30 results about "HMGB1" patented technology

The application provides a group of small interfering RNAs (siRNAs) targeting pyroptosis-related inflammatory reaction genes and application thereof. The pyroptosis-related inflammatory reaction genes include IL1A, IL1B, IL6, HMGB1, S100A8, S100A9 and BACH1. The application designs and synthesizes specific siRNA sequences for the above genes, and verifies that the siRNAs can efficiently and specifically inhibit the mRNA expression level of the corresponding genes through cell transfection and real-time fluorescent quantitative PCR. The application also provides a composition containing the siRNAs, a pharmaceutical composition and application thereof in the preparation of a drug for treating diseases mediated by pyroptosis-related inflammatory reaction genes (especially inflammatory diseases). The siRNAs and the composition thereof provide a new effective strategy for treating diseases related to excessive activation of pyroptosis-related inflammatory reactions, and have a wide application prospect.

The invention relates to the technical field of biological medicine, and discloses a targeting molecule for inhibiting generation of PD-L1 and giant cells mediated by a tumor exosome HMGB1 and application of the targeting molecule, the targeting molecule comprises a first binding unit, a second binding unit and a flexible connecting peptide for connecting the first binding unit and the second binding unit; the amino acid sequence of the first binding unit is Asp-Gly-Arg-Tyr-Phe-Leu-Ser-Pro-Asn-Lys, and the first binding unit can be specifically bound with a binding boundary of a C-terminal acid tail of HMGB1 on the surface of a tumor exosome and RAGE; the amino acid sequence of the second binding unit is Trp-His-Glu-Val-Met-Ala-Gln-Ile-Arg-Ser, and the second binding unit can be specifically bound with an extracellular structural domain of PD-L1 on the surface of the macrophage; the amino acid sequence of the flexible connecting peptide is Gly-Gly-Ser-Gly, and the amino acid sequence of the flexible connecting peptide is Gly-Gly-Ser-Gly. In order to achieve the purpose of specifically inhibiting PD-L1 expression mediated by tumor exosome HMGB1 and giant cell generation, a targeting molecule containing a bispecific binding unit is designed, a first binding unit is specifically bound with a specific binding interface of the tumor exosome surface HMGB1, and a second binding unit is specifically bound with an extracellular structural domain of PD-L1 on the macrophage surface; therefore, the purpose is achieved.

This invention discloses the application of lipoic acid analog formulations in the preparation of anti-cardiomyocyte senescence products. The lipoic acid analog DMAE-LA is N-(2-(dimethylamino)ethyl)-5-(1,2-dithiopentane-3-yl)pentanamide, with a concentration of 2-25 μM. DMAE-LA pretreatment effectively reduces intracellular ROS, improves mitochondrial function, inhibits the overexpression of p21 and HMGB1, and restores Lamin B1 levels, thereby alleviating the senescent manifestations of cardiomyocytes. DMAE-LA reduces H₂S oxidative depletion by inhibiting ROS generation and may promote H₂S synthase activity, increasing endogenous H₂S levels and further enhancing cellular antioxidant capacity. In summary, DMAE-LA can significantly inhibit cardiomyocyte senescence through multiple antioxidant mechanisms and organelle function protection, providing a potential intervention strategy for targeting cellular senescence in cardiovascular diseases.

The present invention provides a method of treating a disease or condition in a subject characterized by an inflammatory response, comprising administering to the subject an effective amount of a nucleic acid encoding HMGB1 Box A wherein the HMGB1 Box A antagonizes an intact HMGB1 in the subject, wherein the nucleic acid comprises a promoter that regulates expression of the nucleic acid encoding HMGB 1 Box A, wherein the promoter is an inflammation-inducible promoter that is activated by an inflammatory signal. Viral vectors encoding HMGB 1 Box A for use in the methods are also provided.

