61 results about "Nuclear translocation" patented technology

The invention relates to the modulation of gene expression in a cell, also called gene control, in particular in relation to the treatment of a variety of diseases. The invention provides a method for modulating expression of a gene in a cell comprising providing the cell with a signaling molecule comprising a peptide or functional analogue thereof. Furthermore, the invention provides a method for identifying or obtaining a signaling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell comprising providing the cell with a peptide or derivative or analogue thereof and determining the activity and / or nuclear translocation of a gene transcription factor.

Disclosed is a conjugate comprising a biologically active agent (drug) linked to a subcellular targeting moiety that targets a drug specifically to the nucleus. Targeting is achieved by attaching a steroid hormone (or an analog) to the drug. The steroid hormone attached to the drug binds its corresponding receptor, the formation of the receptor-ligand complex results in the internalization of the complex into the nucleus, thus resulting in nuclear translocation of the drug. Also disclosed is a conjugate (comprising the complex of the drug and the steroid hormone) bound to a polymer by spacers allowing for concurrent passive targeting to the tumor cell (afforded by attachment to the polymer by the EPR effect) and nuclear targeting of the conjugate (due to the presence of the steroid). Using a suitable degradable spacer allows for the release of free drug in the tumor and enhances nuclear targeting efficacy. The polymer can be further linked to a cellular targeting molecule, where the targeting molecule directs the polymer to specific cells. One may thus be able to effectively target drugs to the nucleus of tumor cells. With little or modifications, several therapeutic agents can be targeted using the invention.

This invention pertains to the identification of two novel epithelial signaling pathways in ER-positive breast cancer s and the discovery that the cellular biology and (likely also the clinical outcome) of ER-positive breast cancer cells is unexpectedly altered when these signaling pathways are activated. The first pathway pertains to the discovery that NF-κB activation and / or DNA binding is implicated in the etiology of ER-positive breast (and other) cancers. The second pathway involves ligand-independent quinine-mediated ER activation by posphorylation (e.g. on SER-118 and SER-167 residues of ER) and nuclear translocation of full-length (67 kDA) ER as well as the phorphorylating activation of a truncated and nuclear-localized ER variant (˜52 kDa).

Agents that stimulate nuclear translocation of Nrf2 protein and the subsequent increases in gene products that detoxify and eliminate cytotoxic metabolites are provided in a method for treating glaucomatous retinopathy or optic neuropathy. The structurally diverse agents that act on the Nrf2 / ARE pathway induce the expression of enzymes and proteins that possess chemically versatile cytoprotective properties and are a defense against toxic metabolites and xenobiotics. Agents include certain electrophiles and oxidants such as a Michael Addition acceptor, diphenol, thiocarbamate, quinone, 1,2-dithiole-3-thione, butylated hydroxyanisole, flavonoid, an isothiocyanate, 3,5-di-tert-butyl-4-hydroxytoluene, ethoxyquin, a coumarin, combinations thereof, or a pharmacologically active derivative or analog thereof.

The invention belongs to the field of pharmaceutical chemistry, and specifically relates to an application of specific chalcone compounds in the preparations of inflammation resisting medicines and medicines used for treating inflammation-related diseases. With the chalcone compounds, expression and release of various inflammatory factors such as TNF-alpha, IL-6, COX-2, IL-1beta and IL-12 can be inhibited; nuclear translocation of an inflammation-regulation-related nuclear factor -kappaB can be substantially inhibited; and phosphorylation of inflammation signal pathways ERK and p38 can be inhibited. As a result of in-vivo experiments, with the compounds, the survival rate of LPS-introduced mice mortality can be substantially improved.

Agents that stimulate nuclear translocation of Nrf2 protein and the subsequent increases in gene products that detoxify and eliminate cytotoxic metabolites are provided in a method for treating diabetic retinopathy or drusen formation in age-related macular degeneration. The structurally diverse agents that act on the Nrf2 / ARE pathway induce the expression of enzymes and proteins that possess chemically versatile cytoprotective properties and are a defense against toxic metabolites and xenobiotics. Agents include certain electrophiles and oxidants such as a Michael Addition acceptor, diphenol, thiocarbamate, quinone, 1,2-dithiole-3-thione, butylated hydroxyanisole, flavonoid other than genistein, an isothiocyanate, 3,5-di-tert-butyl-4-hydroxytoluene, ethoxyquin, a coumarin, combinations thereof, or a pharmacologically active derivative or analog thereof.

The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

The present invention provides a peptide comprising amino acid sequences R I, F I and R I G C and containing 25 or fewer amino acid residues, and capable of transporting a functional molecule into a cell, and also into a nucleus, more efficiently than a previous PTD.

