52 results about "Chronic infection" patented technology

The invention discloses a toxoplasma gondii attenuated vaccine strain RH delta rop67 as well as a construction method and application thereof, and belongs to the technical field of parasitic disease prevention and control and biological product preparation. The attenuated vaccine strain is constructed by performing targeted knockout on the ROP67 gene in a toxoplasma gondii strain RH delta ku80 through a CRISPR / Cas9 mediated gene editing technology. Compared with a wild type strain, the attenuated vaccine strain shows remarkable attenuation characteristic and good immunogenicity. A test result shows that the attenuated vaccine strain can induce a host to generate specific immune response mainly based on cellular immunity, maintains a protection effect on toxoplasma gondii infection in a relatively long immune period, and has a protection effect on tachyzoite infection and a chronic infection stage of toxoplasma gondii strains with different virulence; the survival ability of a host to tachyzoite infection can be improved, and the formation level of cysts in tissues is reduced. The invention provides a technical scheme with long-term immune potential for research and development of toxoplasma gondii attenuated vaccines.

The invention belongs to the field of biological medicine and material science, and particularly relates to an intelligent response type piezoelectric nanofiber dressing and a preparation method and application thereof. According to the preparation method, polyvinylidene fluoride-trifluoroethylene, a high polymer material and inorganic nanoparticles are blended and spun through an electrostatic spinning technology, and then a photo-thermal component coating is subjected to surface in-situ oxidation and self-polymerization, so that the composite fiber membrane is prepared. Under the stimulation of ultrasound (US) and near-infrared laser (Laser), the fiber membrane can cooperatively activate the piezoelectric effect and the photothermal effect, generate a dynamic electric field and local high temperature, realize multi-mode cooperative killing of bacteria (the antibacterial rate exceeds 99%), and simulate an endogenous electric field to promote cell migration and wound healing. The dressing has good mechanical properties (the Young modulus is 15-20 MPa), hydrophilicity (the contact angle is about 30 degrees), biocompatibility and stability, is suitable for treatment of chronic infected wounds such as diabetes mellitus and the like, and has the advantages of on-demand activation and intelligent response.

A method for synergistically promoting wound healing by means of moderate-intensity pulse ultrasonic waves and zinc oxide nanoparticle-type-I collagen hydrogel comprises the following steps that zinc oxide nanoparticles and type-I collagen hydrogel are physically mixed and crosslinked in advance and applied to a chronic infected wound, and then the wound is accelerated to heal through multiple times of MIPUS stimulation. The effect of the ZNP-COL hydrogel is enhanced through MIPUS, immune cell polarization can be activated, and the proportion of anti-inflammatory M2 type macrophages is increased; wherein ZNP is capable of releasing zinc ions and reactive oxygen substances and has antibacterial activity; meanwhile, ZNP can generate current and an electric field under stimulation of MIPUS, calcium ions on the surface of a cell membrane are activated to flow inwards, and proliferation of anti-inflammatory M2 type macrophages is promoted; the COL hydrogel is used as a medium to transmit ultrasonic waves and fix the ZNP, and the function of the ZNP at the local position is enhanced. The method solves the problems of bacterial infection and chronic inflammation at the same time, is safe, simple and reusable, and can be widely applied to infection of other parts besides the application.

The invention discloses application of black phosphorus loaded cerium dioxide composite temperature-sensitive hydrogel in preparation of diabetes wound anti-inflammatory drugs, and relates to the technical field of hydrogel preparation. The black phosphorus-loaded cerium dioxide composite temperature-sensitive hydrogel is used for diabetes wound anti-inflammation, and the preparation method of the black phosphorus-loaded cerium dioxide composite temperature-sensitive hydrogel specifically comprises the following steps that a composite material of black phosphorus nanosheets loaded cerium dioxide nanoparticles is used for preparing the black phosphorus-loaded cerium dioxide composite temperature-sensitive hydrogel, and the black phosphorus-loaded cerium dioxide composite temperature-sensitive hydrogel is used for diabetes wound anti-inflammation. The composite hydrogel with the temperature-sensitive characteristic is jointly prepared from the hydrogel and pluronic F127. The invention further provides application of the black phosphorus loaded cerium dioxide composite temperature-sensitive hydrogel in preparation of diabetes wound anti-inflammatory drugs, antibacterial drugs, antioxidant drugs and arthritis treatment drugs, and the problems that chronic infected wounds are not healed for a long time and multiple drug-resistant bacteria are formed due to abuse of antibiotics are effectively solved.

