48 results about "HMGB1" patented technology

The invention belongs to the technical field of biological medicines, and discloses a B cell and cartilage cell senescence targeting osteoarthritis treatment medicine. The invention provides an application of an anti-MIF antibody or an antigen binding fragment thereof as a B cell targeting immunomodulator in osteoarthritis treatment drugs, the anti-MIF antibody or the antigen binding fragment thereof regulates and controls an MIF / HMGB1 / MMP13 signal axis through a neutralization effect with MIF, so that the MIF and B cells are significantly co-localized, expression of HMGB1 in the B cells is promoted, and the osteoarthritis treatment effect is improved. The senescence of B cells is reduced and the B cells are promoted to regulate or repair phenotype transformation so as to destroy chronic inflammatory circulation and diffusion of pathogenic plasma cells, and the expression of MMP13 in joint tissues is reduced so as to maintain the steady state of cartilage tissues; the preparation method has an excellent application prospect in preparation of an OA intra-articular injection drug which realizes rapid anti-inflammatory and long-term cartilage protection effects and can realize a lasting curative effect through low-frequency drug delivery.

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 present invention relates to HMGB1 protein derivatives for use in removing biofilms. Provided herein are derivatives of HMGB1 that have been engineered to have the same potent anti-biofilm activity, but are smaller and do not cause inflammation.

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 present invention addresses the problem of providing an agent for preventing or treating amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), spinocerebellar ataxia (SCA), aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging, as well as a more stable antibody that exhibits an effect of preventing or treating these diseases, Alzheimer's disease (AD), or frontotemporal lobar degeneration (FTLD). A human monoclonal antibody that specifically binds to human HMGB1, wherein the human monoclonal antibody (anti-human HMGB1 antibody) comprises a heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 each consisting of a specific amino acid sequence and a light chain CDR1, light chain CDR2, and light chain CDR3 each consisting of a specific amino acid sequence, is used as an agent for preventing or treating ALS, PD, HD, SCA, aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging. An antibody in which the light chain complementarity determining region (CDR) 3 of the anti-human HMGB1 antibody has been modified is used.

One aspect relates to a gold nanozyme containing glycol chitosan and gold particles, and a pharmaceutical composition containing the same for preventing or treating inflammatory bowel disease. It has been confirmed that the gold nanozyme according to one aspect and a composition containing the same suppress the expression of inflammatory factors, inhibit the production of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and reduce the production of intracellular nitric oxide (NO). It has also been confirmed that when the gold nanozyme further contains glycyrrhizin, it inhibits the secretion of HMGB1 (High mobility group box 1). It has also been confirmed that the gold nanozyme and a composition containing the same restore the length and weight of damaged colon, making it suitable for use in the industry / market for the prevention and / or treatment of inflammatory bowel disease.

The invention relates to the technical field of anti-saccharification and anti-aging, in particular to anti-saccharification and anti-aging nanoparticles, a preparation method of the anti-saccharification and anti-aging nanoparticles and an anti-saccharification and anti-aging composition. The preparation method comprises the following steps: under the protection of inert gas, hyaluronic acid and L-carnosine are subjected to an acid-amine condensation reaction under the catalytic action of a carboxyl activator to obtain a hyaluronic acid-carnosine derivative; and performing a coordination self-assembly reaction on the digallocatechin a, Zn < 2 + > and the hyaluronic acid-carnosine derivative in deionized water to form the nanoparticles as shown in a formula II. In the nano-particle structure, the HA-CAN component mainly aims at an AGEs / RAGE pathway; the TSA-Zn component mainly aims at an HMGB1 / RAGE pathway, and the TSA-Zn component and the HMGB1 / RAGE pathway cooperatively inhibit dual pathways; the introduction of HA greatly improves the transdermal performance, CAN, TSA and HA are integrated in a nano entity through chemical bonds / coordinate bonds, the stability of the nano structure is improved, and the activity of each component is enhanced.

Provided are: a novel HMGB1 expression regulator including small extracellular vesicles which include a miRNA targeting a gene involved in HMGB1 expression and can regulate HMGB1 expression using the miRNA derived from the small extracellular vesicles; a prophylactic agent or therapeutic agent for acute lung injury, acute respiratory distress syndrome, or sepsis; and a method of ameliorating acute lung injury, acute respiratory distress syndrome, or sepsis. The small extracellular vesicle is preferably exosomes.

