61 results about "Cytokine secretion" patented technology

The application provides an active exosome stent coating, a vascular stent and a preparation method and application, and belongs to the technical field of biomedical intervention instruments. The active exosome stent coating of the application adopts stem cell-derived myocardial cell active exosomes which are strengthened by active components of traditional Chinese medicine. Compared with commercial myocardial cells, the stem cell-derived myocardial cells have more significant effects of promoting blood vessels and tissue repair and regeneration, and stronger cytokine secretion capacity. The preparation method of the active exosome stent coating of the application adjusts the introduction sequence and premixing mode of active components such as exosomes and drugs, and enhances the homogeneity and stability. The vascular stent prepared by using the active exosome stent coating of the application has reasonable sequential release kinetics design, can realize precise targeted regulation on human coronary artery smooth muscle cells (HCASMC) in vitro, does not affect the repair potential of endothelial cells, and solves the contradiction between traditional stents in terms of "anti-proliferation and promotion of healing".

A series of 1, 3, 5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1, 3, 5-triazine compounds as promising antitumor agents.

The invention discloses shRNA (short hairpin Ribonucleic Acid) targeting Zeb2, a recombinant vector, a cell and application of the shRNA in preparation of drugs for enhancing anti-tumor immune response, and belongs to the technical field of research and development of anti-tumor drugs. Experiments prove that the shRNA targeting Zeb2 can reduce the proportion of T cells (Tex, PD1 + Tim3 +), increase the proportion of depleted precursor T cells (Tpex, Ly108 + Tim3-), improve the secretion ability of Granzyme B and TNF-alpha cytokines of CD8 + T cells in tumor tissues, significantly inhibit the tumor growth of skin melanoma mice, increase the infiltration quantity of CD8 + T lymphocytes in the tumor tissues and the anti-tumor ability of the CD8 + T cells, and can be used for preparing anti-tumor drugs for treating skin melanoma. The polypeptide has the potential of being used for preparing drugs for enhancing anti-tumor immune response.

The invention provides application of an arsenene nano preparation and / or beta-elemene in preparation of a product for treating brain tumors, and belongs to the technical field of biology. The arsenene nano preparation and / or beta-elemene are / is applied to brain glioma and lung cancer brain metastatic tumor model mice, so that tumor cells can be effectively killed, tumor metastasis can be inhibited, in-vivo immune response can be activated, maturation of dendritic cells can be promoted, NK cells and CD8 + T cells can be effectively activated, and the secretion amount of tumor suppression cell factors can be increased. Meanwhile, the beta-elemene effectively reduces cardiotoxicity caused by accumulation of the arsenene nano preparation in vivo.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

The invention discloses an NK cell culture solution and culture and application of NK cells, the NK cell culture solution comprises an activation culture solution and an amplification culture solution, the activation culture solution and the amplification culture solution respectively contain a basal culture medium and respective corresponding cell factors, and the activation culture solution also contains calycosin with the final concentration of 0.1-10 [mu] g / mL and formononetin with the final concentration of 1-20 [mu] g / mL; the amplification culture solution also contains astragaloside IV and soyasaponin I. The components such as calycosin, formononetin, astragaloside IV and soyasaponin I added into the NK cell culture fluid can maintain stable and lasting physiological activity of NK cells and slow down cell senescence, so that secretion of cell factors is promoted, the secretion level of the cell factors is higher, and the purposes of enhancing the persistence of cell activity and improving the killing rate of the NK cells are achieved.

This invention belongs to the field of biomedical technology, specifically relating to a method and application for preparing CAR-T cells with enhanced persistence based on the piggyBac transposon system combined with electroporation. This invention, through specific piggyBac dual plasmid ratios and electroporation conditions, can improve transfection efficiency to over 80%, and the integration site is more likely to be located in a safe genomic region, supporting long-term stable CAR expression. Furthermore, cell expansion kinetics are significantly improved, with expansion exceeding 120-fold within 15 days. The results of the examples show that CAR-T cells prepared using the method described in this invention exhibit significantly enhanced tumor cell killing ability and cytokine secretion levels in in vitro models, and are rich in memory T cell subsets (Tcm / Tem) with greater persistence and self-renewal potential. This indicates that this invention not only changes the method of gene delivery but also shapes the intrinsic properties of cells, enabling them to acquire potentially superior in vivo persistence and long-term anti-tumor capabilities.

