287 results about "Pyroptosis" patented technology

The invention belongs to the technical field of biological medicine, and particularly relates to application of magnoflorine in preparation of a product for preventing / treating liver injury. The invention discusses the protective effect and mechanism of magnoflorine on MTX hepatotoxicity for the first time, and magnoflorine regulates ROS accumulation and mPTP permeability through targeting GSK3beta to inhibit pyroptosis of hepatocytes so as to reduce MTX hepatotoxicity. A new target and a new choice are provided for the prevention and treatment of MTX hepatotoxicity, and a research foundation is laid for the research of a new magnoflorine component liver-protecting drug.

The invention relates to an astragaloside-loaded astragalus membranaceus exosome which is prepared by the following steps: crushing astragalus membranaceus, and filtering to obtain juice; performing multi-step differential centrifugation to obtain supernate; carrying out ultrafiltration and centrifugation, and collecting the precipitate; adding to the upper layer of a sucrose stepped gradient solution, centrifuging, and collecting part of strips; after dilution, centrifuging, discarding the supernatant, precipitating, and removing cane sugar to obtain the astragalus membranaceus exosome; the radix astragali exosome loaded with the astragaloside is obtained by mixing the radix astragali exosome with the astragaloside and carrying out ultrasonic treatment or co-incubation, and can be used for preparing medicines for specifically inhibiting cGAS / STING pathway excessive activation in cerebral ischemia reperfusion injury and downstream NLRP3 inflammasome mediated pyroptosis and preparing medicines for protecting and repairing mitochondria in the cerebral ischemia reperfusion injury. The homologous astragalus membranaceus exosome is used as a natural carrier, the blood-brain barrier is effectively overcome, and the enrichment concentration and bioavailability of astragaloside in a cerebral ischemia area are remarkably improved.

The invention discloses application of mangiferin in preparation of a protective agent for testicular sertoli cells and preparation of a medicine for treating male infertility diseases, and relates to the technical field of medicine application. Wherein the mangiferin can play a role in protecting the sertoli cells, and the protection role is reflected in ways of improving the cell viability of the sertoli cells, inhibiting the apoptosis of the sertoli cells, inhibiting the oxidative stress of the sertoli cells, inhibiting the inflammatory response of the sertoli cells and the like; meanwhile, mangiferin can be used for treating male infertility diseases in ways of relieving weight loss, repairing testis, improving endocrine system functions, inhibiting oxidative stress of testis tissues, inhibiting inflammatory response of the testis tissues and the like. Wherein the mangiferin can inhibit the inflammatory reaction mainly by inhibiting the activation of NLRP3 inflammasome to inhibit the NLRP3 pathway, so that the inflammation and even pyroptosis of testicular sertoli cells are remarkably reduced to improve spermatogenesis, and the male infertility disease is well treated.

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to application of Xianglian intestine decoction in preparation of a medicine for treating ulcerative colitis through a targeted TLR4 / NLRP3 / GSDMD channel. According to the invention, the TLR4 is determined as a key target, and experiments show that the active ingredients in the Xianglian intestine soup and the TLR4 have very strong binding affinity. In-vivo experiments prove that the Xianglian intestine soup down regulates the protein levels of TLR4, NLRP3 and GSDMD-N and the mRNA expression (Plt; 0.05) of IL-1beta and IL-18, so that the pyroptosis is inhibited. Furthermore, the Xianglian intestine decoction inhibits NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by targeting TLR4 so as to relieve UC inflammation and intestinal barrier injury. The invention provides a mechanism insight for the clinical curative effect of the Xianglian intestine decoction for treating ulcerative colitis.

