41 results about "APOPTOGENIC PROTEIN" patented technology

Disclosed is a methyl- and trifluoromethyl-containing disubstituted sulfonamide selective BCL-2 inhibitor; specifically disclosed are a compound of formula I, a stereoisomer or pharmaceutically acceptable salt of same, a preparation method therefor, and a pharmaceutical composition comprising the compound. Also disclosed are uses of the compound and of the pharmaceutical composition comprising the compound in treating anti-apoptotic protein BCL-2-related diseases such as cancer.

The invention provides a method for detecting the influence of drug-containing serum of Sijunzi decoction on hepatic stem cells. The method comprises the steps of cell culture, drug-containing serum preparation, cell proliferation experiment, cell damage model establishment and treatment, oxidative stress related index detection, protein expression analysis and the like. According to the method, cell activity is detected through a CCK-8 method, cell nucleus morphological change is observed through Hoechst 33342 staining, the apoptosis rate is detected through Annexin V / PI double staining in combination with flow cytometry, apoptosis-related protein expression is detected through Western blot, and the action mechanism of the drug-containing serum is comprehensively evaluated. Experimental results show that the drug serum of the Sijunzi decoction can promote proliferation of liver stem cells, reduce oxidative stress injury induced by H2O2, improve cell viability and oxidation resistance, reduce cell apoptosis rate, up-regulate expression of anti-apoptotic protein Bcl-2 and inhibit expression of pro-apoptotic protein Bax and Cleaved Caspase-3 at the same time.

This disclosure features structurally-stabilized and / or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and / or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and / or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1 / 2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2 / BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

The present application provides an indole derivative and a preparation method and application thereof. The preparation method comprises the following steps: dissolving copper acetate and triethylamine in isopropyl alcohol, stirring until completely dissolved to obtain a reaction medium; adding 5-bromo indigo and indole into the reaction medium, fully stirring at room temperature until the reaction is completely converted; removing the reaction solvent by distillation to obtain a crude product, purifying and recrystallizing to obtain a high-purity solid powder of the indole derivative. The indole derivative has a significant inhibitory effect on tyrosinase, melanin production and transfer; has high antioxidant capacity for scavenging intracellular active oxygen free radicals; through the mechanisms of affecting the membrane potential of mitochondria, activating the related apoptosis signaling pathway and promoting the expression of apoptosis proteins, etc., the A549 cell is prompted to enter the apoptosis program, thereby providing a new potential strategy and research direction for the apoptosis regulation of tumor cells, and having important research value and application prospect.

A drug conjugate includes a structure shown by the following formula: Z-(linker-[R]m)n. In the formula, Z is a drug compound, R is a sugar, and m and n are independently an integer from 1 to 6. The drug compound Z is a hepatitis virus targeting drug, a hepatitis B virus (HBV) drug, an inhibitor of apoptosis protein (IAP) antagonist, a multidrug resistance (MDR) inhibitor, or analogues, precursors, prodrugs, derivatives thereof.

The invention belongs to the technical field of biological medicines, and particularly relates to lipid nanoparticles as well as a preparation method and application thereof. The invention discloses a lipid nanoparticle. The material of the lipid nanoparticle comprises phospholipid and cholesterol. According to the invention, a lipid nano-carrier delivery system entrapped with apoptotic protein Bax is prepared through a microfluidic technology, and high encapsulation rate and stable delivery of protein drugs are realized. The nano-carrier delivery system capable of actively encapsulating the lipidosome realizes targeted delivery to senescent cells in vivo, so that senescent cell apoptosis is effectively induced, the proportion of senescent cells in tissues is reduced, and a new thought and means are provided for anti-aging treatment.

The invention relates to the technical field of biology, in particular to acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0. 1O3 nanoparticles capable of triggering post-translational modification as well as a preparation method and application of the acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0.1 O3 nanoparticles. Stirring and mixing the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred mixed solution; mixing the stirred mixed solution with sodium hydroxide and polyvinylpyrrolidone, and performing heat treatment to obtain a heat-treated substance; and carrying out solid-liquid separation on the heat-treated substance to obtain a solid, washing the solid to be neutral, and drying. The nanoparticles provided by the invention consume H < + > near mitochondria under ultrasonic stimulation, so that mitochondrial membrane potential depolarization is caused. After mitochondrial membrane potential depolarization, E3 ubiquitin ligase Parkin is transferred from cytoplasm to a mitochondrial outer membrane, and is massively gathered and accumulated on the mitochondrial outer membrane, so that ubiquitination modification and cascade degradation of mitochondrial outer membrane anti-apoptosis protein MCL-1 are caused, and cell apoptosis is promoted.

