41 results about "Apoptosis pathways" patented technology

The invention belongs to the technical field of gene engineering and cell transformation, and discloses a gene engineering construction method and application of anti-apoptosis human mesenchymal stem cells. Through HDAC1 K412 site specific lactic acid mutation, breakthrough improvements are realized: for example, CRISPR-Cas9-mediated accurate gene editing is utilized, only a single amino acid site is changed, that is, K412R mutation simulates persistent lactic acid, and whole genome apparent modification disturbance can be avoided; the modification does not depend on an exogenous metabolic substrate, and the negative feedback effect of traditional metabolic intervention is overcome; the mutant continuously inhibits a P53 apoptosis pathway, so that the oxidative stress mediated apoptosis resistance of the MSC is remarkably improved. According to the design concept of one target spot and one regulation, the core contradiction that long-term effectiveness and specificity cannot be considered in the prior art is fundamentally solved, and a brand new normal form is provided for stem cell treatment.

A series of 1, 3, 5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1, 3, 5-triazine compounds as promising antitumor agents.

The invention discloses a probe BBM for anchoring OPA1 protein and application of the probe BBM, and belongs to the technical field of biological analysis. Based on the characteristic that the OPA1 protein is rich in hydrophobic amino acid residues and polar amino acids, the probe BBM capable of generating multiple interaction forces with the OPA1 protein is designed by reasonably introducing hydrophobic groups and polar groups. Theoretical calculation and experimental results (including OPA1 knock-down and overexpression) show that the probe realizes efficient enrichment in a mitochondrial inner membrane region. By using the unique probe, the hydrogen peroxide induced mitochondrial inner membrane viscosity change is systematically researched, and the myocardial cell oxidative damage is further confirmed to be realized by a p53 protein mediated apoptosis pathway. The method provides a reliable means for accurately evaluating the oxidative stress of the mitochondrial inner membrane, and has important promotion significance for the development of the cardiovascular research field.

The invention discloses a novel application of total glucosides of paeony in preparation of a medicine for treating triple negative breast cancer. In-vitro and in-vivo experiments prove that the total glucosides of paeony can remarkably inhibit proliferation, migration and invasion of triple negative breast cancer cells (MDA-MB-231 and MDA-MB-468), reverse an epithelial-mesenchymal transition process and induce cell apoptosis by inducing mitochondrial injury, inhibiting oxidative phosphorylation and activating a mitochondrial apoptosis pathway. In an MDA-MB-231 cell xenotransplantation tumor nude mouse model, the total glucosides of paeony can effectively inhibit tumor growth. Therefore, the total glucosides of paeony can be used for preparing the medicine for treating the triple negative breast cancer, and a new treatment choice is provided for clinic.

The invention belongs to the technical field of medicines, and particularly discloses an oral squamous cell carcinoma inhibitor and application thereof. The inhibitor takes rutin as an active component. In-vitro experiments prove that rutin can significantly inhibit proliferation, clone formation, migration and invasion ability of OSCC cells in a dose-dependent manner, and effectively induce cell apoptosis. The action mechanism of the rutin is as follows: the rutin can directly target STAT3 protein and inhibit phosphorylation of the STAT3 protein so as to regulate and control a downstream BCL2 / CASP3 apoptosis pathway, thereby playing a role in treating OSCC. Molecular docking results further show that rutin and STAT3 have strong binding capacity. The invention discloses a new application of rutin as an STAT3 inhibitor in treating oral squamous cell carcinoma, and provides a new strategy and a candidate compound for developing high-efficiency and low-toxicity OSCC treatment medicines.

The invention discloses an application of Lumacaftor in the treatment of Parkinson's disease. The treatment effect of Lumacaftor on PD is verified through in-vitro cell experiments and in-vivo animal experiments respectively, and it is found that after Lumacaftor is used in a microglial cell-neuron co-culture PD cell model, apoptosis pathway related protein in neurons is remarkably reduced compared with a model group; after Lumacaftor treatment is performed on a PD mouse in an MPTP mouse PD model, dopaminergic neurons of the PD mouse are remarkably increased, and the motor function is improved. The application provides a new thought for effective treatment of PD, and the application prospect is wide.

