199 results about "DNA damage" patented technology

The invention provides a method for identifying one or more genes in a cell of a cell type which interact with, e.g., modulate the effect of, an agent, e.g., a drug. For example, an identified gene may confer resistance or sensitivity to a drug, i.e., reduces or enhances the effect of the drug. The invention also provides STK6 and TPX2 as a gene that exhibits synthetic lethal interactions with KSP encoding a kinesin-like motor protein, and methods and compositions for treatment of diseases, e.g., cancers, by modulating the expression of STK6 or TPX2 gene and / or the activity of STK6 or TPX2 gene product. The invention also provides genes involved in cellular response to DNA damage, and their therapeutic uses.

The present invention relates a method for the enumeration of in vivo gene mutation. The method utilizes differential staining of GPI-anchor deficient erythrocyte populations to distinguish between wild-type and pig-a gene mutants. Quantitative analyses can be conducted on erythrocytes and / or reticulocytes, and is based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of mutant erythrocytes or reticulcoytes relative to the number of total erythrocytes or reticulocytes can be used to assess the DNA-damaging potential of an exogenous chemical agent, the DNA-damaging potential of an exogenous physical agent, the effects of an exogenous agent which can modify endogenously-induced DNA damage, and the effects of an exogenous agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

A method of prevention / treatment of pathological consequences of DNA damage triggered by incorporation of circulating apoptotic chromatin fragments into healthy cells of individuals / patients in need therefore, said method comprising ex vivo or extra corporeal treatment of blood / plasma for removal of circulating chromatin fragments released from apoptotic cells which apoptotic chromatin fragments are capable of triggering DNA damage leading to genomic instability, senescence, apoptosis and cancerous transformation of healthy cells on being integrated into their genomes

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

The present invention relates to methods and compositions for the modulation of bacterial topoisomerase enzymes within bacterial cells. More specifically, the present invention relates to bacterial assays wherein the levels of bacterial topoisomerase enzymes or the levels of target sites within the enzymes are varied within bacterial test strains in order to screen for compounds that target, i.e., interact with the topoisomerase enzymes, causing DNA damage and hence, bacterial growth inhibition and / or cell death. The present methods and compositions are useful for the identification and characterization of novel therapeutic antibacterial compounds.

This invention relates to embodiment to a molecular beacon, methods and kits for the detection of expression of p21(Waf1 / Cip1), in response to chemotherapy. Specifically, the introduction of a phosphorothioate-modified p21-beacon by transfection in human tumor cells yields increased signal in a dose dependent manner.

The invention provides a method for identifying one or more genes in a cell of a cell type which interact with, e.g., modulate the effect of, an agent, e.g., a drug. For example, an identified gene may confer resistance or sensitivity to a drug, i.e., reduces or enhances the effect of the drug. The invention also provides STK6 and TPX2 as a gene that exhibits synthetic lethal interactions with KSP encoding a kinesin-like motor protein, and methods and compositions for treatment of diseases, e.g., cancers, by modulating the expression of STK6 or TPX2 gene and / or the activity of STK6 or TPX2 gene product. The invention also provides genes involved in cellular response to DNA damage, and their therapeutic uses.

The present invention relates to methods of assessing damage to cellular DNA including the type, frequency and / or distribution of the DNA damage in the genome. The invention further provides methods of evaluating DNA damage in a cell caused by an agent and / or event as well as methods of determining a subject's prior exposure to an agent and / or event that is known or suspected to cause DNA damage. Further provided are methods of determining whether a subject is at an increased risk for a disease or disorder as a result of cellular DNA damage.

The present invention relates to compositions and methods for reducing cell proliferation and / or promoting cell death by inhibiting Drp1. It is based, at least in part, on the discoveries that (i) Drp1 disruption-induced mitochondrial hyperfusion is functionally linked to the cell cycle regulation apparatus, so that Drp1 inhibition results in a disruption of the cell cycle and DNA aberrancies; (ii) inhibition of both Drp1 and ATR are synthetic lethal causing increased DNA damage and apoptotic cell death; and (iii) even in resistant cell lines, Drp1 inhibitor (e.g., mdivi-1) together with a second antiproliferative agent (e.g., cisplatin or carboplatin) act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

