65 results about "Cell permeability" patented technology

The invention discloses a decafluorobiphenyl-based Tat47-57 binding peptide, the amino acid sequence of the binding peptide is shown as SEQ ID NO.1 or SEQ ID NO.2, the fourth amino acid and the eighth amino acid of the SEQ ID NO.1 are bound through decafluorobiphenyl, and the fifth amino acid and the twelfth amino acid of the SEQ ID NO.2 are bound through decafluorobiphenyl. In particular, the decafluorobiphenyl-based Tat47-57 binding peptides (P3 and P6) are efficient CPPs, capable of delivering a variety of cargo molecules into the cytoplasm of mammalian cells. Meanwhile, decafluorobiphenyl cyclization plays a key role in cellular uptake and endosome escape. The two peptides P3 and P6 show remarkable cell permeability, and are speculated to enter cells through gridding protein dependent endocytosis. They also show efficient endosome escape ability, and have successfully applied P3 and P6 as CPPs to deliver phospholipid peptides and avidin.

The invention provides a method for improving cell permeability of mycobacterium neoaurum, a mycobacterium neoaurum engineering bacterium and an application of the mycobacterium neoaurum engineering bacterium in preparation of 9 alpha-hydroxyandrostane-4-ene-3, 17-diketone (9-OHAD). Biotransformation of phytosterol into high-value steroid intermediates such as 9-OHAD in mycobacteria is a footstone of steroid drugs. However, the limited permeability of its dense cell wall of Mycobacterium severely hinders the effective intracellular transport of phytosterols and its bioconversion to 9-OHAD. The endogenous synthesis capability and exogenous circulation capability of mycobacterium neoaurum trehalose are destroyed through gene knockout, the permeability of cells is improved, the molar conversion rate of 9-OHAD is increased to 65.7% from 44.7%, the extracellular production of 9-OHAD is also improved, the extracellular yield of 9-OHAD is increased to 32.1% from 12%, and subsequent separation and purification are facilitated.

The invention discloses a synergetic color protection method for hot-processed eggplants. The eggplants are inhibited from browning through combination of multiple technologies. The method comprises the following steps: pretreatment, preparation of a color protection solution (compounding of ascorbic acid, tea polyphenol and calcium chloride, ultrasonic high and low temperature circulating blanching, pulse vacuum treatment and gradient temperature control secondary enzyme deactivation. After being treated by the method disclosed by the invention, the polyphenoloxidase (PPO) activity can be synergistically inhibited, the cell permeability and the anti-oxidation effect can be regulated and controlled, and the color difference delta E value (less than 5.0) can be obviously reduced. The method is suitable for color protection pretreatment of eggplant processing forms such as hot drying, hot frying and hot steaming, the color protection efficiency is greatly improved, no synthetic preservative needs to be added, and a possible way is provided for deep development of eggplants in the field of prefabricated vegetables.

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 present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.

The present invention discloses an aryltriazene compound and its application in the preparation of anti-tumor drugs. The structure of the aryltriazene compound is shown in Formula I. The anti-cancer activity of the aryltriazene compound of the present invention is superior to that of the existing positive control drug dacarbazine; its safety index for tumor treatment is superior to that of dacarbazine; its cell permeability is superior to that of dacarbazine. The preparation method of the aryltriazene compound of the present invention has the characteristics of mild reaction conditions, simple experimental steps, high yield, high product purity, economy and practicability. #imgabs0#

The invention belongs to the technical field of biomedical materials, and discloses a self-assembly eutectoid gel with cell permeability and multiple anti-inflammatory effects and a preparation method of the self-assembly eutectoid gel. The preparation method comprises the following steps: mixing and heating choline chloride and a hydroxyl type hydrogen bond donor to obtain viscous liquid; dissolving the viscous liquid in water to prepare a DES solution; adding antibacterial active ingredients and lysozyme fibers into the DES solution, heating, carrying out ultrasonic treatment, and standing to room temperature, so as to obtain the self-assembled eutectoid gel. According to the application, the deep eutectic solvent with high biocompatibility, solubility promotion and cell permeability promotion is used as a solvent of the eutectoid gel to prepare the self-assembled eutectoid gel, so that the drug utilization efficiency of small molecule drugs in the eutectoid gel is enhanced, intracellular active oxygen can be effectively removed, and macrophages of M1 pro-inflammatory phenotype are polarized into M2 anti-inflammatory phenotype. The preparation method meets the preparation standard of green chemistry, and is safe and environment-friendly.

