34 results about "Cell entry" patented technology

The present application provides an indole derivative and a preparation method and application thereof. The preparation method comprises the following steps: dissolving copper acetate and triethylamine in isopropyl alcohol, stirring until completely dissolved to obtain a reaction medium; adding 5-bromo indigo and indole into the reaction medium, fully stirring at room temperature until the reaction is completely converted; removing the reaction solvent by distillation to obtain a crude product, purifying and recrystallizing to obtain a high-purity solid powder of the indole derivative. The indole derivative has a significant inhibitory effect on tyrosinase, melanin production and transfer; has high antioxidant capacity for scavenging intracellular active oxygen free radicals; through the mechanisms of affecting the membrane potential of mitochondria, activating the related apoptosis signaling pathway and promoting the expression of apoptosis proteins, etc., the A549 cell is prompted to enter the apoptosis program, thereby providing a new potential strategy and research direction for the apoptosis regulation of tumor cells, and having important research value and application prospect.

The invention discloses vidarabine monophosphate lipidosome freeze-dried powder injection and a preparation method and application thereof, and belongs to the technical field of medicine, and the lipidosome is composed of vidarabine monophosphate, phospholipid, cholesterol, pegylated phospholipid and a freeze-drying protective agent (such as trehalose). By optimizing a formula and a preparation process, the liposome disclosed by the invention has excellent placement stability and freeze-drying stability, and can still keep good encapsulation efficiency and particle size distribution after long-term storage. By introducing polyethylene glycol (PEG), the retention time of liposome in systemic circulation is remarkably prolonged, and passive targeting enrichment of liver and spleen is reduced, so that the toxicity of immune organs is reduced, and the accumulation of drugs at focus parts is facilitated. The liposome has an excellent slow release characteristic, can improve the antiviral ability and cell entry ability of drugs and reduce toxic and side effects, and is suitable for treating viral infectious diseases, such as hepatitis B, herpes and the like.

An immunotherapeutic protein and methods of use and production thereof are disclosed, wherein the immunotherapeutic protein comprises, for example, a cell surface receptor polypeptide which is a cellular entry receptor for the entry of a virus into a host cell, which is linked to a polypeptide comprising an Fc region component. When the cell surface receptor polypeptide is an angiotensin converting enzyme 2 (ACE2) polypeptide or a fragment thereof, the immunotherapeutic protein is capable of binding to a coronavirus spike protein (S protein) and may be useful as an antiviral agent for the prevention or treatment of a coronavirus infection. The Fc region component may comprise an amino acid substitution at the position corresponding to H429 of the amino acid sequence of the human IgG1 heavy chain polypeptide which may enable the production of soluble oligomeric forms or the assembly of oligomeric forms from soluble monomeric forms upon binding to an S protein of a coronavirus (i.e. as present on a virion or the surface of virus-infected cells).

A pharmaceutical composition comprising an influenza A M2 protein channel blocker for use in the treatment or prevention of the virulence of an aminoadamantane resistant influenza A, such as the H1N1 subtype, in a subject is provided. Further provided is a pharmaceutical composition comprising the influenza A M2 protein channel blocker for preventing entry, shelling and / or release from influenza A cells.

The invention discloses a method for preparing a dendritic cell vaccine through in-vitro amplification and induction of hematopoietic stem cells, and belongs to the field of biomedicine.The amplification induction method specifically comprises the following steps that firstly, peripheral blood is collected, the collected peripheral blood is diluted, and then peripheral blood mononuclear cells are separated; according to the invention, the conditions that cells enter an inflammatory emergency state due to a large dose of IL-4 in a traditional scheme, metabolic routes such as cell glycolysis are highly activated, ROS release is caused by oxidative stress, and cell dysfunction is caused by abnormal metabolism are avoided, and a cell combination closest to real DC cell phenotype and function in a human body can be obtained; the antigen presentation of the DC vaccine is improved to the maximum extent, meanwhile, hematopoietic stem cells can be partially differentiated to a myeloid system, DC progenitor cells and DC precursor cells, effective amplification of dozens of times can be achieved in quantity, and the technical bottleneck that the clinical curative effect is limited due to insufficient cell quantity is solved.

