3701 results about "Cytokine" patented technology

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid with one or more sequences of micro interfering ribonucleic acid (miRNA). When the recombinant plasmid interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a cytokine or other mediator molecule of an inflammatory response.

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.

The invention relates to a bone organ constructed based on oxygen-releasing immune hydrogel microspheres and a preparation method and application thereof. An oxygen release material, macrophages and bone marrow mesenchymal stem cells are loaded in the oxygen release immune hydrogel microspheres. And adding the oxygen-releasing immune hydrogel microspheres into a culture medium for culturing to obtain the bone organ constructed based on the oxygen-releasing immune hydrogel microspheres. The oxygen release material (CaO2-HAp) is entrapped in the hydrogel microspheres, so that continuous oxygen supply can be provided in a defect area, the low-oxygen environment is improved, the activity of osteoblasts is improved, osteogenic differentiation is promoted, macrophages are entrapped by the microspheres, the immune microenvironment is regulated and controlled, the release of proinflammatory cytokines is reduced, the osteogenic efficiency is improved, and bone defect repair is accelerated. The micro-fluidic technology is utilized to accurately control the size and shape of the microspheres, so that the microspheres can adapt to irregular bone defects, bone organs are formed through long-term in-vitro culture, and the biological activity and adaptability of the bone repair material are improved.

The invention discloses a novel nano-drug Res (at) LDH and a preparation method and application thereof.Germanium-doped LDH powder and resveratrol are combined to obtain a nanoscale particle mixed material Res (at) LDH, electron paramagnetic resonance (EPR) tests show that both the germanium-doped LDH and the traditional drug resveratrol show excellent reactive oxygen species (ROS) removal characteristics, and the Res (at) LDH can be used for preparing a novel nano-drug Res (at) LDH. The nano-drug Res (at) LDH formed by combining the two has remarkable synergistic ROS removal efficiency which can reach 90%. Meanwhile, in-vivo biological distribution experiments show that the novel nano-drug Res (at) LDH has excellent blood-brain barrier permeability, enhances accumulation in brain tissues, improves neurological dysfunction, reduces infarct volume, shows strong antioxidant activity, and inhibits release of pro-inflammatory cytokines.

The present disclosure provides compositions and methods for the selective transduction and genome editing of human cells (e.g., hematopoietic stem and progenitors cells, HSPCs) using engineered viral like particles (eVLPs). Aspects of the disclosure provide eVLP compositions comprising fusion proteins comprising a targeting moiety. In some embodiments, the fusion proteins comprise a cytokine conjugated to a transmembrane protein and / or an envelope glycoprotein. In other embodiments, the fusion proteins comprise a targeting moiety domain, a stalk protein domain, a transmembrane and / or envelope glycoprotein domain. Targeted-eVLP architectures comprising various targeting domains, stalk domains, transmembrane domains, and envelope glycoproteins are also provided herein. Other aspects of the disclosure provide eVLP compositions comprising envelope glycoproteins comprising non-natural sugars and methods of conjugating said eVLPs to various targeting moieties using bio-orthogonal click chemistry. Polynucleotides, vectors, cells, and kits useful for producing the articles, and performing the methods, described herein are also provided.

The invention discloses bifidobacterium breve BBr69 with an immunoregulation function as well as application, a product and a method thereof, and belongs to the technical field of microorganisms. The preservation number of the bifidobacterium breve BBr69 with the immunoregulation function is CGMCC (China General Microbiological Culture Collection Center) NO. 32425. Based on the strain, the invention also provides application and related products of the strain. The BBr69 strain has broad-spectrum antibacterial performance, has the function of regulating intestinal flora and also has the function of enhancing immunity, and immunity is enhanced by proliferating RAW264.7 cells, increasing the content of cell factors, inhibiting weight loss, increasing the index of immune organs and reducing ileum tissue damage.

