49 results about "Pro-Apoptotic Proteins" patented technology

A unique DHA product, 10, 17S-docosatriene (“Neuroprotectin D1” or “NPD1”), was found to provide surprisingly effective neuroprotection when administered right after an experimental stroke. Moreover, both nerve cells and retinal pigment epithelial (RPE) cells were found to synthesize 10,17S-docosatriene (NPD1) from DHA. NPD1 also potently counteracted H2O2 / TNFα oxidative stress-mediated cell apoptotic damage. Under the same oxidative-stress conditions, NPD1 up-regulated the anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-xL, and decreased expression of the pro-apoptotic proteins, Bad and Bax. Moreover, in RPE cells NPD1 inhibited oxidative stress-induced caspase-3 activation, IL-1β-stimulated human COX-2 promoter expression, and apoptosis due to N-retinylidene-N-retinylethanolamine (A2E). Overall, NPD1 protected both nerve and retinal pigment epithelial cells from cellular apoptosis and damage due to oxidative stress. NPD1 concentration in the brain of Alzheimer's patients was found to be significantly decreased from that of controls. In cultured human brain cells, NPD1 synthesis was up-regulated by neuroprotective soluble β amyloid, and NPD1 was found to inhibit secretion of toxic β amyloid peptides.

The present invention relates to targeted killing of a cell utilizing a chimeric polypeptide comprising a cell-specific targeting moiety and a signal transduction pathway factor. In a preferred embodiment, the signal transduction pathway factor is an apoptosis-inducing factor, such as granzyme B, granzyme A, or Bax.

Live, attenuated recombinant rabies virus vaccines are generated using reverse genetics to combine the antigenic determinants that render the rabies virus non-pathogenic with the determinants that are responsible for the elicitation of an effective anti-rabies immune response. These vaccines do not affect the antigenic, and therefore the immunogenic, properties of the virus. The present invention further relates to recombinant rabies virus vaccines that express a pro-apoptotic protein, such as cytochrome c, to increase the capacity to induce apoptosis, thereby enhancing the protective immunity against rabies. This new generation of live rabies virus vaccines represents a safe and effective approach to the eradication of rabies in wildlife, and subsequently humans and livestock.

Undifferentiated primordial stem cells are manipulated to permit their long term growth in defined media lacking serum and feeder layer cells by shifting the apoptotic balance of the cells, through increasing the activity of Bcl-2 family anti-apoptotic proteins or decreasing the activity of Bcl-2 family pro-apoptotic proteins. In some embodiments of the invention, the Bcl family protein is Bcl-2. The ES cells sustain the characteristics of undifferentiated, pluripotent stem cells during long-term serum- and feeder layer cell-free conditions, including the ability to be expanded in vitro, but maintain their potential to differentiate into mature cell types.

The present invention relates to targeted killing of a cell utilizing a chimeric polypeptide comprising a cell-specific targeting moiety and a signal transduction pathway factor. In a preferred embodiment, the signal transduction pathway factor is an apoptosis-inducing factor, such as granzyme B, granzyme A, or Bax.

Single-domain anti-bodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the active of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and / or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins.

An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and / or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and / or Bax serve as improved immunogens and tumor immunotherapeutic agents.

The present invention provides a nucleic acid comprising a) a nucleotide sequence encoding one or more pro-apoptotic proteins, and b) a nucleotide sequence encoding one or more tumor-specific and / or tissue-specific promoters. Also provided is a method of treating cancer, comprising administering the compositions of this invention to a subject.

The invention discloses application of a pentacyclic triterpene compound and a medicine composition, and further discloses the pentacyclic triterpene compound shown in the formula A or the formula B in the specification, and application of a stereoisomer or a tautomer or pharmaceutically acceptable salt or solvate or polymorph of the pentacyclic triterpene compound in preparing medicine for treating diseases (especially cancer) caused by cell apoptosis or cell damage and a BCL-XL inhibitor. R1, R2, R3, R4, R5, R7, R8, R9, R10 and R11 are independently selected from one of hydroxyl, hydrogen, halogen, COR13, COOR14, C1-C4 alkoxy and C1-C4 alkyl, and R6, R12, R13 and R14 are independently selected from hydrogen or C1-C5 alkyl. The pentacyclic triterpene compound has higher inhibitory activity on binding between BCL-XL and pro-apoptosis protein and has guiding significance on design and research and development of the medicine.

