75 results about "STAT3" patented technology

The invention discloses a preparation method of prune exosomes and application of the prune exosomes in regulation and control of pigment metabolism and skin cell inflammatory response, and the preparation method comprises the following steps: taking prune, washing, peeling, dicing, juicing, adding a compound enzyme preparation, centrifuging at 2,000 g for 20 min, carrying out trehalose-assisted ultracentrifugation, centrifuging at 12,000 g for 30 min, centrifuging at 40,000 g for 60 min, centrifuging at 120,000 g for 70 min, collecting precipitate PBS, re-suspending, and filtering to obtain the high-purity prune exosomes. It is proved for the first time that the prune exosome dose-dependently inhibits the melanin content and tyrosinase activity in B16F10 melanoma cells, the mRNA expression level of key inflammatory factors TNF-alpha, IL-1beta and IL-6 in TNF-alpha-induced Hacat cells is remarkably reduced, in addition, the inhibition effect of melanin can be amplified through an STAT3 channel by combining the prune exosome with luteolin, and the application of the prune exosome to the preparation of the anti-inflammatory drug is promoted. The polypeptide can be used for preparing a preparation for regulating pigment anabolism and skin-related inflammatory response, and a potential biological application value is exerted.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

To provide a method of treating an inflammatory neurological disease or condition that can result in destruction or degeneration of axons or myelin.SOLUTION: Provided is a combination comprising a) a compound of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof; and b) one or more drugs selected from the group consisting of I) a compound of a particular formula or a pharmaceutically or veterinarily acceptable salt thereof; ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator); and iii) a signal transducer and activator of transcription 3 (STAT3) inhibitor.SELECTED DRAWING: None

The invention relates to application of WDR74 and / or ALYREF as molecular targets in esophageal squamous cell carcinoma diagnosis and treatment, and belongs to the technical field of biological medicine. Aiming at the problem that the esophageal squamous cell carcinoma lacks an effective targeted treatment means, the invention discovers that the expression quantity of WDR74 in tumor tissues is obviously higher than that in para-carcinoma tissues, and the high expression of WDR74 prompts poor prognosis of a patient, and reveals that WDR74 protein and ALYREF protein have specific binding, and the mRNA stability of EGFR is enhanced through ALYREF-mediated m5C RNA epigenetic modification, so that STAT3 phosphorylation is activated, and the treatment effect of the esophageal squamous cell carcinoma is enhanced. Further, the STAT3 is combined with the promoter region of the apoptosis-inhibiting gene MCL1, and finally cell apoptosis is inhibited and tumor formation is promoted. The invention provides a new molecular target and a solution for developing a WDR74 and ALYREF targeting medicine for treating esophageal squamous cell carcinoma and related diagnosis and prognosis evaluation products.

This invention discloses a compound having the structure shown in general formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. This invention also discloses a composition, formulation, and application containing the above compound. The compound of this invention degrades the transcription factor STAT3, exhibits antiproliferative inhibitory activity against the Karpas299 cell line, and has a favorable tumor / plasma AUC ratio.

The invention relates to the field of biotechnology and medicine, and discloses a polypeptide targeting molecular chaperonin TRIC / CCT and application thereof. The sequence of the polypeptide is consistent with or truncated from the C-terminal sequence of a CCT subunit, and the polypeptide can be competitively combined with CRL4-DCAF12 ubiquitin ligase, so that the ubiquitination of the CCT subunit is reduced, and the formation of a TRIC / CCT compound is inhibited; the polypeptide inhibits the formation of a TRIC / CCT compound and blocks the activation of key metastasis promoting signal channels such as YAP, STAT3 and mTOR, thereby inhibiting the metastasis of lung cancer. According to systematic in-vivo and in-vitro experiments, the compound has excellent performance in the aspect of inhibiting lung cancer cell migration and metastasis, has the characteristics of clear target spot, clear action mechanism and the like, and provides a new treatment strategy for developing a new generation of lung cancer metastasis resisting medicines.

