41 results about "Cell permeability" patented technology

The invention discloses an application of a compound in preparation of a medicine for protecting pulmonary vascular endothelial cells, and relates to the technical field of medicines, the application of the compound in preparation of the medicine for protecting the pulmonary vascular endothelial cells comprises the compound, and the compound is used as an active component of the medicine. The compounds are useful as inhibitors of OSM causing barrier damage to endothelial cells; the compound is used for inhibiting OSM-induced vascular endothelial cell permeability increase in drugs. The compound is used for improving the reduction of vascular epithelial cell membrane electrical impedance caused by OSM in medicines, so that the integrity of a cell barrier is protected; the compound is used for up-regulating vascular endothelial cadherin expression and reducing vascular endothelial permeability in medicines, and repairing vascular endothelial barrier damage caused by OSM. The compound can reverse the reduction of OSM-induced endothelial adhesion connexin and protect the damage of an endothelial barrier, and has a remarkable application prospect in medicines for protecting pulmonary vascular endothelial cells.

The invention relates to the technical field of biological medicines, in particular to a preparation method of an inhibitor targeting a MAX-PD-L1 promoter specific binding motif and a double-target inhibitor, through ChIP-seq and site-directed mutagenesis experiments, a core binding motif of MAX and a PD-L1 promoter, such as 5 '-CAC [GA] TG-3', is defined, it is ensured that the inhibitor only targets a key site of MAX-PD-L1 interaction, and the activity of the MAX-PD-L1 promoter specific binding motif is improved. The off-target effect is avoided, and a high-specificity target spot is provided for subsequent inhibitor design. The cell permeability of the DNA aptamer screened based on the specific binding motif is improved after cholesterol modification, and the affinity of the DNA aptamer is obviously higher than that of a traditional antibody. A small molecule compound virtually screened through a molecular docking model is optimized through hydrogen bond and hydrophobic interaction, and then the binding affinity with MAX is improved. After treatment with the inhibitor, the combination inhibition rate of MAX and the PD-L1 promoter is high, the transcriptional activity of PD-L1 is obviously reduced, the killing rate of T cells to tumor cells is also improved, and immune escape is effectively blocked.

The invention discloses a method and system for predicting the effect of repairing lung injury by isoliquiritigenin based on machine learning, and relates to the field of drug effect prediction.The method comprises the steps that biomarker data and historical experiment repairing effect data are obtained; on the basis of molecular structure data and biomarker data, calculating a molecular interaction force index and a cell permeability index of the isoliquiritigenin, and analyzing through a multiple regression analyzer in combination with historical experiment repair effect data to obtain a repair effect coefficient; according to the repair effect coefficient, configuring an effect confidence interval, and performing range optimization on the molecular interaction force index and the cell permeability index to obtain an optimized biological activity index; and constructing an effect prediction model based on a neural network, inputting the optimized biological activity indexes into the effect prediction model, and outputting to obtain a lung injury repair effect prediction value. The problems that the prediction precision is insufficient and the prediction is too one-sided due to the lack of comprehensive analysis on a molecular mechanism and a biomarker are solved.

The application belongs to the technical field of fluorescent probe, and particularly relates to a non-oxygen-dependent multi-mode selenium rhodamine-based photodynamic photosensitizer as well as preparation and application. In order to develop a non-oxygen-dependent and efficient photosensitizer, based on the selenium rhodamine spiro ring 'on-off' mechanism, a N-nitroso functionalized selenium rhodamine photosensitizer SeR-NO is developed, which exists in the form of lactone with closed ring in PBS, has very small cell dark toxicity and excellent cell permeability; under light, the photosensitizer can not only produce a large amount of ROS through type I and type II mechanism, but also can catalyze NADPH oxidation and Cyt c reduction in an oxygen-independent manner, therefore, SeR-NO has large phototoxicity, and can induce cell death through ferroptosis in normoxia (21% O2) and hypoxia (2% O2).