The invention discloses short chain polypeptide capable of promoting TFEB nuclear translocation, linear short chain polypeptide based on the short chain polypeptide, and an application of the short chain polypeptide to alleviating cerebral ischemia damage, and belongs to the technical field of biological pharmaceuticals. The short chain polypeptide disclosed by the invention is short chain polypeptide obtained through fusing function areas combined from TFEB protein and 14-3-3 protein, and the nucleotide sequence is as shown in SEQ.ID.NO.1. The invention further discloses the linear short chain polypeptide protecting the short chain polypeptide. The linear short chain polypeptide is obtained through fusing cell-penetrating peptide with the short chain polypeptide. Experiment verifies thatthe synthesized peptide can adjust and control TFEB nuclear translocation, and promote CMA to alleviate cell injury. Therefore, the invention discloses an application of the short chain polypeptide totreatment new target points for alleviating nerve cell death and improving cerebral ischemia damage.

The present invention provides the application of 2-methoxy estradiol, Neomycin sulfate and their mixture in inhibiting the nuclear translocation of angiogenesis factor. Animal test shows that each of 2-methoxy estradiol and Neomycin sulfate can inhibit the growth of human tumor cell in nude mouse and the mixture of them has even high effect. The present invention also provides the medicine composition containing 2-methoxy estradiol and Neomycin sulfate.

There is disclosed an isolated cDNA sequence (SEQ ID NO:1) encoding a P4.33 polypeptide and comprising a coding region (SEQ ID NO:2) of the sequence described in SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1. The P4.33 polypeptide functions as a specific cell-surface receptor for IGFBP-3, and undergoes nuclear translocation in combination with IGFBP-3. In particular aspects, IGFBP-3 and P4.33 (IGFBP-3R) cooperatively suppress DNA synthesis and cell growth, and induce caspase activation and apoptosis in cancer cells, indicating that P4.33 is an important mediator of IGF-independent growth inhibitory actions of IGFBP-3. The P4.33:IGFBP-3 system of the present invention can be used, inter alia, in screening and diagnostic assays, and for therapeutic methods for cancer treatment and tumor suppression.

There is disclosed an isolated cDNA sequence (SEQ ID NO:1) encoding a P4.33 polypeptide and comprising a coding region (SEQ ID NO:2) of the sequence described in SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1. The P4.33 polypeptide functions as a specific cell-surface receptor for IGFBP-3, and undergoes nuclear translocation in combination with IGFBP-3. IGFBP-3 and P4.33 (IGFBP-3R) cooperatively suppress DNA synthesis and cell growth, and induce caspase activation and apoptosis in cancer cells, indicating that P4.33 is an important mediator of IGF-independent growth inhibitory actions of IGFBP-3. The P4.33:IGFBP-3 system of the present invention can be used, inter alia, in screening and diagnostic assays, and for therapeutic methods for cancer treatment and tumor suppression.

The invention discloses a method for detecting the content of soluble CD28 in blood of patients suffering Graves disease. The method comprises: preparing materials, reagents and blood specimens, then sequentially conducting biotin labeling of a monoclonal antibody, identification of the biotin-labeled monoclonal antibody, drawing of an sCD28 standard work curve, separation and purification of T cells in Graves-suffering patient blood, phenotypic analysis of the T cells of the Graves-suffering patients, determination of the content of soluble CD28 in the Graves-suffering patient blood, immunoblotting analysis of the soluble CD28 in the patient blood, determination of the influence of the soluble CD28 on cytokines secreted by dendritic cells, determination of the influence of the soluble CD28 on dendritic cell NF-kB nuclear translocation and other determination steps, as well as statistical analysis. The method for detecting the content of soluble CD28 in blood of patients suffering Graves disease in the invention provides an experimental basis and theoretical base for further investigating the establishment of an optimized in vitro detection scheme by combining other soluble costimulatory molecules and the promotion significance in clinical diagnosis, treatment and prognosis assessment of autoimmune diseases, and for searching new immunologic intervention means.

Agents that stimulate nuclear translocation of Nrf2 protein and the subsequent increases in gene products that detoxify and eliminate cytotoxic metabolites are provided in a method for treating diabetic retinopathy or drusen formation in age-related macular degeneration. The structurally diverse agents that act on the Nrf2 / ARE pathway induce the expression of enzymes and proteins that possess chemically versatile cytoprotective properties and are a defense against toxic metabolites and xenobiotics. Agents include certain electrophiles and oxidants such as a Michael Addition acceptor, diphenol, thiocarbamate, quinone, 1,2-dithiole-3-thione, butylated hydroxyanisole, flavonoid other than genistein, an isothiocyanate, 3,5-di-tert-butyl-4-hydroxytoluene, ethoxyquin, a coumarin, combinations thereof, or a pharmacologically active derivative or analog thereof.

