65 results about "Cell toxicity" patented technology

This invention provides specific sequence nucleic acid molecules and their applications as PDRNs, relating to the field of biotechnology. This invention yields novel specific sequence nucleic acid molecules with deterministic sequences, stable biological activity, and stable product quality. The PDRNs with these specific sequences are non-cytotoxic, exhibit high safety, and have broad application prospects. Furthermore, this invention is the first to discover that specific sequence PDRNs, compared to extracted PDRNs, significantly promote VEGF expression and effectively repair cell damage, providing a novel skincare and repair ingredient for the cosmetics and pharmaceutical industries. This invention also provides a simple method for preparing specific sequence PDRNs, suitable for widespread application and industrial production.

Compounds (I) are provided, where R1 and R2 are H or (C1-C3)-alkyl; X is a linear methylene chain of formula —[CH2]n— with n=0, 1 or 2, or a biradical from a branched saturated (C2-C4)-alkylene chain; and A is either a C-radical from a non-aromatic polycyclic 6- to 15-membered carbocyclic ring system, or a C-radical from a polycyclic 6- to 15-membered heterocyclic ring system having one or two O, S or N; wherein the C-radicals are unsubstituted or substituted. Compounds (I) are simultaneously inhibitors of soluble epoxide hydrolase and inhibitors of glutaminyl cyclase. Besides, they reduce the levels of pro-inflammatory cytokines in LPS stimulated BV2 cells, display low cytotoxicity, and have good BBB permeability. Thus, they are useful as multitarget compounds for the prevention or treatment of Alzheimer's disease.

This invention belongs to the field of pharmaceutical technology and discloses small organic molecules for reducing copper overload toxicity and their applications. Specifically, it discloses four small organic molecules for reducing copper overload toxicity and methods for doing so. These four small organic molecules are not copper chelators and do not reduce intracellular copper levels, thus not affecting the activity of copper-related enzymes. Furthermore, these four small organic molecules are not copper ion transporters and do not transport copper into cells, thus not exacerbating the cytotoxicity of copper overload.

The application relates to a preparation method and application method of a mesenchymal stem cell protective agent composition, and relates to the technical field of stem cell treatment, in particular to a protective agent composition, a preparation technology of the protective agent composition and an application technology of the protective agent composition in mesenchymal stem cell treatment. The application solves the problems of insufficient cell stemness maintenance, complex formula or cell toxicity in the existing mesenchymal stem cell cryopreservation. The protective agent composition prepared by the preparation method comprises a deferoxamine pretreatment protective agent and a sodium lactate Ringer injection storage solution. The application method inhibits low-temperature-induced ferroptosis through DFO pretreatment, so that the mesenchymal stem cells can still maintain the multi-directional differentiation potential, the immunoregulatory function and the proliferation ability after being treated at 4 DEG C for 24-48 hours, the serum or complex nutritional ingredients do not need to be added, and the protective agent composition has the advantages of clear composition, high safety, simple operation and the like. The application is suitable for the fields of stem cell treatment, regenerative medicine, pet medical treatment and the like.

The invention belongs to the technical field of synthetic biology and fermentation engineering, and discloses an engineering bacterium for producing Indigoidine based on membrane vesicle engineering reinforced corynebacterium glutamicum and application of the engineering bacterium. According to the invention, the ncp1 gene of corynebacterium glutamicum is knocked out through a CRISPR-Cas12a gene editing technology, connection between cell walls and cell membranes is relieved, and a chassis strain of high-yield extracellular membrane vesicles (OMVs) is constructed; meanwhile, a recombinant expression vector is introduced, indigo synthetase BpsA is positioned and displayed on membrane vesicles by utilizing PorB anchoring protein, and activating enzyme Sfp is co-expressed. In fermentation production, a staged feeding and IPTG (isopropyl-beta-d-thiogalactoside) and Tween-80 dual induction strategy is adopted to promote thalli to express zymoprotein and release a large number of membrane vesicles at the same time. According to the method, the membrane vesicles are used as an extracellular microreactor, so that the'simultaneous synthesis and secretion 'of the indissolvable indigo is realized, the problems of cytotoxicity and metabolic inhibition caused by intracellular precipitation of the product are effectively solved, and the yield and extraction efficiency of the indigo are remarkably improved.

