65 results about "Globin" patented technology

A milking arrangement comprising a milking machine for milking an animal, wherein the milking arrangement comprises a control unit that is configured to obtain identity of the animal in connection with milking of the animal, obtain a reference point in time of a lactation cycle of the identified animal, determine to take at least one milk sample of the animal, when a predetermined time period has passed from the reference point in time; obtain a Haptoglobin level from the milk sample, compare the obtained Haptoglobin level with a Haptoglobin reference limit, and indicate health condition of the animal, based on the made comparison.

The invention discloses a blood protein precise active peptide capable of tonifying qi and blood, improving microcirculation and promoting vasodilation and a preparation method and application thereof, and belongs to the technical field of blood protein peptide. The blood protein precision active peptide comprises at least one of LGFP, IGFP, FPHFN, LFL, LFI, FESF, ILF, LIF, FLL, FIL, FII or FPHFD. The prepared blood protein precision active peptide has multiple biological activities: an antihypertensive effect is achieved by inhibiting ACE and vasoconstriction substances; vasodilation is promoted by activating a PI3K / AKT / eNOS signal channel; a zebra fish model proves that the traditional Chinese medicine composition has the effects of remarkably improving microcirculation and tonifying qi and blood. The preparation method is low in equipment requirement, simple in process, easy to operate and convenient for industrial large-scale production. The method enriches a bioactive peptide library, and is of great significance in promoting technical progress and industrial upgrading in the field of hemoglobulin peptides.

The present subject matter relates to recombinant lentiviral transfer plasmids for producing lentiviral vectors with increased vector titer and performance. These transfer plasmids are constructed so that a central polypurine tract (cPPT) is centered between the lentiviral LTRs and include a 6x stop codon sequence block downstream of the 3' LTR. When the transfer plasmids comprise a globin expression cassette, the lentiviral vectors produced therefrom are useful for treating hemoglobinopathies by gene therapy. Transduced cells, pharmaceutical compositions and methods of treating or ameliorating hemoglobinopathies with these lentiviral vectors are also provided. Additional transfer plasmids, cells, and compositions are provided that are useful for delivering any gene of interest to a cell, as well as plasmids for production of lentiviral vectors for treating other erythroid-specific diseases or disorders such as anemia and cancer.

The invention relates to the technical field of gene editing, in particular to a composition for treating alpha-thalassemia and application thereof. The composition is used for treating alpha-thalassemia and comprises a gene editing system. By adopting the composition disclosed by the invention, the repair editing of Hb-CS mutation can be realized, the expression of alpha / beta globin can be balanced, and the safety can be ensured.

The invention provides a recombinant exosome as well as a preparation method and application thereof. The preparation method of the recombinant exosome comprises the following steps: transfecting a target cell with an exosome loaded with nucleic acid molecules, and culturing to prepare the recombinant exosome; the nucleic acid molecule sequentially comprises a promoter sequence, a sequence for coding beta-globin, a 5 '-UTR, a target gene sequence, a sequence for coding alpha-globin, a 3'-UTR and a terminator sequence from the 5'end to the 3 'end. The method not only can be used for producing the recombinant exosome of the specific protein, but also has high flexibility and controllability. The recombinant exosome produced by the preparation method disclosed by the invention shows good stability and biological activity in cell culture and in-vivo experiments, and therapeutic protein can be effectively delivered to target cells. According to the technology, a virus-free and non-integrated treatment method is provided, and common risks in traditional gene therapy are reduced.

The invention provides application of pinostrobin in preparation of a medicine for treating gastric ulcer, and belongs to the technical field of biological medicine. The pinostrobin provided by the invention realizes the anti-gastric ulcer effect by improving the gastric mucosa blood flow volume, inhibiting inflammatory reaction, inhibiting oxidation reaction and maintaining the integrity of the gastric mucus barrier. Pinostrobin can reduce the gastric ulcer area of rats and increase the pain threshold value; the content of ET-1 in plasma is reduced, and the repairing effect of gastric mucosa is enhanced; the contents of TNF-alpha and IL-6 are reduced, the content of IL-10 is increased, and the anti-inflammatory effect is enhanced; the content of T-SOD in plasma is increased, the content of MPO is reduced, and the antioxidant effect is enhanced. The pinostrobin is expected to be used as a new medicine for treating gastric ulcer.