Nucleic acid compositions encoding a pro-apoptotic protein, Bok (Bcl-2-related ovarian killer) are identified. Bok has conserved Bcl-2 homology domains 1, 2 and 3 and a C-terminal transmembrane region present in other Bcl-2 related proteins, but lacks the BH4 domain found only in anti-apoptotic Bcl-2 proteins. Over-expression of Bok induces apoptosis. Cell killing induced by Bok is suppressed by co-expression with selective anti-apoptotic Bcl-2 proteins. Bok is highly expressed in the ovary, testis and uterus, particularly in granulosa cells, the cell type that undergoes apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic protein with wide tissue distribution and hetero-dimerization properties facilitates elucidation of apoptosis mechanisms in reproductive and other tissues, and provides a means for manipulating apoptosis.

Single-domain anti-bodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the active of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and / or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins.

The invention belongs to the field of pharmacy and relates to a new application of a traditional Chinese medicine motherwort extract in pharmacy, in particular to the application of the purified motherwort extract in preparing nerve protection medicine for treating cerebral injury, especially the application of the purified motherwort extract in preparing brain protection medicine for treating artery obstruction in the brain. By an animal experiment of the purified motherwort extract, a result indicates that the brain stem volume is obviously reduced after the purified motherwort extract is applied, the obstacle grading of the nerve function is decreased by being compared with a contrast group, the total antioxidant concentration in plasma is increased, the DNA oxidation injury is reduced, the expression levels of apoptosis and apoptosis promoting protein are reduced, and the content of apoptosis resistance protein is also increased. The purified motherwort extract can be used for preparing the nerve protection medicine for treating the cerebral injury and can effectively treat cerebral apoplexy.

The invention discloses a preparation method of lobetyolin, C20H28O8, and application of lobetyolin in the preparation of drugs to treat antagonistic cis-diamminedichloroplatinum (CDDP) induced acute kidney injury, and belongs to the field of compound preparation and isolation and pharmaceutical use development. In-vivo and in-vitro researches show that lobetyolin can effectively alleviate acute kidney injury of mice due to CDDP, including lowering BUN and CRE levels in mouse serum, lowering TNF-alpha and IL-1 beta level in serum, and inhibiting expression levels of pro-apoptotic proteins Bax and Casapase in kidney tissue. In-vitro experiments show that lobetyolin can alleviate the activity reduction of HEK293 kidney cells and cytotoxicity, increase GSH level in the kidney cells and lower the MDA content. Therefore, lobetyolin and an effective component with the same can be prepared into drugs, health products, food additives, compound preparations or the like to prevent acute kidney injury. The drugs or health products with lobetyolin may be of any of forms, such as tablets, capsules, powder injections, injections, pills, soft capsules, granules, plasters and the like.

Undifferentiated primordial stem cells are manipulated to permit their long term growth in defined media lacking serum and feeder layer cells by shifting the apoptotic balance of the cells, through increasing the activity of Bcl-2 family anti-apoptotic proteins or decreasing the activity of Bcl-2 family pro-apoptotic proteins. In some embodiments of the invention, the Bcl family protein is Bcl-2. The ES cells sustain the characteristics of undifferentiated, pluripotent stem cells during long-term serum- and feeder layer cell-free conditions, including the ability to be expanded in vitro, but maintain their potential to differentiate into mature cell types.

The invention relates to the field of natural medicines, and discloses application of salvianolic acid A in preparation of a medicine for treating tumour multi-drug resistance. Compared with salvia extracts of tanshinones, the salvianolic acid A disclosed by the invention has good water solubility, and therefore, the salvianolic acid A has better bioavailability. According to the invention, the salvianolic acid A has obvious inhibiting effect to drug-resistant tumour cells; the mechanism is as follows: apoptosis of drug-resistant tumour cells is induced through up regulation of expression of proapoprotic protein is up-regulated and down regulation of expression of inhibitor of apoptosis protein; tumour drug-resistant protein P-gp expression is inhibited by increasing active oxygen expression level of drug-resistant tumour cells, so that tumour multi-drug drug-resistant cells are overcome, and therefore, the salvianolic acid A disclosed by the invention has the application prospect for preparing the medicine for overcoming tumour multi-drug resistance.

An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and / or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and / or Bax serve as improved immunogens and tumor immunotherapeutic agents.

The invention discloses application of a PCBP1 gene in preparing a radiotherapy sensitivity enhancing kit, and in particular relates to application of the PCBP1 gene in preparing a sensitivity enhancing kit for tumor radiotherapy utilizing ionizing radiation including heavy ion rays. The nucleotide sequence of the PCBP1 gene is as shown in SEQ ID NO.1 and the PCBP1 gene is established in eukaryotic expression plasmid. Together with heavy ion beams, the PCBP1 gene regulates and controls expression of the CD44v6 gene related to tumor metastasis and invasion, inhibits proliferation, migration and invasion of HeLa tumor cells, remarkably down-regulates the cell cycle regulatory protein Cyclin D1, prompts cells to generate G0 / G1 retardation, enhances the radiotherapy sensitivity of HeLa cells, up-regulates pro-apoptotic protein Tap73 and expression of the mitochondria apoptosis pathway MCL, down-regulates the apoptosis inhibition DelNp73 protein, and induces apoptosis of many HeLa cells.