The present invention relates a method for the enumeration of eukaryotic cell micronuclei, while simultaneously acquiring cytotoxicity and mode of action information. The method utilizes differential labeling of chromatin from dead and dying cells to distinguish the chromatin from micronuclei, nuclei, and metaphase chromosomes, and differential labeling of metaphase events to provide additional information regarding cytotoxicity and genotoxic modes of action. Counting of micronuclei events relative to the number of nuclei and quantifying perturbations to the proportion of metaphase events can be used to assess the DNA-damaging potential of a chemical agent, the DNA-damaging potential of a physical agent, the effects of an agent which can modify endogenously-induced DNA damage, the effects of an agent which can modify exogenously-induced DNA damage, and genotoxic mode of action.

A preparation method of crocodile-skin collagen peptide comprises the following steps: boiling fat-free crocodile skin in a solvent; treating the boiled crocodile skin with a protease to obtain an enzymatic hydrolysate; conducting centrifugal separation on the enzymatic hydrolysate; taking supernate and drying, so as to obtain the crocodile-skin collagen peptide. The crocodile-skin collagen peptide obtained according to the prepartion method can be used as an antioxidant, a humectant, an anti-DNA damage agent, or a whitening additive in cosmetics. The preparation method is simple and convenient, is suitable for mass production, not only can improve the development added value of a crocodile product, but also can reduce environmental pollution, brings high economic value and social value.

Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

Substituted urea compounds useful in the treatment of diseases and C1-3alkyleneOR3 conditions related to DNA damage or lesions in DNA replication are disclosed formula (I), wherein X1 is null, —O—, —S—, —CH2—, or —N(R1)—; X2 is —O—, . -£>. -, or —N(R1)—,—. . Y xs 0 or S; or =y represents two hydrogen atoms attached to a common carbon atom, —W is selected from the group consisting of heteroaryl, aryl, heterocycloalkyl, cycloalkyl, and C1-6alkyl substituted with a heteroaryl. or aryl group; R6 is —C≡C—R7 or heteroaryl; R8, R9, and R10, independently, are selected from the group consisting of halo, optionally substituted C1-6alkyl, C2-6alkenyl, C2-6alkynyl, OCP3, CF3, NO2, CN, NC, N(R3)2, OR3, CO2R3, C(O)N (R3)2, C(O)R3, N(R1)COR3, N(R1)C(O)OR3, N(R8)C(O)OR3, N(R1)C(O)C1-3alkyleneC(O)R3, N(R1)C(O)C1 -3alkyleneC(O)OR3, N(R1)C(O)C1-3alkyleneOR3, N(R1)C(O)C1-3alkyleneNHC(O)OR3, N(R1)C(O)C1-3alkyleneSO2.NR3, C1-3alkyleneOR3, and SR3; Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

The present invention relates to methods for decreasing cellular DNA repair in a patient diagnosed with or suspected to have chronic lymphocytic leukemia (CLL); decreasing cellular NAD+ biosynthesis in a patient diagnosed with or suspected to have CLL; or sensitizing a patient diagnosed with or suspected to have CLL to a DNA damaging therapy. The invention relates to methods for treating a patient diagnosed with or suspected to have CLL.

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

The invention discloses a method for detecting genotoxic potential of heavy metal pollutants in soil. The method comprises the steps of 1, soil digestion; 2. preparation of microalgae cells; 3, glue spreading; 4. pyrolysis; 5. electrophoresis; 6. neutralization; 7. dyeing; and 8. DNA damage degree analysis and performing of ANOVA analysis by using statistic Origin 7.5 software. The comet image analysis is performed by adopting CASP software, the OTM (Olive Tail Moment) simultaneously reflects the DNA content and shape features in the comet in evaluation parameters and is a common index for quantifying the DNA damage degree. The method is an effective test method and can evaluate the genotoxic potential of heavy metals in the soil.

The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.