The invention belongs to the field of environmental toxicology and immunology, and particularly relates to an immunotoxicity evaluation method and application thereof. The method comprises the following steps: adding a target pollutant into a culture medium to obtain an exposure culture solution containing the target pollutant, incubating macrophages through the exposure culture solution containing the target pollutant, detecting the macrophages after incubation to obtain results of evaluation indexes, and performing immunotoxicity evaluation based on the results of the evaluation indexes, the target pollutants are chemicals or actual water samples; the evaluation indexes comprise basic cell toxicity, macrophage phagocytic ability and macrophage anti-infection ability. The invention provides a sensitive and reliable immunotoxicity evaluation system, and fills the blank of immunotoxicity evaluation of chemicals, especially raw water. The defects of a traditional concentration method are avoided through a direct exposure method, and the immunotoxicity of the water sample is reflected more truly. The established QSAR model provides a theoretical tool for predicting the immunotoxicity of novel chemicals.

The invention belongs to the field of gene engineering, and relates to a general carrier for blue-green algae genome editing based on an endogenous I-D type CRISPR-Cas system and application of the general carrier. The editing vector contains an artificial blue algae I-D type CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) expression unit (mini-CRISPR). On the basis of the general genome editing carrier, blue-green algae endogenous I-D type Cascade is guided to cut a genome target so as to realize genome editing. Exogenous Cas protein does not need to be expressed in gene editing, so that cytotoxicity is avoided; the method is simple to operate, can realize traceless gene editing, and can be used for various gene editing modes, such as gene knockout, knock-in, point mutation, large fragment knockout, endogenous plasmid elimination and the like.

The application relates to a modified hyaluronic acid antibacterial material, an antibacterial hydrogel and a preparation method and application thereof, relates to the technical field of antibacterial materials, and solves the technical problems that the existing hyaluronic acid-based antibacterial material has weak antibacterial activity, narrow antibacterial spectrum, is easy to rely on oxidation modification, and the hyaluronic acid molecular structure and biological activity are damaged, and the existing nano-silver antibacterial dressing has biological toxicity and poor cell compatibility, and the existing technology is difficult to simultaneously consider the broad-spectrum antibacterial performance, thermal stability, biological compatibility and wound repair capacity. The hyaluronic acid is grafted with quaternary ammonium salt with different quaternary ammonium salt alkyl chain lengths and quaternary ammonium degrees, a hyaluronic acid electrostatic grafting quaternary ammonium salt antibacterial material is prepared, and further crosslinking reaction is carried out on the antibacterial material, a crosslinking agent and glacial acetic acid to obtain an antibacterial hydrogel which has high efficient antibacterial activity, excellent biological compatibility and low cytotoxicity. The application can be applied to the field of hydrogel dressings.

The invention provides an application of SX-682 in preparation of a drug for resisting staphylococcus aureus infection, and the SX-682 has a CAS number of 1648843-04-2. According to the technical scheme, the novel medical application of the SX-682 is disclosed, and the SX-682 has better antibacterial activity on staphylococcus aureus and can inhibit formation of biofilms including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). The SX-682 has no significant toxicity to human cytotoxicity in the bacteriostatic concentration range, and provides key support for subsequent anti-infection application of the SX-682.

The present invention relates to a thiobenzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer, comprising the derivative as an active ingredient. The thiobenzimidazole derivative of the present invention exhibits cell toxicity by blocking the cell cycle of a cancer cell and inducing apoptosis when administered to an individual, as the derivative inhibits tubulin polymerization by being activated in the cancer cell, and, thus, the derivative can be used for prevention or treatment of cancer, desirably for prevention or treatment of triple-negative breast cancer.

