i) a corneal scarring fibrosis, ii) a transforming growth factor beta-induced (TGFBI) corneal dystrophy, iii) a conjunctival fibrotic disease, iv) an intraocular fibrotic disease, and v) a conjunctival bleb scarring and / or shunt encapsulation (e.g., following glaucoma surgery).

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.

Aspects of the disclosure relate to polypeptides comprising a signal peptide, an antigen binding domain that specifically binds to a TGF-β, a spacer peptide, a transmembrane domain, and an endodomain. When expressed in a cell, they are capable of not only neutralizing TGF-β but also specifically triggering T-cell activation in the presence of TGF-β. T-cell activation induces the immune cell to produce immunostimulatory cytokines and to proliferate, thereby converting TGF-β from an immunosuppressive signal to an activating stimulus.

Among the strategies allowing cancer cells to escape the immune system, the presence of Transforming growth factor beta (TGF-β) in the tumor micro-environment (TME) is one of the most potent immunosuppressive mechanisms for many types of tumors. Thus, depleting TGF-β is regarded as a promising potent therapeutic approach to fight cancers, regardless of the type of tumor. However, the major impediment for achieving this objective is that TGF-β belongs to the few cytokines that must be activated once secreted. Moreover, a systemic targeting of TGF-β is associated with profound side effects due to TGF-β ability to sustain the homeostasis of numerous tissues. Hence, selectively targeting of TGF-β activation within the TME appears as a rational approach to boost the anti-tumor response and avoid side effects. The integrin αvβ8 expressed on Tregs specifically promotes TGF-β activation and impairs the anti-CD8 T cell response within the TME of different cancers in both mice and humans. The inventors generated anti-β8 chain of αvβ8 integrin (Itgβ8) neutralizing monoclonal antibodies which specifically bind to Tregs and selectively neutralize the ability of Tregs to activate the TGF-β. Thus, the present invention relates to isolated anti-Itgβ8 neutralizing antibodies which specifically binds to β8 chain of αvβ8 integrin (Itgβ8) expressed on Tregs, and their uses for treating cancer.

Provided are novel serum-free culture media which comprise basic fibroblast growth factor (bFGF), transforming growth factor beta-3 and ascorbic acid at a concentration of at least about 50 microgram / ml; ascorbic acid at a concentration range of about 400-600 microgram / ml, bFGF at a concentration range of about 50-200 ng / ml, xeno-free serum replacement and a lipid mixture; the IL6RIL6 chimera at a concentration range of about 50-200 picogram per milliliter (pg / ml); or leukemia inhibitory factor (LIF) at a concentration of at least 2000 units / ml; cell cultures comprising same with pluripotent stem cells such as human embryonic stem cells and induced pluripotent stem (iPS) cells, and methods of using same for expanding pluripotent stem cells in an undifferentiated state using two-dimensional or three-dimensional culture systems; and methods of expanding iPS cells in a suspension culture devoid of substrate adherence and cell encapsulation.

The present invention focuses on an in vitro method of diagnosis or prognosis of neurogenic heterotopic ossification (NHO) comprising assessing the expression level of transforming growth factor beta-inducing protein (TGFBi) in a biological sample obtained from a subject comprising astrocytes and / or neurosecretome. Furthermore, the present invention relates to a therapeutic strategy for the treatment of NHO based on a TGFBi inhibitor.

Tetravalent TGFβ receptor-extracellular domain-based traps with tailored isoform specificity profiles for neutralizing TGFβ ligands and methods for their use in treating diseases and conditions associated with TGFβ, particularly TGFβ1 and TGFβ3, are provided. In particular, TGFβ binding agents designed to tailor TGFβ isoform specificity to maximize therapeutic efficacy in specific disease indications while minimizing adverse effects are provided. The TGFβ binding agents comprise two polypeptides assembled via a multimerization domain, each polypeptide having two TGFβ II receptor (TGFβR) ligand-binding domains linked as a doublet, where a linker is selected to tailor isoform specificity.