The invention discloses application of lycium barbarum polysaccharide in preparation of a medicine for inhibiting methylamphetamine-induced nerve injury, and relates to the technical field of biological medicines. It is found and proved that lycium barbarum polysaccharide can inhibit methylamphetamine-induced nerve injury, and the effect is remarkable. From the aspect of cell survival, the survival rate of the microglial cells pretreated by the lycium barbarum polysaccharide after METH stimulation is obviously improved. In the molecular mechanism, the lycium barbarum polysaccharide can effectively lower the protein expression level of the METH-induced pyroptosis marker, the content of inflammatory factors IL-1beta and IL-18 can be reduced, and the release of lactic dehydrogenase is reduced. The result shows that the lycium barbarum polysaccharide can alleviate inflammatory response by inhibiting NLRP3 / ASC pathway mediated microglial cell pyroptosis, thereby inhibiting METH-induced nerve injury. The invention provides a new direction for developing METH neurotoxicity intervention medicines.

The invention discloses a composition for enhancing cold resistance based on pyroptosis regulation and a preparation method thereof, and belongs to the technical field of biological medicines. The preparation method of the composition for enhancing cold resistance based on pyroptosis regulation comprises the following steps: S1, respectively preparing an angelica sinensis aqueous extract and an astragalus membranaceus aqueous extract; and S2, mixing the angelica sinensis aqueous extract and the astragalus membranaceus aqueous extract according to the mass ratio of 1: (4-20) to obtain the composition for enhancing cold resistance based on pyroptosis regulation. The invention further provides a composition obtained based on the preparation method, a preparation and application. The composition provided by the invention can significantly prolong the survival time of acute cold exposure mice; the core body temperature of an acute cold exposure mouse is obviously improved, liver injury is relieved, and liver tissue cell pyroptosis pathway protein expression is regulated.

The invention relates to application of epalrestat in preparation of a medicine for treating spinal cord injury, and belongs to the technical field of biological medicine. The invention provides a novel pharmaceutical application of epalrestat, namely an application of epalrestat in preparation of a medicine for treating spinal cord injury. It is found for the first time that epalrestat can reduce the pyroptosis level of neurons after spinal cord injury by inhibiting an aldose reductase mediated NOX4 / ROCK / Poldip2 oxidative stress pathway, and it is proposed that epalrestat is used for preparing the medicine for treating spinal cord injury. Animal model experiments prove that after epalrestat gavage treatment, AR expression of a mouse spinal cord injury area and pyroptosis of neurons are remarkably reduced, and the motor function and nerve injury of a mouse are remarkably improved. The application of the epalrestat-containing medicine in clinical treatment of spinal cord injury is expected to provide benefits and help for improvement of prognosis of patients.

The invention discloses a drug-loaded polymer, an STAT3 inhibitor composite nanoparticle, a preparation method of the STAT3 inhibitor composite nanoparticle and application of the STAT3 inhibitor composite nanoparticle in ophthalmic drugs. The STAT3 inhibitor composite nanoparticle comprises the drug-loaded polymer, an STAT3 inhibitor loaded on the drug-loaded polymer and thermosensitive lipidosome. The drug-loaded polymer is astaxanthin macromolecules, and the astaxanthin macromolecules are prepared by the following steps: in an inert atmosphere, performing condensation polymerization on astaxanthin and HPMDA, and then performing end capping reaction by using mPEG-OH. The compound is used for treating retinal neuron progressive death and ophthalmic diseases caused by axon loss of the retinal neuron progressive death, can show good ROS response and consumption performance, inhibits necrotic apoptosis, apoptosis and pyroptosis of cells, relieves cell death performance, and can show good drug slow release performance.

The invention provides an SLC25A4 gene as well as an interferent and application thereof, and relates to the technical field of biomedicine. The SLC25A4 gene interferent is injected into a mouse body and is continuously released, so that the processes of mitochondrial injury and pyroptosis are inhibited, and the myocardial fibrosis and cardiac remodeling after myocardial infarction are reduced.

