53 results about "Pyroptosis" patented technology

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 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.

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.

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.

This invention discloses a glycyrrhizic acid nanomedicine, its preparation method, and its applications, belonging to the field of biomedical nanomaterials technology. The glycyrrhizic acid nanomedicine is prepared by reacting ammonium glycyrrhizate and sodium oleate at a temperature of 15-40 °C. o Glycyrrhizate nanomedicine was prepared via a microemulsion method at temperature C. After entering tumor cells, the glycyrrhizate nanomedicine was rapidly degraded within the acidic lysosomes of the tumor cells, releasing a large amount of sodium. + The presence of glycyrrhizic acid ions and glycyrrhizic acid ions causes a surge in intracellular ion concentration and osmotic pressure, as well as the accumulation of glycyrrhizic acid within tumor cells. This induces pyroptosis in tumor cells and regulates the expression of proliferation-related proteins. Pyroptosis releases a large number of damage-associated molecular patterns (DAMPs) to trigger immune activation, while the regulation of proliferation-related protein expression inhibits tumor cell proliferation. Under the combined effect of these two factors, glycyrrhizic acid nanomedicines can not only activate the systemic anti-tumor immune response but also reduce tumor cell spread, thereby effectively inhibiting tumor growth and metastasis and enhancing the efficacy of tumor immunotherapy.

This invention relates to the fields of pharmaceuticals and nanomedicine, specifically disclosing the preparation of a dual-targeting liposome drug delivery system and its application in stroke. The dual-targeting liposome drug delivery system comprises neutrophils, artemisinin, edaravone, and liposomes. The liposomes co-load artemisinin and edaravone, and their surfaces are modified with sialic acid derivatives and phosphatidylserine to form liposome nanomedicines. The neutrophils act as carriers, transporting the drug across the brain border (BBB) ​​and targeting it to the ischemic brain region. This dual-targeting strategy achieves precise two-stage drug delivery to the ischemic brain region. This delivery system can inhibit NLRP3 inflammasome activation, reduce pyroptosis, and promote microglial polarization towards the M2 anti-inflammatory phenotype, thereby effectively treating cerebral ischemia-reperfusion injury or ischemic stroke.

The present application relates to the field of biological medicine, in particular to a tumor treatment platform based on endogenous and exogenous zinc overload strategy, a preparation method and application. For the treatment platform, it comprises an acid-sensitive carrier, zinc ions and a sound-sensitive organic ligand; the sound-sensitive organic ligand can generate reactive oxygen under ultrasonic irradiation; the sound-sensitive organic ligand and the zinc ions are connected by a coordination bond to form a metal-organic complex; and the metal-organic complex is loaded on the acid-sensitive carrier. The present application proposes a tumor treatment strategy of "endogenous-exogenous synergy", combines "exogenous Zn 2+ " delivery with "endogenous Zn 2+ " mobilization, successfully induces "Zn 2+ overload" in cells through the synergistic effect of the two, realizes the precise, efficient and controllable induction of local Zn 2+ overload in tumors, and improves the effectiveness of pyroptosis. Through the present application, the limitations of traditional methods in controllability, efficacy and safety are overcome.

This invention relates to an immune-enhancing polypeptide and its applications, specifically providing an immune-enhancing polypeptide, wherein the polypeptide is the N-terminal amino acid sequence of pyroptosis-associated protein GSDMD from position 1 to 500 or a truncated sequence thereof. The immune-enhancing polypeptide described herein can induce a stronger immune response and can simultaneously satisfy multiple antigen loading formats.

The present application relates to the field of biological medicine nanomaterials, and particularly relates to a kind of nanocomposite material and its preparation method and application.The preparation method of nanocomposite material provided by the present application, first, by a kind of room temperature fast, green method is synthesized hollow sodium bismuth fluoride carrier, and doping makes it have excellent upconversion luminescence performance, then using the excellent surface area of hollow sodium bismuth fluoride is successfully loaded photosensitizer MC540, clothing mould toxin, finally using DSPE-PEG-FA is modified, obtains nanocomposite material.It can effectively activate tumor cell endogenous calcium overload, induce tumor cell pyroptosis, realize the effect of efficient cancer treatment.

