26 results about "Caspase" patented technology

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

The application discloses application of a pyrimidinotriazine diketone derivative in preparation of a medicine for inhibiting activity of human protease caspase-1, and belongs to the technical field of medicines. In view of defects of existing caspase-1 inhibitors, the compound has the characteristics of high affinity binding to caspase-1 (K D = 8.11 μM; 8.78 μM) and strong inhibition on the activity (IC 50 = 11.90 nM-14.47 nM). The compound is used for preparation of a medicine for inhibiting the activity of caspase-1 and a medicine for treating inflammation-related diseases such as sepsis-related lung injury, acute respiratory distress syndrome or acute pancreatitis.

The present application belongs to the technical field of hair loss treatment, and particularly relates to a phototherapy and drug synergistic intervention system for androgenetic alopecia of human scalp. In the system, the drug is angelica extract with a concentration of 0.1-500 ug / mL; the phototherapy light source is a red light LED light source with a wavelength of 600-700 nm; the light irradiance is 2-100 mW / cm 2 ; the light dose is 2-20 J / cm 2 ; the irradiation mode is steady light or pulsed light; and the synergistic intervention mode is that the phototherapy and the drug application are performed synchronously or the phototherapy is performed within 0.5-2 hours after the drug application. Experiments show that the light-drug combined intervention significantly improves cell viability, ATP level, migration ability, IGF1 and VEGF secretion, reduces ROS and MDA levels, inhibits Caspase-3 activity, regulates BCL2 / BAX expression, activates Wnt, Hh and PI3K pathways, and inhibits BMP and TGF-beta pathways. The present application provides a treatment scheme with clear timing and standardization, and realizes safe, non-invasive and efficient hair loss treatment.

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 the application of a "Super Brain-Boosting Capsule," belonging to the field of pharmaceutical technology. The Super Brain-Boosting Capsule is used in the preparation of drugs for treating Alzheimer's disease. The capsule enhances the mitochondrial membrane potential of Glu-treated HT22 cells by inhibiting ferroptosis. At the transcriptional level, the capsule activates the expression of key Nrf2 / HO-1 / GPX4 signaling molecules NRF2, HO-1, GPX4, SLC7A11, ACSL4, FTH1, and FPN1, while reversing the expression of Bcl-2, Caspase-3, and Caspase-9 to inhibit apoptosis in AD cells. This invention reveals that the Super Brain-Boosting Capsule, based on the Nrf2 / HO-1 / GPX4 pathway, inhibits Glu-induced ferroptosis in HT22 cells, which can treat Alzheimer's disease. This invention provides experimental evidence and direction for the further development of the Super Brain-Boosting Capsule in the prevention and treatment of Alzheimer's disease and other neurodegenerative diseases.

The application relates to the field of biological medicine, and discloses ascorbyl palmitate nanoliposomes capable of inducing tumor cell oncosis, a preparation method and application thereof. The nanoliposomes are constructed by inserting ascorbyl palmitate as a lipid component into a phospholipid bilayer, and are prepared by a film dispersion method from lecithin, cholesterol, pegylated phospholipid and ascorbyl palmitate. The average particle size of the nanoliposomes is 80-150 nm, the encapsulation rate is high, and the stability is good. The nanoliposomes can be administered through a tail vein, utilize the specific hydrolysis of matrix metalloproteinase MMP-2 which is highly expressed by tumor cells to hydrolyze ascorbyl palmitate, release palmitic acid and ascorbic acid, thereby inducing Caspase-independent oncosis of tumor cells, effectively overcoming apoptosis-related drug resistance, and reversing a tumor immunosuppressive microenvironment. The nanoliposomes avoid the cumulative toxicity of metal-type inducers, and provide a new safe and effective option for reversing chemotherapy resistance.

The application relates to the technical field of pharmaceutical chemistry, and discloses a sulfuryl hydrazone compound, a preparation method thereof and anti-tumor application. The compound is synthesized from isatin derivatives and sulfuryl hydrazine through two-step nucleophilic substitution-elimination reaction, has a chemical structure as shown in formula (I), and is characterized by 1H NMR, 13C NMR and HRMS. The sulfuryl hydrazone compound has significant inhibitory activity on A549 (lung cancer), HepG2 (liver cancer) and Hela (cervical cancer) three human cancer cell strains, the value of some compounds is as low as 0.03 micromole / L, the compound can induce cell apoptosis by mediating ROS generation in tumor cells, inhibiting the NF-kappa B signal pathway and activating Caspase-3 activity, and can effectively inhibit cancer cell migration and colony formation. The compound has a mild synthesis process, simple operation and wide substrate applicability, can be used as a potential anti-tumor active ingredient, can be used for preparing drugs for resisting lung cancer, liver cancer, cervical cancer and other tumors, and can provide new candidate compounds and technical support for cancer treatment.

