84 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.

The invention discloses antibacterial and antioxidant bionic hydrogel as well as a preparation method and application thereof. The antibacterial and antioxidant bionic hydrogel disclosed by the invention comprises a hydrogel bracket, wherein the hydrogel bracket is prepared from methacrylated quaternized chitosan, acrylated cyclodextrin, methacrylated gelatin and dopamine grafted methacrylated hyaluronic acid according to the mass ratio of (2 to 4) to (1 to 3) to (5 to 7) to (0.5 to 1.5). The antibacterial and antioxidant bionic hydrogel disclosed by the invention has a porous intercommunication structure, relatively large porosity and water absorption rate, and excellent hydrophilicity, electroactivity, antibacterial property, oxidation resistance and biocompatibility. The antibacterial and antioxidant bionic hydrogel disclosed by the invention can be used as an antibacterial material, especially used as a dressing for treating chronic infection wound surfaces.

Disclosed are antibodies to anti-hepatitis B surface antigen (HBsAg) (especially humanized antibodies), nucleic acid molecules encoding same, methods for preparing same, and pharmaceutical compositions containing same. The antibodies have higher affinity for HBsAg at neutral pH than at acidic pH, thereby significantly enhancing the virus clearance efficiency and prolonging the virus inhibition time. The antibodies and the pharmaceutical compositions can be used for preventing and / or treating HBV infections or diseases related to HBV infections (e.g., hepatitis B), for neutralizing the virulence of HBV in a subject (e.g., a human), for reducing the serum level of HBV DNA and / or HBsAg in the body of the subject, or for activating the humoral immune response of the subject (e.g., a chronic HBV infected or chronic hepatitis B patient) against HBV.

The invention relates to bispecific antibodies comprising a first antigen-binding domain that specifically binds to TfR and a second, and optionally a third, antigen-binding domain that specifically binds to PD1. The invention further relates to methods of producing these molecules, to methods of using the same, to pharmaceutical compositions thereof, and their use as medicaments for the treatment of cancer, of acute and chronic infections and of Graft-versus-host disease.

The invention belongs to the technical field of probiotics, and particularly relates to a lactobacillus casei MY01 strain with an effect of improving immunity and application of the lactobacillus casei MY01 strain. A new Lactobacillus casei MY01 strain is separated from feces of a healthy infant in Guangzhou city, Guangdong province, a zebra fish immunosuppression model is constructed, and research finds that the Lactobacillus casei MY01 strain can increase the number of macrophages, neutrophil and T cells, increase the expression quantity of if n phi 1, if n phi 3 and if ng genes, inhibit the activity of angiotensin converting enzyme, inhibit the expression quantity of if n is greater than 1, and inhibit the expression quantity of if n is greater than 1, so that the new Lactobacillus casei MY01 strain can be used for preparing the new Lactobacillus casei MY01 strain. The potential effect of improving the immunity is realized. Therefore, the strain can be used in the field of medicine, and can be used for developing immunomodulatory drugs and assisting in treating immunosuppression related diseases, such as chronic infection and tumors; the method can also be applied to the health care product industry, develops health care products for enhancing immunity, and helps people to improve autoimmunity and maintain a healthy state.

The invention discloses a homoserine lactone compound N-(3-cyclobutyrolactone)-4-nitrobenzene butyramide which can effectively inhibit the formation of a multi-drug-resistant pseudomonas aeruginosa biofilm, and an application of the N-(3-cyclobutyrolactone)-4-nitrobenzene butyramide in the treatment of chronic infection of drug-resistant bacteria. The N-(3-cyclobutyrolactone)-4-nitrobenzene butyramide not only can inhibit QS systems of pseudomonas aeruginosa standard strains and clinical strains and enhance the inhibitory activity of antibiotics to pseudomonas aeruginosa, but also is good in safety and can be used for treating chronic infection caused by pseudomonas aeruginosa.

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.

The invention relates to the field of biological medicine, in particular to a medicine for treating HPV infection related diseases. The invention provides antigen combinations, fusion proteins and encoding nucleic acids. The materials are used for preparing self-replicating RNA vaccines for treating cervical HPV persistent infection, intraepithelial neoplasia induced by the cervical HPV persistent infection and cervical cancer, and indications can be expanded to HPV long-term infected people. Therefore, not only can virus host cells be removed to treat long-term infection, but also precancerous lesions and cervical cancer can be treated more effectively.

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%.

