64 results about "Cell entry" patented technology

The invention provides a coordination nano assembly of chiral cyclopeptide and manganese ions as well as a preparation method and application of the coordination nano assembly. According to the method, a manganese superoxide dismutase protein structural domain and a unique tumor microenvironment of melanoma high tyrosinase are combined, and polypeptide sequences L-YD-hL-DD-h, L-YL-HL-DL-H and D-yD-hD-dD-h with different chirality are designed for the first time; the chirality of the polypeptide is regulated and controlled, the in-vivo circulation stability and the cell entry efficiency of the nano assembly are improved, the coordination self-assembly of manganese and different chiral cyclopeptides is realized, and the in-situ oxidation of an in-vivo tumor microenvironment is simulated for photo-thermal therapy and cell membrane coating. The method disclosed by the invention is simple, mild in experimental condition and easy to operate, the prepared cell membrane coated nano assembly not only has long circulation stability and high cell entry efficiency, but also can realize mild photo-thermal therapy through in-situ oxidation, releases manganese ions to activate a CGAS-STING pathway for immunotherapy of tumors, and has a wide application prospect. The potential application value is realized in the field of combined treatment of tumors.

The invention provides a nucleic acid aptamer agonist conjugate as well as a preparation method and application thereof. The nucleic acid aptamer agonist conjugate is prepared by coupling a nucleic acid aptamer, a connexon and an STING agonist, the nucleic acid aptamer agonist conjugate can be used as a medicine to recognize a target spot on the surface of a tumor cell in a targeted manner and enter the cell to start a cGAS-STING signal channel so as to realize an anti-tumor effect. The variety of STING agonists and the variety of connexons are also screened, so that the aptamer agonist conjugate not only has the advantages of easiness in transmembrane and cell entry, strong tumor permeability, long half-life period, small toxic and side effects and the like, but also has a strong inhibition effect on triple-negative breast cancer. The aptamer agonist conjugate can also be combined with an immune checkpoint blocking therapy to further realize long-acting and efficient inhibition of tumor growth.

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.

System and methods for continuous culture comprise performing a first continuous culture of cells in a chamber of a first bioreactor under culture conditions that produce cell growth; moving culture fluid comprising cells from the chamber of the first bioreactor into a chamber of a second bioreactor though one or more fluidic conduits; and performing, in the chamber of the second bioreactor, a second continuous culture of cells under culture conditions that produce at least one culture product. The process is performed under conditions wherein the rate of cell growth in the first continuous culture is greater than that of the second continuous culture, and the production of culture product in the first continuous culture is less than that of the second continuous culture.

The present disclosure relates generally to the use of compounds that inhibit coronavirus entry into an angiotensin converting enzyme 2 (ACE2)-expressing cell, in methods and compositions for inhibiting the interaction of coronavirus to an ACE2-expressing cell and for treating or inhibiting the development of coronavirus infections.

The invention provides the use of a formulation containing cyclodextrine, quercetin and zinc, at appropriate concentrations to mitigate infections by enveloped viruses like SARS-COV-2, influenza and HIV / AIDS, when administered via pulmonary and dermal route. While the different forms of cyclodextrin prevent the entry of coated virus into host cells by extracting and sequestering cholesterol molecules at the virus coat and at the host cell plasma membrane, the natural plant-based ionophore quercetin in the formulation, enables cellular entry of zinc, inhibiting viral replication by altering polymerase activity in the host cell. Hence cyclodextrine, and quercetin plus zinc, either in combination or in tandem order of administration, serves both as prophylactic and therapeutic.

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).

The invention belongs to the technical field of biological medicines, and particularly relates to a tetrahedral framework nucleic acid carrying a small molecule drug as well as a preparation method and application of the tetrahedral framework nucleic acid. According to the invention, good cell entry performance, editability, anti-inflammatory and anti-oxidation capability of tetrahedral framework nucleic acid and anti-inflammatory and osteogenesis promoting effects of a JAK inhibitor are combined, and the JAK inhibitor Upatinib (UPA) is successfully loaded onto the tetrahedral framework nucleic acid (tFNA) to obtain a tFNA / UPA compound (TUC); the TUC can significantly inhibit inflammatory reaction by inhibiting a JAK / STAT pathway on the premise of reducing the drug dosage, enhances a WNT signal pathway, promotes an osteogenesis function, more effectively treats rheumatoid arthritis, and has a wide application prospect.

The invention provides negatively-modified biomineralized lipid nanoparticles as well as a preparation method and application thereof. The negatively-modified biomineralized lipid nanoparticles consist of lipid nanoparticles and mineralized shells, wherein the surfaces of the lipid nanoparticles are modified with negatively-charged molecules, and the mineralized shells are deposited on the surfaces of the lipid nanoparticles. According to the particles, negative molecules can be efficiently modified on the surface of LNP, the negative molecules are effectively prevented from being wrapped in the LNP, mineralization of lipid nanoparticles is promoted, and the stability of the LNP is improved; the cell entering efficiency is improved, and the delivery capacity of the LNP on nucleic acid drugs is enhanced; meanwhile, the compound can be used as a treatment medicine to improve the curative effect of LNP, and has multiple effects.

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.

