251 results about "DNA damage" patented technology

The invention discloses a dynamic identification method for unusual cells before young tumors based on multi-omics data, and relates to the technical field of cell unusual identification. A dynamic correlation intensity matrix and a cumulative effect contribution matrix are constructed, a differentiation screening strategy is implemented according to individual response characteristics, and the unusual cells before young tumors are identified. And the abnormal dynamic high-fidelity identification of the young tumor pre-cells is realized. And aiming at individuals of different response types, an instant path, a long-term path or a double-path fusion strategy is respectively adopted, key behavior data is accurately screened, and the input quality is improved. According to the method, redundant interference is effectively eliminated, the simulation capability of the model on key processes such as immunosuppression and DNA damage accumulation is enhanced, the biological rationality and prediction precision of a cell state evolution sequence are remarkably improved, and the problems of model response lag, low calculation efficiency and output distortion caused by data noise in the prior art are solved; and a reliable technical support is provided for early warning and individualized intervention of precancerous lesions.

The invention provides a polypeptide compound and application thereof, and belongs to the technical field of medical or dressing preparations. According to the invention, three specific polypeptides are synergistically proportioned to obtain the polypeptide compound, and the polypeptide compound has the effect of repairing a skin basement membrane in a targeted manner. The polypeptide compound has the advantages of being small in molecular weight, high in safety, low in allergy risk and high in permeability, and has excellent repairing and anti-aging functions. Experiments prove that the polypeptide compound provided by the invention, as an active peptide raw material, can remarkably promote the production of endogenous collagen IV, VII and XVII of skin, is also beneficial to repairing skin extracellular matrix, resisting DNA damage, improving skin cycle protein, inhibiting release of inflammatory factors and the like, can effectively repair a basement membrane, and has a wide application prospect.

The present invention discloses an anti-aging composition, an anti-aging cosmetic and its preparation method and application. The anti-aging composition includes torreya grandis oil, hydrolyzed Brazil nut protein, angoloside C, carnosic acid and nanovesicle excipients. The present invention uses the above four natural plant components as anti-aging active ingredients, and from multiple perspectives such as promoting collagen synthesis, inhibiting the expression of inflammatory factors, scavenging free radicals, and repairing DNA damage, it exerts a significant anti-aging effect. The present invention encapsulates the above anti-aging active ingredients in the form of nanovesicles, which not only improves the stability of the active ingredients, but also improves the skin absorption effect of the active ingredients. The liposome nanovesicles have good compatibility with the matrix of the cosmetic, effectively solving the compatibility problem between the active ingredients and the cosmetic matrix.

The disclosure provides method of treating cancer in a patient in need thereof, comprising safely and efficaciously administering to the patient PLX038, a long lasting-PEGylated prodrug of the topoisomerase I inhibitor. The disclosure further provides combination therapies of PLX038 with inhibitors of the DNA damage response (DDR).

The invention discloses a traditional Chinese medicine composition for repairing and / or activating residual ovarian functions of an aging ovary, and a preparation method and application thereof, and relates to the technical field of biology. The traditional Chinese medicine composition is prepared from the following components: radix astragali, radix angelicae sinensis, radix ophiopogonis, radix polygonati officinalis, semen cuscutae, radix morindae officinalis, fructus rubi, rhizoma dioscoreae and folium mori. The invention further provides application of the traditional Chinese medicine composition in repairing and / or activating the residual ovarian function of the senescent ovary and improving the quality of the senescent oocyte, the traditional Chinese medicine composition can increase the volume and weight of the senescent ovary, increase the number of follicles of all levels in the senescent ovary, reduce apoptosis of granular cells in the ovary and improve the survival rate of the senescent ovary. The abnormal rate of oocytes, oxidative stress of the oocytes and DNA damage are reduced, development and maturation of residual follicles are promoted and maintained, and the traditional Chinese medicine composition has a wide application prospect.

Methods for treating or ameliorating cancer comprising administering to a mammal a NTSR-1 targeted radiopharmaceutical comprising a radionuclide chelated to a compound of formula I, and DNA damage response inhibitors.

