35 results about "Stat signaling" patented technology

Methods for treating a subject with cancer mediated through dysregulated, aberrant, or defective JAK/STAT signaling, are provided, comprising determining the level of the JAK/STAT signaling in a sample derived from a subject in need of treatment, wherein the presence of dysregulated, aberrant, or defective JAK/STAT signaling is indicated, administering to the subject an effective amount of a triazolone compound as described herein.

The present invention relates to methods for identifying compounds that can reduce immune rejection, for example, transplant- or autoimmune disorder-related immune rejection. The present invention is based, in part, on the discovery, demonstrated herein, that immune rejection can be monitored by determining the amount of particular members of the Jak/Stat signal transduction pathway present within an affected tissue. The present invention is further based, in part, on the discovery, demonstrated herein, that immune rejection can be reduced and tolerance can be induced by modulating the amount of these particular members of the Jak/Stat signal transduction pathway present, expressed or active within an affected tissue. In particular, the results demonstrate that immune rejection can be monitored by determining the amount of mRNA or protein of Stat1, Stat3, Stat4, Stat6, SOCS1, or SOCS3 present, e.g., in an affected tissue.

The present invention provides compounds, compositions and methods for the inhibition or treatment of conditions or disorders modulated by the STAT transcription factors, particularly STAT4 and STAT6. Additionally, the compounds are useful for the diagnosis of conditions dependent on STAT signaling.

The present invention belongs to the technical field of cell biology and particularly relates to a technology for regulating and controlling a Jak-Stat pathway to differentiate, dedifferentiate and rejuvenate cells, and an application of the technology. Rejuvenated cell products and/or cell products of different lineage types are obtained by small molecule compound combination, cytokine combination or recombinant protein combination, a gene editing technology and a transgenic technology to quantitatively and/or regularly regulate and control gene or protein targets of the Jak-Stat signaling pathways in cells. The provided technology for regulating and controlling the Jak-Stat signal pathway, and the product/derivatives of the cell product can be used for re-programming cells, tissues, organs and organisms, construct tissue engineering materials, repair damages of tissues and organs of mammals and the aged and degenerated tissues and organs, delay or reverse aging processes of the cells, tissues, organs and organisms, and can be used for immunoregulation of the cells, tissues, organs and organisms.

The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, inhibit the interaction of MUC1 with NF-κB or a STAT, and block inflammatory response mediated by NF-κB or STAT signaling.

The invention discloses an immune cell capable of simultaneously expressing a fusion protein of an intracellular truncated TGF-beta receptor and a cytokine intracellular stimulation domain and a chimeric antigen receptor on a cell membrane. The immune cell can enhance the proliferation capacity of the cell, reduce the influence of a tumor microenvironment, enhance the tumor killing activity of the CAR-T cell and reduce the depletion under the condition of receiving antigen stimulation, so that the negative regulation of the tumor microenvironment on the immune cell is weakened, the depletion of the immune cell is reduced, the tumor killing function of the immune cell is enhanced, and the inhibition of the tumor microenvironment on the immune cell is reduced; by combining with cell factor receptors, corresponding JAK and STAT signal channels are activated, the cells are induced to secrete various active substances such as IFN-gamma, perforin and granzyme, the growth of tumor cells is inhibited, the anti-tumor capability is enhanced, the killing function of immune cells is optimized, and the inhibition of a tumor microenvironment on the immune cells is reduced.

The present invention belongs to the field of virus immunology and particularly relates to new applications of Lpro protein and applications of an FMDV L gene deletion mutant strain. The present invention finds that the Lpro hinders JAK-STAT signal transduction in a dose-dependent manner. At the same time, a new function of the Lpro is discovered, i.e., intracellular components of a JAK-STAT pathway in cells are degraded in a lysosome-dependent manner through interaction with a specific region of STATs, rather than acting on the JAK-STAT signal transduction through classical protease activityof the Lpro. A protease activity center site of the Lpro of the FMDV is a key site participating in a lysosome degradation pathway. A protease activity center site of the Lpro is a key site of K48 ubiquitination of the Lpro. The new applications of the Lpro protein and the applications of the FMDV L gene deletion mutant strain provide new targets and theoretical supports for prevention and controland vaccine design of viruses of RNA viridae, such as viruses of foot-and-mouth diseases.

