50 results about "Local immunity" patented technology

The invention relates to the technical field of veterinary epidemic disease detection, and discloses a veterinary epidemic disease remote monitoring and intelligent diagnosis system, which comprises a multi-mode biosensor array including an implantable miniature biochip, a wearable flexible physiological monitoring patch and an environment sensing sensor cluster, the implantable miniature biochip is used for being implanted into a key tissue organ area in an animal body and collecting microscopic physiological data such as cellular metabolism signals and local immune reaction marker concentration in real time, and the wearable flexible physiological monitoring patch is used for being attached to the body surface of the animal. By means of the multi-mode biosensor array and the edge intelligent preprocessing unit, animal physiology and environment data are accurately monitored in real time. The multi-modal biosensor array covers the implantable miniature biochip, the wearable flexible physiological monitoring patch and the environment sensing sensor cluster, and can comprehensively collect in-vivo microscopic physiological data, body surface macroscopic physiological parameters and feeding environment information of animals.

The invention provides in-situ forming fluid bionic hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides an injectable GelSSO / PDA (at) SDF fluid bionic niche, after in-situ photo-crosslinking, preferential and sustained release of PDA (at) SDF NPs initiates early signal amplification, which recruits EPCs and MSCs through an SDF-1 alpha / CXCR4 axis, promotes activation of the angiogenic vascular niche through an AKT signal, and repolarizes macrophages to a regenerated M2 phenotype. Subsequently, the gradual degradation of the bionic niche triggers the stable release of SSO, and the later signal is further amplified to form an osteogenic niche with transcriptional activity, thereby maintaining the MAPK / ERK-mediated MSCs osteogenic differentiation. The fluid bionic niche can form a niche conforming to defects through photopolymerization, the local immune imbalance and endogenous progenitor cell recruitment are corrected in the early stage, then formation of new vessels and lamellar bones is promoted, and finally vascularization regeneration of diabetic skull defects is achieved.

The application discloses a method for preparing cell-derived exosomes and products and applications thereof, and the method comprises the following steps: co-culturing immune-activated programmable cells with a stimulating agent with immune-activation effect, and collecting the cell-derived exosomes with immune activity by a natural secretion collection method or an artificial extrusion collection method. The application has safe and controllable local immune activation, and the immune activation strategy based on the exosomes fully overcomes the safety bottleneck of traditional live bacterial preparations in tumor treatment. By replacing live bacteria with engineered exosomes, not only potential risks such as systemic inflammatory response and infection are effectively avoided, but also the local controllability of immune stimulation signals is ensured, the precise activation and directional regulation of tumor region immune cells are realized, the tumor microenvironment is reshaped, the anti-tumor effect is strengthened, and the broad-spectrum cross-tumor potential is verified across models.

The application discloses a human vagina micro-ecological in-vitro model and a construction method and application thereof, and relates to the technical field of medicines.The application discloses a human vagina micro-ecological in-vitro model and a construction method and application thereof.Firstly, a mixed cell group of the vaginal epithelium containing a complete cell lineage and capable of long-term subculture is successfully established, a technical bottleneck that primary vaginal epithelial cells are difficult to expand is solved, and ideal seed cells are provided for model construction.Secondly, a highly-bionic vaginal mucosa model having a tight connection structure, rich layers and an orderly arrangement is constructed, and the physiological barrier and immune regulation functions of the vaginal mucosa are truly simulated.Finally, by introducing lactobacillus symbiosis and confirming the response to estrogen, a multi-element in-vitro research model integrating the anatomical structure of the vagina, resident flora, local immunity and endocrine regulation is constructed, and a reliable technical platform is provided for in-depth exploration of the mechanism of vaginal micro-ecological disorder and efficient screening of related drugs.

