75 results about "HMGB1" patented technology

It is an object of the present invention to provide a human monoclonal antibody that has a high inhibitory activity on phosphorylation of Ser46 of human MARCKS and binds specifically to human HMGB1, and a pharmaceutical composition or the like for treating or preventing Alzheimer's disease, containing the antibody as an active component. A human monoclonal antibody that binds specifically to human HMGB1 and contains a heavy-chain CDR1, a heavy-chain CDR2, and a heavy-chain CDR3 consisting of specific amino acid sequences and a light-chain CDR1, a light-chain CDR2, and a light-chain CDR3 consisting of specific amino acid sequences is used. The human monoclonal antibody can also be used as a pharmaceutical composition for treating or preventing Alzheimer's disease.

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 present invention belongs to the field of biological detection technology, and specifically relates to a monkey high-mobility group protein B1 monoclonal antibody, an enzyme-linked immunosorbent assay kit and its application. Named HMGB1-11, it includes a heavy chain variable region and a light chain variable region; the heavy chain variable region has three complementary determining regions CDR-H1 to CDR-H3, and the amino acid sequences are shown in SEQ ID NO.6-SEQ ID NO.8; the light chain variable region has three complementary determining regions CDR-L1 to CDR-L3, and the amino acid sequences are shown in SEQ ID NO.9-SEQ ID NO.11. The monoclonal antibody of the present invention can specifically bind to monkey high-mobility group protein B1, and the monoclonal antibody can be paired with a monoclonal antibody after screening. Based on the monoclonal antibody combination, a monkey high-mobility group protein B1 enzyme-linked immunosorbent assay kit is constructed, which can detect the content of monkey high-mobility group protein B1 in monkey serum, plasma or tissue fluid.

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.

Provided herein are derivatives of HMGB1 that have been engineered to possess the same efficacious anti-bio film activity but are smaller and do not induce inflammation.

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.

[Problem] To provide a prophylactic or therapeutic agent for amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), cerebellar ataxia (SCA), degenerative diseases associated with aging or neurological diseases, brain aging, or diseases associated with brain aging, alzheimer's disease (AD), frontotemporal lobe degeneration (FTLD) and an antibody having a higher stability and exhibiting a prophylactic or therapeutic effect. A human monoclonal antibody (anti-human HMGB1 antibody) that specifically binds to human HMGB1 is used as a prophylactic or therapeutic agent for ALS, PD, HD, SCA, degenerative diseases associated with aging, neurological diseases, brain aging, or diseases associated with brain aging, said human monoclonal antibody comprising: a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 each comprising a specific amino acid sequence; and a light chain CDR1, a light chain CDR2, and a light chain CDR3 comprising a specific amino acid sequence. An antibody in which the light chain complementarity determining region (CDR) 3 of the anti-human HMGB1 antibody has been modified is used.

The invention discloses a hyssopus officinalis extract and a preparation method and application thereof.The preparation method of the hyssopus officinalis extract comprises the following steps that a mixed solution of hyssopus officinalis and honey is covered, moistened and stir-fried, and a primary product is obtained; and heating a mixed solution of the head product and polyhydric alcohol at the temperature of 80-100 DEG C for 5-10 hours to prepare the hyssopus officinalis extract. The hyssopus officinalis extract prepared by the preparation method disclosed by the invention can activate endogenous antioxidation of a human body, inhibit expression of MMP-1, promote synthesis of elastin in human true epidermis cells, promote expression of HSP27 in HaCaT cells and down-regulate expression of HMGB1 in the HaCaT cells, and has a better anti-photoaging effect.

The invention provides a nano delivery system based on copper death induction and application of the nano delivery system in preparation of tumor immunotherapy drugs, according to the novel copper death induction nano drug Cu / ZIF-90 (at) DSF, 30 mol% of Cu (acac) 2 and disulfiram are loaded through a high-porosity structure of ZIF-90, and pH / ROS dual-responsiveness copper ion release is achieved. Animal experiments show that the Cu < 2 + > accumulation concentration of the nano-drug at a tumor site reaches 23.7 mu M, and efficient copper death is induced (the apoptosis rate is 41.3% vs and the control group is 9.2%). More importantly, by releasing HMGB1 and ATP, the CD8 < + > T cell infiltration in a tumor microenvironment is increased by 5.8 times, and the CD8 < + > T cell infiltration and the alphaPD-1 antibody generate a synergistic effect, so that the complete remission rate is increased from 18% to 67%. According to the technical breakthrough, a brand new solution is provided for solving the cold tumor immunotherapy drug resistance.

