1124 results about "Suppressor cell" patented technology

The present invention provides a class of small molecule compounds for targeted degradation of a pan-KRAS protein, a preparation method therefor, and use thereof as a therapeutic agent for preventing and / or treating cancer. The compound of the present invention can effectively degrade and / or inhibit the pan-KRAS protein in cells, and can be used for preparing a drug for treating and / or preventing related diseases or disorders caused by pan-KRAS mediation.

KLRB1 binding agents (in particular anti-KLRB1 antibodies and antigen binding portion thereof) and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, INKT, peTh2, ILC2, ILC3, NK cells, and / or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer.

Disclosed in the present invention are a KRAS G12D degradation agent as well as a preparation method therefor and the use thereof. The present invention provides compounds as shown below, and / or stereoisomers, enantiomers, diastereoisomers, atropisomers, deuterated compounds, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof. The compounds provided by the present invention can effectively degrade and / or inhibit KRAS G12D protein in cells, and can be used for preparing drugs for treating and / or preventing related diseases or disorders caused by KRAS G12D mediation. G-L-E I

The invention belongs to the technical field of engineered probiotics, and particularly relates to engineered probiotics for radiosensitization and tumor metabolism regulation as well as a preparation method and application of the engineered probiotics. The engineering probiotics comprise probiotics and core-shell type metal nanoparticles which are loaded on the probiotics and are synthesized through a biological directional mineralization effect; the core of the core-shell type metal nanoparticle is a palladium element, and the outer layer of the core-shell type metal nanoparticle is a palladium element and a gold element. The engineering probiotics provided by the invention have excellent enzyme catalysis performance and can target and retain in tumor sites, and through the synergistic effect of all components in the engineering probiotics, adenosine metabolism is effectively inhibited, secretion of pro-inflammatory cytokines is enhanced, tumor microenvironment is promoted to be converted into an inflammatory state, up-regulation of immune checkpoints is inhibited, and the immune checkpoints are inhibited. And T cells are inhibited from being transformed into depletion phenotype and transformed into effect type from depletion type. After the SBRT and the immune checkpoint inhibitor are combined for use, the growth of tumors can be effectively inhibited, and the effect of enhancing immune radiotherapy is achieved.

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

The invention belongs to the technical field of immunotherapy, and particularly relates to a method for improving NK cell functions by targeted inhibition of lactylation. The invention provides a method for improving functions of NK cells by targeted inhibition of lactylation, NK cell lactic acid transporters or modification enzymes in inhibition of the lactylation process are targeted, the modification enzymes are NK cell lactylation modification enzymes Writer or lactic acid coenzyme A synthetase, NK92MI lactylation modification is blocked, so that function depletion of the NK cells is reversed, and the NK cell function is improved. The function of the NK cell can be partially reversed by inhibiting the lactic acid modification, and the expression level of effector molecules of the NK92MI cell can be recovered.

The invention provides cubilose peptide derived from cubilose and capable of promoting silk polyprotein and inhibiting expression of inflammatory factors and application of the cubilose peptide. The amino acid sequence of the peptide is as shown in at least one of SEQ ID NO: 1-5. The peptide disclosed by the invention is derived from cubilose, has the performance advantages of being small in molecular weight, promoting the expression of cell filament protein, inhibiting the expression of cell inflammatory factors and reducing the level of reactive oxygen free radicals of cells, has the biological activity of moisturizing, resisting inflammation and resisting oxidation, can be used for preparing medicines, daily chemical products, moisturizing products, anti-oxidation products or anti-inflammatory products, and is wide in application prospect.

The invention relates to the technical field of oxidation resistance, in particular to a glutamic acid derivative, a preparation method thereof and application of the glutamic acid derivative in rhythm gene regulation and oxidation resistance. The glutamic acid derivative has a structure as shown in a formula I. The glutamic acid derivative provided by the invention can up-regulate expression of CLOCK protein and Per3 protein, can inhibit ROS in cells and up-regulate expression of Nrf2, and can be applied to relieving skin problems caused by disorder of circadian rhythm. # imgabs0 #

The invention belongs to the field of biological medicine, and discloses an oral flora marker related to tongue squamous cell carcinoma (TSCC) and application of the oral flora marker. The oral cavity flora marker is Stomatobacterium longum (SBL), and the oral cavity flora marker is SBL (Stomatobacterium longum); the invention further discloses a diagnostic product of the TSCC, application of the SBL in preparation of a medicine for treating the TSCC and the medicine for treating the TSCC. The diagnosis product prepared by taking the SBL as the marker can quickly and effectively carry out early diagnosis on the TSCC so as to achieve the purposes of early discovery, early treatment and improvement of the survival rate. The medicine provided by the invention can specifically inhibit the SBL from secreting the nano extracellular vesicles so as to inhibit the expression of BRCA1 and further inhibit the expression of EXO1 and TP53BP1, so that the proliferation and cell cycle progress of TSCC cells are inhibited, and the treatment on the TSCC is realized. The medicine has good specificity and can be used for effectively treating TSCC.

