40 results about "HIF-1alpha" patented technology

The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte / macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

The invention is suitable for the field of biological medicines, and provides a constructing method of a bone marrow stem cell expressing an osteogenic gene. The method utilizes a lentivirus carrying a hypoxia-inducible factor 1alpha to infect a bone marrow stem cell and to express the osteogenic gene. The method includes following steps: constructing a lentivirus expression vector Lenti-HIF-1alpha-eGFP; packaging the lentivirus expression vector Lenti-HIF-1alpha-eGFP carrying the hypoxia-inducible factor 1alpha; and infecting the bone marrow stem cell with the lentivirus expression vector Lenti-HIF-1alpha-eGFP to obtain the infected bone marrow stem cell capable of expressing the osteogenic gene.

The invention discloses a novel medicinal application of fucoidan polysaccharide sulfate. The application refers to the application of fucoidan polysaccharide sulfate in the preparation of the following products: 1), a product for preventing and / or treating diabetic retinopathy, 2), a product for inhibiting retinal new capillaries, 3), a product for inhibiting VEGF (vascular endothelial growth factor) protein expression of retina tissue, and 4), a product for inhibiting HIF-1 alpha (hypoxia inducible factor-1 alpha)) protein expression of retina tissue. Preferably, the fucoidan polysaccharide sulfate is LMWF with the weight-average molecular weight of 3KD to 30KD. The pharmacodynamic experiment proves that the LMWF has a function in improving the retinopathy of STZ (streptozocin) induced diabetes mellitus mouse; under the function, the function of the retina capillaries is improved and the ischemia and anoxic state in retina are improved, therefore the down-regulation of expression of VEGF and HIF-1alpha are related; because the molecular weight of the LMWF is relatively small, the fucoidan polysaccharide sulfate can be adsorbed after being taken orally, the side effect is less, and therefore, the fucoidan polysaccharide sulfate has latent application significance in preventing and treating retinopathy.

The invention relates to a radiosensitizer and a preparation method thereof, and the radiosensitizer can improve a radiation resistance problem of solid tumors; the radiosensitizer comprises 50%-80% of PLGA-PEI / hypericin nano colloidal particles, 5%-8% of HIF-1alpha-siRNA, and 12%-45% of hyaluronic acid, wherein the hyaluronic acid molecular weight can be any one of 11000, 6600 and 800. The preparation method comprises the steps of firstly preparing the PLGA-PEI / hypericin nano colloidal particles by an emulsion solvent evaporation method, then dropwise adding the HIF-1alpha-siRNA, and finally wrapping with HA. The preparation process is simple and easy to implement.

The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte / macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

The invention provides application of progesterone and pharmaceutically acceptable derivatives thereof to preparation of medicines for inhibiting expression of hypoxia-inducible factor HIF-1alpha. Experimental examples can prove that the progesterone and the pharmaceutically acceptable derivatives have the effect of inhibiting the expression of the hypoxia-inducible factor HIF-1alpha, can significantly reduce the expression level of the hypoxia-inducible factor HIF-1alpha, thus is of a great significance in inhibiting airway remodeling, and can also be applied to preparation of medicines for preventing or treating cancers, an abdominal aortic aneurysm (AAA) disease and bone atrophy during senescence, improving long-term survival of cancer patients, and preventing or treating rheumatoid arthritis, chronic lung diseases, pregnancy-related diseases and inflammatory intestinal diseases.

The invention discloses an amiRNA-HIF-1alpha (artificial microRNA-hypoxia-inducible factor-1alpha) sequence containing recombinant plasmid, which contains a coding sequence of amiRNA-HIF-1alpha and a vector plasmid DNA sequence. The vector plasmid DNA sequence contains a regulatory sequence in connection with the amiRNA-HIF-1alpha, and the vector plasmid is a eukaryotic expression plasmid able to replicate and survive in a host. Construction of the recombinant plasmid includes synthesis of the amiRNA-HIF-1alpha sequence, connection of a target fragment and the vector plasmid, transformation of escherichia coli competent cells by the connection product, electrophoresis identification of the recombinant plasmid and sequencing, and other steps. The recombinant plasmid provided by the invention can be used for studying the action mechanism of amiRNA-HIF-1alpha in tumor angiogenesis, proliferation and apoptosis, invasion and metastasis, and development and production of amiRNA-HIF-1alpha based antitumor drugs, thus providing a new way for prevention and treatment of malignant tumors.

