734 results about "Inducer Cells" patented technology

The invention provides a membrane protein targeted degradation agent based on cell autophagy, the degradation agent has a first structure combined with membrane protein and also has a second structure capable of inducing cell autophagy, and the first structure is connected with the second structure. According to the membrane protein targeted degradation agent based on cell autophagy, the cell autophagy mechanism is utilized for membrane protein degradation for the first time, due to the fact that autophagy is an internal mechanism of various cells, universal induction can be achieved in various cells, and the autophagy does not depend on factors such as lysosome transporter protein and E3 ligase on cell membranes; the method has the characteristics of broad spectrum and higher universality; the design route of direct connection of the first structure and the second structure is simple and easy to realize.

The invention discloses a pharmaceutical composition for reversing pancreatic cancer gemcitabine drug resistance and application of the pharmaceutical composition, and belongs to the technical field of biological medicine. The composition comprises a generic FGFR inhibitor delatinib and gemcitabine, the concentration of the delatinib is 25 to 50 mg / kg, and the concentration of the gemcitabine is 20 to 30 mg / kg. By inhibiting an FGFR2 / FGFR3 signal channel and reducing the expression of FGFR protein in drug-resistant cells, the chemosensitivity of gemcitabine is synergistically enhanced, the apoptosis induction rate is increased by more than two times, and the synergic index (CI) is less than 1. In-vitro and nude mouse transplantation tumor experiments prove that the composition can significantly inhibit the proliferation of gemcitabine drug-resistant pancreatic cancer cells. The Gemcitabine drug-resistant pancreatic cancer drug can be used for preparing a drug for treating Gemcitabine drug-resistant pancreatic cancer with high FGFR3 expression, patients are screened through immunohistochemistry or gene sequencing, intravenous injection or oral administration is adopted, dosage forms comprise freeze-dried powder injection, capsules or tablets, and a new strategy is provided for pancreatic cancer drug-resistant treatment.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

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 provides an application of Ectoine or a derivative thereof as a human beta-defensin-2 expression promoter. According to the application, it is found for the first time that Ectoine or the derivative thereof has the effect of inducing cell expression of beta-defensin 2 (hBD-2), so that Ectoine or the derivative thereof is used for improving the defensive mechanism of skin antimicrobial.

This application relates the use of a combination of a membrane-associated tyrosine and threonine- specific CDC2-inhibitory kinase (Myt1) inhibitor with a Weel inhibitors in treating cancer or inducing cell death. The synergistic effect of the combination results in a subtherapeutic dose or a reduced dosing schedule of the Myt1 inhibitor, the Wee1 inhibitor, or both relative to a monotherapy of either the Myt1 inhibitor or the Wee1 inhibitor in isolation.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and / or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and / or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin− and / or pagP−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd−, purI−, and msbB−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and / or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and / or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The present invention relates in part to nucleic acids encoding proteins, nucleic acids containing non-canonical nucleotides, therapeutics comprising nucleic acids, methods, kits, and devices for inducing cells to express proteins, methods, kits, and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods for inducing cells to express proteins and for reprogramming and gene-editing cells using RNA are disclosed. Methods for producing cells from patient samples, cells produced using these methods, and therapeutics comprising cells produced using these methods are also disclosed.

The invention discloses DLL3 serving as a cervical neuroendocrine cancer treatment target and application of the DLL3, and belongs to the technical field of biology. The invention discloses specific expression of a DLL3 gene in cervical neuroendocrine carcinoma (NECC) and application of the DLL3 gene as a therapeutic target. Single cell sequencing and immunohistochemistry find that a DLL3-NOTCH1 / 2 signal axis is activated in NECC, and functional experiments prove that the DLL3-NOTCH1 / 2 signal axis drives malignant progression by promoting tumor proliferation and inducing T cell depletion. In addition, the invention also constructs an NECC organ-TILs co-culture model, and verifies the synergistic effect of the DLL3 targeted drug AMG757 combined with EP chemotherapy. The invention provides new target selection and theoretical basis for precise diagnosis and treatment of NECC, and has important clinical transformation value.

The invention provides a method for generating platelet-like particles based on MEG-01 cells and evaluating functions of the platelet-like particles, and belongs to the technical field of cell biology. The invention provides a method for generating PLPs by inducing MEG-01 cells. According to the method, the MEG-01 cells are differentiated into PLPs with platelet characteristics by utilizing a PMA inducer. The PLPs disclosed by the invention has characteristic surface marker expression consistent with that of natural platelets, can respond to stimulation of an activator ADP, and shows biological functional characteristics of the platelets. The method for generating PLPs is simple and economical, experimental conditions are highly controllable, and an economical, efficient and repeatable in-vitro model is provided for functional research related to platelets.