The present invention concerns the use of a molecule chosen from a globin, a globin protomer or an extracellular hemoglobin of Annelids, for treating and / or preventing at least one complement-activation associated disease, preferably ischemia / reperfusion injury and / or transplant rejection.

This invention provides compounds for the treatment, prevention, or suppression of various pathological conditions (such as proliferative disorders like cancer, β-globin disorders, fibrosis, pain, neurodegenerative diseases, Prader-Willi syndrome, malaria, viral infections, myopathy, and autism) by inhibiting G9a. [Solution] The following general formula (I) TIFF2026062914000401.tif2449 A compound represented by or a pharmacoposly acceptable salt thereof is provided.

The invention relates to the technical field of animal breeding, in particular to a method for breeding black sheep. The method comprises the following steps: introducing an expression cassette into a cell to obtain a transgenic cell; and carrying out somatic cell nuclear transplantation cloning by adopting the transgenic cells to obtain the black sheep. The expression cassette comprises an intron of PK5 and beta-globin, and an EDN3 gene, the PK5 comprises a nucleotide sequence as shown in SEQ ID NO. 2; and the EDN3 gene comprises a nucleotide sequence as shown in SEQ ID NO. 4. A specific expression cassette and a carrier are researched, the black sheep of which the skin, hair, tongue, oral mucosa, eye white mucosa, epididymis and ears all become black can be prepared through somatic cell cloning on the basis of cells edited by the carrier, and important application value and economic value are achieved.

This invention provides a high-recovery heme iron extraction method and apparatus using enzymatic hydrolysis-multi-stage centrifugal coupling, relating to the fields of biopharmaceuticals and fluid dynamics processing technology. The method first constructs a polyanionic electrolyte shielding system, utilizing electrostatic potential energy to induce conformational instability of globin and pre-exposure of hydrophobic cavities, reducing binding energy at the molecular level and solving the problem of heme's encapsulation resistance in high-concentration systems. Then, high-shear coupled enzymatic hydrolysis is performed within a micron-sized liquid film generated by a hypergravity field, utilizing the instantaneous synergy of mechanical shear stress and enzymatic degradation to achieve directional exfoliation of heme, eliminating secondary re-adhesion effects. Finally, directional phase transition regulation is performed based on density gradient drive, and a high-frequency pulsed pressure field is introduced for in-situ exchange washing, distinguishing and retaining impurities and crystal cores, outputting a high-purity, flavor-neutral heme iron product. This invention effectively improves the controllability of the extraction process and the stability of industrial continuous production.

The invention provides a characteristic protein spectrum model for detecting uremia and a construction method. Wherein the marker polypeptide composition is mainly carbamoyl hemoglobin of alpha / beta globin, and comprises eight marker polypeptides with the following mass-to-charge ratios: 7564 m / z, 7585 m / z, 7934 m / z, 7956 m / z, 8476 m / z, 15127 m / z, 15170 m / z, 15868 m / z, 15911 m / z and 16952 m / z. The mass spectrum model disclosed by the invention can be used for detecting uremia. The detection method provided by the invention is simple, easy to operate and high in accuracy, and provides a new method and idea for uremia detection.

Methods and compositions for increasing hemoglobin levels (e.g., fetal hemoglobin) and / or gamma-globin in a cell or subject by the administration of at least one FTP A inhibitor and / or at least one TIPRL inhibitor to the cell or subject is disclosed. In another aspect methods of treating and / or preventing a hemoglobinopathy (e.g., sickle cell disease) or thalassemia in a subject by the administration at least one PTPA inhibitor and / or at least one TIPRL inhibitor to the subject in need thereof are further disclosed.

The present invention relates to a method for the extraction of oxygen from an aqueous medium, the method comprising the following steps: - providing an oxygen-permeable extraction membrane (18); then - bringing a first aqueous medium (14) containing oxygen (12) into contact with a first face (20) of the membrane; - bringing a second aqueous medium (16) comprising a carrier compound (30) into contact with a second face (22) of the membrane; - diffusing the oxygen from the first aqueous medium into the second aqueous medium through the membrane (18); and forming a complex compound (32) by binding the oxygen (12) to the carrier compound (30). The carrier compound (30) is an organic molecule selected from among an annelid globin, an annelid globin protomer, and an annelid extracellular hemoglobin.