The invention belongs to the field of medicines, relates to novel pharmaceutical application of ginkgolic acid and particularly relates to application of ginkgolic acid (C17:1), which is a syzygiumtetragonum extract having a structural formula show in the specification, in preparation of a medicine for preventing and / or treating diseases caused by overactivity of osteoclast. The ginkgolic acid (C17:1) is capable of preventing nuclear translocation of NFATc1 and inhibiting differentiation and bone erosion of osteoclast and thus is used for preparing the medicine for preventing and treating the diseases including osteoporosis, osteolysis, rheumatoid arthritis, multiple myeloma, Paget's disease, hypercalcemia of tumors, osteogenesis imperfect, alveolar bone deficiency or bone loss caused during immunosuppressive therapy or long-term use of glucocorticoid.

The present invention relates to a novel type of PPARγ modulator having a pyrimido[5,4-d]pyrimidine main structure. The PPARγ modulator can enhance the expression and nuclear translocation of PPARγ in cells. The present invention also relates to a pharmaceutical composition comprising the PPARγ modulator of the invention encapsulated in a pharmaceutically acceptable cell-penetrating drug delivery system so that it can be directly delivered into cells. The present invention thus provides a method of preventing or treating PPARγ-related disorders or conditions comprising administering to a subject in need thereof a therapeutically effective amount of the PPARγ modulator of the invention or the pharmaceutical composition of the invention.

The present invention provides an intercellular protein delivery system comprising an engineered peptide (EP), composed of secretion part (SP) and nuclear translocation part (NTP), a functional or therapeutic protein (FP), cells that express the fusion proteins and cells that accept the fusion proteins. The system can be used in vivo or in vitro to sustainably supply proteins of interest for cellular reprogramming, cellular differentiation and cell-based protein therapies.

The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

The invention provides a new detection index for drug sensitivity under the state of an inflammatory bowel disease and application of the new detection index in the design of a drug therapy scheme, relates to multiple fields of pharmaceutical pharmacokinetics, pharmacology, cytobiology and molecular biology, creatively reveals natural drug-resistant phenomena of the inflammatory bowel disease and expounds related mechanisms. According to the new detection index, the phosphorylation of STAT3 is promoted by virtue of cell factors TNF-a, IL17 and LPS, which are excessively secreted in mice with the inflammatory bowel disease, in a way of STAT3 / Nf-kb, then the phosphorylation and the nuclear translocation of P65 are induced, the expression of peripheral blood monouclear cells P-gp is promoted, and the drug concentration of an immune inhibitor in the cells is reduced, the treatment effect of the immune inhibitor is inhibited, and the natural drug resistance is generated; by administering a P-gp specific inhibitor, the drug resistance phenomenon can be reverted. The new detection index prompts that P-gp expression quantity of peripheral blood lymphocyte can serve as an evaluation index of the natural drug resistance of patients with IBD (inflammatory bowel disease), and by virtue of the combination of the P-gp inhibitor, the decrease of the pharmaceutical effect caused by the natural drug resistance can be reverted, so that a new thought is provided for the treatment scheme of IBD.

A peptide which is formed from an amino acid sequence selected from the group comprising amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3, according to the present invention, has osteoclast differentiation and activation inhibition and is highly effective for preventing or treating bone diseases related to the destruction of the bone. A peptide, according to the present invention, reduces expression of cathepsin K and TRAP related to osteoclast differentiation, inhibits nuclear translocation of NF-kB, and ultimately inhibits osteoclast differentiation. Provided is a composition, for preventing or treating bone diseases, comprising the peptide.

The invention discloses application of carnosol in preparation of medicines for preventing and treating experimental autoimmune encephalomyelitis. Whole animal model experiments verifies that the carnosol not only can effectively delay the occurrence and development of the experimental autoimmune encephalomyelitis, significantly reduces the infiltration of peripheral inflammatory cells into the central nervous system and relieves the degree of demyelination, but also can promote the transformation of infiltrating macrophages and intrinsic microglial proinflammatory phenotypes to an M2 phenotype with an immunoregulatory function. Furthermore, the carnosol can inhibite Th17 cell differentiation and STAT3 phosphorylation and block NF-kappa B nuclear translocation of a transcription factor. Therefore, the carnosol has a great potential in the preparation of the medicines for preventing and treating the autoimmune diseases such as multiple sclerosis.