The invention discloses application of HSF1A in preparation of a medicine for resisting lung cancer metastasis, and relates to the technical field of anti-tumor medicines. It is found for the first time that HSF1A can be used for inhibiting non-small cell lung cancer metastasis. The HSF1A is specifically combined with a CCT1 subunit ATPase structural domain of a TRIC / CCT compound, so that the protein folding function of the TRIC / CCT compound is interfered, and three key transfer promoting signal channels including YAP, STAT3 and mTOR are inhibited at the same time. In a pulmonary metastatic tumor model constructed by mouse tail intravenous injection, the formation of pulmonary metastatic tumor is obviously reduced by the HSF1A, and the fact that the HSF1A also has strong anti-metastatic capability in an in-vivo environment is proved; the safety is high, and the development and utilization prospects are good. The invention not only provides a new application of the HSF1A, but also provides a new thought and method for adjuvant therapy of cancers.

Described herein are compositions relating to cell-penetrating conjugates of formula (I) or (IV). The compositions are capable of penetrating cells and recognizing intracellular targets (e.g., STAT3) and are, inter alia, useful for diagnostic and therapeutic purposes.

The invention relates to application of a reagent for inhibiting STAT3 gene expression in treatment of oxidative damage of trabecular meshwork cells. According to the invention, a signal channel STAT3 to EIF4E to TGF-beta-SMAD < 2 / 3 > for regulating and controlling the oxidative damage of the trabecular meshwork cells is innovatively found, and the STAT3 activates the TGF-beta-SMAD < 2 / 3 > channel by combining with EIF4E3, so that the apoptosis, oxidative stress and fibrosis of the trabecular meshwork cells caused by the oxidative damage are promoted. After the expression of the STAT3 gene in trabecular meshwork cells is inhibited, the EIF4E3 level can be reduced, and the apoptosis, oxidative stress and fibrosis of the trabecular meshwork cells induced by EIF4E3 are improved. Therefore, a reagent for inhibiting STAT3 gene expression can be used for treating trabecular meshwork cell oxidative damage and eye diseases related to the trabecular meshwork cell oxidative damage, including glaucoma and the like.

The invention discloses a phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting. The phototherapy nano-drug is ATO / CR nano-particles formed by self-assembling a compound CR and atorvaquone under the action of distearoyl phosphatidyl ethanolamine-polyethylene glycol; the structure of the compound CR is shown as a formula I in the specification. The invention discloses an application of the phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting in preparation of drugs for treating tumors. The phototherapy nano-drug can target mitochondria and STAT3 protein in tumor cells through ATO, and can also passively target tumor sites through the high-permeability long-retention effect of nano-particles, so that more nano-therapeutic agents are enriched around tumors, and the curative effect is improved. The phototherapy nano-drug provided by the invention has good photothermal performance, can effectively enhance the PTT effect of gastric cancer, and exerts the tumor synergistic treatment ability by promoting cell apoptosis, inhibiting angiogenesis and hindering the cell cycle.

This invention belongs to the field of biomedical technology and relates to the application of OSM inhibitors in the preparation of drugs for the prevention or treatment of calcific aortic valve disease. This invention reveals for the first time that OSM drives osteogenic differentiation and calcified nodule formation of valvular interstitial cells through the OSM-OSMR-JAK2 / JAK3-STAT3-RUNX2 signaling axis, which is the core pathogenic mechanism leading to calcific aortic valve disease. This invention utilizes anti-OSM neutralizing antibodies or sulforaphane to effectively block this signaling axis, significantly inhibiting macrophage infiltration, valvular calcification, and improving hemodynamic abnormalities. This invention provides a precise target and a novel strategy for the modification therapy of calcific aortic valve disease, solving the technical problem of the ineffectiveness of traditional broad-spectrum anti-inflammatory therapy in valvular calcification.

