22 results about "Stat signaling" patented technology

The invention discloses a pig IFNAR2 protein mutant, which is characterized in that the 399th site in the amino acid sequence of the pig IFNAR2 protein is mutated from glycine to alanine, and the amino acid sequence of the pig IFNAR2 protein is as shown in SEQ ID NO. 1. The invention provides a specific cleavage site of ASFV protease pS273R, and the site is mutated through a gene editing technology so as to block the cleavage of pig IFNAR2 by the pS273R and improve the ability of pigs to resist African swine fever virus infection. By blocking ASFV from damaging type I IFN mediated JAK-STAT signal activation, on the basis of retaining pig autoimmune performance, higher specificity and higher efficiency are achieved, negative effects of genetic engineering on pig growth performance and reproductive performance can be greatly reduced, and biosafety is higher.

The present disclosure provides cytokine signaling receptors to provide STAT3 and STATS signaling in cells such as iPSC-derived CD8+ T cells. The cytokine signaling receptors may be under the control of endogenous or exogenous promoters to regulate their expression in a cell. The present disclosure also provides engineered cells comprising the cytokine signaling receptors, or a combination of a cytokine signaling receptor and a secreted cytokine, as well as methods of use of the engineered cells.

This invention discloses a composite scaffold for promoting bone regeneration in diabetic patients, its preparation method, and its applications, relating to the field of medical biomaterials technology. The composite scaffold for promoting bone regeneration in diabetic patients comprises: a three-dimensional porous framework; and a bioactive hydrogel layer loaded with naringin. The bioactive hydrogel layer loaded with naringin is coated on the surface and pore walls of the three-dimensional porous framework. The technical solution provided by this invention uses a 3D-printed PLGA / HA porous framework to provide mechanical support and osteoconductivity, and a supramolecular hydrogel coating loaded with naringin to endow it with immunomodulatory and drug sustained-release functions. This scaffold has good hydrophilicity and biocompatibility, and can effectively induce macrophage polarization towards the M2 anti-inflammatory phenotype by activating the JAK-STAT signaling pathway, improving the local inflammatory microenvironment of diabetic bone defects. Simultaneously, it indirectly promotes vascular endothelial cell migration, lumen formation, and osteogenic differentiation of bone marrow mesenchymal stem cells by regulating macrophages.

The application discloses application of VK4 in preparation of a drug for treating leukemia, and belongs to the leukemia treatment field. The application research finds that VK4 can inhibit proliferation of leukemia cells through cycle arrest and induction of apoptosis, and VK4 can inhibit proliferation of HL60 cells and K562 cells through blocking of a JAK / STAT signal path. The results of Wright's staining, immunohistochemical staining and H&E staining of a mouse leukemia model show that VK4 also has an anti-leukemia effect in vivo, and has no obvious liver and kidney damage, and can provide a new drug selection for clinical treatment of leukemia.

This invention relates to the application of cucurbitacin Q1 in the preparation of drugs for treating gliomas, belonging to the field of biomedical technology. The cucurbitacin Q1 of this invention has a significant inhibitory effect on glioma cell activity. It can inhibit the protein expression of JAK1, JAK2, and STAT4 by regulating the JAK-STAT signaling pathway, and block the phosphorylation activation of STAT3 protein, thus weakening downstream signal transduction in this pathway. Simultaneously, it can also exert an anti-tumor effect by regulating the phosphorylation level of related proteins in the PI3K-AKT signaling pathway. The cucurbitacin Q1 of this invention not only significantly inhibits the proliferation, invasion, and migration of glioma cells, but also significantly increases the apoptosis rate of glioma cells.

Provided is an engineered TGFβ receptor system to be expressed in immune cells (e.g., T cells) that is repurposed, upon TGFβ binding, to transduce immunosupportive interleukin 9 (IL-9) signaling rather than the usual immunosuppressive TGFβ signaling mediated by endogenous TGFβ receptors expressed in the immune cells. The engineered TGFβ receptor system includes two engineered chimeric TGFβ receptor chains, with their extracellular portions respectively encoding the extracellular domains of TGFβR1 and TGFβR2, and their intracellular portions respectively encoding the intracellular domains of IL9R and IL2γ. T cells modified with such engineered TGFβ receptor system exhibit strong JAK-STAT signaling, and high survival and proliferation capacity upon TGFβ stimulation, especially under repeated antigen stimulation. Such engineered immune cells are expected to have an enhanced persistence and improved control in treating solid tumors which is commonly characterized to have a TGFβ-enrich immunosuppressive environment.