The invention discloses a nerve cell senescence resisting medicine containing p-hydroxybenzaldehyde and application thereof.The p-hydroxybenzaldehyde is adopted as the only active substance, and the p-hydroxybenzaldehyde can reduce accumulation of DNA damage in cells, reduce activity of beta-galactosidase in the cells and slow down reduction of cell metabolic capacity, so that the nerve cell senescence resisting medicine is obtained. Therefore, the senescence of nerve cells is effectively slowed down, the cognitive function is improved, and a potential treatment effect is achieved in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

The invention discloses a dual-targeting macrophage membrane nano system and a preparation method and application thereof, and belongs to the field of biological medicine, MKA is wrapped in a macrophage membrane after AuNPs and mitochondrial targeting peptide KLA are connected. The preparation method comprises the following steps: firstly synthesizing AuNPs and modifying, and then wrapping with a macrophage membrane. In treatment, the compound can realize double targeting of tumor cells and mitochondria, enhance radiation-induced DNA damage, inhibit DDR, activate immune pathways and promote T cell infiltration, and can also consume glutathione and amplify oxidative stress to enhance immune effect, and the dose enhancement ratio of the compound in cooperation with 8GyX-rays reaches 3.1. In addition, the MKA is good in biocompatibility in vivo, long in blood circulation time, high in tumor targeting and capable of being quickly cleared through the kidney. The invention provides a new way for tumor radioimmunotherapy, and is helpful for promoting the progress of clinical tumor treatment.

Provided herein are releasable conjugates of inhibitors of DNA damage response suitable for use as therapeutic agents in the treatment of disease.

The disclosure provides method of treating cancer in a patient with ATM-deficient or ATR-deficient tumors, comprising safely and efficaciously administering to the patient PLXO38, a long lasting-PEGylated prodrug of the topoisomerase I inhibitor. The disclosure further provides combination therapies of PLXO38 with inhibitors of the DNA damage response (DDR).

The invention provides a composition for improving the permeation effect of a Campania maculata bark extract as well as a preparation method and application of the composition, and relates to the technical field of cosmetics. The invention provides an anti-aging composition for improving the permeation effect of a Campandra maculata bark extract. The anti-aging composition comprises recombinant human III type collagen, the Campandra maculata bark extract, an annona squamosa fruit extract, a Flos Magnoliae extract and a film-forming agent, the film-forming agent is composed of rhamnose and a trimethyl pentanediol / adipic acid / glycerol cross-linked polymer. The combination of the recombinant human III type collagen and the film-forming agent can strengthen hydration of cuticle, optimize the controlled release efficiency of active ingredients and broaden the permeation path, thereby forming an efficient permeation network from the skin surface to the deep layer. The combination of the Campandra mollissima bark extract, the Annona mollissima fruit extract and the Flos Magnoliae extract can construct a multi-dimensional antioxidant network, activate longevity proteins to resist saccharification and DNA damage, and comprehensively delay skin aging.

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, the inventors conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin remodelers. They revealed that the histone H3 methyltransferase SETDB1 plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 knockdown triggers decreased expression of genes related to replication and cell cycle and promotes growth arrest associated with increased markers for DNA damage and senescence entry. Using pre-clinical model, they further demonstrated that anti-SETDB1 therapy tumor growth in vivo. The inventors identify SETDB1 as a new relevant therapeutic target for the treatment of metastatic uveal melanomas. The present invention relates to a method for treating uveal melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of SETDB1 inhibitor.

The invention discloses a whole genome methylation detection method based on MeDIP-MSRE, and belongs to the technical field of epigenetics detection. According to the method, methylation immunoprecipitation sequencing and a methylation sensitive restriction enzyme technology are innovatively combined, firstly, a methylation specific antibody is used for conducting immunoprecipitation on sample DNA, and whole genome methylation fragments are enriched; then carrying out enzyme digestion on the enriched product by adopting methylation sensitive restriction enzyme, specifically removing an unmethylated DNA region, and reserving a complete methylation sequence; and finally, constructing a methylation map through high-throughput sequencing. According to the method, traditional hydrosulfite chemical conversion is not needed, DNA damage and base conversion deviation caused by the traditional hydrosulfite chemical conversion are avoided, meanwhile, high sensitivity of MeDIP and high specificity of methylation sensitive restriction endonuclease are fused, and the fidelity, sensitivity and specificity of detection are remarkably improved.