The invention belongs to the technical field of microorganisms, and relates to a lactobacillus paracasei JNL0025 strain and application thereof. Compared with a commercial strain lactobacillus casei substitute strain, the lactobacillus paracasei JNL0025 provided by the invention has the advantages that the guanine nucleoside conversion rate is improved, the inhibition rate of supernate on XOD is equivalent, and the inhibition on PNP activity can be realized; according to the lactobacillus paracasei JNL0025 disclosed by the invention, the lactobacillus paracasei JNL0025 has the effects of reducing the tendency of pro-inflammatory M1 type macrophages, increasing the proportion of anti-inflammatory M2 type macrophages and inhibiting secretion of pro-inflammatory cytokines TNF-alpha and IL-6, and the lactobacillus paracasei JNL0025 has a better inflammation inhibition effect than the lactobacillus rhamnosus LGG; animal experiment results show that the lactobacillus paracasei JNL0025 provided by the invention can significantly reduce the blood uric acid level of a hyperuricemia model mouse, alleviate the kidney inflammation level and alleviate DSS-induced colitis, and shows a huge application value.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

The invention provides lactobacillus reuteri HNU872 and application of the lactobacillus reuteri HNU872 in preparation of intestinal inflammation related products. The invention discloses how the Lactobacillus reuteri HNU872 effectively alleviates the phenotype of DSS-induced mouse enteritis. The invention also discloses a preparation method of the Lactobacillus reuteri HNU872. Research results show that the Lactobacillus reuteri HNU872 can significantly relieve weight loss caused by enteritis, improve colon length, significantly improve the level of anti-inflammatory cytokines in serum and reduce the concentration of pro-inflammatory cytokines. In addition, the expression of the intestinal tight junction protein ZO-1 is obviously promoted. The lactobacillus reuteri HNU872 can regulate diversity and structure of intestinal microbiota of mice, inhibit enrichment of pathogenic bacteria and relieve inflammatory response. According to the invention, the action mechanism of the lactobacillus reuteri HNU872 in improving enteritis is clarified, and a solid scientific basis is provided for developing a microbial product based on probiotics as an alternative treatment strategy for ulcerative colitis.

The invention relates to lactobacillus crispatus LC30 for preventing and treating female genital tract infection and application of the lactobacillus crispatus LC30. The lactobacillus crispatus LC30 is preserved in the China General Microbiological Culture Collection Center with the preservation number of CGMCC NO.31923. The lactobacillus crispatus LC30 has good hydrogen peroxide production capacity and adhesion capacity, has a strong inhibition effect on main vaginitis pathogenic bacteria, and can be used for preventing and treating female genital tract infection. The composition is effective to nutritional pathogenic bacteria, and can also reduce form transformation and biological membrane formation of the pathogenic bacteria and prevent and treat drug resistance; besides, the fermentation product can reduce the content of pathogenic bacteria metabolites, regulate the secretion of cytokines and achieve the effect of relieving inflammation, so that the fermentation product can be used for preparing products for preventing and treating genital tract pathogenic bacteria infection, preventing and treating vaginitis and / or removing pudendum peculiar smell.

The invention belongs to the field of new application of medicines, and particularly relates to gastrodia elata polysaccharide and application thereof. The gastrodia elata polysaccharide component GEP-2 is separated from crude gastrodia elata polysaccharide, structural characterization detection is conducted on the GEP-2, the result shows that the gastrodia elata polysaccharide GEP-2 is prepared from, by mass, 89.08% of glucose, 2.40% of galactose, 7.12% of galacturonic acid, 0.86% of arabinose and 0.54% of rhamnose, and the animal experiment result shows that the GEP-2 relieves the symptoms of mouse colitis, relieves weight loss and shortens the colon length; the traditional Chinese medicine composition has the advantages of reducing serum TNF-alpha, IL-1beta and IL-6 proinflammatory cytokine levels, improving the intestinal barrier function, reducing inflammatory cell infiltration, regulating the intestinal flora composition structure of mice and relieving ulcerative colitis.

The invention discloses a bran coat polypeptide GR-12 with an immunoregulation function and an application of the bran coat polypeptide GR-12, and the amino acid sequence of the bran coat polypeptide is Gly-Gln-Pro-Trp-Pro-Pro-Ala-Ser-Phe-Ala-Cys-Arg (GQPWPPASFACR, which is called GR-12 for short). Experiments find that the GR-12 can significantly enhance the proliferation activity and phagocytic activity of macrophages RAW264.7 and promote the macrophages RAW264.7 to secrete cytokines; meanwhile, it is found that the GR-12 can significantly enhance the immunomodulatory function of an immunosuppressive mouse induced by cyclophosphamide, specifically, the body weight, thymus index and spleen index of the immunosuppressive mouse are significantly recovered; and the secretion of cytokines and immune globulins in mouse serum is obviously increased. The bran coat polypeptide GR-12 is expected to be further researched and developed into a related medicine product with an immune regulation function, and has a wide application prospect.

