112 results about "DNA damage" patented technology

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 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).

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 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 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.

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 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 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.

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.

The application discloses a detection mixture for predicting the sensitivity of PRMT5 inhibitor in treating tumors, and belongs to the technical field of biological medicine. The detection mixture comprises: a BRCA gene mutation detection agent; and / or, a DNA damage level detection agent; and / or, an IFN pathway level detection agent. The application verifies the use of the BRCA gene mutation, the DNA damage level and the IFN pathway level in the reagent for predicting the sensitivity of the PRMT5 inhibitor in preventing and / or treating solid tumors. The BRCA gene mutation detection agent, the DNA damage level detection agent or the IFN pathway level detection agent can be used for preparing the reagent for predicting the sensitivity of the PRMT5 inhibitor in preventing and / or treating solid tumors.

The invention discloses application of a reagent for detecting the expression quantity of BCKDK protein in preparation of a kit. The kit is used for at least one of detecting whether breast tissue to be detected is tumor tissue or not, evaluating stages of breast cancer, evaluating the prognosis effect of breast cancer patients and evaluating the treatment effect of breast cancer drugs or DNA damage drugs. Therefore, by detecting the expression quantity of the BCKDK protein in the to-be-detected breast tissue, whether the to-be-detected breast tissue is a tumor tissue or not can be determined, or the stages of the breast cancer of an individual from the to-be-detected breast tissue can be determined; if the breast cancer patient is in the treatment stage, the prognosis effect of the breast cancer patient or the treatment effect of the applied medicine can be determined by detecting the expression quantity of the BCKDK protein in the breast tissue to be detected.

This invention discloses a method for preserving surgical transplant materials, a combination of transplant materials, and a skull transplant material, belonging to the field of biomedical engineering and surgical transplant material processing technology. The method includes the following steps: skull harvesting and pretreatment, preparation and precooling of preservation solution, pulsed xenon light sterilization, sealing of the surgical transplant material, and cryopreservation. This application employs a pulsed xenon light sterilization method for preserving surgical transplant materials, which solves the problems of chemical sterilization potentially causing residual penetration and toxicity to bone cells, high-temperature sterilization leading to collagen denaturation and cell inactivation, and irradiation sterilization potentially causing DNA damage to cells and incurring high equipment costs. This method maintains the cell activity of the transplant material after long-term cryopreservation while improving the osteogenic induction and healing quality of the transplant material, and also has low preservation costs.

The present application relates to the technical field of biological medicine, in particular to a kind of nano-molecular probe with targeting and its preparation method and application.The plasmid of immune checkpoint corresponding receptor of stable expression tumor surface negative regulation molecule is synthesized in the present application, which is prepared into targeted nano-molecular probe with cell membrane nanocapsule of enhancing T cell activity ligand and being marked with fluorescence, and melanin nanosphere of simultaneously loading therapeutic drug.The targeted nano-molecular probe provided in the present application can be long-circulated in vivo, reduce the dosage and administration frequency of chemotherapeutic drug.It also has the advantages of improving the drug resistance of tumor site to therapeutic drug, targeting tumor DNA damage and significantly enhancing the infiltration and activation of immune cells in tumor site.

The invention discloses a traditional Chinese medicine formula with a reproductive system radiation damage protection effect as well as a preparation method and application of the traditional Chinese medicine formula. The traditional Chinese medicine formula comprises the following components in parts by mass: 15-30 parts of Chinese yam, 6-15 parts of dogwood, 10-30 parts of astragalus membranaceus, 10-30 parts of prepared rehmannia root, 10-15 parts of spina date seed, 6-15 parts of fructus psoraleae, 5-15 parts of fructus lycii and 3-9 parts of rhodiola rosea. In the traditional Chinese medicine formula provided by the invention, all the components have a synergistic effect, so that the injury of ionizing radiation to a reproductive system can be effectively relieved, the pathological change of testis tissues is remarkably improved, sperm quality parameters are improved, the apoptosis process of testis cells is inhibited, the injury caused by oxidative stress is repaired, and the DNA injury degree is reduced; therefore, the technical defects of high toxicity, high cost, insufficient protective effect on the reproductive system and the like of the existing radiation protective agent are overcome.