The invention discloses a whitening, anti-wrinkle, firming and soothing multi-effect composition, which is prepared from the following raw material components: nicotinamide, hydroxypropyl tetrahydropyrantriol, p-hydroxyacetophenone, glycerol, 1, 2-pentanediol, 1, 2-hexanediol, a barley extract composition, panthenol, a radix gentianae extract composition, an oat kernel extract composition and the balance of water. The barley extract, the radix gentianae extract and the oat kernel extract are added into the whitening, anti-wrinkle, firming and soothing multi-effect composition, so that melanosome can be inhibited from being transferred to the skin surface, DNA damage caused by UV is repaired, photoimmunosuppression is intervened, elastase and hyaluronidase are inhibited, and the whitening, anti-wrinkle, firming and soothing multi-effect composition has the advantages that the whitening, anti-wrinkle, firming and soothing functions are realized; the face cream prepared from the multi-effect composition for whitening, resisting wrinkles, tightening and relieving has the effects of whitening, resisting wrinkles, tightening and relieving.

The invention discloses application of cucurbitacine I in preparation of cisplatin sensitization drugs for treating ovarian cancer, and belongs to the technical field of sensitization drugs for tumor chemotherapy. CuI and CDDP have a good synergistic tumor inhibition effect on ovarian cancer, CuI may directly act on EGFR and can be combined with CDDP to significantly inhibit phosphorylation of EGFR and downstream STAT3 protein thereof, induce DNA damage and ROS accumulation, amplify a pyroptosis effect, increase release of TAAs and DAMPs, promote DC maturation and promote infiltration of CD8 + T cells and memory T cells in TIME in vivo, so that the tumor inhibition effect on ovarian cancer is improved. The expression of an inhibitory costimulatory molecule PD-1 in CD8 + T cells is reduced, the whole body immune effect is activated, and the TIME of the ovarian cancer is remarkably improved. The combined treatment strategy of CuI-CDDP controls the progress of ovarian cancer from a dual mechanism of directly inhibiting tumor cells and promoting anti-tumor immune activation.

The invention relates to the technical field of biological medicine, and provides application of a PDLIM4 inhibitor in preparation of a medicine for regulating and controlling sensitivity of gastric cancer to cis-platinum. According to the present invention, the PDLIM4 inhibitor is applied to the preparation of the drug for regulating the sensitivity of the gastric cancer cells to the cis-platinum, and the expression of the PDLIM4 in the gastric cancer cells is inhibited so as to reduce the expression of the HSP70 and promote the DNA damage signal channel, such that the sensitivity of the gastric cancer cells to the cis-platinum is enhanced;

The application discloses application of a cerium monatomic functional material in preparation of a tumor radiotherapy sensitizer. SA In the material, cerium is dispersed on a nitrogen-doped carbon carrier in a monatomic form and forms a stable coordination structure with N / O. The application determines the structure-activity relationship of the unique physical and chemical structure and multiple enzyme activities, verifies the radiotherapy sensitization effect and biological safety in and out of the body. The material has multiple enzyme activities such as simulating peroxidase and glutathione oxidase, can efficiently catalyze ROS and consume GSH, and enhances DNA damage and apoptosis induced by ionizing radiation. In vitro clone formation experiments show that the radiotherapy sensitization ratio reaches 1.38, which is better than that of CeO2 nano clusters (1.17). In vivo experiments on tumor-bearing mice prove that the material combined with radiotherapy can significantly inhibit tumor growth, prolong survival time, and has good biocompatibility. The application provides a new strategy of high efficiency and low toxicity for tumor radiotherapy sensitization, and has a good clinical application prospect.

The invention relates to the field of biological medicine, in particular to a cancer treatment medicine composition and application thereof in preparation of esophageal cancer treatment medicine. The purpose of the present invention is to provide a cancer treatment pharmaceutical composition, which comprises a therapeutically effective amount of an inhibition component, and the inhibition component is used for inhibiting the expression of ALKBH3. The pharmaceutical composition provided by the invention can effectively inhibit the expression level of the ALKBH3 gene, has an inhibiting effect on growth, proliferation and migration of esophageal cancer cells, and can also induce esophageal cancer cell DNA damage and increase the sensitivity of tumor cells to radiotherapy and chemotherapy.

