35 results about "Nuclear factor κb" patented technology

This invention relates to a method for prevention and treatment of aging, age-related disorders and / or age-related manifestations including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging, age-related disorders and / or age-related manifestations including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and / or inhibition of the signal transduction pathway

This invention relates to a method for prevention and treatment of aging and age-related disorders including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging and age-related disorders including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and / or inhibition of the signal transduction pathway.

Devices and methods for stimulation of the vagus nerve to modulate (e.g., reduce, suppress, etc.) bone erosion. Methods and apparatus for modulating bone erosion may modulate levels of Receptor Activator for Nuclear Factor κB Ligand (RANKL), and / or to modulate (increase, enhance, etc.) osteoprotegerin (OPG) and / or OPG / RANKL ratio. Devices may include electrical stimulation devices that may be implanted, and may be activated to apply current for a proscribed duration, followed by a period without stimulation.

The invention can prepare the microarray of double -stranded DNA(ds DNA) on the surface of solid substrates. By this method, the probes of ds DNA can engomphosised in the nuclear factor kappa B(NF-kappa B) to high-throughpput detect NF-kappa B inside of caryon and screen ds DNA / NF-kappa B molecules interfering dsDNA / NF-kappa B interaction. First, depending on patent technic and others methods of this invention, the invention prepare the microarray of double -stranded DNA(ds DNA) on the surface of solid substrates to allow mounts of dsDNA explorer on the dsDNA micro embattle to link with locus. Second, allow dsDNA micro embattle to across and link with specifically cell nuckoproteides or NF-kappa pure albumen. Third, do qualitative determination or quantiative determination to NF-kappa albumen in special caryon by reaction of NF-kappa B with dsDNA as micro embattle butt.

The invention discloses a culturing method of osteoclasts utilizing mesenchymal stem cells and cytikines, mainly utilizing the mesenchymal stem cells from mouse bone substance and the mouse splenic mononuclear cells and then adding nuclear factor kB receptor activator ligand and macrophage-colony to stimulate the factors. The invention has the advantages: the invention has the advantages of simpleoperation, convenience and practicality, capability of getting osteoclasts at the earliest time, and saving the culture time; the invention gets a large quantity of osteoclasts, solves the problem that osteoclasts are difficult to prepare in large scale, and can meet the need of a general cell biology experiment; the osteoclasts gotten through the invention has high maturity and strong bone substance absorptive capability, which is favorable for the function study; the cell factors needed by the invention is few, which saves expenditure.

The invention relates to 'a preparation method of OPG-HSP70 fusion protein and an application thereof', pertaining to the new technology field of biological medicaments. The preparation method provides an OPG-HSP70 fusion protein (osteoprotegerin-heat shock protein 70) medicament. According to the most significant pathological features of the rheumatoid arthritis (RA) i.e. the arthrosynovitis with cartilage and bone destruction, the medicament uses the osteoprotegerin as the decoy receptor to combine with the receptor activator of nuclear factor-kB ligand (RANKL) of the nuclear factor kB expressed by osteoblast and other cells, and to interrupt the combination between the RANKL and the RANK expressed by the osteoclast so as to inhibit the bone resorption involved by the osteoclast; and the medicament uses the protective polypeptide segments of the heat shock protein (HSP) to inhibit the inflammatory arthritis. The method contains the DNA sequence which encodes the fusion protein, the method for generating the fusing protein by the recombinant technology, the biological activity of the fusion protein and the like.

The present invention relates to the use of triterpenes of the formula (I): which are inhibitors of nuclear factor kappa B (NF-KB for use in the treatment of inflammatory diseases and for cancers susceptible to an NF-KB inhibitor. The present invention also relates to compounds and methods useful to inhibit cell proliferation and for the induction of apoptosis.

Cyano and carboxy derivatives of substituted styrenes are inhibitors of tumor necrosis factor α, nuclear factor κB, and phosphodiesterase and can be used to combat cachexia, endotoxic shock, retrovirus replication, asthma, and inflammatory conditions. A typical embodiment is 3,3-bis-(3,4-dimethoxyphenyl)acrylonitrile.

Interaction of Rel proteins and steroid receptors is known to result in repression of target genes. Here we describe the discovery of a new mechanism in which Rel proteins and steroid receptors act synergistically to activate a regulatory element. This mechanism is shown to influence the expression of the brain-specific 5HT1A receptor wherein the estrogen receptor acts synergistically with the Nuclear Factor kappa B to enhance the activity of the promoter for the 5HT1A receptor gene. In addition, synergistic effects of Rel proteins with the mineralocorticoid receptor were observed, showing that synergism with Rel proteins may be expected for other steroid receptors as well. The synergism between Rel proteins and estrogen receptor or mineralocorticoid receptor provides a tool for the development of compounds that interact with the estrogen or mineralocorticoid receptor in such a way that only the synergistic effect is modulated whereas other effects are left intact. Such compounds would be invaluable for the development of medicaments for the treatment of diseases of the central nervous or cardiovascular system and other disorders in which Rel proteins play a role.

