1778 results about "Cellular Cytotoxicity" patented technology

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) another anti-cancer agent. The other anti-cancer agent can be a platinum-based doublet chemotherapy, an EGFR-targeted tyrosine kinase inhibitor, an anti-VEGF antibody, an anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibody, or any other therapy used to treat lung cancer in the art or disclosed herein.

Platinum-acridines and analogs thereof as cytotoxic agents for cancer treatment. Also provided methods of using hMATE1 (SLC47A1) as a biomarker to identify tumors that are likely to respond to the agents, and epigenetically sensitizing tumor tissue to anticancer drugs targeting this membrane transporter.

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

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 belongs to the technical field of biological medicines, and particularly discloses an epidermal growth factor-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The linker polypeptide capable of connecting the EGF and the collagen is designed and synthesized, the N end of the linker polypeptide simulates an EGF receptor structure and can be combined with the EGF, and the linker polypeptide is connected with the EGF through non-covalent Van der Waals force, so that the structure of the EGF cannot be damaged; the C terminal of the linker polypeptide is rich in lysine residues, and can be covalently crosslinked to collagen through glutamine transaminase to form EGF-linker polypeptide-collagen. The protein solution taking EGF-linker polypeptide-collagen as active ingredients is low in cytotoxicity and high in biological safety, and meanwhile, the action time of the epidermal growth factor can be remarkably prolonged. In addition, a stable repairing microenvironment can be formed on the surface of the endometrium, and the endometrium injury repairing effect is remarkably improved.

The invention discloses preparation and application of bionic cerium-based polyphenol nano-enzyme for treating rheumatoid arthritis, and belongs to the field of medical preparations. The method comprises the following steps: respectively complexing cerium ions and tannic acid or epicatechin gallate to prepare cerium-based polyphenol nano-enzyme, and then preparing the cerium-based polyphenol nano-enzyme wrapped by a macrophage membrane. And loading the cerium-based polyphenol nano-enzyme wrapped by the macrophage membrane into the hydrogel to prepare the hyaluronic acid-based hydrogel. The cerium-based polyphenol nano-enzyme and the hyaluronic acid-based hydrogel are characterized, it is verified that the cerium-based polyphenol nano-enzyme and the hyaluronic acid-based hydrogel are successfully synthesized, the particle size of CeTA is about 22 nm, the particle size of M-CeTA is increased to 273 nm, the particle size of CeECG is about 95 nm, and the particle size of M-CeECG is increased to 292 nm. In-vitro experiments prove that the M-CeTA and the M-CeECG do not show obvious cytotoxicity when being less than 80 mu g / mL, and have an obvious inhibition effect on expression of cell inflammatory factors on inflammatory cells.

The present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of peripheral blood mononuclear cells (PBMC) and a cancer organoid. Specifically, the present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of cytotoxic T cells differentiated from PBMC and cancer organoids. According to the method for evaluating the efficacy of an anti-cancer drug, the screening method, the efficacy evaluation system, or the screening system of the present invention, a tumor microenvironment, i.e. The form in which cancer cells are present in a living body, can be very closely reproduced. Furthermore, since PBMCs derived from normal individuals are used and differentiated into cancer patient-specific cytotoxic T cells, the burden of collecting biological samples such as blood and tissue samples from cancer patients can be reduced, and the efficacy of an anti-cancer drug can be evaluated with high accuracy.

Described herein are polypeptides and related antibodies comprising a variant Fc domain. The variant Fc domain provide for stabilized Fc:Fc interactions when the polypeptide(s), antibody or antibodies are bound to its target, antigen or antigens on the surface of a cell, thus providing for improved effector functions, such as CDC-response.