The application discloses a kind of young tumor pre-cell abnormal dynamic identification method based on multi-omics data, it is related to cell abnormality identification technical field, the application is by constructing dynamic correlation strength matrix and cumulative effect contribution matrix, according to individual response characteristics Implementation of differentiating screening strategy, realize the high fidelity identification of young tumor pre-cell abnormal dynamics.For different response type individuals, respectively using instant path, long-term path or double-path fusion strategy, accurately screening key behavior data, improve input quality.The method effectively eliminates redundant interference, enhances the model's ability to simulate key processes such as immune suppression and DNA damage accumulation, significantly improves the biological rationality and prediction accuracy of cell state evolution sequence, solves the model response lag, low computational efficiency and output distortion problems caused by data noise in the prior art, and provides reliable technical support for early warning and individualized intervention of pre-tumor lesions.

The invention relates to application of an active component in preparation of a medicine for treating tumor diseases. Specifically, it is found for the first time that small-molecule isovaleric acid and the prodrug thereof can inhibit DNA homologous recombination so as to efficiently inhibit tumor growth, and isovaleric acid and the prodrug thereof can be combined with chemotherapeutic drugs for radiotherapy, DNA damage induction or DNA synthesis inhibition to generate a synergistic tumor treatment effect.

The present invention discloses a dual-targeted macrophage membrane nanosystem, its preparation method and application, which belongs to the field of biomedicine. MKA is formed by connecting AuNPs with the mitochondrial targeting peptide KLA and then encapsulating it in the macrophage membrane. During preparation, AuNPs are first synthesized and modified, and then encapsulated with the macrophage membrane. During treatment, it can dual-target tumor cells and mitochondria, enhance radiation-induced DNA damage, inhibit DDR, activate immune pathways, promote T cell infiltration, and consume glutathione and amplify oxidative stress to enhance immune effects. The dose enhancement ratio synergistic with 8GyX-rays is 3.1. In addition, MKA has good biocompatibility in the body, a long blood circulation time, high tumor targeting, and can be quickly cleared through the kidneys. This invention provides a new approach for tumor radioimmunotherapy and helps promote progress in clinical tumor treatment.

Compounds of formula (I), compounds of formula (II), and compounds of formula (III) are disclosed. Also disclosed are compounds, compositions, and methods to inhibit CUL4A expression or activity, CUL4B expression or activity, and / or DDB1 expression or activity for the treatment or prevention of cancer, DNA damage, or related conditions. In some aspects, the interaction between CUL4A and / or CUL4B and the beta-propeller B of DDB1 is disrupted with the compounds, compositions, or methods.

The present invention relates to dual payload antibody drug conjugates comprising at least one topoisomerase inhibitor and at least one DNA damage response (DDR) inhibitor, pharmaceutical compositions thereof, and uses of the antibody drug conjugates and compositions thereof in the treatment of diseases and conditions, including proliferative diseases.

The application discloses an antioxidant composition and a preparation method and application thereof, relates to the fields of antioxidant and nutritional health, and comprises a mitochondrial guardian factor module, a free radical capturing factor module, a glutathione cycle and endogenous antioxidant support module and a cell repair factor module. Through partition pretreatment and directional compounding of each module, a multi-level antioxidant synergistic system covering active oxygen source head control, free radical removal, glutathione cycle support and oxidative damage repair is constructed, oxidative stress state can be improved, cells can be protected, mitochondrial function can be improved, and DNA damage can be reduced. The composition can be used for preparing oral products, and is used for antioxidant, reducing oxidative stress damage, protecting cells, improving mitochondrial function, repairing DNA damage, protein damage and lipid damage caused by oxidative stress, and can also be used as a synergistic system to improve the stability, bioavailability and efficacy performance of other bioactive ingredients.