The application discloses application of NDUFB4 as a target point in preparation of a drug for treating bladder cancer. Single cell analysis results show that NDUFB4 is highly enriched in bladder cancer epithelial cells, and can be used as a key coordinator to participate in the regulation of multiple carcinogenic signal pathways. Through shRNA-mediated gene silencing and CRISPR / Cas9-mediated gene knockout experiments, it is found that NDUFB4 deletion can significantly inhibit the proliferation, migration and invasion ability of bladder cancer cells, and cause a serious bioenergy crisis, and activate the endogenous apoptosis pathway. In a subcutaneous xenotransplant tumor model, it is further verified that NDUFB4 silencing can significantly inhibit tumor growth. The application discloses that NDUFB4 is a key coordinator between mitochondrial high-functionality and carcinogenic signal pathways, and it is suggested that NDUFB4 can become a potential target for bladder cancer treatment.

Provided are biomarkers for predicting the efficacy of an MDM2 inhibitor or a Bcl-2 / Bcl-xL dual inhibitor or a Bcl-2 inhibitor or a Bcl-xL inhibitor in treating a cancer patient. Also provided are compositions, e.g., kits, for assessing gene levels of the biomarkers, and methods of using such gene levels to predict the response of a cancer patient to an MDM2 inhibitor or a Bcl-2 / Bcl-xL dual inhibitor or a Bcl-2 inhibitor or a Bcl-xL inhibitor. Such information can be used to determine the prognosis and treatment selection of a cancer patient.

The invention provides nanoparticles for tumor photodynamic therapy and a preparation method, a pharmaceutical composition and application thereof, and belongs to the technical field of nano biomedicine. The nanoparticle for tumor photodynamic therapy comprises: an up-conversion nanoparticle; the phospholipid layer is used for coating the up-conversion nano-particles; the nucleic acid aptamer and the endoplasmic reticulum targeting peptide are modified on the surface of the phospholipid layer; and a photosensitizer supported on the surface of the nanoparticle. The nucleic acid aptamer and the endoplasmic reticulum targeting peptide are further co-modified on the basis of the surface of the upconversion nano-particle subjected to phospholipidation treatment, so that the nano-particle can actively recognize tumor cells and deliver the tumor cells to the endoplasmic reticulum, and dual targeting on the tumor cells is realized. The loaded photosensitizer can generate reactive oxygen species (ROS) under excitation of near-infrared light, endoplasmic reticulum stress is specifically induced, then a cell apoptosis pathway is activated, and tumor cells are killed.

The invention provides application of a preparation for activating RIPKs / MLKL mediated necroptosis signal transduction in preparation of a medicine for reversing taxol drug resistance of ovarian cancer, and belongs to the technical field of biological medicine. It is found for the first time that disulfiram (DSF) can reverse ovarian cancer paclitaxel drug resistance and enhance sensitivity of ovarian cancer paclitaxel drug-resistant cells to paclitaxel. A further research discovers that the DSF is used for enhancing RIPKs / MLKL mediated necroptosis signal transduction by combining an apoptosis-inducing factor (AIF), and finally, the chemosensitivity of the paclitaxel drug-resistant ovarian cancer cells is enhanced through a caspase-dependent apoptosis pathway. The invention deeply studies an ovarian cancer paclitaxel drug resistance mechanism, discovers a new application of DSF in reversing ovarian cancer paclitaxel drug resistance, and provides a new choice for treating paclitaxel drug-resistant ovarian cancer.

The invention discloses application of salvianolic acid C in preparation of a medicine for preventing and / or treating retinal ischemia hypoxic nerve injury diseases, and relates to the technical field of biological medicines. The invention proposes and verifies for the first time that salvianolic acid C can significantly promote the formation of stress particles in photoreceptor cells under retinal ischemia and hypoxia conditions, and drives the salvianolic acid C to be assembled into a stress particle-mitochondrial micro-region in a mitochondrial adjacent region. The microcell is enriched in DDX3X, LARP1 and other key RNA binding proteins and multiple mitochondrial related proteins to cooperatively maintain mitochondrial membrane potential, inhibit mPTP opening and reduce ROS generation, so that an endogenous apoptosis pathway is inhibited, and the neuroprotective effect on a photoreceptor is achieved. On the basis, the salvianolic acid C is used for preparing the medicine for preventing and / or treating the retinal ischemia hypoxia nerve injury disease, can be used as a nerve protection supplement for existing anti-VEGF treatment, and has innovativeness and application value.