The invention provides an application of a natural compound astragaloside in preparation of an HMGB1 inhibitor. Proved by experiments on a protein level, a cell level and an animal level, astragaloside can be directly combined with HMGB1 to influence a protein space structure of the HMGB1 and inhibit HMGB1-induced inflammation, has a certain protection effect on drug-induced liver injury, can reduce the death rate of mice with septicopyemia induced by cecum ligation perforation (CLP), and can be used for preparing medicines for treating liver injury. Astragaloside is expected to become a medicine for preventing and treating HMGB1 induced diseases.

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,

The invention belongs to the technical field of biology, and particularly relates to a kit for detecting HMGB1 and a detection method. According to the detection method, the monoclonal antibody is specifically combined with HMGB1 for detection; the complementarity determining region of the heavy chain variable region of the monoclonal antibody is mainly composed of H-CDR1, H-CDR2 and H-CDR3; the sequences are respectively shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; a complementary determining region of a light chain variable region of the monoclonal antibody is mainly composed of L-CDR1, L-CDR2 and L-CDR3, and the sequences of the L-CDR1, the L-CDR2 and the L-CDR3 are respectively shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6; according to the detection method and the kit, the disulfide bond structure of the oxidized HMGB1 can be specifically recognized through the specific antibody, and the cross reaction rate of the specific antibody and the reduced HMGB1 is 1t; and 3% (30% of the traditional antibody gt).

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 an application of HMGB1 (High Mobility Group Box 1) in predicting TKI (Tumor Kinase Inhibitor) drug resistance of lung cancer brain metastatic tumor. The invention finds that tumor cells respond to TKI treatment by adaptively secreting HMGB1 and up-regulate CTLA-4 expression in T cells, which may be a factor for increasing TKI drug resistance. The invention also provides an application of the HMGB1 / NF-kappa B inhibitor in improvement of TKI drug resistance. The diagnosis and treatment method disclosed by the invention has an application prospect in the field of tumor treatment.

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.

The invention provides application of a GSDMD inhibitor in preparation of a chronic obstructive pulmonary disease (COPD) treatment preparation, and relates to the technical field of biological medicines.The COPD mouse model induced by cigarette smoke is established and divided into a control group, a COPD group and a COPD + inhibitor group (GS DMD inhibitor), and the GS DMD inhibitor and the COPD + inhibitor group (GS DMD inhibitor) are combined through methods of Western Blot, ELISA, qPCR, a transmission electron microscope and the like, so that the chronic obstructive pulmonary disease (COPD) treatment preparation is obtained. And detecting GSDMD pathway related protein and gene expression, inflammatory factor release level and alveolar barrier function change. A GSDMD channel in the COPD model group is obviously activated, which shows that the expression levels of GSDMD-N and Caspase-1 are increased; the concentration of IL-1beta and IL-18 is obviously increased; the expression levels of NLRP3, ASC and pro-Caspase-1 and the concentration of HMGB1 in BAL F are increased, the alveolar epithelial cell structure is damaged, and the wet-to-dry ratio and the total protein content are increased. The GSDMD inhibitor significantly reduces the above indexes and improves the airway epithelial barrier function. It is determined that the GSDMD pathway aggravates the airway epithelial cell injury and inflammatory response of COPD by inducing pyroptosis. The GSDMD inhibitor can significantly inhibit pyroptosis and improve COPD-related pathological changes, and provides a new target and theoretical basis for treatment of COPD.

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.

Provided herein are synthetic polypeptides derived from the high mobility group box 1 (HMGB1) host protein that can disrupt bacterial biofilms and prevent the formation of neutrophil extracellular traps (NETs). Also provided herein are methods for disrupting abnormal or excessive NET formation, particularly suitable for treating high-risk populations, such as those infected with SARS-CoV-2, sepsis, autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and small vessel vasculitis), autoinflammatory diseases (such as gout and inflammatory bowel disease), and metabolic diseases (such as type 2 diabetes and obesity).

The present inventors discovered that an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect of suppressing erythema, scaling (desquamation), and thickening (infiltration) of the skin in an animal model of psoriasis. Based on these findings, pharmaceutical compositions for the prevention and / or treatment of psoriasis, which comprise the HMGB1 fragment peptide having the specific amino acid sequence are provided.

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.