KLRB1 binding agents (in particular anti-KLRB1-antibodies and antigen binding portion thereof) with increased humanness and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells, (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, iNKT, peTh2, ILC2, ILC3, NK cells, and / or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer.

The present invention relates to a nucleic acid molecule for inhibiting FXI gene expression through RNAi, and more particularly, to a nucleic acid molecule for inhibiting FXI gene expression through RNAi, the nucleic acid molecule comprises a sense sequence and an antisense sequence which are complementary to each other or is composed of a sense sequence and an antisense sequence which are complementary to each other, and the FXI inhibition rate of the nucleic acid molecule is significantly superior to that of other small nucleic acid molecules for inhibiting FXI expression through RNAi.

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

A siRNA that inhibits the expression of apolipoprotein C3 is provided. Provided are a small interfering RNA (siRNA) for inhibiting expression of APOC3 in a cell, a vector and a cell comprising a nucleotide encoding the same, and a method for treating a disease or symptom associated with expression of APOC3 in a subject using the siRNA, the vector or the cell.

A use of a GPR1 as a target in preparing an endometriosis-related diagnostic and / or therapeutic formulation, relating to the technical field of biomedicine. The present invention provides a use of a GPR1 target as a diagnostic marker in preparing a reagent or kit for diagnosing endometriosis. The endometriosis is selected from one of uterosacral ligament endometriosis, peritoneal endometriosis, rectovaginal endometriosis, deep infiltrating endometriosis, and ovarian endometriosis. The present invention discovers that the expression of the GPR1 is significantly increased in endometriosis tissues and cells, indicating that the GPR1 can be used as a diagnostic marker for endometriosis. It has been discovered in in-vitro and in-vivo models that GPR1 knockout significantly inhibits the abilities of hEM15A cells to proliferate, migrate, and invade and the growth of ectopic foci in animals, indicating that the GPR1 can be used as a new intervention target for clinically treating endometriosis.

The invention discloses a polypeptide with a whitening effect and a preparation method and application thereof.The polypeptide is obtained from hydrolyzed protein of babylonia areolata, the amino acid sequence of the polypeptide is cysteine-arginine-proline-threonine-cysteine-serine-arginine-leucine-alanine-cysteine, and the amino acid sequence of the polypeptide is cysteine-arginine-proline-threonine-cysteine-serine-arginine-leucine-alanine. The compound can obviously inhibit the generation of melanin in cells and the activity of tyrosinase in vitro, has the characteristics of low toxicity, low irritation, good stability, safety and high efficiency, and can be applied to whitening cosmetics.

The present application is directed to methods and compositions that are useful for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both in a subject. The methods include administering an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or administering a modified T cell or NK-92 cell that expresses an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or a combination of both, to a subject. For example, the antigen binding protein can bind to CD33 expressed by MDSC and / or TAM. The methods and compositions are useful for treating a disease associated with MDSC and / or TAM infiltration into a tissue or tumor.

Methods for selecting a cancer patient for immunotherapy comprise establishing a total passenger gene mutation burden from a tumor of a cancer patient, generating a background distribution for the mutational burden of the tumor, normalizing the total passenger gene mutation burden against the background distribution, and categorizing the cancer patient as an immunotherapy responder when the total passenger gene mutation burden is greater than the mean of the background distribution. When the cancer patient is an immunotherapy responder, the patient may be administered an immunotherapy regimen that comprises activation / inhibition of T cell receptors that promote T cell activation and / or prolong immune cytolytic activities.

The invention belongs to the field of biological medicine, and particularly relates to application of an anti-IGF-1R antibody or an antigen binding part thereof in weight loss. The invention provides an application of an anti-IGF-1R antibody or an antigen binding part thereof in weight loss. The anti-IGF-1R antibody or the antigen-binding portion thereof is reduced in weight by at least one of the following mechanisms: (1) inhibiting or blocking the binding between IGF-1R and IGF-1; (2) the activity of IGF-1R is reduced, weakened or neutralized; (3) inhibiting cell proliferation; (4) inhibiting fat synthesis and / or accumulation of cells; and (5) inhibiting collagen synthesis of cells. The anti-IGF-1R antibody or the antigen binding part thereof can significantly inhibit the generation and accumulation of fat and effectively inhibit the formation of collagen, and has a significant effect in the treatment of obesity and weight loss.