The invention discloses a label-free nano plastic and single cell interaction monitoring imaging method which comprises the following steps: placing a sensing chip attached to cells on an SPRM, and recording a cell SPR image in the interaction process of the cells on the sensing chip and nano plastic; after the cell SPR image and the cell bright field image are compared to determine the corresponding area of the single cell in the SPR image, the deformation data of the cell membrane in the interaction process of the single cell and the nano plastic are obtained according to the SPR signal intensity of the area of the single cell, and the monitoring of the interaction of the nano plastic and the single cell under the resolution of the single cell is realized. The technical support is provided for researching the binding kinetics and cytotoxicity of the nano plastic.

The invention discloses a beta-lactoglobulin fluorescent probe as well as a preparation method and application thereof, the structural formula of the probe is (C30H25N4I), the probe is combined with beta-lactoglobulin through non-covalent interaction, a fluorescence signal is triggered to be remarkably enhanced, and low-background fluorescence detection of the beta-lactoglobulin is realized. The probe has low cytotoxicity and excellent mitochondrial targeting ability, and provides a powerful tool for visualization of beta-lactoglobulin in living cells. After being combined with beta-lactoglobulin, a sample can generate obvious color change under the irradiation of an ultraviolet lamp, and the change can be used for evaluating the content of active beta-lactoglobulin in the sample, so that the rapid detection of the milk protein level in a beverage is realized. The beta-lactoglobulin fluorescent probe disclosed by the invention has a wide application prospect in the fields of biological imaging, milk protein detection, beverage quality control and the like.

The invention provides a lipid compound based on a lipoic acid derivative, a composition as well as a preparation method and application of the lipid compound. When the lipoic acid-derived lipid provided by the invention is used as a delivery carrier of a nucleic acid drug, because disulfide bonds in the compound are split under the action of glutathione in cells, the compound is degraded, so that the timely release of nucleic acid is triggered, the cytotoxicity caused by accumulation of the compound in the cells is well reduced, and the bioavailability of the nucleic acid drug is improved. The biocompatibility is good. When the lipid nanoparticle composition is used as a carrier to deliver nucleic acid drugs, the lipid nanoparticle composition has excellent delivery efficiency and excellent spleen targeting performance, and the nucleic acid drugs can be preferentially delivered to the spleen.

The present invention relates to a novel pomalidomide derivative that exhibits improved pharmacological effects compared to pomalidomide, and is used to treat brain diseases. The novel pomalidomide derivative developed in the present invention has excellent binding ability to cereblon, is almost non-cytotoxic, has low possibility of teratogenic side effects, and can regulate TNF-α expression, as well as suppress oxidative stress and has excellent in vivo pharmacokinetic stability, and shows excellent effects of improving the decrease in motor ability, which is a symptom of Parkinson's disease, and increasing the expression of tyrosine hydroxylase, which is decreased in Parkinson's disease, and can be used for the prevention or treatment of brain diseases such as Parkinson's disease.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

The invention discloses an E3 ubiquitin enzyme mutant as well as modification and a protein targeted degradation system and application thereof, and particularly relates to a series of targeted protein degradation enhanced E3 ubiquitin enzymes (Trim21-N) and a modification method thereof, the E3 ubiquitin enzymes (Trim21-N) are obtained by modifying a wild type Trim21 (wtTrim21) protein structural domain, and the E3 ubiquitin enzymes comprise Trim21-a, Trim21-b, Trim21-c, Trim21-d, Trim21-e and Trim21-f. The efficiency of degrading the target protein through the ubiquitin proteasome is remarkably improved, and the method has the characteristics of strong endogenous and exogenous universality, high specificity, ubiquitin proteasome dependence, low cytotoxicity, strong cell compatibility and the like on the degradation of the target protein. The invention provides E3 ubiquitin enzyme (Trim21-N) based on a targeted protein degradation enhancement version and an exogenous fluorescence report degradation system of the E3 ubiquitin enzyme (Trim21-N), preferably Trim21-e with the optimal degradation effect, and the E3 ubiquitin enzyme (Trim21-N) is named as delta Trim21. The invention further provides an endogenous protein degradation system based on the delta Trim21. The method has the characteristics of high specificity, rapidness and small module, so that the method can be used for researching various biological and disease mechanisms, including the fields of cell targeted therapy, cell mechanism exploration, genetic engineering and the like.