The invention belongs to the technical field of pharmaceutical compositions for removing senescent cells, and discloses a pharmaceutical composition for removing senescent cells and a preparation method and application thereof, and the pharmaceutical composition for removing senescent cells contains NK cells and fisetin. According to the pharmaceutical composition for removing senescent cells, the fisetin and the NK cells are combined for use, on one hand, the fisetin can enable the NK cells to easily recognize senescent cells; on the other hand, fisetin can relieve inhibition of SASP factors on NK cell activity, enough amount of cytotoxic particles such as perforin and granzyme are synthesized and released in NK cells, the killing efficiency on senescent cells is high, fisetin can directly trigger an apoptosis pathway of the senescent cells, and the effect of killing the senescent cells is achieved. The NK cells release cytotoxic particles to further accelerate death of the senescent cells, and fisetin and the NK cells have a synergistic effect, so that the senescent cell clearing efficiency is high.

The invention discloses application of TAB2 in diagnosis and treatment of Parkinson's disease. According to the present invention, the PD patient midbrain single cell data set analysis results show that the microglial cells are significantly increased, and the Bulk transcriptome data is combined to screen the microglial cell differential gene TAB2; after TAB2 is knocked down in PD animal and cell models, apoptosis pathway related proteins in neurons are significantly reduced compared with a model group, and the motor function of PD mice is improved. Therefore, the TAB2 has a good effect of blocking the progress of the PD, and a new direction is provided for effective diagnosis and timely treatment of the Parkinson's disease.

The application provides a semi-florin chemotherapy drug and a synthesis method thereof, relates to the technical field of drug synthesis, and the semi-florin derivative exhibits significant selective anti-tumor activity, and the mechanism of action is that after entering tumor cells, the semi-florin derivative can induce the increase of the level of reactive oxygen species (ROS) in the cells, causes the collapse of the mitochondrial membrane potential, and finally triggers the late apoptosis pathway of the cells.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

The invention discloses application of phascolosoma esculenta-sourced oligopeptide and 5-FU in preparation of a medicine for resisting colorectal cancer, and belongs to the technical field of biological medicine. The oligopeptide is separated from a phascolosoma esculenta body, and tests prove that when the small-molecule oligopeptide and 5-FU are jointly applied at high concentration, colon cancer cell proliferation can be remarkably inhibited, and a dose-dependent synergistic effect is achieved. Oligopeptide 659 and 5-FU synergistically activate a mitochondrial apoptosis pathway, and combined medication can enhance gamma-H2AX focus formation and aggravate DNA double-chain breakage, so that CRC cell proliferation is synergistically inhibited. DLD-1 cells are inoculated to NOD-SCID female mice for modeling, then in-vivo analysis is carried out on the anti-tumor effect of the peptide 659, and the effect of the oligopeptide 659 on resisting colorectal tumors is proved again. An analysis result after mouse dissection shows that compared with a control group, the oligopeptide 659 inhibits growth of mouse tumors.

The invention relates to application of beauveria bassiana in preparation of a medicine for treating multiple myeloma. The invention shows that the Beauverin has a remarkable effect of resisting multiple myeloma, and the action mechanism of the Beauverin is that the expression of anti-apoptotic protein Bcl-2 is inhibited, the expression of pro-apoptotic protein Bax is promoted, the release of cytochrome C is promoted, the activation of Caspase proteases such as Caspase 3 and the like is caused, and finally the apoptosis of cells is caused. Beauveria bassiana regulates an apoptosis pathway through multiple targets, plays a role in resisting multiple myeloma, and provides an experimental basis for developing a novel treatment strategy. Compared with the prior art, the specific action mechanism of the beauveria bassiana is defined, and the value of the beauveria bassiana as a potential anti-tumor drug is highlighted.

The present application relates to the application of Necrostatin-1 in the preparation of a drug for preventing and / or treating acute aristolochic acid nephropathy. The typical pathological change of acute aristolochic acid nephropathy is the necrosis of renal tubular epithelial cells, and Necrostatin-1 can target this change to prevent and / or treat acute aristolochic acid nephropathy. Necrostatin-1 can significantly inhibit the kinase activity of RIPK1, block the endogenous and exogenous apoptosis pathways dependent on RIPK1, delay the apoptosis and GSDME-dependent pyroptosis of renal tubular epithelial cells, effectively improve the damage of renal tubular epithelial cells, and achieve the purpose of treating acute aristolochic acid nephropathy. The present application can provide a new strategy for the treatment of acute aristolochic acid nephropathy. Necrostatin-1 can be widely used in the preparation of drugs for treating acute aristolochic acid nephropathy.