Protein phosphatase 5 (PP5) is a serine / threonine protein phosphatase involved in the maturation and activation of numerous signaling pathways essential for cancer growth. PP5 activity is essential for the survival of clear cell renal cell carcinoma (ccRCC), however the mechanism remains unclear. Data demonstrates that PP5 interacts with caspase-8, FADD, and RIPK1, components of extrinsic apoptotic pathway Complex II. Specifically, PP5 dephosphorylates and inactivates the death effector proteins RIPK1 and FADD, preserving Complex II integrity and regulating extrinsic apoptosis. Protein phosphatases are considered to be ‘undruggable,’ however we have developed a specific inhibitor of PP5 (P-053) that prevents substrate binding to the active site. Encouragingly, PP5 inhibition using P-53 in VHL-null ccRCC robustly induces extrinsic apoptosis. Taken together, the data suggests that PP5 promotes ccRCC survival by suppressing extrinsic apoptosis, and small molecule inhibition of PP5 presents a viable therapeutic strategy for ccRCC.

The invention provides a novel application of melia diol. The melia diol has a remarkable senescence cell removing capability in a bleomycin induced cell senescence model, an etoposide induced cell senescence model and a replicative cell senescence model; the activity of anti-apoptotic protein Bcl-2 can be obviously inhibited; the neem diol has no obvious liver and kidney toxicity while selectively removing senescent cells; the neem diol has the effects of remarkably lightening wrinkles on the back skin of a photoaged mouse, improving the transdermal moisture loss condition of the back skin of the photoaged mouse, increasing the moisture content of the back skin of the photoaged mouse, reducing the thickness of an epidermal layer and improving the fracture and content of collagenous fibers in a corium layer; the method has a wide application prospect in preparation of anti-aging products.

The application discloses a kind of targeted dual anti-apoptotic protein polymer micelles and its preparation method and application, to overcome single drug resistance with two kinds of small molecule drugs for inhibiting the expression of anti-apoptotic protein BCL-2 and MCL-1 simultaneously loaded by polymer carrier.VEN and SOR in clinical treatment are obviously hematological toxicity due to the need to use high dose, reduce the overall treatment effect, the application discloses new targeted dual anti-apoptotic protein polymer micelles, effectively solve the problems of large dose, toxicity in the prior art.The experimental results show that TPMs-V / S effectively reduces the dose, toxic side effects of VEN and SOR, effectively improves the curative effect of double drug.

The application provides semi total flavonoids of Liquidambar, which is obtained by using stems of Liquidambar cathayensis Hung T.Chang as raw materials and adopting ultrasonic-assisted low eutectic solvent extraction, wherein the yield of the total flavonoids is 71.95%±6.49%. The application also provides a preparation method and application of the semi total flavonoids of Liquidambar. The semi total flavonoids of Liquidambar have significant antioxidant activity, can be used for nerve protection, can be used for treating cerebral ischemia or anti-ischemic stroke, can improve cerebral ischemic nerve function injury, can reduce cerebral infarction volume, can reduce neuron damage degree, can reduce activation of astrocytes, can reduce expression level of apoptotic proteins, can protect neurons and synapses, and can protect vascular endothelial cells. The drug efficacy is clear and controllable, is equivalent to that of positive drug nimodipine, can reach significant drug efficacy at a low dose, is safer in clinical use, and provides a new selection for clinic.

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 invention discloses a method for detecting the influence of bilirubin stimulation on human umbilical cord mesenchymal stem cells, and relates to the technical field of experimental medicine. Comprising the following steps: S1, culturing cells; s2, preparing a bilirubin solution; s3, detecting the cell survival rate by a CCK-8 method; s4, adipogenic differentiation induction; s5, osteogenic differentiation induction; s6, determining the concentration of cell factors through an ELISA method; and S7, detecting the expression of the apoptotic protein by using Western blotting. The invention provides a detailed and clear experimental method which is used for detecting the influence of bilirubin stimulation on human umbilical cord mesenchymal stem cells. The influence of bilirubin on hUC-MSCs can be comprehensively evaluated through the steps of detecting the cell survival rate through a CCK-8 method, inducing adipogenesis and osteogenesis differentiation, determining the cell factor concentration through an ELISA method, detecting apoptosis protein expression through Western blotting and the like.