A crystal form includes: crystal form I and crystal form III, using X-ray diffraction method to have characteristic diffraction peaks at about 8.4°, 10.0°, 13.6°, 16.4°, and 19.7°, respectively; and at about 8.2°, 9.8°, 17.2°, and 26.8°. A production method of the crystal form I and III includes: aromatic heterocyclic compound is added with a suitable solvent for stirring, filtering, and drying to obtain crystal form I or III; and the use of crystal form I or crystal form III is for the production of drugs for preventing or treating diseases caused by abnormal JAK-STAT signaling pathways.

This invention belongs to the field of biotechnology, specifically relating to a complex peptide for enhancing animal immunity and its preparation method. The complex peptide is composed of InflamBlock-9 peptide and ImmunoEnhance-7 peptide in a mass ratio of 3:1. InflamBlock-9 peptide reduces the excessive secretion of pro-inflammatory factors IL-1β, IL-6, and TNF-α by targeting and inhibiting the key protein IκB kinase (IKK) in the NF-κB signaling pathway. ImmunoEnhance-7 peptide promotes the synthesis of immunoglobulins IgG, IgA, and apolipoprotein A1 (Apo-A1) by activating the JAK-STAT signaling pathway. The combined use of these two peptides significantly reduces the levels of IL-1β, IL-6, and SAA in cat serum under stress (P<0.05) and increases the levels of IL-10, IgG, and Apo-A1 (P<0.05 or P<0.10), effectively alleviating excessive inflammatory response and improving immunosuppression. The preparation method of this invention achieves efficient peptide preparation through a dual prokaryotic and eukaryotic expression system. The process is controllable and low-cost, making it suitable for the development of functional pet foods or health products.

The invention provides interfering RNA (Ribonucleic Acid) targeting Janus kinase 1 (JAK1), and the interfering RNA can reduce the expression of JAK1 and further inhibit the activation of a JAK / STAT (JavaScript Association Protein) signal channel, so that the purpose of treating related diseases caused by disorder of the JAK / STAT signal channel is achieved. The invention further provides a lipid nanoparticle drug containing the interfering RNA, and the lipid nanoparticle drug is used for treating related diseases of JAK / STAT signal channel disorder. The invention also provides an antibody-nucleic acid coupled drug, which contains interfering RNA and is used for treating related diseases of JAK / STAT signal pathway disorder.

The application belongs to the technical field of biological medicine, and particularly relates to a kind of polyphenol-protein self-assembly material and its preparation method and application.The application effectively forms polyphenol-protein self-assembly material (NE APs) by using multiple physical interactions between EGCG and growth factor NRG-1.NRG-1 can be continuously released from NE APs, and EGCG protects NRG-1 from oxidative stress, maintains its biological activity related to stem cell recruitment, migration and angiogenesis.In addition, NE APs utilize the ability of EGCG to scavenge ROS, maintain mitochondrial homeostasis and promote osteogenic differentiation, while synergistically regulating immune response through TNF / NF-κB / JAK-STAT signaling pathways.In vivo experiments show that NE APs accelerate the repair of inflammatory bone defects by enhancing stem cell recruitment, angiogenesis and immune regulation, and have good practical application value.

The invention provides application of isoliquiritigenin in relieving toxicity of pinellia ternate and a pinellia ternate detoxification medicine, and belongs to the technical field of biology. The invention proves that the ISL can inhibit the expression increase of TNF-alpha and IL-1beta mRNA caused by pinellia ternate poison needle crystals and PTL, inhibit the increase of ROS in macrophages caused by pinellia ternate poison needle crystals, and weaken inflammatory response caused by pinellia ternate poison needle crystals. According to the present invention, the ISL can inhibit the oxidative stress reaction caused by PTL by inhibiting the combination of PTL and the macrophage membrane, and inhibit the excessive generation of ROS in the macrophage so as to block the MAPK inflammation pathway activation, such that the activation of the JAK-STAT signal pathway is inhibited, the secretion of inflammatory factors TNF-alpha, IL-1beta and IL-6 is reduced, the inflammatory cascade reaction process is blocked, and the inflammatory reaction degree is significantly weakened;

