95 results about "Pyroptosis" patented technology

The invention relates to a reagent (ii) ROS inducing agent comprising (i) iron ions or a drug composition of a combination of a pharmaceutically-acceptable salt thereof and application in treating tumors. The drug composition can cause the pyroptosis of tumor cells, can inhibit the growth and transfer of the tumor, and can be used as a candidate drug for treating the tumor.

The invention relates to a pre-stimulating stem cell as well as a preparation method and application thereof. The preparation method comprises the following steps of selecting non-target stem cells asauxiliary cells; inducing the auxiliary cells for pyroptosis; obtaining pyroptosis cells, secreta of pyroptosis cells and / or extracts of the pyroptosis cells for culturing stem cells. The preparationmethod provided by the invention can be used for obtaining the stem cells prestimulated by the secreta of the pyroptosis cells; the stem cells can adapt to the natural inflammatory environment; the restoration capability of the stem cells on the damage region can be improved; the method belongs to new breakthrough in the seed material pretreatment in the tissue engineering field; meanwhile, a feasible scheme is provided for pre-stimulating stem cells and solving the problem of clinic disease treatment.

The invention discloses application of evodiamine and rutaecarpine in preparation of a medicine for enhancing the activation of NLRP3 inflammasomes. The evodiamine and the rutaecarpine can generate active Caspase-1 by enhancing activiation of macrophage inflammasomes so as to release manure inflammatory mediators such as IL-1beta and promote pyroptosis of sensitized macrophages. The activity of the evodiamine and the rutaecarpine can be used for enhancing the inflammatory response intensity of a human body and treating related diseases of insufficient activation of inflammasome including pulmonary tuberculosis and oral tuberculosis caused by intracellular infection of mycobacterium tuberculosis, diseases caused by listeria monocytogenes, related diseases caused by other intracellular infection bacteria, related diseases caused by pathogenic fungal infection, furunculosis, dental-root periapical diseases, chronic gastritis, chronic enteritis, dysentery and diarrhea and the like.

The invention discloses application of pyroptosis-associated protein GSDMD (Gasdermin-D) for preparing a bacterial ghost vaccine. A bacteriolysis plasmid containing a pyroptosis-associated protein GSDMD coding gene is constructed and is converted into salmonella enteritidis; under the induction of gum sugar, bacteria are split to successfully obtain a salmonella novel bacterial ghost vaccine. An experiment proves that GSDMD mediated bacteriolysis has an extremely long persistent period, and a splitting rate is 99.9985% or more. After a novel bacterial ghost immune mouse prepared by the invention is adopted, an organism can be stimulated to generate powerful humoral immunity and cellular immunity; protective immunity response is induced; an experiment animal can be protected so as to resistsalmonella infection. The salmonella bacterial ghost vaccine prepared by the invention has a good immune protection effect.

The invention belongs to the field of nanomedicine and relates to a preparation method of a light-controlled tumor pyroptosis system. An up-conversion long afterglow luminescent material is selected as a light supply factor; and the light-controlled tumor pyroptosis system is combined by using a pyroptosis sensitive plasmid A (Cry2-GSDMD-CAAX) and an accessory protein plasmid B (Cib-Caspase-1). The preparation method of the light-controlled tumor pyroptosis system comprises the steps of (1) preparing a mesoporous silica (mSiO2) template; (2) preparing near-infrared-excited up-conversion long afterglow nanoparticles (mUPLNs) by adopting a template method; (3) modifying a gene targeting delivery vector; (4) establishing precursor genes Cib-GSDMD-CAAX and Cry2-Caspase-1 for light control; and(5) after expression of the plasmids A and B, mixing the plasmids A and B with the up-conversion long afterglow luminescent material exposed to near-infrared light to induce pyroptosis.

The invention relates to the technical field of medicines, in particular to an application of a bromodomain protein 4 (BRD4) inhibitor JQ1 or a derivative thereof in preparation of a medicine for treating sepsis intestinal barrier injury. Experiments show that in a lipopolysaccharide (LPS)-induced sepsis mouse intestinal barrier injury model, the BRD4 inhibitor JQ1 can effectively inhibit LPS-induced sepsis mouse intestinal mucosa damage, release of inflammatory factors TNF[alpha], IL1[beta] and IL18, release of NLRP3 complex inflammasome, and high expression of pyroptosis marker genes GSDMD,GSDME, P2X7 and Aim2. Results show that the BRD4 inhibitor JQ1 can effectively prevent the sepsis mouse intestinal barrier injury by inhibiting intestinal tissue cell pyroptosis, and can be used for preparing a pharmaceutical preparation for treating the sepsis intestinal barrier injury.