The invention discloses a micro-degraded genomic DNA methylation library building and sequencing method. By testing different library building technologies and optimizing the reaction processes, a methylation library building technology capable of detecting severely-degraded genomic DNA as low as 1 ng is established. Through testing different enzyme combinations, the end repair of the degraded DNAand the repair of a notch formed by the degradation of 3-terminal plus A and DNA double chains are realized and completed in a same reaction system; by optimizing the reaction system, the connectionof a sequencing connector in an original reaction solution is realized; after a connector biotin marker is further tested, through specific binding of biotin and streptomycin beads, the fishing of connected connector genome fragments before subsequent sulfite treatment is realized, so that the loss of target fragments before is reduced; in addition, a sulfite reaction system and the reaction timeare also established through optimization, the DNA damage in the treatment process is reduced, the methylation conversion rate is ensured, and methylation library building and sequencing of micro-degraded samples are realized.

The invention provides a mariculture wastewater discharge and disposal method. The method comprises the steps of A, conducting primary organic matter purification through reaction of mariculture wastewater flowing out of a culture pond in a biochemical pool; B, conducting primary purification and pollution discharge on mariculture wastewater obtained from the step A in a water tank; C, conducting ionization and organic matter decomposition on mariculture wastewater obtained from the step B by means of an electrocatalytic oxidation device; D, filtering out suspended pollutants in mariculture wastewater obtained from the step C by means of a filtering basin, and discharging up-to-standard mariculture wastewater. The technology is high in feasibility, economical and practical, no agentia is needed, no complicated biological purification mode is needed, equipment is simple, using is convenient, toxic and harmful substances affecting the ecological environment of a sea area including organic matter, bacteria, ammonia nitrogen, suspended matter and COD in mariculture wastewater can be effectively discharged, and mariculture wastewater which is purified to meet the discharge standard is discharged. Under the action of ionization, bacteria, viruses and algae in circulating seawater are killed due to DNA damage, and the kill ratio can be over 90%.

The invention relates to a method for carrying out enzyme-linked immunoadsorption detection on an integral zebra fish and application of the method in drugs for identifying genotoxic compounds, screening anti-tumor drugs and repairing DNA damage. On one hand, the invention can be used for evaluating the genotoxicity of the compounds including environmental compounds, drugs, cosmetics, food additives and the like, and on the other hand, the invention can be used for screening new drugs, such as the anti-tumor drugs, antioxidants, anti-aging drugs, anti-neurodegenerative disease drugs and the like. The invention has very important guiding significance on diagnosing and treating certain diseases and novel drug research and development and compound toxicity screening. By applying the zebra fish to evaluate the compound toxicity and screen the novel drugs, the advantages of low cost, low use level of samples, automatic operation and the like can be achieved, and an in vivo physiological environment of a live animal can be provided, therefore, the goals of simple and convenient evaluating and screening works, rapidness, economy, high efficiency and high flux can be achieved.

The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.

The present invention is a system and methods of establishing a Melanocyte Protection Factor (MPF), which indicates the level of protection against DNA damage to a target cell, such as the level of protection a particular sunscreen offers against UVA rays when compared to the unprotected case, i.e., no sunscreen. The present invention determines and records levels of stable melanin radicals (SMR) in a target cell. Light is applied to the target cell forming light-induced melanin radicals (LIR). The levels of SMR and intensity of LIR are measured to determine the amount of incident light reaching the target cell. Since LIR is proportional to the square root of light intensity reaching the target cell, the ratio of light reaching the target cell is defined as the MPF: MPF=UV⁢ ⁢reaching⁢ ⁢melanocytewithout⁢ ⁢sunscreenUV⁢ ⁢reaching⁢ ⁢melanocytewith⁢ ⁢sunscreen=[SMR+screenLIR+UV+screen]2[SMRcontrolLIR⁢+UV⁢ ⁢control]2

The invention discloses an enzymatic methylation library-building method. According to the method, through TET enzyme methylation treatment, DNA damage in the methylation library-building process is lowered to a certain extent, and thus the requirement for the input amount of DNA in a nucleic acid sample is lowered; besides, by further cooperating with a one-step reagent for terminal repair and Aaddition reaction, one-tube library building can be realized, and the purification step is reduced; and by further cooperating DNA ligase enhancing liquid, the connection efficiency can be improved, and the library-building quality and the sequencing quality are improved; and the method provided by the invention is low in library-building initial quantity, the DNA input amount can be as low as to1 ng, and the method is suitable for trace library building including cfDNA.