Macrocyclic peptides (MPs) are a class of compounds that have been shown to be particularly well suited for engaging difficult protein targets. However, their utility is limited by their generally poor cell permeability and bioavailability. The present disclosure reports an efficient solid-phase synthesis of novel MPs by trapping a reversible intramolecular imine linkage with a 2-carbonyl pyridine to create an imidazopyridinium (IP+)-linked ring. This chemistry is useful for the creation of macrocycles of different sizes and geometries, including head-to-side and side-to-side chain configurations. Many of the IP+-linked MPs exhibit far better passive membrane permeability than expected for "beyond Rule of 5" molecules, in some cases exceeding that of much lower molecular weight, traditional drug molecules. This chemistry has been demonstrated to be suitable for the creation of libraries of IP+-linked MPs and show that these libraries can be mined for protein ligands.

The invention discloses application of a small molecule compound in preparation of a medicine for protecting pulmonary vascular endothelial cells, and relates to the technical field of medicine, the application of the small molecule compound in preparation of the medicine for protecting the pulmonary vascular endothelial cells comprises the small molecule compound, and the small molecule compound serves as an active component of the medicine; the small molecule compound is used for inhibiting damage of OSM to an endothelial cell barrier. The medicine takes a small molecule compound as an active ingredient of the medicine and is used for inhibiting damage of OSM to an endothelial cell barrier, and the use dosage of the medicine is 1-10 [mu] M; the small molecule compound in the medicine is used for inhibiting the reduction of vascular epithelial cell VE-cadherin expression caused by OSM; the permeability of the endothelial cells is reduced, the damage to the endothelial barrier is prevented, and the obvious application prospect in the protection of the lung vascular endothelial cells is realized.

This invention discloses a near-infrared fluorescent probe for the rapid and sensitive detection of biothiols (Cys / Hcy) with a large Stokes shift targeting mitochondria. The structural formula of the fluorescent probe is shown in Formula (I). The probe of this invention not only exhibits rapid response time, high sensitivity, and selectivity to cysteine / homocysteine, but also a near-infrared emission response with a large Stokes shift (approximately 200 nm). Furthermore, this probe possesses good cell permeability and mitochondrial targeting ability, making it highly suitable for imaging and detection of Cys / Hcy in live cells.

The present disclosure provides an antimicrobial peptide (AMP) for controlling Pseudomonas syringae pv. actinidiae (PSA) and a preparation method and use thereof, belonging to the technical field of biological control. In the present disclosure, the AMP has an amino acid sequence of Trp-Trp-Lys-Leu-Leu-Arg-Lys-Leu-NH2, and has a typical amphiphilic structure. The AMP can target a cell membrane of the PSA, increasing permeabilization and dissipating a membrane potential, which leads to calcium ion leakage. The AMP also acts on intracellular targets, affects DNA functions, reduces an activity of esterases, and induces the generation of reactive oxygen species (ROS). The AMP has a minimal inhibitory concentration (MIC) of 3.13 μg / mL and a half maximal effective concentration (EC50) of 1.67 μg / mL for the PSA, showing an activity significantly higher than that of agricultural streptomycin.

The invention discloses a high-flux toxicity pre-evaluation substitution method based on an acetylcholin esterase target. By integrating an SH-SY5Y nerve cell endogenous AChE and recombinant exogenous AChE dual detection system and relying on an automatic screening system constructed by integrating core equipment such as an automatic pipetting workstation, a constant-temperature incubator and a multifunctional microplate reader, a high-flux toxicity pre-evaluation substitution method based on an AChE target is successfully established and is used for evaluating the neurotoxicity of a compound, and the method has the advantages of high sensitivity, high sensitivity, high sensitivity and the like. The method solves the limitation that a single screening method in the prior art cannot evaluate factors such as target inhibition, cell permeability and metabolic transformation at the same time, and the method is simple, convenient, rapid, high in accuracy and suitable for large-scale primary screening of the AChE inhibitor and early warning of neurotoxicity risks.