The invention relates to an application of a chromatin remodeled protein 4A (CHMP4A) in promoting growth of tumour cells, in particular to an application of CHMP4A in enhancing the stability and transcriptional activity of a hypoxia- inducible factor 1alpha(HIF-1alpha) and an application thereof in screening a lead compound capable of inhibiting growth of tumour cells. In the invention, a cis-reporter gene screening system is adopted to find that CHMP4A can obviously enhance the stability and transcriptional activity of the hypoxia-inducible factor 1alpha in a Hela cell.

The invention discloses a new biological function of Phosphatidylinositol4-kinase type II alpha PI4KIIalpha and an application based on the new function. PI4KIIalpha plays a key role in regulating andcontrolling a hypoxia-inducible factor HIF-1alpha and a downstream vascular endothecial growth factor VEGF. The selective reduction of PI4KIIalpha expression can obviously inhibit tumor growth and tumor angiogenesis. The PI4KIIalpha can be used as a target molecule for intervening in diseases which are relevant to a gene regulated and controlled by the HIF-1alpha and the diseases which are relevant to angiogenesis. In addition, the target molecule can be used for screening medicines for the relevant diseases.

The invention provides a kit for predicting recurrence and transference risk of a patient suffering from early-stage operable esophageal squamous carcinoma. The kit contains amplification primers of 32 genes of BCL2, Survivin, STAT3, cIAP1, cIAP2, beta-catenin, Cyclin D1, CDKN2A, TCF4, EGFR, HER-2, AREG, EREG, TFPI-2, WNT1, BMI-1, MTOR, ATM, ATR, XRCC1, XRCC2, XRCC3, XRCC4, XRCC5, HIF-1alpha, HIF-2alpha, VEGF, RAD51, beta-actin, GAPDH, GUS and TFRC in all. The kit is capable of accurately predicting transference potential of early-stage operable esophageal squamous carcinoma, so that the transference and recurrence risk of the patient suffering from the early-stage operable esophageal squamous carcinoma after radical operation can be accurately predicted and evaluated, patients with high risk can be particularly monitored and effectively interfered, recurrence and transference of esophageal squamous carcinoma can be reduced, and prognosis of the patients can be further improved.

The invention relates to application of a natural small molecular compound in inflammation and tumor resistance. The small molecular compound is separated from a mesquite amorpha fruticosa fruit and is a novel active monomer named Amorfrutin A. Through a series of researches, Amorfrutin A blocks transfer of p50-p65 from cytoplasm to nucleus and inhibits expression of genes such as proinflammatory genes, cell survival genes, proliferation genes, invasive genes, angiogenesis genes and the like as well as expression of up-regulated apoptosis genes caused by activation of NF-kB. The invention provides a method for treating abnormal activation related disease by changing the activity of the transcription factor NF-kB. Moreover, Amorfrutin A has an obvious inhibiting effect on expression of HIF-1alpha induced by CoCl2.

The present invention provides an isolated myeloid-like cell population comprising a majority of cells that are lineage negative, and which express both CD44 antigen, CD11b antigen, and hypoxia inducible factor 1alpha (HIF-1alpha). These cells have beneficial vasculotrophic and neurotrophic activity when intraocularly administered to the eye of a mammal, particularly a mammal suffering from an ocular degenerative disease. The myeloid-like cells are isolated by treating bone marrow cells, peripheral blood cells or umbilical cord cells with an antibody against CD44 (hyaluronic acid receptor), against CD11b, CD14, CD33, or against a combination thereof and using flow cytometry to positively select CD44 and / or CD11b expressing cells therefrom. The isolated myeloid-like bone marrow cells of the invention can be transfected with a gene encoding a therapeutically useful protein, for delivering the gene to the retina.

The present invention relates to a method for quantitative analysis of interactions between fluorescein-labeled HIF-1α (alpha) C-terminal peptides and cAMP-responsive element binding protein (CBP) or p300 proteins, and a method of screening inhibitors against the formation of HIF-1α-p300 or HIF-1α-CBP protein complexes using the above method.Therefore, the fluorescence polarization (FP) measurement method of the present invention is useful for systemically evaluating the HIF-1α-CBP or HIF-1α-p300 interactions, and examining the effects of posttranslational modifications (hydroxylation, S-nitrosylation, and phosphorylation) of the C-TAD peptide of HIF-1α on the recruitment of p300.

It is intended to provide a pharmaceutical product with a high therapeutic effect in the treatment of a retinal disease accompanied by angiogenesis such as age-related macular degeneration or diabetic retinopathy. A therapeutic agent for a retinal disease containing a substance that specifically inhibits the expression of HIF-1alpha and a substance that specifically inhibits the expression of HIF-2alpha. The inhibitor which is an active ingredient of the therapeutic agent of the invention is an RNAi-inducible nucleic acid, an antisense nucleic acid, or a ribozyme against HIF-1a and HIF-2a, or an expression vector therefor.