Immunoassays to detect the presence of Bcl-2 family heterodimeric complexes are described. The immunoassays are designed to detect one or more of BIM-Bcl-2, BIM-Bcl-xL, BIM-Mcl-1 and BAX BAK heterodimers. The assays can be used, for example, to select a BH3 mimetic, or other drug targeting the apoptosis pathway, that is effective for treating a specific cancer, or to select a subject who is likely to respond to a particular BH3 mimetic.

A series of 1,3,5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1,3,5-triazine compounds as promising antitumor agents.

The invention discloses an application of a vitamin E compound in preparation of a cIAPs protein stabilizer, and particularly, the vitamin E compound or a pharmaceutically acceptable salt thereof is combined with a BIR3 structural domain of cIAPs protein to directly inhibit degradation of cIAPs, so that a caspase-dependent apoptosis pathway and an RIPK1 / RIPK3 / MLKL-mediated programmed necrosis pathway are blocked. The new mechanism not only expands biological function cognition of vitamin E, but also provides a brand new strategy and a compound basis for developing drugs for treating diseases (such as tissue damage, autoimmune diseases and the like) related to cIAPs degradation.

The application discloses application of TAB2 in diagnosis and treatment of Parkinson's disease. Through analysis of a cerebral single cell data set of PD patients, it is shown that microglia cells are significantly increased, and a microglia cell differential gene TAB2 is screened in combination with bulk transcriptome data; after TAB2 is knocked down in a PD animal and cell model, apoptosis pathway related proteins in neurons are significantly reduced compared with a model group, and the motor function of a PD mouse is improved. It is shown that TAB2 has a good effect on blocking the progress of PD, and a new direction is provided for effective diagnosis and timely treatment of Parkinson's disease.

The invention discloses application of TRPV1, NUDT9 and MT-ND5 as targets in preparation and screening of drugs for treating brain glioma, and belongs to the technical field of biology. According to the application disclosed by the invention, experiments prove that the expression of NUDT9 and MT-ND5 in brain glioma cells is knocked down, the proliferation of the brain glioma cells is reduced, TRPV1 in the brain glioma cells is knocked down, the proliferation of the brain glioma cells is promoted, the expression of NUDT9 and MT-ND5 in the brain glioma cells is reduced by beta-elemene, and the beta-elemene has the effect of inhibiting tumor growth; the application prospect of the TRPV1, the NUDT9 and the MT-ND5 serving as the target spot in screening the medicine for treating the brain glioma is shown. According to the application disclosed by the invention, the condition that the beta-elemene and the TMZ are combined to enhance DNA damage accumulation through a synergistic effect, continuously activate a cell apoptosis pathway and increase the sensitivity of glioma cells to the TMZ is determined for the first time, so that the curative effect is improved, and the toxicity is reduced.

This invention relates to a method for extracting compound Alisma alkaloid A from Alisma plantago-aquatica and its application, effectively solving the problem of extracting Alisma alkaloids from Alisma plantago-aquatica and enabling its application in the preparation of drugs for treating lung cancer. This compound, Alisma alkaloid A, significantly reduces cell viability and Bcl2 expression, induces apoptosis and mitochondrial membrane depolarization in A549 lung cancer cells, and significantly increases the expression of Bax, Caspase3, and Caspase9, without affecting normal human lung epithelial cells BEAS-2B. It has the effect of inducing apoptosis in A549 cells through the mitochondrial apoptosis pathway, thus realizing the application of Alisma alkaloid A in the preparation of drugs for treating lung cancer. The method of this invention is scientifically sound, novel, unique, and easy to operate, effectively extracting compound Alisma alkaloid A from Alisma plantago-aquatica. This compound has the effect of inducing apoptosis in A549 cells through the mitochondrial apoptosis pathway, realizing the application of Alisma alkaloid A in the preparation of drugs for treating lung cancer, and expanding the medicinal and commercial value of Alisma plantago-aquatica.