The present invention relates to a compound of the formula: H2N-AXBAXB-HOOC (wherein A is a sequence of consecutive amino acids, the sequence of which (1) contains the same sequence as amino acids 90 to 93 of wild-type HMGB1, (2) has 1 to 6 consecutive amino acids, e.g., 1, 2, 3, 4, 5, or 6 amino acids, at its amino terminal side, whose sequence is the same as the sequence of the corresponding 1 to 6 amino acids preceding amino acid 90 of wild-type HMGB1, and optionally (3) the amino terminus is methionine, and X is a sequence of consecutive amino acids, the sequence of which is the same as amino acid 94 of wild-type HMGB1. (1) a sequence identical to the sequence of amino acids 163 to 168 of wild-type HMGB1; and (2) a sequence identical to the sequence of 1 to 6 consecutive amino acids, e.g., 1, 2, 3, 4, 5, or 6 amino acids, at its carboxy terminus, whose sequence is identical to the sequence of 1 to 6 corresponding amino acids after amino acid 168 of wild-type HMGB1, and each - represents a peptide bond between A and X, X and B, B and A, A and X, and X and B, respectively. The present invention provides a polypeptide represented by the formula:

The invention discloses a drug for combined treatment of breast cancer bone metastasis, the drug comprises two active components, namely a first active component and a second active component, the first active component is Bufalin and its pharmaceutically acceptable salt, prodrug and derivative, and the second active component is RANKL targeted drug; bufalin and a derivative thereof are combined with an RANKL targeted drug for use, the Bufalin and the derivative thereof are synergistically complementary, and the Bufalin is used for regulating and controlling a tumor microenvironment, reducing secretion of high bone metastatic breast cancer cells HMGB1 and inhibiting differentiation of mononuclear / macrophages in bone marrow to osteoclasts, so that occurrence and development of breast cancer bone metastasis are inhibited; the RANKL targeted drug can specifically block an OPG / RANK / RANKL signal channel, inhibit osteoclast activation, reduce bone destruction and block vicious circle of bone metastasis; when the two active ingredients are combined for use, the effect of inhibiting breast cancer bone metastasis is obviously better than that of single use of any active ingredient, the occurrence of breast cancer bone metastasis can be effectively prevented and delayed, the progress of bone metastasis focus is controlled, and the occurrence risk of bone related events is reduced.

The invention relates to an application of an indole base compound or a pharmaceutically acceptable salt of the indole base compound and a pharmaceutically acceptable carrier in preparation of a medicine or a skin care product for treating or preventing high HMGB1 (High Mobility Group Box 1) type skin diseases, the indole base compound comprises at least one functional group of quaternary ammonium cations, amino groups or amino groups containing substituent groups; the HMGB1 type skin disease is marked by an increase in the level of high mobility group protein B1 (HMGB1) or is abnormal in signal path. According to the present invention, the N37 residue of the HMGB1 can be specifically bound, the pathological release of the N37 residue from the cell nucleus to the cytoplasm can be accurately blocked, the physiological functions of the N37 residue in the nucleus and the like are not affected, and the potential side effect of the existing broad-spectrum HMGB1 inhibitor is overcome.

The invention provides a gene marker combination and application thereof in a risk prediction model of premature eclampsia. The gene marker combination comprises a combination selected from GTF2H1, CD48, PBX1, PLA2G2A, ACVR1B, HMGB1, ERBB2, XRCC5, TGFBR2, NFKB1, EGF, TLR6, EZH2, IKZF1, EGFR and CD36, a combination of HIPK1, MTHFR, IL6R, RAB27A, UBE2I, CREBBP, SOX8, HNF4A, ICOS, LIF, TMPRSS6, DNMT3A, WWTR1, RASSF1, FOXP1, TLR2 and MAPK14, AGRN, ATP2B1, ELAC2, HDAC5, GABARAP, FXR2, NFE2L2,

One aspect according to the present invention relates to: a gold nanozyme including glycol chitosan and gold particles; and a pharmaceutical composition for preventing or treating inflammatory bowel disease, the composition comprising the gold nanozyme. The gold nanozyme and the pharmaceutical composition comprising same according to one aspect of the present invention was found to inhibit the expression of inflammatory factors, inhibit the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) inside cells, and reduce the production of nitric oxide (NO) inside cells. In addition, the gold nanozyme was found to inhibit the secretion of Hight Mobility Group Box 1 (HMGB1) when further including glycyrrhizin. In addition, the gold nanozyme and the composition comprising same were found to enable the recovery of the length, weight, etc., of damaged intestines, and thus can be used in the inflammatory bowel disease prevention and / or treatment industry / market.