This invention proposes an anti-CD3 antibody or its antigen-binding fragment and its applications. It comprises: heavy chain variable region CDRs and light chain variable region CDRs; wherein the heavy chain variable region CDRs have an amino acid sequence as shown in any one of SEQ ID NO: 1-3, 7-8, and 74-86 or a conserved modified form thereof; and / or the light chain variable region CDRs have an amino acid sequence as shown in any one of SEQ ID NO: 4-6, 9, and 87-92 or a conserved modified form thereof. The anti-CD3 antibody or its antigen-binding fragment of this invention can bind to human CD3 protein and can reduce the production of pro-inflammatory cytokines. Bispecific antibodies constructed using this antibody exhibit high PBMC-based tumor-killing activity and weak pro-inflammatory cytokine secretion-promoting properties. Therefore, pharmaceutical compositions prepared using this anti-CD3 antibody or its antigen-binding fragment or its multispecific antibody have better safety and high clinical application and drug development value.

This invention belongs to the field of biomedical technology, specifically relating to the application of a functional lipid in the preparation of drugs for treating systemic lupus erythematosus (SLE). Specifically, the functional lipid MLnM exhibits significant therapeutic effects in a pristane-induced SLE mouse model, effectively alleviating SLE-related clinical symptoms, improving intestinal barrier function, reducing oxidative stress levels, regulating the balance of inflammatory cytokine secretion, and reducing systemic inflammatory responses by inhibiting the expression of immune cell migration-related genes. The discovery of MLnM provides a new direction for the treatment of SLE and other autoimmune diseases.

The invention provides a tumor infiltration capacity enhanced TIL and a preparation method and application thereof, and belongs to the technical field of cells. The tumor infiltration capacity enhanced TIL provided by the invention is a TIL which enables the expression of the DGKZ gene to be reduced or the function to be eliminated, and has enhanced tumor infiltration capacity compared with the TIL without the DGKZ gene knockout. The tumor infiltration ability enhanced TIL provided by the invention is higher in survival rate in a depletion induction experiment, and shows depletion antagonism characteristics; experiments for performing stimulation culture on the TIL cells by using PMA show that the cytokine secretion ability is remarkably enhanced compared with that of wild TIL cells. A mouse in-vivo experiment shows that compared with a wild TIL, the DGKZ-edited cervical cancer-derived TIL cell has the advantages that the in-vivo tumor infiltration capacity and retention time are more lasting, the tumor killing capacity is higher, a better treatment effect can be achieved, and the DGKZ-edited cervical cancer-derived TIL cell has an important application value in tumor treatment.

The application discloses a gel preparation preparation method for improving cervical HPV infection and establishing a preventive barrier, relates to the technical field of gel preparation, and aims to solve the technical problems that the existing treatment methods are mostly focused on treating infected patients, and there are obvious deficiencies in the prevention of HPV infection, especially in establishing an effective preventive barrier in uninfected people, including: a crushing mechanism, which is mainly used for crushing raw materials, the crushing mechanism comprises a cabinet body, a cabinet door is arranged on one side of the cabinet body, a crushing barrel is arranged in the cabinet door, and a rotating motor matched with the crushing barrel is arranged on the cabinet door; a reverse osmosis mechanism, which is mainly used for controlling the osmotic pressure of the gel. The application has the advantages of activating local immune cells of the cervix, promoting cytokine secretion, enhancing the immune clearance ability of the body to HPV virus, providing long-acting preventive protection for the cervix, and reducing the risk of HPV infection.

The present application provides chemical compounds useful, for example, in inhibiting gasdermin pore formation in a CA cell, inhibiting inflammasome-mediated death of a cell (pyroptosis); inhibiting cytokine secretion from a cell, inhibiting an inflammatory caspase in a cell, and / or covalently reacting with a cysteine of a gasdermin protein in a cell. These compounds are also useful in treating or preventing diseases or conditions in which inflammasome activation is implicated in pathogenesis. One example of such disease or condition is sepsis.

A cell expressing a fusion protein and its applications. This cell possesses enhanced capabilities, such as cell proliferation, cytokine secretion, and tumor cell killing.