The application discloses application of xanthohumol in preparation of a medicine for resisting Aeromonas hydrophila infection of aquatic animals, and the xanthohumol can inhibit the activity of aerolysin of the Aeromonas hydrophila at a sub-inhibitory concentration, has a significant inhibitory effect on cell toxicity mediated by the aerolysin of the Aeromonas hydrophila, and further constructs an animal model infected by the Aeromonas hydrophila, and finds that the treatment of the xanthohumol can significantly improve the survival rate of the infected animals. The xanthohumol is one of main components of Chinese medicine hop, belongs to isoprenyl flavonoids, has biological functions such as bacteriostasis, anticancer, antioxidation, antiviral and hypoglycemic, and has high safety, and is an ideal medicine raw material or feed additive for preventing and treating the Aeromonas hydrophila infection of the aquatic animals.

The application discloses application of a swertianol derivative in preparation of a glioma treatment drug and belongs to the technical field of medicines. The application finds that the compound has significant inhibitory activity on SF126, T98G, A172, U-87 MG, U251 and various glioma cell lines, and the activity is better than that of temozolomide, a commonly used clinical anti-glioma drug, and the compound has lower toxicity to normal brain cells. The application further provides a preparation method of the compound and a pharmaceutical composition containing the compound, and the pharmaceutical composition can be prepared into injection, tablets and various dosage forms. The application provides a new effective drug selection for the treatment of glioma, has a mature preparation process, various drug dosage forms and a wide clinical application prospect.

A calix[4]arenes of the formula (1a),wherein: Y1, Y2, Y3 and Y4 are selected from hydrogen, halogen, NO2, N3, CN, CHO, COOR′, CONR″2, NR2, triazole moiety and C1-C3-alkyl group, the C1-C3-alkyl group being optionally substituted, Z is a heterocyclic moiety which is selected from the group including of imidazole, benzimidazole, benzothiazole, benzoxazole, purine, tetrazine, oxazole, pyrazole and thiazole, the heterocyclic moiety being optionally substituted, R1 and R2 are selected from hydrogen and C1-C8-alkyl, the C1-C8-alkyl group being optionally substituted, n being an integer between 1 and 4, They exhibit high cytotoxicity against cancer cells.

The invention belongs to the technical field of nano material preparation and application, and discloses a method for liquid-phase stripping of iron oxychloride by cysteine and application. The method comprises the following steps: firstly, preparing blocky iron oxychloride through partial thermal decomposition of ferric chloride hexahydrate; and adding L-cysteine into the iron oxychloride solution, and carrying out ultrasonic treatment at 20-40kHz and 10-40 DEG C for 0.5-6 hours to finally prepare the cysteine-iron oxychloride nano material. The average size of the material is 20-200nm, and the material is strip-shaped, is rich in ferrous iron and oxygen vacancies, and has excellent peroxidase-like activity and Fenton reaction activity. The method is green, simple, convenient and low in cost. The prepared nano material can efficiently catalyze and generate active oxygen species such as hydroxyl free radicals, effectively kills drug-resistant escherichia coli and staphylococcus aureus through multiple mechanisms such as initiation of bacterial lipid peroxidation, DNA degradation and protein leakage consumption, shows good biocompatibility in a cytotoxicity test, and can be used for preparing a drug-resistant nano material. Wide application prospects are realized in the field of antibacterial preparations.

The invention discloses a precise editing method of a gamma-PGA high-yield strain based on CRISPR-Cas9n, and relates to the technical field of high-yield strains. According to the invention, a CRISPR-Cas9n double-nickase system is adopted, and adjacent DNA nicks are generated through the synergistic effect of double sgRNA, so that the non-specific cutting risk is greatly reduced; the double sgRNA targeting design is combined with a homologous recombination template, so that directional editing of key genes is realized, the homologous recombination efficiency reaches 75 + / -5%, and target modification is ensured to be stably integrated into a genome; by virtue of a PEG-mediated protoplast conversion method, the limitation of low efficiency of traditional electrotransfection is overcome, and the CRISPR carrier is rapidly removed in combination with a temperature-sensitive plasmid elimination system, so that cytotoxicity caused by continuous expression is avoided; under optimized fermentation conditions, the gamma-PGA yield of the edited strain reaches 15 + / -2g / L and is increased by 200% compared with that of the original strain.