The invention provides a musk ketone-based self-emulsifying preparation, a musk ketone-decitabine self-emulsifying nano particle as well as a preparation method and application of the musk ketone-based self-emulsifying nano particle, and belongs to the technical field of preparation of the musk ketone-based self-emulsifying preparation and a decitabine preparation. The musk ketone-based self-emulsifying preparation is prepared from musk ketone, tween-80 and 1, 2-propylene glycol according to the mass ratio of 0.3 to (0.05 to 0.15) to (0.05 to 0.15). The musk ketone-based self-emulsifying preparation is a nano preparation, is clear and transparent and does not have floating oil drops, and the cell permeability of decitabine can be remarkably improved by utilizing the musk ketone-based self-emulsifying preparation. The musk keto-decitabine self-emulsifying nanoparticles can be successfully loaded with decitabine, and after the musk keto-decitabine self-emulsifying nanoparticles are incubated and cultured with cells, the cell permeability of decitabine can be remarkably improved, so that the dosage of a decitabine drug is reduced, and the musk keto-decitabine self-emulsifying nanoparticles have the potential of reducing the toxic and side effects of decitabine. The preparation method is simple to operate and suitable for industrial production.

The present disclosure relates to a composition for enhancing the cell permeability and gene correction efficiency of Cas protein and guide RNA. The currently used CRISPR-Cas-based gene correction technology has the problems of difficult intracellular injection in a complex form, unverified stability and low efficiency even after injection, and the off-target problem. In contrast, the composition for gene correction of the present disclosure can be usefully used for gene therapy due to remarkably high intracellular delivery efficiency, inhibited off-target, and ensured stability.

This invention provides a polyamplifier-based cell cryopreservation protectant and a method for preparing a polyamplifier-based cell cryopreservation solution, as well as their applications. It relates to biomedical materials technology and the field of cell cryopreservation, aiming to solve problems such as low cell recovery rates and short cryogenic storage times in existing cell cryopreservation technologies. The polyamplifier-based cell cryopreservation protectant comprises polyacrylic acid, betaine, and graphene oxide linked by chemical bonds. The mass ratio of polyacrylic acid to betaine is 10:1–2:1, and the total mass of polyacrylic acid and betaine to the mass of graphene is 1:2–10:1. The polyamplifier-based cell cryopreservation protectant provided by this invention can not only reduce cell permeability damage by regulating osmotic pressure, but also improve cryopreservation efficiency, effectively inhibit ice crystal formation and growth, and increase cell survival rate. Due to its excellent cell protection properties and good stability, this protectant can also be used in the cryopreservation of stem cells, immune cells, and other cells, possessing significant socio-economic value.

The application discloses a cutting treatment method for improving the rooting rate of Buddleja officinalis, and belongs to the technical field of plant cutting propagation. The method comprises the following steps: S1, cutting pretreatment: placing the base of Buddleja officinalis cutting in an ultrasonic generator for ultrasonic pretreatment; S2, rooting agent treatment: immersing the base of the pretreated cutting in a composite rooting agent solution, wherein the composite rooting agent comprises naphthaleneacetic acid, indolebutyric acid and vitamin B1; S3, cutting and maintenance: cutting the treated cutting in a special substrate, and performing post-cutting management. The application improves the cell permeability through ultrasonic treatment, promotes root growth in cooperation with the composite rooting agent with a specific formula, and optimizes the rhizosphere environment in cooperation with the special substrate, thereby improving the rooting rate, the number and quality of the root system of Buddleja officinalis, solving the problems of low rooting rate and poor rooting quality of the existing cutting method, and having the advantages of simple operation, good rooting effect and high seedling raising efficiency.

The application belongs to the technical field of medicine, and particularly relates to a pollen typhae acidic polysaccharide, a preparation method and application thereof; the pollen typhae acidic polysaccharide is characterized in that the structure of the polysaccharide comprises rhamnose, galactose, galacturonic acid, arabinose, glucose, xylose and mannose. A brand new pollen typhae acidic polysaccharide TPP-4 is prepared in the application, the acidic polysaccharide can improve vascular integrity, and then can improve the change of vascular endothelial cell permeability caused by inflammation, that is, has a protective effect on the integrity of endothelial cells in an inflammatory state, and can be used for preventing and / or treating blood stasis and bleeding.