The invention relates to the technical field of biological medicines, and particularly discloses application of brucea javanica oil in preparation of a medicine for inhibiting radiation pneumonitis or idiopathic pulmonary fibrosis. When the brucea javanica oil is used for preparing the medicine for inhibiting radiation pneumonitis, the symptom of radiation pneumonitis can be remarkably relieved, the curative effect of the medicine is equivalent to that of dexamethasone, release of proinflammatory factors can be effectively inhibited, and inflammatory cascade reaction is blocked and lung tissue injury is relieved by down-regulating mRNA and protein expression of an HMGB1 / TLR4 / NF-kappa BP65 axis. The brucea javanica oil is applied to preparation of the medicine for treating idiopathic pulmonary fibrosis, lung tissue inflammatory cell infiltration can be effectively inhibited, abnormal collagen deposition can be reduced, expression of fibrosis promoting proteins COL1A1, VIM and ACTA2 can be down-regulated, and the pulmonary fibrosis process can be relieved by inhibiting fibroblast activation and extracellular matrix excessive deposition.

The invention provides a chimeric polypeptide for enhancing immunogenicity of a tumor vaccine as well as a preparation method and application of the chimeric polypeptide. The chimeric polypeptide comprises at least two connected immunological enhancement molecular fragments, and the immunological enhancement molecular fragments comprise CD40L or a functional fragment thereof, and one or more selected from a group consisting of GM-CSF or a functional fragment thereof, HMGB1 or a functional fragment thereof, HSP70 or a functional fragment thereof, FLT3L or a functional fragment thereof, and OX40L or a functional fragment thereof. According to the chimeric polypeptide provided by the invention, the mRNA has a good immunological enhancement effect in cells, antigen-specific cellular immune response can be remarkably induced, and the chimeric polypeptide serving as an immunologic adjuvant can be used for constructing an anti-tumor drug (such as an mRNA vaccine) with a better tumor treatment effect.

This invention relates to the field of biomedical technology, and in particular to mesenchymal stem cells, their preparation methods, and applications. The method for preparing mesenchymal stem cells includes the following steps: culturing the mesenchymal stem cells under hypoxic conditions with an oxygen volume fraction of 2%–4%, and during the hypoxic culture, pre-activating the mesenchymal stem cells by contacting them with an induction system containing 1–3 ng / mL Oncostatin M, 1–10 ng / mL IL-1β, and 2–10 ng / mL HMGB1 for 6–24 hours. Mesenchymal stem cells treated by this method can significantly inhibit lymphocyte proliferation, reduce the proportion of pro-inflammatory T cell subsets such as Th1 and Th17, increase the proportion of Treg cells, and effectively reduce the level of the inflammatory factor TNF-α.

The invention relates to a tissue marker for proton radiation heart injury and application of the tissue marker. The tissue marker comprises one or more of a transcription marker and a protein marker. Wherein the transcription marker comprises one or more of PIK3R5, CCR7, IL7R, CD7, CD22, CR2, CCL5 and VAV1, and the transcription marker comprises one or more of PIK3R5, CCR7, IL7R, CD7, CD22, CR2, CCL5 and VAV1; and the protein marker comprises one or more of SIRT1 and HMGB1 (High Mobility Group Box 1). According to the invention, the differential marker is used as a potential biomarker of the radioactive heart loss, and a research method for researching the radioactive heart loss by using a mouse model is provided, so that a demonstrative research is provided for multi-omics analysis of the radioactive heart loss and explanation of an action mechanism of the radioactive heart loss.