Helicobacter pylori (HP) is a chronic bacterium that infects the gastric mucosa. It is widespread in the general population, with an infection rate between 55% and 70%. HP is closely related to gastric ulcers and gastritis. Western medicine treatment for HP infection is relatively complex, including bismuth substituents and proton pump inhibitors plus two antibiotics. Gastric ulcers and gastritis are common digestive system diseases. Compound 1, "Exterminate the Ghost," is a traditional Chinese medicine composition mainly composed of Coptis chinensis, plus Scutellaria baicalensis and Fraxinus chinensis, which can eradicate HP. Compound 2, "Ulcer Relief," is a traditional Chinese medicine composition mainly composed of Coptis chinensis, plus Rheum palmatum and Bletilla striata, which can cure gastric ulcers. Compound 3, "Gasitis Relief," is a traditional Chinese medicine composition mainly composed of Coptis chinensis, plus Glycyrrhiza uralensis or Taraxacum mongolicum, made into a tea bag, which can cure chronic gastritis.

The application discloses an N-(3-cyclobutyrolactone)-4-nitrophenyl butyryl amide and amikacin composition and application of the composition in treating chronic infection of drug-resistant bacteria. After the N-(3-cyclobutyrolactone)-4-nitrophenyl butyryl amide and the amikacin are combined, not only the sensitivity of pseudomonas aeruginosa to the amikacin can be obviously increased, but also the formation amount of the pseudomonas aeruginosa biofilm can be greatly reduced, so that the composition can be applied to preventing and treating chronic infection of drug-resistant pseudomonas aeruginosa.

The invention discloses antibiotic-loaded in-situ modified platelet-rich fibrin gel as well as a preparation method and application thereof. The antibiotic-loaded in-situ modified platelet-rich fibrin gel is prepared from the following components in percentage by mass: 88 to 92 percent of PRF (platelet-rich fibrin) matrix, 5 to 8 percent of antibiotic and 3 to 4 percent of modifier, the PRF matrix comprises platelets, leukocytes and fibrin, the antibiotic is vancomycin or gentamicin, and the modifier is a zinc ion-containing compound or quaternized chitosan. The gel can be applied to preparation of chronic infection wound dressing, the antibiotic loading rate of the gel is increased, the gel has the slow release characteristic, the accumulative release within 7 days is 82.3 + / -5.6%, the burst release within 24 hours is less than 15%, the wound healing speed is increased by 40%, and the biological membrane clearance rate is 100%.

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

The present invention relates to enhanced antisense oligonucleotides that are complementary to the Far Upstream Element-Binding Protein 1 (FUBP1) and are capable of reducing a FUBP1 target nucleic acid, such as FUBP1 mRNA. The invention relates to enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for use in treating and / or preventing a hepatitis B virus (HBV) infection, in particular a chronic HBV infection. The invention in particular relates to the use of the enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for destabilizing cccDNA, such as HBV cccDNA. The invention further relates to enhanced antisense oligonucleotides targeting FUBP1 or conjugates thereof for use in treating cancer. A pharmaceutical composition and its use in the treatment and / or prevention of an HBV infection, or its use in the treatment of cancer is also disclosed.

The invention relates to a multifunctional bacterial cellulose gel film and a preparation method and application thereof.The gel film is synthesized by acetobacter xylinum in situ in a fermentation medium containing polymyxin B and panax notoginseng saponins, the gel film is of a three-dimensional network structure, the polymyxin B and the panax notoginseng saponins are wrapped in a bacterial cellulose network, and the polymyxin B and the panax notoginseng saponins are evenly distributed in the bacterial cellulose network. And the fiber diameter of the gel film is 48.68 + / -5 nm. The prepared wound dressing has the wet adhesion characteristic and can effectively promote rapid and scar-free healing of chronic infectious wounds and large-area wounds, so that the method is expected to be widely applied to green synthesis of the wound dressing with antibacterial and wound healing promoting functions, and a new form is provided for use of the pseudo-ginseng powder and the polymyxin B.

This invention discloses the construction of a Toxoplasma gondii progesterone-responsive kinase-deficient strain and its application as a live attenuated vaccine. The Toxoplasma gondii progesterone-responsive kinase-deficient strain is derived from Toxoplasma gondii RHΔ... ku80 As a maternal strain, the gene-editing technology was used to knock out the enzyme encoding progesterone-responsive kinase. prk The gene-deleted strain was named RHΔ ku80 Δ prk Experiments have shown that RHΔ ku80 Δ prk The virulence of the strain was significantly reduced, and immunized mice showed good immunoprotection against acute infection with highly virulent and moderately virulent Toxoplasma gondii strains, and significantly inhibited brain cyst formation in a chronic infection model. Therefore, RHΔ ku80 Δ prk This invention has potential application value as a live attenuated vaccine against Toxoplasma gondii. It has significant application prospects.