The invention discloses an engineered exosome for breaking through a pyroptosis immune starting and maintaining barrier as well as a preparation method and application of the engineered exosome. The exosome is constructed by loading an immune checkpoint inhibitor into a pre-stimulated exosome, and the exosome is derived from immune cells, high-expression interferon gamma and granzyme A. The expression of the tumor cell GSDMB is up-regulated by delivering the interferon gamma through the exosome, and the exogenous granzyme A cuts the GSDMB to trigger pyroptosis; meanwhile, an immune checkpoint inhibitor blocks a PD-1 / PD-L1 pathway in situ, T cell depletion is reversed, and release of endogenous granzyme A is promoted; the pyroptosis cells release antigens to activate the T cells, the activated T cells continuously secrete granzyme A / interferon gamma to form a cascade amplification effect, and the problem of double barriers existing in the pyroptosis immune cycle of granzyme A-GSDMB is solved. The engineered exosome can improve the infiltration degree of CD8 + T cells, and is suitable for treating tumors such as liver cancer and non-small cell lung cancer.

Provided are a compound of formula (I) or a tautomer, enantiomer, diastereomer, isotope-labeled compound, solvate, or pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof, and use thereof in the preparation of a drug for preventing and treating pyroptosis-related autoimmune diseases, infections, and non-infectious diseases.

The application provides a group of small interfering RNAs (siRNAs) targeting pyroptosis-related inflammatory reaction genes and application thereof. The pyroptosis-related inflammatory reaction genes include IL1A, IL1B, IL6, HMGB1, S100A8, S100A9 and BACH1. The application designs and synthesizes specific siRNA sequences for the above genes, and verifies that the siRNAs can efficiently and specifically inhibit the mRNA expression level of the corresponding genes through cell transfection and real-time fluorescent quantitative PCR. The application also provides a composition containing the siRNAs, a pharmaceutical composition and application thereof in the preparation of a drug for treating diseases mediated by pyroptosis-related inflammatory reaction genes (especially inflammatory diseases). The siRNAs and the composition thereof provide a new effective strategy for treating diseases related to excessive activation of pyroptosis-related inflammatory reactions, and have a wide application prospect.

The present invention discloses the use of a BCL3 inhibitor in the preparation of a drug for treating glaucoma. The present invention discovers the role of the BCL3 / NF-κB / NLRP3 signaling pathway in glaucoma and demonstrates that BCL3 inhibitors (such as JS-6) have never been reported to reduce retinal ganglion cell apoptosis and pyroptosis, and are therefore useful in treating glaucoma-related diseases.

The invention discloses application of cucurbitacine I in preparation of cisplatin sensitization drugs for treating ovarian cancer, and belongs to the technical field of sensitization drugs for tumor chemotherapy. CuI and CDDP have a good synergistic tumor inhibition effect on ovarian cancer, CuI may directly act on EGFR and can be combined with CDDP to significantly inhibit phosphorylation of EGFR and downstream STAT3 protein thereof, induce DNA damage and ROS accumulation, amplify a pyroptosis effect, increase release of TAAs and DAMPs, promote DC maturation and promote infiltration of CD8 + T cells and memory T cells in TIME in vivo, so that the tumor inhibition effect on ovarian cancer is improved. The expression of an inhibitory costimulatory molecule PD-1 in CD8 + T cells is reduced, the whole body immune effect is activated, and the TIME of the ovarian cancer is remarkably improved. The combined treatment strategy of CuI-CDDP controls the progress of ovarian cancer from a dual mechanism of directly inhibiting tumor cells and promoting anti-tumor immune activation.

The invention discloses an application of a coix seed extract in preparation of a medicine for preventing and treating acute lung injury. The semen coicis extract is obtained by performing reflux extraction on semen coicis by using ethanol, recovering an extraction solvent by using a rotary evaporator and then performing evaporation concentration by using a water bath. The coix seed extract can obviously increase the thymus index, improve the pathological injury of lung tissues, reduce the level of inflammatory factors in serum and lung tissues, possibly inhibit the expression of NLRP3, Caspase-1 and GSDMD-N in NLRP3 signal channel key proteins in the lung tissues, inhibit the NLRP3 signal channel, inhibit inflammation and pyroptosis, and play a role in protecting ALI. The coix seed extract can inhibit the activation of an NLRP3 signal channel and play a role in treating the acute lung injury disease.