The application discloses a FRET fluorescent probe with dual response to acetylcholinesterase and viscosity, a preparation method and application thereof, wherein the structure of the FRET fluorescent probe is shown in the following formula: The fluorescent probe is based on a fluorescence resonance energy transfer (FRET) mechanism, responds to acetylcholinesterase (AChE) at a short wave of 520 nm, and the detection limit is as low as 0.104 U / L, and responds to viscosity at a long wave of 680 nm, and the wavelength difference is as high as 160 nm, and the dual-channel response has no crosstalk. Cell toxicity test shows that the probe has good biocompatibility, and confocal fluorescence microscopic imaging experiment shows that the probe has good light stability for cells, has the ability of simultaneously monitoring the concentration change of AChE in cells and the viscosity fluctuation of cells, and is suitable for confocal fluorescence imaging for tracing the concentration change of AChE in cells and the viscosity fluctuation.

The invention discloses application of carabrone derivatives in preparation of glioma drugs, and belongs to the technical field of medicines. It is found for the first time that the compound has remarkable inhibitory activity on multiple glioma cell lines such as SF126, T98G, A172, U-87 MG and U251, the activity of the compound is superior to that of temozolomide which is a clinically common anti-glioma drug, and meanwhile the compound is low in toxicity to normal brain cells. The invention also provides a preparation method of the compound and a pharmaceutical composition containing the compound. The pharmaceutical composition can be prepared into various dosage forms such as injections, tablets and the like. The invention provides a new effective drug choice for the treatment of glioma, and has the advantages of mature preparation process, various dosage forms and wide clinical application prospect.

The invention discloses a method for chimeric expression of recombinant small RNA (Ribonucleic Acid) in escherichia coli by utilizing active tRNA (Ribonucleic Acid) and application, and the method is characterized in that target small RNA is expressed in escherichia coli by taking an active tRNA chimeric functional miRNA precursor as a bracket. In addition, the invention also discloses application of the recombinant small RNA produced by the method in preparation of a diagnostic reagent, a scientific research reagent, a prodrug, a drug, a bulk drug or a pharmaceutical composition. According to the invention, the human tRNA is used as the stent, so that the toxicity and immunogenicity are possibly lower; in addition, the active tRNA is used as a bracket, so that the effect of targeted treatment of diseases can be achieved, and a synergistic interaction effect can be achieved with carried small RNA. The cell toxicity is reduced, the expression quantity is improved, and a tRNA scaffold with activity is screened, so that the tRNA scaffold and chimeric small RNA synergistically exert a treatment effect.

The application provides a degradable small-molecule double quaternary ammonium salt with high antibacterial activity, a degradation product thereof and a synthesis and degradation method thereof, and relates to the technical field of organic small molecules. The synthesis method specifically comprises the following steps: S1, under the catalysis of an organic base, a silane compound and a halogenated alkyl alcohol compound are combined to obtain a condensation intermediate with silicon-oxygen groups and halogen atoms at both ends; S2, the intermediate obtained in the synthesis is subjected to a nucleophilic substitution reaction with a triamine compound, thereby obtaining a silicon-based small-molecule double quaternary ammonium salt. The double quaternary ammonium salt has high antibacterial capacity, the minimum inhibitory concentration of the double quaternary ammonium salt on Staphylococcus aureus can reach 0.1 mu g / mL, the minimum inhibitory concentration of the double quaternary ammonium salt on Escherichia coli can reach 5 mu g / mL, and the double quaternary ammonium salt has low toxicity on human normal cells. In addition, the double quaternary ammonium salt also has the ability of pH response and temperature response controlled degradation. The degradation product, a single quaternary ammonium salt, has almost no bactericidal effect. Thus, the bactericidal toxicity is changed from yes to no through the degradation reaction.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to application of PHA-767491 or pharmaceutically acceptable salt thereof as an H3N2 subtype swine influenza virus replication inhibitor. In-vitro cell experiments show that the GPCR small molecule compound PHA-767491 has a remarkable inhibition effect on the H3N2 subtype swine influenza virus, the median inhibitory concentration (IC50) of the GPCR small molecule compound is 6.07 M, and the median cytotoxic concentration (CC50) of the GPCR small molecule compound is greater than 200M. The inhibition rate exceeds 97% when the drug is administered when the H3N2 subtype swine influenza virus is infected and after the H3N2 subtype swine influenza virus is infected. The results show that the PHA-767491 can be used as a new drug for the H3N2 subtype swine influenza virus replication inhibitor, and the PHA-767491 is high in inhibition activity, high in safety to normal cells, easy to popularize and wide in application prospect.