The present invention relates to a RTEL1 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of RTEL1 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to antisense oligonucleotides which are complementary to RTEL1 and capable of reducing a RTEL1 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment and / or prevention of a HBV infection.

The application discloses a method for constructing an animal model of chronic pulmonary infection / persistence of Acinetobacter baumannii, and belongs to the technical field of infectious disease animal model construction and microbial preparation. Compared with the acute infection and rapid clearance mode formed by directly inoculating free bacteria, the live bacterial microspheres prepared in the application can prolong the local exposure and detectable time of Acinetobacter baumannii in the lung, so that the Acinetobacter baumannii is more likely to form a low-load, long-term persistence pulmonary infection state, thereby providing a more stable experimental platform for the mechanism of chronic infection formation, host immune dynamic change and related intervention evaluation.

The invention belongs to the technical field of biological medicine, and discloses an anti-PD-L1 nano antibody and application thereof. And the amino acid sequences of CDR1-3 of the PD-L1 nano antibody are respectively shown as SEQ ID NO.2-4. The PD-L1 nano antibody is a PD-L1 antibody. The nano antibody can effectively block the combination of PD1 and PDL1, is high in affinity and strong in specificity, can be used for immunoblotting, enzyme-linked immunosorbent assay kits and flow cytometry counting, can also be used for treating diseases such as tumors, autoimmune diseases and chronic infectious diseases, and has the potential of being developed as an immune checkpoint inhibitor.

The invention discloses a cholestasis index-based liver cancer risk prediction model construction method, which comprises the following steps: collecting chronic HBV infected person data containing 16 parameters, carrying out desensitization, carrying out stratified random sampling to divide a data set, and carrying out two-stage screening to obtain HBsAg, ALT, ALP, GGT, PLT and AFP core features; after Min-Max Scaling processing, L1 regularization logistic regression is combined with grid search and 5-fold cross validation to construct the model, and the model constructed by the method is obviously superior to a traditional CU-HCC model and a REACH-B model, especially has higher recognition capability for early HBV-PLC, and can effectively reduce the missed diagnosis rate.

This invention relates to a fusion antigen mRNA molecule, which encodes a protein comprising at least two of the following: hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein Core, hepatitis B X antigen protein HBxAg, and hepatitis B preS1 antigen protein PreS1, preferably comprising hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat chronic hepatitis B virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing target antigen-specific humoral and cellular immune responses. It can also effectively overcome immune tolerance in a mouse model of chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the immune tolerance breakthrough threshold, providing a candidate vaccine and a new immunotherapy strategy for the immunotherapy of patients with chronic HBV infection.

The invention provides an extraction method of autologous neutrophil physical activation multi-component protein and application of the autologous neutrophil physical activation multi-component protein in chronic infectious wound treatment. According to the method, the neutrophil is physically activated, so that chemical irritant residues are avoided, and the compound protein component rich in MPO, NE, Lysozyme, Lactoferrin and other multiple bactericidal proteins is obtained. And the protein component is directly delivered to the basal part of the chronic wound surface in a multi-point and layered injection mode (1 time / 3 days, 250 [mu] L / time) in a focus area, so that bacterial biofilms and necrotic tissues can be effectively removed, wound debridement, cell migration and matrix remodeling are promoted, and the healing of the chronic infectious wound surface is accelerated. The method disclosed by the invention has the advantages of autologous source, good biocompatibility, accurate treatment and the like, is particularly suitable for treating chronic infectious wounds such as diabetic foot ulcer and the like, and provides a new thought for treating the chronic wounds.

