290 results about "Pancreatic islets" patented technology

The invention provides a stem cell exosome vesicle induced by traditional Chinese medicine functional components as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the preparation method of the stem cell exosome vesicle, traditional Chinese medicine functional components serve as an exosome inducer, stem cells can be induced to proliferate and secrete exosome with the enhanced function, the yield of the exosome can be increased, bioactive molecules can be loaded, and the bioavailability of the exosome in diabetes treatment is remarkably improved. The stem cell exosome vesicle disclosed by the invention can be applied to treatment of diabetes and complications thereof, not only can improve functions of islet cells, but also can treat chronic inflammation, microangiopathy and other metabolic diseases related to diabetes, and has a wide clinical application prospect.

The invention belongs to the technical field of organoid culture, and particularly relates to a co-differentiated vascularized islet organoid and a construction method thereof. Aiming at the problems that the existing pancreatic islet organ vascularization mostly adopts a co-culture mode, the operation process is long, the difficulty is high, the randomness is realized, the uniformity is poor and the like, the invention provides the construction method of the co-differentiated vascularized pancreatic islet organ. The method comprises the following steps of: sequentially inducing and culturing directional endoderm cells, original intestinal canal cells and posterior preintestinal cells, and adding a culture medium containing VEGF (vascular endothelial growth factor), BMP4 (bone morphogenetic protein 4) and FGF2 (fibroblast growth factor 2) for culturing in subsequent induced differentiation, so as to obtain the co-differentiated vascularized islet organ. Under the condition that exogenous endothelial cells are not added, the iPS cells are directionally differentiated to generate the vascularized islet organ containing beta, alpha and delta cells and vascular endothelial cells for the first time, the vascularized islet organ is more mature than non-vascularized islet organs and has a stronger insulin secretion function, and a new thought and an experimental basis are provided for realizing functional healing of diabetes mellitus.

The invention provides a pancreatic islet organ capable of efficiently maintaining pancreatic islet beta cell identity and a preparation method and application thereof. Specifically, the invention provides the preparation method for the in-vitro pancreatic islet organ, and the preparation method comprises the following steps: carrying out induced differentiation culture on the ZnT8-knocked-out pluripotent stem cells, so as to obtain the mature pancreatic islet organ. The invention also provides a corresponding transplantation composition and application thereof. The invention discloses that ZnT8 knockout is a key factor for effectively maintaining the identity stability of beta cells in pancreatic islet organs. In addition, the pancreas islet beta cell identity maintenance agent is combined with the ZnT8-knocked-out pancreas islet organ for use, so that the identity stability of the pancreas islet organ beta cell can be obviously maintained. The invention provides a new strategy for transplantation treatment of type 2 diabetes, and has excellent clinical transformation value.

The invention discloses a composition for assisting in reducing blood sugar and blood fat as well as a preparation method and application thereof, and relates to the technical field of functional compositions. The composition comprises highland barley powder and modified inulin, the preparation method of the highland barley powder comprises the following steps: soaking highland barley grains in a weakly alkaline aqueous solution, and sequentially carrying out first pulse microwave treatment, enzyme deactivation treatment and segmented baking treatment; the segmented baking treatment comprises first-stage baking treatment and second-stage intermittent infrared irradiation treatment; the temperature of the first-stage baking treatment is 40-60 DEG C; the temperature of the second-stage intermittent infrared irradiation treatment is 60-80 DEG C, and the emission wavelength is 2.5-4 microns; the preparation method of the modified inulin comprises the following steps: performing acidolysis treatment on inulin in a weakly acidic aqueous solution, and then drying. The highland barley powder and the modified inulin in the embodiment can synergistically improve glycometabolism and lipid metabolism, effectively reduce the body weight, blood sugar, blood fat and the like under high-glucose and / or high-fat diet, and protect and repair the pancreas islet function.

The present invention belongs to the field of biomedical engineering technology, and specifically relates to a hydrogel microfiber carrying pancreatic islet α and β cells, a preparation method and an application thereof; the preparation method comprises: dissolving a photoinitiator in a cross-linked water-soluble polymer solution, filtering and sterilizing, adding pancreatic islet α and β cells to obtain a hydrogel cell prepolymer solution, passing the hydrogel cell prepolymer solution into an inner phase tube, passing an ionically cross-linked aqueous phase solution into an outer phase tube, and adjusting the flow rates of the solutions in the inner and outer phase tubes so that the liquids form a mutually immiscible laminar flow state; in a microfluidic device, after the inner phase solution contacts the outer phase solution, the ionically cross-linked components in the inner phase solution undergo ionically cross-linking with the outer phase solution to preliminarily form hydrogel microfibers, which are then secondary cross-linked by 405nm blue light irradiation to ultimately form hydrogel microfibers carrying pancreatic islet α and β cells.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

The invention relates to a heparinized gelatin / sodium alginate pancreas islet packaging material with an anti-fibrosis function as well as a preparation method and application of the heparinized gelatin / sodium alginate pancreas islet packaging material. The preparation method comprises the following steps: adding gelatin into normal saline, soaking, performing autoclaved sterilization to obtain a gelatin solution, then adding epsilon-polylysine hydrochloride into the gelatin solution, and finally adding glutamine transaminase for reaction to obtain an epsilon-polylysine grafted gelatin solution; adding heparin into the solution, and reacting to obtain a heparinized gelatin solution; adding sodium alginate and glutamine transaminase, reacting, diluting, preparing hydrogel microspheres by adopting an electrostatic spraying method, and cross-linking to obtain the hydrogel microspheres. According to the invention, heparin molecules are incorporated into a pancreas islet packaging system, so that fibrosis at the periphery of the microspheres can be relieved, the pancreas islet cells are packaged by using the pancreas islet packaging material to prepare the biological artificial pancreas, the pancreas islet cell proliferation and insulin secretion can be promoted, and the pancreas islet packaging material has a good diabetes treatment effect.