The invention provides an application of a combined STAT signal channel related gene in a colorectal cancer prognosis model. The combined STAT signal channel related gene is CAV1, EPO, IL13, LEP and NEUROD1. The establishment method of the colorectal cancer prognosis model comprises the following steps: (1) collecting and sorting data; (2) screening differentially expressed STAT signal pathway related genes; (3) constructing a prognosis model of the STAT signal pathway related genes; and (4) constructing a column diagram. The prognosis model has the advantage of high accuracy, can clinically provide a new method for disease diagnosis and prognosis for colorectal cancer patients, reveals the prediction effect of the prognosis model on tumor microenvironment, and provides important information for the development of targeted therapy.

The invention discloses an immune cell for expressing a cytokine receptor fusion type chimeric antigen receptor and application of the immune cell. A cytokine receptor fusion type chimeric antigen receptor is expressed on a cell membrane of the immune cell, and a cytokine receptor intracellular domain is fused in an intracellular domain structure of the cytokine receptor fusion type chimeric antigen receptor. The immune cell can enhance the proliferation capacity of the cell, reduce the influence of a tumor microenvironment and enhance the tumor killing activity of the immune cell under the condition of receiving antigen stimulation, so that the negative regulation of the tumor microenvironment on the immune cell is weakened, the exhaustion of the immune cell is reduced, and corresponding JAK and STAT signal channels are activated by combining with a cytokine receptor, the cells are induced to secrete various active substances such as IFN-gamma, perforin and granzyme, so that the growth of tumor cells is inhibited, the anti-tumor capability is enhanced, and the inhibition of a tumor microenvironment on immune cells is reduced.

The invention discloses an application of a pueraria flower extract in preparation of drugs for preventing, treating and relieving inflammatory bowel diseases, protecting intestinal barriers and stabilizing intestinal morphology, provides a reliable anti-inflammatory agent to help to maintain the balance of the intestinal environment, and has the advantages of good curative effect on the inflammatory bowel diseases, low price and no obvious side effect. The invention finds and verifies that the pueraria flower extract has a remarkable curative effect on inflammatory bowel diseases, is low in price and side effect, and can macroscopically improve the intestinal inflammation state by improving the body health level, reducing the intestinal permeability, prolonging the intestinal length and the like. The pueraria flower extract can relieve excessive proliferation and differentiation of precursor cells caused by exogenous proinflammatory factors by negatively regulating an important factor, namely a JAK-STAT signal channel, of a colitis pathogenesis and maintain the homeostasis of intestinal cells, so that the effect of treating the inflammatory bowel disease is achieved.

PURPOSE: A method for sharing an e-mail address between a mobile terminal and a PC is provided to allow a mobile terminal and a PC to maintain a shared address book with respect to an e-mail address through a POP3 server. CONSTITUTION: A POP3 server(140) receives an initialization signal for socket connection from a POP3 terminal(110)(301) and transmits a preparation completion signal to the POP3 terminal(110)(302). The POP3 terminal(110) transmits a user ID to the POP3 server(140)(303). The POP3 server(140) transmits a user ID recognition signal to the POP3 terminal(110)(304). The POP3 terminal(110) transmits a PASS password to the POP3 server(140)(305). The POP3 server(140) processes a transaction state and transmits a password recognition ACK signal to the POP3 terminal(110)(306). The POP3 terminal(110) transmits an STAT signal to the POP3 server(140)(307). The POP3 server(140) processes the STAT signal and transmits information on the number and a size of the next messages to the POP3 terminal(110)(308). The POP3 terminal(110) transmits a request signal as to whether there is an e-mail address of a person called Steven to the POP3 server(140)(309). If there is an e-mail address of Steven, the POP3 server(140) searches the e-mail address of Steven and transmits a corresponding result to the POP3 terminal(110)(310). The POP3 terminal(110) transmits the e-mail address of Steven to the POP3 server(140) and the POP3 server(140) adds and registers the e-mail address of Steven(311).

