613 results about "Inducer Cells" patented technology

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 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.

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 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 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 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.

The invention discloses application of an ENOPH1 gene, and relates to the technical field of biological medicines. According to the application, a key metabolic gene closely related to CRC prognosis is analyzed and identified by adopting bioinformatics, and the expression of ENOPH1 in KRAS mutant CRC tissues and cell lines is evaluated. The function of the ENOPH1 in the KRASG12D / G13D mutant CRC is verified through CCK8, a wound healing experiment, an in-vivo subcutaneous xenotransplantation tumor model and other in-vitro experiments. The result shows that the ENOPH1 is highly expressed in the KRAS mutant CRC and is subjected to MEK / ERK signal cascade regulation and control. The ENOPH1 is knocked down through shRNA, so that CRC cell proliferation, migration and tumorigenesis can be inhibited, cell apoptosis is induced, and the reaction to chemotherapy is enhanced. The application provides a new strategy and direction for treatment of colorectal cancer, has extremely high clinical application value, and can bring a better treatment effect for patients with colorectal cancer.

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.

Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Combinations of anti-ICOS antibodies and other drugs for immunooncology.

Provided in the present invention are an anti-CD155 antibody and the use thereof. Moreover, an obtained anti-CD155 chimeric antibody, a humanized anti-CD155 antibody, and a humanized affinity-matured anti-CD155 antibody can only specifically target and bind to a CD155 receptor and block the binding of CD155 to receptors TIGIT, CD96, and CD226 thereof, but also have the characteristic of not inducing the apoptosis of CD155 cells.

The present invention relates to the technical field of traditional Chinese medicine. Disclosed is use of zedoarondiol in the preparation of a drug for preventing, treating, and inhibiting lung cancer. It has been discovered that zedoarondiol can effectively induce apoptosis of A549 cells, inhibit the growth of non-small cell lung cancer, significantly inhibit the migration of A549 cells, hinder the development of non-small cell lung cancer, and simultaneously inhibit tumor growth. The present invention provides new use of zedoarondiol, expanding the medical application of zedoarondiol and offering a new technical means for lung cancer treatment.

The invention belongs to the technical field of dental pulp blood supply reconstruction, and relates to a multi-omics data fusion analysis method for EDTA (Ethylene Diamine Tetraacetic Acid) induced cell differentiation in dental pulp blood supply reconstruction. A space-time matched multi-level data basis is provided for analyzing a dynamic rule; then through standardization processing and difference analysis, screening out differential molecules which realize corresponding modes and are strongly related to phenotypes, focusing on core regulation and control candidate objects, and avoiding limitation of single omics; the method comprises the following steps: constructing a dynamic multi-layer regulation and control network comprising a transcription layer, a protein layer, a metabolism layer and interlayer connections thereof, finally identifying key nodes and modules through network topology analysis, tracking a time evolution rule in combination with dynamic trajectory analysis, and finally screening a core regulation and control module and predicting a cross-level key path. System analysis from multi-omics data to a hierarchical regulation and control mechanism and a dynamic rule is realized, and the limitation of single-dimension research is effectively broken through.

The invention discloses a carbon dot, hydrogel containing the carbon dot as well as a preparation method and application of the hydrogel, and relates to the technical field of carbon materials. The carbon dot is prepared from the following raw materials: a hydroxyl-containing flavonoid compound and epsilon-polylysine; the carbon dots contain aniline bonds formed by hydroxyl groups of the hydroxyl-containing flavonoid compounds and amino groups of the epsilon-polylysine. The carbon dot shows higher tumor cell killing property and lower normal cell toxicity than the raw material hydroxyl-containing flavonoid compound at the cellular level, can obviously induce immunogenic death of cancer cells and does not induce up-regulation of extracellular matrix collagen, and also has a better effect of regulating a tumor immune microenvironment.

