277 results about "Human disease" patented technology

The invention belongs to the technical field of biology, and particularly relates to an SLC44A1 gene and / or SLC44A5 gene knockout animal model as well as a construction method and application thereof. The construction method of the animal model comprises the following steps: deleting exon regions from the fourth exon region to the thirteenth exon region of the SLC44A1 gene and / or the second exon region of the SLC44A5 gene in mouse brain oligodendroglia cells in a high-efficiency manner by utilizing gene editing and a Cre-loxP recombinase system, so as to realize the knockout of a target gene. The animal model constructed by the invention can be used for researching the regulation mechanism of the choline transporters (SLC44A1 and SLC44A5) on myelin sheath formation, deeply knowing the biological functions of the choline transporters (SLC44A1 and SLC44A5), simulating the occurrence and development processes of human related diseases, revealing the pathogenesis of the related diseases, providing a new thought for prevention and treatment of brain myelin sheath dysplasia, and providing a new foundation for the prevention and treatment of brain myelin sheath dysplasia. And an effective drug or a treatment mode aiming at the disease is screened by utilizing a gene knockout animal model, so that a new choice is provided for clinical treatment of the disease.

In some embodiments, methods of expanding tumor infiltrating lymphocytes using AKT pathway inhibitors and methods of using the expanded tumor infiltrating lymphocytes in the treatment of human diseases, including cancers, are disclosed.

The present invention provides a real-time flow cytometric analyzer of single-cell dynamics combining droplet microfluidics and multimodal optical microscopy, and belongs to the field of cell biology experimental devices. The analyzer comprises a cell / signal loading & acquisition and control system, a high-throughput microfluidic single-cell manipulation chip, a multi-channel optical microscopy and multimodal signal acquisition and control system, and a data processing and analysis system. Based on droplet-based microfluidic chip technology, multimodal optical microscopy technology, single-cell dynamics theoretical modeling and analysis methods, and artificial intelligence technology, the integrated detection of spatiotemporal information of single-cell dynamics can be realized. The analyzer provides a new rapid and accurate single-cell dynamics analysis platform for exploring the occurrence and development mechanism of major human diseases, disease diagnosis, cell sorting and drug screening, etc.

Isolated or recombinant EphA5 or GRP78 targeting antibodies are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and / or therapeutic treatment of human diseases, such as cancer. A method of rapidly identifying antibodies or antibody fragments for the treatment of cancer using a combination of in vitro and in vivo methodologies is also provided.

The invention relates to the field of immunology, and discloses a polypeptide and a kit for distinguishing bovine and sheep brucella natural infection from a vaccine immune antibody. Polypeptides as shown in SEQ ID NO: 1 and SEQ ID NO: 2 are artificially synthesized and used as antigens to coat an elisa plate and a nitrocellulose membrane, and according to response characteristics of antibody level, identification and detection of natural infection and vaccine immunity of cattle and sheep populations are realized. The peptide fragment and the detection kit provided by the invention can make up the blank of identifying bovine and sheep brucella natural infection and immune antibodies. The method solves the problem that the antibody induced by the attenuated live vaccine and the naturally infected antibody are difficult to distinguish, provides a scientific basis for quarantine and purification of Brucella, and provides a technical guarantee for preventing human diseases and animals, advancing the mouth and protecting the body health of people.

The disclosure described herein provides for enzymatically stable and potent GLP-1 analogs (i.e., derivatives) for the treatment of metabolic disease or disorder in a subject. In some embodiments, the GLP-1 analog is a derivatized GLP-1 peptide, wherein the derivatized peptide has 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences from any one of GLP-1, GLP-1(7-39), GLP-1(7-36), GLP-1(7-37). In certain embodiments, the GLP-1 analog comprises at least one lysine substituent. The GLP-1 analogs described herein demonstrate potent receptor binding and extended plasma half-life. A pharmaceutical composition of the GLP-1 analogs is described herein for the treatment of metabolic disease or disorder in a subject, such as diabetes or obesity.