The invention discloses a preparation method and application of an RNA interfering medicine for treating a pulmonary hypertension syndrome and an efficacy validation method thereof. The preparation method comprises the following steps: firstly, establishing a slow virus expression vector, namely HIF-1alpha-shRNAi; secondly, packaging HIF-1alpha-shRNAi recombinant plasmids into a preparation; thirdly, injecting the plasmids into bodies of broilers, silencing an HIF-1alpha gene, inhibiting expressions of a vascular endothelial growth factor (VEGF), endothelin 1 (ET 1) and an insulin-like growth factor II (IGF - II) of a downstream gene and the like, controlling a pulmonary vascular remodeling (PVR) phenomenon, reducing damage of a cardiopulmonary function and ascites formation and finally achieving the clinical treatment to the pulmonary hypertension syndrome. The preparation method has the advantages of specificity, high efficiency and multifunctionality and the like on an aspect of treatment.

The invention relates to the technical field of biological medicine, in particular to an application of an HIF-1alpha micromolecular activator in preparation of a medicine for treating neurodegenerative diseases, particularly PD (Parkinson's disease).

The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte / macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

The invention discloses a nucleotide sequence shown in SEQ ID NO.1, and further discloses a recombinant virus containing the nucleotide sequence and application thereof. The recombinant lentivirus can inhibit expression of drug resistance protein Pgp and a drug-resistance related gene HIF-1alpha and also can decrease the pumping rate of a drug, can reverse the drug resistance of intractable epilepsy, can be jointly used with other drugs for treating epilepsy to treat the intractable epilepsy and is good in clinical application prospect.

The invention discloses a mixture of rare ginsenoside and application of the mixture. The mixture of rare ginsenoside comprises rare ginsenoside and a pentose metabolic pathway inhibitor. A rare ginsenoside monomer promotes ubiquitination and degradation of HIF-1alpha (hypoxia-inducible factor-1alpha) through proteasome; the content of the HIF-1alpha in a tumor cell is lowered, theoretically, tumor glycometabolism pathways including pentose-phosphate pathways can be inhibited, and thus the anti-tumor effect is achieved. According to the mixture of rare ginsenoside and the application of the mixture, it is innovatively achieved that the rare ginsenoside monomer and a pentose-phosphate pathway inhibitor 6-amidogen nicotinamide (6-AN) are jointly applied in vitro to act on a hepatoma cell line (HepG2), and the rare ginsenoside monomer and the pentose-phosphate pathway inhibitor 6-amidogen nicotinamide (6-AN) have an obvious synergistic anticancer effect. Therefore, rare ginsenoside and atumor glycometabolism pathway inhibitor which have the effect of regulating glycometabolism pathways are jointly applied to strengthening the anti-tumor effect of the mixture, and the mixture is usedfor therapy of malignant tumors and has a wide application prospect.

The present invention relates to oligooxopiperazines that mimic helix alphaB of the C-terminal transactivation domain of HIF-1alpha. Also disclosed are pharmaceutical compositions containing these oligooxopiperazines and methods of using these oligooxopiperazines (e.g., to reduce gene transcription, treat or prevent disorders mediated by interaction of HIF-1alpha with CREB-binding protein and / or p300, reduce or prevent angiogenesis in a tissue, induce apoptosis, and decrease cell survival and / or proliferation).

The invention provides nano lipidosome for sensitizing tumor radiotherapy, in particular to hemoglobin-lipidosome which is obtained by generating complex emulsion in an oil-in-water manner and then removing an organic solvent through evaporation. The lipidosome can provide stable and safe oxygen supply, can realize the controlled release on a tumor part, can alleviate the low-oxygen state of a tumor micro environment, and can overcome the resistance of the tumor to the radiotherapy. By virtue of intravenous injection, the hemoglobin-lipidosome has effective tumor targeting performance; and moreover, HIF-1alpha and VEGF levels inside the tumor are lowered, and the low-oxygen environment of the tumor is apparently improved. Under X rays, the active oxygen amount of the tumor is apparently increased. By applying the hemoglobin-lipidosome, the radiotherapy effectiveness can be significantly reflected in a living animal model with different radiotherapy resistances. The nano lipidosome is used as an oxygen carrier for sensitizing tumor radiotherapy and is extremely high in bio-compatibility, and the antitumor activity can be significantly improved.