Embodiments described herein relate to restorative solutions for segmental peripheral nerve (PN) defects using allografted PNs for stimulating PN repair. More specifically, embodiments described herein provide for localized immunosuppression (LIS) surrounding PN allografts as an alternative to systemically suppressing a patient's entire immune system. Methods include localized release of immunosuppressive (ISV) agents are contemplated in one embodiment. Methods also include localized application of immunosuppressive (ISV) regulatory T-cells (Tregs) and / or mesenchymal stomal cells in other embodiments. Hydrogel carrier materials are also described herein.

A phototherapy device is disclosed for irradiating tissues, such as those within a patient's body cavity, with light to induce various biological effects. These biological effects may include at least one of the following: inactivation and / or inhibition of the growth of one or more pathogens, upregulation of local immune responses, increase of endogenous nitric oxide reserves, release of nitric oxide from endogenous reserves, and induction of anti-inflammatory effects. The biological effects may also include upregulation and downregulation of inflammatory immune response molecules within the target tissue. The wavelength of light is selected based on the expected biological effects on one or more of the target tissue type and target pathogens. Whether using light of a single wavelength or light of multiple wavelengths, phototherapy can provide a variety of pathogenic biological effects. A device for phototherapy is disclosed that provides a light dose to induce biological effects on various target pathogens and tissues with enhanced efficacy and reduced cytotoxicity.

The invention discloses a self-adaptive fluorescent immune layer quantitative detection feature extraction method and system, and relates to the technical field of fluorescent immune detection.The method comprises the steps that a fluorescent speckle image sequence is obtained, an image gradient difference value between adjacent frames is calculated, a three-dimensional interference disturbance tensor is constructed, and a main disturbance modal map is obtained through sparse principal component analysis; constructing a self-supervised triple training sample based on the main disturbance modal map, and training an image block encoder by taking a disturbance value as a pixel-level weighting factor; extracting image block features by using the trained encoder, and matching the image block features with the response feature dictionary to generate a response probability map; calculating perturbation spectrum entropies of the time sequence maps, and generating a fusion response probability map according to reciprocal weighted fusion of the perturbation spectrum entropies; and through mask screening and response integral calculation, outputting through a fitting method. According to the method, the local immune response recognition capability can be effectively enhanced, the adaptivity of feature extraction and the stability of response fusion under interference are improved, and high-precision quantification of fluorescence immunodetection is realized.

To provide parenteral nutrition formulations.SOLUTION: The present disclosure relates to multi-chamber containers and to parenteral nutrition formulations, including ready-to-use parenteral nutrition formulations reconstituted from and amino acid formulations. More specifically, the present disclosure relates to formulations comprising butyrate derivatives, specifically arginine butyrate, for use in adult or pediatric patients. The present disclosure further provides methods for reducing or preventing systemic and local inflammation in patients receiving parenteral nutrition, as well as methods for maintaining or improving their systemic and local immunity and intestinal barrier function.SELECTED DRAWING: None

The invention discloses a bimodal nucleic acid removal system for treating an intervertebral disc degenerative disease as well as a preparation method and an application method of the bimodal nucleic acid removal system. A nucleus pulposus cell membrane vesicle is used for entrapping a small molecule mitochondrial membrane stabilizer, and the engineered nano vesicle is prepared. The preparation method comprises the following steps: mixing a polyamidoamine (PAMAM) dendritic polymer with a hyaluronic acid solution, adding the PAMAM dendritic polymer, and carrying out Schiff alkali reaction crosslinking to form hydrogel, so as to obtain the bimodal nucleic acid removal system. The hydrogel is combined with negative cfDNA released in tissue gaps through positive charges, inflammatory nucleic acid in the tissue microenvironment is efficiently removed, polarization of M1 type macrophages and release of inflammatory factors are inhibited, and the local immune microenvironment is improved. The engineered nanovesicles are used for targeted delivery of a small-molecule mitochondrial membrane stabilizer into nucleus pulposus cells, DNA leakage caused by increase of permeability of mitochondrial outer membranes is inhibited, the cell steady state is recovered, cell function degeneration is delayed, and inflammatory response is inhibited from two aspects of intracellular sources and tissue external environments through synergistic effects.