The present application relates to pyrazole derivatives as inhibitors of the PD-1 / PD-L1 interaction. The applicants have designed compounds of general formula (I) wherein R ', R2, y3, R3, R4, R5, R6 and R7 are as defined herein, which are effective in blocking PD-1 / PD-L1 interactions to restore an anti-tumor immune response in a subject and eradicate any tumors in which dormant tumor cells and PD-L1 participate in immune escape. The inventor verifies that these compounds block the PD-1 / PD-L1 interaction by performing physical and chemical tests (MST, NanoDSF) and in vitro biological tests (FRET assay, Pralomig block assay, T cell assay). These compounds have affinity (Kd) in the order of pM, which Kd is higher than the Kd of the antibody Atezumab used in clinical use, and have IC50 comparable to or higher than that observed using Atezumab. Therefore, the invention also relates to a pharmaceutical composition containing the compound and application of the pharmaceutical composition in treatment of PD-1-PD-L1 interaction related diseases (cancers, chronic inflammatory diseases, neurological diseases and chronic infections).

The embodiments of the present application provide a method for establishing in vitro CD8 + T cell exhaustion model and application thereof. The method comprises: using T cell receptor signal stimulator combined with interleukin-10 to continuously stimulate CD8 + T cells under in vitro culture conditions. The cells induced by the method not only highly express exhaustion key transcription factor TOX and various surface inhibitory receptors (such as PD1, TIM3, LAG3 and the like), but also significantly reduce the secretion ability of effector cytokines, highly reduce the real exhaustion performance in in vivo chronic infection or tumor microenvironment in vitro, and effectively overcome the defect of few CD8 + T cells in traditional in vivo animal model, and high-quality exhaustion cells can be obtained in vitro in large scale in only 6 to 8 days.

The application relates to the field of biological medicine, and particularly discloses an oral double-targeting brucellosis nano-vaccine CS-CKS9-MEV-DCpep-NPs construction method and application thereof, the nano-vaccine comprises chitosan nanoparticles and a double-targeting peptide vaccine CKS9-MEV-DCpep encapsulated in the chitosan nanoparticles, the double-targeting peptide vaccine CKS9-MEV-DCpep comprises, from N-terminal to C-terminal, an M cell targeting peptide CKS9, a polyepitope vaccine MEV and a DC targeting peptide DCpep; the application also provides a method for constructing the nano-vaccine and application thereof. The application successfully constructs the oral CS-CKS9-MEV-DCpep-NPs nano-vaccine through a systematic strategy of integrating 'bioinformatics precise screening, double-targeting molecular modification and excellent carrier delivery', the nano-vaccine has double-targeting functions of mucosal immunity and cellular immunity, can effectively induce mucosal immunity, cellular immunity and humoral immunity, and exhibits excellent protection efficacy in acute and chronic infection models, thereby providing a new effective solution for brucellosis prevention and control.

The application discloses an intelligent responsive composite hydrogel dressing and a preparation method and application thereof, and belongs to the field of biomedical materials. The preparation method comprises the following steps: preparing arginine grafted quaternary ammonium chitosan LQ; preparing phenylboronic acid functionalized oxidized sodium alginate P-OSA; preparing a multifunctional nanoenzyme complex PMZG; mixing polyvinyl alcohol, LQ, honeysuckle extract and / or PMZG, and then cross-linking with a P-OSA solution to obtain a hydrogel. Through progressive modular design, the hydrogel is endowed with injectability, self-healing, multiple microenvironment responsiveness and cascade catalytic antibacterial, photothermal therapy and pro-angiogenesis capabilities, and can be used for synergistically treating chronic infected wounds, diabetic foot ulcers and drug-resistant bacterial infection wounds, and has a wide clinical application prospect.

The present invention relates to a metal-organic framework for inhibiting the activity of M2 macrophages, and a pharmaceutical composition comprising same, wherein the metal-organic framework of the present invention is non-toxic to cells and can exhibit an effect of inhibiting the activity of M2 macrophages. More specifically, the metal-organic framework of the present invention can be provided as an anticancer composition for tumor-related macrophage-mediated diseases, particularly solid cancer, through the inhibition of M2 macrophages capable of increasing the expression of genes associated with parasite invasion, tissue remodeling, and tumor proliferation (immunomodulatory function), and can also be provided as a pharmaceutical composition for treating chronic infectious diseases, liver cirrhosis, obesity-related metabolic diseases, scar formation and idiopathic lung diseases.

The application belongs to the technical field of microorganisms, and discloses a method for inducing formation of living unculturable state bacteria in the presence of host cells and application thereof. The method is as follows: cells in the 3th to 20th generation are transferred to a well plate to obtain induced cells; bacteria in the logarithmic growth phase are washed by a buffer, and modified cell culture solution is resuspended to obtain a bacterial suspension. The bacterial suspension is added to the induced cells, and after incubation in a constant-temperature incubator for 1-5 hours, 10-500 mg / L gentamicin-containing modified cell culture solution is added. After cell treatment for 3-10 days, intracellular bacteria are collected by adding cell lysis solution, and then washed, centrifuged and resuspended to obtain living unculturable state bacteria. The application can induce bacteria to enter the living unculturable state in the presence of host cells, which not only expands the understanding of living unculturable state bacteria, but also provides theoretical and technical support for recurrent and chronic infectious diseases in clinical practice.