The invention relates to the technical field of nanoprobe preparation and application, and specifically discloses a fluorescent nanoprobe COF-H1 / H2-Peptide and a preparation method and application thereof. 1,3,5-Tris(4-aminophenyl)benzene and 2,5-dimethoxyterephthaldehyde are mixed with acetonitrile, glacial acetic acid is added, mixed and centrifuged to obtain a precipitate as COF NPs nanoparticles; the COF NPs nanoparticles are dispersed in a PBS buffer to obtain a COF NPs solution; the COF NPs solution is mixed with a hairpin DNA labeled with Texas Red to obtain a COF-HI / H2NPs solution, and then the COF-H1 / H2NPs solution is mixed with a peptide labeled with Cy5 to obtain a fluorescent nanoprobe COF-H1 / H2-Peptide. The fluorescent nanoprobe COF-H1 / H2-Peptide prepared by the present invention is used for cyclic amplification detection of miRNA-221, and realizes simultaneous detection of apoptotic protein caspase-3, has high specificity, a detection limit of 2.79 pM, good biocompatibility, and is easy for cell imaging, and realizes CHA cyclic amplification detection of low-abundance miRNA-221 in living cells.

The invention discloses application of INO80E in preparation of an anti-atherosclerosis medicine, and belongs to the technical field of biological medicines. The invention reveals for the first time that INO80E can interact with histone deacetylase 1 (HDAC1) so as to deacetylate a transcription factor YY1, so that vascular endothelial cell apoptosis is inhibited, and the purpose of delaying an atherosclerosis process is achieved. Experiments prove that the expression level of INO80E in an atherosclerosis model is remarkably reduced; overexpression of INO80E can effectively reverse endothelial cell apoptosis induced by oxidized low-density lipoprotein (ox-LDL) and restore expression balance of anti-apoptotic protein Bcl-2 and pro-apoptotic protein BAX. Therefore, the INO80E can be used as a brand new drug target for treating or preventing atherosclerosis related diseases, can be used for preparing diagnostic reagents or drugs, and has the advantages of no equipment dependence and strong targeting.

The present invention discloses a tetrahedral framework nucleic acid-lipoic acid complex, which is formed by the complexation of tetrahedral framework nucleic acid and lipoic acid; the molar ratio of the tetrahedral framework nucleic acid to lipoic acid is 1:40 to 1:480. The present invention uses tFNA as a carrier for the co-delivery of lipoic acid, transports lipoic acid into cells, inhibits the production of reactive oxygen species, regulates the apoptotic protein pathway Bcl-2 / Bax / Caspase-3, inhibits the expression of the inflammatory pathway NF-κB, effectively treats the oxidative stress and inflammation caused by photo-damage, achieves the purpose of treating skin photo-damage, has a clear mechanism, obvious effects, and has good application prospects.

The invention relates to the technical field of medicines. The invention provides the application of the DOR agonist in preparing the medicine for regulating and controlling the phosphorylation level of the Tau protein, and the DOR agonist can inhibit excessive phosphorylation of the Tau protein, so that the effect of preventing and / or treating the degenerative nervous system diseases (such as Alzheimer's disease) related to Tau protein lesion is achieved. The invention further provides application of the DOR agonist in preparation of drugs for regulating and controlling expression levels of protein kinase CDK5, protein kinase AMPK, cyclin D1, cyclin B1 and apoptosis protein c-caspase 3, the DOR agonist can inhibit the expression levels of the protein kinase and the like, further inhibits excessive phosphorylation of Tau protein, prevents damage of Tau protein to the brain, and can be used for preparing drugs for regulating and controlling the expression levels of the protein kinase and the like. Therefore, the effect of preventing and / or treating degenerative nervous system diseases such as Alzheimer's disease is achieved.

