15 results about "Zymogen" patented technology

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

Disclosed herein, are peptides that bind urokinase-type plasminogen activator receptors. The peptides may comprise amino acid sequences of IPPWEAPK (SEQ ID NO: 1), DLAQCQTPTQAAPPTPVSPR (SEQ ID NO: 2), or LHVPLMPAQPAPPK (SEQ ID NO: 3), or retro-inverso amino acid sequences of the above enumerated sequences. Also described herein, are methods of administering compounds comprising peptides that bind urokinase-type plasminogen activator receptors to subjects for the treatment of ovarian cancer and improving wound closure.

A method comprising the steps of: (a) assessing an expression level of at least one protein, selected from Table 1, 2 or 3 in a sample from a subject, where in the at least one protein may be selected from the list comprising: Beta-Ala-His dipeptidase, Apolipoprotein L1, Methanethiol oxidase, Vitamin K-dependent protein S, von Willebrand factor, Plasminogen, Selenoprotein P, Protein disulfide-isomerase A6 and Inter-alpha-trypsin inhibitor heavy chain H3, and (b) using the expression level to determine whether the subject has endometriosis.

The application discloses an engineered exosome targeting human urokinase-type plasminogen activator receptor uPAR and a preparation method and application thereof. Firstly, a high-affinity anti-human uPAR single-domain antibody VHH is prepared; then, a human umbilical cord mesenchymal stem cell engineering cell line expressing a VHH-PTGFRN fusion protein is constructed, and the engineered exosome is prepared and purified by combining three-dimensional hypoxic culture, chemical induction and size-exclusion chromatography technology. The engineered exosome comprises four comparative samples, wherein the core sample Exo^(VHH / miR) can simultaneously display the anti-uPAR VHH on the membrane surface to realize targeted delivery and enrich miR-193b-3p in the chamber to realize gene silencing, and the synergistic effect of the two can efficiently remove the uPAR high-expression senescent cells and inhibit the senescence-associated secretory phenotype SASP. The engineered exosome has the advantages of standardized preparation process, high yield and high purity, strong targeting, excellent curative effect and good safety, and can be used for preparing a treatment preparation for anti-aging and aging-related diseases, and has important clinical application value.

Provided is a pharmaceutical composition with which it is possible to prevent the development of late-onset cerebral ischemia and obtain a prognosis-improving effect by performing active hematoma removal using a tissue plasminogen activator. This pharmaceutical composition contains a tissue plasminogen activator as an active ingredient and is for use in hematoma removal therapy in the cerebral cistern to remove a dislodged hematoma by suction by using the tissue plasminogen activator in an aqueous solution state as a cleansing agent, said therapy being performed at the same time as treatment of a cerebral aneurysm by means of craniotomy with clipping during the acute phase of a subarachnoid hemorrhage associated with a ruptured cerebral aneurysm.

This invention discloses a sonodynamic synergistic thrombolysis system and its application. The system includes a tissue plasminogen activator variant, a sonosensitive agent, and an ultrasound source. The tissue plasminogen activator variant is an intravenously administered formulation, the sonosensitive agent is an intravenously infused formulation, and the ultrasound source is used to emit ultrasound during sonosensitive agent administration to activate the agent. This invention significantly improves thrombolysis efficiency and reduces thrombolytic agent dosage and bleeding risk through the dual synergistic effect of TNK-tPA enzymatic hydrolysis and sonodynamic chemical oxidation. The system can significantly improve vascular recanalization rate and blood flow velocity recovery rate, and has high biocompatibility. This invention is applicable to thrombolytic treatment of various thrombotic diseases and has the advantages of simple operation, strong targeting, and wide application range.

This invention belongs to the field of biotechnology and provides an antibody or its antigen-binding fragment against the urokinase plasminogen activator receptor and its applications. The antibody or its antigen-binding fragment of this invention comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region includes heavy chain complementarity-determining regions HCDR1, HCDR2, and HCDR3, and the light chain variable region includes light chain complementarity-determining regions LCDR1, LCDR2, and LCDR3. The antibody or its antigen-binding fragment of this invention can bind with high affinity to human uPAR protein and can induce an anti-tumor specific immune response.