The present application provides a kind of containing sulfuryl bridge physalin compound small physalin S and its preparation method and application, from Physalis pubescens Franch. Isolated and extracted to the new compound small physalin S of physalin, it has the molecular structure of I:Small physalin S of the present application has anti-inflammatory activity, can significantly improve the viability of PC12 cell of hypoxia reperfusion injury, its mechanism of action is related to the expression of inhibiting NLRP3 inflammasome and cell pyroptosis related protein, inhibits the release of inflammatory factors, suggests that small physalin S of the present application can be used as the medicine popularization of treating ischemic brain injury, with good development, application prospect.

The application discloses a construction method and application of an NLRP3 humanized mouse model, and belongs to the technical field of genetic engineering. The construction method of the NLRP3 humanized mouse model comprises the step of mutating the 708th amino acid of mouse Nlrp3-201 protein into a non-acidic amino acid; the Ensembl ID of the mouse Nlrp3-201 is ENSMUST00000079476.10. It is verified that the 708th amino acid of the mouse NLRP3 protein is mutated into a non-acidic amino acid (for example, alanine), the NLRP3 of the obtained mutant transgenic mouse is similar to human NLRP3, and cannot be cut by caspase-3, and humanization is realized. The mutant mouse model can better reflect the biological processes such as human inflammasome activation, cell pyroptosis and inflammatory reaction, and provides a more accurate animal model for understanding human diseases and drug screening.

This invention provides a peptide targeting graft-versus-host disease, its expression system, and a local in-situ regulatory system, belonging to the field of biomedical technology. This invention also provides the application of the peptide BigLEN in the preparation of macrophage pyroptosis inhibitors. BigLEN has a high affinity for the NLRP3 NACHT domain, and in vitro experiments have confirmed its effective inhibition of NLRP3-mediated pyroptosis in macrophages. This invention constructs a fusion protein and expression vector based on arabinose-induced expression, and an arabinose-inducible engineered EcN strain. Oral administration significantly improves survival rate, reduces intestinal pathological damage, decreases the infiltration of pro-inflammatory T cells, and promotes macrophage polarization towards an anti-inflammatory phenotype. This invention develops an orally administered engineered probiotic to precisely inhibit NLRP3-driven pyroptosis in intestinal macrophages.

The embodiment of the application discloses a natural small molecule inhibitor targeting NLRP3 inflammasome and application thereof, and belongs to the technical field of biological medicine. Chuanxiongdiolide R11 is a phthalide dimer compound with clear stereochemistry found in traditional Chinese medicine Chuanxiong, which can target NLRP3 inflammasome, prevent the activation and assembly of the inflammasome, thereby inhibiting caspase-1 activation, GSDMD cleavage, pyroptosis and the maturation and release of IL-1beta / IL-18. The compound can be used for preparing a drug for treating NLRP3 related inflammatory diseases such as systemic inflammation and peritonitis, and has a good clinical application prospect, and provides a new idea for developing and applying NLRP3 inhibitors in clinic.

The application of diosgenin in the preparation of drugs for the prevention or treatment of acute kidney injury falls within the pharmaceutical field. Specifically, this invention discloses that diosgenin, by directly binding to the PIK3CA protein, regulates the PI3K / Akt-NF-κB pathway, inhibiting inflammatory responses, apoptosis, and pyroptosis in renal tubular epithelial cells, thereby alleviating kidney damage. Cellular experiments show that diosgenin at concentrations of 0.1–5 μM can significantly protect renal tubular epithelial cells; animal experiments show that doses of 1–20 mg / kg can significantly improve renal function and reduce pathological damage in mice with acute kidney injury. This invention clarifies a complete chain of evidence from "compound—target—pathway—efficacy," providing a new drug candidate for the treatment of acute kidney injury and offering a paradigm for the mechanistic study of active ingredients in traditional Chinese medicine, contributing to the transformation of traditional Chinese medicine from empirical medicine to evidence-based and molecular medicine.