The invention discloses aromatic acid salt of apolipoprotein E mimetic peptide as well as a preparation method and medical application of the aromatic acid salt. The aromatic acid salt, namely the compound ZYH-76, regulates and controls miR-29a-5p, inhibits an iNOS / HMGB1 / TLR4 / MMP-9 signal channel, reduces polarization of A1 type astrocytes, promotes polarization of A2 type astrocytes and protects the integrity of a blood-brain barrier, so that hemorrhagic transformation (HT) after acute ischemic stroke is inhibited. The compound ZYH-76 has a remarkable drug effect in various HT animal models, excellent pharmacokinetic properties and high safety, can be prepared into a freeze-dried preparation for injection, is suitable for HT risk prevention and treatment, and has a good clinical application prospect.

The invention discloses an anti-biological reduction protective agent applicable to phenothiazine photosensitive dyes and application of the anti-biological reduction protective agent in the aspects of phototherapy and immunological enhancement. The protective agent is a biosafe electron acceptor (such as thymoquinone TQ, cytochrome c and ethidium dihydrogen), can effectively inhibit MB from being reduced into colorless LMB in a physiological simulation environment containing NADH / NADPH, accelerates reoxidation of LMB into active MB, and significantly improves the ROS yield (up to 4 times or more). The combined system not only greatly enhances the photodynamic effect of MB in tumor cells and bacteria, but also can strengthen the release of immunogenic death factors (CRT, HMGB1 and ATP), and provides a brand new strategy for developing high-performance phototherapy materials, in-vitro antibacterial systems and immune regulation tools.

A biomarker composition which is for diagnosing or inducing senescence and comprises HMGB1, particularly reduced HMGB1, according to the present invention enables more sensitive and specific diagnosis of secondary senescence than existing typical senescence markers, and enables the provision of a candidate drug screening tool for senescence therapeutic agent development and the prediction and monitoring of senescence treatment responses.

The present invention relates to an orally administered anti-inflammatory low-molecular-weight compound for treating inflammatory bowel disease, and use thereof. More specifically, the low-molecular-weight compound of the present invention can inhibit the activation of immune cells mediated using RAGE and TLR by targeting HMGB1 and directly binding thereto, and thus can inhibit the expression or secretion of inflammatory cytokines, enzymes and the like from immune cells, acts effectively even with respect to HMGB1 non-mediated inflammatory responses, effectively inhibits inflammatory responses in intestinal tissues when orally administered to inflammatory bowel disease animal models, and induces the regeneration of the intestinal mucosal layer by alleviating inflammatory responses, thereby being used the prevention or treatment of inflammatory bowel disease.

The invention belongs to the technical field of biosensing, and particularly relates to a biosensor for detecting high-mobility group protein B1 as well as a preparation method and application of the biosensor. The biosensor is an organic electrochemical transistor and comprises a substrate; the source electrode, the drain electrode and the gate electrode are arranged on the substrate; an organic semiconductor channel connecting the source electrode and the drain electrode; the nucleic acid aptamer molecular layer is fixed on the surface of the gate electrode and can be specifically combined with HMGB1; the sealing agent molecular layer is used for passivating uncombined sites on the surface of the gate electrode; and when the HMGB1 is combined with the aptamer, electrolyte ions are caused to be doped into an organic semiconductor channel, so that the output current is efficiently modulated, and rapid, high-sensitivity and high-specificity label-free electrical detection is realized. The biosensor is suitable for dynamic monitoring of HMGB1 in various diseases such as acute kidney injury and sepsis, and a novel tool is provided for disease early diagnosis and disease course management.