The present invention relates to the use of triterpenes of the formula (I): which are inhibitors of nuclear factor kappa B (NF-κB for use in the treatment of inflammatory diseases and for cancers susceptible to an NF-κB inhibitor. The present invention also relates to compounds and methods useful to inhibit cell proliferation and for the induction of apoptosis.

The present invention relates to a use of ZFP91 based on the functions of ZFP91 (Zinc Finger Protein 91) and the interaction of ZFP91 with NF-κB (Nuclear factor kappa B) signal transduction pathway proteins, more precisely a method to inhibit the activation of NF-κB alternative pathway by regulating ZFP91 activation, to inhibit tumor growth by inhibiting the transcription factor HIF-1 (hypoxia inducible factor-1) activation, to inhibit cancer malignancy by inhibiting angiogenesis, or reversely a method to increase the activation of NF-κB alternative pathway or to increase angiogenesis by increasing activation of HIF-1. The method of regulating ZFP91 activation of the present invention can increase or reduce HIF-1α stability by increasing or reducing the activation of NF-κB alternative pathway, so that it can be effectively used for the development of an anticancer agent, a therapeutic agent for arthritis, a therapeutic agent for ulcerative colitis, an anti-inflammatory agent and an angiogenesis inducer.

The invention discloses application of nuclear factor kappa B arrestin 3 combined with A20 in preparation of drugs for treating fatty liver and related diseases, and belongs to new use of ABIN3. An L02 cell line, an ABIN3 over-expressing L02 cell line, a mouse primary hepatocyte cell, and an ABIN3 over-expressing mouse primary hepatocyte cell are used as an experimental object, and a fatty liver cell model is induced through combination of palmitic acid and oleic acid. Oil red O staining results show that compared with L02 cells, an area of red fat droplets in ABIN3 over-expressing L02 cells is significantly reduced under combined stimulation of the palmitic acid and the oleic acid at the same concentration. A same trend of the oil red O staining results is also observed in the ABIN3 over-expressing mouse primary hepatocyte cell, indicating that ABIN3 overexpression significantly inhibits lipid accumulation in fatty liver cells induced by the palmitic acid and the oleic acid. Therefore, ABIN3 has the functions of inhibiting liver lipid accumulation and protecting liver.

The present invention relates to novel inhibitors of the Nuclear factor kappa B (NF-κB) activating pathway useful in the treatment of NF-κB related diseases and / or in the improvement of anti-tumor treatments. These inhibitors interfere early in the TRAF induced signaling pathway and are therefore more specific than IκB.

The invention relates to a novel application of 2,3,5,4-tetrahydroxy-stilbene-2-O-beta-D-Glucoside (TSG) in preventing and / or treating hyperhomocysteinemia (HHcy). The invention discloses pharmacologic actions of TSG which can remarkably relax superior mesenteric arteries of rats, inhibit homocysteine induced B type endothelin receptor up-regulation and inhibit activation of mitogen-activated protein kinase / nuclear factor kB / B type endothelin receptor signal axes so as to significantly treat the HHcy, and the blank that no drugs for treating the HHcy exist clinically is filled up.

The invention relates to the application of beta-interferon to medicament making. After the immunological effect substances is immunized and intervened by the beta-interferon, the levels of the immunological effect substances which are closely related to a rheumatoid arthritis disease, such as a T lymphocyte antigen receptor, autoreactivity CD3+T cell proliferation, matrix metalloproteinase and a nuclear factor kB and receptor activating factor ligand are obviously reduced in serum and focal synovia of a patient, thereby the beta-interferon can be used for immunizing, intervening and treating rheumatoid arthritis.

The invention provides an in vitro test tool and method for evaluating biological activity of RANKL target spot compound. The in vitro test tool and method transfers two plasmids with target genes into HEK293 cell (human embryonic kidney cell), then using the tool cell to evaluate biological activity of monoclonal drug in vitro through drug screening to obtain the tool cell for detection, which compared with traditional test method, the method has advantages of short experimental period, convenient operation, high accuracy and precision, so as to guarantee the stability, reliability and the like of the test results. The test tool cell provided by the invention can be used for biological activity evaluation of therapeutic monoclonal antibodies taking RANKL (receptor activator of NF-kappaB ligand) as target spot, antidrug neutralizing antibodies test in animal trials and clinical trials and the like.

Methods are provided of treating obesity or an obesity comorbidity in a mammalian subject comprising administering to the subject an amount of an agent effective to treat obesity or the obesity comorbidity, which agent inhibits (i) IκB kinase β (IKKβ) activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) or (ii) Notch signaling in a manner so as to permit the agent to enter the hypothalamus of the subject. Assays are also provided for identifying candidate agents for treating obesity.