The invention discloses an application of nano-iron carried lncRNACACF in a vascular endothelial cell (VEC). According to the invention, nano-iron-carried lncRNA CACF is taken as a research object, and the application of the nano-iron-carried lncRNA CACF in vascular endothelial cells is researched by adopting a molecular and cell biology method: through EdU, CCK8, flow cytometry, autophagy double-labeled adenovirus and Transwell cell chambers, it is found that nano-iron significantly promotes proliferation, activity, cycle process, autophagy and migration of the vascular endothelial cells and inhibits apoptosis; through qRT-PCR (quantitative real-time polymerase chain reaction), cell proliferation, cycle and expression of autophagy pathway marker genes are promoted, and expression of apoptosis pathway marker genes is inhibited; western Blot finds that cell proliferation and the level of autophagy pathway marker protein are remarkably promoted, and the level of apoptosis pathway marker protein is inhibited. In-vitro angiogenesis of vascular endothelial cells is promoted by simulating an in-vitro angiogenesis environment through matrigel.

The invention relates to the field of treatment of neurodegenerative diseases, and discloses a method for treating ALS through intrathecal targeted drug delivery of an extremely low dose of KN93 after a disease is attacked, and the method comprises the following steps: screening ALS model objects showing disease symptoms; within 24 hours after the ALS model object is confirmed to be diseased, the KN93 pharmaceutical composition is applied to the space in the spinal cord sheath for a single time; and evaluating the curative effect of the ALS model object after the KN93 pharmaceutical composition is applied. In a treatment window period within 24 hours after an ALS model object is attacked, an extremely low dose of KN93 pharmaceutical composition is directly delivered to a spinal cord intrathecal gap in an intrathecal administration manner, so that the medicine can quickly enter cerebrospinal fluid circulation and is enriched in a central lesion target region in a targeted manner without penetrating through a blood brain barrier and a blood-spinal cord barrier; therefore, pathological excessive activation of CaMKII is specifically inhibited, and injury mechanisms such as neuronal excitatory toxicity, calcium overload and pro-apoptosis pathway mediated by CaMKII are blocked.

This invention belongs to the field of pharmaceutical technology, specifically relating to the use of charred astragalus in the preparation of drugs that inhibit aristolochic acid-induced kidney damage. Animal experiments have shown that charred astragalus inhibits aristolochic acid-induced kidney damage through anti-oxidative stress, anti-inflammation, and inhibition of apoptosis pathways.

The application discloses application of Reb B in preparation of a medicine for treating lung ischemia-reperfusion injury. The application screens a natural compound Reb B by establishing an alveolar type II cell A549 ischemia-reperfusion model and combining a high-throughput drug screening mode. The Reb B can significantly enhance the OGD / R tolerance of the A549 cell by inhibiting a mitochondrial apoptosis pathway, and provides a theoretical basis for clinical application of the Reb B in ischemia-reperfusion related diseases.

The invention relates to the technical field of medical biology, in particular to application of A-674563 in killing neuroblastoma cells, and finds for the first time that A-674563 can efficiently kill various neuroblastoma cells in a concentration-dependent manner, the IC50 value is as low as 0.1508 mu M, and proliferation, migration and clone formation of the neuroblastoma cells can be remarkably inhibited. The study on the mechanism of action shows that A-674563 accurately targets anaplastic lymphoma kinase (ALK) and is combined with a key residue through a hydrogen bond to down-regulate the expression of ALK protein and activate a downstream apoptosis pathway. Molecular docking and dynamics simulation prove that the two are stably and strongly combined. The invention provides an efficient novel candidate drug and a precise treatment strategy for solving the problems of limited curative effect, insufficient synergism and poor metastasis control of the existing treatment of neuroblastoma, and has a remarkable clinical transformation prospect.

The invention discloses a fusion protein containing mitochondrial pro-apoptotic protein and a preparation method thereof, and belongs to the technical field of biomedicine. The fusion protein is iRGD-MitoPen-Smac N55 (SEQ ID NO: 4), and a triple mechanism of'tumor targeting-cell / mitochondrial delivery-apoptosis activation 'is constructed by connecting an iRGD targeting peptide, a MitoPen bifunctional peptide and a Smac N55 active fragment in series. The preparation method comprises the steps of gene synthesis and optimization, vector construction, cell transfection expression and affinity purification, and the recombinant protein with the purity larger than or equal to 94% is obtained. The fusion protein can be specifically combined with alpha v integrin highly expressed by tumor cells and NRP-1, targeted delivery and mitochondrial apoptosis pathway activation are achieved, proliferation of tumor cells such as breast cancer and colon cancer is efficiently inhibited, in-vivo and in-vitro experiments prove that the anti-tumor effect of the fusion protein is remarkably superior to that of a Smac simulant LCL161, the fusion protein can be used for preparing anti-tumor drugs, and a new strategy is provided for tumor treatment.