This application discloses a precise active peptide of hemoglobin with the functions of replenishing qi and blood, improving microcirculation, and promoting vasodilation, as well as its preparation method and application, belonging to the field of hemoglobin peptide technology. The precise active peptide of hemoglobin contains at least one of LGFP, IGFP, FPHFN, LFL, LFI, FESF, ILF, LIF, FLL, FIL, FII, or FPHFD. The prepared precise active peptide of hemoglobin exhibits multiple biological activities: it exerts a hypotensive effect by inhibiting ACE and vasoconstrictive substances; it promotes vasodilation by activating the PI3K / AKT / eNOS signaling pathway; and it has been shown to significantly improve microcirculation and replenish qi and blood in a zebrafish model. The preparation method has low equipment requirements, is simple and easy to operate, and is suitable for large-scale industrial production. This invention enriches the bioactive peptide library and is of great significance for promoting technological progress and industrial upgrading in the field of hemoglobin peptides.

The application relates to the technical field of polypeptide preparation, and particularly discloses a preparation method of animal blood globin polypeptide powder. The preparation method of the animal blood globin polypeptide powder comprises the following steps: adding trisodium citrate into fresh animal blood, stirring for 10-30 min, adding cyanidin and polylysine, stirring uniformly, placing in a temperature-10 to-20 DEG C environment for 1-2 h, increasing to room temperature, homogenizing for 1-5 min, centrifuging, removing supernatant, and obtaining animal blood globin solution; adding the animal blood globin solution and rare earth lanthanum chitosan amine chelate salt into a glycine-sodium hydroxide buffer solution, stirring at 40-50 DEG C for 10-30 min, adding compound protease, and continuing to stir for 10-20 h to obtain an enzymatic solution; adjusting the pH value of the enzymatic solution to 5-6, increasing the temperature to 90-100 DEG C for 5-10 min, decreasing to room temperature, centrifuging for 5-10 min, and taking supernatant for low-temperature spray drying.

The invention relates to the technical field of biology, in particular to recombinant spider silk protein, modified polyurethane and application of the recombinant spider silk protein and the modified polyurethane. The recombinant spider silk protein provided by the invention comprises spider silk protein or spider silk-like protein; the spider silk protein or spider silk-like protein comprises at least one spider silk globulin NT, at least one spider silk protein repeat region and at least one spider silk globulin CT from the N end to the C end. Research finds that when the recombinant spider silk protein is applied to waterborne polyurethane, the mechanical strength of a polyurethane material is remarkably improved, the mechanical property of the polyurethane material is enhanced, and the polyurethane material is environmentally friendly and non-toxic, has the characteristics of no toxicity, high strength, high elasticity and the like, and keeps the original characteristics of low organic matter emission, no pollution, high elasticity, air permeability and the like at the same time. The recombinant spider silk protein can have a CBM structure, so that the mechanical property can be improved. Fluorescent protein and / or chromoprotein can be fused on the recombinant spider silk protein, polyurethane with different appearances can be obtained, and color combination is firm.

The invention discloses a DNA (Deoxyribonucleic Acid) molecule for promoting mRNA (Messenger Ribonucleic Acid) expression and 3'UTR (Untranslated Region) in the mRNA molecule obtained by transcription of the DNA molecule, and the DNA molecule is derived from COX7B of a cytochrome C oxidase family. The invention also discloses an application of the composition containing the 3 'UTR in preparation of RNA (Ribonucleic Acid) therapeutic drugs or mRNA (Messenger Ribonucleic Acid) vaccines. Compared with a control group alpha-globin, the insertion of the 3'UTR fragment provided by the invention has the advantages that the expression quantity of renilla luciferase in Lent-X 293T cells is increased by 2.03 times, and the expression quantity of renilla luciferase in HeLa cells is increased by 3.62 times. The invention shows that the 3 'UTR has an excellent prospect of being applied to RNA (Ribonucleic Acid) therapeutic drugs or mRNA vaccines.