Provided herein include new antibodies reactive for canine CD3, which are shown to substantially increase activation of canine T cells; new multi-specific immune cell engager molecules based on the canine CD3 antibodies, which are shown to effectively bind canine cancer antigens and recruit T cells for killing of the cancer cells; as well as new recombinant proteins derived from canine cartilage protein fragments and hydrogels thereof. Uses of these compositions are also provided, which include therapeutic uses of antibodies and multi-specific immune cell engager molecules for treatment of cancers or other diseases in dogs, as well as uses of hydrogels for local immunotherapy delivery for reduction of post-surgical recurrence risk, reduction of cancer at surgically inoperable sites, provision of palliation, and / or substitution for surgery.

The invention discloses a sperm-friendly medical lubricant and a preparation method thereof. The lubricant comprises the following components: a water-based matrix, an active component, phosphate, a humectant, an osmotic pressure regulator and water, the active ingredients comprise small molecule peptidoglycan and alkaline polypeptide. The alkaline polypeptide is alkaline protein, can mildly improve the pH environment of the vagina and is beneficial to maintaining the activity of sperms, and the small molecule peptidoglycan has a good adhesion effect on vaginal epithelial cells, can be adhered to the vaginal epithelial cells and prevents the alkaline polypeptide from stimulating the vaginal inner wall; the small molecule peptidoglycan also can promote local immune regulation, enhance secretion of anti-inflammatory factors and immune response of macrophages, and improve the anti-infection ability of vagina; the composition of the two active substances can maintain sperm activity and protect and resist infection on the vagina at the same time, and is a lubricant which is friendly to the vagina and sperms.

This disclosure provides the use of nanoparticles of self-assembled acidic molecular clusters (NP-AMCs) of ammonium salts to lower the pH of skin and underlying tissue of a human or other mammal as a means of stimulating the localized immune response to a wound.

The present invention relates to bacterial probiotics useful in aquaculture. Specifically, it discloses a selection of non-hemolytic, proteolytic, stress-tolerant bacterial strains with enhanced quorum- quenching capabilities. Moreover, the method allows detection of novel species of bacteria whose probiotic attributes could be massive for aquaculture. From the isolated bacteria, selected species were tested for their probiotic efficacy in Nile tilapia (Oreochromis niloticus), a key fish species in global finfish aquaculture. The species demonstrated significant efficacy in improving the health and growth performance of Nile tilapia juveniles. Specific growth rates and weight gain, and improved feed conversion ratios without adverse effects on fish health were observed. The gut microbiome was positively influenced by promoting beneficial bacteria while reducing harmful (opportunistic) species, leading to improved immune modulation. Survival rates were significantly boosted during a pathogenic challenge, and key immune genes were upregulated, indicating stronger local immune defenses. These findings show that the selected probiotic species offer substantial benefits for growth, feed efficiency, and disease resistance, emphasizing their potential for widespread application as probiotics in aquaculture.

The invention discloses a nasal delivery double-chain RNA / Mn < 2 + > nano-drug as well as a preparation method and application thereof in immunotherapy. And adding the polymer into a solution containing double-stranded RNA and manganese salt, and self-assembling to form the nasal delivery double-stranded RNA / Mn < 2 + > nano-drug. The invention provides a new technical scheme for the barrier of the BBB. The nano delivery system has the advantages in the aspects of overcoming the BBB and improving the in-vivo biological distribution of the drug, and the surface of the nano carrier is modified with a ligand targeted to an endothelial cell overexpression receptor, such as ApoE peptide and the like, so that the drug can be delivered to penetrate through the BBB; a non-invasive nasal-brain delivery strategy becomes a new scheme for improving drug availability and reducing toxic and side effects, the drug can bypass BBB and rapidly enter brain parenchyma through olfactory bulb and trigeminal nerve conduction pathways, and an immune drug delivered by the nasal cavity can rapidly enter nasopharynx-related lymphatic tissue (NALT) and is transferred to CLN through a lymphatic network around the nasal cavity, so that the immune drug can be rapidly delivered to the nasopharynx-related lymphatic tissue (NALT). Further, a potent local immune response aiming at the in-situ GBM is induced.