The invention relates to Pediococcus pentosaceus PP90 for preventing and treating alcoholic nerve injury and application of the Pediococcus pentosaceus PP90, the Pediococcus pentosaceus PP90 is preserved in China General Microbiological Culture Collection Center (CGMCC), and the preservation number is CGMCC NO.32034. The Pediococcus pentosaceus PP90 can be used for preventing and treating alcoholic nerve injury. The fermentation product of the pediococcus pentosaceus PP90 can degrade the alcoholic strength of alcohol, can generate ethanol dehydrogenase and acetaldehyde dehydrogenase, can improve the activity of nerve cells, can regulate the expression of cytokines, can inhibit the activation of astrocytes, can regulate the expression of brain-derived neurotrophic factors, and can inhibit the growth of the brain-derived neurotrophic factors. The compound can improve the disordered neurotransmitter level, and can be used for preparing products for preventing or improving alcoholic nerve injury.

The invention discloses a patient immune response monitoring method and system for cell drug clinical research, and the method comprises the following steps: 1, obtaining a peripheral blood sample of a patient, and preprocessing the peripheral blood sample to obtain patient sample components; multi-dimensional immune indexes and cell drug specific immune response are detected by comprehensively utilizing multiple technologies, immune cell subsets, cell factors, immune globulin, T cell response and the like are covered, and therefore a complex immune response system is comprehensively reflected; peripheral blood samples are collected at multiple time points according to a cell drug action mechanism and a half-life period, and the whole-course change of the immunoreaction is effectively tracked, so that the development trend of the immunoreaction is accurately grasped; the method has the advantages that the characteristics are visually presented by constructing the immune response atlas of the patient, evaluation and prediction are assisted, real-time monitoring reports and treatment suggestions are provided according to evaluation and prediction results, doctors are assisted to adjust treatment in time, and accordingly the safety and effectiveness of cell drug treatment are improved.

The invention discloses photocuring hydrogel capable of being combined with cytokines and used for tumor organoid culture and application, and belongs to the technical field of organoid culture. According to the invention, the hydrogel which can fix cells, can be combined with cell factors and can realize organoid recovery is developed through norbornene modified heparin, norbornene modified gelatin, sulfydryl four-arm polyethylene glycol, glucan, matrix metal protein peptidomimetic MMP and a photoinitiator. The hydrogel can be used for directly preparing organoids, heparin of various structures can be used, the cost is reduced, the modified heparin can bind factors or matrix protein and can controllably release the factors, the modified gelatin provides amino acid energy for collagen hydrolysate, and the hydrogel is formed by photocuring in a stepwise polymerization mode, is controllable in structure and can be used for preparing collagen collagen. The adjustable bionic modulus and the adjustable bionic stress relaxation are realized. The hydrogel disclosed by the invention can be used for culturing various organs, overcomes the problems of low repeatability, instability and the like in the prior art, and is suitable for the fields of tumor drug evaluation and the like.

Provides herein are multifunctional polypeptide molecules comprising T cell receptor variable alpha-binding moieties, T cell receptor variable beta-binding moieties, TAA-binding moieties, and / or cytokines, and methods of treating conditions or diseases in a subject using the same.

The invention provides a stem cell exosome composition for treating erectile dysfunction and application thereof, the stem cell exosome composition comprises stem cell exosome and vasoactive intestinal peptide, and the amino acid sequence of the vasoactive intestinal peptide is shown as SEQ ID NO: 2. The amino acid structure of the vasoactive intestinal peptide is modified, so that the biological stability can be improved; the vasoactive intestinal peptide is combined with the adipose-derived mesenchymal stem cell exosome for use, so that the ED symptom can be relieved; the vasoactive intestinal peptide and the adipose tissue-derived stem cell exosome are combined for use, so that the expression level of cell factors can be adjusted, and the microenvironment of penis tissues can be improved.

The present invention provides a Lactiplantibacillus plantarum ( Lactiplantibacillus plantarum ), strain 24, which is deposited in the China General Microbiological Culture Collection Center, deposit number: CGMCC No. 31278. The Lactiplantibacillus plantarum 24 of the present invention can secrete sphingomyelinase to promote the production of ceramide in HaCaT cells; Lactiplantibacillus plantarum 24 or its metabolite or its lysate can up-regulate the expression of key enzymes in the sphingomyelinase and / or ceramide synthesis pathway of skin cells, repair the skin barrier; down-regulate the expression of pro-inflammatory cytokines, inhibit autophagy, and has a good anti-inflammatory effect; at the same time, it also has good antioxidant and whitening effects. The Lactiplantibacillus plantarum 24 or its metabolite or its cell lysate of the present invention can be used in the preparation of products having the above-mentioned effects or functions.