This invention discloses a neutralizing nanobody targeting soluble interleukin-17 receptor D (sIL-17RD), its preparation method, and its applications. The heavy chain variable region (VHH) of this nanobody contains a heavy chain complementarity-determining region 3 (CDR-H3) that specifically binds to sIL-17RD, with a length of 10 amino acids and containing 2–6 lysine residues. This invention provides four nanobodies: CQ5, CQ13, CQ11, and CQ6, corresponding to well-defined CDR-H1, CDR-H2, and CDR-H3 sequence combinations. This nanobody can specifically bind to and neutralize the biological activity of sIL-17RD, reducing chondrocyte death, promoting proliferation, and maintaining extracellular matrix homeostasis by inhibiting the P2rx7-NLRP3 inflammasome-mediated chondrocyte pyroptosis pathway. This invention also protects the nucleic acid encoding this nanobody, the recombinant expression vector, the host cell, the pharmaceutical composition, and the preparation method. The nanobodies described can be used to prepare drugs for the prevention and treatment of inflammatory osteoarthritis and other osteoarthritis. They can inhibit synovitis, reverse cartilage and subchondral bone degeneration, and relieve pain, showing promising application prospects.

This invention discloses the application of the scorpion venom polypeptide BmK AS in the treatment of chronic epilepsy. BmK AS exerts potent anti-epileptic and neuroprotective effects through a confluence mechanism. In a lycine-induced mouse model, BmK AS significantly shortened seizure duration, reduced seizure frequency, prolonged seizure latency, and improved cognitive and mental outcomes. Electrophysiologically, BmK AS nonlinearly inhibited multiple VGSC subtypes, with a particularly significant effect on Nav1.6, reducing peak sodium current by 43% at a concentration of 5 nM. Furthermore, BmK AS alleviated hippocampal neuroinflammation by inhibiting the NLRP1 inflammasome pathway and related pyroptosis. This invention establishes BmK AS as a promising multi-mechanism therapeutic candidate, highlighting the value of a dual therapeutic strategy of Nav1.6 blockade and neuroinflammation suppression for epilepsy treatment.

This application discloses the use of an NLRP3 agonist for tumor treatment; wherein the NLRP3 agonist is compound 18, which enhances IL-1β secretion, promotes mitochondrial ROS production, ASC spot formation, and Caspase-1-dependent GSDMD cleavage, leading to pyroptosis in drug-resistant tumor cells, with minimal impact on normal macrophages. When used in combination with antitumor drugs, this agonist can significantly inhibit tumor growth and promote the remodeling of the immune microenvironment in vivo.

The present application mainly relates to the application of small molecule compound TA in the preparation of drugs and inhibitors. The application discloses the application of tannic acid, a GSDMD specific inhibitor obtained by designing computer virtual auxiliary screening, in the preparation of drugs for inhibiting myocardial cell pyroptosis inflammation to prevent or treat myocardial ischemia reperfusion injury. The role of GSDMD mediated myocardial cell pyroptosis in promoting myocardial ischemia reperfusion injury is clear, the drug active ingredient tannic acid (TA) in the application is easy to obtain, can directly inhibit the activity of GSDMD protein, resist myocardial cell pyroptosis, and play an anti-inflammatory effect to prevent or treat myocardial ischemia reperfusion injury, and the effect is remarkable. Tannic acid (TA) provides a new drug target strategy for myocardial ischemia reperfusion injury, and has a wide application prospect.

This invention belongs to the field of nanobiomedicine technology, specifically relating to a mitochondrial-targeting copper-based nanoparticle (Qu@Cu-SS31) and its application in the preparation of drugs for treating myocardial infarction. The nanoparticles consist of quercetin (Que) and copper ions (Cu²⁺). + The nanoparticles, consisting of a self-assembly of the mitochondrial-targeting peptide SS31, exhibit a uniform, near-spherical morphology with an average particle size of 17.2 ± 1.6 nm. These nanoparticles specifically target cardiomyocyte mitochondria, responsively releasing Cu²⁺. + Furthermore, Qu@Cu-SS31 restores cardiomyocyte copper homeostasis by downregulating the copper metabolism negative regulator COMMD1, the copper uptake protein CTR1, and the copper chaperone protein CCS. Based on this, Qu@Cu-SS31 exhibits remarkable SOD-like and CAT-like enzyme activities, efficiently scavenging various reactive oxygen species / reactive nitrogen species and significantly reducing oxidative stress. Simultaneously, it inhibits NLRP3 inflammasome activation and Caspase-1-mediated pyroptosis, regulates the Bcl-2 / Bax balance to inhibit apoptosis, and promotes vascular endothelial growth factor expression and angiogenesis.