The invention discloses an image processing method and device for judging suspension red blood cell hemolysis. The method comprises the following steps: acquiring a blood image set; the blood image set comprises a plurality of blood images and corresponding label information; acquiring a blood parameter information set; the blood parameter information set comprises a plurality of blood parameters and corresponding label information; the blood parameters comprise hemoglobin concentration, reticulocyte concentration, indirect bilirubin concentration, lactic dehydrogenase concentration and globin concentration; utilizing the blood image set and the blood parameter information set to construct a blood hemolysis composite detection model; based on the blood hemolysis composite detection model, processing the collected blood image and blood parameters to obtain hemolysis detection result information; the hemolysis detection result information is used for representing erythrocyte hemolysis information of the blood corresponding to the collected blood image and blood parameters.

The invention belongs to the field of biological medicine. Specifically, the invention relates to an antibody specifically binding to Hb-CS protein, and an antigen binding fragment and application thereof. The antibody or the antigen binding fragment thereof provided by the invention can be specifically bound with Hb-CS protein instead of normal alpha globin, can be used for immunodetection of Hb-CS protein and effective recognition of Hb-CS protein positive red blood cells, and has important effect and value for development of alpha thalassemia drugs.

CD39 (CAG>TAG) is one of the most common β0-thalassemic mutation in the Mediterranean area and Latin America, representing >40% of β-thalassemic mutations in Tunisia, Argentina and Italy3. This is a nonsense mutation within the codon of amino acid 39, thus it causes premature translation termination and absence of β-globin4. Here, the inventors exploited adenine base-editors (ABEs) to correct the CD39 (CAG>TAG) mutation in HSPCs from β-thalassemia patients and demonstrated the potential of this strategy to correct the pathological phenotype observed during erythroid differentiation. In particular the inventors demonstrated that reverting the CD39 (CAG>TAG) mutation using base editing corrected in vitro the β-thalassemic cell phenotype in terms of erythroid differentiation, enucleation, RBC size and apoptosis. The present invention thus relates to base editing approaches for the treatment of β-thalassemia, including sickle β-thalassemia.

The invention discloses a method for improving human alpha-globin expression through double-site gene editing and application of the method, and belongs to the technical field of gene editing. The method comprises the following steps: editing an HBA1 gene regulatory region and / or an HBA2 gene regulatory region and an HBA1 gene pathogenic mutation site and / or an HBA2 gene pathogenic mutation site by using a gene editing system, so that at least one cytosine in the HBA1 gene regulatory region and / or the HBA2 gene regulatory region is converted into thymine, and the pathogenic mutation site of the HBA1 gene and / or the pathogenic mutation site of the HBA2 gene are / is repaired. By performing double-site editing on the gene regulation region and the gene pathogenic mutation site, on one hand, the pathogenic mutation site is repaired, and normal translation of part of alpha-globin is recovered; on the other hand, an HBA1 gene regulation region and / or an HBA2 gene regulation region of the alpha-globin can be edited, transcription or translation of the alpha-globin can be promoted, the HBA1 gene regulation region and the HBA2 gene regulation region generate a synergistic effect, and finally the purpose of further improving the expression quantity of the alpha-globin is achieved.

A method for single-base editing to repair HBA2 gene mutations and its application, belonging to the field of gene editing technology. This method includes the following steps: contacting a single-base editor and gRNA with the HBA gene sequence to be edited and repaired, so that the codon target cytosine base at CD142 in the HBA gene sequence is deaminated and converted into thymine. This method can accurately edit pathogenic mutation sites, does not produce double-strand breaks, does not affect chromatin conformation and genomic stability; nor does it produce random insertions of large fragment genes in the genome, and has a low impact on oncogene activation or tumor suppressor gene inactivation; it will not produce random insertions / deletions at other sites in the genome; and the expression of the repaired target gene is regulated by all natural HBA2 regulatory elements, having high safety and being more capable of balancing the expression of α / β globin.

According to the present disclosure, a simple and accurate method for quantifying ergothioneine in a sample containing globin protein can be provided. A method for quantifying ergothioneine in a collected sample, comprising: (A) heating the sample; (B) mixing the heated sample with trichloroacetic acid; and (C) subjecting the sample obtained in step (B) to a quantitative operation; A method comprising:

To provide a composition that can improve the quality of sleep. [Solution] A composition for improving sleep quality containing globin protein hydrolysate.

