191 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 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).

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 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 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.

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.

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.

The invention relates to an application of a dasatinib and quercetin pharmaceutical composition in preparation of a medicine for improving the outcome of elderly adverse pregnancy, belongs to the technical field of biological medicines, and particularly discloses an application of the dasatinib and quercetin pharmaceutical composition. The technical problem of placenta dysfunction caused by elderly pregnancy is solved. The dasatinib and the quercetin form the pharmaceutical composition, so that the autophagy activity of trophoblasts is promoted, DNA (deoxyribonucleic acid) damaged cells are eliminated, the adverse pregnancy outcome caused by the elderly is remarkably improved, the embryo absorption rate is reduced by about 10%, and the weight of a fetus is increased by about 20mg. The invention provides a new targeted intervention strategy for the outcome of elderly adverse pregnancy.

The present invention addresses the problem of developing a drug for inhibiting the DNA damage restoration mechanism in a cancer which does not have a mutation in BRCA 1 / 2 and in which homologous recombination repair functions normally.　The inventors of the present invention have clarified that cell death can be induced by inhibiting PARP functions and mitochondrial respiration functions in cells, and indicated that the problem can be solved. In other words, the present invention provides: a method for inducing cell death by inhibiting PARP functions and mitochondrial respiration functions in cells; and a pharmaceutical composition for treating cancer, the pharmaceutical composition containing a PARP inhibitor and a mitochondrial respiration inhibitor.

The application belongs to the technical field of biological medicine, and particularly relates to application of calcium chelator BAPTA and a pharmaceutical composition. The calcium chelator BAPTA delays aging of lung fibroblasts and lung tissues by eliminating calcium accumulation in lung fibroblasts, reducing accumulation of reactive oxygen species ROS (ROS) in lung fibroblasts, DNA damage, and release of inflammatory factors. The calcium chelator BAPTA ultimately realizes the function of treating pulmonary fibrosis by inhibiting weight loss, lung tissue inflammatory cell infiltration, lung collagen deposition, and expression of fibrosis markers. The application provides a new drug source for delaying aging of lung fibroblasts and lung tissues and studying occurrence and development of pulmonary fibrosis. The drug is safe and reliable, has strong pharmacological action, small side effects, and definite curative effect.

The invention discloses application of rehmannia D in preparation of a product for preventing and / or treating myocardial injury, and belongs to the technical field of medicines. The myocardial injury comprises myocardial injury induced by doxorubicin (DOX), and experiments prove that the rehmannia D can obviously improve the heart function decline caused by the DOX; the myocardial cell atrophy induced by DOX can be obviously inhibited; the level of myocardial tissue fibrosis induced by DOX can be obviously inhibited; the DOX-induced myocardial tissue oxidative stress level can be obviously inhibited; in addition, DOX-induced myocardial tissue DNA damage (gamma-H2AX is taken as a marker) can be obviously inhibited. The invention proves that the rehmannia glycoside D can be used as a novel treatment means to be applied to treatment of adriamycin-induced myocardial injury, and the risk of treatment interruption or heart failure due to cardiotoxicity caused by chemotherapy of a patient can be possibly reduced, so that the disease burden of the patient and the pressure of a medical system are relieved.

The invention relates to the technical field of biological medicine, and particularly discloses application of nefenavir. Nefinavir is used for preparing a medicine for treating or preventing castration-resistant prostate cancer, and the medicine can specifically up-regulate expression of DHCR7, induce DNA damage of tumor cells and activate a cell cycle arrest pathway mediated by periodic protein of the cells so as to inhibit key biological processes such as proliferation of the tumor cells, cholesterol metabolism and the like; especially, formation and amplification of multinuclear giant cells in castration-resistant prostate cancer can be effectively inhibited by up-regulating expression of DHCR7, so that malignant progression of multinuclear giant cell mediated tumors and treatment of drug resistance are blocked. Finally, the castration-resistant prostate cancer is prevented and treated, and the technical bottlenecks that an existing castration-resistant prostate cancer treatment means is limited in curative effect, and the drug resistance and metastasis capability mediated by multinuclear giant cells are difficult to inhibit in a targeted manner are solved.

