506 results about "Reticulum cell" patented technology

Provided are an adenosine triphosphatase sarcoplasmic / endoplasmic reticulum Ca2+ transporting 2 (ATP2A2) gene-based molecular marker for identifying a chicken feed efficiency trait, and an identification method and use thereof. A nucleotide sequence of the molecular marker is shown in SEQ ID NO: 1, and a base at locus 926 in the nucleotide sequence is T or G. In the present application, by identifying a genotype of the molecular marker in a chicken genome and then selecting the chicken feed efficiency trait according to the genotype, a breeding method for early selection of the poultry feed efficiency trait is established. The method is simple, rapid, and low-cost, does not require special instruments, and is suitable for the needs of marker-assisted selection experiments.

Fusion proteins are provided that consist of essential elements such as one or more proteins / polypeptides capable of transporting into the endoplasmic reticulum (ER) and fragments or variants of interleukin 18 (IL-18) or IL-18. The proteins / polypeptides capable of transporting into the ER include, but are not limited to, immune globular proteins (e.g., Fc regions, VHH antibodies, and scFv), and globular proteins (e.g., serum albumin). In some embodiments, the IL-18 may be a pro-IL-18 similar to a natural precursor cytokine, wherein IL-18 is fused to the C-terminus of a propeptide or a propeptide variant thereof. In some embodiments, the fusion protein may further comprise a cleavable peptide linker.

The invention relates to the technical field of biological medicine, in particular to a ferroptosis inhibition type phospholipid-like material and application thereof. The ferroptosis inhibition type phospholipid-like material is one of the following structural general formulas (1)-(5). The biomimetic phospholipid-like ferroptosis inhibitor has a long retention characteristic in main positions (cell membranes, endoplasmic reticulum and other organelle membranes) of cell ferroptosis, so that the ferroptosis inhibition efficiency is remarkably improved. The novel phospholipid-like material not only can be used as an active drug molecule, but also can be used as a pharmaceutic adjuvant for constructing drug delivery carriers such as lipidosome and micelle and implant coatings, and is suitable for various administration routes such as oral administration, injection and local administration. The novel biomimetic ferroptosis inhibitor can efficiently relieve cell ferroptosis and has a wide application prospect in the field of treating or retarding ferroptosis-related diseases.

The invention provides an ER targeting self-assembly AIE probe with cascade ROS / RNS generation performance, and belongs to the technical field of material chemistry, the probe is composed of four units: 1) an AIE photosensitizer OTBS used for generating ROS; 2) deriving peptide FFVLK from beta amyloid protein, and promoting the self-assembly of the peptide to form a nanofiber with a beta-sheet structure; (3) an oligomerization arginine unit RRRR which is used as an NO donor; and 4) ER targeting signal peptide KDEL to endow ER with targeting ability. Based on ER targeting and a self-assembly process, the self-assembly AIE probe is subjected to ER in-situ self-assembly in cells to form nanofibers, ROS / RNS is generated in a cascading manner under illumination, and strong ICD is induced. In addition, the tumor residence time of the photosensitizer is prolonged due to the formation of the nanofibers, and the treatment effect is further improved. The invention provides a new thought for the design of a novel light-operated II-type ICD inducer.

The invention discloses novel application of notoginsenoside Rg1, namely application of the notoginsenoside Rg1 in preparation of a cathepsin D (CTSD) inhibitor, the notoginsenoside Rg1 can inhibit CTSD enzyme activity so as to recover lysosome structure and function, relieve endoplasmic reticulum stress reaction and relieve alpha-syn aggregation and dopaminergic neuron apoptosis, has a remarkable protection effect on a Parkinson's disease model, and can be used for preparing a novel anti-inflammatory drug. The invention provides a new thought and a potential drug basis for targeted intervention of Parkinson's disease. The invention discloses a new mechanism that Rg1 plays a role in neuroprotection through a CTSD-lysosome-endoplasmic reticulum stress pathway.