The present application relates to the application of food and composition in the preparation of functional food and dairy products. The food comprises a composition, which is composed of epigallocatechin gallate, ginseng powder and polydextrose; the mass ratio of the epigallocatechin gallate, the ginseng powder and the polydextrose is 1:(0.62-10):(0.6-46.16); the mass percentage of ginsenosides in the ginseng powder is 8% or more; the purity of the polydextrose solid is 90% or more; and the purity of the epigallocatechin gallate is 94% or more. In addition, the present application also provides the application of the above-mentioned composition in the preparation of functional food and dairy products. In the food provided by the present application, the components can effectively inhibit the M1 polarization of macrophages, promote the M2 polarization of macrophages, reduce the secretion level of pro-inflammatory cytokines, inhibit the inflammatory response, and realize the rapid improvement of the immune response ability of the body through synergistic effect at the cellular level.

The invention belongs to the field of biological medicine, and discloses a preparation method and application of CEP20 knockout type TIL for enhancing tumor microenvironment adaptability, CEP20 genes in TIL are knocked out in a targeted mode through the CRISPR / Cas9 technology, the specific method comprises the steps that tumor tissue is obtained, TIL is subjected to isolated culture, gRNA and Cas9 nuclease form an RNP compound, CEP20 gene knockout is achieved through electrotransduction, and the knockout efficiency can reach 61%; and carrying out recovery culture and rapid amplification to obtain the CEP20 knockout type TIL. Experiments prove that the CEP20 knockout type TIL does not influence cell proliferation and secretion of cell factors (TNF-alpha and IFN-gamma) in vitro, and in a cervical cancer PDX mouse model, the anti-tumor capacity of the CEP20 knockout type TIL is remarkably higher than that of unmodified TIL. By relieving negative regulation of CEP20, adaptability of TIL in a tumor microenvironment is enhanced, a new strategy is provided for immunotherapy of solid tumors (such as cervical cancer and malignant melanoma), and the TIL can be used for preparing drugs for treating solid tumors.

Provided herein are chimeric antigen receptors, comprising an extracellular domain capable of binding to an antigen, an Fc region, a flexible linker, a transmembrane domain, and may further comprise at least one intracellular domain that is designed to increase the anti-tumor activities of granulocytes, macrophages, and dendritic cells by increasing their phagocytosis and / or proinflammatory cytokines secretion and / or antigen presentation. Provided herein are vectors and nucleic acid molecules encoding any of the chimeric antigen receptors described herein. Provided herein are methods to genetically engineer granulocyte-macrophage progenitors (GMPs) to express the chimeric antigen receptors described herein. The CAR-Fc-GMPs may be induced to differentiate into macrophages or granulocytes. Provided herein are macrophages and granulocytes that express a CAR-Fc prepared by any of the methods described herein. Provided herein is an immunotherapy method for treating a subject having cancer with GMPs or macrophages or granulocytes that express the chimeric antigen receptors described herein.

The present disclosure relates to engineered bacteria, compositions and methods for immune modulation, specifically Bacteroides ovatus strains locked in a defined orientation at a genomic locus undergoing phase variation. The resulting "ON" and "OFF" mutants showed distinct immunomodulatory effects in vitro and in vivo, including differential cytokine secretion, regulatory T cell induction, and antitumor activity. These engineered strains offer a novel platform for modulating immune responses in cancer, autoimmune, and inflammatory diseases.

The invention provides a bispecific antibody targeting PVRIG and PDL1 and an application of the bispecific antibody. The bispecific antibody comprises a first antigen binding region and a second antigen binding region, wherein the first antigen binding region has PVRIG molecular binding activity; and a second antigen binding region, wherein the second antigen binding region has PDL1 molecule binding activity; wherein the first antigen binding region is connected with the second antigen binding region. The anti-PVRIG-PDL1 bispecific antibody prepared by the invention has high affinity, can be efficiently combined with human PVRIG and PDL1 proteins, effectively blocks the combination of the PVRIG and CD112 and the combination of the PDL1 and PD1, contributes to enhancing the killing ability of human peripheral blood mononuclear cells (PBMC) to tumor cells, and improves the function of secreting cytokines by CD8T cells.

