17 results about "APOPTOGENIC PROTEIN" patented technology

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 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.

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 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 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 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 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.

Compounds that inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions comprising the compounds, and methods of treating diseases during which anti-apoptotic Bcl-2 proteins are expressed are provided.SOLUTION: A compound having the following formula (I) or therapeutically acceptable salts thereof: 4 - {4 - [(4 ' - Chloro-1, 1 ' - biphenyl-2-yl) methyl] piperazin-1-yl} - N - ({3-nitro-4 - [(tetrahydro-benzamide pyran-4-ylmethyl) amino] phenyl} sulphonyl) - 2 - (2H pyrrolo [2, 3-b] pyridin-5-yloxy) 1H.SELECTED DRAWING: None

The present application relates to the technical field of renal cell carcinoma, and particularly relates to a method for predicting the lipid metabolism regulation mechanism of renal cell carcinoma, which is characterized by the following steps: determining the expression difference of EMT, cell proliferation and apoptosis proteins in groups through molecular detection, and determining the difference of fat pathway genes, oil accumulation degree and fat factor expression level in groups, and determining the correlation between lipid metabolism and GAD2, the present project first proposes the miR-metabolic enzyme-lipid pool regulation axis, which is different from the traditional mode of miR directly targeting proliferation genes. Previous studies have focused on the regulation of miRNA on directly related genes such as tumor cell proliferation and apoptosis, and the present project starts from the fat metabolism pathway and deeply explores the regulation of miR-362-5p targeting GAD2 gene on the progression of renal cell carcinoma (RCC). This innovation provides a new perspective and theoretical framework for RCC research, and is expected to open up a new treatment idea, and a systematic research system from clinical samples, cell experiments, molecular detection to animal experiments is constructed.

Provides a structurally stabilized and / or cysteine-reactive NOXA peptide. [Solution] This disclosure relates to a structurally stabilizing and / or cysteine-reactive NOXA BH3 peptide that can covalently bind to BFL-1 and can also bind to BFL-1 and / or MCL-1 by non-covalent interactions. This disclosure also features methods for using such peptides alone or in combination with other therapeutic agents (e.g., inhibitors of DNA damage response pathway members (e.g., ATM kinase inhibitors, ATR kinase inhibitors, CHK1 / 2 inhibitors, PARP inhibitors), selective inhibitors of MCL-1, selective inhibitors of BCL-2, inhibitors of BCL-2 / BCL-XL) in the treatment of BFL-1 and / or MCL-1-dependent or MCL-1-expressing cancers (e.g., hematopoietic malignancies, melanoma).