The application discloses a Sting agonist liposome-warm sensitive gel, a preparation method and application thereof. The Sting agonist liposome-warm sensitive gel comprises a Sting agonist-loaded liposome and a warm sensitive gel, and the preparation method comprises the following steps: preparing the Sting agonist-loaded liposome, adding the warm sensitive gel into a prepared Sting agonist-loaded liposome solution, and stirring until completely dissolved, and the Sting agonist liposome-warm sensitive gel is obtained. The Sting agonist liposome-warm sensitive gel has the advantages of small liposome particle size, good stability, effectively improved cell entry and release behavior of the Sting agonist, avoided burst release effect, in-vivo continuous and stable stimulation of the Sting agonist, better drug efficacy, increased local drug concentration and reduced side effects; the gel matrix can protect the integrity of the liposome and improve the stability of the liposome. The advantages of the liposome and the gel are combined, the drug uptake into cells is increased, and good sustained and controlled release performance is achieved.

The invention discloses a method for solving the problem of lactic acid accumulation of senescent cells in the later culture period, which comprises the following steps of: adding nicotinamide into a culture system in the later culture period of fed-batch culture of mammalian cells to eliminate a lactic acid tail-raising state, so that lactic acid is continuously maintained in a low-level stable state; the lactic acid tail raising means that the concentration of lactic acid is increased again after cells enter a stable phase or a decline phase, and the total concentration of nicotinamide added in a culture system is 5 mM to 14 mM. According to the method, the lactic acid tail raising phenomenon in the later period of cell culture is precisely regulated and controlled, secondary accumulation of lactic acid of senescent cells is inhibited, the low lactic acid level is maintained, serious negative effects on cell growth and motility rate are avoided, the yield and quality stability of target protein are guaranteed, the process robustness is enhanced, the industrial amplification risk is reduced, and the method is suitable for industrial production. And a method library for regulating and controlling lactic acid in a protein biological medicine production process is enriched.

The present invention addresses the problem of providing a virus cell entry inhibitor that inhibits the entry of viruses into cells and makes it possible to prevent viral infections.　A virus cell entry inhibitor that solves the problem of the present invention is characterized by containing at least one selected from an eyebright extract, a kasoori methi extract, a Tartary buckwheat extract, an okra extract, a cinnamon extract, a berberry extract, and a shell ginger extract.

This invention discloses a hair cell protectant based on a ferritin nanoplatform and its application in treating hearing loss, belonging to the field of biomedicine. The ferritin nanoparticles of this invention, loaded with cimicifugin, include ferritin (Fn) as a carrier and cimicifugin (Ci@Fn) loaded within the ferritin. By loading cimicifugin (Ci), an extract of cimicifugin, into ferritin, it is endowed with additional anti-inflammatory and tissue-protective functions, thereby achieving a more precise and effective therapeutic effect. After injection through the round window membrane (RWM) behind the ear, Ci@Fn is transported to the basement membrane along with the flow of perilymph and endolymph, ultimately targeting the inner ear hair cells (HCs). After entering the hair cells, Ci@Fn is taken up and degraded by lysosomes, releasing cimicifugin (Ci), thereby exerting a protective effect on the hair cells.

The invention belongs to the technical field of drug carriers, and particularly relates to tumor-targeted luteoloside liposome loaded paclitaxel and a preparation method thereof. According to the tumor targeted liposome, luteoloside and soya bean lecithin are used as membrane materials, a blank liposome (C-Blank) is prepared through a membrane hydration method and a high-pressure homogenization method, and a hydrophobic drug paclitaxel (PTX) is loaded to obtain a drug-loaded liposome (C-PTX). Wherein the luteoloside can significantly enhance the mechanical strength and thermodynamic stability of the lipid bilayer, and also can realize active tumor targeting through a glucose transporter GLUT1 mediated endocytosis pathway, and meanwhile, PTX is efficiently entrapped in a liposome hydrophobic core. The C-PTX liposome prepared by the invention is small in particle size, relatively good in endocytosis capability, good in blood long-circulation effect and drug delivery capability, good in stability and dispersity, high in drug encapsulation efficiency and beneficial to effective delivery and release of drugs. The oral bioavailability of PTX is improved, and C-PTX has an obvious inhibition effect on lung cancer cells. The drug loading system effectively overcomes the defects that a traditional paclitaxel preparation is poor in water solubility, large in system toxicity, insufficient in targeting performance and the like, the highly-uniform dispersion state and long-term storage stability of the drug loading system lay a foundation for industrial production, and the drug loading system shows important clinical application potential in the fields of precision medicine and transformation medicine.