The invention discloses a skin wound nursing ointment based on fish scale gelatin and a preparation method thereof, particularly relates to the technical field of skin nursing, and relates to the skin wound nursing ointment based on the fish scale gelatin and the preparation method thereof. The skin wound nursing ointment based on the fish scale gelatin is prepared from glyceryl monooleate, deionized water, docosyl, Span 60, a fish scale gelatin protein extract, an antibacterial component extract and sodium silicate. According to the method, the fish scale collagen is subjected to directional enzymolysis under the low-temperature condition by adopting the restrictive endonuclease extracted from deep-sea psychrophilic bacteria, the collagen peptide with the ultra-small molecular weight is accurately prepared, the active peptide fragments have excellent cell permeability and migration guiding capacity, the wound healing speed is remarkably increased, and the treatment effect is remarkably improved.

A method and apparatus for promoting the delivery of a molecule across a cell membrane comprises delivering a molecule to a delivery site of a region of tissue surrounding the cell membrane. A suction component applies a suction through a suction tip that surrounds the surface of the delivery site creating a seal to promote delivery of the molecule across the cell membrane. The application of the suction is controlled to create a predetermined negative pressure for a predetermined period of time before releasing the negative pressure. Suction is used to enhance permeabilization and transfection of cells. The technique can be used to enhance the uptake and subsequent transfection and expression of plasmid DNA vaccines, mRNA vaccines and other nucleic acid molecules, that are introduced subcutaneously. It can be used in combination with coated microneedles.

Methods of treating and preventing malaria infection, comprising administering a therapeutically effective amount of cell permeability modulating therapy are provided herein.

This invention provides a two-photon fluorescent probe for detecting hypoxia levels. The probe comprises a core fluorophore composed of a 2-dimethylamino-7-hydroxynaphthalene two-photon fluorophore and a probe composed of a sulfonate methylene group. This invention also provides a method for preparing and applying the two-photon fluorescent probe for detecting hypoxia levels. The fluorescent probe of this invention enables the monitoring of hypoxia levels in tumor and normal tissues by in-situ detection of nitroreductase (NTR) content within tissues. It features fast response, high sensitivity, high optical stability, good biocompatibility, high selectivity, and high depth, high resolution, and low biological background in two-photon imaging. In cell imaging applications, this probe exhibits good cell permeability and can detect NTR content at the cellular level, indicating cellular hypoxia.

The present invention provides the use of a PNA oligomer comprising a modified PNA for the prevention or treatment of coronavirus infectious diseases. The PNA oligomer of the present invention can be delivered into a virus-infected cell without a delivery vehicle and inhibits viral proliferation, and thus does not have side effects caused by a delivery vehicle for increasing cell permeability of a conventional drug, and can be used as a target-specific drug due to its high binding affinity. Virus proliferation can be inhibited by binding to a target even if there is a mismatch. Therefore, it is expected that the PNA oligomer will be used as an effective coronavirus therapeutic agent that can respond to rapidly mutated viral infectious diseases.

According to the green tea extraction process provided by the invention, the extraction efficiency and quality of active ingredients of tea leaves are remarkably improved through combination of pulsed electric field pretreatment and a two-stage enzymolysis technology. The pulsed electric field enhances the cell permeability; cellulase and pectinase degrade cell walls in stages and release intracellular substances; as a natural activator, saccharicterpenin stabilizes chitinase activity and enhances antioxidant protection. And in the enzymolysis process, near infrared spectrum is combined to monitor the dissolution dynamic state of tea polyphenol in real time, so that the enzymolysis end point is accurately controlled, the obtained extract tea is high in active ingredient and excellent in oxidation resistance, and the batch stability is ensured.