The invention discloses an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC), and belongs to the technical field of biological medicine, in particular to an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC). According to the application, it is found for the first time that SGC has a specific killing effect on PRCC-TFE3 rRCC cells and has extremely low toxicity on normal kidney cells; the SGC has multiple anti-tumor action mechanisms: on one hand, the SGC is directly combined with and antagonizes a VEGFR2 receptor on a cell membrane to block autocrine signal transduction of VEGFB; on the other hand, the SGC inhibits transcription of VEGFB (vascular endothelial growth factor B) through ROS / p-STAT3 axis epigenetics; besides, the SGC can inhibit the production of lactic acid and the acylation of H3K18, and down-regulate the secretion of chemotactic factors, so that the infiltration of polymorphic myeloid-derived suppressor cells (PMN-MDSCs) in a tumor microenvironment is remarkably inhibited; in an immune sound mouse model, the SGC shows an excellent in-vivo anti-tumor effect, and a brand new targeting and immunoregulation double-effect candidate drug is provided for clinically treating the PRCC-TFE3 rRCC lacking an effective standard therapy.

The invention discloses a THPC cross-linked heart valve and a preparation method thereof. The preparation method of the THPC cross-linked heart valve comprises the following steps: performing decellularization treatment on biological tissues; soaking the biological tissue subjected to the decellularization treatment in a THPC cross-linking solution, and carrying out a cross-linking reaction; and after a preset time period, a reducing agent is adopted to terminate the cross-linking reaction and wash the biological tissue, and the THPC cross-linked heart valve is obtained. Through the mode, the preparation method of the THPC cross-linked heart valve, provided by the invention, can be used for preparing the THPC cross-linked heart valve under a mild reaction condition, so that the original characteristics of biological tissues can be reserved to the greatest extent, and various mechanical properties of the biological tissues can be improved; and the low toxicity of THPC ensures that the cross-linked material does not cause serious cytotoxic reaction and immunoreaction in the process of implanting into a human body or contacting with human tissues, so that the adhesion, proliferation and differentiation of cells on the surface of the material are facilitated, the repair and regeneration of tissues are promoted, and the safety and effectiveness of biomedical products are ensured.

The application discloses application of a small molecule inhibitor in preparation of an anti-Ebola virus infection product. The application firstly confirms the anti-Ebola virus capability of TOFA, and the cell toxicity of TOFA is small (CC50 value is 7.717 muM), and TOFA can effectively inhibit replication of Ebola pseudovirus at a low concentration (IC50 value is 1.976 muM), so that a new candidate small molecule compound for developing a novel anti-Ebola virus infection drug is provided, a new technical selection for effectively preventing a severe infectious disease is provided, and the application has a wide application prospect.

The application discloses a furan coumarin compound and application thereof in preparation of a drug for treating osteoporosis, and belongs to the technical field of drug research and development. 50 The furan coumarin compound has an IC of 37.86 nM, has no obvious cytotoxicity and systemic toxicity, can inhibit a key path of RANKL-induced osteoclast differentiation, and can be used for preparing the drug for treating osteoporosis.

This application discloses the use of artesunate in the preparation of drugs for enhancing the therapeutic effect of PARP inhibitors, belonging to the field of biomedical technology. The artesunate described in this application is a sesquiterpene lactone derivative extracted from the traditional Chinese medicine Artemisia annua. It has an inhibitory effect on the proliferation of BRCA wild-type ovarian cancer cells and low toxicity to normal human ovarian epithelial cells. This application's research found that artesunate can enhance the DNA damage and apoptosis induced by PARP inhibitors (such as olaparib, niraparib, and rucaparib), and improve the sensitivity of PARP inhibitors to BRCA wild-type ovarian cancer.