The invention belongs to the technical field of cytotoxicity intervention, and particularly relates to application of an iNOS inhibitor in preparation of a medicine for relieving cellular injury caused by toxin combined exposure. KK-1 cells serve as a research model, it is shown for the first time that MC-LR and NaNOS combined contamination can remarkably up-regulate the expression level of iNOS protein, and it is found through tests that Nos2 gene silencing can remarkably relieve tight junction damage and cell apoptosis caused by toxin combined exposure in the KK-1 cells; it is revealed for the first time that iNOS is a core target of toxin combined exposure induced cell tight junction damage and apoptosis, and the blank of toxic mechanism research in toxin combined exposure is filled. The application provides a new direction for a detoxification strategy of environmental toxin combined exposure, provides a theoretical basis for developing an iNOS-targeted inhibitor, and also provides a new target for etiological recognition, early diagnosis and prevention of related diseases caused by environmental toxin combined exposure.

Provided herein are combinations of first and second antibodies having modified Fc effector functions resulting from amino acid substitutions in the Fc region, the amino acid substitutions allow for co-dependent activation of effector functions such as CDC and / or ADCC. Also provided are combinations of first and second antibodies having agonistic activity or enhanced agonistic activity resulting from amino acid substitutions in the Fc region where the agonistic activity is co-dependent of both a first and second antibodies.

The present disclosure provides antibodies specifically targeting CD142, antibody drug conjugates, preparation and uses thereof. An antibody, or antigen-binding fragment thereof, that binds to CD142 is covalently linked to a cytotoxic payload via a linker. Antibodies, or antigen-binding fragments thereof, and antibody drug conjugates that bind to CD142 exhibit a cytotoxic effect on tumor cells.

The invention provides a hydrogen bond organic framework material, a preparation method and application of the hydrogen bond organic framework material in dopamine detection, the preparation method of the hydrogen bond organic framework material comprises the following steps: S1, dissolving 1, 3, 5-tri (4-carboxyphenyl) benzene in an organic solvent to obtain an organic solution; and S2, dropwise adding an alcohol solvent into the organic solution to react to obtain turbid liquid, and drying to obtain the hydrogen bond organic framework material. The hydrogen bond organic framework material HOF-BTB prepared by the invention is a porous material, has two-dimensional (2D) pi-pi stacked hexagonal lamellas and complex eight interpenetration, generates a one-dimensional channel in the framework, and is simple in preparation process, mild in synthesis condition, low in cost, good in biocompatibility and low in cytotoxicity; and due to rigid organic construction molecules, the compound shows excellent fluorescence performance. The HOF-BTB material has high selectivity due to differential recognition of binding sites, and can be effectively applied to detection of dopamine.

The present invention discloses a complete medium for culturing DF-1 cells, including DMEM basal medium 13.7g / L, insulin, non-essential amino acids, transferrin, glutathione, ascorbyl phosphate, sodium selenite, ethanolamine, hydrocortisone, and newborn calf serum. Wherein non-essential amino acids include glycine, alanine, proline, serine, and asparagine. A complete medium for culturing DF-1 cells provided by the present invention can well promote the proliferation of DF-1 cells, can achieve the same proliferation effect as high-concentration fetal bovine serum, and is suitable for the adherent culture of DF-1 cells; using low-concentration newborn calf serum, it is possible to greatly avoid the batch differences, unstable culture results, cytotoxicity, and high risk of carrying pathogens brought by the culture medium with high-concentration serum, narrow application range, expensive fetal bovine serum, and high culture cost; the components are simple, the culture medium preparation process is short in time consumption, the culture efficiency is high, the repeatability is good, and it is suitable for batch production.

The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which a coronavirus peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the coronavirus peptide epitope in an epitope selective / specific manner, and accordingly, for treating individuals with a coronavirus infection including long COVID. Alternatively, when the T-Cell-MP-epitope conjugate is redirected to a neoplastic cell by a targeting sequence, the redirected T-Cell-MP-epitope conjugate may be used to treat neoplasms including various cancers.