The invention discloses a photoresponse self-assembly type PROTAC as well as a preparation method and application of the photoresponse self-assembly type PROTAC. A light cyclization addition reaction of 9, 10-phenanthrenequinone and electron-rich olefin is utilized to realize space-time controllable coupling of a target protein POI ligand and an E3 ligase ligand. The preparation method comprises the following steps: covalently coupling a 1, 9, 10-phenanthrenequinone molecule with an E3 ligase ligand, covalently coupling an electron-rich olefin group with a POI targeting ligand, and respectively administering. Afterwards, the optical fiber probe is inserted into a colon cancer part with a cavity, local illumination provided by the optical fiber is utilized to induce a cyclization addition reaction, complete and active PROTAC molecules are formed, specific degradation of key target protein (such as BRD4) of colon cancer is achieved, and the degradation process is dynamically monitored in real time. According to the invention, the molecular weight of PROTAC is reduced and the cell permeability of molecules of PROTAC is improved in a split delivery-in-situ assembly-dynamic monitoring mode, and meanwhile, space-time specific activation is realized by utilizing light control, and the toxicity of non-target tissues is reduced.

The invention discloses a near-infrared self-flickering fluorescent dye as well as a preparation method and application thereof. The near-infrared self-flickering fluorescent dye has one of structures as shown in a formula I and a formula II. Azetidine is introduced to inhibit a twisted charge transfer effect in molecules, so that silicon rhodamine has the characteristics of high light stability, high brightness, cell permeability and the like. Based on thermodynamic equilibrium of intramolecular spiralization of a benzyl alcohol structure in the dye, the fluorescent dye can realize single-molecule localization super-resolution fluorescence imaging of various subcellular structures in living cells, and realizes visualization of structures including lysosomes, mitochondria, cell nucleuses, microfilaments and the like on a nano scale. Besides, the absorption wavelength of the dye is 650nm, the fluorescence emission wavelength reaches 666nm and reaches a near-infrared region, damage of exciting light to cells is reduced in the super-resolution imaging process, and the dynamic life process of the cells under normal physiological conditions can be visualized;

The invention belongs to the technical field of food processing, and discloses a processing method of a dried kiwi fruit product. According to the invention, cold plasma pretreatment, composite enzymatic hydrolysis and segmented microwave vacuum drying processes are cooperated, so that the obtained dried kiwi fruit product is less in nutrient loss, high in vitamin C retention rate and long in preservation time, and has good sensory quality. Firstly, plasmas are generated under the action of a high-frequency electric field, isoactive particles in the plasmas can penetrate through microbial cell membranes to destroy DNA structures of the microbial cell membranes, efficient sterilization is achieved, and the shelf life is prolonged; meanwhile, micro holes are formed in the surfaces of the kiwi fruit slices through the plasma etching effect, the cell permeability is improved, more acting sites are provided for subsequent enzymolysis, and the enzymolysis efficiency is improved. The surface microstructure of the fruit slice is changed, and the compound enzyme permeates into intercellular substances, so that the cell structure is loosened, and drying is facilitated. The two-stage microwave vacuum drying is matched with the micro-hole structure formed by the cold plasma, so that the drying time can be shortened, and the degradation of nutritional ingredients is avoided.

The invention discloses a polypeptide for activating BACE1 lactylation and application of the polypeptide, and belongs to the technical field of biological medicine. The polypeptide for activating BACE1 lactylation is a combined body TAT-B300P formed by a polypeptide taken from a functional segment near a BACE1 protein K300 site and a cell penetrating peptide TAT, and the sequence of the TAT-B300P is TAT-NLRLPKKVFEAAV. The polypeptide drug provided by the invention is introduced into a cell-penetrating peptide structure, has good cell permeability, is beneficial to play a role in a central nervous system, enables a drug delivery mode to be more flexible, can act on a BACE1K300 key site in a targeting manner and regulate and control the functional state of the BACE1K300 key site, has relatively high targeting and specificity, and is beneficial to reducing abnormal activation of an APP beta-lysis pathway.