The invention belongs to the field of biomedicine, and particularly belongs to the crossing field of biomedical engineering and regenerative medicine. The technical problem to be solved by the invention is to provide an effective means for functional repair of premature ovarian failure or premature ovarian insufficiency. The technical means for solving the technical problem is to provide a method for preparing ovarian granular cell precursor cells and extracellular vesicles. The method comprises the following steps: culturing mesenchymal stem cells in the presence of estradiol, follicle stimulating hormone and transforming growth factor beta so as to differentiate the mesenchymal stem cells into ovarian granular cell precursor cells; wherein the precursor cells of the ovarian granulosa cells express granulosa cell markers FOXL2 and AMHR2. The extracellular vesicles obtained by culturing and collecting the precursor cells of the ovarian granular cells obtained by the method can achieve a better ovarian function repairing effect, so that a new means is provided for treating ovarian insufficiency diseases such as premature ovarian failure and the like.

The application discloses a nasal secretion biomarker composition for diagnosing type 2 chronic rhinosinusitis with nasal polyps and application thereof, relates to the technical field of biological medicine, and the nasal secretion biomarker composition comprises glial cell-derived neurotrophic factor, cystatin 5, transforming growth factor beta 1 and monocyte chemoattractant protein 4. When the nasal secretion biomarker composition is used for diagnosing CRSwNP intrinsic type, nasal secretion is used as a detection sample, polyp biopsy is not needed, the nasal secretion biomarker composition is non-invasive, simple, convenient, has high sensitivity and specificity, can classify CRSwNP patients before operation without damaging mucosa, can predict the disease intrinsic type of the CRSwNP patient in advance and accurately, and is an ideal non-invasive method.

Provided herein are self-assembling peptide amphiphiles (PAs) comprising a bioactive Transforming growth factor beta 1 (TGF-β1) mimetic epitope, high-aspect-ratio nanostructures of PAs displaying a TGF-β1 mimetic epitope, and methods of enhancing cartilage regeneration / repair and / or treatment of osteoarthritis and other musculoskeletal injuries and diseases.

The present invention relates to a method for treating metabolic dysfunction-associated steatohepatitis through co-administration of a CCR2 inhibitor and a TGF-beta receptor inhibitor. Specifically, when administering a C-C chemokine receptor 2 (CCR2) inhibitor and a transforming growth factor beta (TGF-beta) receptor inhibitor alone or in combination to an animal model in which steatohepatitis was induced by diet, it has been identified that the TGF-beta receptor inhibitor alone significantly alleviated liver fibrosis but increased fat accumulation in liver tissue, and the CCR2 inhibitor alone inhibited inflammatory cell accumulation and fat synthesis in liver tissue but did not completely alleviate fibrosis, whereas, in the group to which these two substances were co-administered, liver fibrosis was significantly alleviated and, at the same time, inflammatory cells accumulated in liver tissue and fat accumulation were also inhibited, and ER stress and mitochondrial dysfunction were alleviated. Therefore, a combination formulation of the CCR2 inhibitor and the TGF-beta receptor inhibitor can be effectively used for the purpose of preventing, alleviating or treating metabolic liver diseases including metabolic dysfunction-associated steatohepatitis.

Provided herein are compositions, systems, kits, and methods for generating dorsal foregut endoderm (DFE) cells by contacting pluripotent stem cells with a retinoic acid signaling pathway agonist and a bone morphogenetic (BMP) pathway inhibitor without exposing the stem cells to a transforming growth factor beta (TGFβ) pathway agonist. In certain embodiments, the DFE cells are contacted with a retinoic acid signaling pathway agonist and a FGFR pathway inhibitor to generate pancreatic endoderm (PE) cells (e.g., with dorsal identity). In other embodiments, the PE cells are contacted with an ALK5 inhibitor and a Notch inhibitor to generate endocrine cells (e.g., insulin expressing endocrine cells). In certain embodiments, compositions, systems, kits, and methods are provided for generating anterior domain endoderm (ADE) cells.