47 results about "Transcription factor activity" patented technology

The invention provides an application of a type of berbamine derivatives and salts thereof in the preparation of drugs for the treatment of tumors, which is mainly applied in the preparation of the drugs for the prevention and treatment of nuclear transcription factor NF-kBp65 activity-related diseases and BCR / ABL transcription activity-related diseases. The drugs are combined and prepared by the compounds of the invention and one or more pharmaceutically acceptable excipients. The preparation forms comprise solid preparations, semi-solid preparations or liquid preparations. The type of berbamine derivatives and the salts thereof provided by the invention have broader and stronger anti-leukemia and anti-solid-tumor activity, the tumors proved to be sensitive are leukemia, multiple myeloma, liver cancer, osteosarcoma and breast cancer; the toxicity and the side effects are lighter. An in vitro cell culture system and animal experiments confirm that the berbamine derivatives and the salts thereof have no significant toxicity or side effects to the growth of normal human hematopoietic cells and experimental animals under the anti-tumor dosage, which are superior to the commonly used chemotherapy drugs.

The present invention relates generally to transcription factor pathways, the modulation of such pathways, agents which modulate the activity of transcription factors, screening molecules to identify transcription factor modulators and cell or animal models for tumor-related transcription factors. More particularly, the present invention relates to the modulation of transcription factors in which the DNA binding domain is distinct from the activation domain by binding an inhibitory agent to a region adjacent to the DNA binding domain.

An RNA polymerase transcription accelerator comprising a compound represented by the following Formula (I) or salts thereof.A method of sequencing DNA in which nucleic acid transcripts are obtained using an RNA polymerase and a DNA fragment as a template, the resulted nucleic acid transcripts are separated, the nucleic acid sequence is determined from the separated fractions wherein the nucleic acid transcription reaction is carried out in the presence of a compound selected from a group of compounds represented by the above formula (I).The polyamine compounds above have outstanding accelerating activity on transcription activity of RNA polymerase. Therefore, use of the polyamine compounds in a DNA sequencing method using RNA polymerase can make a length of DNA sequence that can be determined in one sequencing longer.

Embodiments of the invention provides, among other things, methods for identifying agents that inhibit oncogenic transcription factors, induce apoptosis, inhibit the growth of transformed cells and cancer cells, and potentiate the effects of other agents that induce apoptosis and that inhibit the growth of transformed cells and cancer cells. Embodiments of the invention further provide compositions useful for the same comprising an agent the inhibits one or more oncogenic transcription factors and an agent that induces apoptosis, particular compositions wherein the apoptotic effect of the combination is greater than either agent by itself. Embodiments of the invention further provide for the use of such agents and compositions to treat cancer. In illustrative embodiments the agents that inhibit transcription factor activity are thiazole antibiotics, such as Siomycin and thiostrepton, and the apoptosis inducing agent is a member of the TNF ligand superfamily, such as TNF-alpha. In illustrative embodiments the cancers are those in which both the FoxM1 and the NF-kB oncogenic pathways are activated.

The invention discloses the influence of melatonin on hulless oat seedlings under drought stress, and an application of melatonin to promotion of transcription factor activity in eukaryotic organismsunder drought conditions. The invention lays a foundation for exploring possible actions of melatonin in an anti-oxidation and defense system of a hulless oat drought resistance mechanism.

This invention provides an implant that enable satisfactory bone / cartilage regeneration by allowing sustained release of virus vectors carrying the transcription factor gene in vivo and persistent maintenance of transcription factor activity.

The invention discloses application of a 4N heterocyclic compound as an inhibitor for Th17 cell differentiation. In virtue of a luciferase activity screening system based on the activity of transcription factors, it is found that the 4N heterocyclic compound with a general formula as described in the specification has capability in inhibiting the key transcription factor ROR gamma t of Th17 cell differentiation and the inhibition capability EC50 is in a range of 0.2 to 1.5 [mu]M. In-vitro Th17 cell differentiation experiments prove that the 4N heterocyclic compound is capable of inhibiting Th17 differentiation, including substantially reducing the transcription expression of ROR gamma t, inhibiting the transcription expression of the effector molecules IL17A and IL17F of Th17 and obviously inhibiting the secretion level of IL17A cytokines in a culture. The 4N heterocyclic compound is expected to be developed into a drug used for treating autoimmune diseases, especially psoriasis, systematic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, asthma or inflammatory intestinal diseases.