The invention provides an anti-leukemia pharmaceutical composition based on DNA damage activated NKT cells and application of the anti-leukemia pharmaceutical composition. A mouse leukemia model is adopted as a research object, and experimental results show that in a C1498 homotransplantation tumor C57BL / 6 immune sound mouse leukemia model, the tumor inhibition rate of a daunorubicin and alpha-galactosylceramide combined treatment group reaches 67.4%, the survival time is remarkably prolonged, and obvious toxicity is not caused; in a C57 mouse leukemia model constructed by caudal vein injection of C1498, daunorubicin and alpha-galactosylceramide are combined to treat and reverse leukemia-related hepatosplenomegaly (the weight of liver and spleen is equivalent to that of a normal group), leukocyte proliferation is inhibited, and the survival state of mice is improved. The invention provides a new direction for treatment of leukemia.

Provided is a combination of at least two of creatine, bifida ferment lysate and sechium edule fruit extract to repair DNA damage to the skin caused by light in the range 280-1400 nm. These agents are combined with UV filters and optionally one or more blue light and / or one or more IR reflector(s) in cosmetic compositions used to prevent sun-induced damage to the skin, in particular to prevent senolytic or senomorphic senescence and / or appearance of the visible signs of skin aging, in particular one or more of fine lines, wrinkles, age spots, skin dryness, thinning of the skin and loss of elasticity.

The invention belongs to the technical field of biological medicines, and particularly relates to application of long-chain non-coding RNA MILIP in colorectal cancer treatment. The invention finds that the LncRNA MILIP gene in colorectal cancer tissues and colorectal cancer cells is obviously higher than that in normal tissues and normal colorectal cell lines beside cancer; the LncRNA MILIP inhibitor can inhibit the proliferation of colorectal cancer cells and the growth of tumors by inhibiting the expression of the LncRNA MILIP gene, so that the LncRNA MILIP can be used as a treatment target of the colorectal cancer, and the LncRNA MILIP inhibitor can prevent, relieve or / and treat the colorectal cancer. The invention also finds that by inhibiting the expression of the LncRNA MILIP gene, the sensitivity of colorectal cancer cells to chemotherapeutics can be improved, and DNA damage induced by the chemotherapeutics can be promoted, so that the LncRNA MILIP inhibitor can be used for preparing a colorectal cancer chemosensitizer; moreover, the LncRNA MILIP inhibitor is combined with a chemotherapeutic drug for use, so that the growth of tumors can be remarkably inhibited.

The invention discloses a metal organic framework compound ZIF-8 modified platinum nanoparticle entrapped apoptin truncation nanometer platform and a preparation method and application thereof, the general formula of the nanometer platform is [AP (at) ZIF-8Pt], AP is an Apoptin truncation with an amino acid sequence shown as SEQ ID NO.01, ZIF-8Pt is a metal organic framework compound ZIF-8 for modifying platinum particles, and AP is loaded on ZIF-8Pt. The drug carrier has excellent drug carrying capacity and tumor acidic microenvironment response capacity, and can effectively kill liver cancer cells through the combined action of various mechanisms such as improvement of hypoxia conditions of tumor parts, promotion of DNA damage, inhibition of cell proliferation and promotion of cell apoptosis.

Provided are compositions and methods for treating Lewis Y antigen positive cancers in mammalian subjects by administering an effective amount of a radionuclide-labeled Lewis Y antigen targeting agent such as an antibody labeled with an alpha particle-emitting radionuclide such as 225Ac. The methods may further include administration of additional agents, such as radiosensitizing agents, immune checkpoint therapies, CD47 blockades, and / or DNA damage response inhibitors.

The invention belongs to the technical field of biological medicine, and particularly relates to application of REXO4 interference polypeptide in tumor treatment. It is found for the first time that the REXO4 interference polypeptide can inhibit breast cancer tumor cell proliferation, promote chemotherapy drug-induced DNA damage and improve the breast cancer chemotherapy effect, in addition, through combination of the REXO4 interference polypeptide and Olaparib, the remarkable synergistic anti-tumor effect can be shown, and the effect is better than that of single medication. The invention also finds that the REXO4 interference polypeptide can reverse the drug resistance of breast cancer to chemotherapeutic drugs, and a brand new solution is provided for overcoming the drug resistance of PARP inhibitors.