The invention discloses an inhibitor for HIF-1alpha relevant to non-small cell lung cancer radiotherapy, and discloses application of a miRNA-21 inhibitor in preparation of drugs for reducing the HIF-1alpha level in non-small cell lung cancer cells. The nucleotide sequence of the miRNA-21 is 5'-UAGCUUAUCAGACUGAUGUUGA-3' and is shown as SEQ ID NO.1. When the miRNA inhibitor is used, the content of HIF-1alpha which has radiotherapy resistance in the non-small cell lung cancer cells can be reduced, therefore, radiosensitivity of the non-small cell lung cancer cells can be improved, and the miRNA-21 inhibitor is more beneficial for the curative effect of radiotherapy of a non-small cell lung cancer.

The invention discloses construction of a 21ShRNA fluorescent expression vector of a long-term silencing esophageal cancer cell HIF-1Alpha gene. The construction method comprises the following steps of: acquiring HIF-1Alpha gene ID NM_001530.3 from NCBI (National Center of Biotechnology Information), designing 21 oligonucleotide siRNA interference sequences by software forecasting, designing a shRNA-encoded DNA sequence according to plasmid insertion sites and joint structures, and connecting pEZsiRNA6.1 vectors to obtain pEZsiRNA6.1hif-1Alpha recombinant plasmid of the long-term silencing HIF-1Alpha gene. The invention designs the HIF-1Alpha interference sequence and constructs the shRNA long-term interference fluorescence expression vector by utilizing a shRNA principle, can obtain a stable cell line expressed by long-term silencing HIF-1Alpha protein after cell transfection, screening and identification and provide a new material for new drug development and gene therapy which take HIF-1Alpha as a target.

The invention discloses a tumor microtubulin HIF-1alpha double target inhibitor and a preparation method thereof. A synthesized compound inhibits capacity of glycolysis of tumor cells while blocks tumor vessels. As a vascular disrupting agent takes microtubulin and colchicines binding site as a target spot and inhibition of glycolysis takes a hypoxia-inducible factor 1alpha as a target, serial 3',4',5'-trimethoxyl-7-hydroxyl flavone derivatives or 2',3',4'-trimethoxyl-7-hydroxyl flavone derivatives or 4',5',6'-trimethoxyl-7-hydroxyl flavone derivatives are designed and synthesized by taking a flavone natural compound as a nuclear parent and modifying a tumor blood blocking agent. Compounds which act on the microtubulin and inhibit the hypoxia-inducible factor 1alpha at the same are screened by means of in vitro antineoplastic activity and the inhibiting level of a target protein. A candidate drug which acts on a tumor vessel and inhibits glycolysis at the same is selected. A novel potential candidate drug is provided for treating tumor.

Oligonucleotides directed against the hypoxia-inducible factor-1α (HIP-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.

It is intended to provide a pharmaceutical product with a high therapeutic effect in the treatment of a retinal disease accompanied by angiogenesis such as age-related macular degeneration or diabetic retinopathy. A therapeutic agent for a retinal disease containing a substance that specifically inhibits the expression of HIF-1alpha and a substance that specifically inhibits the expression of HIF-2alpha. The inhibitor which is an active ingredient of the therapeutic agent of the invention is an RNAi-inducible nucleic acid, an antisense nucleic acid, or a ribozyme against HIF-1a and HIF-2a, oran expression vector therefor.

In the present invention, the mechanisms to coordinately regulate EMT marker genes during EMT and the interplay between these chromatin modifiers were examined. According to the experimental results, a set of marker consisting of HIF-1α, HDAC3, and WDR5 is provided to predict prognosis or overall survival of cancer patients. By determining if the set markers are co-expressed in a biological sample, it can reach relatively higher predictability of prognosis situation or overall survival as compared with the current markers.

The invention discloses a nucleotide sequence shown in SEQ ID NO.1, and further discloses a recombinant virus containing the nucleotide sequence and application thereof. The recombinant lentivirus can inhibit expression of drug resistance protein Pgp and a drug-resistance related gene HIF-1alpha and also can decrease the pumping rate of a drug, can reverse the drug resistance of intractable epilepsy, can be jointly used with other drugs for treating epilepsy to treat the intractable epilepsy and is good in clinical application prospect.

The invention discloses drug targets for treating colon cancer. The drug targets are PTBP3 and HIF-1alpha. The invention takes in-vitro stable transfection cell lines or xenografts formed by the sameas research objects, and proves that the inhibition of HIF-1alpha can enhance the inhibition of PTBP3 through the drug synergistic effect so as to realize the treatment effect on colon cancer. The twodrug targets are simultaneously inhibited to have obvious drug synergistic anti-tumor effect, and can be used as a novel treatment method for colon cancer.