33 results about "RELA" patented technology

This invention provides a novel pyrin-only protein (POP2), polypeptides, nucleic acids encoding them and methods for making and using them. The polypeptides of this invention have nuclear factor-κB (NF-κB) modulating activity. NF-κB is pivotal for transactivation of cell-cycle regulatory, cytokine and adhesion molecule genes and is dysregulated in many cancers, neurodegenerative disorders, and inflammatory diseases. Proteins with Pyrin and / or caspase recruitment (CARD) domains have roles in apoptosis, innate immunity, and inflammation. Many pyrin domain proteins modulate NF-KB activity as well as participate in assembling both the perinuclear “apoptotic speck” and the pro-IL1β / IL-18 converting inflammasome complex. ‘Pyrin-only’ proteins are attractive as negative regulators of pyrin domain-mediated functions and one such protein, POP1, has been reported. We teach a second Pyrin-only protein (POP2). POP2 is a 294 nt single exon gene located on human chromosome 3 encoding a 97 amino acid protein with sequence and predicted structural similarity to other pyrin domains. Highly similar to pyrin domains in CATERPILLER (CLR, NLR, NALP) family proteins, POP2 is less like the prototypic Pyrin and ASC pyrin domains. POP2 is expressed principally in peripheral blood leukocytes and displays both cytoplasmic and nuclear expression patterns in transfected cells. TNFα-stimulated and p65 (RelA) induced NF-KB-dependent gene transcription is inhibited by POP2 in vitro by a mechanism involving changes in NF-κB nuclear import or distribution. While colocalizing with ASC in perinuclear specks, POP2 also inhibits the formation of specks by the CLR protein CIAS1 / NALP3. Together these observations indicate that POP2 is a negative regulator of NF-KB activity that may influence the assembly of pyrin-domain dependent complexes.

The invention provides a construction method for delaying attenuation and increasing an expression exogenous antigen salmonella suipestifer carrier through regulation and control of gene, which is characterized in that receptor bacterium C78-3 is combined with manA, crp, relA and asd -containing deleted suicide carrier escherichia coli donor bacterium, mutants delta manA, delta Pcrp: : TT ara C PBAD crp, delta relA: : araC PBAD lacI TT and delta asd A are introduced in wild-type salmonella suipestifer C78-3, the introduced salmonella suipestifer after mutation can be called x0011; and four types of mutation enable phenotype identification. The method of the invention makes salmonella suipestifer to become safe and effective vaccine carrier of many exogenous antigens; and provides the delaying attenuation and increasing expression exogenous antigen salmonella suipestifer carrier through regulation and control of gene for various pig diseases, especially many bacteria diseases of pig, and has great market applicability.

The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.

The invention relates to a method for preventing and treating tumors by using a microRNA sponge technology. Specifically, activation of canonical and non-canonical NFkappaB pathways can be regulated through a RelA factor, thereby regulating and controlling tumor growth. According to the invention, microRNA sponge miR-221 / 222 is a RelA gene inhibitor which can substantially reduce colorectal cancer cell proliferation and in vivo tumorigenesis; miR-221 / 222 is positively correlated to colorectal cancer cell proliferation and in vivo tumorigenesis, so activation of the canonical and non-canonical NFkappaB pathways can be substantially blocked by inhibiting miR-221 / 222 highly expressed in the colorectal cancer through the microRNA sponge technology; and the RelA factor or a coding sequence thereof can be used as a target point during tumor inhibition, and the RelA factor inhibitor is used for preparing drugs for tumor prevention or treatment.

The invention discloses sgRNAs targeting a pig RelA gene. The sgRNA pair comprises sgRNA-F and sgRNA-R. Each of the sgRNA-F and sgRNA-R comprises 102 nucleotides. A RNA fragment comprising 2th-21th sits of the tail end 5' can identify a pig chromosome RelA gene. A RNA fragment comprising 22th-102th sites is a skeleton RNA fragment capable for bonding with Cas9n nuclease. The sgRNA-F is shown in the sequence 2 in the sequence table. The sgRNA-R is shown in the sequence 4 in the sequence table. Through a Cas9n system, in a cell or individual level, the pig RelA gene is knocked out or modified so that pig RelA gene functions are analyzed and a pig RelA gene mutant library is constructed for pig breeding service.