The invention belongs to the technical field of biological medicines, and particularly relates to tetrahedral framework nucleic acid related to microRNA-200c as well as a preparation method and application of the tetrahedral framework nucleic acid. The tetrahedral framework nucleic acid delivery system related to the microRNA-200c is provided by combining the extremely strong cell entry performance and lysosome escape ability of the tetrahedral framework nucleic acid (tFNAs) and the gene targeting specificity of the microRNA-200c, and the system has good stability, biological safety, cell entry efficiency and tissue permeability. In the aspect of periodontitis treatment, tFNAs and miR-200c play a synergistic treatment role, inflammation can be effectively relieved, ROS generation can be inhibited, osteogenic differentiation and matrix mineralization can be promoted, alveolar bone resorption can be relieved, a new treatment strategy is provided for periodontitis, and the application prospect is good.

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 liquid pumping device comprises a liquid pumping pipe assembly, the top end of the liquid pumping pipe assembly is fixed on a top cover of a bioreactor, and the liquid pumping pipe assembly is inserted into a tank body of the bioreactor. By means of the liquid extraction device, in the extraction process of the culture medium liquid and the separation process of the culture medium and the micro-tissue, due to the fact that a traditional microfiltration mode is not used, blocking can be effectively avoided, and the culture medium liquid can be continuously extracted for a long time; meanwhile, the liquid extraction pipe assembly is inserted into the tank body of the bioreactor, so that the cells on the micro-tissues cannot leave the culture environment in the tank of the bioreactor when entering or leaving the liquid extraction pipe assembly, and the relatively fragile cells are prevented from being greatly influenced.

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 utility model belongs to the technical field of cell culture devices, and relates to a bioreactor. The bioreactor comprises a tank body which is provided with an accommodating cavity; the first mounting assembly is arranged on the inner wall of the tank body; the periphery of the first microporous membrane is installed on the first installation assembly, the first microporous membrane is used for dividing the containing cavity into a mixing area and a first stirring area in the height direction of the tank body, and through holes of the first microporous membrane communicate with the first stirring area and the mixing area; the diameter of a through hole of the first microporous membrane is set to be permeable to a culture solution and smaller than the diameter of a cultured cell; and the first stirring assembly comprises a first rotating piece arranged in the first stirring area. The first microporous membrane is installed in the tank body, and the containing cavity is divided into the first stirring area and the mixing area. The diameter of the through holes of the first microporous membrane is smaller than that of the cells, the cells are prevented from entering the stirring area, only the culture solution is allowed to flow, the cells are prevented from being exposed to a shear force environment, and cell damage is reduced.

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 relates to the technical field of biological genetic engineering, in particular to a lung exempt type MSLN CAR-T cell, application and an anti-tumor preparation. The CAR-T cell is constructed by adopting a recombinant vector, the recombinant vector comprises an MSLN binding structural domain nucleotide sequence, and further comprises an LIR-1 inhibitory nucleotide sequence and a nucleotide sequence used for being specifically bound with a lung high-expression gene, and a lung high-expression molecule is an AQP3 gene. When the CAR-T cell enters lung tissue, the LIR-1 inhibitory sequence inhibits the killing function of the CAR-T by being combined with lung high-expression molecules, so that lung toxicity is avoided; when the CAR-T cells infiltrate tumor tissues, the inhibitory sequence is inactivated, and the CAR-T is activated and normally plays a role, so that the tumor cells are effectively killed; the medicine has the advantages of accurate treatment, low side effect and safety.

The invention discloses a single cell operation device which comprises an objective table, a probe, a probe control assembly, a microscopic imaging assembly and an air pressure source assembly, and the air pressure source assembly provides positive and / or negative air pressure for the probe in a pulse mode. The invention also provides a method for extracting a single cell by using the single cell operation device, a method for injecting a reagent into the single cell and extracting contents from the single cell, and a method for spotting. The pulse type positive and negative air pressure is provided for the probe, target cells can be accurately extracted in situ, meanwhile, the extracted cells enter the probe, namely, the probe can serve as a temporary storage place of the cells, continuous extraction of multiple cells can be achieved, and the operation efficiency is improved.

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.

A fusion protein comprising a LIGHT protein and an antigen-binding domain that specifically binds to FAP may exhibit anti-cancer effects. In particular, the fusion protein efficiently targets cancer cells which overexpress FAP, and LIGHT may bind to a lymphotoxin beta receptor and HVEM to promote the formation of tertiary lymphoid structures and normalize blood vessels. Accordingly, the fusion protein enables effective treatment of cancer through efficient infiltration of immune cells into tumor tissue. Furthermore, it was confirmed that the fusion protein of the present invention can treat cancer more effectively when administered in combination with an anti-PD-1 antibody compared to when administered individually.

Disclosed is a method for evaluating cell differentiation state, comprising: inducing differentiation of pluripotent stem cells into mesodermal cells in a liquid medium by a first differentiation treatment for inducing differentiation of pluripotent stem cells into mesodermal cells and a second differentiation treatment for inducing differentiation of the mesodermal cells into cardiomyocytes; collecting a supernatant of the liquid medium comprising cells induced differentiation by the second differentiation treatment; and measuring miRNA-3p from miR-1 / 133a cluster in the supernatant, wherein the miRNA-3p is at least one selected from a group consisting of miR-1-3p and miR-133a-3p, and the obtained measurement value of miRNA-3p serves as an index of cell differentiation state of the differentiation-induced cells.