The application belongs to the field of biological medicine research and development, and particularly relates to application of umbilical cord mesenchymal stem cell-derived vascular endothelial precursor cells in preparation of medicines for preventing and treating atherosclerosis. By interfering with expression of related factors in a pyroptosis inflammatory signaling pathway of NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 at a transcription and protein level, the serum triglyceride concentration, total cholesterol concentration and low-density lipoprotein concentration can be reduced, the serum oxidized low-density lipoprotein and oxygen free radical concentration can be reduced, the serum high-density lipoprotein concentration can be increased, and the atherosclerotic plaque area can be reduced and cell apoptosis in the atheromatous plaque can be inhibited.

The application discloses a ternary carrier-free nanoparticle and a preparation method and application thereof. The ternary carrier-free nanoparticle comprises a nanoparticle formed by intermolecular interaction force of chlorin e6, lonidamide and RG108. The nanoparticle can improve effective absorption and accumulation of the drug in a tumor, and can also induce tumor-specific pyroptosis under laser irradiation, induce immunogenic effects, promote maturation of antigen-presenting cells and recruitment and activation of cytotoxic T lymphocytes, so as to start adaptive anti-tumor immunity.

This invention discloses the application of the combined use of tanshinone and decitabine in the preparation of drugs for treating breast cancer, belonging to the field of antitumor drug application technology. This invention reveals a novel mechanism by which the combined use of tanshinone (Miltirone) and decitabine (DAC) inhibits breast cancer development by inducing pyroptosis and inhibiting epithelial-mesenchymal transition (EMT). Experimental verification shows that the combined treatment of Miltirone and DAC significantly reduces the viability of 4T1 breast cancer cells, inhibiting their proliferation, migration, and invasion abilities; simultaneously, this combined regimen induces significant pyroptosis by promoting the cleavage of pyroptosis-related proteins such as GSDME, accompanied by an increase in the release of LDH and ATP. This invention provides important experimental evidence and new ideas for the development of combination therapy strategies for breast cancer and the preparation of highly effective pyroptosis-inducing antitumor drugs.

The application discloses a pH-responsive bismuth-based nanodrug and a preparation method and pharmaceutical application thereof. The nanodrug is hyaluronic acid modified cuprous oxide / iodine bismuth oxide heterojunction nanoparticles (Cu2O@BiOI-HA), the cuprous oxide has a double-layer hollow mesoporous structure, the iodine bismuth oxide is loaded on the surface of the cuprous oxide in a nanolayer to form a heterojunction, the particle size is 200-700 nm, and the band gap is 1.46-1.49 eV. The nanodrug produces active oxygen by promoting the separation of electron-hole pairs through band bending under the excitation of ultrasound, releases Cu + ions under acidic conditions, generates hydroxyl radicals by means of a Fenton-like reaction, realizes the synergistic treatment of sonodynamic and chemical dynamics, and simultaneously, the Cu + ions induce copper death, the active oxygen activates the pyroptosis pathway, the multimodal cell death synergistically triggers immunogenic cell death, and the anti-tumor immune response is activated. The application establishes a structure-activity relationship between synthesis parameters and sonodynamic performance, and has application value in the treatment of breast cancer.

This disclosure provides a biomimetic nanomedicine delivery system for inhibiting pyroptosis and its application. The biomimetic nanomedicine delivery system has a shell-core structure, wherein the core is a nanozyme particle loaded with anti-inflammatory active molecules to form a nanozyme particle loaded with anti-inflammatory active molecules, and the shell is a biomimetic cell membrane that encapsulates the nanozyme particle loaded with anti-inflammatory active molecules. The novel nanodelivery system provided by this disclosure not only achieves effective drug delivery but also possesses comprehensive functions such as continuous scavenging of reactive oxygen species, regulation of inflammatory responses, and inhibition of pyroptosis signaling pathways.