The invention provides a recombinant engineering bacterium for preparing recombinant human albumin based on a transport secretion way and application, and relates to the technical field of gene engineering. One or more of endoplasmic reticulum related genes SRP54 and ERJ5, vesicle transport related genes YOS1 and SLY1 and Golgi apparatus related genes GOS1 and YIP1 are integrated into a recombinant engineering bacterium genome through a gene recombination technology, so that efficient secretory expression of recombinant human albumin is realized. According to the method provided by the invention, the expression quantity of the recombinant human albumin is remarkably improved, and the method has a wide application prospect.

The invention provides a polypeptide for inducing tumor cell immunogenic death, a bioactive solution and application of the polypeptide and the bioactive solution, and belongs to the technical field of biological medicine. Comprising an end-capping group, a phosphorylated gelling factor, a matrix metalloproteinase-2 response sequence and a transient receptor potential vanillic acid receptor 1 (TRPV1) agonist which are connected in sequence, the amino acid sequence of the phosphorylated gelling factor is GFFpY, and the response sequence of the matrix metalloproteinase-2 is PLGVR. The anti-tumor polypeptide provided by the invention can generate enzymatic in-situ self-assembly through the action of ALP and MMP-2 overexpressed outside tumor cells, and sequentially release pharmacophores outside and inside the cells to cause mitochondrial stress and endoplasmic reticulum stress and synergistically induce immunogenic death of the tumor cells.

The invention provides a culture system for simulating neutrophile granulocyte extracellular trap net intervention oligodendrocyte in vitro, and belongs to the technical field of cell and function detection. The invention establishes a stable and repeatable research system by screening and determining the optimal condition for in-vitro co-culture of the neutrophil extracellular trap net and the oligodendroglia. Based on the condition, the experiment can observe the obvious change of the oligodendroglia after the intervention, and the result shows that the condition can accurately simulate the endoplasmic reticulum stress regulation effect of the neutrophile granulocyte extracellular trap net on the oligodendroglia, thereby providing a necessary experimental basis for the subsequent mechanism research.

The invention relates to recombinant pichia pastoris for high expression of porcine pancreatic phospholipase A2 and application of the recombinant pichia pastoris, and belongs to the technical field of genetic engineering. According to the method disclosed by the invention, a vacuole sorting receptor Vps10 is knocked out by utilizing a CRISPR-Cas9 system, a CPY sorting way between a trans-golgi apparatus and a vacuole is interrupted, and ppPLA2 degradation is reduced; then, in order to relieve unfolded protein response in the endoplasmic reticulum, molecular chaperones are introduced into the genome, and synthesis of ppPLA2 is enhanced; the expression intensity of the ppPLA2 is improved by increasing the gene copy number of the ppPLA2; and finally, high-density fermentation is performed in a 3-L bioreactor, so that high-efficiency expression of the ppPLA2 in the pichia pastoris is realized.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The invention discloses a recombinant VII type collagen as well as a preparation method and application thereof. The recombinant VII type collagen is obtained by repeating a short amino acid sequence GLPGAKGEKGAP for a plurality of times. The secretion yield of the recombinant VII type collagen in a commercial pichia pastoris expression system can be up to about 17.3 g / L, the extracellular secreted protein is basically not degraded in the fermentation process, the purity can reach 90% or above through simple ultrafiltration and decoloration, and industrial mass production can be achieved; and the recombinant VII type collagen has better biological activities of promoting autophagy, improving an endoplasmic reticulum stress state, promoting collagen secretion and inhibiting matrix metalloproteinase from degrading collagen, and shows good tightening and anti-wrinkle effects.

