95 results about "Pyroptosis" patented technology

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 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 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 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 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.