The invention discloses application of irisin in the preparation of drugs for preventing myocardial ischemia reperfusion injuries. Experimental results show that irisin can decrease the myocardial infarction area caused by ischemia reperfusion, reduce the increase of the contents of lactate dehydrogenase (LDH), troponin (cTnI), creatine kinase (CK), and other myocardial enzyme markers caused by ischemia reperfusion, meanwhile reducing the inflammatory response, myocardial apoptosis, and oxidative stress response caused by myocardial ischemia reperfusion, promote peroxysome proliferator-activated receptor γ nuclear translocation, and inhibit nuclear transcription factor NF-κB nuclear translocation and accordingly decrease myocardial structure injuries and load increase caused by ischemia reperfusion. Therefore, irisin can be used for preventing and decreasing myocardial reperfusion injuries and has important clinical significance on the treatment of myocardial ischemia.

A peptide which is formed from an amino acid sequence selected from the group comprising amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 3, according to the present invention, has osteoclast differentiation and activation inhibition and is highly effective for preventing or treating bone diseases related to the destruction of the bone. A peptide, according to the present invention, reduces expression of cathepsin K and TRAP related to osteoclast differentiation, inhibits nuclear translocation of NF-kB, and ultimately inhibits osteoclast differentiation. Provided is a composition, for preventing or treating bone diseases, comprising the peptide.

Methods and reagents for determining treatment efficacy of a MALT1 inhibitor in a human subject are described. The method involves determining NF-κB nuclear translocation in stimulated PBMCs of a blood sample obtained from the subject. The method provides information for guiding treatment decisions for those subjects receiving a MALT1 inhibitor therapy, improves the accuracy of optimizing therapy, reduces toxicity, and / or monitors the efficacy of therapeutic treatment.

The invention discloses application and a detection method of a circRNA0003307 gene, and belongs to the technical field of molecular biology of rheumatism. A preparation for detecting the expression quantity of the circRNA0003307 gene comprises a primer pair with nucleotide sequences as shown in SEQ ID NO. 1 and NO. 2, and the preparation for detecting the expression quantity of the gene can be applied to preparation of an ankylosing spondylitis detection preparation. A specific interference sequence si-circRNA0003307can significantly inhibit the expression level of circRNA0003307 in synovialcells, and can cause that the proliferation ability of the synovial cells is obviously weakened compared with the previous proliferation ability, LPS-induced inflammatory cytokines are reduced, and PI3K and AKT phosphorylation and nuclear translocation are obviously reduced. The discovery is expected to further enrich and perfect the research of AS pathogenesis, and also brings hope for developingnovel biomarkers for AS early diagnosis, targeted therapy and prognosis evaluation.

The invention provides application of a reagent for detecting the expression level of RIG-I-Sport in preparation of a product for tumor diagnosis and / or prognosis, and belongs to the technical field of biology. According to the present invention, the protein sequence of the RIG-I-Sport is represented by SEQ ID No. 1; rIG-I-Shart is a variable spliceosome of RIG-I, and expression of MHC I type molecules is reduced by inhibiting nuclear translocation of a transcription factor STAT1. According to the invention, high expression of RIG-I-Shart in tumor tissues of colorectal patients is found. The invention discovers that the tumor cells overexpressing RIG-I-Shart can escape from the attack of the host immune system, thereby promoting the growth of the tumor. The invention finds that the sensitivity of tumor cells overexpressing RIG-I-Shart to immunotherapy such as tumor vaccines and the like is reduced.

Provided herein are compositions containing photoactivatable caged tamoxifen and tamoxifen derivative molecules. Also provided are kits containing one of these compositions and a light source. Also provided are methods of optically inducing nuclear translocation of a fusion protein containing a mammalian estrogen receptor ligand binding domain in a eukaryotic cell and methods of optically inducing recombination in a eukaryotic cell that include contacting a eukaryotic cell with at least one of these compositions. Also provided are methods of treating breast cancer in a subject that include administering a photoactivatable caged tamoxifen or tamoxifen derivative molecule to a subject having breast cancer.

A peptide which is formed from an amino acid sequence selected from the group comprising amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3, according to the present invention, has osteoclast differentiation and activation inhibition and is highly effective for preventing or treating bone diseases related to the destruction of the bone. A peptide, according to the present invention, reduces expression of cathepsin K and TRAP related to osteoclast differentiation, inhibits nuclear translocation of NF-kB, and ultimately inhibits osteoclast differentiation. Provided is a composition, for preventing or treating bone diseases, comprising the peptide.