The invention provides a diagnosis and treatment integrated nano platform as well as a preparation method and application thereof. According to the diagnosis and treatment integrated nano platform, an organic-inorganic nano hybrid is constructed through structure optimization and function integration, four modes of PTT, PDT, SDT and CDT are organically combined innovatively, and efficient synergistic treatment of GBM is achieved through real-time monitoring of photoacoustic imaging. First, a dOMV encapsulation strategy significantly improves the ability to penetrate through the blood brain barrier. Meanwhile, the IEICO-4F has a strong near-infrared absorption characteristic and has a synergistic effect with the high catalytic activity of the mesoporous platinum nanoparticles. Under the laser / ultrasonic excitation condition, the diagnosis and treatment integrated nano platform shows excellent photo-thermal conversion performance, the Fenton reaction rate can be increased, endogenous hydrogen peroxide can be continuously catalyzed to be decomposed to generate oxygen, and the tumor hypoxia state is effectively relieved. The series of reactions further enhance the generation of ROS, activate a Caspase-1 / GSDMD mediated pyroptosis pathway, finally achieve an efficient tumor inhibition effect, and successfully break through the limitation of a single treatment mode.

The disclosure belongs to the technical field of medicine. Provided are a CD97 and GSDME interaction inhibitor having anti-tumor activity and an application thereof. A compound screened in the disclosure enhances the susceptibility of NK cells to kill tumor cells by inhibiting the interaction between GSDME and CD97 in tumor cells, so as to induce an immune anti-tumor effect. Moreover, the compound enhances the susceptibility of tumor cells to pyroptosis by blocking the protective effect of CD97 on cleavage of GSDME proteins. Therefore, the compound can be used for treating GSDME and CD97 double-positive malignant tumors, and combined chemotherapy, immunotherapy, etc., to enhance the susceptibility of malignant tumors to chemotherapy and immunotherapy, prolonging the overall survival period of patients with malignant tumors. Specifically provided is a compound having a structure set forth in formula (I), a pharmaceutically acceptable salt, a solvent compound or a deuterated compound thereof.

The application relates to the field of biological medicine, and particularly discloses application of a sophora japonica extract in preparation of a product for improving the reproductive performance of ewes. The sophora japonica extract can effectively inhibit pyroptosis of ovarian granulosa cells by down-regulating expression of cysteine protease B, further reverses follicle atresia and ovulation disorders caused by pyroptosis, and improves the reproductive performance; animal experiments show that the sophora japonica extract can optimize the follicle development structure of ewes, inhibit overdevelopment of large follicles, and significantly improve the ovulation efficiency, thereby providing a new scheme for inhibiting pyroptosis of ovarian granulosa cells and improving the reproductive performance of livestock.

The invention discloses a lung adenocarcinoma prognosis and immune infiltration related prediction model. By deeply mining data in TCGA and GEO databases, a prognosis model based on eight pyroptosis related genes is constructed, and compared with a traditional method, the five-year survival prognosis of a lung adenocarcinoma patient can be more accurately predicted. A verification result shows that the model has relatively high accuracy (AUC = 0.687) in prediction of the total survival of one year, and through Kaplan-Meier analysis and Log-Rank inspection, survival differences of patients in high and low risk groups in a training set and a verification set are remarkably distinguished. The research method and the model have strong universality, provide important reference for research and application of a pyroptosis related mechanism in other cancer types, promote the progress of the oncology field in the research related to the pyroptosis mechanism, and have wide clinical application value.