This invention discloses a method for preparing and applying a chimeric peptide nanomedicine for photodynamic immunotherapy of triple-negative breast cancer. The nanomedicine uses the functional chimeric peptide Fmoc-K(PpIX)-PLGLAG-CVRARTR as its self-assembly core and is loaded with the exosomal PD-L1 inhibitor GW4869. This chimeric peptide contains an MMP-2 responsive sequence, the photosensitizer PpIX, and the PD-L1 targeting peptide CVRARTR. It is structurally stable in the bloodstream and can specifically accumulate in tumor tissues that highly express PD-L1 via the targeting peptide. Enzymatic degradation is triggered by the highly expressed MMP-2 in the tumor microenvironment, achieving structural deformation, controlled drug release, and enhanced deep tumor penetration. This invention can simultaneously achieve a triple synergistic therapeutic effect: PDT generates reactive oxygen species that directly kill tumor cells and trigger immunogenic cell death, enhancing immunogenicity; the targeting peptide competitively blocks PD-L1 on the cell surface, relieving local immunosuppression; and the inhibitor downregulates exosomal PD-L1 secretion, inhibiting systemic immune escape. This approach effectively overcomes the bottleneck of low response rates in existing TNBC immunotherapy.

The invention relates to a composite bio-ink, a preparation method thereof and a bone organ constructed based on the composite bio-ink. The composite bio-ink can be used for extrusion type 3D bio-printing, and the composite bio-ink adopts methylacryloylated gelatin (GelMA) as a matrix, and aloe gel with M2 polarization capability and nano-clay which endows the material with structural stability are introduced. The composite bio-ink provided by the invention is multifunctional composite bio-ink with an endogenous immunoregulation function and excellent osteogenesis performance, and breaks through the traditional immunoregulation mode depending on short-term exogenous cytokines, so that precise regulation and control of a local immune microenvironment are realized, functional regeneration of bone tissues is promoted, and the osteogenesis effect is improved. Higher biological safety and clinical transformation potential are realized. According to the composite bio-ink, a 3D extrusion type printing forming method is adopted, and a composite scaffold with multiple functions of immune induction, biocompatibility, mechanical strengthening, osteogenesis promotion and the like can be constructed. Based on the composite scaffold, a bone organ can be further prepared.

This disclosure provides the use of nanoparticles of self-assembled acidic molecular clusters (NP-AMCs) of ammonium salts to lower the pH of skin and underlying tissue of a human or other mammal as a means of stimulating the localized immune response to a wound.

The invention discloses a recombinant oncolytic adenovirus for expressing IL-27 as well as a construction method and application thereof, and belongs to the technical field of biological medicines, and the recombinant oncolytic adenovirus H101 + IL-27 is constructed by integrating a human IL-27 gene into an oncolytic adenovirus H101 genome through a genetic engineering technology. The virus can specifically replicate and express IL-27 in tumor cells, synergistically activate congenital and adaptive immune response through a dual mechanism of oncolytic effect and local immune regulation, effectively remodel a tumor immune microenvironment, and convert a cold tumor into a hot tumor. In-vitro and in-vivo experiments prove that H101 + IL-27 can remarkably inhibit liver cancer cell proliferation, induce cell apoptosis, promote anti-tumor immunity and effectively inhibit growth of mouse transplanted tumors. The recombinant oncolytic adenovirus constructed by the invention is applied to medicines for treating tumors such as hepatocellular carcinoma and the like, and has a wide clinical prospect.