The invention discloses an organelle targeting photosensitizer capable of activating pyroptosis of tumor cells and a preparation method and application thereof. The Mito-ZS photosensitizer is a mitochondrial targeting photosensitizer; the Lyso-ZS photosensitizer is a lysosome targeting photosensitizer; the ER-ZS photosensitizer is an endoplasmic reticulum targeting photosensitizer. The photosensitizer activates a pyroptosis pathway by performing precise targeting therapy on organelles in tumor cells so that photodynamic therapy and immunotherapy strategies are perfectly combined, and the photosensitizer has a wide application prospect in the field of cancer therapy.

The invention discloses application of GL-V9 in preparation of a medicine for preventing and / or treating sepsis. Compared with the prior art, it is found that in an in-vitro experiment, the GL-V9 can be used for remarkably recovering J774A.1 cell viability decline and increased cytotoxic damage caused by two ways of transfecting lipopolysaccharide (LPS) into macrophages by lipidosome 2000 and infecting the macrophages by Escherichia coli to cause pyroptosis, and inhibiting the expression condition of the pyroptosis related protein mediated by the Caspase-11. In in-vivo experiments, the GL-V9 can reduce the death rate of cecum ligation paracentesis (CLP) sepsis model mice, weaken organ function damage and inhibit release of inflammatory factors. The effects show that the GL-V9 can be used for treating sepsis and has a medicine development prospect.

The invention belongs to the field of medicine, and relates to application of dehydronitrosonisoldipine (NTS) in preparing drugs for sepsis prevention and treatment, wherein the sepsis includes endotoxemia and multi-bacterial infectious sepsis. A particular mechanism involves the inhibition of pyroptosis by NTS. The drugs in the application refer to an intraperitoneal injection, and a dosage of the injection is within a range of 14.8 to 44.4 mg / kg ( body weight). In a septic mouse model, the drugs can inhibit the expression of plasma inflammatory factors, prolong the survival time of a mouse and raise the survival rate of the mouse.

The invention relates to application of triclabendazole in preparation of drugs for treating breast cancer. According to the application of the triclabendazole in the preparation of the drugs for treating the breast cancer, the drugs for treating the breast cancer are tablets, granules, pills or capsules. Application of a triclabendazole composition in the preparation of the drugs for treating thebreast cancer is also included. Cancer cells of the to-be-treated breast cancer are MCF-7 or MDA-MB-231. The application has the advantages that the triclabendazole can induce apoptotic pyroptosis invitro and in vivo, and GSDME is cut by activated caspase-3 to generate GSDME-NT that take effects and forms vacuoles; the discovery suggests that the triclabendazole plays a role in cancer treatmentby inducing apoptosis of the cancer cells, specifically inducing GSDME-dependent apoptosis through the activated caspase-3 and at least partially through enhanced ROS / JNK / bax mitochondrial apoptosis pathways.

The invention belongs to the technical field of medicine, and particularly relates to novel application of Plerixafor in preparation of drugs for treating or preventing diseases related to GSDMD protein. The affinity between Plerixafor and the human GSDMD protein is detected through an MST technology, and the effects of Plerixafor on the mortality of macrophages of humans and mice and secretion amount of IL-1 beta inflammatory factors and the control effect of Plerixafor on mouse EAE and mouse sepsis are evaluated through pharmacodynamic tests. It is shown that the mortality of macrophages ofhumans and mice can be reduced significantly by Plerixafor, secretion of the IL-1 beta inflammatory factors can be reduced, and Plerixafor has a high binding force on the human GSDMD protein; meanwhile, the symptoms of mouse EAE can be alleviated significantly, and the survival rate of sepsis model mice can be improved; and it is indicated that Plerixafor is a human GSDMD protein-targeting drug, the symptoms of MS and sepsis can be alleviated through prevention of cell pyrolysis and inflammatory factor release, and therefore Plerixafor can be used as novel and optional drugs for prevention ortreatment of MS, sepsis and other autoimmune diseases and infectious inflammatory diseases, and has a broad development and application value.