The invention relates to the field of biological medicine, in particular to application of a reagent for measuring or regulating the expression level of HIF-1alpha in preparation of a kit for diagnosing or gout, the kit containing the reagent and a gout prediction device. The HIF-1alpha is applied as a gout diagnosis target and a treatment target for the first time, the polarization degree of Th17 cells in an inflammatory microenvironment of a gout patient can be specifically reflected, early dynamic monitoring of gout related inflammatory activities is achieved, polarization of Th17 cells and expression of related proinflammatory factors are inhibited in a targeted mode, and a new strategy is provided for prediction, diagnosis and treatment of gout.

A composition of matter includes an antisense phosphorodiamidate morpholino oligomer (MO) that includes an MO base sequence. The MO base sequence is arranged to bind a corresponding complementary base sequence of messenger RNA (mRNA) transcribed from one or more genes for the beta subunit of human chorionic gonadotropin (hCG-β). An inventive method, for suppressing intracellular synthesis of a beta subunit of human chorionic gonadotropin (hCG-β), includes introducing such an MO into one or more cells.

The invention discloses a method for researching the influence of triptolide on the proliferation of multiple myeloma cells by regulating miR-381 / HMGB1 (High Mobility Group Box 1), and relates to the technical field of biology. Research results of the research method show that miR-381 methylation silencing in RPMI8226 cells is an important reason for promoting cell proliferation, TPL inhibits proliferation of the RPMI8226 cells by reversing a miR-381 methylation modification state, inducing and restoring expression and regulating HMGB1 genes in a targeted manner, and the research lays a theoretical basis for exploring an anti-MM action mechanism of TPL.

A preparation method for a micro-vehicle formed by enveloping siRNA-loaded polypeptide dendrimer nanogel with a cell membrane of engineered MSCs, and the use of same. The method comprises: using lentivirus-mediated gene transfection technology for constructing MSCs that highly express CXCR4 and PSGL-1; using cytokinin B for stimulating a cell to generate vesicles, and then performing centrifugation to collect the vesicles; by means of the electrostatic attraction between polypeptide dendrimer nanoparticles and siRNAs, attaching the siRNAs of IL-6 and HIF-1α into the polypeptide dendrimer nanoparticles; and by means of using a membrane extruder, enveloping the siRNA-loaded polypeptide dendrimer nanogel with the cell membrane. The prepared micro-vehicle exhibits a good property of aggregating at inflammatory blood vessel sites and a targeting function for joint cavities with rheumatoid arthritis. In addition, the loaded siRNAs can inhibit the expressions of IL-6 and HIF-1α in the joint cavities and inhibit the cell migration and angiogenesis. The micro-vehicle targeting inflammation sites has the advantages of excellent biocompatibility, ideal siRNA loading ratio, good inflammation targeting function, etc.

Described herein are methods of inhibiting an allele that contains a mutation in a cell (e.g., treating a subject with an allele that contains a mutation). The method includes delivering to the cell an antisense oligonucleotide that targets a variant allele that is in cis with the mutation (e.g., the mutation is a gain of function mutation or a dominant negative mutation), wherein the cell or subject is heterozygous for the target variant, and the antisense molecule is effective at knocking down expression the target variant allele (e.g., effective at preventing, treating, or ameliorating at least one symptom associated with the mutation). Also described herein are methods of haplotyping a cell or subject, and antisense oligonucleotides that target mutant superoxide dismutase 1 (SOD1) and other genes.

A cholesterol oxidase-loaded biological material is a nanometer material and is characterized by comprising polyacrylic acid, cobalt oxyhydroxide and cholesterol oxidase, cobalt oxyhydroxide is adsorbed on polyacrylic acid to form a compound, and cholesterol oxidase is loaded on the compound. The size of the nano-biological material is about 100-150 nm, the nano-biological material is combined with ultrasound to obtain multiple nano-enzyme activities with enhanced effects and more excellent capabilities of generating active oxygen and relieving hypoxia, and a lipid raft structure on a cell membrane is damaged by the loaded cholesterol oxidase, so that cell migration is inhibited, and the effect of resisting tumor metastasis is achieved.