The invention discloses a preparation method and application of porcine pseudorabies virus multi-epitope polypeptide, and belongs to the technical field of veterinary biological products. The multi-epitope polypeptide comprises a cytotoxic T cell epitope, a helper T cell epitope and a linear B cell epitope; the cell epitopes are screened from key immunogenic proteins of the pseudorabies virus by using an immunoinformatics method. The porcine pseudorabies virus multi-epitope polypeptide designed by the invention is high in safety, has better antigenicity and physicochemical properties, can be efficiently expressed, and can be recognized by a pseudorabies virus specific antibody. By applying the porcine pseudorabies virus multi-epitope polypeptide, high-level specific antibodies and cellular immune response can be continuously induced to generate, strong protective efficacy is generated, and mice can be protected from death when infected with a lethal dose of porcine pseudorabies virus. Therefore, the multi-epitope polypeptide disclosed by the invention can be used as an alternative antigen of a porcine pseudorabies virus vaccine, the use of active virus is avoided, and a tool is provided for eradication of porcine pseudorabies virus.

The invention relates to a coumarin-based fluorescent probe as well as a preparation method and application thereof in the aspect of HClO detection, and belongs to the technical field of HClO detection. The invention discloses a coumarin-based fluorescent probe W (O-(3-((2-morpholinyl ethyl) carbamoyl)-2-oxo-2hydrogen-benzopyran-7-yl) dimethyl thiocarbamate) prepared on the basis of an intramolecular charge transfer (ICT) mechanism, and a preparation method of the coumarin-based fluorescent probe W. The novel lysosome targeting fluorescent probe contains coumarin as a fluorophore, a morpholine group as a targeting group and a dimethyl thiocarbamate group as a recognition group, is a novel lysosome targeting fluorescent probe, and has excellent performances of high selectivity, low detection limit, low cytotoxicity, high resolution and the like in the aspect of HClO detection; the method can be used for detecting the content of endogenous and exogenous hypochlorous acid in living cells.

The invention discloses a medicine for treating osteoarthritis, and belongs to the field of medicine, the medicine comprises a reagent capable of stimulating chondrocyte development, and the medicine L-arginine can promote expression of chondrocyte anabolic factors and reduce expression of cartilage degradation markers, so that chondrocytes are protected to a certain extent; in addition, the medicine provided by the invention has an excellent cartilage repair function, can inhibit the progress of degenerative osteoarthritis, has good biocompatibility, and has no cytotoxicity to cartilage cells.

The invention provides an ionizable lipid compound, a liposome, a lipid nanoparticle and application thereof. The ionizable lipid compound is selected from a structure as shown in a formula I in the specification. The lipid nanoparticles prepared from the ionizable lipid compound provided by the invention are uniform in particle size distribution and low in cytotoxicity, and the active substances can be specifically delivered to cells, tissues or organs in a targeting manner, so that the targeting delivery of the active substances is realized. # imgabs0 #

The invention belongs to the technical field of cytotoxicity intervention, and particularly relates to application of an inhibitor JSH-23 in preparation of a medicine for preventing and / or treating ovarian toxicity caused by environmental toxin combined exposure. Aiming at the condition that MC-LR and NaNON combined exposure can activate NF-kappa B to induce KK-1 cell nitrification stress and cause mouse ovarian dysfunction, JSH-23 is selected as an intervention agent, and it is found that after KK-1 cells are pretreated by JSH-23, NF-kappa B nuclear translocation induced by the KK-1 cells due to MC-LR and NaNON combined exposure is remarkably inhibited, iNOS protein rising induced by toxin combined exposure is remarkably reduced, and NF-kappa B nuclear translocation induced by the KK-1 cells due to NF-kappa B combined exposure is remarkably inhibited. The increase of the levels of ONOO and 3-NT of nitration stress markers is effectively relieved, which indicates that JSH-23 can participate in the nitration stress of KK-1 cells caused by combined exposure of MC-LR and NaNO2 by inhibiting NF-kappa B activation, and a foundation is laid for screening antidotes after exposure of environmental toxins.