The invention relates to the technical field of biological medicines, in particular to application of an EIF3A inhibitor in preparation of a medicine for treating hepatic fibrosis. The EIF3A inhibitor relieves the hepatic fibrosis process by inhibiting EIF3A expression of hepatic tissue, relieving endoplasmic reticulum stress, inhibiting an NF-kappa B inflammation pathway and reducing pathological damage of hepatic cells, and the EIF3A inhibitor can be selected from a medicine for knocking down or knocking out EIF3A, a medicine for inhibiting EIF3A protein synthesis or a medicine for promoting EIF3A protein degradation. New mechanism research is provided for occurrence and development of hepatic fibrosis, hepatic cell damage and inflammation can be relieved through targeting EIF3A, hepatic fibrosis related pathological phenotypes are relieved, the protection and treatment effects are achieved, safety is higher, and therefore the application has good practical application value.

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a scrophularia ningpoensis extract for relieving chemotherapy-induced acute kidney injury and application of the scrophularia ningpoensis extract in preparation of a product for relieving chemotherapy-induced acute kidney injury. The preparation method comprises the following steps: putting fresh ginseng into a high-temperature and high-pressure sterilization pot, steaming at 110-120 DEG C for 1-3 hours, taking out, cooling to room temperature, and repeating the steaming cooling process for 2-5 times; and crushing the treated ginseng materials, adding a mixed strain of saccharomyces cerevisiae and lactobacillus plantarum in a mass ratio of 1: 1, fermenting for 24-72 hours, filtering fermentation liquor, and drying filter residues to obtain the black ginseng extract. The cisplatin-induced acute kidney injury is prevented and / or treated by improving oxidative stress and mitochondrial functional activity, reducing the content of lipid peroxide, inhibiting expression of inflammatory factors TNF alpha, IL1beta and COX2 and remarkably reducing the cell apoptosis rate and the level of inflammatory factors related to endoplasmic reticulum stress.

The disclosure provides methods for preparation of carbohydrate replacement therapies (CRT) that include nanocarriers of carbohydrates and glycolipids for pharmaceutical delivery to cell interior, endoplasmic reticulum, and Golgi for treating CDG type I and CDG type II diseases as well as other metabolic disorders.

A model that closely resembles human excessive myopia can be prepared by mounting a minus lens (2) and a protector (4) to a juvenile mouse, the minus lens having an angle and a width adjustable in response to growth of the mouse. Further, this model analysis shows that myopia induction causes endoplasmic reticulum stress in a sclera and the endoplasmic reticulum stress induces myopia. Furthermore, it is revealed that an endoplasmic reticulum stress suppressant, particularly, phenylbutyrate and tauroursodeoxycholic acid act as a myopia prevention / suppression agent.

The invention discloses a recombinant bacterium and application of the recombinant bacterium in production of benzophenanthridine alkaloid. The synthetic route of the benzophenanthridine alkaloid is divided into a plurality of modules for research, and de novo synthesis of the benzophenanthridine alkaloid is realized through a plurality of strategies, for example, in order to improve the activity of BBE, a new endoplasmic reticulum engineering strategy is developed, so that the yield of a key intermediate S-Soulerine is increased by 3 times; the McDBOX2 is identified as the only reported DBOX gene which plays a role in saccharomyces cerevisiae at present, and the reconstruction of the whole biosynthetic pathway of the benzophenanthridine alkaloid is completed; by carrying out N-terminal truncation operation on DBOX, cytoplasmic expression and endoplasmic reticulum amplification are improved, and supply of a cofactor FAD is increased, so that the yield of benzophenanthridine alkaloid is increased. Experiments prove that the recombinant strain constructed by the invention can be used for efficiently producing benzophenanthridine alkaloid. The method has an important application value.

The invention relates to an endoplasmic reticulum-based chimeric protein construct for targeting protein degradation and application thereof, for example, the chimeric protein construct is used for treating cancers, virus infectious diseases, autoimmune diseases, neurodegenerative diseases and the like. The chimeric protein constructs comprise an endoplasmic reticulum-related degradation mechanism protein binding domain and a targeting domain. The ERAD mechanism protein binding domain of the chimeric protein construct may be a transmembrane domain of a viral endoplasmic reticulum resident protein or a functional variant thereof and an endoplasmic reticulum resident domain or a functional variant thereof. The targeting domain of the chimeric protein construct can target any target protein of interest, which can be a natural ligand of the target protein, an antibody that specifically recognizes the target protein, or an antigen-binding fragment thereof. The targeting domain of the chimeric protein construct may also be an antigen that can be specifically recognized by an antibody.