Disclosed is use of a combined compound medicine in treating pathogenic bacteria persistent infection. Existing antibiotic monotherapy or combination therapy is usually difficult to kill pathogenic bacteria in the persister state, especially nutrient-insensitive persister bacteria, which often lead to a series of problems of long treatment period, frequent condition recurrence and deterioration, treatment failure, drug-resistant mutation, etc. At present, drugs capable of efficiently killing highly persistent pathogenic bacteria in a clinically applicable concentration range are still unavailable. The novel compound medicine of polymyxin and aminoglycoside antibiotics disclosed in the present disclosure without precedence is capable of destroying bacterial cell membranes in a short time within a relatively wide range of clinically achievable plasma concentrations, leading to rapid death of a large number of bacteria, but is safe for human-derived cells. Therefore, the compound medicine is expected to be applied to the clinical treatment of various acute or chronic infectious diseases caused by pathogenic bacteria in the persister state, shortening the treatment course, preventing the recurrence of infection recurrence, and slowing down the emergence of drug-resistant mutations.

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.

To provide a COPS3 inhibitor to be used in treating HBV infection particularly chronic HBV infection.SOLUTION: Provided is use of a COPS3 inhibitor for destabilizing a cccDNA (covalently closed circular DNA) such as an HBV cccDNA. Also provided is a nucleic acid molecule which is complementary with COPS3, and can reduce a COPS3 mRNA level. A pharmaceutical composition and use thereof in treating HBV infection are also included.SELECTED DRAWING: None

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.

To provide IL-2 compositions, and methods of use thereof.SOLUTION: Provided are activatable proprotein homodimers comprising at least two separate polypeptide chains, in which each chain comprises an IL-2 protein, a cleavable linker, and an IL-2 binding protein, among some optional features, as well as related pharmaceutical compositions and methods of use thereof are provided. Interleukin-2 (IL-2) immunotherapy has proven useful in the treatment of cancers, such as malignant melanoma and renal cell carcinoma, and chronic infections, such as HIV infection.SELECTED DRAWING: None

The present invention relates to the field of biomedicine technology, and in particular to the use of POSTN protein in the preparation of diagnostic and therapeutic products for Treg cell disorder diseases, which include one or more diseases of tumors, autoimmune diseases, chronic infections and chronic inflammation. Cell experiments have shown that POSTN protein can regulate the differentiation of initial CD4 cells into Treg cells, and the results of bioinformatics analysis show that POSTN protein is highly expressed in the tumor microenvironment. The above results suggest that the secretion of Treg cells can be stimulated by POSTN protein, or a pharmaceutical preparation can be prepared using POSTN protein in the tumor microenvironment as an identification target, or a diagnostic product can be prepared using POSTN protein biomarkers in the tumor microenvironment. POSTN protein is expected to be used in the preparation of diagnostic and therapeutic products for Treg cell disorder diseases.

The invention relates to the technical field of biological medicines, and discloses a preparation method of chlorella vesicles, which comprises the following steps: taking a chlorella solution, and carrying out primary centrifugation at 4 DEG C to obtain primary supernate; carrying out secondary centrifugation on the primary supernate at 4 DEG C to obtain secondary supernate; carrying out third centrifugation on the secondary supernatant, and discarding the supernatant to obtain a chlorella vesicle precipitate; the invention also discloses an application of the chlorella vesicle in relieving T cell depletion. The invention provides an immunotherapy preparation with active chlorella vesicles, aiming at the problems of chronic infection and T cell depletion in a tumor microenvironment, the immunotherapy preparation relieves ammonia accumulation in the tumor microenvironment through ammonia metabolism, regulates the ammonia metabolism process in the tumor microenvironment, relieves the inhibition effect on T cells, and improves the immunotherapy effect of the tumor microenvironment. The T cell depletion state is reversed to a certain extent.

The invention discloses a hydrogel film loaded with an antibacterial agent as well as a preparation method and application of the hydrogel film. Specifically, the hydrogel film disclosed by the invention is prepared from the following raw materials: two or more polyethylene glycol monomers with different end groups, polyphenol substances and an antibacterial agent. The hydrogel film loaded with the antibacterial agent has good hemostatic performance in acute wound nursing, has good anti-infection, anti-oxidation and wound healing promoting performance in chronic infection wound nursing, and has good biocompatibility in the environments of wounds, blood and the like.

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 present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy. Thus, the present invention relates to humanized anti-claudin-1 antibodies and uses thereof, in particular for the prevention and treatment of hepatitis C virus infection, virus-induced liver diseases, hepatocellular carcinoma (HCC), nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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.