The invention belongs to the field of biological medicines, and discloses application of a Meis1 inhibitor in preparation of a medicine for relieving acute renal tubule injury. Aiming at the clinical problem that acute kidney injury (AKI) lacks a specific drug, the invention firstly discovers that marrow cytophilic virus integration site 1 (Meis1) is obviously up-regulated in AKI kidney tissues, and a folic acid (FA) and ischemia reperfusion (IR) double-animal model proves that the Mis1 inhibitor MEISi-2 (0.1-1mg / kg) is given; and intraperitoneal injection is carried out 1 day to 2 days before injury), so that the serum creatinine can be obviously reduced, the pathological injury of renal tubules (PAS score is more than or equal to 50%) can be improved, and injury markers KIM-1 / NGAL and apoptotic protein Cleaved Caspase 3 can be inhibited. In-vitro experiments further prove that MEISi-2 (1 [mu] M) can relieve apoptosis of renal tubular epithelial cells induced by hypoxia and reoxygenation (the apoptosis rate reaches 21.9%) by inhibiting Meis1. The invention also provides a pharmaceutical composition containing MEISi-2 (10-100 [mu] g / mL) and a normal saline injection preparation. The scheme is high in safety (no liver and kidney cardiotoxicity is found), and a brand new means is provided for targeted therapy of AKI.

The invention belongs to the technical field of biomedicine, and particularly relates to application of an exogenous recombinant protein ANXA5 in preparation of a medicine for treating cerebral hemorrhage. The invention reveals that the expression level of ANXA5 after cerebral hemorrhage is increased; by adding the recombinant ANXA5 protein, the expression level of ferroptosis related protein can be reduced; meanwhile, the expression level of apoptotic protein is reversed, the oxidative stress level is reduced, and the MDA and active oxygen levels are obviously reduced, which proves that the recombinant protein ANXA5 plays an inhibiting role in neuronal ferroptosis after cerebral hemorrhage. The invention provides a basis for using the recombinant protein ANXA5 as a novel medicine for treating cerebral hemorrhage, especially ferroptosis caused by cerebral hemorrhage.

The present application relates to the technical field of medicine, and particularly relates to application of ganoderma triterpene in preparation of medicine for treating cervical cancer. Ganoderma triterpene (Ganodecalone A, referred to as GDA) can inhibit migration, proliferation and clonogenic capacity of cervical cancer cells; GDA can arrest the cell cycle of cervical cancer cells in G0 / G1 phase, and with the increase of the concentration of GDA, the proportion of cells in G0 / G1 phase is significantly increased; GDA can promote apoptosis of cervical cancer cells, and with the increase of the concentration of GDA, the proportion of late apoptotic cells is significantly increased; GDA can promote apoptosis of cervical cancer cells by reducing the phosphorylation level of Akt in the cervical cancer cells. GDA and Akt phosphorylation agonist SC79 are mutually antagonistic, and when GDA is combined with Akt phosphorylation inhibitor MK-2206, the apoptosis of two strains of cervical cancer cells is promoted. GDA can induce apoptosis of cells by inhibiting phosphorylation of Akt, up-regulating pro-apoptotic protein Bad and down-regulating anti-apoptotic protein Bcl-2, and thus the anti-tumor effect is exerted.

The present invention provides a new use of cycloeugenol. The cycloeugenol has a significant ability to eliminate senescent cells in a bleomycin-induced cell senescence model, an etoposide-induced cell senescence model, and a replicative cell senescence model; can significantly inhibit the activity of the anti-apoptotic protein Bcl-2; cycloeugenol selectively eliminates senescent cells while having no obvious liver or kidney toxicity; cycloeugenol can significantly reduce the expression levels of aging biomarkers such as P16 and P21 in naturally aged mice, improve the antioxidant capacity of naturally aged mice, restore the abnormal number of immune cells caused by natural aging, and significantly reduce skin wrinkles in naturally aged mice. The cycloeugenol has a clear anti-aging effect and has broad application prospects in the preparation of anti-aging products.

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.

The invention provides an indole derivative as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving copper acetate and triethylamine in isopropanol, and stirring until copper acetate and triethylamine are completely dissolved to obtain a reaction medium; adding 5-bromoisatin and indole into the reaction medium, and fully stirring at room temperature until reactants are completely converted; and distilling to remove the reaction solvent to obtain a crude product, and purifying and recrystallizing to obtain solid powder of the high-purity indole derivative. The indole derivative has a remarkable inhibition effect on generation and transfer of tyrosinase and melanin; the antioxidant capacity of efficiently removing active oxygen free radicals in cells is achieved; the A549 cell is promoted to enter an apoptosis procedure by influencing the membrane potential of mitochondria, activating a related apoptosis signal channel, promoting the expression of apoptosis protein and other mechanisms, so that a new potential strategy and a research direction are provided for the apoptosis regulation and control of tumor cells, and the method has important research value and application prospect.