The application discloses application of a petroleum ether extract of a root of a roadside green plant in preparation of a drug for treating colorectal cancer by regulating a PI3K / AKT / MDM2 / p53 pathway. In the application, the petroleum ether extract of the root of the roadside green plant for treating colorectal cancer is obtained by petroleum ether reflux extraction of the root of the roadside green plant. Pharmacological experiments show that the petroleum ether extract of the root of the roadside green plant treats colorectal cancer by regulating the PI3K / AKT / MDM2 / p53 signal pathway through down-regulating p-PI3K / PI3K and p-AKT / AKT ratio, up-regulating p-MDM2 and down-regulating p53 level; the extract has an anti-malignant proliferation effect, induces G1 phase arrest by targeting CDK2, up-regulating p21, down-regulating Cyclin E1-CDK2 and Cyclin D1-CDK4; the extract induces HCT-116 cell apoptosis through a mitochondrial pathway by up-regulating Bax / Bcl-2, reducing ΔΨm, releasing Cyt C, activating Caspase-9 / 3 and cleaving PARP; the extract inhibits migration and invasion of HCT-116 cells by targeting MMP9, down-regulating MMP-2, MMP-9 and N-cadherin expression and up-regulating E-cadherin expression. In addition, the extract inhibits growth of a transplanted tumor in a nude mouse transplanted tumor model by inducing apoptosis of transplanted tumor cells.

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.

The present application belongs to the technical field of biomedical materials and nano drugs, and discloses a polypeptide nano drug capable of inducing necrosis and autophagy related synergistic apoptosis and a preparation method and application thereof. X-DDP1 and DDP1 are self-assembled to form a responsive polypeptide nano drug, which provides a delivery platform for broad-spectrum chemotherapy drugs such as buforin RBG, irinotecan CPT11 or camptothecin CPT, realizes a Caspase-3 / GSH double-response mechanism, improves drug release specificity and spatial controllability, can promote RIPK3 aggregation and activate necrotic apoptosis in cells, can effectively inhibit the growth of cancer, and has potential clinical application value.

The present invention relates to the field of biotechnology and the use of chemically modified antisense oligonucleotides (AONs) for the deamination of one or more target adenosines in the transcript of (mutant) human Huntingtin (HTT) for use in the treatment, prevention, or delay of Huntington's disease (HD). In particular, the target adenosines are in the GAU codon coding for aspartic acid at position 572 that is part of a caspase-1 proteolytic cleavage site in the human HTT protein, and / or in the GAC codon coding for aspartic acid at position 586 that is part of a caspase-6 proteolytic cleavage site in the human HTT protein.

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.

This invention belongs to the field of biomedicine and discloses the application of palmitoyltransferase ZDHHC21 in the preparation of drugs for treating breast cancer. This invention demonstrates that ZDHHC21 knockdown upregulates RIPK1 expression, which is related to signal feedback induced by CD82 palmitoylation deficiency. Depalmitoylated CD82 competitively binds to RIPK1 inhibitory molecules, thereby releasing the regulation of RIPK1, promoting the interaction and phosphorylation activation of RIPK1 and RIPK3, and subsequently upregulating MLKL expression and inducing its activation. Downstream activation of Caspase-3 ultimately initiates necroptosis. A specific regulatory axis of "ZDHHC21–CD82–pan-apoptosis" is established. This provides a potential novel therapeutic target for triple-negative breast cancer and offers a theoretical and experimental basis for therapeutic strategies targeting tumor cell death. Further research can explore the role of this regulatory axis in vivo, providing support for clinical translation.

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 application discloses a sea cucumber polysaccharide cancer inhibiting preparation and a preparation method and application thereof, and belongs to the technical field of biological medicine. The preparation is prepared from high-purity sea cucumber polysaccharide extracted from Apostichopus japonicus as a core active ingredient, and is matched with a folic acid modified polyethylene glycol-poly lactic acid copolymer targeting carrier and medicinal adjuvants, and is prepared through steps of standardization extraction and purification, targeting carrier preparation, granulation and coating. The application adopts an enzymolysis process combining with self-lyase and exogenous enzyme, and cooperates with multi-step purification and ultrafiltration grading technology to precisely control the purity and molecular weight of the polysaccharide, realizes active targeting of tumor cells through the FA-PEG-PLA targeting carrier, and improves the bioavailability through enteric coating technology. The preparation can up-regulate the expression of TNFR1 protein, activates the caspase cascade reaction to induce tumor cell apoptosis, has a significant inhibiting effect on solid tumors such as lung cancer, kidney cancer and liver cancer, and has very low toxicity to normal cells.

This invention provides a Ganoderma lucidum oligopeptide with anti-tumor effects and its preparation method. The Ganoderma lucidum oligopeptide with anti-tumor effects provided by this invention is an LC-R polypeptide. This polypeptide exhibits a high apoptosis rate in HepG2 cells and can effectively promote the increase of caspase-3 activity, thereby promoting cell apoptosis. Animal experiments have confirmed that this polypeptide can effectively inhibit tumor growth and has broad application prospects.

