376 results about "Reticulum cell" patented technology

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 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 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 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 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.

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.

The invention discloses an application of 4-octyl itaconic acid (4-OI) in preparation of a medicine for improving pulmonary arterial hypertension (PAH). In-vivo experiments show that 4-OI can significantly reduce pulmonary vascular wall thickening and collagen deposition of a PAH rat model, and effectively improve PAH and vascular remodeling. In-vitro experiments further reveal that 4-OI reduces endoplasmic reticulum stress (ERS) by inhibiting a PERK-eIF2alpha pathway, further blocks SM22 dependent smooth muscle cell phenotypic transformation and endothelial-mesenchymal transformation (EndMT) processes, finally inhibits vascular remodeling, and plays a role in treating PAH. The three key pathological processes of ERS, EndMT and vascular remodeling are closely linked, a new perspective is provided for deeply understanding the correlation among oxidative stress, endothelial dysfunction and vascular structure change in PAH, meanwhile, a theoretical foundation is laid for developing PAH and vascular remodeling accurate treatment drugs, and clinical transformation value is achieved.

The present invention relates to a composition for anti-cancer treatment, the composition including immunogenic tumor-derived extracellular vesicles using an endoplasmic reticulum stress inducer, and a method for producing the same. The composition according to the present invention includes extracellular vesicles in which tumor immune-activating protein is increased and immune-suppressive protein is decreased so that immunogenicity is enhanced, and thus can be used as a pharmaceutical composition or a food composition for anti-cancer treatment.

Disclosed herein are compositions and methods for activating a light responsive modified protein kinase R-like endoplasmic reticulum kinase (PERK) and the Integrated Stress Response (ISR) pathway in a cell.

The present invention relates to a novel purine derivative compound and a composition for enhancing an immune response comprising same as an active ingredient. The compound of the present invention not only has a nanomolar EC50 value for TLR7, which is an intracellular membrane receptor of immune cells, but also has high selectivity for TLR7 compared to TLR8, which has a similar structure and is mainly distributed in the endoplasmic reticulum (ER), thereby being able to induce sustained immune activation. Therefore, the compound of the present invention can be effectively used as an efficient vaccine adjuvant composition against various RNA viruses including influenza virus, SARS-CoV-2, and hepatitis C virus.

To provide an endoplasmic reticulum stress suppressing composition and a liver function improving composition.SOLUTION: A composition for suppressing endoplasmic reticulum stress and / or a composition for improving hepatic functions, comprising one or more plants selected from the group consisting of Plantago asiatica, Hamilton's spindle tree, panicled hydrangea, Japanese plum yew, Japanese mallotus, and Papaver rhoeas, and / or an extract thereof.SELECTED DRAWING: None

The invention belongs to the technical field of biological medicine, and particularly relates to application of small peptide PEARL in diagnosis and targeted therapy of acute myelogenous leukemia. When leukemia patient samples and leukemia cell lines are detected, obvious low expression of the small peptide PEARL in acute myelogenous leukemia patients is found. Meanwhile, the research finds that PROSER2-AS1 does not play a role, but plays a role through the coded small peptide PEARL. A mouse leukemia model experiment further finds that the overexpressed small peptide PEARL can significantly inhibit the survival of acute myelogenous leukemia cells and significantly prolong the life cycle of a model mouse. Finally, through mechanism research, it is found that the endoplasmic reticulum pressure of acute myelogenous leukemia cells is remarkably increased through overexpression of PEARL, the UPR reaction is activated, and therefore the functions of the acute myelogenous leukemia cells are affected. Therefore, the invention can provide a new accurate judgment or treatment strategy for diagnosis or targeted treatment of acute myelogenous leukemia.

An endoplasmic reticulum-targeted long-wavelength fluorescent probe for detecting hydroxyl free radicals, and its preparation method and application. The structure of the fluorescent probe is shown in Formula I. The present invention also provides a method for preparing the fluorescent probe and its application in hydroxyl free radical detection. The fluorescent probe provided by the present invention can sensitively and specifically detect hydroxyl free radicals in the long analytical wavelength region of 640 nm. It also has the advantages of selectively targeting the endoplasmic reticulum, low biological background fluorescence signal, minimal photodamage to biological samples, good biocompatibility, and easy preparation and use. It has great application prospects in the fields of chemistry, biology, medicine, etc.

The present disclosure relates to endoplasmic reticulum protein HYOU1-binding compounds for inhibiting endoplasmic reticulum-mitochondrial interactions and uses thereof.The features and advantages of the present disclosure may be summarized as follows:(a) The present disclosure provides a compound that can bind to the endoplasmic reticulum protein HYOU1 and inhibit endoplasmic reticulum-mitochondrial interactions increased by oxLDL (oxidized low-density lipoprotein).(b) The present disclosure provides a composition capable of preventing, ameliorating or treating autophagy disorder-related diseases, particularly arteriosclerosis or pulmonary hypertension, which contains the above-described compound as an active ingredient.(c) Since the composition of the present disclosure reduces intracellular lipids by inducing autophagy in atherosclerosis-induced tissues, it can be useful used in the amelioration or treatment of atherosclerosis.(d) Since the composition of the present disclosure reduces smooth muscle cell proliferation by inducing autophagy in smooth muscle cells in which contraction is induced by TGF-β, it can be usefully used in the amelioration or treatment of pulmonary arterial hypertension.

The invention belongs to the technical field of agricultural biology, and particularly relates to application of an endoplasmic reticulum protein antioxidant (reducing agent) in prevention and treatment of bombyx mori nuclear polyhedrosis virus. A screening test finds that the related endoplasmic reticulum protein antioxidants beta-mercaptoethanol (BME), dithiothreitol (DTT) and / or tris (2-carboxyethyl) phosphine (TCEP) have the effect of inhibiting the bombyx mori nuclear polyhedrosis virus (BmNPV), and the antioxidants interfere the replication and proliferation of the virus by destroying disulfide bonds in key proteins of the BmNPV, so that the bombyx mori nuclear polyhedrosis virus can be inhibited. The stability and activity of virions are directly influenced, so that the infection of the viruses on the silkworms is inhibited, a brand new thought is provided for the development of antiviral drugs of the silkworms, and the application value is good.