Chimeric antigen receptor-transduced T cells (CAR-T cells) show significant efficacy on some hematological malignancies. However, the CAR target is limited to a few antigens, which is primarily due to the non-tumor targeted toxicity of CAR-T cells. Although several strategies are proposed to avoid non-tumor targeted toxicity, the majority of which use complex designs including dual gene expression to achieve specificity. In this study, we have shown that switchable CAR immune cells (e.g., CAR-T cells) with tumor-targeting adapters can mitigate non-tumor-targeting toxicity against tumor antigens, due to which conventional CAR immune cells cannot target tumor antigens such as CD40 and CS1. Therefore, the switchable CAR system is a valuable tool for controlling the toxicity of CAR-T cells while keeping the treatment effect so as to realize CAR anti-tumor targeting expansion.

The invention relates to a fluorescent probe applied to hypochlorous acid detection of allergic diseases as well as a preparation method and application of the fluorescent probe, and belongs to the field of fluorescent probes. The preparation method of the probe comprises the following steps: mixing 1, 3-indandione and 6-(dimethylamino)-naphthaldehyde with an organic solvent, carrying out a condensation reaction under the catalysis of a basic catalyst and under the heating reflux condition of 60-100 DEG C, and treating after the reaction is finished to obtain the fluorescent probe with the structure shown in the formula (I). The fluorescent probe prepared by the invention is high in specificity, strong in anti-interference capability, good in selectivity to hypochlorite ions, good in cell membrane penetrability and biocompatibility, capable of entering living cells in a lossless manner and relatively low in toxicity; the hypochlorous acid concentration (chemical signal) in inflammatory cells can be detected, the viscosity change (physical microenvironment) in the inflammatory cells can also be detected, the dual-function effect is achieved, and a powerful tool is provided for studying the pathological process of allergic diseases.

The present application relates to the technical field of biological chemical industry, and particularly relates to an acid-responsive gene carrier, a construction method and application thereof.The present application provides acid-responsive supramolecular nanoparticles SNs based on star cationic polymer beta-CD-PDMAEMA and Pasp-benzoic imine-Ad host-guest interaction of adamantane modified polyaspartamide, and experimental results show that the mixing ratio (Ad / CD) of Pasp-benzoic imine-Ad and beta-CD-PDMAEMA, and the mixing ratio (N / P) of SNs and DNA can affect cell toxicity, transfection efficiency and phagocytosis efficiency, wherein the complex has high cell transfection endocytosis efficiency and stability when the N / P ratio is 20 and the Ad / CD is 2 or 4; based on this, the carrier can be used for expression, gene silencing and / or intracellular endocytosis of tobacco or other plant and animal genes, or for breeding improvement of tobacco and other plant and animal cells, or for gene therapy, and has a wide application prospect.

The present application discloses a method of delivering a protein drug into a cell, including utilization of a cationic lipid analog material. The cationic lipid analog material of the present application has an efficient intracellular delivery of a protein, and is effective for proteins of different molecular weights and charges. Moreover, the biological activity of the protein can still be maintained when the protein is delivered into the cell. At the same time, the ionizable cationic lipid analog material has low toxicity to cells and good biocompatibility, and can be used as delivery carriers for protein drugs.

The present application belongs to the field of biotechnology, and particularly relates to a kind of production alpha-ketoglutaric acid recombinant escherichia coli engineering strain and its construction method and application.The present application engineering strain A09 can realize high-efficiency catalysis to high-concentration L-glutamic acid sodium without adding any membrane breaker such as Triton X-100.Under the condition of high-intensity catalysis for 6 hours, the cell membrane structure of the bacterial cell is kept intact without obvious damage.This characteristic completely eliminates the problems such as cell toxicity, product purification complexity, cost increase and process safety reduction caused by the use of surfactant in traditional methods, realizes the perfect unity of "cell integrity" and "high catalytic efficiency", and provides an unprecedented technical solution for the large-scale, industrialized and low-cost production of alpha-ketoglutaric acid.