The invention discloses a group of chicken PGC-1alpha gene promoters as well as a construction method and application thereof, and belongs to the field of gene engineering. The chicken PGC-1 alpha gene promoter is any one of A1-A5 sequences of which the nucleotide sequences are shown as SEQ ID NO: 1 to SEQ ID NO: 5. The promoter is applied to the promotion of expression of firefly luciferase in chicken preadipocytes, and is applied to the regulation and control of the chicken PGC-1 alpha gene promoter by a specific transcription factor PPAR gamma. The five PGC-1alpha gene promoters have promoter activity in chicken preadipocytes, and can directly regulate and control transcription expression of the chicken PGC-1alpha gene. The chicken PGC-1alpha promoter disclosed by the invention can predict the transcriptional activity of the PGC-1alpha at the in-vitro cellular level, so that the chicken PGC-1alpha promoter has potential application values for revealing a transcriptional regulation mechanism of the chicken PGC-1alpha, breeding low-abdominal-fat broilers, revealing molecular mechanisms after various human diseases occur and developing drugs for targeting PGC-1alpha expression.

The present invention relates to an oligonucleotide comprising from 10 to 25 nucleotides, at least one nucleotide having a modification wherein said oligonucleotide hybridizes to a transcript or mRNA of leucine-rich repeat kinase 2 (LRRK2) of SEQ ID NO. 1 and / or to a pre-mRNA of LRRK2 of SEQ ID NO. 2 and / or a fragment thereof. The invention further relates to a pharmaceutical composition comprising such oligonucleotides, and to the use of said oligonucleotides and pharmaceutical compositions, respectively, in methods for the prevention and / or treatment of human diseases.

The invention provides a method, a system, equipment, a medium and a program product for identifying candidate functional SNP (Single Nucleotide Polymorphism), and a method, a system, equipment, a medium and a program product for identifying myopia-related candidate functional mutation sites, and relates to the field of biological analysis. According to the invention, transcription and post-transcription regulation are comprehensively integrated, and a macroscopic view of myopia potential genetic molecule imbalance is provided for the first time. The method can be used for researching the possible genetic mechanism of the SNP with the undefined function to other human diseases, so that the interpretability of the SNP related to the diseases is enhanced.

This invention provides antibodies or functional antibody fragments or probes thereof targeting a unique set of antigens recognized in cancer. The invention comprises a nucleotide sequence derived from the L2A5 monoclonal antibody. The antibodies or functional antibody fragments or probes thereof include variable heavy chain domains and variable light chain domains having the amino acid sequences provided herein. The DNA / amino acid sequence binding is unique and has never been previously described. The invention further provides antibodies or functional antibody fragments or conjugates or recombinant proteins useful for the detection, treatment, and prevention of human diseases, including cancer.

The present disclosure relates to multispecific proteins comprising designed ankyrin repeat domains with binding specificity for different targets, such as, e.g. CD40 and FAP. In addition, the present disclosure relates to nucleic acids encoding such multispecific proteins, pharmaceutical compositions comprising such multispecific proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer, in a mammal, including a human.

Disclosed herein are systems for LNP-mediated delivery of circular single-stranded DNA (cssDNA). The systems can be used to facilitate integration of the cssDNA into a cellular genome for a variety of purposes, including treatment of human diseases.

The disclosure relates to the use of atovaquone or a salt thereof, and, optionally, proguanil or a salt thereof, for the treatment of various human diseases and conditions, including gastrointestinal disorders and, in particular, those associated with inflammation, such as inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD).

Disclosed herein are methods for improving detection and monitoring of human diseases. The methods can be used to provide spatial and / or developmental localization of the source of each differential mutation within the body. The methods can also be used to generate a mutation map of a subject. And the mutation map can be used to monitoring state(s) of health of one or more tissues of a subject.