The invention provides streptomyces diastatochromogenes with high yield of toyocamycin in genetic engineering as well as a construction method and application of the streptomyces diastatochromogenes. According to the method, a recombinant plasmid pIB139-RelA is constructed by a genetic engineering method, and is transferred into streptomyces diastatochromogenes 1628, the streptomyces diastatochromogenes with high yield of toyocamycin overexpresses a streptomyces coelicolor ppGpp synthetase RelA gene, and the overexpression product of the RelA gene can positively regulate and control the biosynthesis of toyocamycin, and is used for the production of toyocamycin. The yield of toyocamycin produced by fermentation of the strain obtained by the invention is at least increased to 1568mg / L, which is 10 times of the yield of the original strain, and a new technical support is provided for increasing the yield of toyocamycin in industrial production.

The invention belongs to the technical field of a prognostic marker, and particularly relates to an application of PDIA3P1 as a glioma prognostic marker. The research disclosed by the invention investigates a mechanism of the PDIA3P1 in MES transformation of low-oxygen induced glioma, confirms that the expression of the PDIA3P1 and the tumor level of glioma patients, and transcriptome subtypes aretightly associated with prognosis. The PDIA3P1 is used as ceRNA, through miR-124-3p, the RELA expression is regulated, and a downstream NF-KB route is activated, so that the MES transformation of glioma cells is promoted. In addition, the prognostic marker also confirms that a low-oxygen induction factor 1 directly combines with a PDIA3P1 promoter region and the transcript is activated. The PDIA3P1 can achieve the key connection effect between low oxygen and MES transformation of the glioma through a PDIA3P1-miR-124-3p-RELA shaft, and can be used as a prognostic indicator and a potential treatment target point of the glioma.

This invention provides a novel pyrin-only protein (POP2), polypeptides, and nucleic acids encoding them and methods for making and using them. POP2 is a 294 nt single exon gene located on human chromosome 3 encoding a 97 amino acid protein with sequence and predicted structural similarity to other pyrin domains. Highly similar to pyrin domains in CATERPILLER (CLR, NLR, NALP) family proteins, POP2 is less like the prototypic Pyrin and ASC pyrin domains. POP2 is expressed principally in peripheral blood leukocytes and displays both cytoplasmic and nuclear expression patterns in transfected cells. TNFα-stimulated and p65 (RelA) induced NF-κB-dependent gene transcription is inhibited by POP2 in vitro by a mechanism involving changes in NF-κB nuclear import or distribution. While colocalizing with ASC in perinuclear specks, POP2 also inhibits the formation of specks by the CLR protein CIAS1 / NALP3. POP2 is a negative regulator of NF-κB activity that may influence the assembly of pyrin-domain dependent complexes.

The invention discloses RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme for targeted therapy of tuberculosis. A nucleotide sequence is one of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3. The invention simultaneously discloses use of the RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme for targeted therapy of tuberculosis in a drug for treating latent infection caused by L-type mycobacterium tuberculosis. By adopting the RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme, the advantages of effects of gene therapy and immunological therapy are integrated; and the therapeutical effect is played specifically aiming at drug-resistant tuberculosis of infection in the body, especially the L-type mycobacterium tuberculosis.

The invention relates to application of an MIIP pS303 blocking agent to preparation of antitumor drugs. According to researches, PKC epsilon (protein kinase C epsilon) phosphorylated MIIP (migration and invasion inhibitory protein) protein serine 303 (S303) is discovered after EGFR (epidermal growth factor receptor) signal activation, the phosphorylated MIIP can be combined with a significant functional molecule RelA in an NF-kB signal pathway, and accordingly a RelA acetylation level is maintained after EGFR signal activation, RelA mediated migration promoting molecule expression is further promoted, and colonic cancer cell migration is promoted finally. Therefore, drugs can be developed by taking the phosphorylated site (MIIP pS303) as a target and clinically used for treating EGFR / PKC epsilon abnormal activation type malignant tumors. In addition, correlation between colorectal cancer migration and poor prognosis and MIIP S303 phosphorylation is verified, so that reagents for detecting MIIP S303 phosphorylation level can be used for diagnosis or prognosis of colorectal cancers.