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.

Embodiments of the disclosure include compositions comprising peptides with C-terminal capping motifs, and methods for making the compositions. The capping motifs impart helicity to C-termini of peptides that otherwise do not exhibit helicity. The helix capping motifs are conformationally rigid, stable in serum, and increase cell permeability of peptides.

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 invention provides a proteolysis targeting chimera as well as a preparation method and application thereof. The proteolysis targeting chimera is prepared from a target protein ligand containing a phosphoramidite structure and an E3 ubiquitin ligase ligand containing a phosphoramidite structure through a DNA (Deoxyribonucleic Acid) automatic solid-phase synthesizer, the protein hydrolysis targeting chimera is prepared by a solid-phase synthesis method, and the method has the advantages of rapidness, accuracy, modularization, automation and large-scale preparation; by selecting a proper connexon, the cell permeability of the proteolysis targeting chimera is improved, and the target protein degradation capability of the proteolysis targeting chimera is improved; an enzyme activatable group is modified on a hydroxyl group of an E3 ubiquitin ligase ligand, and only when the enzyme activatable group is removed from a corresponding enzyme, a protein hydrolysis targeting chimera can be released to play a role, so that the target protein is controllably degraded. The proteolysis targeting chimera prepared by the method provided by the invention can effectively inhibit proliferation of human cervical cancer HeLa cells, has the advantages of strong specificity, good stability and high membrane permeability, and provides a new solution for tumor treatment.

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.

Embodiments of the disclosure include compositions comprising peptides with an N-terminal capping motif or with the combination of an N-terminal capping motif and a C-terminal capping motif, and methods for synthesizing the peptides. The capping motifs can impart helicity to peptides that otherwise do not exhibit helicity. The helix capping motifs are conformationally rigid, improve peptide serum stability, and increase cell permeability of peptides.

Methods, systems, processes and devices for transcellular membrane delivery are provided herein. In one aspect, a device includes a substrate including a mixing channel, a processing chamber and a dilution channel to perform a process of transporting an effective load across the entire cell membrane. On the other hand, a system includes a reservoir for a cell suspension, a transfer solution reservoir and a stop solution connected to a pump. The system also includes an agitator, a heater, a temperature controller and a controller for operating the system. On the other hand, cells in the suspension are mixed with a transfer solution in a microfluidic mixing chip. The transfer solution contains a permeabilizing agent that causes cell permeabilization, thereby allowing the effective load to be transported from the transfer solution through the cell membrane into the cell.

To provide compounds that realize effective treatment of Huntington's disease (HD).SOLUTION: The invention provides a compound of formula (I), W-L-ULM, or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, or isotopically enriched analog thereof. In the formula: W is a compound targeting mutant huntingtin protein (mHTT); L is a bond or linking moiety optionally substituted with B; ULM is an E3 ubiquitin ligase targeting moiety; and B is a moiety that crosses the blood brain barrier and / or enhances cell permeability.SELECTED DRAWING: None

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.

The present invention relates to a cell-penetrating repeating peptide in which a plurality of cell-penetrating peptides are repeatedly linked, and has been completed by confirming that the cell-penetrating repeating peptide has significantly higher cell permeability than a single peptide, and thus can enhance the efficiency of intracellular transport of a conjugated protein. Thus, a neurotransmitter secretion-blocking peptide conjugated to the cell-penetrating repeating peptide, of the present invention, can move into cells with high efficiency, and thus can more effectively block the secretion of neurotransmitters by cells. Therefore, the neurotransmitter secretion-blocking peptide can be used not only for cosmetic purposes such as improving skin wrinkles, but also for ameliorating or treating neuromuscular diseases caused by excessive neuronal signal transduction, muscle tension, and the like.

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.