The invention discloses application of piperine in preparation of drugs for resisting pyroptosis and multiple organ injury. The invention is provided on the basis that an inventor of the invention firstly discovers that the piperine has effect of resisting pyroptosis and multiple organ injury. The inventor of the invention discovers that the piperine can remarkably inhibit pyroptosis induced by bacterial infection, release of LPS+ATP induced proinflammatory factors IL-1 beta and dangerous signal molecules HMGB1 is inhibited remarkably, and multiple organ injury caused by bacterial infection can be prevented effectively. At present, specific drugs which can effectively prevent pyroptosis and multiple organ injury which are induced by bacterial infection and fungal infection do not exist clinically. The application of the piperine in preparation of the drugs for preventing pyroptosis and multiple organ injury which are caused by infection has significance on clinical treatment of septicemia and the like, and can be used for developing associated drugs.

The invention discloses a caspase-3 inhibitor and a purpose. The caspase-3 inhibitor comprises two molecule forms, core function regions are respectively DMPD (aspartic acid-methionine-proline-aspartic acid) and DMLD (aspartic acid-methionine-leucine-aspartic acid) polypeptide fragments, and two ends are respectively subjected to chemical modification to be used for improving biological characteristics, activity and druggability of polypeptide. The inhibitor can directly be combined with active caspase-3 to restrain enzymic activity, and effectively restrain caspase-3 / PARP mediated apoptosis and apoptosis necrosis, and caspase-3 / GSDME mediated cell apoptosis. The caspase-3 inhibitor can be used for preparing cell death resistant relevant tool molecules or reagents, and powerful medicines for resisting cell death or histoorgan apoptosis relevant diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to an application of ellagic acid and metabolites thereof as natural inhibitors to preparation of an anti-pyroptosis medicine. The inventor finds that high glycolipid has a promotion effect on pyroptosis of pancreatic cells and liver cells, and expression levels of pyroptosis proteins GSDMD and GSDME in a pyroptosis signal path are increased, which indicates that pyroptosis plays a role in high-glucose and high-fat induced pancreatic and liver inflammatory reactions. GSDMD and GSDME mediated pyroptosis participates in diabetes pancreas and liver injury. It is found for the first time that the ellagic acid and intestinal tract metabolite uridine A thereof can inhibit GSDMD and GSDME mediated pyroptosis in an in-vivo experiment of a diabetic model mouse, and therefore, an anti-inflammatory protection effect on cells is achieved.

The invention relates to a method for inducing pyroptosis of lung adenocarcinoma NCI-H1299 cells through a traditional Chinese medicine monomer sodium new houttuyfonate, and belongs to the field of traditional Chinese medicine monomer application, sodium new houttuyfonate promotes the lung adenocarcinoma NCI-H1299 cells to release inflammatory factors IL-1beta and IL-18, inflammasome NLRP3 is used as a mediation, and through ASC protein oligomerization, caspase1, IL-1beta and GSDMD protein shearing, the classical path of pyroptosis is activated, thereby conducing pyroptosis of NCI-H1299 cells. The sodium new houttuyfonate can be used for inhibiting tumor growth of a lung adenocarcinoma model mouse caused by NCI-H1299 cells, so that the sodium new houttuyfonate is expected to be used as an active component for preparing the lung adenocarcinoma resisting medicine, and has obvious clinical application value.

The invention provides a tumor enzyme response type recombinant pyroptosis protein drug delivery system and an anti-tumor purpose thereof. Specifically, the invention provides fusion protein which hasthe structure, which is disclosed by Z0-Z1-Z2-Z3-Z4 (formula I), from the N terminal to the C terminal,wherein Z0 is an optional tag element, Z1 is an N structural domain element of pyroptosis protein, Z2 is a cell-penetrating peptide sequence element, Z3 is a peptide sequence element which can be specifically segmented by specific expression protease in a tumor microenvironment, Z4 is a C structural domain element of the pyroptosis protein, and "-" shows a peptide bond for connecting the above elements. In the fusion protein, the Z4 element can be specifically combined with the Z1 element toinhibit the activity of the Z1 element. The fusion protection of the invention shows good anti-tumor activity in in vitro and vivo experiments.