The present invention relates to methods of detecting agents that cause or may potentiate DNA damage, and to assays that may be employed in such methods. In particular, the invention relates to methods of detecting DNA damage in in vitro cultures of human cells.

The present invention discloses aryl and heteroaryl substituted urea compounds useful in the treatment of diseases and disorders associated with DNA damage or impaired DNA replication. The invention also discloses methods of making the compounds, and the use of the compounds as therapeutic agents for the treatment of, for example, cancer and other diseases characterized by defects in DNA replication, chromosome segregation or cell division.

The present invention discloses herein a synergistic composition(s) of bioactive agents for optimizing cellular health. Particularly, a synergistic bioactive composition for optimizing cellular health, wherein the composition comprising therapeutic blend of betaine of thiol histidine and sirtuin activator(s) or salts thereof present in the ratio of 1:0.5 to 1:90, along with pharmaceutically acceptable excipients. In another embodiment, the invention discloses novel synergistic nutritional composition comprising synergistic combination of bioactives L-ergothioneine and nicotinamide mononucleotide chloride present in the ratio ranges from 1:1 to 1:80. The present invention provides promising and effective nutritional composition for improving cellular health by regulating expression of transcriptional factor, pro-inflammatory cytokines, and reducing cell apoptosis, ROS level and DNA damage in the cell.

The present disclosure provides highly multiplexed base editing methods and compositions that minimize the induction of DNA damage sensors in eukaryotic cells and maintain cell viability. The disclosed base editing methods improve the survival of eukaryotic cells after large-scale genome editing. These methods are based upon the discovery that use of a dead Cas9 base editor and optimal cell conditions during and after base editing enhances cells' tolerance to and survival following thousands of edits to the genome. Optimal cell conditions after base editing include the use of a combination of small molecule factors and / or inhibitors. These methods are facilitated by the design and use of tens to hundreds to thousands of gRNAs for guiding the base editor to the target sequences. The disclosed methods are capable of inducing between ten and 300,000 edits to the genome of a eukaryotic cell. Further disclosed are pharmaceutical compositions and compositions of eukaryotic cells comprising fusion proteins and a plurality of unique gRNAs, and a combination of small molecule factors and inhibitors. Also disclosed are kits for the generation of the fusion protein-gRNA complexes described herein.

Isolated compounds and combinations of isolated compounds isolated from Scutellaria barbata D. Don are effective in the generation of reactive oxygen species, induction of DNA damage and induction of apoptosis in cancer cells. The compounds and combinations may be prepared as pharmaceutical compositions for administration to mammals, such as humans, for the treatment of solid cancers, such as epithelial cancers. Such epithelial cancers include breast cancer and ovarian cancers.

The invention relates to a preparation method?of a hot start DNA polymerase,?comprising the following steps:?obtaining a?single stranded DNA binding protein, a Taq DNA polymerasemonoclonal antibody?and?a Taq DNA polymerase; and mixing the?single stranded DNA binding protein, the Taq DNA polymerase?monoclonal antibody?and the Taq DNA polymerase in accordance with?aproportion. The contents of the?single stranded DNA binding protein, the Taq DNA polymerasemonoclonal antibody?and the Taq DNA polymerase are all 20-40%?respectively. The invention also relates to the hot start DNA polymerase prepared by the above method and an application thereof. The hot start DNA polymerase provided by the invention can also be used to solve problems which appear easily in hot start PCR technology such as DNA damage, product contamination?and bad effect of hot start caused by incomplete sealing.

The invention relates to the technical field of biomedicine engineering and provides application of a reagent for inhibiting or down-regulating expression of a GTSE1 gene in preparation of a tumor radiotherapy sensitization drug, particularly application in preparation of a lung cancer radiotherapy sensitization drug. Experiments prove that GTSE1 knockdown promotes DNA damage of exposure to lung cancer cells, increases the radiosensitivity of three lung censer cells significantly and increases the apoptosis rate of the three lung cancer cells after exposure significantly with the increase of an exposure dose, and the cell survival rate of the three lung cancer cells is obviously lower than that of a normal lung cancer cell group. Therefore, the application provides a new exploration for improving the sensitivity of radiotherapy, contributes to radiotherapy sensitivity of malignant tumor and has certain clinical application prospects.