A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

In one or more embodiments, the present invention provides novel artificial, non-naturally-occurring double stranded DNA segments (and related methods) capable of acting as decoy binding sites for oncogenic transcription factors and a general method for suppressing aberrant activity of oncogenic transcription factors that promote cancer progression. In various embodiments, the present invention involves the sequestration of targeted oncogenic transcription factors at these artificial, non-naturally occurring engineered transcription factor binding sites, which have been introduced into the cells using oncolytic or other viruses that can be engineered to selectively target cancer cells. These artificial, non-naturally occurring engineered transcription factor binding sites act as decoys for binding so as to competitively sequester oncogenic transcription factors away from the host genomic DNA, thus abolishing or reducing oncogenic transcription factor activity and resulting in restored sensitivity to chemotherapy, increased apoptosis, and reduced cancer cell proliferation.

The present disclosure relates to an isolated compound including a phosphorothioated oligodeoxynucleotide (ODN) sequence conjugated to a short-activating RNA (saRNA) or an antisense oligonucleotide sequence (ASO), compositions of such a compound, and method of treatment of cancer and autoimmune diseases (with or without stimulating immune response), method of immune stimulation, method of activating CEBPA, and method of reducing activity of STAT transcription factor, by one of the disclosed compounds or compositions.

This invention relates to methods of modulating the development of blood vessels and / or endothelial cell differentiation in a mammal comprising altering the activity of an Ets transcription factor, which activates vascular specific genes. More particularly, the transcription factor comprises ELF-1, and transcription factors that are homologous to ELF-1. The invention further relates to methods of screening for compounds that affect the activity of these transcription factors, and therefore, affect the development of blood vessels and / or endothelial cell differentiation. The invention also relates to methods of using these compounds to treat diseases, or symptoms of diseases, by either increasing or decreasing blood vessel development and / or endothelial cell differentiation.

The present invention provides rapid, sensitive, consistent and economical methods and assays for measuring analytes and transcription factor activity based on amplification of a nucleic acid-tracer and the subsequent measurement of amplified product that is ultimately correlated with the presence of analyte or transcription factor activity.

Methods for modulating production of a T helper type 2 (Th2)-associated cytokine, in particular interleukin-4, by modulating the activity of a transcription factor, in particular the proto-oncoprotein c-Maf, that regulates expression of the Th2-associated cytokine gene are disclosed. Methods for modulating development of T helper type 1 (Th1) or T helper type 2 (Th2) subsets in a subject using agents that modulate transcription factor activity are also disclosed. The methods of the invention can further involve use of agents that modulate the activity of additional transcription factors that contribute to the regulation of Th1- or Th2-associated cytokines, such as a Nuclear Factor of Activated T cells (NF-AT) protein and / or an AP-1 family protein. Compositions for modulating Th2-associated cytokine production, recombinant expression vectors and host cells, as well as screening assays to identify agents that modulate c-Maf activity, are also disclosed.

The invention discloses a cell signal transduction activity detection method based on a tetrahedral DNA nano-material, which comprises a specific DNA binding sequence of a transcription factor capable of characterizing signal transduction activity to be detected and a fluorescent label, when a target transcription factor is bound with TDNs, a fluorophore and a quenching group are prevented from approaching, and when the target transcription factor is bound with TDNs, the signal transduction activity to be detected is detected. Therefore, the transcription factor activity can be analyzed by detecting the fluorophore. The method is simple, convenient and efficient, qualitative, quantitative and imaging analysis can be synchronously completed, and the operation time is short. In addition, the synthesis method of the tetrahedral DNA nano material is simple and convenient, has good reproducibility, can be flexibly designed according to target molecules to be detected, and has strong universality.

Transgenic oleaginous yeast having increased oil content comprising increased Yap1 transcription factor activity, wherein the increased oil content is compared to the oil content of a non-transgenic oleaginous yeast, are described herein. The increased Yap1 transcription factor activity results from overexpressing a Yap1 transcription factor, by increasing the interaction between the transcription factor and a protein that is capable of activating the transcription factor, or by a combination thereof. Methods of using these yeast strains are also described.