The invention discloses a method for establishing a hemophagocytic syndrome in-vitro cell disease model, and belongs to the technical field of biology. Based on human PBMC construction, the reaction of a human immune system can be truly reflected, experimental result deviation caused by species difference in an animal model is avoided, and a more accurate model basis is provided for research of human diseases. In addition to T cell over-activation, the HLH model of the present application has a clear key feature of NK cell reduction, which is HLH, accompanied by up-regulation of cytokines such as interferon-gamma and IL-10. The establishment process of the model is rapid and efficient, the experimental period is remarkably shortened, a large number of samples or drugs can be rapidly screened, the research efficiency is improved, and the conversion process from basic research to clinical application is accelerated. The method can be used for researching various mechanisms related to the HLH, is beneficial to more comprehensive understanding of pathogenesis of the HLH, and provides a theoretical basis for developing preliminary screening of targeted drugs.

The invention provides a construction method of an animal model of chronic low-dose cadmium exposure induced hepatic fibrosis, and provides a research basis for the reason of chronic cadmium exposure induced hepatic fibrosis and the drug efficacy analysis of the chronic cadmium exposure induced hepatic fibrosis. The method simulates a chronic low-dose cadmium exposure condition, is convenient to operate and stable, can help scientific researchers to visually observe the occurrence and development process of chronic liver injury and hepatic fibrosis induced by heavy metal exposure, and can provide a powerful basis for mechanism research of heavy metal poisoning. According to experimental results, in the body shape, living state, liver appearance and liver tissue pathological change process of a mouse, the mouse shows the mouse liver chronic injury and fibrosis change process under the chronic low-dose cadmium exposure environment, the direct relation between the cadmium exposure time and the liver fibrosis progress can be directly obtained, and the obtained animal model is stable. Researchers can create a disease process similar to human diseases through construction of the animal model in the future, the disease process can be quickly simulated, mass copying can be performed in a short time, the research period can be shortened, the animal model can be used for large-scale experimental research, and powerful support is provided for drug research and development and treatment strategies.

The invention discloses a medicinal arc scraping therapy device prepared from a Chinese herbal medicine composition and a preparation method of the medicinal arc scraping therapy device, the medicinal arc scraping therapy device prepared from a plurality of different negative and positive Chinese herbal medicine raw material compositions is used for carrying out physical therapy on different human diseased organs in the scraping therapy process, and the medicinal arc scraping therapy device has the characteristics that the medicinal arc scraping therapy device takes effect immediately, has a remarkable effect and can control the treatment course.

Disclosed herein are engineered LSR sequences, compositions, and uses including in genome-editing systems and therapeutic compositions. The LSRs can facilitate nucleic acid recombination at particular attachment sites, using suitable donor sequences. The disclosed LSRs may be used to site-specifically recombine or integrate nucleic acid sequences for a variety of purposes, including treatment of human diseases.

The present disclosure provides methods of amplifying tissue samples derived from humans for purposes of treating certain diseases. The method comprises: isolating a small amount of associated tissue by biopsy or other tissue acquisition methods; the tissue is amplified in vitro, and meanwhile, natural functions are reserved; and re-implanting the amplified tissue to alleviate human disease. One example includes ex vivo expansion of human pancreatic islet tissue and reimplantation of the expanded cells into an individual with Type 1 diabetes for treatment and long term relief or cure of disease.

The invention provides a mouse PDX cell and a construction method of a humanized systemic lupus erythematosus (SLE) mouse model, and belongs to the technical field of animal model construction. The invention provides a mouse PDX cell L0407-6-P3 which is preserved in the China Center for Type Culture Collection (CCTCC), and the preservation number is CCTCC NO: C2024181. After the mouse PDX cell L0407-6-P3 is intravenously injected into an NSG mouse, the mouse disease is stable, the human SLE disease phenotype can be generated, the multi-system and multi-organ inflammatory response and injury of human SLE can be better simulated, the mouse PDX cell L0407-6-P3 can be used for constructing a humanized systemic lupus erythematosus mouse model, the blank of the current humanized SLE animal model is filled, and the mouse PDX cell L0407-6-P3 has better popularization and application values.