Here, the inventors developed a strategy to modify the chromatin status of HSPCs at the HBG promoters to reactivate HbF expression. In particular, the inventors used from 1 to 4 single guide RNA (sgRNA) molecules spanning from the -220 to the -20 region of the HBG promoters together with CRISPR-based epigenome editors, namely dCas9-CBPcore and Tet1-dCas9. The first editor is capable of inserting histone acetylation while the second editor is performing DNA demethylation. Both epigenetic marks are associated with active transcription and are present in fetal erythroid cells expressing HbF. This strategy allows the ex vivo modification of adult HSCs to recreate a fetal-like epigenetic context leading to HbF production. Moreover, it avoids the genotoxicity associated with classical genome editing tools relying on DNA cleavage. Thus, the present invention relates to a method of increasing the expression of gamma globin in a population of eukaryotic cells through epigenome editing.

In certain embodiments a lentiviral vector for the treatment of sickle cell disease (SCD) is provided. In certain embodiments the vector comprises an expression cassette that encodes that an anti-sickling β-globin gene and an shRNA that inhibits expression of a BCL11A gene (BCL11A shRNA) wherein said expression cassette is in reverse orientation in the vector; a β-globin locus control region (LCR) comprising a reduced length hypersensitive site 1 (HS1) sequence, a reduced length hypersensitive site 2 (HS2) sequence, a reduced length hypersensitive site 3 (HS3) sequence, and a reduced length hypersensitive site 4 (HS4) sequence, where said anti-sickling β-globin gene is operably linked to the human β-globin locus control region;.

The invention discloses a DNA (Deoxyribonucleic Acid) molecule for promoting mRNA (Messenger Ribonucleic Acid) expression and 3'UTR (Untranslated Region) in the mRNA molecule obtained by transcription of the DNA molecule, and the DNA molecule is derived from a COX17 gene of a cytochrome C oxidase family. The invention also discloses an application of the composition containing the 3 'UTR in preparation of RNA (Ribonucleic Acid) therapeutic drugs or mRNA (Messenger Ribonucleic Acid) vaccines. Compared with a control group alpha-globin, the insertion of the 3 'UTR fragment provided by the invention enables the expression quantity of renilla luciferase in LentiX 293T cells to be increased by 2.76 times and the expression quantity of renilla luciferase in HeLa cells to be increased by 6.41 times, and shows that the 3' UTR has an excellent prospect of being applied to RNA (Ribonucleic Acid) therapeutic drugs or mRNA (Messenger Ribonucleic Acid) vaccines.

Provided is a method of treating or alleviating one or more pathologies associated with β- thalassemia in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of an anti-matriptase-2 antibody or antigen-binding fragment thereof. The one or more pathologies may be insoluble liver iron stores: α-globin precipitates in ery throid cells; reactive oxidized species formation; apoptosis of erythroid cells; reticulocytosis; or a combination thereof.

BCL11A plays a critical role in the regulation of hemoglobin production, specifically in the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA) during development. BCL11A represents a target to develop therapies for β-hemoglobinopathies by reactivating HbF. The inventors leading to a better yield for the proteomic analysis of histidine phosphorylations in a whole proteome. They identify a phosphorylation on histidine of BCL11A by immunoprecipitation of BCL11A and by the detection of its phosphorylations on histidines by Western blot. Furthermore, the knock down of NME1 and NME2 by CRISPR / Cas9 in HUDEP2 erythroid cell line induces the expression of fetal hemoglobin, suggesting that NME1 / 2 could be involved in fetal to adult globin switch probably through the regulation of histidine phosphorylation of BCL11A. HUDEP-2 cell line is still able to differentiate until the orthochromaic erythroblast stage and do not show any increase in cell death.

The invention provides a UTR element HBB-G and a construction method and application thereof, and relates to the technical field of mRNA. According to the present invention, ribosome load prediction and secondary structure optimization are performed on the 5 'UTR of Homo sapiens haplotype T7 delta-globin (the NCBI number is AF339412.1) through the PadleHelix platform, and the obtained optimized sequence avoids the inhibitory hairpin structure, such that the luciferase expression quantity is significantly improved compared with the natural UTR. On the basis of an optimized sequence, an ncRNA sequence without a secondary structure is introduced, translation inhibition of a 5 'cap region is further relieved, and a constructed HBB-G mutant (the DNA sequence of HBB-G is as shown in SEQ NO.1, and the RNA sequence is as shown in SEQ NO.2) enables the protein expression quantity to be further improved.