This invention discloses a STAT3-mutated cell product and its uses, belonging to the interdisciplinary field of genetic engineering and tumor immunotherapy. Through saturation mutation screening, this invention is the first to discover that STAT3 gain-of-function mutations promote CAR-T anti-tumor responses. Furthermore, through cell and animal experiments, it is demonstrated that activating STAT3 can alleviate CAR-T cell immune exhaustion and significantly enhance the in vivo and in vitro killing ability of CAR-T cells against tumor cells, thereby improving the efficacy of anti-tumor therapy. This invention provides a new therapeutic target and strategy for the field of tumor immunotherapy, possessing significant scientific and clinical application value.

The present invention relates to a single domain antibody specifically binding to STAT3 or an antigen-binding fragment thereof, a fusion protein comprising the single domain antibody or the antigen-binding fragment thereof, and a use of the fusion protein.

The present disclosure provides cytokine signaling receptors to provide STAT3 and STATS signaling in cells such as iPSC-derived CD8+ T cells. The cytokine signaling receptors may be under the control of endogenous or exogenous promoters to regulate their expression in a cell. The present disclosure also provides engineered cells comprising the cytokine signaling receptors, or a combination of a cytokine signaling receptor and a secreted cytokine, as well as methods of use of the engineered cells.

The application discloses an application of a small molecule compound in preparation of an IL-6R inhibitor and belongs to the technical field of medicines. Through various calculation methods and in-vitro experiments, two novel small molecule compounds targeting IL-6R are successfully identified, and are named as Z1268663363 and Z1268663684 respectively. The small molecule compound can inhibit IAV and SARS-CoV-2 induced IL-6 signaling pathway, and phosphorylation of STAT3, JAK2 and gp130 induced by IL-6. In addition, the small molecule compound can inhibit IL-6 stimulated TF-1 cell proliferation and block the binding of IL-6 and IL-6R. In addition, MD simulation confirms the spontaneous and sustained binding between the compound and IL-6R. The research reveals the flexible binding site of IL-6R, and determines a promising small molecule binder, and promotes the development of new drugs for IL-6 related diseases.

The disclosure is generally directed to spherical nucleic acids (SNAs), nanostructures with a core surrounded by a radial presentation of oligonucleotides, that can activate a cytoplasmic DNA sensor including but not limited to cyclic GMP-AMP synthase (cGAS). In some embodiments, the SNAs also inactivate a transcription factor including but not limited to signal transducer and activator of transcription 3 (STATS). Methods of making and using the SNAs are also provided herein. In some aspects, the present disclosure provides a spherical nucleic acid (SNA) comprising (a) a nanoparticle core; and (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising a double-stranded or single-stranded stem loop DNA oligonucleotide that activates cyclic GMP-AMP synthase (cGAS) and is at least 15 base pairs in length.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

The present invention relates to a kind of Angong Niuhuang Wan quality evaluation method based on STAT3 protein biological effect, it is to use surface plasmon resonance (SPR) detection technology, specifically including the following steps: 1) construction of protein chip;2) preparation of test solution;3) preparation of reference solution;4) test solution and reference solution injection are taken respectively and carry out SPR detection, analyze and flow through protein chip surface and STAT 3 protein binding, measure corresponding response value (RU value).Quality evaluation standard is that the ratio of test sample RU value to reference substance RU value should be not less than 1.The present invention is optimized and verified by methodology, and accuracy is high, can reflect the effectiveness of Angong Niuhuang Wan clinical treatment, further improves the quality control system of Angong Niuhuang Wan, possesses practical application promotion value.