Compounds of formula (I) as defined in the present application, or pharmaceutically acceptable salts thereof, are potent modulators of human IL-17 activity, and thus are beneficial for the treatment and / or prevention of various human diseases, including inflammation and autoimmune disorders.

The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal / Skeletal Anomalies and / or Scoliosis (CLOVES) syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

The present disclosure provides transgenic mice for use as mouse models, and methods related thereto. The transgenic mice described herein comprise a humanized mouse telomerase (hmTert) gene included in a background mouse germline that provides shortened telomeres capable of reproducing humans and various human disease states.

The invention provides a keloid disease in-vitro model as well as a construction method and application thereof, and relates to the technical field of cell biology. The construction method comprises the following steps: constructing a full-thickness skin model with an epidermal layer and a corium layer by utilizing a cell culture chamber or a cell culture micro-fluidic chip, and then performing induced culture by adopting TGF-beta to obtain the keloid disease in-vitro model. According to the construction method, by selecting the concentration and culture time of TGF-beta in the induction process, keloid-like change of the full-thickness skin model can be effectively promoted, and the pathological state of keloid is truly simulated; meanwhile, the human fibroblasts and the human keratinocytes are adopted to prepare the in-vitro model with the full-thickness skin structure, the in-vitro model has the human attribute, the individual difference of species difference bases is reduced, and the real effectiveness of the model is greatly improved; the defect that keloid which is a special human disease cannot be effectively simulated by an animal model is overcome.

Provided are a novel bispecific antigen-binding antibody, an antigen-binding fragment thereof, and a Trop2 * HER2 bispecific antibody drug conjugate (Trop2 * HER2 Abs ADC) which comprise a Trop2-binding arm and an HER2-binding arm, are capable of simultaneously specifically binding to HER2 and Trop2, have a high binding affinity to HER2 and Trop2, can be endocytosed by cells expressing HER2 and / or Trop2, and can be used as an antigen-binding fragment of a Trop2 * HER2 bispecific antibody drug conjugate. Endocytosis of the two binding arms L has a synergistic effect; the Trop2 * HER2 Abs ADC can inhibit the growth of tumor cells expressing HER2 and / or Trop2 in vitro and in vivo, and the bispecific antibody can be used for preventing and treating human diseases related to HER2 and / or Trop2, such as cancers.

Methods of treating or preventing a disease resulting from a respiratory syncytial virus (RSV) infection in a human subject is disclosed. The methods disclosed include administering to the human subject a compound of Formula (I), or pharmaceutical composition including a compound of Formula (I). In certain embodiments, the compound is celgosivir.

Cyclopropyl N-[(S)-[3-[1-(2,2-difluoropropylcarbamoyl)-3-hydroxy-3-methyl- cyclobutyl]imidazo[1,2-b][1,2,4]triazin-6-yl]-[4- (trifluoromethyl)cyclohexyl]methyl]carbamate, or a pharmaceutically acceptable salt thereof, being a potent modulator of human IL-17 activity, is accordingly of benefit in the treatment and / or prevention of various human ailments, including inflammatory and autoimmune disorders.

Cell-based compositions and methods for targeting and treating human diseases, including cancers and infectious diseases, are provided, wherein exogenous intracellular sarcosine is used for improved delivery of the composition.

Embodiments are directed to novel GPR52 activators. In particular, a series of novel 1-(pyrimidin-4-yl)indoline-4-carboxamide analogs that have been identified as potent and selective GPR52 agonists. The optimized GPR52 agonist that, for example, can be used as a valuable pharmacological tool or a drug candidate for investigating the physiological and therapeutic potential of GPR52 activation for various human diseases.