The invention discloses a packaging method for constructing an oncolytic adeno-associated virus oAAV-SP-GSDM-NT for expressing pyroptosis protein and application of the oncolytic adeno-associated virus oAAV-SP-GSDM-NT. According to the invention, oAAV-SP-GSDM-NT is packaged by utilizing SP and sf9 insect cells of mammal specific promoters, so that the expression of the pyroptosis protein with strong cytotoxicity in the packaging process is avoided, safe, efficient and high-titer oAAV-SP-GSDM-NT is successfully obtained, and the oAAV-SP-GSDM-NT enables various tumor cells to be subjected to pyroptosis in vitro, has a good tumor cell killing effect, and can be used for treating animal tumor models in vivo. The oAAV-SP-GSDM-NT and an immunomodulator are combined to form a combined medicamentfor treating tumors, the combined medicament has a more remarkable oncolytic effect on an animal tumor model than the single use of the oAAV-SP-GSDM-NT or the immunomodulator, and therefore, it indicates that the combined medicament for treating tumors has a very good tumor treatment application prospect.

The invention provides application of ligustilide in preparing a medicine for alleviating microglial cell damage, preventing and treating cerebral arterial thrombosis or repairing cerebral injury andbelongs to the technical field of biomedicines. Ligustilide can be adopted to alleviate microglial cell damage by inhibiting microglial cell pyroptosis and / or inhibiting activation of NLRP3 inflammasome, and furthermore, purposes of preventing and treating cerebral arterial thrombosis and repairing cerebral injury can be achieved.

The invention relates to the technical field of biological medicines, in particular relates to application of a GSDMD inhibitor in preparation of a medicine for treating helicobacter pylori infection,and aims to solve the problem that a death signalling pathway of neutrophile granulocyte after helicobacter pylori infection, in particular change of pyroptosis molecular mechanism, is unclear in theprior art. After the signalling pathway is definite, the condition that stomach helicobacter pylori infection can be treated by utilization of the GSDMD inhibitor can be prompted; the pyroptosis process of the neutrophile granulocyte infiltrated at the infection part is inhibited; therefore, the clinical existing antibacterial medicine combined therapy is replaced; and generation of the medicinetolerance is reduced.

The invention relates to the technical field of biomedicine, in particular to application of a product for detecting a TRPC6 gene or an expression product of the TRPC6 gene, more particularly application of the product for detecting the TRPC6 gene or the expression product of the TRPC6 gene in preparation of a tool for diagnosing type 2 diabetes mellitus. The type 2 diabetes mellitus is caused by insular beta cell pyroptosis. The product comprises a product for detecting an mRNA level of the TRPC6 gene, a product for detecting a protein level of the TRPC6 or a product for detecting a DNA methylation level of a promoter region of the TRPC6 gene. According to the application, the correlation between the TRPC6 gene or the expression product thereof and insular islet beta pyroptosis and the type 2 diabetes mellitus is found for the first time, and research proves that the TRPC6 is highly expressed in the insular beta pyroptosis caused by homocysteine, so that a theoretical basis is provided for early diagnosis and prognosis evaluation of the type 2 diabetes mellitus from a molecular level in the future, and the application has a great clinical significance.

The invention belongs to the field of medicines, and discloses application of piperine to preparing medicines for regulating AMPK immunometabolism pathways of immune cells. The piperine is used as an active constituent in the medicines for regulating the AMPK immunometabolism pathways of the immune cells. AMPK metabolism signal pathways of the cells can be changed when the immune cells are stimulated by inflammation such as bacterial infection, AMPK metabolism signal balance can be broken under stimulation effects of second signals of ATP (adenosine triphosphate) and the like, the activity can be subjected to sharp up-regulation, but the AMPK activity of the cells treated by the piperine can be inhibited, and the cells can be prevented from pyroptosis death. The application has the advantages that the piperine has definite AMPK immunometabolism pathway regulation activity and has important significance on preventing functional depletion of the cells in the aspect of cell immunometabolism repair.