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 invention belongs to the technical field of biological medicine, and provides dimethyl fumarate and application of a signal channel thereof in inhibition of arsenic-induced rat liver and kidney immune inflammation reaction. According to the present invention, with the application of the sodium arsenite in the rat liver and kidney immune inflammation reaction, the activation of the HMGB1 / TLR4 / NF-kappa B signal channel is inhibited through the intervention of the dimethyl fumarate, the Th1 / Th2 / Th17 / Treg balance disorder caused by the sodium arsenite and the CD4 + T cell subset differentiation disorder are antagonized, and the arsenic-induced rat liver and kidney immune inflammation reaction is alleviated; a rat subchronic arsenic exposure model is established, dimethyl fumarate is adopted for intervention, arsenic-induced liver and kidney tissue immune inflammatory response and CD4 + T cell subset differentiation disorder are discussed on the basis of an HMGB1 / TLR4 / NF-kappa B signal channel, and the antagonism and potential action mechanism of dimethyl fumarate in arsenic-induced rat immune injury are preliminarily clarified. And a theoretical basis and a research thought are provided for arsenic poisoning prevention and treatment.

The invention relates to an application of an anti-CD73 monoclonal antibody combined with an Adora1 inhibitor in treatment of intestinal fibrosis. In the invention, the inventor finds that long-term WD generates GSDME-mediated pyroptosis by inducing intestinal epithelial cells and releases a large amount of intracellular molecules HMGB1 and ATP, the HMGB1 promotes CD39 + CD73 + CD8 + T cell amplification, the group of cells catalyzes extracellular ATP into Ado, and finally the Ado activates intestinal fibroblasts through a receptor Adara1 so as to participate in a complex intestinal fibrosis process. Based on this, the inventor finds that the CD-related intestinal fibrosis can be effectively improved by blocking the generation of intestinal adenosine or / and inhibiting the receptor of the intestinal adenosine, and a combined medicine, namely the anti-CD73 monoclonal antibody combined Adara1 inhibitor, is researched and developed, can be used for treating the CD-related intestinal fibrosis, and has important clinical application value.

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.

As described herein, inhibitors of high-mobility group box protein 1 (HMGB1) can significantly reduce nuclear-cytoplasmic transport of HMGB1, gliosis, neurodegeneration, tau pathology, and myelin loss, particularly in subjects having the APOE4 allele. Accordingly, methods are described herein that include administering to a subject having at least one genomic APOE4 allele, one or more inhibitors of high-mobility group box protein 1 (HMGB1).

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.

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).

The invention relates to the technical field of medicines, in particular to application of amlexanol in preparation of a medicine for treating or preventing respiratory syncytial virus infection, and provides application of amlexanol in treatment or prevention of diseases caused by respiratory syncytial viruses. Amlexinol can significantly inhibit the expression of F protein and inhibit the release of HMGB1 from cells to cell supernatant, and the survival rate of animals infected by respiratory syncytial virus can be significantly increased and inflammation can be effectively inhibited by using mlexinol.

Provided herein is a synthetic polypeptide derived from a high mobility group cassette 1 (HMGB1) host protein that can both disrupt bacterial biofilm and prevent the formation of neutrophil extracellular traps (NETs). Also provided herein are methods of disrupting abnormal or excessive NET formation, which are particularly suitable for treating high risk populations, the composition can be used for people suffering from infection of SARS CoV-2, septicemia, autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes mellitus and small vasculitis), autoinflammatory diseases (such as gout and inflammatory bowel disease) and metabolic diseases (such as type 2 diabetes mellitus and obesity).

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.