The preparation method of the paeonol derivative with the antitumor activity and the neuroinflammation relieving function is characterized in that the molecular structure of the paeonol derivative is shown in the specification, wherein R is a phenyl or aryl derivative. The invention designs and synthesizes a paeonol derivative with a novel structure, and the compound not only can induce Hela cervical cancer cell apoptosis, but also can inhibit LPS-induced microglial cell inflammation through a JAK-STAT signal channel, and has the potential of becoming a lead compound for resisting tumors and relieving neuroinflammation.

Provided is an interfering RNA targeting Janus kinase 1 (JAK1). The interfering RNA can reduce the expression of JAK1 and further inhibit the activation of a JAK / STAT signaling pathway, thereby achieving the purpose of treating a JAK / STAT signaling pathway dysregulation-associated disease. Further provided is a lipid nanoparticle drug containing the interfering RNA for use in treating a JAK / STAT signaling pathway dysregulation-associated disease. Further provided is an antibody-nucleic acid drug conjugate containing the interfering RNA for use in treating a JAK / STAT signaling pathway dysregulation-associated disease.

A method for producing self-rejuvenating and safe cells, and a self-rejuvenating and safe repair cell are provided. [Solution] A technology and its use are provided for controlling the Jak-Stat pathway to differentiate, dedifferentiate, and rejuvenate cells. By quantitatively and / or periodically controlling gene or protein targets of the Jak-Stat signaling pathway in cells using combinations of small molecule compounds, cytokines, or recombinant proteins, gene editing technology, or genetic recombination technology, rejuvenated cell products and / or different types of cell products are obtained. This product can be applied to the reprogramming of cells, tissues, organs, and living organisms; the construction of tissue engineering materials; the repair of damaged and aging, degenerated tissues and organs in mammals; the delay or reversal of the progression of aging in cells, tissues, organs, and living organisms; and the immunomodulation of cells, tissues, organs, and living organisms.

The application discloses application of leptin in preparation of a medicine for promoting hair growth, and belongs to the technical field of biological medicines. The leptin provided in the application is expressed in hair matrix cells of a growing hair follicle, activates a JAK-STAT signal path, and induces continuous proliferation of hair matrix cells, so as to promote the hair follicle to enter the growing period in advance, prolong the time length of the growing period of the hair follicle, promote differentiation of the hair matrix cells into keratinocytes, maintain continuous growth of the hair shaft, and further prolong the length of the hair shaft.

The invention provides a hydrogel medicine for treating alopecia hair disease and a preparation method, and belongs to the technical field of biological medicine. The miR-665 provided by the invention can target an STAT3 gene and inhibit a JAK-STAT signal channel, so that IFN-gamma induced hair follicle cell proliferation inhibition is counteracted, and the miR-665 can be applied to preparation of drugs for promoting hair follicle cell proliferation. The miR-665 and ROS response hydrogel are combined to prepare a hydrogel preparation for treating alopecia hair disease, the proliferation and migration ability of hair papilla cells and keratinocytes can be remarkably enhanced, hair regeneration of an alopecia areata model is effectively promoted, and lymphocyte infiltration is reduced. The invention has the advantages of high biocompatibility, small side effect, lasting curative effect and the like, and provides a new strategy for the treatment of alopecia areata.

The invention discloses an application of a PD-L1 single-domain antibody in preparation of a preparation for promoting hair growth or preventing and treating alopecia, belongs to the technical field of biological medicines, and particularly discloses an effect of the PD-L1 single-domain antibody in regulation and control of expression of cytokines IL-6 and Leptin so as to activate a JAK-STAT signal channel and provides a new preparation source for treatment of non-scar alopecia. The invention further provides a preparation containing the PD-L1 single-domain antibody, the side effect of an existing medicine for treating alopecia can be overcome, the treatment effect is good, and after a subject takes the medicine for 3-4 times and 8 weeks after the medicine is stopped, hair growth at the original alopecia position still continues.