The invention relates to the technical field of NK cell culture, and discloses a serum-free medium for NK cells from umbilical cord blood after cryopreservation and a culture method thereof.The medium comprises a coating solution, an induction medium and an amplification medium; wherein the coating liquid is prepared from an anti-CD16 monoclonal antibody and DPBS (diphenylphosphonic acid); the induction culture medium comprises a basic culture medium, a human-derived platelet lysate and cell factors IL-15, IL-18 and IL-21; the amplification culture medium comprises a basic culture medium, a human-derived platelet lysate and IL-2. The culture method comprises the following steps: obtaining mononuclear cells from fresh umbilical cord blood, and then cryopreserving and resuscitating; and carrying out multiplication culture on the recovered umbilical cord blood mononuclear cells by using the serum-free culture medium. According to the NK cell culture medium, the NK cells with high purity, high killing activity and high cytotoxic activity can be obtained without autoserum culture.

The invention provides an in-vitro culture method of T cells, and belongs to the technical field of genetic engineering.The culture method comprises the steps that immune cell serum-free culture media are added into peripheral blood mononuclear cells, and activated culture is conducted in the presence of cell factors to obtain activated T cells; the cell factor comprises an IL-2 monoclonal antibody and a CD3 monoclonal antibody, and further comprises two or three of an iCAM1 protein, a CCL21 protein and OK432. The T cells obtained through activation and multiplication culture are relatively stable in cell phenotype, relatively large in amplification multiple, relatively high in cell viability and relatively high in tumor killing efficiency. T cells are obtained after activation is performed for 24 hours and then multiplication culture is performed for 14 days, and the number of the cells is 6.2-8.9 * 10 < 9 >; the killing rate on Hela cells is 51.9 to 74.1 percent, and the killing rate on LOVO cells is 55.7 to 80.5 percent.

The invention discloses a bispecific cytokine fusion protein, which comprises an amino acid sequence of a type I cytokine and an amino acid sequence of a type II cytokine, and the amino acid sequence of the type I cytokine and the amino acid sequence of the type II cytokine are directly connected through a connecting peptide or are connected in series or in parallel through a fusion partner and the connecting peptide. Amino acid sequences of type I and type II cytokines are connected in series or in parallel to form the bispecific cytokine fusion protein, and the fusion protein can synergistically activate precursor depleted CD8 + T cells and terminal depleted CD8 + T cells, improve immunosuppression of a solid tumor complex microenvironment and release the potential of tumor immunotherapy. The invention further discloses nucleic acid, a carrier, a cell, a medicine or a medicine composition related to the bispecific cytokine fusion protein. The invention also discloses application of the bispecific cytokine fusion protein in preparation of drugs for treating cancers.

A bifidobacterium animalis strain, a probiotic formulation, and a preparation method for and a use of the bifidobacterium animalis strain. The bifidobacterium animalis strain has a preservation number of CGMCCNo. 25681. The bifidobacterium animalis strain and the probiotic formulation containing same can produce extracellular polysaccharides, lactic acid and short-chain fatty acid at high yield, stimulate a mouse to generate cytokines TNF-α and IL-6, have an immunity enhancement function, improve the ink propulsion rate, and have a bowel relaxing function; and the single bacterial powder of the bifidobacterium animalis strain can significantly enhance the cellular immune function and the mononuclear-macrophage function of mice.

In various embodiments, the disclosure provides compositions, such as polypeptides, polynucleotides, gene editing systems, small molecules, vectors, or host cells, comprising and / or modulating the expression or activity of an immunomodulatory-related protein, such as a cytokine. In various embodiments, the disclosure also provides methods of treating inflammation, aging, senescence, fibrosis, autoimmunity, cancer, infection, and / or immunological disease using agents comprising and / or modulating the expression or activity of an immunomodulatory-related protein, as well as methods of identifying the agents.

The present disclosure relates activatable immunocytokines targeted to immune checkpoint molecules such as PD-1, compositions comprising the activatable immunocytokines, and methods of use thereof. The present disclosure also relates activatable IL-2 polypeptides linked to anti-PD-1 polypeptides (e.g., anti-PD-1 antibodies).