The application discloses an arylate of apolipoprotein E mimetic peptide and a preparation method and medical application thereof. The arylate, namely compound ZYH-76, can inhibit hemorrhagic transformation (HT) after acute ischemic stroke by regulating miR-29a-5p, inhibiting an iNOS / HMGB1 / TLR4 / MMP-9 signal path, reducing polarization of A1 type astrocytes, promoting polarization of A2 type astrocytes and protecting integrity of a blood-brain barrier. The compound ZYH-76 has remarkable effects in various HT animal models, excellent pharmacokinetic properties and high safety, can be prepared into a freeze-dried preparation for injection and is suitable for HT risk prevention and treatment, and has a good clinical application prospect.

The present invention provides a computer implemented method for predicting the risk of posttransplant lymphoproliferative disorder as well as a computer implemented method for simultaneous predicting the risk of posttransplant lymphoproliferative disorder and differentiation of Epstein Barr Virus (EBV)-positive from EBV-negative patients in posttransplant lymphoproliferative disorder and associated systems. The method for predicting the risk of posttransplant lymphoproliferative disorder PTLD, comprises the following steps: receiving information representative for expression level of biomarkers, acquired from a sample to be assessed, said biomarkers being at least three selected from the group comprising HSPA6, CD300A, IFITM1, SHFL, HMGB1, TMEM163, ELL3, GRHPR, GMDS, GALNT10, IRF1-AS1, IFIT5, MLLT3, KIR2DL4, CD1C, SP3, SLC6A16, COP1, classifying said information representative for expression level of said at least three biomarkers, outputting the classification results, said results being indicative of whether the assessed sample belongs to one of two classes: PTLD or non-PTLD patient. The present invention provides further biomarkers for predicting, diagnosing and differentiating of posttransplant lymphoproliferative disorders and use thereof.

To provide a measuring method of HMGB1 in a specimen suppressing non-specific aggregation of a carrier on which an anti-HMGB1 antibody is immobilized and thereby suppressing rise of a reagent blank caused by the aggregation, measurement reagent, etc.SOLUTION: A measuring method of HMGB1 in a specimen, etc. measures the concentration of HMGB1 in a specimen by bringing HMGB1 in the specimen into contact with an anti-HMGB1 antibody-immobilized carrier and measuring aggregation of the anti-HMGB1 antibody-immobilized carrier bound via HMGB1. The measuring method is characterized in that when HMGB1 in the specimen and the anti-HMGB1 antibody-immobilized carrier come into contact, 0.001% (w / v)-0.01% (w / v) of glycerin / propylene oxide / ethylene oxide adduct or 0.0054% (w / v)-0.022% (w / v) of glycerin / propylene oxide adduct coexists therein.SELECTED DRAWING: None

The present disclosure provides polypeptides, polynucleotides, compositions, systems, and methods for genome editing involving a chromatin remodeler. In some aspects, provided herein is an HMGB1 polypeptide comprising HMGB1 Box B domain, and nucleic acid molecules encoding an HMGB1 polypeptide comprising HMGB1 Box B domain.

This invention belongs to the field of pharmaceutical technology. Addressing the lack of reported applications of Astragalus injection in the preparation of drugs for treating cerebral hemorrhage, this invention proposes the use of Astragalus injection in the preparation of drugs for treating cerebral hemorrhage. Experimental results show that Astragalus injection can protect brain tissue neurons by inhibiting the HMGB1 / RAGE signaling pathway, inhibiting neuronal apoptosis, and reducing the expression of inflammatory factors in brain tissue, thereby achieving a protective effect against cerebral hemorrhage in rats. Therefore, Astragalus injection has the potential to be used as a drug for treating cerebral hemorrhage.

The invention relates to the technical field of biomedical engineering and drug delivery systems, in particular to an ROS-responsive hydrogel eye drop preparation, a preparation method thereof and application of the ROS-responsive hydrogel eye drop preparation in treatment of corneal diseases. Aiming at the problems of short ocular surface residence time, low bioavailability and the like of an existing eye drop preparation, glycyrrhizic acid is added on the basis of polyvinyl alcohol to jointly serve as a skeleton of ROS response type hydrogel TPG, and the obtained hydrogel eye drops have injectability, shear thinning characteristic and thixotropy, are suitable for being used as eye drops and have good application prospects. The composition can effectively prolong the retention time of the ocular surface, and can regulate the keratitis immune microenvironment by inhibiting the amplification process of neutrophil inflammation related to HMGB1 (High Mobility Group Box 1).