This invention provides the application of JAK1 inhibitors in the preparation of drugs for treating adverse reactions related to immune checkpoint blockade. The CD8 inhibitor of this invention... + CTLs in T cells irAE Subgroups are key mediators of adverse reactions associated with multi-organ immunotherapy, specifically overexpressing JAK1 and activating the JAK-STAT signaling pathway, while anti-tumor CD8... + T cell subset 1 (CTL1) shows low JAK1 expression. Inhibitors specifically targeting JAK1 can block CTL expression. irAE‑Ⅱ Inhibiting the JAK-STAT pathway in subpopulations alleviates adverse reactions in multiple organs, including the heart and lungs, without affecting the anti-tumor CD8 inhibitors. + The anti-tumor function of T cell subsets can also enhance the efficacy of immune checkpoint inhibitors.

The invention relates to application of coniferyl ferulate serving as a traditional Chinese medicine component to treatment of neuroinflammation related diseases. Through a large number of researches, it is found that the natural compound CF derived from traditional Chinese medicine can promote transformation of macrophages from M1 phenotype to M2 phenotype by adjusting a JAK / STAT signal channel. According to the effect, neuroinflammation is inhibited in a dose-dependent mode, and the motor function and the activity capacity of mice after SCI are remarkably improved. The CF can effectively promote scar healing, enhance the survival rate of motor neurons, reduce the cavity area and increase the number of the motor neurons. Besides, the CF shows an excellent motor function recovery effect, which indicates that the CF has huge potential in the aspect of preventing and improving central nervous system diseases, especially spinal cord injury, as a functional food supplement with anti-neuroinflammation and neuroprotective activity, and is high in safety and suitable for long-term use; meanwhile, the invention effectively expands the types of medicines of the natural source SCI treatment active agent, and provides a new direction for the subsequent research and development of new medicines.

The application provides application of a combined STAT signal pathway related gene in a colorectal cancer prognosis model, the combined STAT signal pathway related gene is CAV1, EPO, IL13, LEP and NEUROD1; wherein the establishment method of the colorectal cancer prognosis model comprises the following steps: 1) data collection and arrangement, 2) screening of differentially expressed STAT signal pathway related genes, 3) construction of a prognosis model of the STAT signal pathway related genes, and 4) construction of a nomogram. The prognosis model has the advantages of high accuracy, can provide a new method for disease diagnosis and prognosis of colorectal cancer patients in the clinic, reveals the prediction effect on the tumor microenvironment, and provides important information for the development of targeted therapy.

The invention discloses a SOCS1 antagonistic peptide for preventing and treating avian infectious bronchitis and application of the SOCS1 antagonistic peptide, the amino acid sequence of the SOCS1 antagonistic peptide is LPQDKEYYKVKEP, and Y is phosphorylated tyrosine. Reasonable design is carried out on the basis of a molecular mechanism of interaction of a JAK2 activation ring and the SOCS1 protein, a molecular docking result shows that the SOCS1 antagonistic peptide can be precisely combined to KIR and SH2 functional domains of the chicken SOCS1 protein through a specific phosphorylated tyrosine residue of the SOCS1 antagonistic peptide, and the combination can competitively block combination of SOCS1 and endogenous JAK2 of cells, so that the chicken SOCS1 antagonistic peptide can be used for preparing the chicken SOCS1 antagonistic peptide. Therefore, the inhibition effect of SOCS1 on a JAK-STAT signal channel is relieved, the I-type interferon antiviral immune response of a host is recovered, and virus replication is inhibited fundamentally.

The application belongs to the field of biological medicine, and particularly relates to application of a biological product for reducing expression of lncRNA Gm16984 in preparation of a preparation for treating chronic kidney disease, wherein the nucleotide sequence of the lncRNA Gm16984 is shown as SEQ ID NO. 1. It is found in the application that knocking out the lncRNA Gm16984 can reduce HHcy-induced kidney injury and podocyte injury. The lncRNA Gm16984 regulates podocyte injury by activating a JAK-STAT signaling pathway; further, Hcy mediates m6A modification of the lncRNA Gm16984 through METTL3, and IGF2BP1 binds the m6A-modified lncRNA Gm16984 and stabilizes the expression thereof. It is clarified in the application that the lncRNA Gm16984 can be used as a treatment target point of HHcy kidney injury, and a related inhibitor thereof provides a new technical scheme for clinical diagnosis and treatment of HHcy kidney injury.