The invention relates to a mitochondrial delivery system and a preparation method and application thereof. According to the mitochondrial delivery system, safe and efficient cell entry of active mitochondria can be achieved, the mitochondrial delivery system has appropriate particle size and surface potential, toxicity to cells is avoided while the entrapment rate of the mitochondria is effectively improved and the electrochemical stability and biological activity of a mitochondrial membrane are guaranteed, and the mitochondrial cell entry efficiency is remarkably improved. The mitochondrial delivery system not only can transplant active mitochondria into common cells to repair cell damage, but also can transplant the active mitochondria into egg cells to play a role across a zona pellucida and a plasma membrane barrier. The mitochondrial delivery system can be used for treating mitochondrial diseases related to mitochondrial dysfunction, especially infertility caused by mitochondrial dysfunction of egg cells.

The invention discloses a high-light-resistant algal strain high-speed screening method and system based on micro-fluidic single cell sorting, and relates to the field of bioengineering.The high-light-resistant algal strain high-speed screening method comprises the steps that haematococcus free cells in the logarithmic phase are taken and added into a double-fluorescence probe mixed solution, and incubation is conducted in a dark place to obtain a haematococcus solution; bBM sheath fluid and haematococcus fluid are introduced into a sample introduction area of the micro-fluidic chip, the BBM sheath fluid and the haematococcus fluid are focused by the sample introduction area and then enter a highlight stress area, highlight treatment is carried out to induce motile cells to be transformed into spores, and the transformed cells enter a detection area. Through in-situ high light stress and single cell continuous sorting of the micro-fluidic chip, the sorting efficiency is high, and the screening period is greatly shortened; three parameters of chlorophyll fluorescence, astaxanthin fluorescence and forward scattering light are adopted for cooperative detection, and a threshold value which is quantitatively set based on a control group is combined, so that the proportion of a false positive strain is reduced to be less than 5%, and the screening accuracy of a double-superior strain is greatly improved; the microfluidic chip is extremely low in single reagent consumption, greatly reduces the screening cost of single strains, and is easy for large-scale popularization and application.

The invention discloses an application of a protein substance in preparation of a composition for inhibiting coronavirus. The coronavirus inhibition comprises the following steps: inhibiting adhesion of the coronavirus on host cells; the invasion of coronavirus to host cells is hindered; the after-cell entry process of coronavirus infection is inhibited. In-vitro verification is carried out on the antiviral effect of the coronavirus GXP2V on various nutritional ingredients (whey protein, milk fat globule membrane, lactoferrin and milk-derived osteopontin), and the result shows that the coronavirus resisting activity of the whey protein, the milk fat globule membrane, the lactoferrin and the milk-derived osteopontin (LPN, short for lactopontin). At present, it is rarely reported that protein substances are used for resisting the coronavirus, the coronavirus GXP2V is a novel coronavirus-like virus, a new thought is developed for resisting the novel coronavirus-like virus, and the application value and prospect are very good.

The present disclosure relates to systems, methods and compositions for decoding ligand- receptor interactions, for delivering nucleic acids and proteins into target cells and for performing single cell multiomics. Disclosed are engineered lentiviruses displaying ligands that deliver cargo into target cells upon cognate receptor-ligand interaction. Also disclosed are compositions and methods including pMHC or antigen epitopes displaying lentiviruses for identifying pMHC / T-cell receptors and antigen / B-cell receptor interactions.