The invention discloses an application of butyric acid and salts thereof in the preparation of medicines for treating or preventing gastric ulcer, and belongs to the field of medicine. According to the above application, the butyric acid and salts thereof, through anti-inflammation and antioxidation, promote the secretion of gastric mucus, upregulate the apoptin BCL2, downregulate the pro-apoptotic protein Bax, have positive curative and preventive effects on gastric ulcer injury, effectively reduce falling, defect, atrophy and bleeding of the gastric mucous membrane, and have important significance to the prevention or treatment of gastric ulcer.

The invention discloses a synthetic method of a mineralized sendai virus-based tumor combined treatment nano preparation, the method is used for synthesizing the photo-thermal tumor combined treatmentnano preparation through bionic simulation of a strategy of mineralizing sendai virus and ICG ((ICG + SEV) coated CaHPO4) by CaHPO4. The method comprises the following specific steps: 1) preparing anindocyanine green aqueous solution; and 2) synthesizing (ICG + SEV) coated CaHPO4 nano particles by a one-pot method. The sendai virus (SEV) can activate the immune function of the body in a whole body mode, and all-around killing and removing of tumors are achieved. The ICG has high photo-thermal conversion efficiency under near-infrared laser irradiation, and tumor photo-thermal treatment can be efficiently guided. The pro-apoptotic protease which promote each other and cause and cause each other exist in a pathway formed by calcium ion signals and tumor cell apoptosis, so that tumor cell apoptosis is accelerated. The composite nanoparticle integrating virus immunotherapy and photothermal therapy can improve the tumor treatment effect.

The invention discloses use of neuregulin 1, belongs to the technical field of a biomedicine, and particularly relates to application of the neuregulin 1 inpreparation of a drug for treating lead encephalopathy. The characteristics of the lead encephalopathy are high expression of inflammatory cells and inflammatory factors and wide neuronal cell death. Neuron loss and nerve inflammatory reaction play a crucial role in the lead encephalopathy process. The neuregulin 1 has a significant nerve inflammatory reaction and a role of protecting cell apoptosis in the lead encephalopathy, can inhibit inflammatory activation, reduces the quantities of microglial cells and astrocytes, reduces the expression level of inflammatory cytokines COX-2, and improves the learning and memory defects caused by lead poisoning. In addition, the quantity of ErbB4 positive cells can be increased by the neuregulin 1; the inhibition apoptosis activity of anti-apoptosis protein Bc1-2 is improved; expression of pro-apoptotic protein Bax is reduced, so that apoptosis is inhibited, and neuregulin 1 has significant neuroprotective effects on the lead encephalopathy.

The invention belongs to the field of traditional Chinese medicine, and particularly relates to application of icaritin in preparation of anti-NK / T cell lymphoma drug. Experiments of intervening human NK / L cell lymphoma cell strains (SNK-10 and SNT-8) through icaritin confirm that icaritin in vitro can remarkably inhibit proliferation of SNK-10 and SNT-8 cells, obviously promote apoptosis of the SNK-10 and SNT-8 cells, increase endogenous Caspase protein, promote expression of apoptin Bax and inhibit expression of Bc1-2 and pBad, and can induce activation of EB viruses in the SNK-10 cells and improve sensitivity, to anti-virus drug, of tumor cells. Icaritin can serve as a pharmaceutically active ingredient to prepare the anti-NK / T cell lymphoma drug and can serve as a pharmaceutically acceptable carrier to prepare drug combinations resistant to NK / T cell lymphoma, and further, icaritin can be combined with the anti-virus drug to prepare anti-NK / T cell lymphoma sensitizing drug.

It has been discovered the BH3-only proapoptotic Bcl-2 proteins like PUMA (the p53 upregulated modulator of apoptosis) can be activated in fibroblast-like synoviocytes present in the joints of subjects with rheumatoid arthritis. This bypasses the p53 apoptotic pathway, which normally clears FLS fomr the joints, but is often defective in arthritis. Suitable therapeutic agents of this invention include gene vectors that cause increased expression of BH3-only proapoptotic proteins in target cells. These agents are formulated in pharmaceutical compositions for administration directly to joint. Reestablishing apoptosis in synoviocytes decreases their pro-inflammatory and destrcutive activity, improving the clinical condition.