The invention relates to the technical field of biomedicine, in particular to a nano-composite hirudin protein line capable of remodeling glycolipid metabolism and a preparation method of the nano-composite hirudin protein line. The nano-composite hirudin protein line for remodeling glycolipid metabolism is prepared from the following components in parts by weight: 60 to 85 parts of type I collagen line, 5 to 10 parts of recombinant hirudin, 2 to 5 parts of liraglutide, 1 to 5 parts of ursodesoxycholic acid, 1 to 4 parts of polydopamine and 2 to 5 parts of N-hydroxysuccinimide-polyethylene glycol-maleimide. 2-5 parts of phenylboronic acid modified sodium alginate and 2-5 parts of gallic acid chitosan; according to the invention, on-demand accurate release of drugs in a pathological microenvironment is realized, the intervention efficiency is remarkably improved, the side effects of the system are reduced, meanwhile, a collaborative treatment network is formed, root intervention on complex metabolic disorders is realized, the product can actively remodel a local immune microenvironment while delivering the drugs, the process is controllable, the safety is excellent, and the application prospect is wide. And the benefit of traditional wire embedding weight reduction is greatly improved.

The invention discloses gene modification carrying an immunological enhancement element and application of the gene modification, and relates to the technical field of biological medicine and gene engineering. B, at least one coding nucleic acid sequence IE of an immunological enhancement element, wherein the immunological enhancement element is used for enhancing antigen presentation, immunological co-stimulation signal transmission or positive regulation of a local immune microenvironment; c, at least one of a signal peptide segment SP and a membrane anchoring localization domain TM; the d expression regulation unit comprises a promoter Pr for driving the expression of Ag and IE and a transcription termination signal pA; the e-site strategy related sequence organization comprises a homologous segment left side HS-L and a homologous segment right side HS-R; wherein the Ag and the IE are assembled in the same expression framework, the IE is located at one of the upstream and the downstream of the Ag, antigen presentation and costimulatory signals are synchronous and stable, the immune response intensity and durability are improved, and inter-individual and inter-batch fluctuation is reduced.

This invention discloses a gynecological antibacterial hydrogel, its preparation method, and its application. The hydrogel comprises a water extract of traditional Chinese medicines including Verbena officinalis, Salvia miltiorrhiza, Portulaca oleracea, Sophora flavescens, Viola yedoensis, Phellodendron chinense, and Artemisia argyi, as well as lactic acid, chitosan, and water. The preparation involves a water extraction and alcohol precipitation purification process to obtain the herbal extract, which is then mixed with a chitosan-lactic acid swelling matrix, adjusted to pH 3.8-4.4, and then filled and sterilized. Based on the principles of traditional Chinese medicine (TCM) formulation and combined with modern pharmaceutical technology, this invention's gel possesses the effects of clearing heat and drying dampness, detoxifying and killing parasites, and promoting blood circulation and removing blood stasis. It exhibits strong inhibitory activity against common gynecological pathogens, restores the acidic environment of the vagina, regulates local immunity and microenvironment, has an adjunctive therapeutic effect on HPV infection, is non-irritating to the vaginal mucosa, and has high safety and good stability.

Monoclonal antibodies that specifically bind CD25, as well as conjugates of the anti-CD25 antibodies, are described. The CD25-specific monoclonal antibodies and conjugates thereof do not block binding of IL-2 to CD25 and induce little to no antibody-dependent cellular cytotoxicity (ADCC). The anti-CD25 antibodies and conjugates can be used, for example, to target photoimmunotherapy to T regulatory (Treg) cells in tumor beds to enhance the local host immune response to the tumor.

Provided herein are nucleic acid molecules (e.g., recombinant expression vectors) encoding cytokines and uses thereof for the preparation of modified tumor infiltrating lymphocytes (TILs) wherein the modified TILs comprise one or more immunomodulators (e.g., cytokines) associated with its cell surface. Immunomodulators associated with TIL can provide local immunostimulation, thereby advantageously enhancing survival, proliferation, and / or anti-tumor activity of TIL in a patient. Thus, the compositions and methods disclosed herein can provide effective cancer therapy.