The invention belongs to the technical field of tumor treatment, and particularly relates to a nano boron drug for boron neutron capture therapy and a preparation method and application thereof, the nano boron drug is PAMAM-BSH, and PAMAM is a third-generation (G3), fourth-generation (G4) or fifth-generation (G5) dendritic macromolecule. The PAMAM-BSH provided by the invention has good biocompatibility and can be well internalized into tumor cells, the cell entering mode of the PAMAM-BSH is energy-dependent, and the boron concentration in B16F10 cells can reach 5300ng / 106 cells and is 61% higher than that of BSH. The nano boron drug provided by the invention is PAMAM-BSH and has a wide application prospect in the field of boron neutron capture therapy.

The application provides a coordination nanometer assembly of a chiral cyclic peptide and a manganese ion, a preparation method and application thereof, the method of the application combines a manganese superoxide dismutase protein domain with a unique tumor microenvironment of a melanoma high tyrosinase, and first designs polypeptide sequences with different chirality L‑ Y D‑ h L‑ D D‑ h、 L‑ Y L‑ H L‑ D L‑ H and D‑ y D‑ h D‑ d D‑ h, regulates polypeptide chirality, improves in-vivo circulation stability and cell entry efficiency of the nanometer assembly, coordinates self-assembly of manganese and the chiral cyclic peptide, simulates in-situ oxidation of the tumor microenvironment for photothermal therapy, and coats cell membranes. The method of the application is simple, the experimental conditions are mild, and the method is easy to operate, the cell membrane coated nanometer assembly prepared by the method not only has long circulation stability and high cell entry efficiency, but also can realize mild photothermal therapy through in-situ oxidation, release manganese ions to activate the CGAS-STING pathway for tumor immunotherapy, and has potential application value in the field of tumor combination therapy.

The invention belongs to the technical field of biomedical materials, and particularly relates to a porous polyester microsphere filler for improving the volume and form of an external nose, which comprises degradable polyester polymer microspheres with porous structures; the porous structure is a penetrating type porous structure, and the porosity is 50%-90%; the particle size of the polymer microspheres is 100-500 [mu] m, and the polymer microspheres account for 1-60% of the mass of the filler; and a thickening agent, an excipient, a carrier, a medicine and nutritional ingredients, according to the invention, the porous microsphere filler has a rich microscopic hole structure, so that fixation on the nose of a human body is facilitated, and exposure and infection due to external force are avoided; meanwhile, the porous microspheres and the penetrating through hole structure in the porous polyester microsphere filler are beneficial to cell entry, a large volume and a large surface area are provided for transportation of nutrient substances / removal of wastes, adhesion, proliferation and differentiation of the cells are finally caused, a regenerated collagen net structure is finally formed, and a more natural repairing effect is achieved.

The invention discloses application of RG108 in heart transplantation immunosuppression by regulating T cell functions, and relates to the technical field of medical bioengineering. The invention innovatively provides a method for inhibiting the activity of DNA methyltransferase 1 (DNMT1) by using a small molecule compound RG108, and by reducing the methylation level of a CDKN1A gene promoter, restoring the expression of the promoter and inducing T cells to enter an aging state, the proliferation and effect activity of the promoter is reduced, and rejection reaction is inhibited. The RG108 is a non-nucleoside DNMT1 selective inhibitor with a clear structure, the activity of the inhibitor is inhibited by combining with a catalytic structural domain, DNA is not doped, off-target toxicity is not caused, and the RG108 is an ideal molecule for realizing controllable and reversible epigenetic regulation. A new transplantation immune tolerance strategy is established, and the defects that an existing immunosuppressor is large in side effect and cannot induce immune memory tolerance are overcome.

The invention discloses an application of 89Zr-labeled umbilical cord mesenchymal stem cells in preparation of a systemic sclerosis pharmacokinetic tracing reagent. The radiochemical purity of the radionuclide 89Zr-labeled umbilical cord mesenchymal stem cells is greater than or equal to 90%, the cell activity is greater than or equal to 90%, and the in-vitro 24-hour retention rate is greater than or equal to 85%. The in-vivo distribution rule of the human umbilical cord-derived mesenchymal stem cells is detected, and a relationship is established between dynamic distribution of the marker after the cells enter the body and the cell curative effect, so that the clinical curative effect of a cell drug is effectively improved, the risk is reduced, and the drug interaction is reduced. A visual and reliable technical means is provided for evaluating targeting and efficacy of stem cell treatment, and the method has important clinical research and transformation values.