The invention discloses a pharmaceutical composition for resisting tumors, and belongs to the field of medical biology. The STING antagonist can be used in combination with chemotherapy drugs to enhance the inhibition effect on tumors, the endoplasmic reticulum stress inducer can also be used in combination with chemotherapy drugs to achieve a better inhibition effect on tumors, and a good tumor inhibition effect is achieved in vivo and in vitro by combining chemotherapy, STING inhibition and endoplasmic reticulum stress treatment schemes. The invention provides a new medication idea for tumor treatment.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The ruthenium (II) complex has excellent anti-tumor activity, can induce tumor cells to generate ICD death, can be quickly positioned in an endoplasmic reticulum, causes the intracellular active oxygen level to rise, blocks the cell cycle in the S phase, and finally induces the tumor cells to generate pyroptosis. More importantly, MCF-7 cells can be caused to generate endoplasmic reticulum stress, so that an ICD effect is triggered, DC in tumor tissues is increased, chemotaxis of effector T cells in the tumor tissues is improved, and meanwhile, the number of Treg cells with an immunosuppression effect can be reduced, so that tumor immunity of an organism is activated. In addition, the Ru (II) complex can activate a cGAS-STING pathway, the proportion of CD8 + T cells is increased, and the anti-tumor immunocompetence is further improved.

The invention relates to a dual-targeting fluorescent carbon dot for endoplasmic reticulum and lipid droplets and a preparation method and application thereof.The preparation method comprises the steps that o-phenylenediamine and phenylalanine are dissolved in pure water to obtain a first dissolved solution; transferring the first dissolving solution into a poly-tetrafluoroethylene lined reaction kettle, carrying out a first heating reaction to obtain a precipitate, and sequentially carrying out column chromatography purification, rotary evaporation and drying on the precipitate to obtain a target solid; dissolving caffeic acid in dichloromethane, adding CDI, and stirring to obtain a second dissolved solution; and adding the target solid into the second dissolving solution, and carrying out a second heating reaction to obtain the dual-targeting fluorescent carbon dots for the endoplasmic reticulum and the lipid droplets. The dual-targeting fluorescent carbon dots obtained by the preparation method can distinguish endoplasmic reticulum and lipid droplets, and solve the problem of lack of life-sensitive dual-targeting fluorescent carbon dots capable of simultaneously positioning the endoplasmic reticulum and lipid droplets and sensitively monitoring microenvironment changes of the endoplasmic reticulum and lipid droplets.

The invention relates to the technical field of medicines, in particular to a composite nano vaccine and application thereof. The composite nano vaccine is prepared by coupling a natural compound with endoplasmic reticulum stress induction capability on the surface of Ga-MOF nano particles. The composite nano vaccine can significantly enhance the anti-tumor effect through a ferroptosis mechanism, an endoplasmic reticulum stress and immunogenic cell death mechanism and a cryoablation technology synergistic effect mechanism, reverses an immunosuppressed tumor microenvironment, inhibits the growth of primary tumors and distant metastatic tumors, and has a good anti-tumor effect. A brand new strategy is provided for comprehensive treatment of tumors, and the application prospect is wide.

The invention relates to the technical field of antitumor drugs, in particular to a cyclometalated iridium (III) complex as well as a preparation method and application thereof. The cyclometalated iridium (III) complex has a structure as shown in a formula I which is described in the specification. Experimental results show that the cyclometalated iridium complex provided by the invention has excellent anti-tumor activity, can enter tumor cells in an energy-dependent manner, and gathers on endoplasmic reticulum and lysosome. Caspase-1 can be activated to induce cells to generate a large amount of ROS, the cells are further induced to generate pyroptosis by activating the Caspase-1, and a large amount of inflammatory factors are released. In in-vitro experiments, migration of tumor cells can be effectively inhibited. In further in-vivo experiments, the cyclometalated iridium complex can influence normal development of zebrafish embryo blood vessels to different degrees. The cyclometalated iridium complex provided by the invention can induce tumor cell death by inhibiting angiogenesis.