This invention discloses a piezoelectric nanocomposite for regulating pyroptosis, its preparation method, and its applications, relating to the field of tumor immunotherapy. The composite comprises barium titanate nanocubes, gold nanoparticles assembled on the surface of the barium titanate nanocubes, and thiol-modified polyethylene glycol, endoplasmic reticulum-targeting peptides, and cell-penetrating peptides modified on the surface of the gold nanoparticles and / or the barium titanate nanocubes. This invention utilizes ultrasound to excite the endoplasmic reticulum-targeting nanoprobes in the composite, achieving radio-induced tumor cell pyroptosis immunotherapy based on endoplasmic reticulum-mitochondrial crosstalk. Pharmaceutical compositions containing the composite of this invention, after radio-induced stimulation, effectively inhibit the growth of both primary and distal tumors, and this effect is enhanced when combined with anti-CTLA-4 antibodies, inhibiting tumor recurrence. The composite provided by this invention can reverse the immunosuppressive tumor microenvironment and activate systemic anti-tumor immune responses, possessing significant application value in the field of tumor immunotherapy.

The present application relates to a kind of glutathione-responsive exosome biomimetic dendrimer nanogel vaccine and its preparation method and application.The vaccine is loaded with 5-Aza, coated with tumor cell Ex and modified R837 in turn to prepare dendrimer nanogel as carrier.The vaccine realizes precise drug delivery of tumor by virtue of the homologous targeting characteristics of Ex, and can target drug release in response to the high glutathione characteristics of tumor microenvironment.5-Aza exerts epigenetic therapy effect through DNA demethylation, while inducing pyroptosis type ICD of tumor cells.R837 immunoadjuvant can synergize with tumor-associated antigens carried by Ex to promote the maturation of dendritic cells, promote the polarization of M2 type tumor-associated macrophages to M1 type, and reverse the tumor immunosuppressive microenvironment.The present application combines epigenetic therapy and immunotherapy, providing a new strategy for the clinical treatment of pancreatic cancer, and has wide clinical application prospect.

Provided in the present invention are an AAV vector and use thereof in the treatment of brain glioma. The AAV vector comprises a pyroptosis effector protein-N-terminal fragment (GSDMD NTD) coding gene, and a promoter operably linked to the GSDMD NTD coding gene.

This invention proposes a photo-triggered pyroptosis nanomedicine composition, its preparation method, and its application, belonging to the field of pharmaceutical technology. The nanomedicine composition consists of spherical nanoparticles with a core-shell structure: an outer carrier (bovine serum albumin); a middle photothermal agent (poly(dithiophene-pyrrolopyrroledione); and a core demethylating agent (lipophilic demethylating agent RG108). This invention achieves successful triggering of pyroptosis and a sustained anti-tumor immune cycle with only a single dose and minimal light exposure, significantly improving the response rate of immunotherapy and providing a novel and highly innovative strategy for photo-immunotherapy of tumors.

The present disclosure belongs to the technical field of biological medicine, and particularly relates to the application of finerenone in the preparation of a drug for treating hypertensive renal injury. The present disclosure provides the application of finerenone in the preparation of a drug for preventing and / or treating hypertensive renal injury, specifically, by using a deoxycorticosterone acetate-salt-induced hypertensive mouse model and a primary mouse renal tubular epithelial cell-bone marrow-derived macrophage co-culture model, it is first revealed that aldosterone and salt corticosteroid receptor signals mediate cell-to-cell communication by promoting PANX1-dependent ATP release in renal tubular epithelial cells, and then activate macrophage P2X7, activate NLRP3-mediated macrophage pyroptosis, and aggravate the molecular mechanism of aldosterone-driven renal inflammation and fibrosis. The present disclosure also provides the application of a substance targeting a PANX1 / extracellular ATP / P2X7 signal axis in the preparation of a drug for preventing and / or treating hypertensive renal injury.

This invention belongs to the field of pharmaceutical technology and discloses a novel use of S-propynylcysteine ​​or a pharmaceutically acceptable salt thereof in the preparation of a drug for the prevention and treatment of schizophrenia. The technical problem to be solved by this invention is to provide a drug for the prevention and treatment of schizophrenia based on a novel mechanism of action. The key technical points are: the drug achieves its preventive and therapeutic purpose through at least one mechanism, such as promoting the expression and / or activity of endogenous hydrogen sulfide-related enzymes, inhibiting the transcriptional activity of inflammation-related signaling pathways, and / or inhibiting pyroptosis; these mechanisms may act simultaneously or separately. The drug may further comprise a pharmaceutically acceptable carrier, excipient, or diluent. The main use of this invention is the prevention and treatment of schizophrenia.