The invention discloses a marsdenia tenacissima extract as well as a preparation method and application thereof, and belongs to the technical field of medicines. The marsdenia tenacissima extract is Marsdenside A or Marsdenside C, and the structural formulas of the marsdenside A and the Marsdenside C are respectively shown as a formula I and a formula II. Marsdenside C can induce ferroptosis and inhibit liver cancer, and the liver cancer is liver cancer caused by HepG2 or Huh7 cells; the Marsdenside A induces pyroptosis to play a role in inhibiting the gastric cancer, and the gastric cancer is caused by HGC-27 or AGS cells, so that the Marsdenside C can be used for preparing the medicine for resisting the liver cancer, and the Marsdenside A can be used for preparing the medicine for resisting the gastric cancer.

The invention belongs to the technical field of organic-inorganic compounding, and aims to solve the problem of treatment of temporomandibular joint osteoarthritis (TMJOA). Magnesium-gallic acid metal organic framework (Mg-GA MOF) particles are synthesized through a hydrothermal method, hyaluronic acid is subjected to hydroformylation and double-bond modification to obtain OHAMA, and the magnesium-gallic acid metal organic framework (Mg-GA MOF) particles and the OHAMA particles are compounded to prepare the MOF-Gel composite hydrogel. The hydrogel is injectable and high in tissue retention rate, has dual effects of inhibiting pyroptosis and promoting regeneration on condylar cartilage cells, can effectively promote cartilage repair, shows a good effect in TMJOA treatment, and has a wide application prospect.

The invention relates to an application of an MYOF protein in preparation of a product for preventing, relieving and / or treating acute lung injury. According to the application, the MYOF protein can be combined with GSDMD-NT, and up-regulation of expression of the MYOF protein can effectively inhibit activation of GSDMD and pyroptosis mediated by GSDMD, so that the MYOF protein has an application prospect in preparation of products for preventing, relieving and / or treating acute lung injury, and the technical problem that alveolar epithelial barriers are easily damaged during treatment can be solved.

The invention provides a method for treating autoimmune diseases mediated by regulatory T cell (Treg) programmed necrosis. Specifically, the invention provides application of an O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) accelerant, and the O-linked beta-N-acetylglucosamine glycosylation accelerant is used for preparing a medicine or a preparation for treating programmed necrosis type autoimmune diseases. It is found for the first time that when the O-GlcNAcylation promoter is used for improving the O-GlcNAcylation level of RIPK1 / 3 protein, Treg programmed necrosis can be effectively inhibited, and therefore autoimmune diseases are improved.

This invention discloses the application of American ginseng glycoprotein extract in the preparation of drugs for treating alcoholic liver disease, belonging to the field of biomedical technology. This invention verifies that TD can significantly reduce serum ALT, AST, and TG levels in ALD mice, effectively reducing liver damage and lipid accumulation; inhibit NLRP3 protein expression and its downstream targets, effectively alleviating liver inflammation and pyroptosis; and improve intestinal flora imbalance in ALD mice. American ginseng glycoprotein extract has multi-target protective effects against alcoholic liver disease, reducing alcohol-induced liver tissue inflammation and oxidative stress damage. It has a mild composition and high safety profile, and can synergistically exert effects in liver protection, anti-inflammation, and antioxidation, making it suitable for adjunctive intervention and long-term management of alcoholic liver disease, providing a natural, mild, and effective protective pathway for alcoholic liver damage.

A small molecule compound DHN and a preparation method and application thereof relate to the technical field of biological medicine.The compound DHN can induce the opening of a mitochondrial membrane permeability transition pore (mPTP), promote the release of mitochondrial DNA (mtDNA) into the cytoplasm, activate a cGAS-STING signal pathway, cut pyroptosis execution protein GSDME, induce pyroptosis death of melanoma cells, and provide a new target and a lead compound for the treatment of melanoma.