The invention belongs to the technical field of biological pharmacy, and provides application of glycyrrhizin in preparation of a medicine for treating white matter injury. Animal experiment results show that the HMGB1 inhibitor Gly can obviously improve rat WMI pathological changes, reduce rat brain white matter region HMGB1 expression, obviously reduce the number of rat brain white matter region NG2 + Olig2 + double positive cells and improve rat WMI afterbrain white matter region OLs differentiation disorder; the myelination disorder of the white matter region of the rat after WMI can be improved, and the number of myelination axons of the rat is obviously increased; and the learning ability and the spatial memory ability of the rats are improved. It is clear that Gly can inhibit expression of HMGB1, and an effective technical means is provided for treatment of white matter damage.

The invention discloses application of sulodexide in preparation of a medicine for treating sepsis-related encephalopathy, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the effect of preventing and / or treating sepsis-related encephalopathy of sulodexide is found for the first time; animal experiments prove that sulodexide improves cognitive impairment of a patient with sepsis-related encephalopathy by improving the survival rate of the patient with sepsis-related encephalopathy, inhibits brain neuroinflammation of the patient with sepsis-related encephalopathy, reduces brain tissue damage of the patient with sepsis-related encephalopathy, and improves the curative effect of the patient with sepsis-related encephalopathy. According to the present invention, with the application of the compound in the prevention and / or treatment of the sepsis-related encephalopathy, the microglial cell excitation of the sepsis-related encephalopathy patient can be inhibited, and the HMGB1 and / or RAGE pathway of the sepsis-related encephalopathy patient can be inhibited so as to prevent and / or treat the sepsis-related encephalopathy, such that the new idea is provided for the preparation of the sepsis-related encephalopathy product, and the wide application prospect is provided.

The invention provides a nano-composite with a function of recovering HMGB1 stimulating activity by removing active oxygen and a preparation method and application of the nano-composite, and the nano-composite can recover the stimulating activity of high mobility protein 1 (HMGB1) and maintain the function of T cells by removing excessive active oxygen after cold-heat composite ablation operation, so that the preparation method and application of the nano-composite can be used for preparing the high mobility protein 1 (HMGB1). The nano drug-loading platform for promoting smooth proceeding of immune death of tumor cells is prepared by wrapping an immunologic adjuvant with a drug-loading molecule R1P or R1PR2 through a nano coprecipitation method, and the R1PR2 drug-loading molecule has a fluorescence imaging function at the same time. The invention provides a method for preparing the drug-loading molecule and the nano drug-loading platform, and an application of the drug-loading molecule and the nano drug-loading platform in tumor treatment. The polythioether group in the drug-loading molecule can relieve the oxidative stress environment of the microenvironment, can change the configuration at a fixed point in the presence of active oxygen, and has the active oxygen response capability.

The application discloses a compound for targeted degradation of HMGB1 and a preparation method and application thereof, and the compound for targeted degradation of HMGB1 is a compound shown in formula (I) or a pharmaceutically acceptable salt thereof, wherein R is -(CH2) m -, -C(=O)-(CH2) n - or -(CH2CH2O) k -, m is any integer from 6 to 10, n is any integer from 5 to 9, and k is 2 or 3. The compound is a PROTAC compound spliced together by a linker from glycyrrhizic acid and an E3 ubiquitin ligase CRBN protein ligand, can specifically degrade a target protein HMGB1 through a ubiquitin-protease pathway, has the characteristics of low dosage, low toxicity and high drug efficacy, is used for preparing a drug for treating diseases related to abnormal activity or expression of HMGB1, can effectively degrade the expression level of HMGB1 protein in tumor cells, and reduces clinical drug resistance of an EGFR inhibitor.