335 results about "Pyroptosis" patented technology

The invention relates to the field of biomedical materials, in particular to composite hydrogel as well as a preparation method and application thereof. The composite hydrogel prepared by the invention realizes step-by-step release and time sequence regulation of a polypeptide drug through the combined action of Gel-PBA and GelMA: the anti-inflammatory peptide (Ac2-26) is quickly released under the conditions of high ROS and low pH, so that inflammation and pyroptosis are reduced; osteogenic peptide (OGP) is continuously and slowly released, and osteogenic differentiation is promoted. The step-by-step release mechanism of the anti-inflammatory peptide and the osteogenic peptide can realize accurate drug release, and is helpful for synergistically regulating inflammation and promoting bone regeneration. The composite hydrogel is used as a biological medicine material, can realize timely anti-inflammatory effect and long-term osteogenesis in a complex pathological environment such as diabetic periodontitis, and has a good application prospect.

The invention relates to the technical field of medicines, and provides mitoxantrone-loaded ZIF-8 nanoparticles, a preparation method thereof and an application of the mitoxantrone-loaded ZIF-8 nanoparticles in tumor chemical-immunotherapy. Aiming at the defects of combined chemotherapy and immunotherapy clinically at the present stage, MIT ZIF-8 synthesized by a normal-temperature full-water-phase one-pot method is used as a novel chemical-immunotherapy scheme, and the capability of inducing cell immunogenic death of a chemotherapeutic drug mitoxantrone is enhanced by utilizing pyroptosis; the anti-tumor immune activation capability is enhanced while tumor cells are killed through chemotherapy, effective chemical-immune therapy is achieved, and the responsiveness of tumors to immune checkpoint inhibitor therapy is enhanced.

The invention discloses a system for controllably inducing pyroptosis of tumor cells and application of the system. The system comprises a red light activated Cre recombinase system and an expression vector of a GSDMDNT gene sequence of loxP flanking; the Cre recombinase system comprises: (1) an expression vector 1 containing a photosensitive protein PhyA gene sequence and a CreN59 sequence, and a connecting peptide located between the PhyA gene sequence and the CreN59 sequence; (2) an expression vector 2 containing a nucleoplasm shuttle protein FHY1 gene sequence and a CreC60 sequence, and a connecting peptide located between the FHY1 gene sequence and the CreC60 sequence; and (3) phycocyanobilin is contained. The system disclosed by the invention can be used for artificially and controllably regulating and controlling the expression of the cytotoxic gene GSDMDNT, so that directional and controllable pyroptosis induction is realized. The method can be applied to the fields of tumor therapy, gene therapy, cell biology and the like, and particularly has a wide application prospect in application scenarios requiring accurate control of gene expression.

The invention belongs to the field of tumor drug research, and particularly relates to a cell vesicle co-delivery system, an anti-tumor drug and application. The cell vesicle-like co-delivery system is constructed according to the following steps: co-transfecting a recombinant expression vector of tumor targeting protein or targeting peptide and a recombinant plasmid of circRNA of effector molecules related to pyroptosis to a tool cell, and collecting to obtain the cell vesicle-like co-delivery system, a recombinant expression vector of the tumor targeting protein or the targeting peptide contains a DNA sequence for coding MCP protein, and a recombinant plasmid of circRNA of an effector molecule related to pyroptosis contains a DNA sequence for coding MS2 protein. According to the cell vesicle co-delivery system provided by the invention, tumor cell death is directly induced by delivering the cell death related effector molecule RNA through the cell vesicles, the killing efficiency is high, the side effect is relatively small, and the problems of mass production and drug loading can be solved.

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 discloses an application of a pyroptosis inhibitor in preparation of a product for treating biliary atresia, the pyroptosis inhibitor 2-bromohexadecanoic acid has a certain treatment effect on biliary atresia mice, can significantly prolong the survival time of the mice, improve jaundice, improve the liver function of the mice, reduce the infiltration quantity of inflammatory cells around intrahepatic bile ducts, and can be used for treating the biliary atresia. A new potential target and a treatment strategy are provided for treatment of biliary atresia.

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 belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a tumor stem cell targeting plasmid based on a logic gating circuit, a nano-carrier and a preparation method and application of the tumor stem cell targeting plasmid and the nano-carrier. The tumor stem cell targeting plasmid provided by the invention comprises a first plasmid pGal4 and a second plasmid pUAS, a logic AND gate circuit based on protein degradation is designed by utilizing two transcription factors Sox4 and Maff specifically expressed by liver cancer stem cells, and only the liver cancer stem cells with Sox4 and Maff simultaneously highly expressed can express stable target protein GAL4; meanwhile, a target protein GAL4 of an AND gate circuit is set as a primary signal by utilizing a cascade amplification principle of signal transduction, and the signal is used for driving expression (secondary signal) of downstream GSDMD-N and immune activation factors and improving the expression quantity of GSDMD-N in liver cancer stem cells, so that specific pyroptosis of tumor stem cells is induced, and the effect of cancer immunotherapy is enhanced.

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 ternary carrier-free nanoparticle as well as a preparation method and application thereof. The ternary carrier-free nanoparticles comprise nanoparticles which are formed by the chlorine e6, the lonidamine and the RG108 through an intermolecular interaction force. The nanoparticles can improve effective absorption and accumulation of drugs in tumors, can induce tumor specific pyroptosis and immunogenic effect under laser irradiation, and can promote maturation of antigen presenting cells and recruitment and activation of cytotoxic T lymphocytes, thereby starting adaptive anti-tumor immunity.

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.

Disclosed herein include methods, compositions, and kits suitable for use in programmable cell death control. Compositions (e.g., nucleic acid compositions, synthetic protein circuits) provided herein can comprise one or more apoptosis polypeptides; and / or one or more pyroptosis polypeptides; and / or one or more input polypeptides. In some embodiments, expression of a synthetic protein circuit of the disclosure can induce, e.g., apoptosis and / or pyroptosis in a cell.

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 4-octyl itaconic acid liposome loaded nano-particles wrapped by a metal-phenolic aldehyde network coating. The nano-particles are used for adjusting a myocarditis microenvironment after acute myocardial infarction. The drug-loaded nanoparticle provided by the invention can be divided into a drug-loaded liposome inner core and a shell layer; the inner core is functionalized liposome nanoparticles loaded with 4-octyl itaconic acid, and the shell layer is a metal-phenolic network coating formed by self-assembly of tannic acid and Mn < 2 + >. The invention further provides application of the drug-loaded nanoparticles in preparation of drugs for treating inflammation causing myocardial injury. The tannic acid of the shell layer of the drug-loaded nanoparticle has high affinity to an extracellular matrix of cardiac muscle tissue, and the drug-loaded nanoparticle injected from caudal vein can be efficiently enriched to a myocardial injury area to play roles in inhibiting pyroptosis of cardiac muscle cells, regulating macrophage functions and remodeling a damaged myocarditis microenvironment; accurate, effective and safe acute myocardial infarction treatment is achieved.

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 relates to the field of biology and medicine, and discloses application of dapam nitrile in prevention and / or treatment of radioactive intestinal injury. The inventor of the invention finds that dapam nitrile can protect radioactive intestinal injury induced by ionizing radiation local irradiation, including improvement of tissue pathological injury, promotion of intestinal crypt cell regeneration, inhibition of intestinal cell apoptosis, improvement of intestinal cell pyroptosis and reduction of serum inflammatory factor level; therefore, the compound can be used as a potential medicine for preventing and / or treating radioactive intestinal injury.

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.