The invention belongs to the technical field of cell biology, and provides an oocyte in-vitro maturation culture solution additive and application thereof. Experimental results show that coumarin 106 can improve the retardation of the meiosis process of oocytes, reduce the form proportion of abnormal spindles of oocytes and the proportion of wrongly arranged chromosomes, recover the level of acetylated tubulin and improve the stability of microtubules; the actin expression level in the spindle body of the oocyte is improved; the conditions of wrong distribution and expression decline of mitochondria in oocytes are improved; the mitochondrial membrane potential level is improved; fluorescence signals of oocyte cortical particle and specific cortical particle protease are improved; the fertilization rate is improved; the active oxygen level and the DNA damage level in the oocytes are reduced, and the occurrence of early apoptosis in the oocytes is reduced. A culture solution prepared from the coumarin 106 can be used for promoting in-vitro maturation of oocytes.

The invention relates to the technical field of biological medicines, and discloses an application of a plant extract composition in preparation of a medicine for improving DNA damage of testicular spermatogenic cells, and the plant extract contains a herba epimedii extract and a rhizoma polygonati extract. The invention provides new application of the composition containing the herba epimedii extract and the rhizoma polygonati extract in preparation of the medicine for improving DNA damage of the testicular spermatogenic cells, the composition can remarkably improve the DNA damage of the testicular spermatogenic cells of mice caused by cyclophosphamide, recover the multiplication capacity of the mice, inhibit apoptosis of the mice and relieve spermatogenic function damage caused by cyclophosphamide, and the composition can be used for preparing the medicine for improving the DNA damage of the testicular spermatogenic cells of the mice. And the combined administration shows a synergistic effect instead of a simple additive effect, and the drug effect is obviously superior to that of any one of the epimedium extract and the rhizoma polygonati extract which are independently administered.

Compounds represented by Formula I in which A0-A2, R0-R6, L, Z and Q are defined herein. The compounds of Formula I are CHK 1 inhibitors. Therefore, the compounds can be used to treat diseases, disorders and conditions associated with continuous activation of CHK1 or with high internal DNA damage or injury during DNA replication, such as cancers.

The invention discloses an in-vitro prediction method for cell DNA damage caused by simulated radiation. According to the invention, by introducing the bionic oxidative stress regulation and control module, the simulation precision of the in-vitro model on the in-vivo physiological microenvironment is improved. The dynamic microenvironment intervention system can respond to oxidative stress changes in the radiation process in real time, the redox state of cells is closer to an in-vivo real radiation exposure scene by precisely regulating and controlling the perfusion rate of the active oxygen scavenger, experimental deviation caused by out-of-control oxidative stress level in traditional static culture is avoided, and the experimental accuracy is improved. A more reliable physiological basis is provided for subsequent damage signal detection, a dynamic regulation and control mechanism of the micro-fluidic chip can effectively correct baseline drift caused by oxidative stress fluctuation, and it is ensured that damage site space distribution data captured by the nano biosensor array has a higher signal-to-noise ratio; the influence of external environment interference on experimental data is reduced, and high-quality original data support is provided for follow-up repair trajectory tracking and neural network prediction.

The application belongs to the technical field of cell biology, and provides an oocyte in vitro maturation culture medium additive and application thereof. The experimental results of the application show that coumarin 106 can improve the meiosis process blockage of oocytes, reduce the morphological proportion of abnormal spindle and the proportion of misaligned chromosomes, restore the level of acetylated tubulin, improve microtubule stability, improve the expression level of actin in the spindle of oocytes, improve the misdistribution and expression decrease of mitochondria in oocytes, improve the level of mitochondrial membrane potential, improve the fluorescence signal of cortical granules and specific cortical granule proteases in oocytes, improve the fertilization rate, reduce the level of reactive oxygen species and DNA damage in oocytes, and reduce the occurrence of early apoptosis in oocytes. The culture medium prepared by using coumarin 106 can be used for promoting oocyte in vitro maturation.