The invention discloses a mesenchymal stem cell with anti-apoptosis and in-vivo tracing functions as well as preparation and application thereof, and relates to the technical field of biology. The invention specifically discloses a mesenchymal stem cell for overexpressing anti-apoptotic protein, luciferase and fluorescent protein. The mesenchymal stem cell surface marker retains the characteristics of the mesenchymal stem cell surface marker, has multidirectional differentiation potentials of adipogenesis, osteogenesis and cartilage formation, and has no tumorigenicity in immunodeficient animal bodies; the method can track the cell distribution and survival ability in real time, has a good application prospect in the aspects of treating neurodevelopmental disorders or neurodegenerative diseases, researching a treatment mechanism and in-vivo / in-vitro proliferation, migration, colonization, differentiation or integration behaviors of the neurodevelopmental disorders or neurodegenerative diseases, provides a standardized and visual research platform for the field of stem cell research, and has a wide application prospect. The important scientific value and clinical transformation potential are realized.

The application belongs to the technical field of biomedicine, and particularly relates to application of exogenous recombinant protein ANXA5 in preparation of a medicine for treating cerebral hemorrhage. The application discloses that the expression level of ANXA5 is increased after cerebral hemorrhage; by adding the recombinant ANXA5 protein, the expression level of an iron death related protein can be reduced; meanwhile, the expression level of an apoptosis protein is reversed, the oxidative stress level is slightly reduced, and the levels of MDA and active oxygen water are obviously decreased, which proves that the recombinant protein ANXA5 plays an inhibiting role on neuron iron death after cerebral hemorrhage. The application provides a new type of medicine basis for using the recombinant protein ANXA5 as a treatment for cerebral hemorrhage, especially iron death caused after cerebral hemorrhage.

The application relates to the technical field of biology, and particularly relates to a sound electricity Ba that triggers post-translational modification 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles, a preparation method and application thereof. A titanium tetrachloride solution and a mixed reagent solution are stirred and mixed to obtain a stirring mixed solution; the stirring mixed solution is mixed with sodium hydroxide and polyvinylpyrrolidone and then subjected to heat treatment to obtain a heat-treated product; the heat-treated product is subjected to solid-liquid separation to obtain a solid, and the solid is washed to be neutral and dried. + The nanoparticles provided by the application consume H + around mitochondria under ultrasonic stimulation, leading to depolarization of a mitochondrial membrane potential. After the mitochondrial membrane potential is depolarized, E3 ubiquitin ligase Parkin is transferred from a cytoplasm to a mitochondrial outer membrane, and is massively aggregated and accumulated on the mitochondrial outer membrane, leading to ubiquitination modification and cascade degradation of an anti-apoptotic protein MCL-1 of the mitochondrial outer membrane, so that cell apoptosis is promoted.

Disclosed is a BCL-2 protein apoptosis inducer, and further disclosed are the uses of the compound and a pharmaceutical composition comprising the compound in the preparation of a drug for treating diseases related to anti-apoptotic protein BCL-2. The compound has potent BCL-2 / BAK blocking activity, and can be used for treating diseases such as infectious diseases, immune diseases, inflammatory diseases or cell proliferation abnormalities that benefit from the inhibition of anti-apoptotic protein BCL-2.

The invention discloses a product for reducing the phosphorylation level of a Serine 99 site of a BAD protein and an anti-tumor application of the product. The invention provides the BAD S99A mutant, phosphorylation is specifically blocked through the BAD S99A mutant, accurate regulation and control of an apoptosis pathway are achieved, and the problems that in the prior art, due to the fact that the phosphorylation state of BAD cannot be controlled, the apoptosis activation efficiency is low, and the mechanism is indefinite are solved.

The invention discloses an application of aucubin in preparation of a medicine for improving ischemia-reperfusion pan apoptosis of lower limbs, on one hand, an in-vitro cell experiment shows that the aucubin treatment can improve the cell viability of a mouse primary gastrocnemius muscle pan apoptosis model and reduce the cell apoptosis, so that the scratch healing rate is improved; meanwhile, the expression of related death proteins of a pan-apoptotic cell model can be reduced; on the other hand, animal in-vivo experiments show that aucubin can regulate a TNF-NFKB pathway through negative feedback and inhibit polarization of M1 inflammatory macrophages, so that expression of lower limb ischemia reperfusion pan-apoptosis protein is reduced, and the effect of improving pan-apoptosis caused by lower limb ischemia reperfusion is achieved.