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 provides medical application of glycyrrhizin chalcone B derivative CTG12 in preparation of NLRP3 inflammasome inhibitors, and belongs to the technical field of biological medicine.The application provides the glycyrrhizin chalcone B derivative CTG12 in preparation of NLRP3 inflammasome inhibitors, and application in preparation of drugs for preventing or treating diseases related to abnormal activation of NLRP3 inflammasome; the compound CTG12 synthesized in the application has significant inhibition on caspase-1 activity generated by BMDM cells, the effect is about eight times higher than that of glycyrrhizin chalcone B, and the compound CTG12 has broad-spectrum and specific inhibition effect, and can effectively inhibit activation of NLRP3 inflammasome.

Disclosed herein are methods and compositions for treating cancer using an incomplete autophagy inducer, such as metixene (aka. “methixene”), to trigger caspase-mediated apoptosis in cancer cells. The described methods and compositions can cause a significant decrease in tumor size and a significant prolongation in survival. The methods and compositions are useful for the treatment of cancers, such as brain cancer, breast cancer, lung cancer, and melanoma.

The application belongs to the technical field of biological medicine, and particularly relates to a preparation method and application of a polyketide compound from a fungus of the genus Arenarius. The polyketide compound can dose-dependently reduce the NO generation level in cells, significantly inhibit M1 phenotype polarization and promote the conversion of the M1 phenotype to the M2 phenotype, significantly down-regulate the expression of key inflammatory-related proteins (including IL-1beta, IL-6, TNF-alpha and COX-2) in cells, and inhibit the generation of NLRP3 inflammasome and caspase-1, revealing the potential anti-AD activity and indicating that the polyketide compound has a good application prospect in the preparation of anti-neuroinflammatory drugs. In addition, the polyketide compound can be prepared from a marine microorganism Arenarius fungus, and the preparation method is simple and the source is rich.

This invention relates to the field of nanomedicine technology and discloses the application of nano-Amy@NPs-MM / PL1 in the treatment of endometriosis. The nano-Amy@NPs-MM / PL1 comprises a nanocarrier PEG-PLGA, a nanomedicine Amy, a nano-coated macrophage membrane, and a targeting peptide PL1. The steps are: S1, macrophage membrane extraction: using a cell membrane extraction kit, macrophage membranes are separated; S2, targeting peptide insertion into the macrophage membrane: the targeting peptide PL1 is inserted into the macrophage membrane to obtain the targeting macrophage membrane MM / PL1; S3, preparation of PEG-PLGA-loaded Amy. This invention demonstrates that Amy@NPs-MM / PL1 inhibits the activation of the TNF-α / TNFR1 / NF-κB signaling pathway, blocks the downstream caspase-1 / GSDMD-mediated pyroptosis cascade, reduces the release of inflammatory factors, and inhibits angiogenesis and the expression of invasive factors. It achieves multi-level intervention from anti-oxidation and anti-pyroptosis to neuroprotection and metabolic regulation, providing a new strategy with both theoretical innovation and clinical translational potential for the comprehensive treatment of endometriosis.

The application discloses an anchor COX-2 protein responsive photosensitizer and a preparation method and application thereof, relates to the technical field of biological medicine and disease treatment. The compound IRID-SS shown in formula (I) prepared by the application is provided with a near-infrared cyanine as a photosensitive unit, an indomethacin as a COX-2 targeting ligand and a disulfide bond as a glutathione response unit. The compound can be activated under the condition of high glutathione in a tumor microenvironment, specifically anchors Golgi COX-2 protein, generates reactive oxygen species in situ through near-infrared laser irradiation, realizes irreversible oxidative damage of COX-2 protein, and induces pyroptosis of tumor cells through a Caspase-3 / GSDME channel. The compound has a simple synthesis method, does not introduce toxic reagents, does not have the problem of toxic reagent residue, has high biological safety, and therefore has good practical application value.

The application provides application of ipomoea nil exocyst in preparation of a medicine for preventing, alleviating or treating osteomyelitis. The application creatively finds that the ipomoea nil exocyst can significantly inhibit the expression of macrophage pyroptosis markers GSDMD-NT and Caspase-1, promote the expression of osteogenesis markers RUNX2 and OPN, and mediate immune regulation to achieve the treatment of osteomyelitis. The ipomoea nil exocyst is loaded in a three-dimensional cross-linked skeleton formed by oxidized dextran, aminopolysaccharide and gelatin, has better mass transfer delivery effect, and significantly improves the treatment effect on osteomyelitis.

The present application refers to a method of preventing or reducing metastasis of tumor cells, senescence, differentiation or inflammation wherein the caspase-activated DNAse which induces strand breaks in the genomic DNA of cells causing changes of the behavior of the cell involving aggressive growth, senescence, differentiation and metastasis and / or inflammation is inactivated.