This invention discloses a triphenylamine-based D-A type AIE molecule targeting STAT3, its preparation method, and its application in the diagnosis and treatment of colorectal cancer. This molecule uses triphenylamine as a donor and pyridinium as an acceptor, linked by a rigid conjugated trans-vinyl group, exhibiting aggregation-induced emission (AIE) properties. The preparation method employs a Knoevenagel condensation reaction, using 4-(diphenylamino)benzaldehyde and 1,4-dimethylpyridinium iodide as raw materials, and proceeds via a nucleophilic addition-dehydration reaction catalyzed by pyrrolidine, with a yield of 50±3% and a purity ≥98%. This molecule exhibits a fluorescence emission wavelength of 640 nm, demonstrates a significant AIE effect, can penetrate the colorectal cancer cell membrane and specifically aggregate, and shows activity against the IC50 of HCT116 and DLD1 cells. 50 The concentrations were 6.41 μM and 11.46 μM, respectively, which exerted anti-tumor effects by inhibiting STAT3 phosphorylation, enabling integrated diagnosis and treatment of colorectal cancer.

The subject matter disclosed herein is directed to modulating STAT3 gene expression using siRNA compositions and methods directed to affecting key cell populations supporting the growth and metastasis of cancer to affect the beneficial treatment, remission or removal of the underlying tumor in a patient.

The invention discloses a multivalent triangular DNA origami delivery system as well as a preparation method and application thereof, which can be used as a novel method for treating osteoarthritis, and is particularly suitable for patients with cartilage degeneration and joint inflammation caused by age, obesity, joint reuse, sport injury or genetic factors and the like. Specific siRNAs (small interfering RNAs) are delivered by the use of multivalent triangular DNA origami. According to the scheme, the expression of inflammation and degeneration related genes, such as Stat3, MMP3 and MMP13, in cartilage cells in joints can be specifically inhibited, so that the inflammatory response is relieved, cartilage decomposition is inhibited, and repair and regeneration of cartilage tissues are promoted. The invention provides a method for treating osteoarthritis, which has the advantages of strong targeting property, small side effect and obvious curative effect, is suitable for clinical treatment and basic medical research, and has wide application prospect.

The invention relates to the technical field of tumor early warning, and discloses an LAMA-IL-6-JAK-STAT3 axis-targeted uveal melanoma micro-metastasis early warning and immune escape blocking system, which comprises a micro-metastasis early warning module, a cooperative control module and an immune escape blocking module, the system executes the following steps: S1, target anchoring and sample collection: the micro-transfer early warning module specifically binds LAMA protein, IL-6 cell factors and JAK / STAT3 kinase in a sample through a targeting probe, and collects uveal melanoma nidus tissue cells and a peripheral blood sample to complete target anchoring. In the system, an LAMA-IL-6-JAK-STAT3 axis is used as a specific action target, an LAMA antagonist, an IL-6 receptor inhibitor and a JAK kinase inhibitor in the composite targeting preparation respectively and accurately act on key nodes of a signal axis, and down-regulation of STAT3 activity is realized through stepped regulation, so that non-specific damage of traditional treatment to normal cells is avoided, toxic and side effects of intraocular tissues are reduced, and the treatment effect is good. The local diagnosis and treatment requirements of uveal melanoma are particularly met.

The invention belongs to the field of medicines, and discloses application of a reagent for inhibiting phosphorylation of STAT3 and / or reducing the expression level of a 20S proteasome beta 5 subunit in preparation of a sensitizer. The sensitizer is a reagent for improving the sensitivity of the proteasome inhibitor acting on solid tumor cells. A reagent for inhibiting the phosphorylation of STAT3 and / or for reducing the expression level of the 20S proteasome beta 5 subunit is used for preparing a sensitizer for assisting the proteasome inhibitor to improve the sensitivity, and the sensitizer can be used for improving the sensitivity of the proteasome inhibitor when acting on cancer cells. In addition, the invention also discloses a medicine containing the sensitizer.