The invention belongs to the technical field of organic synthesis and medicine. The invention develops a method for constructing a delta-fluoroalkyl substituted alkenyl phosphate compound with a brand-new structure by sequentially adding olefin and alkyne with fluoroalkyl free radicals driven by visible light for the first time. Further, it is found that the delta-fluoroalkyl substituted alkenyl phosphate compound has multiple inhibition effects on porcine epidemic diarrhea virus (PEDV), not only can inhibit virus cell entry and replication, but also can further relieve cell apoptosis caused by PEDV, and it is indicated that the compound has the effect of treating porcine epidemic diarrhea. The compound provides a new thought for the development of multifunctional anti-PEDV medicines.

The invention comprises a housing with a separation chamber. The separation chamber may comprise a first chamber, a second chamber and a membrane between the first chamber and the section chamber. The membrane prevents non-motile cells from a semen sample in the first chamber, and allows motile cells from the semen sample, to enter the second chamber. The housing has an inlet for the semen sample to enter the separation chamber and at least one outlet opening for extracting the motile cells from the separation chamber. A hollow interior of a straw is connected with the at least one outlet opening of the separation chamber of the housing. A fluid pressure difference extracts motile cells from the separation chamber to the hollow interior of the straw.

The application discloses a cervical cell seven-classification method and system based on hierarchical routing and boundary expert fusion, and belongs to the technical field of image processing. In order to solve the technical problem that the existing technology directly adopts a single multi-classification model for cell classification, resulting in unreliable gray area boundary discrimination and finally leading to unstable cell classification result discrimination, the application utilizes multi-dimensional morphological indexes and detection confidence to calculate quality points; single cells and cell groups and halo cells are shunted for processing, the cell groups and the halo cells are directly outputted in types, the single cells enter subsequent processes, different morphological cells are avoided from being mixed into the same classifier, the single model training target inconsistency and feature deviation problem is solved; the single cell five-classification basic probability is acquired firstly, target areas of ASC-US and LSIL and ASC-H and HSIL are screened out through boundary uncertainty comprehensive points and quality points, finally probability is obtained through fusion of morphological indexes, bias probability and fusion strength, and the class with the maximum probability is selected as the seven-classification result. The application is used for cervical cell classification.

The application provides a G-quadruplex RNA-based protein degradation targeting chimera as well as a preparation method and application thereof. The structural general formula of the protein degradation targeting chimera is G-L-E; wherein G is G-quadruplex RNA that specifically binds to fragile X mental retardation protein (FMRP) of mammals, E is a ligand of a small molecule E3 ubiquitin ligase, and L is a connecting arm between the G-quadruplex RNA and the ligand of the small molecule E3 ubiquitin ligase. The protein degradation targeting chimera provided by the application has greatly improved stability in an in-vivo environment and cell entry capability, and also has the capability of efficiently degrading FMRP and changing a secretion mode of cancer cells, thereby providing many conveniences for development of nucleic acid-based PROTAC drugs.

This invention discloses a method for constructing an in vitro model of senescent astrocytes, belonging to the interdisciplinary fields of cell biology, neuroscience, and biomechanics. The method includes: isolating and culturing primary astrocytes; performing adherent cell culture on the obtained primary astrocytes; and applying a compressive stress of 3-10 kPa to the adherent astrocytes for induced culture to obtain a model of senescent astrocytes. By simulating the changes in the mechanical microenvironment during brain tissue aging, the model successfully induces astrocytes into a senescent state using continuous vertical compressive stress. The constructed model can be used to screen anti-aging drugs or drugs for treating neurodegenerative diseases.