The invention provides lipid nanoparticles with a function of targeting M2 type tumor-associated macrophages as well as a preparation method and application of the lipid nanoparticles, and relates to the technical field of biology. According to the lipid nanoparticles with the function of targeting M2 type tumor-associated macrophages, manganese phosphate is taken as a core, so that on one hand, the lipid nanoparticles have good biocompatibility and stability, mRNA can be prevented from being degraded in a living body, and the delivery efficiency of loaded nucleic acid is improved; on the other hand, the immunologic effect can be activated, DNA damage can be induced, a cGAS-STING signal channel can be activated, and immunotherapy can be enhanced. In the lipid nanoparticles, the RP182 peptide is coupled with albumin through a disulfide bond, and the disulfide bond is broken in a tumor microenvironment to expose the RP182 peptide, so that the targeting of M2 type tumor related macrophages is realized.

The present application relates to the technical field of biological medicine, and in particular to a molecular marker of alveolar rhabdomyosarcoma and application thereof, wherein the molecular marker is circFOXO1R-loop site, and a DNA-RNA hybridization region thereof is located at chr13:41133915-41134263 of a human genome. In the present application, the circFOXO1R-loop site is verified by CUT&Tag-qPCR and DRIP-qPCR, and it is found that the circFOXO1R-loop can promote the combination of FOXO1 gene and RNAPol II and DNA damage, and it has important clinical application value for developing a reagent or kit for diagnosing alveolar rhabdomyosarcoma, a drug or a gene therapy strategy for preventing and / or treating alveolar rhabdomyosarcoma aiming at the target.

The invention provides a cosmetic composition for broad-spectrum UV protection and beautifying light-reversal light damage repair and application of the cosmetic composition, and belongs to the technical field of cosmetics. The cosmetic composition comprises a photoactivating enzyme repair factor, a hedychium coronarium root extract and a white water lily flower extract, and the composition also comprises a QUERCARE royalin. The light activating enzyme repair factor, the hedychium coronarium root extract and the white water lily flower extract are compounded, so that light injury recovery is accelerated, the efficiency of a sunscreen product is improved, after-sun adverse reactions are reduced, the sunscreen composition has soothing and whitening effects, the phogenin not only absorbs ultraviolet rays, but also converts the ultraviolet rays into beautifying light, light for skin injury is converted into light beneficial to skin from the source, and the skin care effect is improved. The anti-inflammatory and soothing effects are achieved, collagen degradation is reduced, DNA damage and mutation are inhibited, cell nucleus aging is reduced, and grease secretion is inhibited. The cosmetic composition disclosed by the invention is suitable for a skin care product with high sunscreen requirement and light aging resistance, and has instant protection and long-term repair functions.

The subject of the application is a 2'-deoxyadenosine derivative in the form of 8-(4-trifluorothio)benzylamino-2'-deoxyadenosine of formula 1 and its use as a radiosensitizer of DNA damage, which sensitizes cancer cells to ionizing radiation. The application also covers a method for obtaining 8-(4-trifluorothio)benzylamino-2'-deoxyadenosine of formula 1, characterized in that 8-bromo-2'-deoxyadenosine of formula 2 is mixed with 4-trifluorothiobenzylamine of formula 3 in a molar ratio of 1:8, in the presence of methanol, and then the mixture is heated to reflux and stirred for 72 h.

The present application relates to the use of a substance that regulates BCL11A gene and / or its encoded product in the preparation of a drug for reversing skin photoaging, wherein the skin photoaging includes skin cell aging caused by sunlight, light, etc., and the skin cells include keratinocytes, dermal fibroblasts, melanocytes. The regulation is to up-regulate the expression of BCL11A gene and / or promote the production of its encoded product. Typical clinical manifestations of the skin photoaging include wrinkles, dry skin, loose skin, dilated capillaries, uneven skin pigmentation, and skin itching. The substance that regulates BCL11A gene and / or its encoded product includes a substance that regulates BCL11A gene DNA molecules and a substance that regulates the expression of BCL11A translation product protein molecules. The reversal of skin photoaging is manifested in reducing the proportion of cells positive for aging-related beta-galactosidase staining in skin cells and reducing the expression of aging-related protein p16 and DNA damage protein gammaH2AX.