The invention relates to application of dimethyl fumarate (DMF) in preparation of a medicine for inhibiting pyroptosis of macrophages induced by silicon dioxide crystals and a medicine for treating silicosis. The specific mechanism is that shearing of Gsdmd and Gsdme is remarkably inhibited at the same time, and release of inflammatory cytokines IL-1beta and IL-18 is inhibited. DMF has a function of inhibiting pyroptosis of macrophages induced by silicon dioxide crystals by inhibiting activation of Gsdmd and Gsdme, and has an effect of inhibiting lung inflammation and pulmonary fibrosis in a mouse silicosis model induced by the silicon dioxide crystals.

The invention discloses an application of an amide compound in preparation of a drug for treating sepsis. The structure of the amide compound is shown as follows: the amide compound can inhibit Caspase11 induced macrophage pyroptosis, can inhibit release of pro-inflammatory cytokines IL-1alpha and IL-1beta, and can inhibit macrophage pyroptosis by inhibiting GSDMD protein oligomerization. Therefore, the amide compound has a certain treatment effect on sepsis, and a novel treatment method and a novel treatment medicine are provided for clinical treatment of sepsis.

The present invention relates to application of alpha-NETA in the induction of cell death. In particular, the alpha-NETA has a very good death-inducing effect on tumor cells, particularly tumor cells of the reproductive system and the digestive system. The alpha-NETA can induce cells to rapidly die in a pyroptosis manner in a short time, and the required dosage is very low and is tens of times different from the dosage of conventional alpha-NETA.

The invention discloses an application of CY-09 in preparation of a medicine for resisting prosthesis wear particle induced osteolysis. Experimental results show that high-concentration CoCrMo wear particles can induce the increase of the level of reactive oxygen species (ROS) in macrophages, activate intracellular inflammasomes and secondary pyroptosis, generate various inflammatory factors including IL-18, IL-1[beta] and HMGB1, and promote the formation of an extracellular inflammatory microenvironment. After the CY-09 is added, the content of the inflammasomes in the macrophages stimulatedby the high-concentration wear particles is remarkably inhibited, and then the degree of macrophage inflammatory factor exocytosis can be reduced. In addition, the CoCrMo wear particles are implantedinto a model for skull subcutaneous induction of skull dissolution, then subcutaneous injection of the CY-09 is carried out to apply effective intervention, and in-vivo experiments further prove thatthe CY-09 has a remarkable inhibition effect on the osteolysis induced by the wear particles.

The invention belongs to the technical field of chemical biological materials, and particularly relates to a porphyrin tetraazacyclo-based light-operated pyroptosis material as well as a preparation method and application thereof. The light-controlled pyroptosis material provided by the invention is a porphyrin tetraazacyclo positive ion salt and a related metal complex material thereof, and has a rapid multi-band light-controlled pyroptosis property, the action wavelength can be maximally adjusted to a visible light range of 640nm, the damage of a light source to cells or organisms is greatly reduced, and meanwhile, the light penetrability is also enhanced; the feasibility is provided for the light-operated pyroptosis technology in the field of tumor treatment. The light-controlled pyroptosis material provided by the invention takes an aqueous solution as an environment, so that the light-controlled pyroptosis material is good in biocompatibility and non-toxic; the raw materials are cheap and easy to obtain, synthesis is simple, and large-scale commercialization is easy.

The present disclosure contemplates methods for identifying candidate compounds or gene products useful in treating or ameliorating bacterial, fungal or viral infections; or for treating or ameliorating cancers or tumors characterized by interruption of pyroptosis. Compositions, methods of making, as well as kits, which utilize such pharmaceutical composition are also contemplated.

The invention provides an application of tripdiolide in preparation of a medicine for preventing and / or treating NLRP3 inflammasome mediated inflammatory diseases. The structure of the tripdiolideis shown in the specification. The tripdiolide can effectively inhibit the assembly of the NLRP3 inflammasome so as to inhibit inflammatory reaction and pyroptosis, in addition, the tripdiolide is excellent in activity and low in toxicity, and a new solution is provided for the development of drugs for treating inflammatory diseases mediated by the NLRP3 inflammasome.

The invention discloses application of cinobufagin in a medicine for treating acute myelogenous leukemia. The cinobufagin is used for inducing swelling death of cells HL60 and THP-1 of an AML cell line, and meanwhile, massive secretion of inflammatory factors IL1beta and IL18 is caused. The invention indicates that the cinobufagin can induce inflammatory death in a classic pyroptosis form of the AML cells in a targeted mode, and also shows that the cinobufagin has a potential treatment effect on the AML.