28 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 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 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 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.

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 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 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.

The present invention relates to a peptide that inhibits the secretion of neurotransmitters from cells, and provides a composition and kit for skin whitening or wrinkle reduction, and a method for skin whitening or wrinkle reduction, each containing the peptide as an active ingredient. The peptide is characterized by having cell permeability without being fused to a protein transport domain such as a cell-penetrating peptide, and having an efficient skin whitening or wrinkle reduction effect.

The present application relates conjugate 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 inhibiting moiety; and L1 is a linker; or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, to processes for their preparation, and their use in therapy such as in the treatment or prevention of fungal-related diseases, disorders or conditions.

The present application provides a kind of proteolysis targeting chimera and its preparation method and application, by containing phosphoramidite structure target protein ligand and containing phosphoramidite structure E3 ubiquitin ligase ligand is prepared by DNA automatic solid-phase synthesizer;Proteolysis targeting chimera is prepared by solid-phase synthesis method, with the advantages of fast, accurate, modular, automation, large batch preparation;By selecting suitable linker, increase the cell permeability of proteolysis targeting chimera, improve its ability to degrade target protein;In the hydroxyl modification of E3 ubiquitin ligase ligand, an enzyme activatable group, only when the corresponding enzyme removes the enzyme activatable group can release proteolysis targeting chimera to play its role, so as to carry out controllable degradation to target protein.The proteolysis targeting chimera prepared by the method provided by the present application can effectively inhibit the 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 invention provides an application of MF-438 in preparation of drugs for treating peripheral nerve adhesion diseases, relates to the technical field of biomedicine, and aims to fill the technical blank of clinical lack of targeted small molecule drugs for treating peripheral nerve adhesion. A verification experiment also proves that the MF-438 can obviously reduce the expression of proinflammatory factors such as IL-1alpha, IL-1beta and TNF-alpha, effectively inhibit the excessive inflammatory response of a nerve adhesion part and create a stable local microenvironment for nerve repair; meanwhile, the compound can effectively protect the sciatic nerve myelin sheath structure, increase the myelin sheath thickness and maintain the myelin sheath integrity, and the nerve protection and repair effects are directly achieved; in addition, the MF-438 has good cell permeability and oral bioavailability, the administration mode is simple and convenient, the action effect is clear, and the experimental safety is good, so that the MF-438 has higher clinical transformation and industrialization potential, and a safe, efficient and clear-mechanism brand new treatment strategy is provided for peripheral nerve adhesion diseases.

This invention discloses the application of a PIAS4 inhibitor in the preparation of AML therapeutic drugs. The inhibitor provided by this invention, i-PIAS4, is named [4-(diphenylmethyl)piperazin-1-yl][7-(trifluoromethyl)-5,6-dihydrobenzo[h]pyrazolo[5,1-b]quinazolin-10-yl]methanone, and its code in the ZINC database is ZINC000033358359. The inhibitor i-PIAS4 targets and interferes with the interaction between the E3 ubiquitin ligase PIAS4 and its substrate protein, inhibiting the PIAS4-mediated SUMOylation or ubiquitination modification function of the substrate protein, thereby blocking its abnormal regulation of downstream signaling pathways. It exerts its inhibitory effect on AML by inhibiting the ubiquitination degradation of the substrate and activating downstream pathways. i-PIAS4 also exhibits good cell permeability, selectivity, and stability, specifically targeting the PIAS4 protein and demonstrating a high binding affinity for it. This invention provides a new strategy for targeted therapy of AML.

The application discloses a kind of polypeptides for activating BACE1 lactification and application thereof, belong to biological medicine technical field.The polypeptide for activating BACE1 lactification of the present application is the combination TAT-B300P formed by polypeptide taken from the functional segment near the K300 site of BACE1 protein and cell-penetrating peptide TAT, and the sequence of TAT-B300P is TAT-NLRLPKKVFEAAV.The polypeptide drug provided in the present application introduces cell-penetrating peptide structure, has good cell permeability, is conducive to its function in central nervous system, so that the administration mode is more flexible, can be targeted to the key site of BACE1 K300, regulates its functional state, has higher targeting and specificity, and helps to reduce the abnormal activation of APP beta-cleavage pathway.

The present application relates to the technical field of medicine, in particular to the use of a substance specifically binding to KLK8 in the preparation of a product for the prevention, treatment or diagnosis of sepsis, which treats sepsis by: 1) reducing endothelial cell permeability or improving capillary leakage; 2) stimulating the VE-cadherin / Akt / FOXM1 signaling pathway; preferably, selected from up-regulating the expression level of FOXM1 and its downstream target genes, up-regulating the protein level of AKT or p-AKT, or up-regulating the protein level of VE-cadherin; 3) increasing the proliferation rate of endothelial cells; 4) reducing the mortality rate of endothelial cells; 5) increasing the activity of endothelial cells. The present application provides a new treatment strategy for sepsis complicated with microvascular barrier dysfunction.