The invention relates to the technical field of genetic engineering and biological agents, in particular to a hybrid peptide with immunoregulation and anti-oxidation functions and a preparation method and application of the hybrid peptide. The polypeptide provided by the invention has immunoregulation and antioxidation functions at the same time, and in a normal or immunosuppression state, the polypeptide can significantly improve the immunologic function of a body and reduce the damage of immunosuppression to the body; the oxidation resistance of cells and organisms can be enhanced; meanwhile, the polypeptide has the advantages of low cytotoxicity, high safety, simplicity and convenience in preparation and low cost, can be used as an ideal immunomodulator and an antioxidant, is widely applied to the fields of medicines, foods, health care, feeds, nutrition and the like of human and animals, and has very good application potential and value.

The invention relates to the field of biological medicine, in particular to a prodrug structure with ROS signal response performance and a preparation method and application thereof. The prodrug molecule with ROS signal response performance developed by the invention can quickly release living active molecules in a disease signal ROS-enriched environment, and plays a role in targeted therapy. The method has good universality, prodrug modification can be carried out on multiple molecules, four kinds of drug molecules approved to appear on the market are included, and it is verified that the solubility and biocompatibility of drugs can be improved, cytotoxicity can be reduced, and the effect of targeted therapy can be improved. Based on the structural characteristics of the molecules, the molecules can also be complexed with PVA hydrogel, and responsive controllable release of the medicine is further achieved.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

Provided in the present invention is a nitrogen-containing heterocycle-branched cationic lipid. The structure thereof is as represented by general formula (1), wherein the definition of each symbol is consistent with that described herein. The nitrogen-containing heterocycle-branched cationic lipid has a nitrogen-containing heterocycle as a branched core, an amino acid or an amino acid derivative as a linker arm, and a saturated or unsaturated hydrocarbon group as a tail chain; and has the advantages of low toxicity, low immunogenicity and high biocompatibility. In the new cationic lipid of the present invention, the electropositivity of the nitrogen on the nitrogen-containing heterocycle is delocalized to the whole ring, so that the cationic lipid shows higher transfection efficiency and lower cytotoxicity. The new cationic lipid of the present invention contains one or more biodegradable groups between the nitrogen-containing heterocycle and the hydrophobic tail, and the presence of the degradable groups enables a lipid nanoparticle (LNP) prepared from the cationic lipid to be timely degraded in the endosome, such that the problem in the prior art whereby LNPs prepared from a non-degradable lipid accumulate in the endosome and acidify the endosomal environment, thereby hindering the endosomal escape of a drug molecule (such as a nucleic acid) and thus the drug delivered into a cell not being able to function is solved.

The invention relates to the technical field of pharmaceutical preparations, and provides double-shell JAK inhibitor nanoparticles, a preparation method thereof and targeted delivery eye drops. The double-shell JAK inhibitor nanoparticle provided by the invention comprises a core, an inner shell and an outer shell, wherein the core comprises a nanostructure lipid carrier and a JAK inhibitor; the inner shell layer is a cationic polymer, and the outer shell layer is hyaluronic acid. Through the design of the positive charge inner shell layer and the negative charge outer shell layer, the dual functions of mucosa adhesion and active targeting are achieved, the surface of the nanoparticle is electronegative finally, cytotoxicity possibly caused by direct exposure of a cationic polymer is reduced, non-specific aggregation of the cationic polymer and electronegative protein in tears is avoided, and the stability of tears is improved. And the stability of the preparation is improved. The eye drops provided by the invention can obviously prolong the residence time of the JAK inhibitor on the ocular surface, enhance the cornea permeability, can actively target to ocular inflammatory cells, and have a wide application prospect.