The invention discloses naphthyl urea-piperazine compounds and a preparation method and application thereof.The naphthyl urea-piperazine compounds can remarkably inhibit activation of cell signal transduction JAKs/STATs signals under the low dosage, and the experimental results of a cell proliferation experiment, an immunoblotting experiment, a cell cycle experiment, a protein transfer membrane transport experiment, a cell invasion and migration experiment and the like show that the naphthyl urea-piperazine compounds have the advantages that the naphthyl urea-piperazine compounds can be used for remarkably inhibiting activation of cell signal transduction JAKs/STATs signals; the compound can specifically inhibit JAK2 signal activation and expression of downstream STAT3, CyclinD1, CyclinB1, MMP9 and other target genes, induce blocking of a cell cycle G1 phase and cell apoptosis, can significantly inhibit proliferation of breast cancer, liver cancer, lung cancer, colon cancer, leukemia, lymphoma, multiple myeloma, retinoblastoma and other tumor cell strains, and can be used for preparing drugs for treating breast cancer, liver cancer, lung cancer, colon cancer, leukemia, lymphoma, multiple myeloma, retinoblastoma and the like. Therefore, the compound has a prospect of being developed into a targeted anti-cancer drug of a related target spot of a JAKs/STATs cell regulation signal transduction pathway.

The invention described herein pertains to selective Janus kinase (JAK) inhibitors and methods of use thereof. Also described are methods for treating diseases involved abnormal JAK/STAT signaling pathway in mammals using the described selective JAK inhibitors or a pharmaceutical formulation thereof.

The role of the JAK/STAT signal transduction pathway cellular mechanisms that lead to the onset and progression of degenerative joint diseases or disorders such as osteoarthritis (OA) is disclosed. Certain known effective OA therapeutics such as hymenialdisine, debromohymenialdisine, and its variants and derivatives are shown to function as JAK3-specific inhibitors, which downregulate steady state mRNA levels of key cellular components involved in cartilage degradation. Another JAK3-specific inhibitor, not previously known as an OA therapeutic, is shown to downregulate steady state mRNA levels of various cellular components involved in cartilage degradation in a manner identical to that of the known OA therapeutics.

The invention discloses application of IL-6 in preparation of drug for treating lumbar disc herniation. The IL-6 regulates expression of TSLP by a JAK/STAT signal path, and the TSLP can promote infiltration of macrophages to intervertebral disc tissue by inducing expression increase of monoeyte chemotactic protein-1 (MCP-1) so as to promote the re-absorption process of the intervertebral disc tissue.

The invention discloses an ROSresponsive JAK3 covalent inhibitor prodrug and a preparation method thereof, and application to treatment of rheumatoid arthritis. The prodrug has a chemical structure shown in the specification. According to the JAK3 covalent inhibitor prodrug, the difference of ROS levels under physiological and pathological conditions is utilized and an active compound shown in a formula (1) in the prior art can be selectively released at an attacked part; and the prodrug has high membrane permeability, the anti-proliferation activity and the capability of regulating and controlling an STAT signal path and has the good treatment effect in a rheumatoid arthritis inflammation mouse model. The prodrug has extremely low toxicity in ICR healthy mice, so that covalent binding between JAK inhibitor molecules and thiol functional groups in various biomacromolecules or other normal physiological tissues is avoided. The prodrug can be used for preparing anti-rheumatoid arthritisdrugs.

The invention discloses a neuroprotection effect of biochanin A. The biochanin A achieves the neuroprotection effect through the regulatory mechanism of a growth hormone JAK/STAT signal path. The 125ng/ml of GH and 10<-5>mol/L of Bio A are used for stimulating a hippocampal neuron independently or jointly, combined medicine has a better effect for promoting cell reproduction of hippocampal neuronsthan that of a single medicine, when the Bio A at 10<-8>mol/L acts for 60 minutes, the cell SOCS2 protein has the most remarkable expression difference. Combined administration of the Bio A and GH can remarkably increase the expression level of STAT5 and P-STAT5 proteins, and further, administration of treating the Bio A 60 minutes earlier than treating the GH can cause up-regulation of the expression level of the STAT5 and P-STAT5 proteins more than simultaneous administration of the Bio A and GH; and the expression level of SOCS2 protein can be down regulated.