The present invention relates to genetically-edited swine comprising an introgressed heterologous nucleic acid sequence in the RELA gene. In particular it relates to genetically- edited swine comprising an introgressed warthog allele in the RALA gene of domestic pigs. The invention also related to methods of producing such swine, and cells derived from swine having such introgressed sequences.

The invention discloses a composition for detecting chemoradiotherapy sensitivity of rectal cancers, a micro array and a computer system. The composition of the invention includes oligonucleotides that are specifically bound to a part of contiguous regions of a gene selected from a group consisting of ABL1, AR, CDK1, HDAC1, IRF1, JUN, PRKCB, RELA-3, STAT1-2, SUMO1-3, ACTB, CSNK1G2, FARP1, GAPDH, and RPLP0. The composition can be used to detect the relative expression level of each gene. In addition, based on expression level differences, and a sensitivity index (RSI) is obtained via a specificalgorithm, and can be used to effectively determine the chemotherapy sensitivity of a detection sample.

The invention relates to application of an MIIP pS303 blocking agent to preparation of antitumor drugs. According to researches, PKC epsilon (protein kinase C epsilon) phosphorylated MIIP (migration and invasion inhibitory protein) protein serine 303 (S303) is discovered after EGFR (epidermal growth factor receptor) signal activation, the phosphorylated MIIP can be combined with a significant functional molecule RelA in an NF-kB signal pathway, and accordingly a RelA acetylation level is maintained after EGFR signal activation, RelA mediated migration promoting molecule expression is further promoted, and colonic cancer cell migration is promoted finally. Therefore, drugs can be developed by taking the phosphorylated site (MIIP pS303) as a target and clinically used for treating EGFR / PKC epsilon abnormal activation type malignant tumors. In addition, correlation between colorectal cancer migration and poor prognosis and MIIP S303 phosphorylation is verified, so that reagents for detecting MIIP S303 phosphorylation level can be used for diagnosis or prognosis of colorectal cancers.

The invention relates to a method for preventing and treating tumors by using a microRNA sponge technology. Specifically, activation of canonical and non-canonical NFkappaB pathways can be regulated through a RelA factor, thereby regulating and controlling tumor growth. According to the invention, microRNA sponge miR-221 / 222 is a RelA gene inhibitor which can substantially reduce colorectal cancer cell proliferation and in vivo tumorigenesis; miR-221 / 222 is positively correlated to colorectal cancer cell proliferation and in vivo tumorigenesis, so activation of the canonical and non-canonical NFkappaB pathways can be substantially blocked by inhibiting miR-221 / 222 highly expressed in the colorectal cancer through the microRNA sponge technology; and the RelA factor or a coding sequence thereof can be used as a target point during tumor inhibition, and the RelA factor inhibitor is used for preparing drugs for tumor prevention or treatment.

The invention belongs to the technical field of a prognostic marker, and particularly relates to an application of PDIA3P1 as a glioma prognostic marker. The research disclosed by the invention investigates a mechanism of the PDIA3P1 in MES transformation of low-oxygen induced glioma, confirms that the expression of the PDIA3P1 and the tumor level of glioma patients, and transcriptome subtypes aretightly associated with prognosis. The PDIA3P1 is used as ceRNA, through miR-124-3p, the RELA expression is regulated, and a downstream NF-KB route is activated, so that the MES transformation of glioma cells is promoted. In addition, the prognostic marker also confirms that a low-oxygen induction factor 1 directly combines with a PDIA3P1 promoter region and the transcript is activated. The PDIA3P1 can achieve the key connection effect between low oxygen and MES transformation of the glioma through a PDIA3P1-miR-124-3p-RELA shaft, and can be used as a prognostic indicator and a potential treatment target point of the glioma.