The invention provides an application of a heat shock protein 90 inhibitor in preparation of a medicine for treating intestinal injury and complicated intestinal inflammation thereof. The HSP90 inhibitor is suitable for treating colon tissue injury caused by a medicine for inducing Gasdermin E (GSDME) mediated pyroptosis. The HSP90 inhibitor specifically inhibits the expression of GSDME protein in normal intestinal epithelial cells and reduces the sensitivity of the normal intestinal epithelial cells to drug-induced GSDME-mediated pyroptosis, so that the damage to colon tissues is relieved, and the induced inflammatory response of the colon tissues is effectively inhibited. TAS-116 and BIIB021 are used as representative drugs of the HSP90 inhibitor, 4 mg / kg of TAS-116 and BIIB021 are used for a mouse colon injury model constructed by 5-FU and CDDP, and the result shows that the HSP90 inhibitor can obviously improve weight loss and colon tissue injury of mice caused by the drugs, and has a good application prospect. Therefore, the HSP90 inhibitor has remarkable curative effect and application value in the aspect of relieving or preventing and treating intestinal injury caused by drugs.

The invention provides application of lncMCL1 in regulating and controlling the pyroptosis degree of neuronal cells and relieving and treating related diseases, and relates to the technical field of biological medicine. The invention specifically discloses regulation and control of pyroptosis of neuronal cells by enhancing or reducing expression of lncMCL1, and further discloses application of a substance for regulating and controlling expression enhancement of lncMCL1 in preparation of drugs for relieving and treating neuronal function deficiency related diseases, especially epilepsy. In-vivo experiments and in-vitro experiments prove that lncMCL1 can be used as a key regulatory factor for pyroptosis of neuronal cells by regulating inflammatory response of the neuronal cells, and can effectively regulate pyroptosis of the neuronal cells and relieve and treat diseases related to neuronal function deficiency.

The application provides application of Trapidil in preparation of a drug for preventing and / or treating doxorubicin-induced organ toxicity, and belongs to the technical field of biological medicines.The application discloses that Trapidil plays an organ protection role by activating a cAMP / PKA / CREB signal axis and driving two parallel downstream effect channels: on the one hand, up-regulating an NRF2-GPX3 positive feedback loop to inhibit doxorubicin-induced myocardial cell pyroptosis and glomerular podocyte pyroptosis; and on the other hand, activating an NRF2 / HO-1 channel to inhibit myocardial cell apoptosis and glomerular podocyte apoptosis.In-vivo and in-vitro experiments prove that Trapidil can improve doxorubicin-induced cardiac dysfunction and kidney function damage, reduce histopathological damage, reduce the level of oxidative stress, inhibit the pyroptosis and apoptosis of myocardial cells and glomerular podocytes, and does not affect the antitumor effect of doxorubicin.The application provides a new drug strategy for doxorubicin chemotherapy-induced multi-organ toxicity.

The invention belongs to the technical field of biological medicines, and particularly relates to application of chenodeoxycholic acid in preparation of drugs for treating allergic diseases. It is found that CDCA can effectively inhibit pyroptosis and secretion of proinflammatory factors, expression of complement inhibition proteins CD46, CD55 and CD59 is remarkably up-regulated, expression of the complement inhibition proteins CD46, CD55 and CD59 is finally promoted, and occurrence and development of allergic diseases are effectively relieved. In a mouse model, CDCA can significantly improve OVA-induced food allergy symptoms, and has application prospects in treatment of allergic diseases.

The present application belongs to the technical field of coordination chemistry and biomedical science, and provides a multifunctional iridium (III) complex, a preparation method and application thereof. The multifunctional iridium (III) complex (Mito-Ir) is composed of an iridium (III) complex cation and a coordination anion shown in the following formula. Mito-Ir can efficiently target mitochondria, and also has the abilities of phosphorescence imaging, type I and type II active oxygen generation, and photocatalytic oxidation of nicotinamide adenine dinucleotide. Under light irradiation, Mito-Ir triggers severe mitochondrial dysfunction through the above synergistic effect, and then specifically activates the caspase-3 / GSDME signaling pathway, and significantly induces pyroptosis; this pyroptosis-based cell death mechanism can effectively overcome the apoptosis tolerance of tumor cells, and is accompanied by the release of a large amount of inflammatory factors and damage-associated molecular patterns, stimulates immunogenic cell death, and activates the body's anti-tumor immune response.