Provided are an anti-CD3 antibody or an antigen-binding fragment thereof, and a use thereof. The anti-CD3 antibody comprises: heavy chain variable region CDRs and light chain variable region CDRs, the heavy chain variable region CDRs having amino acid sequences as shown in any one of SEQ ID NOs: 1-3, 7-8 and 74-86 or a conservatively modified form thereof, and / or the light chain variable region CDRs having amino acid sequences as shown in any one of SEQ ID NOs: 4-6, 9 and 87-92 or a conservatively modified form thereof. The provided anti-CD3 antibody or antigen-binding fragment thereof can bind to human CD3 protein and reduce the production of pro-inflammatory cytokines, and a bispecific antibody constructed using same has high PBMC tumor-killing activity and weak promotion of the secretion of pro-inflammatory cytokines. A pharmaceutical composition prepared using the anti-CD3 antibody or the antigen-binding fragment thereof or a multi-specific antibody thereof has better safety, and has value for clinical applications and drug development.

The invention relates to a novel application of animal bifidobacterium subsp. Lactis BGI-N3, in particular to an application of the animal bifidobacterium subsp. Lactis BGI-N3 in preparation of a preparation for relieving skin allergy. The invention finds that the bifidobacterium animalis subsp. Lactis BGI-N3 has a very remarkable effect in the aspect of relieving skin allergy, and the effect is specifically shown as follows: in an atopic dermatitis animal model, the dermatitis score, scratching times and percutaneous water loss are remarkably reduced, and the atopic dermatitis skin tissue damage condition is relieved; the immune organ edema condition is improved, the levels of Th2 type cell factors and inflammatory factors IL-6, TNF-alpha and IFN-gamma related to dermatitis are reduced, and the immune balance of the body is recovered; expression of fibroin and endothelial protein in skin tissue is improved, and the skin barrier is repaired; the level of antibacterial peptide in skin tissues is recovered, and the antibacterial activity of the skin is enhanced. Meanwhile, compared with a traditional chemical medicine for treating atopic dermatitis, the animal bifidobacterium subsp. Lactis BGI-N3 has no side effects such as weight loss, immune organ atrophy, immune imbalance and the like.

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

The invention provides a lactobacillus plantarum 24 which is preserved in the general microbiological center of the China Committee for Culture Collection of Microorganisms, and the preservation number of the lactobacillus plantarum 24 is CGMCC No.31278. The lactobacillus plantarum 24 has the advantages that the lactobacillus plantarum 24 is prepared from lactobacillus plantarum, lactobacillus plantarum, lactobacillus plantarum, lactobacillus plantarum, lactobacillus plantarum, lactobacillus plantarum, lactobacillus plantarum and lactobacillus plantarum; the plant lactobacillus 24 disclosed by the invention can secrete sphingomyelinase and promote HaCaT cells to generate ceramide; the plant lactobacillus 24 or the metabolite or lysate thereof can up-regulate expression of key enzymes in a synthetic route of skin cell sphingomyelinase and / or ceramide, and repair a skin barrier; expression of proinflammatory cytokines is lowered, autophagy is inhibited, and a good anti-inflammatory effect is achieved; meanwhile, the anti-oxidation and whitening effects are relatively good. The plant lactobacillus 24 or the metabolite or the cell lysate of the plant lactobacillus 24 can be applied to preparation of products with the effects or the effects of the plant lactobacillus 24 and the metabolite or the cell lysate of the plant lactobacillus 24.

The invention belongs to the technical field of medicines, and particularly discloses application of moss phenol glucoside in preparation of medicines for preventing and / or treating tumors. According to the method, activated CD8 + T cells, MC38-OVA cells and traditional Chinese medicine monomeric compounds are co-cultured, the traditional Chinese medicine monomeric compounds capable of effectively promoting the anti-tumor activity of the CD8 + T cells are selected by utilizing a high-content screening technology, and finally, the experiment is carried out by taking the moss phenol glucoside as a research object. In-vitro experiment results show that the moss phenol glucoside can significantly promote T cell activation, promote release of cell factors such as IFN-gamma and TNF-alpha, and enhance the killing effect of T cells on tumors. A mouse in-vivo tumor-bearing experiment result shows that the moss phenol glucoside can promote the anti-tumor activity of T cells so as to inhibit tumor growth, has no obvious toxic or side effect, can be used for preparing the medicine for preventing and / or treating tumors, and has a potential clinical application prospect and a relatively high economic value.