Provided herein are therapeutic nanoparticles having a diameter of between 10 nm to 30 nm, and containing a polymer coating, and a nucleic acid containing a sequence complementary to a sequence within a micro-RNA identified as having a role in cancer cell metastasis or anti-apoptotic activity in a cancer cell (e.g., miR-10b) or a sequence within an mRNA encoding a pro-apoptotic protein that is covalently linked to the nanoparticle. Also provided are pharmaceutical compositions containing these therapeutic nanoparticles. Also provided herein are methods of decreasing cancer cell invasion or metastasis in a subject having a cancer and methods of treating a metastatic cancer in a lymph node in a subject that require the administration of these therapeutic nanoparticles to a subject.

The invention discloses a pharmaceutical composition of fingolimod hydrochloride and curcumol and application in the preparation of an anti-oral-cancer medicine. The fingolimod hydrochloride is used combined with curcumol to obtain an unexpected synergistic effect on oral cancer treatment. Compared with independently using any one of the fingolimod hydrochloride and the curcumol, the pharmaceutical composition has higher functions of inhibiting oral cancer cell proliferation, migration and significantly inducing apoptosis, can be made into a variety of preparation forms, and has a good clinical promotion effect and development prospects with a view to clinical treatment of oral cancer patients in the future. According to the principle of the pharmaceutical composition, the combination useof fingolimod hydrochloride and the curcumol may activate the expression of various pro-apoptotic proteins of mitochondrial BH3-only, the apoptosis of the oral cancer cells is synergistically and significantly induced, and meanwhile, the combination of the two medicines further cause cell cycle arrest on the oral cancer cells and inhibit the migration and the proliferation of the oral cancer cells.

Provided nucleic acid- based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell thatis associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and / or eliminating the growth and / or survival of a cell, such as a senescent cell and / or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression constructfor the target cell-specific, production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a targetcell that is a senescent cell or a cancer cell.

The invention relates to the application of icariin in the preparation of a medicine for preventing and treating Alzheimer's disease. According to the invention, experiments such as a Morris water maze experiment, a Western blot experiment, an HE staining method and the like are carried out in an SAMP8 model mouse; it is proved that learning and memory disorder of SAMP8 mice can be reversed afterintragastric administration of ICA, icariin can down-regulate expression of BACE1 so as to reduce deposition of cytotoxic A beta 1-42. Besides, icariin can improve cognitive defects by increasing theexpression of anti-apoptotic protein Bcl-2, reducing the expression of pro-apoptotic protein Bax and remarkably increasing the ratio of Bcl-2 to Bax, so that neuronal apoptosis is inhibited, and neurons are protected. The invention provides further evidences for the clinical curative effect of icariin on Alzheimer's disease.

Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and / or eliminating the growth and / or survival of a cell, such as a senescent cell and / or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

Nucleic acid compositions encoding a pro-apoptotic protein, Bok (Bcl-2-related ovarian killer) are identified. Bok has conserved Bcl-2 homology domains 1, 2 and 3 and a C-terminal transmembrane region present in other Bcl-2 related proteins, but lacks the BH4 domain found only in anti-apoptotic Bcl-2 proteins. Over-expression of Bok induces apoptosis. Cell killing induced by Bok is suppressed by co-expression with selective anti-apoptotic Bcl-2 proteins. Bok is highly expressed in the ovary, testis and uterus, particularly in granulosa cells, the cell type that undergoes apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic protein with wide tissue distribution and hetero-dimerization properties facilitates elucidation of apoptosis mechanisms in reproductive and other tissues, and provides a means for manipulating apoptosis.

The invention discloses use of glaucocalyxin A in the preparation of a medicament for treating liver cancer. Specifically, the invention discloses the action of the glaucocalyxin A on liver cancer cells, and by destroying the mitochondrial membrane potential, causing Cyto-C outflow, inhibiting anti-apoptotic protein Bcl-2, promoting the expression of pro-apoptotic protein Bax, and triggering caspase cascade reaction to induce apoptosis, a new therapeutic medicament for the treatment of liver cancer is provided.

The invention relates to treatment of autoimmune diseases, and particularly discloses compositions for treatment of autoimmune diseases or conditions that result in hair loss, such as alopecia. The compositions include first and second polynucleotides, wherein a) the first polynucleotide comprises a sequence encoding an autoantigen or an antigenic fragment thereof, with at least about 50% of CpG dinucleotide of the first polynucleotide being methylated; and b) the second polynucleotide comprises a sequence encoding a pro-apoptotic protein, or a functional pro-apoptotic fragment thereof, with the pro-apoptotic protein being selected from a group consisting of BAK, BAX, BIM, a death receptor 4, a death receptor 5 or a FAS receptor, wherein 15% or less of said CpG dinucleotide of the second polynucleotide is methylated. The compositions are used intradermally for inducing a tolerogenic immune response against said autoantigen.