The invention belongs to the technical field of biological medicine, and particularly relates to application of pseudo-ginseng carbon quantum dots in preparation of a medicine for treating renal ischemia-reperfusion injury, the carbon quantum dots are synthesized by taking pseudo-ginseng as a raw material through a hydrothermal method, and the pseudo-ginseng carbon quantum dots have the antioxidant enzyme activity property, can effectively relieve cell oxidative stress and inhibit secretion of proinflammatory cytokines, and can be used for preparing a medicine for treating renal ischemia-reperfusion injury. The pseudo-ginseng carbon quantum dots specifically gather in the damaged kidney, so that the renal ischemia reperfusion injury of the mouse is obviously relieved; the pseudo-ginseng carbon quantum dots can relieve kidney injury through the following ways: reducing abundance of escherichia coli-shigella, reducing the level of indol sulfate in the kidney, regulating tryptophan-indole metabolism, regulating an AHR-Raf-ERK signal channel, down-regulating the levels of TNF-alpha and malonaldehyde, and regulating the level of glutathione. A catalytic mechanism and a multi-omics regulatory pathway of the pseudo-ginseng carbon quantum dots in renal ischemia reperfusion injury are disclosed, and experimental evidence is provided for'intestinal tract-kidney axis' in kidney disease treatment.

The present disclosure relates to manipulation of splicing of the Fas (tumor necrosis factor (TNF) receptor superfamily, member 6) gene in non-naïve cell of the T lineage for enhanced skipping of exon 6. The manipulated non-naïve cells predominantly express a soluble form of Fas (sFas) and display reduced expression of the membranal Fas (mFas), increased cytokine secretion, increased expression of activation markers, increased cell survival, increased cytotoxicity, and / or reduced expression of exhaustion markers. The present disclosure further provides specific splicing modulatory agents comprising gene editing systems and / or splice switching antisense oligonucleotide (SSO), methods and therapeutic uses thereof.

The invention discloses application of timosaponin AIII in preparation of a curative effect enhancer for CAR-T cell therapy and a product for overcoming drug resistance. The invention proves that TAIII is an allosteric inhibitor of an adenosine A2A receptor, and blocks a downstream signal channel through allosteric combination with A2AR, so that expression of a transcription factor FoxP3 is inhibited, Tregs in a CAR-T product is selectively cleared, immunosuppression of the Tregs on effector T cells is relieved, meanwhile, the proportion of central memory T cells is increased, and amplification, durability and cytokine secretion functions of the CAR-T cells are enhanced. The invention further provides a CAR-T cell composition containing the TAIII, and the TAIII and the CAR-T cells are combined or used as a pretreatment agent, so that the tumor removal capability can be remarkably enhanced, and recurrence after treatment can be effectively prevented. The invention provides a safe and effective new strategy for enhancing the anti-tumor activity of the CAR-T cells and overcoming the drug resistance of the CAR-T therapy.

The invention discloses a blood preserving fluid suitable for preserving immune cells, which is composed of the following components in terms of 100 ml: 1 to 5 g of glucose, 2 to 4 mg of glutathione, 0.2 to 0.4 g of citric acid, 0.1 to 0.3 g of sodium dihydrogen phosphate, 1 to 3 g of sodium citrate, 8 to 12 mg of sodium ferulate, and 8 to 12 mg of notoginsenoside. The composition comprises L-glutamine, L-arginine, L-aspartic acid, L-histidine, L-glutamine, L-arginine, L-aspartic acid, L-histidine and the like, and the balance of sterile water. By optimizing the formula of the preserving fluid, the stability of the PBMC in the transportation process is specifically maintained, granulocyte activation and pollution are effectively inhibited, immune cell apoptosis is reduced, the multiplication capacity and the cell factor secretion function of the immune cells are maintained, and the recovery rate and activity of the immune cells after long-distance transportation are remarkably improved.

The invention discloses an immune effect evaluation method of a cysticercus cellulosae recombinant TPx protein vaccine, and belongs to the technical field of biological medicines. The vaccine takes recombinant thioredoxin peroxidase (TPx) from cysticercus cellulosae as an immunogen, and an adjuvant (such as a Freund's adjuvant) can be optionally supplemented to enhance the immune effect. A mouse is immunized through subcutaneous injection of the vaccine, it is proved that the vaccine can effectively induce an organism to generate humoral immune response and cellular immune response, specifically, the levels of serum IgG, IgG2a and IgG1 antibodies are remarkably increased, the proliferation capacity of splenic lymphocytes is enhanced, and the secretion levels of Th1 type cell factors (TNF-alpha and IL-12) and Th2 type cell factors (IL-13 and IL-10) are remarkably increased. The invention provides a new candidate vaccine for prevention of cysticercosis, and has important application value.