The invention discloses an application of a protein substance in preparation of a composition for inhibiting coronavirus. The coronavirus inhibition comprises the following steps: inhibiting adhesion of the coronavirus on host cells; the invasion of coronavirus to host cells is hindered; the after-cell entry process of coronavirus infection is inhibited. In-vitro verification is carried out on the antiviral effect of the coronavirus GXP2V on various nutritional ingredients (whey protein, milk fat globule membrane, lactoferrin and milk-derived osteopontin), and the result shows that the coronavirus resisting activity of the whey protein, the milk fat globule membrane, the lactoferrin and the milk-derived osteopontin (LPN, short for lactopontin). At present, it is rarely reported that protein substances are used for resisting the coronavirus, the coronavirus GXP2V is a novel coronavirus-like virus, a new thought is developed for resisting the novel coronavirus-like virus, and the application value and prospect are very good.

The present invention relates to compositions, combinations and methods for the expression of a gene sequence of interest in a target cell wherein the composition comprises; (a) a first vector comprising a non-native receptor sequence, wherein the first vector is capable of introducing and / or expressing the non-native receptor sequence in the target cell, resulting in the exhibition of the non-native receptor on the target cell surface; and (b) a second vector comprising the gene sequence of interest wherein the second vector uses the non-native receptor for cell entry and enables the expression of the gene of interest in the target cell.

The present invention belongs to the field of biopharmaceutical technology, and specifically relates to a polypeptide targeting IDO1 and an IDO1 protein degradation targeting chimera. The polypeptide targeting IDO1 provided by the present invention is a high-affinity and targeted IDO1 extracellular domain protein binding polypeptide successfully selected using phage display technology. The polypeptide has a strong binding force with the IDO1 extracellular domain structural protein, and has the characteristics of high sensitivity, high recognition efficiency and small molecular weight. The present invention further combines the above-mentioned polypeptide with the E3 ubiquitin ligase ligand thalidomide through rational design to obtain PROTAC, which has good cell entry ability and IDO1 targeted degradation ability, can make the therapeutic drug for cancer disease more selective, and provide higher therapeutic efficiency while reducing systemic toxicity. Therefore, the present invention can provide a new treatment strategy and effective technical support for the development of new tumor targeted drugs and the treatment of related cancers.

This invention discloses a method for preparing T cells for tumor therapy by reducing the content or activity of SARDH protein. The method for preparing T cells for tumor therapy includes: reducing the content or activity of SARDH protein in recipient T cells, or reducing the expression level of the SARDH gene in recipient T cells, or knocking out the SARDH gene in recipient T cells, to obtain target T cells for tumor therapy. This invention discovers a novel target with significant innovative mechanisms of action. By reducing the content or activity of SARDH protein, or reducing the expression level of its encoding gene, or knocking out its encoding gene, the efficacy of T cell immunotherapy can be further improved. This invention provides a new perspective on elucidating the mechanism by which T cells enter tumors and become exhausted.

The invention provides retroviral envelope glycoproteins in which the cytoplasmic C-terminal tail (CTT) from N-terminus to C-terminus comprises or consists of a T-domain and an R-domain, wherein the R-domain is truncated from its C-terminus, and hybrid glycoproteins and retroviral, especially alpharetroviral, lentiviral or gammaretroviral vector particles containing the glycoprotein. The glycoproteins target the SLC1A5 receptor for target cell entry.

According to the surface-modified anti-angiogenesis nano assembly and the preparation method thereof, the KK polypeptide is modified and grafted at the tail end of the anti-VEGF functional polypeptide, so that the electropositivity of the anti-VEGF functional polypeptide is enhanced to promote penetration, and meanwhile, the anti-VEGF functional polypeptide is self-assembled with copper ions to form stable nano particles; the nano-particles can effectively treat inflammatory reaction and revascularization problems after eye alkali burn. A penetrating peptide and an ROS scavenger TEMPO are further inoculated through an amidation reaction, and activation of an NF-kappa B signal channel is inhibited by regulating and controlling the ROS level, so that the immune cell state is regulated, oxidative stress is eliminated, and tissue damage is relieved. The method disclosed by the invention is simple and convenient to operate, mild in experimental condition and relatively high in ocular surface retention time and cell entry efficiency, and the obtained nano-particles can be used for treating the eye alkali burn, have a remarkable curative effect, are particularly suitable for combined treatment of anti-angiogenesis and anti-oxidative stress, and have wide clinical application potential.