The invention discloses an ExPEC (extraintestinal pathogenic escherichia coli) double-gene deleted strain and a vaccine prepared from the same. A construction method of the ExPEC double-gene deleted strain comprises the following steps: knocking out a relA gene and a spoT gene in an ExPEC virulent strain DE205B by a Red homologous recombination method to obtain an ExPEC relA and SpoT double-gene deleted strain DE205B[delta]relA / spoT, the strain is preserved in the China Center for Type Culture Collection, and the preservation number of the strain is CCTCC NO: M 2020610. The deleted strain has good biological safety and immunogenicity, is relatively weak in toxicity, and can be used for preparing the attenuated vaccine and preventing ExPEC infection. The attenuated vaccine prepared from the ExPEC double-gene deleted strain has an immune protective effect on ExPEC infection, and has a good toxin attacking immune protective effect.

The present invention relates to antisense oligonucleotides that are capable of modulating expression of RelA in a target cell. The oligonucleotides are complementary to mammalian RELA pre-m RNA intron sequence. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of cancer, inflammation or autoimmune diseases using the oligonucleotide.

The invention relates to the technical field of medicine and biology, in particular to a kit for the detection of NF-κB RelA / p65 protein site-specific phosphorylation. Specifically, the kit can specifically detect the phosphorylation status of Ser276 and Ser536 sites of NF-κB RelA / p65 protein to guide the targeted antitumor drug treatment of NF-κB inhibitors or RelA / p65 S276A / S536D Gene therapy has important clinical application value.

The present invention relates to genetically-edited swine comprising an introgressed heterologous nucleic acid sequence in the RELA gene. In particular it relates to genetically-edited swine comprising an introgressed warthog allele in the RALA gene of domestic pigs. The invention also related to methods of producing such swine, and cells derived from swine having such introgressed sequences.

The invention discloses applications of human genome NF-kappaB pathway RelA gene rs7101916 single nucleotide polymorphism (SNP) or genotype in preparation of products used for detecting or screening hepatitis C infectibility or in preparation of hepatitis C-related single nucleotide polymorphism products. In practical applications, rs7101916 single nucleotide polymorphism (i.e. allelic genes) or genotype substances are combined with other substances (such as other hepatitis C-related single nucleotide polymorphism or genotype substances) to prepare the products used for screening patients withhepatitis C infectibility.

A method for determining probability that prostate cancer will metastasize, as well as a diagnostic reagent used therefor is disclosed. It was discovered that the percentage that NF-κB-p65 / RelA has the 254th amino acid threonine which is phosphorylated is significantly higher in the prostate cancer cells in the cases where the bone metastasis was observed than in the cases where bone metastasis was not observed. Thus, the method for determining probability that prostate cancer will metastasize comprises measuring human NF-κB-p65 / RelA in which 254th amino acid threonine is phosphorylated, which human NF-κB-p65 / RelA is contained in a prostate tissue separated from human.

The present invention relates to a genetically edited animal, especially to a genetically edited pig in which expression or activity of the RELA protein has been modified. Such pigs have at least partial protection against the African Swine Fever Virus. The invention also provides, a cell nucleus, germ cell, stem cell, gamete, blastocyst, embryo, foetus and / or donor cell of a non-human animal comprising a genetic modification which alters the expression or function of RELA protein, methods for editing the genome of animals and methods for screening the efficacy of a pharmaceutical agent in such an animal.

The purpose of the present invention is to provide a method and a reagent for enhancing lentivirus vector production in a 293T cell. The invention relates to a method for producing a lentivirus vector, which enhances the amount of lentivirus vector production by expressing HTLV-1 Tax, HIV-1 Tat or NF-kB RelA in a 293T cell when cotransfecting the 293T cell with a packaging mix that includes multiple plasmids each comprising a gene that encodes a protein essential for formation of a lentivirus particle, and a plasmid comprising a gene that transcribes an RNA included in the lentivirus particle and a target transgene to be expressed.