The application discloses a Mycoplasma bovum LP586 protein, a polyclonal antibody thereof and application. The amino acid sequence of the LP586 protein is shown as SEQ ID NO. 1, the LP586 protein has high conservation, is positioned on the cell membrane surface of the Mycoplasma bovum, and has multiple biological functions such as specific adhesion to EBL cells, combination with extracellular matrix molecules and activation of plasminogen in the presence of tPA. The application further provides a high-titer specific polyclonal antibody prepared by immunization. The LP586 protein can be used as a key antigen for preparing a Mycoplasma bovum subunit vaccine, a diagnostic reagent or a therapeutic drug; and the polyclonal antibody thereof can be used for preparing a diagnostic reagent or a passive immunotherapy preparation. The application provides a brand-new high-efficiency target and product development basis for prevention and control of the Mycoplasma bovum disease.

A fusion protein is provided. [Solution] The fusion protein of the present invention comprises a tissue plasminogen activator or a variant thereof, a disintegrin or a variant thereof, and a connector that binds the tissue plasminogen activator or a variant thereof and the disintegrin or variant thereof and comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 7. The present invention further provides a method for using the fusion protein in the treatment or prevention of a disease associated with thrombus formation.

The present invention provides fusion proteins for targeted delivery of plasminogen activators to platelet-VWF complexes, or alternatively to the site where these are located, in a fibrin-independent manner. The fusion protein of the invention are for use in methods for the prevention or treatment of diseases or conditions associated with such platelet-VWF complexes, which may cause microvascular thrombosis in diseases such as e.g. thrombotic thrombocytopenic purpura. Preferred targeting agents for incorporation into the fusion proteins are e.g. nanobodies against VWF or platelets. Preferred plasminogen activators for use in the fusion proteins comprise the protease domains of uPA or tPA. The invention further pertains to nucleic acid molecule encoding the fusion proteins of the invention, e.g. a gene therapy vector, and to pharmaceutical compositions comprising the fusion proteins of the invention or such gene therapy vectors.

The present disclosures provides new technologies for treatment and / or prevention of certain dermatological conditions, specifically including graying hair. Among other things, the present disclosure provides an insight that plasminogen activator inhibitor -1 (PAI-1) inhibitors may be useful in the treatment and / or prevention of certain dermatological conditions, and in particular in treatment and / or prevention of graying hair.

The application provides a milk protein source urokinase-type plasminogen activator inhibitory peptide and application thereof. Through a combination of virtual screening by molecular docking and in-vitro experiment verification, two u-PA inhibitory activity polypeptides PEVMGVSK and HIQKEDVPSE derived from bovine milk casein are obtained. The two polypeptides can be stably combined with the u-PA active site through multiple intermolecular forces, have a significant inhibitory effect on u-PA-mediated plasminogen activation, can effectively improve the storage period stability of ultra-high temperature instant sterilized milk, delay protein hydrolysis and aging gel formation, and can inhibit the plasmin clot lysis and MDA-MB-231 human breast cancer cell migration in a concentration-dependent manner. The polypeptides obtained by the application have application potential and practical value in the fields of dairy product quality improvement, hemostatic drugs and anti-cancer drug research, etc. as natural source active ingredients.

This invention discloses an engineered Trichoderma reesei strain that secretes and expresses lysostaphin, its construction method, and its applications, belonging to the field of genetic engineering technology. This invention obtains the lysostaphin proenzyme and its encoding gene by modifying lysostaphin with a secretory peptide. The encoding gene, promoter, and terminator are then ligated into a shuttle plasmid to obtain a lysostaphin expression plasmid. This plasmid is transformed into Trichoderma reesei, and the endogenous protein encoding gene cbh1, which has the highest secretion expression level in Trichoderma reesei, is replaced with the aforementioned encoding gene, thus constructing an engineered Trichoderma reesei strain that secretes and expresses lysostaphin. This invention is the first successful construction of an engineered Trichoderma reesei strain capable of secreting and expressing lysostaphin, which simplifies the production process of lysostaphin, significantly reduces its production cost, and lays the foundation for large-scale industrial production of lysostaphin.