Provided herein are immunoconjugate molecules containing a TNF-alpha polypeptide and a masking moiety capable of inhibiting and activating TNF-alpha activity under suitable conditions. Also provided herein are methods for producing immunoconjugate molecules. Finally, provided herein is the therapeutic use of the immunoconjugate molecules for the treatment of diseases such as cancer and other chronic infectious diseases due to its modulating effect on the immune system.

The invention relates to a hydrogel adhesive for repairing acute and chronic infected wounds and inhibiting scars as well as a preparation method and application of the hydrogel adhesive. Specifically, the invention provides a hydrogel adhesive which comprises a) 3-aminophenylboronic acid modified hyaluronic acid (HA-PBA) and b) a short-chain molecule M containing more than two amino groups. The hydrogel adhesive has good biological properties of wound adhesion, sterilization, scar hyperplasia inhibition and the like, and can be used as a hydrogel adhesive for repairing acute and chronic infected wounds.

The invention relates to a TCR-T cell and application thereof in preparation of a product for treating chronic virus infection, a method for preparing the TCR-T cell comprises the steps of knocking out a KLF2 gene in the TCR-T cell and knocking out the KLF2 gene in the TCR-T cell to obtain an improved TCR-T cell, so that the in-vivo accumulation capacity, the killing function and the chronic infection pathogen removal efficiency of the cell can be remarkably improved, and the TCR-T cell can be used for treating chronic virus infection. And a new strategy is provided for cell therapy of chronic virus infection.

The invention relates to the technical field of biological medicine, in particular to fusion protein and application thereof in preparation of products for treating or preventing hepatitis B virus. PreS1 is used as a core antigen component and modified IgM is used as a basic skeleton to obtain a preS1-IgM monomer, then J chain connection is performed to obtain fusion protein, the fusion protein is used as an active component to construct the therapeutic vaccine, anti-preS1 antibody response can be effectively stimulated, and Th1 / Th2 immune response can be synergistically activated. Experiments show that serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model can be remarkably reduced by using the vaccine alone, and serological conversion of part of animals is realized; when the compound is combined with entecavir, the compound shows an excellent synergistic effect. According to the vaccine, the treatment effect is remarkably improved, meanwhile, remarkable liver injury is not caused, and an innovative immunotherapy with prevention and treatment functions is provided for chronic hepatitis B treatment.

The application discloses a N-(3-cyclobutyrolactone)-4-bromobenzamide and meropenem composition and application of the composition in treatment of chronic infection of drug-resistant bacteria. After the N-(3-cyclobutyrolactone)-4-bromobenzamide and the meropenem are combined, not only can the sensitivity of a biofilm bacterium to the meropenem be significantly increased, the killing effect of the meropenem on the biofilm bacterium be improved, but also the formation amount of a Pseudomonas aeruginosa biofilm can be greatly reduced; the composition can be applied to preventing and treating chronic infection of drug-resistant Pseudomonas aeruginosa.

The present application relates to the technical field of biological medicine, and particularly relates to a fusion protein and application thereof in preparation of a product for treating or preventing hepatitis B virus. The present application takes preS1 as a core antigen component and takes an improved IgM as a basic skeleton to obtain a preS1-IgM monomer, and then connects the preS1-IgM monomer through a J chain to obtain a fusion protein. The fusion protein is taken as an active component to construct a therapeutic vaccine, which can effectively stimulate an anti-preS1 antibody response and synergistically activate a Th1 / Th2 immune response. Experiments show that the vaccine alone can significantly reduce the serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model, and realize seroconversion of part of the animals. When the vaccine is used in combination with entecavir, a remarkable synergistic effect is exhibited. The vaccine significantly improves the therapeutic effect without causing significant liver damage, and provides an innovative immunotherapy with both prevention and treatment functions for chronic hepatitis B treatment.

The present invention describes combination therapies comprising a PD-1 axis binding antagonist and an agent that reduces or inhibits TIGIT expression and / or activity and methods of use thereof, including methods of treating conditions where enhanced immunogenicity is desired, such as increasing tumor immunogenicity to treat cancer or chronic infection.