Unit dosage forms, devices, and kits for the topical delivery of topical immunosensitizers are provided, including skin patches, glass swabs, and kits including skin patches and glass swabs. Among other advantages, the unit dosage forms, devices, and kits provided in this disclosure deliver a more consistent and controlled volume of drug solution, prevent under- or over-dosing, prevent or discourage repeated dosing, and provide a more consistent area of ​​skin to which the drug solution is applied.

The application discloses a preparation method and application of a metal organic framework composite coating of active molecules loaded on a zinc alloy surface, and belongs to the technical field of biomedically degradable metal materials. The preparation method of the organic metal framework composite coating comprises the following steps: S1, preparing a ZnO nanostructure transition layer; S2, in-situ generating a metal organic framework coating induced by 2,5-dihydroxyterephthalic acid; and S3, preparing a metal organic framework composite coating loaded with deferoxamine. The application can effectively slow down the degradation rate of a zinc alloy substrate containing Mg, Ca and Sr, and makes the zinc alloy substrate containing Mg, Ca and Sr free of local corrosion, so that no toxicity is caused to cells and tissues around an implantation site. Slow release of the loaded deferoxamine can significantly accelerate blood supply reconstruction at a fracture / bone defect site, and can balance osteogenesis and osteoclastogenesis. The application solves the problems of uncontrollable degradation and lack of regulation on local immune inflammation and osteogenesis-osteoclastogenesis balance.

This application relates to the field of chemical pharmaceutical technology, and more particularly to an imidazoquinoline compound having an alkylthio or alkyldithio group, its preparation method, and its application. The imidazoquinoline compound of this application includes the imidazoquinoline compound shown in Formula I and its pharmaceutically acceptable salt. This imidazoquinoline compound can activate TLR7 and TLR8 receptors, and after local injection, the level of the inflammatory factor IL6 in the blood is further reduced compared to the prototype molecule 78A1. While achieving local immunostimulation, it minimizes the non-specific immunotoxicity caused by cytokine storms, thus significantly improving safety. Therefore, the imidazoquinoline compound provided in this application can be used more safely for local immune activation, such as for tumor treatment or as an immunostimulatory adjuvant for vaccines.

The application provides a method for constructing a local inflammation model of an experimental animal brain, which comprises the following steps: anesthetizing the experimental animal and fixing the experimental animal on a positioning device; injecting an immunomodulator into a target region according to the coordinates of the target region by using a puncture tool; controlling the injection speed and dose of the immunomodulator by using a micro-infusion device; keeping the puncture needle in the body for a period of time after injection to reduce the backflow of the liquid medicine; verifying the local immune activation by quantitatively detecting the expression change of an inflammation marker in the target region, and synchronously detecting the expression level of the inflammation marker in a peripheral medium to exclude a systemic immune response. The application can effectively solve the problem that the peripheral inflammation effect is difficult to distinguish in the research of brain diseases caused by systemic administration in the prior art, and can be applied to the research of the local immune activation effect of diseases such as Alzheimer's disease, ischemic stroke and glioblastoma, and the evaluation of the efficacy and mechanism of STING agonists in these diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to a spermidine functionalized Janus hydrogel microneedle system as well as a preparation method and application thereof. The Janus hydrogel microneedle system is composed of a mucous membrane adhesion layer (HTSO hydrogel) and an anti-adhesion layer (GSC hydrogel), the mucous membrane adhesion layer is formed by dynamic Schiff base crosslinking of hyaluronic acid-spermidine conjugate and oxidized dextran loaded with lidocaine, and the anti-adhesion layer is composite hydrogel composed of carboxymethyl chitosan, gelatin and silk fibroin. The Janus hydrogel microneedle system provided by the invention can directly deliver a drug to mucous membrane tissues, so that the permeability of the drug is improved, the compliance of a patient is improved through painless local drug delivery, and the Janus hydrogel microneedle system shows lasting adhesion in an oral environment, effectively inhibits ferroptosis activity and active oxygen, remodels a local immune microenvironment and has a good application prospect. In-vivo angiogenesis and epithelium regeneration are promoted.