The present invention relates to a pharmaceutical composition for preventing and treating cancer, cancer metastasis and bone metabolic diseases, which comprises FSTL1 (Follistatin-like 1) protein as an active ingredient. More specifically, FSTL1 inhibits AKT activity and increases activity of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome 10), while inhibiting DNA binding of NF-κB (nuclear factor-κB) and blocking the expression of target genes IL-6, GM-CSF, MMP-9, VEGF and ICAM1, and exhibits significant inhibitory effects on breast cancer growth and metastasis in animal models. Therefore, it can be useful for inhibiting cancer metastasis including breast cancer.

Compounds inhibiting the activation of the nuclear factor κB (NF-κB) are used for the preparation of medications adapted for the treatment of malignant hemopathies and solid tumors, and for the prevention of the appearance or the treatment, of phenomena of resistance to cytotoxic molecules used in the scope of treatment of the above pathologies, appearing in patients treated with these molecules when the latter are adapted to activate NF-κB.

The present invention describes a method for targeting a tumor cell comprising contacting the tumor cell with a composition comprising a macrophage and a factor that upregulates nuclear factor-kappa B (NFκB) activity.

The invention discloses application of a nuclear factor chiB inhibition protein 1 combined with A20 to preparation of a medicine for treating fatty livers and related diseases and belongs to novel application of ABIN1 (A20binding Inhibitor of NF-KB Activation). According to the application, an L02 cell line, an ABIN1 over-expression L02 cell line, mouse primary hepatocyte cells and ABIN1 over-expression mouse primary hepatocyte cells are adopted as experiment targets, fatty liver cell models are induced through palmitic acid and oleic acid together, and oil red O dyeing results show that undercombined irritation of the palmitic acid and the oleic acid of a same concentration, the areas of red fat granules in ABIN1 over-expression L02 cells are remarkably reduced when being compared with those of L02 cells. The same oil red O dyeing result trend is also observed in mouse primary hepatocyte cells with over-expressed ABIN1, the result shows that ABIN1 over-expression has a remarkable inhibition function on lipid accumulation in palmitic acid and oleic acid induced fatty liver cells. Therefore, ABIN1 has functions of inhibiting liver lipid accumulation and protecting livers.

The present invention relates to a polypeptide for use as a medicament in the treatment and / or prevention of a disease wherein the RANKL-RANK signaling pathway is involved, in particular a bone resorptive disease.

The invention discloses the application of alpha-lactose for preparing health care foods capable of preventing and treating acute pancreatitis, and belongs to the field of health care foods. The alpha-lactose can reduce pancreatic tissue oedema, serum amylase, and the level of pancreatic tissue medulla peroxidase MPO so as to reduce an inflammatory reaction in an acute pancreatitis process; besides, the alpha-lactose can reduce inflammation mediators in pancreatic tissues and pancreatic acinar cells, such as an MCP-1 level and a TNF- alpha level. In addition, the alpha -lactose has the effect of restraining the activation of signal routes for regulating protein kinase (ERK1 / 2MAPK) and nuclear factors KB (NF-KB) protein outside cells, reduces the soaking of immunocyte, such as neutrophilic granulocyte and macrophage, in pancreatic tissues, has a notable protective effect on acute pancreatitis, and can be used for preparing health care foods capable of preventing and treating acute pancreatitis.

The present invention relates to the use of certain novel myriceric acid derivatives of the formula:which are inhibitors of nuclear factor kappa B (NF-κB) and inhibit the activity of the endothelin receptor for use in the treatment of cardiovascular and inflammatory diseases and for cancers susceptible to an NF-κB inhibitor and an endothelin receptor inhibitor. The present invention also relates to compounds and methods useful to inhibit cell proliferation and for the induction of apoptosis.

Antisense oligonucleotides which hybridize with nuclear factor-κB(NF-κB) mRNA and methods of using these oligonucleotides.

The invention is a "preparation method and application of OPG-HSP70 fusion protein", which belongs to the field of biomedical new technology. The invention provides an osteoprotegerin-heat shock protein 70 (OPG-HSP70) fusion protein drug. The drug targets synovitis, the most important pathological feature of rheumatoid arthritis (RA), accompanied by destruction of cartilage and bone. Through osteoprotegerin (OPG) as a decoy receptor, it can interact with cells expressed by osteoblasts and other cells. Receptor Activator of Nuclear Factor κB Ligand (RANKL) binds, blocks the binding of RANKL to RANK expressed by osteoclasts, thereby inhibiting bone resorption involving osteoclasts; uses the protective polypeptide fragment of heat shock protein (HSP) to inhibit joint inflammation. The invention includes the DNA sequence encoding the fusion protein; the method of producing the fusion protein through recombinant technology; and the biological activity of the fusion protein, etc.

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.