Disclosed herein are fluidic devices that facilitate gas diffusion between biological samples and gas-filled compartments or an external atmosphere to stabilize dissolved gas levels within the biological samples. The fluidic devices can include a gas-permeable spacer separating the biological sample-containing channel from the gas-filled compartments or external atmosphere to facilitate rapid gas exchange within the biological sample. Further disclosed herein are methods of using the fluidic devices to incubate and determine characteristics of the samples, including methods for measuring cytokine secretion from individual cells.

The invention belongs to the technical field of medicines, and particularly relates to preparation of CD146 + MSC cells and application of the CD146 + MSC cells in treatment of type 2 diabetes mellitus. Researches find that the CD146 + MSC has better pluripotency in the aspect of being differentiated into fat cells, bone cells and cartilage cells; the proliferation speed is low; the in-vivo and in-vitro immunosuppressive activity is enhanced. Meanwhile, the CD146 + MSC has higher differentiation capacity and immunosuppressive activity, the CD146 + MSC has higher dryness, lower telomerase activity and higher migration and homing capacities, shows higher biological characteristics of immunosuppression and cytokine secretion, and is remarkable in proliferation and angiogenesis activity, so that the CD146 + MSC has better immunosuppressive activity and immunosuppressive activity. A cell type with higher stemness and more original characteristics is represented. In addition, the CD146 + MSC cells can treat type 2 diabetes mellitus by reconstructing beta cells, enhancing and regulating blood glucose homeostasis, relieving insulin resistance, and reducing or regulating systemic inflammation.

A series of 1,3,5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1,3,5-triazine compounds as promising antitumor agents.

The application provides an enhanced CAR-T cell overexpressing CD200 and an application thereof, and belongs to the technical field of biological medicine. The application provides an application of CD200 in preparation of a product for improving the anti-tumor effect of a CAR-T cell. CD200 can improve the cytokine secretion capacity of a CAR-T cell, thereby improving the killing and anti-tumor effect of the CAR-T cell. The application overexpresses CD200 on a CD19 CAR-T cell, and compared with a conventional CD19 CAR-T cell, has stronger cytokine secretion capacity, and can better play the killing and anti-tumor function.

The invention relates to the technical field of bioinformatics, and discloses an immunocompetence prediction method and system for NK cell culture, and the method comprises the following steps: collecting surface receptor signal intensity, cell factor secretion rate, culture solution metabolism characteristic parameters and cell population morphological indexes in the NK cell culture process; performing normalization and time sequence reconstruction on the parameters to form a receptor activation trend, a secretion rate change track, a metabolic flux fluctuation curve and a morphological uniformity vector; constructing a logic judgment path based on the factor groups, and sequentially identifying the immune activation state, the metabolic failure risk and the system stability; and mapping the judgment result into an immunocompetence prediction state diagram, and outputting high-activity, medium-activity or low-activity prediction results in combination with the evolution trend of the node trajectory. According to the NK cell immunocompetence prediction method, through multi-parameter collection and sequential processing, unified evaluation of the immune function, metabolic adaptation and morphological stability is achieved, and the comprehensiveness and reliability of NK cell immunocompetence prediction are improved.

Targeting the ability of T cells to enhance aerobic glycolysis upon TCR stimulation or glucose supplementation represents an attractive strategy for the treatment of autoimmune diseases. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), the inventors demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Altogether, these results indicated that targeting can be envisioned to reduce auto-immune reactions. Thus, the present invention relates to the use of Foxk1 inhibitors for the treatment of inflammatory autoimmune diseases.

The invention discloses an application of lactobacillus rhamnosus or afterbiogen thereof in preparation of a product for inhibiting pyroptosis of immune cells. The application of the lactobacillus rhamnosus BD4047 or the afterbiogen of the lactobacillus rhamnosus BD4047 in at least one of the following aspects: A1) preparing a product for resisting the pyroptosis of immune cells; a2) preparing an immune cell pyroptosis inhibitor; and A3) inhibiting the pyroptosis of the immune cells in vitro. The invention discovers that the lactobacillus rhamnosus BD4047 or the afterbiogen thereof can inhibit inflammasome activation, pyroptosis symbolic protein expression and inflammatory cytokine secretion through a TLR4-NF-kappa B-NLRP3 way for the first time. Therefore, the lactobacillus rhamnosus BD4047 or the afterbiogen of the lactobacillus rhamnosus BD4047 can be used for preparing medicines for preventing or treating the diseases related to the immune cell pyroptosis, and a new treatment choice is provided for preventing or treating the diseases related to the immune cell pyroptosis.