The application discloses a cell penetrating peptide and application thereof; the cell penetrating peptide is selected from SEQ ID NO. 1, SEQ ID NO. 14, SEQ ID NO. 16, SEQ ID NO. 18, SEQ ID NO. 20, SEQ ID NO. 22, SEQ ID NO. 24, SEQ ID NO. 26 or SEQ ID NO. 28; the cell penetrating peptide of the application has more excellent cell penetration rate and cell permeability compared with the cell penetrating peptide H16 which is recognized in the art; and the cell penetrating peptide has no cytotoxicity; and further has no immunogenicity, and can be used for human body imaging or treatment, and expands the application range of the existing cell penetrating peptide. The fusion protein with tumor cell penetration and tumor environment specific activation is designed and constructed for GSDME, and a new idea is provided for development of an anticancer targeted drug.

The present application relates to a kind of drug-loaded silk fibroin emulsion and its preparation method and application, belong to biological medicine technical field.The drug-loaded silk fibroin emulsion of the present application includes silk fibroin emulsion and the oil phase material encapsulated in the inside of silk fibroin emulsion;Oil phase material has oil-soluble drug molecule dispersed in it.The silk fibroin emulsion of the present application presents strong positive electric property under gastric acid environment, improves its with gastric mucosa cell, the ability of combination of the protein of negative electricity exposed in ulcer affected area.In addition, the design of nanoscale size makes it have higher surface area and the " amphiphilic multi-block " characteristics of silk fibroin, further improve its with gastric mucosa and ulcer affected area's combination ability and cell permeability, further improve the passive targeting effect and cell permeability of emulsion.Because silk fibroin has good membrane forming capacity, it can form protective layer around drug, prolong the residence time of drug in gastrointestinal tract, improve the absorption efficiency of drug, reduce the frequency of administration.

The invention discloses a method for extracting sweet potato peel soluble dietary fibers, an obtained product and application, the sweet potato peel soluble dietary fibers are efficiently extracted by adopting the synergy of graded incremental intermittent pulsed electric field treatment and a deep eutectic solvent system, and meanwhile, the activity of the soluble dietary fibers is reserved as much as possible. The method comprises the following steps: removing impurities through electric field-assisted freezing and thawing circulation, pre-activating by using a pulsed electric field, and fumigating by using tartaric acid to enhance the cell permeability. And then realizing non-thermal wall-breaking extraction by combining a graded incremental intermittent pulsed electric field with a deep-eutectic solvent, stabilizing fiber molecule conformation by glycerol, and synergistically enhancing the penetrating power of the solvent with urea. And finally, freeze-drying to obtain a dietary fiber product with high purity, good water binding capacity and good expansibility. The method is high in extraction efficiency, high in solvent recycling rate, green and environment-friendly and capable of keeping functional integrity of products, and an innovative scheme is provided for high-value utilization of agricultural wastes.

The present application relates to conjugated compounds of formula (I): A-L1-B (I) wherein: A is a moiety that increases fungal cell uptake and / or fungal cell permeability; b is a CK1 suppression part; and L1 is a linker; the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, compositions comprising these compounds or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, processes for their preparation, and their use in treatments such as the treatment or prevention of fungal related diseases, disorders or conditions.

The application discloses a polypeptide specifically binding to Sestrin2 protein and application thereof in treatment of digestive tract cancer. Specifically disclosed is a STAMBPL1 polypeptide with an amino acid sequence of SEQ ID No. 1, which is a polypeptide specifically binding to Sestrin2 protein and can block the interaction between Sestrin2 and STAMBPL1 through competitive binding. The application further provides a chimeric peptide tat-STAMBPL1 with cell permeability comprising the STAMBPL1 polypeptide and a cell-penetrating peptide. The polypeptide and the chimeric peptide of the application have high affinity, clear target, target the Sestrin2 / STAMBPL1 interaction site, and can effectively inhibit tumor (especially digestive tract tumor) formation. The application further provides an anti-tumor drug comprising the STAMBPL1 polypeptide and / or the chimeric peptide tat-STAMBPL1.