The invention provides a method for detecting the expression quantity of HOXD9 after peripheral nerve injury. The method comprises the following steps: (1) separating dorsal root ganglion neuron nucleoproteins at different time points after sciatic nerve injury of a rat, performing transcription factor activity detection, and determining the expression quantity change trend of a transcription factor HOXD9 in the nerve regeneration process; (2) observing the expression quantity and the expression trend of related messenger RNA results of HOXD9 by applying a PCR technology; (3) displaying intracellular localization of the HOXD9 in an DRG neuron by adopting an immunofluorescence staining technology; and (4) counting the HOXD9 fluorescence intensity change trends at different time points afterthe sciatic nerve injury, and enabling the fluorescence intensity to be the highest on the third day and to be consistent with a result trend obtained by a PCR experiment. The expression quantity change of HOXD9 after peripheral nerve injury is clarified, and the regulation effect of THE HOXD9 on neuron axon regeneration is discovered.

A method for screening a vitamin D derivative wherein the blood calcium level-elevating effect alone has been relieved or eliminated while sustaining useful physiological activities. A method for screening a compound having an affinity for vitamin D receptor which comprises measuring the activity of a test compound of promoting the VDRE-mediated transcription by vitamin D receptor and the effect of the test compound of inhibiting the activity of the transcription factor of the vitamin D receptor, thereby selecting a compound showing the transcription factor activity inhibitory effect relatively stronger than the VDRE-mediated transcription promoting activity.

The invention provides a fluorescent biosensor and method for detecting a transcription factor and an application of the fluorescent biosensor and belongs to the technical field of detection analysis.The invention provides a two-way EXPAR and endonuclease IV-assisted circulatory digestion signal probe-based super-sensitive fluorescence strategy for detecting the transcription factor. Compared with conventional EXPAR, two-way EXPAR can initiate extension reaction in two directions to generate abundant trigger signals, so as to improve the amplification efficiency. The method is simple in operation, economic, high in sensitivity, low in background and good in specificity, and super-sensitive detection for the activity of the transcription factor in cells can be achieved by using the method,therefore, the method has good practical application value.

The invention provides a reporter gene carrier which comprises an AP2alpha specific cis acting element. The carrier is characterized in that the AP2alpha specific cis acting element consists of four GCCCGCGG nucleotide sequences connected in series, wherein the four GCCCGCGG nucleotide sequences are connected in series through a nucleotide sequence TT. The reporter gene carrier designed by the invention is easy to prepare, simple to operate and good in repeatability, and can effective transfect different mammalian cells. The carrier is more accurate and reliable than EMSA (Electrophoretic Mobility Shift Assay) when is used to detect activity change of a dominant negative mutant-mediated transcription factor. The carrier is suitable for in vitro study of biological activity of the AP2alpha transcription factor in various mammalian cells.

The present invention relates to a method for targeted inactivation of transcription factor using an artificial small interfering peptide and a use thereof. According to the present invention, an artificial small interfering peptide (a-siPEP) as a truncated from of the transcription factor for regulating transcription by dimerization was produced. It was also confirmed that, as a-siPEP forms a heterodimer with a transcription factor, DNA binding and transport into a nucleus of the transcription factor are inhibited, so that inactivation of the transcription factor is achieved at protein level. The method for inhibiting transcription factor activity using a-siPEP can replace a gene knock-out method and it allows protein-level inhibition of a transcription factor. Also, it is a transcription regulation method with high precision and high efficiency that can be applied for both monocot and dicot plants.

The active transcription factor detecting method and kit is the improvement of ELISA detection method, and features that the new double-stranded oligonucleotide probe is constructed to overcome the demerits of available ELISA detection method in double-stranded oligonucleotide probe design. Experiment shows that the detection method of the present invention has very high sensitivity and detection specificity, and the designed probe is suitable for transcription factor detection. The combined sequence probe detection effect with one copy and that with two copies are the same. The present invention also relates to the kit for the transcription factor detection method.

Embodiments of the invention provides, among other things, methods for identifying agents that inhibit oncogenic transcription factors, induce apoptosis, inhibit the growth of transformed cells and cancer cells, and potentiate the effects of other agents that induce apoptosis and that inhibit the growth of transformed cells and cancer cells. Embodiments of the invention further provide compositions useful for the same comprising an agent the inhibits one or more oncogenic transcription factors and an agent that induces apoptosis, particular compositions wherein the apoptotic effect of the combination is greater than either agent by itself. Embodiments of the invention further provide for the use of such agents and compositions to treat cancer. In illustrative embodiments the agents that inhibit transcription factor activity are thiazole antibiotics, such as Siomycin and thiostrepton, and the apoptosis inducing agent is a member of the TNF ligand superfamily, such as TNF-alpha. In illustrative embodiments the cancers are those in which both the FoxM1 and the NF-kB oncogenic pathways are activated.