The invention discloses a method for efficiently expressing laccase by regulating endoplasmic reticulum stress reaction of coprinus cinereus, and belongs to the field of gene engineering and fermentation engineering. According to the invention, by regulating endoplasmic reticulum stress reaction action genes der1, Anhac1 and Cchac1 of filamentous fungi coprinus cinereus, recombinant extracellular expression of laccase Lcc5 is finally improved and regulated. Wherein the extracellular laccase activities of the recombinant bacteria can be respectively improved by 18%, 70% and 26% through interference of der1, overexpression of Anhac1 and overexpression of Cchac1, and the obtained extracellular laccase activities are respectively 31.4 U / mL, 45.1 U / mL and 33.6 U / mL, which is the highest level of coprinus cinereus homologous recombination expression laccase Lcc5 reported at present. The invention firstly indicates that the regulation and control of the coprinus cinereus endoplasmic reticulum stress reaction can promote the efficient expression of laccase in coprinus cinereus, and the invention further promotes the development of a coprinus cinereus expression system.

The invention relates to the field of biological medicine, and discloses application of a GADD34 inhibitor in preparation of a medicine for enhancing CAR-T cell tumor treatment. The invention provides an innovative strategy for inhibiting CAR-T cell depletion through targeted regulation and control of an endoplasmic reticulum stress pathway to solve the problems that in an existing CAR-T therapy, the anti-tumor activity is reduced, and the solid tumor treatment effect is insufficient due to T cell depletion. Researches find that an IRE1-XBP1 pathway is used as a core signal axis of endoplasmic reticulum stress, and excessive activation of the IRE1-XBP1 pathway can drive CAR-T cell depletion related phenotypes (such as PD-1 / LAG-3 up regulation and cytokine secretion reduction). Screening experiments show that inhibiting the upstream regulatory factor GADD34 of the IRE1 not only can effectively reduce the IRE1-XBP1 signal intensity, but also can cooperatively relieve the endoplasmic reticulum stress pressure by regulating protein translation recovery, so that the CAR-T cell steady state is more comprehensively maintained. Therefore, the GADD34 inhibitor can provide a new way for enhancing CAR-T cell tumor treatment.

The invention relates to an endoplasmic reticulum targeting polypeptide nano-drug with glutathione responding to morphology transformation, a preparation method and a related performance characterization method. The endoplasmic reticulum targeting polypeptide nano-drug with glutathione responding to morphology transformation comprises a targeting unit, an assembling unit and a functional unit, wherein the targeting unit comprises one or more of targeting peptide sequences RVMLIGK, RVMLIEK, KDEL and sulfonyl groups with an endoplasmic reticulum targeting function; the functional unit comprises a glutathione response group disulfide bond, and the assembly primitive sequence and the assembly regulation sequence are covalently connected through the disulfide bond. The assembly structure of the polypeptide nano-drug has sensitive glutathione responsiveness, so that the polypeptide nano-drug can generate assembly morphology transformation in glutathione overexpressed tumor cells, and the polypeptide nano-drug is simple and convenient to synthesize and prepare and has wide application prospects in the aspects of drug delivery, tumor treatment and the like.

A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3 / 19K) (TCR-E3 / 19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.