The invention discloses a culture method for hypoxia culture of umbilical cord mesenchymal stem cells, which comprises the following steps: hypoxia pre-adaptive culture: inoculating umbilical cord mesenchymal stem cells in a culture medium containing bFGF (basic fibroblast growth factor), glutathione, astragalus polysaccharide and salidroside, and transferring the umbilical cord mesenchymal stem cells into a 5% O2 environment after the umbilical cord mesenchymal stem cells are preliminarily adhered to the wall in a normal oxygen environment; performing low-oxygen enrichment culture: replacing a second culture medium containing astragalus polysaccharide, salidroside, D-ribose, sodium pyruvate and D-glucose, and promoting efficient cell proliferation under 2% O2; performing function strengthening culture: adding tanshinone IIA and GSK-269962A, inducing cells to secrete VEGF under 1% O2, and maintaining high dryness. According to the method, through the synergistic effect of the three-stage gradient oxygen concentration and the specific serum-free culture medium, the cell proliferation multiple is remarkably increased, the total apoptosis rate is reduced, VEGF secretion is promoted, the multidirectional differentiation potential is reserved, the culture method is standardized in operation, the serum-free culture medium is definite in component, and a high-quality stem cell culture scheme is provided for the field of regenerative medicine.

Provided are a method for inducing differentiation of pluripotent stem cells into CD34+ hematopoietic stem / progenitor cells and a culture medium composition thereof. Provided are a method for inducing differentiation of pluripotent stem cells into CD34+ hematopoietic stem / progenitor cells or NK cells and a culture medium composition thereof. The NK cells obtained using the provided culture method have high purity and good in vitro expansion effect; the yield of iNK cells is high, and a single iPSC can differentiate into approximately 2,000 NK cells; and the obtained iNK cells highly express CD16 (over 70%). As a result, the problem of low CD16 expression in iNK cells in the prior art, which requires genetic modification methods to solve, has been addressed.

The application discloses a photosensitizer conjugate for targeted treatment of tongue squamous cell carcinoma and a preparation method and application thereof, and belongs to the technical field of biological medicines. A novel PROTAC-PDT conjugate Gef-PRO-SS-TPE is synthesized, and the compound connects a PROTAC molecule Gef-PRO targeting EGFR and an AIE photosensitizer TPE derivative through a breakable disulfide bond. On one hand, Gef-PRO can specifically degrade EGFR and block tumor cell proliferation signals; on the other hand, the TPE derivative can generate ROS under light conditions and induce cell apoptosis. More importantly, the disulfide bond can be broken in response to high concentrations of glutathione (GSH) in tumor cells, realizing controllable release of Gef-PRO and TPE molecules, so as to exert a synergistic anti-tumor effect.

A method for modifying a gene encoding or processed to a non-coding RNA molecule having no RNA silencing activity in a eukaryotic cell is disclosed, with the proviso that the eukaryotic cell is not a plant cell. The method comprises introducing a DNA editor into the eukaryotic cell, the DNA editor conferring a silence specificity of the non-coding RNA molecule for a target RNA of interest. Also disclosed is a method of modifying a gene for encoding or being processed into an RNA silencing molecule for a target RNA in a eukaryotic cell. Also disclosed are methods of preventing and treating various diseases, methods of inducing apoptosis, and methods of producing an eukaryotic non-human organism.

The application provides a kind of HLA-A24:02 APC cell preparation method and application, it is related to cell preparation technical field.The present application constructs the APC cell (K562-HLA-A24:02) that can replace HLA-A24:02 subtype DC cell, fills the blank of HLA-A24:02 subtype special engineering APC cell, and the cell can realize the antigen presentation function consistent with natural HLA-A24:02 subtype DC cell, provides special tool cell for the immune research for the HLA subtype;The present application constructs APC cell with K562 cell line as base, K562 cell can be in vitro permanent passage amplification, without repeatedly separating and inducing DC cell from human peripheral blood, reduces the use amount of peripheral blood, reduces the raw material dependence and cost of cell acquisition, while avoiding the influence of individual difference of peripheral blood source on experimental results.