1385 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 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 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.

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.

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 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 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 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.

The invention particularly relates to application of a ganoderma lucidum exosome or a composition thereof in preparation of an anti-breast cancer product. The invention proves that the ganoderma lucidum exosome can be taken by breast cancer cells and exerts in-vitro activity of inhibiting proliferation and migration of the breast cancer cells and hindering repair of the breast cancer tumor cells, and in an in-vivo disease model, the ganoderma lucidum exosome also exerts the toxicity of the breast cancer tumor cells and effectively inhibits the process of the breast cancer. The research conclusion of the invention provides a development direction of taking the ganoderma lucidum exosome as an anti-breast cancer active component, and the ganoderma lucidum exosome has a good development prospect.

The present invention belongs to the technical field of optimized coding gene, and discloses a recombinant human type IV collagen, a preparation method and an application thereof. The amino acid sequence thereof is shown as SEQ ID No.1. The collagen provided by the present invention has been verified by experiments to have a high yield, good cell proliferation promoting performance, no cytotoxicity, high safety, and can be widely applied in the fields of medicine, medical devices, biological materials, tissue engineering and the like.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

The invention relates to recombinant humanized collagen as well as a preparation method and application thereof, and belongs to the technical field of genetic engineering. The amino acid sequence of the recombinant humanized collagen is as shown in SEQ ID NO. 1, and the nucleotide sequence of the recombinant humanized collagen is as shown in SEQ ID NO. 2. According to the present invention, the effective sequence of the human VII type collagen is selected to construct and express the recombinant humanized collagen HF3, and the recombinant humanized collagen HF3 has characteristics of no cytotoxicity and good safety, and can effectively improve the skin epidermis and dermis structure and provide the anti-oxidation effect when the recombinant humanized collagen HF3 is applied to the skin care product so as to achieve the effects of skin repairing, skin whitening, skin whitening, skin whitening and skin care. Therefore, the traditional Chinese medicine composition has a good application prospect.

Herein are antibodies or antigen-binding fragments specifically binding to GPRC5D. Additionally, monovalent antibodies or antigen-binding fragments specifically binding to GPRC5D are also included. The Fc region of these antibodies contains K248E and T437R mutations (designated as "RE mutations") per the EU numbering system. The described antibodies, expressed in host cells that lack fucosylation capabilities, exhibit enhanced antibody¬ dependent cellular cytotoxicity (ADCC) and enhanced complement-dependent cytotoxicity (CDC).

Novel multispecific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity, were discovered. Since the molecules of the present invention show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce novel pharmaceutical compositions for treating or preventing various cancers.

The invention belongs to the technical field of biological medicine, and particularly relates to application of anethomycin in preparation of medicine for inhibiting cysteine protease activity. The invention discovers that anethomycin has the function of inhibiting the activity of virus cysteine protease, especially 3C or 3CL protease, for the first time. Molecular docking proves that anethomycin can effectively bind to the catalytic activity center of Senecavirus (SVA) 3C protease. An in-vitro FRET enzyme activity experiment proves that the inhibition rate of 50 [mu] M of anethomycin on SVA 3C protease reaches up to 88.5%. Cellular level experiments show that the anethomycin can significantly inhibit replication of SVA viruses, shows broad-spectrum antiviral activity on various viruses such as encephalomyocarditis viruses (EMCV), porcine reproductive and respiratory syndrome viruses (PRRSV) and porcine deltacoronaviruses (PDCoV), and is low in cytotoxicity and high in selectivity index (SI).

The invention discloses a method for treating chicken chronic respiratory diseases by using MG-sEV-miRNA-200, and belongs to the technical field of exosomes, and the method comprises the following steps: step 1, constructing an MG infected cell model, and carrying out fluorescence quantitative analysis on gga-miR-200a-3p in cells / exosomes in different time periods of infection; step 2, carrying out overexpression on the miR-200 in the ACE II cells, and extracting an exosome (MG-sEV-miRNA-200) rich in the miR-200; step 3, constructing a cell model for exosome treatment, and carrying out RNA-seq sequencing to identify an exosome treatment target and a pathway rich in gga-miR-200a-3p; step 4, constructing a chick embryo model infected by MG, and injecting MG-sEV-miRNA-200 to intervene in respiratory diseases caused by MG; 5, evaluating the curative effect; mG-sEV is taken as a medium, miRNA can be protected from being influenced by RNA enzyme activity, the gga-miR-200a-3p-rich MG-sEV has the advantages of low immunogenicity, low cytotoxicity, relatively high stability, relatively high biocompatibility and the like, and the MG-sEV rich in gga-miR-200a-3p can be used for remarkably relieving lung inflammation injury caused by MG infection and reducing the bacterium carrying amount of MG in lung tissues; the method has a wide application prospect in the treatment of chicken chronic respiratory diseases.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The invention relates to betulinic acid type saponin derivatives as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The structural general formula of the betulinic acid type saponin derivative is # imgabs0, R1 is selected from hydroxyl or-O-G, and G is monosaccharide; r2 is selected from dopamine, 5-aminovaleric acid, 4-aminobutyric acid or 3-aminopropionic acid and the like and salts thereof. The betulinic acid type saponin derivative does not show obvious cytotoxicity to THP-1 macrophages, and can obviously reduce the release of IL-6 and IL-1beta in the THP-1 macrophages induced by LPS (lipopolysaccharide). Compared with betulinic acid and positive control medicine mesalazine, the pharmaceutical composition has better anti-inflammatory activity, has the treatment effect of improving diarrhea and hemafecia of mice with colitis remarkably superior to those of betulinic acid and positive control medicine mesalazine, has the treatment effect of dermatitis superior to that of positive control medicine dexamethasone, and does not have obvious toxic or side effects such as weight loss and immunosuppression. Therefore, the betulinic acid type saponin derivative has good in-vivo and in-vitro safety and druggability.