95 results about "STAT3" patented technology

The invention discloses application of THBS1 in preparation of pancreatic cancer diagnosis and treatment products. Wherein THBS1 in pancreatic cancer cells is high in expression, and the higher expression level of THBS1 is related to poor prognosis of pancreatic cancer patients; in addition, migration and invasion of pancreatic cancer cells can be inhibited by reducing THBS1 gene expression, and apoptosis is promoted at the same time; in addition, the THBS1 inhibitor can also be used for preparing a medicine for inhibiting a JAK2 / STAT3 signal channel (reducing phosphorylation of JAK2 and STAT3).

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 present invention relates to a series of antisense oligonucleotides containing morpholine 3- thiophosphoramidate nucleotides or morpholine 3-thiophosphoramidate and DNA / RNA (modified) nucleotides having phosphorothioates (pS) linkers. They are specifically designed to be complementary to nucleic acid sequences within the Signal Transducer and Activator of Transcription 3 (STAT3) pre-mRNA or mature sequences, leading to the degradation of STAT3 mRNA or inhibition of STAT3 translation, or induce alternative splicing of STAT3 resulting in an increase of STAT3β isoform relative to STAT3α isoform. The antisense oligonucleotides are used for the treatment of diseases that could be modulated by the STAT3 pathway, which has been implicated in tumor initiation, progression, metastasis, drug resistance and immune suppression. As a result, these novel antisense oligonucleotides could be used for the treatment of STAT3 related diseases, such as cancer or autoimmune diseases.

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.

The subject matter disclosed herein relates to modulating STAT3 gene expression using siRNA compositions and methods that involve affecting key cell populations that support cancer growth and metastasis to achieve beneficial treatment, alleviation or removal of potential tumors in a patient.

Provided herein are improved delivery systems for oligonucleotides, said delivery system comprising a liposome that comprises neutral phospholipids and a P-ethoxy oligonucleotide, which targets a STAT3-encoding polynucleotide. Methods of treating patients with said delivery systems are also provided.

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 invention relates to an exosome and application thereof, and belongs to the technical field of tumor immunotherapy. According to the scheme, the repolarization effect of exosomes secreted after oral squamous cell carcinoma cells are stimulated by phenformin on M2 macrophages is researched, miRNA-17 and / or miRNA-20 capable of acting on STAT3 mRNA in the M2 macrophages are / is found, and it is found through further research that miRNA-17 and / or miRNA-20 can act on 3 '-UTR areas of STAT3 mRNA in the M2 macrophages, so that repolarization of the M2 macrophages is promoted. According to the application, deep research is carried out from the perspective of the action pathway of miRNA, and a brand new technical route which is feasible for tumor immunotherapy is provided through experimental verification of different levels, so that the application has a wide clinical application prospect and a huge commercial value.

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 application discloses an antigenic peptide targeting the phosphorylation of Tyr705 of the STAT3 protein and its application. The antigenic peptide has an amino acid sequence as shown in SEQ ID NO. 6 to 9, or an amino acid homologous sequence with the same function as the sequence. The antibody prepared using the antigenic peptide can recognize the Tyr705 phosphorylation level of ΔS701 and FL subtypes, which will be of great significance for exploring the mechanism of the STAT3 protein ΔS701 subtype in cells, as well as the biological function research in animals and humans and drug development. In addition, the present application discloses a method for preparing an antibody against the phosphorylation of Tyr705 of the STAT3 protein. The antibody prepared by the method has strong specificity, high purity and good stability.

To provide a novel prophylactic or therapeutic agent for coronavirus infection, the agent containing a substance that has not been known for its therapeutic effect on coronavirus infection as an active ingredient.SOLUTION: The present invention provides a prophylactic or therapeutic agent for coronavirus infection, the agent containing stanniocalcin 1 (STC1) as an active ingredient.SELECTED DRAWING: None

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.