The invention discloses a method for preparation and transformation of a wheat endosperm cell protoplast. The invention provides a method for preparing the wheat endosperm cell protoplast, comprisingthe following steps of: taking fresh wheat grains 8-11 days after flowering, splitting along abdominal seams to obtain endosperm tissues, soaking and washing in a buffer solution 1, then putting in abuffer solution 2 for enzymolysis, and carrying out ice bath standing time gradient sedimentation to obtain a purified wheat endosperm cell protoplast. The invention provides an efficient, economicaland rapid protoplast preparation and transformation method for wheat endosperm cells containing a large number of stored starch particles. According to the method, the endosperm cell protoplast can berapidly and effectively separated; the method can be used for subcellular localization, transcription factor activity analysis, protein interaction identification and enzyme activity analysis of wheat endosperm expression factors, creates conditions for in-vivo molecular biological research of the factors, and effectively avoids experimental deviation caused by error expression of endosperm specific expression genes in other cells.

An RNA polymerase transcription accelerator comprising a compound represented by the following Formula (I) or salts thereof. A method of sequencing DNA in which nucleic acid transcripts are obtained using an RNA polymerase and a DNA fragment as a template, the resulted nucleic acid transcripts are separated, the nucleic acid sequence is determined from the separated fractions wherein the nucleic acid transcription reaction is carried out in the presence of a compound selected from a group of compounds represented by the above formula (I). The polyamine compounds above have outstanding accelerating activity on transcription activity of RNA polymerase. Therefore, use of the polyamine compounds in a DNA sequencing method using RNA polymerase can make a length of DNA sequence that can be determined in one sequencing longer.

The present invention relates to a method for inferring activity of a transcription factor of a signal transduction pathway in a subject. The method comprises performing (101) a first staining for detecting the transcription factor in cells of a sample of the subject and performing (102) a second staining for detecting a protein encoded by a target gene of the transcription factor in cells of thesample. The method further comprises quantifying (103) cells of the sample that show both a nuclear presence of the transcription factor and a presence of the target gene-encoded protein based on thefirst staining and the second staining, and inferring (104) the activity of the transcription factor in the subject based on the quantifying. This allows the presented method to more reliably infer the activity of the transcription factor in the subject.

The present invention relates to a method of treating or preventing insulin resistance syndrome in an animal body by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof or a method of reducing activity of transcription factors of the FOXO family (Foxo 1, 3a, 4 and 6) by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof. The present invention also relates to different compounds and methods for using PERK gene or PERK protein.

Provided herein is, inter alia, methods and compositions useful in therapeutic interrogation of complex physiologic pathways by massively parallel and permissive transcriptional screening. Thus, methods and compositions are provided herein that are useful for high-throughput functional analysis of complex, transcriptionally regulated physiological pathways. While examples are provided relating to nuclear receptors, the methods and composition can be generalized and applied to any class of transcription factor or any class of gene product that can regulate the activity of transcription. For example, in addition to nuclear receptors, the methods and compositions provided herein are generally applicable to all known transcription factors and any gene encoded product that modulates said transcription factor activity. Moreover, data obtained through the methods provided herein are directly comparable thereby facilitating high-throughput functional analysis.

The invention discloses an application of a quinoline-sulfamide compound as an inhibitor for Th17 cell differentiation. Through a luciferase activity screening system based on the transcription factor activity, it is found that the quinoline-sulfamide compound with the structural formula shown in the description (X is a halogen element) has the capability of inhibiting key transcription factor RORgammat for Th17 cell differentiation, the inhibition capability EC50 is 0.391[mu]M; an in vitro Th17 cell differentiation experiment proves that the compound has the function of inhibiting Th17 differentiation, specifically, including obviously reducing the transcription expression of RORgammat, and inhibiting the transcription expression of effector molecule IL17A of Th17, and further, the secretion level of the IL17A cell factor in a culture is also obviously inhibited. The compound and a hydrochloride derivative thereof are expected to be developed into the medicines for treating autoimmune diseases, in particular psoriasis, systemic lupus erythematosus, multiple sclerosis, rheumatic arthritis, asthma or inflammatory bowel diseases.