The invention belongs to the technical field of biological medicines, and particularly relates to a long-acting STAT3 inhibition polypeptide and application thereof in tumor resistance. The long-acting STAT3 inhibition polypeptide is designed by taking an SH2 structural domain in a negative regulatory protein SH2 adapter protein F (Shf) of STAT3 protein as a template and combining single-point mutation and active fragment splicing and N-terminal long-acting fatty acid chain modification, the tumor inhibition effect is enhanced while template targeted affinity STAT3 protein and high selectivity to tumor cells are reserved, and the tumor inhibition effect is improved. Meanwhile, the plasma stability is enhanced, the half-life period is prolonged, and the bioavailability is improved. The long-acting STAT3 inhibitory polypeptide provided by the invention is stable in chemical property and relatively low in toxicity to normal cells, and has potential anti-tumor clinical application value and wide development prospect.

The invention relates to siRNA targeting TRIM29, the sequence of the siRNA is shown as SEQ ID NO.1. Through cell level and animal level experiment detection, the siRNA can inhibit expression of the TRIM29, and the sensitivity of gallbladder cancer to gemcitabine is remarkably improved; the invention further relates to gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles and a preparation method and application thereof, the preparation method comprises the steps that firstly, gemcitabine and TRIM29 siRNA wrapped lipid nanoparticles are constructed, then the gemcitabine and TRIM29 siRNA are co-incubated to obtain GSL, the GSL is oval in microcosmic shape and good in stability, through cell level and animal level experiment detection, the GSL has a good anti-tumor effect, and the GSL has a good anti-tumor effect on the gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles. The GSL can significantly reduce the protein expression level of TRIM29, significantly improve the sensitivity of gallbladder cancer to gemcitabine, inhibit tumor growth, and inhibit STAT3 pathway, and the GSL prepared by the method has good biological safety, and opens up a new channel for treatment of gallbladder cancer.

Methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency are disclosed in this patent application. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and / or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and / or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein the one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

Pharmaceutical compositions and compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized an RNA aptamer are useful in methods of treating cancer (such as leukemia) and methods of inhibiting DNA methyltransferase. In embodiments, the RNA aptamer binds to an intracellular target such as DNMT1, NF-kB, RUNX1, MYC, MYB, ETS, PAX5, MDM2, F0XM1, PU.l, STAT3, STATS. STAT6, FAD, ATP5B, or beta-catenin.

The invention discloses an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC), and belongs to the technical field of biological medicine, in particular to an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC). According to the application, it is found for the first time that SGC has a specific killing effect on PRCC-TFE3 rRCC cells and has extremely low toxicity on normal kidney cells; the SGC has multiple anti-tumor action mechanisms: on one hand, the SGC is directly combined with and antagonizes a VEGFR2 receptor on a cell membrane to block autocrine signal transduction of VEGFB; on the other hand, the SGC inhibits transcription of VEGFB (vascular endothelial growth factor B) through ROS / p-STAT3 axis epigenetics; besides, the SGC can inhibit the production of lactic acid and the acylation of H3K18, and down-regulate the secretion of chemotactic factors, so that the infiltration of polymorphic myeloid-derived suppressor cells (PMN-MDSCs) in a tumor microenvironment is remarkably inhibited; in an immune sound mouse model, the SGC shows an excellent in-vivo anti-tumor effect, and a brand new targeting and immunoregulation double-effect candidate drug is provided for clinically treating the PRCC-TFE3 rRCC lacking an effective standard therapy.

The application relates to the fields of biological medicine and antibody engineering technology, and particularly relates to a STAT3 hybridoma-derived antibody affinity maturation method based on computational biology, which comprises the following steps: (1) obtaining an antibody variable region sequence; (2) constructing STAT3 antigen and antibody models and evaluating; (3) performing antigen-antibody molecular docking and optimization, and screening out models; (4) performing docking model analysis, and obtaining potential saturation mutation sites; (5) performing site saturation mutation, and obtaining mutation results; (6) performing mutation site analysis, and determining final mutation sites; (7) amplifying a target fragment containing the mutation sites; (8) constructing a recombinant expression vector, and obtaining a reformed STAT3 recombinant antibody through eukaryotic expression and purification; and (9) performing relative affinity determination.