A nitrogen-containing polycyclic fused ring compound of formula I, a pharmaceutical composition thereof, a preparation method therefor and use thereof are related to the field of medicinal chemistry. The compound can be used as a selective and effective RET inhibitor. It has strong inhibitory effect on the RET gatekeeper residue mutant RET V804M, RET solvent-front residue mutant RET G810R and other clinically relevant RET mutants, as well as RET wt. The compound can also inhibit the growth of TT cell line derived from thyroid cancer and Ba / F3 cells transformed with various RET mutants, and induce the death of TT cells.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

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 provides a copper death inducer independent of a copper ion carrier and application of the copper death inducer. According to the novel copper death inducer, copper ions do not need to be additionally added in an extracellular environment. Experimental results show that under the coexistence of the ferroptosis inducer and the ferroptosis inhibitor, the treatment of the glutathione inhibitor can induce the cells to generate obvious death. The cell death can be inhibited by a specific inhibitor TTM of copper death, and has typical forms and biochemical characteristics of copper death, namely oligomerization of DLAT protein. Because copper death and copper death drugs have basic and clinical application prospects, the provided new inducer combination will provide a new small molecule induction strategy and research and application directions for copper death related research.

The invention discloses a method for in-vitro induction of T cell immune memory differentiation and application, CD8 + T memory differentiation can be enhanced by verifying in-vitro itaconic acid and derivative supplement thereof, and then anti-tumor and anti-infection immune response is enhanced after in-vivo feedback. The invention can be used in malignant tumors and infectious diseases to enhance the curative effect of T cell adoptive therapy.

The invention discloses a microneedle patch loaded with a sorafenib and copper-doped Prussian blue nano material and application of the microneedle patch in in-situ triple-negative breast cancer treatment. The sorafenib and the copper-doped Prussian blue nano material are loaded in a needle body of the microneedle patch. The microneedle patch can accurately deliver nanoparticles and sorafenib to tumor tissues, the chemical kinetics effect is enhanced through an efficient and mild photothermal therapy, the ferroptosis of triple negative breast cancer cells is enhanced through ferroptosis induced by the nanoparticles and sorafenib in cooperation with drugs, then cell death is induced, and the curative effect is improved. And a brand-new and promising treatment method is provided for in-situ triple-negative breast cancer treatment.

The invention belongs to the technical field of cell culture, and particularly relates to a method for promoting proliferation and differentiation of cervical squamous epithelial cells. The method comprises the following steps: S1, extracting and culturing primary cervix uteri squamous epithelial cells from cervix uteri tissues to obtain primary cervix uteri squamous epithelial cells; s2, adding the primary cervical squamous epithelial cells into a cell proliferation induction culture solution to induce cell proliferation, so as to obtain proliferated cervical squamous epithelial cells; and S3, uniformly mixing the proliferated cervical squamous epithelial cells with differentiation matrigel, and inducing cell differentiation by using a cell differentiation induction culture solution to obtain differentiated cervical squamous epithelial cells. Proliferation and differentiation of the cervical squamous epithelial cells are promoted by preparing a proper culture medium, and influence factors of proliferation and differentiation of the cervical squamous epithelial cells are researched by culturing the cervical squamous epithelial cells in vitro, so that the pathogenesis of cervical erosion and cervical cancer can be clarified; therefore, a direction is provided for research and development of medicines for treating cervical erosion and cervical cancer.

The invention provides application of a deacetylase inhibitor or a derivative thereof and application of a pharmaceutical composition, and belongs to the technical field of biology. The application of the deacetylase inhibitor or the pharmaceutically acceptable derivative thereof comprises the application of the deacetylase inhibitor for preparing a medicine for treating osteoporosis; wherein the deacetylase inhibitor is used for inducing histone acetylation in a cell nucleus. By inducing acetylation of histone in a cell nucleus, the differentiation direction of the bone marrow mesenchymal stem cells is accurately and efficiently controlled, and a treatment scheme for osteoporosis related diseases is developed.

The invention discloses a nanoparticle for targeted protein degradation and a degradation method. The nanoparticles can enhance uptake of cells and effectively encapsulate specific antibodies for recognizing target proteins, and meanwhile, the interferon component can induce expression of TRIM family proteins in the cells. After ingestion into the cell, the antibody released by the nanoparticle can bind to the target protein and bind to the TRIM family protein to mediate degradation of the target protein. In this process, although the TRIM family protein is continuously consumed, the TRIM family protein can be compensated by the TRIM family protein expression induced by the particle of the invention, thereby maintaining efficient degradation.

The invention relates to a quinoxalinone derivative targeting poly ADP ribose polymerase and an androgen receptor as well as a preparation method and application of the quinoxalinone derivative. The structural formula of the quinoxalinone derivative is as follows: # imgabs0 #, R1 is one of hydrogen, methoxyl, methyl and halogen, the substituent position of R1 is at least one of 5, 6, 7 and 8 sites of a quinoxalinone ring, and X is a carbon atom or a nitrogen atom. The quinoxalinone derivative provided by the invention can be used as an active photosensitizer, a PARP inhibitor and an androgen receptor antagonist and can induce cell synthesis and death, and the process can improve the oxidation state and oxygen concentration in cells and improve the hypoxic microenvironment in tumors, so that the photodynamic therapy effect is further enhanced, namely, the effect of the quinoxalinone derivative is improved. The PDT therapy and the PARP inhibitor have a synergistic effect.