The invention discloses sgRNAs targeting a pig RelA gene. The sgRNA pair comprises sgRNA-F and sgRNA-R. Each of the sgRNA-F and sgRNA-R comprises 102 nucleotides. A RNA fragment comprising 2th-21th sits of the tail end 5' can identify a pig chromosome RelA gene. A RNA fragment comprising 22th-102th sites is a skeleton RNA fragment capable for bonding with Cas9n nuclease. The sgRNA-F is shown in the sequence 2 in the sequence table. The sgRNA-R is shown in the sequence 4 in the sequence table. Through a Cas9n system, in a cell or individual level, the pig RelA gene is knocked out or modified so that pig RelA gene functions are analyzed and a pig RelA gene mutant library is constructed for pig breeding service.

The invention discloses RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme for targeted therapy of tuberculosis. A nucleotide sequence is one of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3. The invention simultaneously discloses use of the RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme for targeted therapy of tuberculosis in a drug for treating latent infection caused by L-type mycobacterium tuberculosis. By adopting the RelA cut and TLR7 active sequence modified locked nucleic acid deoxyribozyme, the advantages of effects of gene therapy and immunological therapy are integrated; and the therapeutical effect is played specifically aiming at drug-resistant tuberculosis of infection in the body, especially the L-type mycobacterium tuberculosis.

The invention relates to the technical field of the medical biology, and specifically relates to a kit for NF-kappaB RelA / p65 protein loci specificity phosphorylation detection. Specifically, the kitcan specifically detect the phosphorylation state of the NF-kappaB RelA / p65 protein Ser276 and Ser536 site so as to guide the NF-kappaB inhibitor targeting anti-tumor drug therapy or RelA / p65 S276A / S536D; and the kit has important clinical application value.

The invention relates to the field of biomedical technology, a primer for detecting inflammatory cytokines in rats with rheumatoid arthritis and a method thereof are disclosed, when the test animals and their tissues are ready, total RNA was extracted from CIA rat joints, the purity and concentration of total RNA were detected, and 5 pairs of specific primers were synthesized by reverse transcription of total RNA. Using CIA rat cDNA as template, 15 [mu]L system PCR was used to detect total RNA. In the gel imaging system, the ultraviolet ray was separated by a partition plate, and the rat RelA,TLR4, AKT1, IL6, NF-kB cDNA fragment gel, rapid agarose gel DNA recovery kit, and ligation of the recovered DNA fragment to T-Vector, screening and sequencing of transformed blue and white spots. A CIA rat model is established, detecting the expression of NF-kB subunit p65, toll-like receptor 4, AKT serine / threonine kinase 1, interleukin 6 and NF-kB subunit in the joints of rats with rheumatoid arthritis by molecular biological methods is of great significance for the early prevention and treatment of RA. The results showed that the expression of NF-kB subunit p65, toll-like receptor 4, AKT serine / threonine kinase 1, interleukin 6 and NF-kB subunit in the joints of rats with rheumatoid arthritis was significantly higher than the of normal joints.

The present invention relates to a genetically edited animal, especially to a genetically edited pig in which expression or activity of the RELA protein has been modified. Such pigs have at least partial protection against the African Swine Fever Virus. The invention also provides, a cell nucleus, germ cell, stem cell, gamete, blastocyst, embryo, foetus and / or donor cell of a non-human animal comprising a genetic modification which alters the expression or function of RELA protein, methods for editing the genome of animals and methods for screening the efficacy of a pharmaceutical agent in such an animal.

A method for determining probability that prostate cancer will metastasize, as well as a diagnostic reagent used therefor is disclosed. It was discovered that the percentage that NF-κB-p65 / RelA has the 254th amino acid threonine which is phosphorylated is significantly higher in the prostate cancer cells in the cases where the bone metastasis was observed than in the cases where bone metastasis was not observed. Thus, the method for determining probability that prostate cancer will metastasize comprises measuring human NF-κB-p65 / RelA in which 254th amino acid threonine is phosphorylated, which human NF-κB-p65 / RelA is contained in a prostate tissue separated from human.