The invention provides application of combined use of thymopentin, salinomycin and IR780 iodide in preparation of a medicine for treating and inhibiting tumor dryness. The invention also provides a pharmaceutical composition for inhibiting tumor dryness. The invention relates to an endoplasmic reticulum stress nano inducer (DTSS) based on salinomycin, which is used for synergistically inhibiting the dryness of cancer cells and effectively sensitizing cancer immunotherapy. The endoplasmic reticulum targeted phototherapy drug s-780 is prepared by coupling p-toluene sulfonamide and IR780 iodide (IR780), is assembled together with thymopentin and salinomycin, and is finally functionalized by biotin to obtain a delivery nano-platform (DTSS) at a specific site, so that systemic anti-tumor immune response can be effectively activated, metastasis and recurrence of cancers can be inhibited, and the application prospect is wide. And a promising solution is provided for sensitizing cancer immunotherapy by inhibiting cancer cell dryness.

The invention discloses a saccharomyces cerevisiae strain for de novo synthesis of fucoxanthine precursor neoxanthine and application of the saccharomyces cerevisiae strain, and belongs to the technical field of biology. According to the recombinant saccharomyces cerevisiae disclosed by the invention, the 3-hydroxy-3-methylglutaryl coenzyme A reductase, the isopentenyl pyrophosphate isomerase, the farnesyl pyrophosphate synthase and the endoplasmic reticulum size regulation factor are expressed in an enhanced manner; according to the method, geranyl geranyl diphosphate synthase, phytoene dehydrogenase, 15-cis-phytoene synthase, bifunctional lycopene cyclase / phytoene synthase, beta-carotene hydroxylase, zeaxanthin epoxidase truncated mutant and violaxanthin deep oxidase-like protein are subjected to heterologous expression, so that the zeaxanthin deep oxidase-like protein is obtained; the ROX1 and GAL80 genes in the saccharomyces cerevisiae are knocked out, and the expression of squalene synthase ERG9 is down-regulated. When the strain is subjected to shake flask fermentation, the contents of neoxanthine and violaxanthin of the strain respectively reach 1.78 mg / L and 26.77 mg / L, so that the strain has a wide application prospect.

The invention relates to a mitochondrial uncoupling inhibitor sustained-release nanodot, a preparation method thereof and application of the nanodot in type 2 diabetes mellitus, and belongs to the technical field of nano-drugs. According to the preparation method disclosed by the invention, glycine and genipin are subjected to Schiff reaction to prepare the slow-release nanodot, and the slow-release nanodot is of a monodisperse spherical structure, has surface negative charges, and can slowly release genipin under physiological conditions, so that the mitochondrial protection effect of the genipin is fully exerted. The mitochondrial uncoupling inhibitor slow-release nanodot prepared by the invention can obviously improve the mitochondrial membrane potential, increase the cell ATP content, effectively inhibit mtDNA release under the stimulation of IL-1beta and palmitic acid, effectively inhibit STING inflammation pathway activation under the stimulation of IL-1beta and PA, obviously reduce pancreatic beta cell apoptosis, obviously relieve endoplasmic reticulum stress, and can be used for preparing the mitochondrial uncoupling inhibitor slow-release nanodot. The T2DM mouse blood sugar is obviously reduced, the glucose tolerance dose and the insulin sensitivity are improved, and good biocompatibility is achieved.

The invention discloses application of an Hspa5 inhibitor in preparation of a medicine for preventing or treating anxiety disorder. An anxiety mouse model is constructed through chronic constraint stress (CRS), and in combination with medial amygdala kernel (MeA) transcriptome sequencing and qPCR verification, it is found that the endoplasmic reticulum molecular chaperone Hspa5 is remarkably up-regulated in the anxiety state. Furthermore, an Hspa5 specific inhibitor HA15 is locally injected into a MeA brain region, so that the anxiety-like behavior induced by the CRS is remarkably improved, and the exploration time of an open field experiment central region, the exploration time of an open arm of an elevated cross labyrinth and the exploration time of a bright box of a bright-dark box experiment are prolonged. The invention discloses the function of Hspa5 as a novel anti-anxiety target for the first time, and provides a direct experimental basis and a transformation direction for developing a novel anti-anxiety drug which is non-monoamine and targets an endoplasmic reticulum homeostasis.