The disclosure provides methods to chemically and photochemically initiate cell membrane blebbing to induce cell vesicle production, modifications thereof, and uses thereof, including for drug delivery, gene therapy, cell-free cell therapy, and molecular therapy.

The present invention discloses the use of 3,4-dihydropsoralen in the preparation of a drug for preventing or treating rheumatoid arthritis. The present invention simulates RA by constructing TNF-a-induced SW982 cells. The results show that 3,4-dihydropsoralen (DP) can downregulate the mRNA expression of inflammatory factors, chemokines, and matrix degrading enzymes through the IL-17 signaling pathway, and affect the IL-17 signaling pathway and the NF-κB signaling pathway to jointly exert an anti-inflammatory effect, thereby effectively improving rheumatoid arthritis. This provides a theoretical basis for the application of 3,4-dihydropsoralen in the clinical treatment of rheumatoid arthritis and opens up new therapeutic drugs and approaches.

The disclosure relates to nanoparticles comprising a surface-exposed immune cell binding moiety, a transposable element comprising a gene sequence flanked by inverted terminal repeats (ITRs), a nucleic acid encoding a transposase with specificity for the ITRs, and an mRNA encoding a first chimeric antigen receptor (CAR) or T-cell receptor (TCR). Methods are also described for treating a disease or disorder by administering such nanoparticles to a subject in need thereof.

The disclosure relates to growing cells, directing cells to grow into specified cell types, genetically and physically manipulating cells, and addressing one or more individual cells within a mixed cell population. Aspects of the disclosure relate to vectors useful to induce developmental changes in cells, in which those vectors have a temporal component. Vectors of the disclosure encode a controllable, temporal series of events. Once the vectors are delivered into target cells, a series of discrete and different genetic events may be induced. The disclosed methods generally provide for the temporal encoding of multiplex genetic effectors in vector format for cell state transitions.

The invention belongs to the technical field of biological medicine, discloses a novel venom polypeptide composite dendrimer as well as a preparation method and application thereof, and particularly discloses scorpion venom polypeptide, and the amino acid sequence of the scorpion venom polypeptide is FLGGSLSSIF. According to the invention, a novel scorpion venom polypeptide (marked as C9) is separated and identified, and a novel polypeptide-polyamidoamine dendritic compound G5C9 (i.e., nanoparticles) with a glioblastoma (GBM) targeting effect is constructed. Compared with the polypeptide C9, the cell uptake efficiency of the G5C9 is obviously improved. G5C9 can enter cells through endocytosis and target lysosome to destroy functions of the lysosome and mTORC1, so that nuclear translocation of TFEB is promoted, and autophagic death of the cells is induced. Therefore, the G5C9 provides a novel mode for targeting the anti-GBM in vitro and in vivo.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention relates to the technical field of medical nano-materials, and discloses a pH-responsive drug self-delivery nano-system and a preparation method and application thereof.The preparation method comprises the steps that 1, CMNPs is prepared, specifically, through an amidation reaction, the CMNPs are prepared from methotrexate and cis-aconitic anhydride; step 2, synthesizing DSPE-PEG-T12: synthesizing the DSPE-PEG-T12 by virtue of a nucleophilic addition reaction; step 3, preparing a T12 peptide modified erythrocyte membrane; and step 4, preparing T12-RBCM (at) CMNPs: modifying the T12 peptide of the targeted tumor cell transferrin receptor on an erythrocyte membrane, and coating the CMNPs to construct the nano-acquisition system T12-RBCM (at) CMNPs. According to the nano system T12-RBCM (at) CMNPs obtained by the scheme, the tumor cell uptake efficiency can be remarkably improved, cell apoptosis is induced, and proliferation is inhibited; the long-acting circulation and tumor targeting capability is realized, the tumor growth can be effectively inhibited, and the biological safety is good.

The present invention addresses the problem of providing a novel therapeutic agent for treating patients with anti NMDAR encephalitis. Patients with an anti NMDAR encephalitis have a pathogenic anti-human NR1 antibody that induces internalization of NMDAR on cell surface. As a result, NMDAR function is weakened in the patients' brain. The present inventors found that the one-armed anti-human NR1 antibody according to the present invention binds to NR1 competitively with the pathogenic anti-human NR1 antibody and inhibits the internalization of NMDAR by the pathogenic anti-human NR1 antibody to thereby exhibit therapeutic effect on anti NMDAR encephalitis. Accordingly, the present invention provides a one-armed anti-human NR1 antibody, a polynucleotide encoding the antibody, an expression vector containing the polynucleotide, a host cell transformed by the expression vector, a method for producing the antibody, a pharmaceutical composition comprising the antibody, a use of the antibody in the manufacture of the pharmaceutical composition, and a method for treating anti NMDAR encephalitis using the antibody.