The invention provides an anti-CD40 monoclonal antibody and application of the anti-CD40 monoclonal antibody. The anti-CD40 monoclonal antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) as shown in SEQ ID NOs: 1-3, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) as shown in SEQ ID NO: 4, YAS and SEQ ID NO: 5. The antibody has binding activity with in-vitro CD40 and CD40 on the cell surface, and can be competitively bound with CD40L to block binding of the antibody and CD40L so as to inhibit CD40 / CD40L signal transduction and inhibit B cell proliferation and activation, so that immune overexpression and rejection can be inhibited. Therefore, when the antibody is applied to preparation of drugs for treating immune diseases, the antibody has the advantages of high targeting specificity, high affinity, few side effects and the like, and has a great application prospect.

The invention belongs to the technical field of biology, and particularly relates to application of ginsenoside Rh1 in preparation of a product for relieving skin photoaging. It is found for the first time that the rare ginsenoside Rh1 efficiently removes ROS caused by UV and inhibits cell aging by activating a Sirt3 / Nrf2 / HO-1 pathway, and a brand new strategy is provided for developing a natural anti-photoaging preparation with repair and protection functions.

The invention belongs to the technical field of medicines, and discloses application of hyperforin in preparation of a medicine for preventing or treating amyotrophic lateral sclerosis. The hyperforin can improve the survival rate of stable transfection cell lines of amyotrophic lateral sclerosis related cell models (SOD1G93A / TDP43M337V), and the hyperforin is prompted to play a protective role in the two cell models. After the hyperforin is given, the expression levels of HO-1 and Drp1 proteins in SOD1G93A cells are increased, which indicates that the hyperforin has certain antioxidant activity; and mitochondrial division in cells can be inhibited, so that cell apoptosis is inhibited and retarded, and a protection effect is achieved. Hypericin can help to improve the SOD1G93A cell morphology and promote synaptic generation, and it is prompted that hypericin has a positive effect on maintaining normal functions of cells. In conclusion, the hyperforin plays a protective role in an SOD1G93A cell model and a TDP43M337V cell model, and the mechanism of the hyperforin is possibly related to the antioxidant activity, the mitochondrial function improvement and the like of the hyperforin.

The invention discloses a phosphorylated peptidomimetic compound and a medical application thereof. The invention provides a phosphorylated peptidomimetic compound with a novel structure. Activity research shows that the phosphorylated peptidomimetic compound has excellent Cbl-b inhibitory activity and is an effective Cbl-b inhibitor. Technicians in the field know that Cbl-b overexpression can inhibit T cell immune response, and inhibition of Cbl-b can activate killing of an immune system on tumor cells. Therefore, the phosphorylated peptidomimetic compound or pharmaceutically acceptable salts and solvates thereof provided by the invention can be developed and prepared into drugs for treating diseases (such as non-small cell lung cancer, breast cancer, prostate cancer, head and neck squamous cell carcinoma, liver cancer, pancreatic cancer, colorectal cancer, ovarian cancer and other tumors) treated or relieved by inhibiting Cbl-b (such as non-small cell lung cancer, breast cancer, prostate cancer, head and neck squamous cell carcinoma, liver cancer, pancreatic cancer, colorectal cancer, ovarian cancer and the like) the medicine prospect is promising.

The invention provides a new application of luteoloside, and luteoloside inhibits mutual combination of IGF2BP3 protein and RNA, so that protein expression of IGF2BP3 target genes c-Myc, c-Met, CDK6 and the like is reduced, cell growth is remarkably inhibited, growth of 4T1 mouse transplanted tumors is inhibited, and the luteoloside can be used as a good targeting inhibitor for treatment of IGF2BP3 high-expression tumors.

The invention discloses application of GPR1 as a target spot in preparation of endometriosis related diagnosis and / or treatment preparations, and belongs to the technical field of biological medicines. The invention provides application of a GPR1 target spot serving as a diagnostic marker in preparation of a reagent or a kit for diagnosing endometriosis. The endometriosis is selected from one of a uterus-sacral ligament type endometriosis, a peritoneal type endometriosis, a rectum-vagina type endometriosis, a deep infiltration type endometriosis and an ovarian type endometriosis. The invention discovers that the expression of GPR1 in endometriosis tissues and cells is obviously increased, which prompts that GPR1 can be used as a diagnostic marker of endometriosis. In-vitro and in-vivo models find that the knockout of GPR1 significantly inhibits the proliferation, migration and invasion ability of hEM15A cells and the growth of ectopic lesions in animals, indicating that GPR1 can be used as a new intervention target for clinical treatment of endometriosis.