The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

The invention relates to the technical field of biological medicines, in particular to a mesenchymal stem cell preparation for treating diabetes and a preparation method thereof. The stem cell preparation is prepared from the following components: umbilical cord mesenchymal stem cells and naringin coated SiO2, and preparation raw materials of the naringin coated SiO2 are prepared from the following components in parts by weight: 10 to 15 parts of tetraethoxysilane (TEOS), 4 to 6 parts of 3-mercaptopropyl oxysilane (MPTMS), 2 to 3 parts of naringin, 0.8 to 1.2 parts of succinic anhydride and 2 to 3 parts of cysteamine hydrochloride. The prepared stem cell preparation has synergistic blood lineage of each component, and can repair pancreas islet injury and inhibit inflammatory response.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some embodiments, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some embodiments, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

The invention belongs to the technical field of biomedicine, and relates to a method for increasing the yield of pancreas islet organs differentiated by pluripotent stem cells and improving the stability. The method comprises the following steps: (1) inoculating pluripotent stem cells, and culturing by adopting a basic culture medium containing Y-27632; (2) changing the liquid, and continuously culturing by adopting a basic culture medium; (3) culturing for 1 day by using an S1D1 culture medium, and then culturing for 2-3 days by using an S1D2 culture medium; (4) changing the liquid, and culturing for 2-3 days by adopting the S2 culture medium; (5) changing the liquid, and culturing for 1-2 days by adopting an S3 culture medium; (6) changing the liquid, and culturing for 4-7 days by adopting a culture medium S4; (7) changing the liquid, and culturing for 3-10 days by adopting an S5 culture medium; and (8) carrying out cell sphere repolymerization, and culturing for 3-21 days by using an S6 culture medium to obtain the pancreas islet organ. The present invention increases the yield and differentiation efficiency at each differentiation stage and increases the scale yield at the cellular level.

The present disclosure provides methods of producing a population of endodermal stem cells (EnSC), a population of EnSC-derived PP cells, a population of EnSC-derived EP cells, or regenerative pancreatic islet tissue (E-islets). The disclosure also relates to EnSC, EnSC-derived PP cells, EnSC-derived EP cells or regenerated pancreatic islet tissue obtained using the method, and therapeutic uses thereof.

The invention relates to the technical field of biological pharmacy, in particular to application of a recombinant protein DEL-1 in preparation of a medicine for resisting pancreatic beta cell inflammation. The recombinant protein DEL-1 has a remarkable inhibition effect on pancreatic beta cell inflammatory response induced by high glucose and high fat. Experiments show that in an islet beta cell inflammation model constructed by combining high glucose with palmitic acid, DEL-1 can significantly reduce the expression level of inflammatory factors such as IL-1beta, IL-6, TNF-alpha and the like. The DEL-1 is proved to have a definite effect of resisting pancreatic beta cell inflammation.

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 a composite combined preparation for synergistically treating and conditioning diabetes, relates to the technical field of foods, health foods or dietary supplements for adjuvant therapy and health care of diabetes, and in particular relates to a composite combined preparation for synergistically treating and conditioning diabetes. The preparation comprises albumin peptide, saussurea involucrata culture, vitamin B1, vitamin B2, wheat oligopeptide, corn oligopeptide, collagen peptide, mulberry leaf extract, rhizoma polygonati extract, sea-buckthorn extract, isomaltitol, maltodextrin, ginseng extract and bitter gourd extract. Through the synergistic effect of all the components, comprehensive auxiliary conditioning on diabetes is realized from multiple targets of maintaining colloid osmotic pressure and nutrition, regulating glycolipid metabolism in multiple ways, protecting pancreatic beta cell functions, enhancing insulin sensitivity, preventing nerve and blood vessel complications, meeting special diet requirements and the like. The composition can be prepared into food, health-care food or dietary supplement and other dosage forms.

The invention relates to an islet repair ICK mode oral polypeptide optimization system taking VDAC1 as a target based on ESM2 and a genetic algorithm, and the system comprises a mutation module which is used for carrying out mutation and recombination by adopting the genetic algorithm according to original protein sequence data to generate an initial population; the prediction module is used for respectively inputting the protein sequence data of the initial population into a protein dimer dissociation energy prediction model, a protein toxicity prediction model and a protein cell penetrability prediction model to obtain a dissociation energy prediction value delta G, a toxicity probability value T and a cell membrane passing transmission probability Ed; and the optimization module is used for acquiring the optimal individual performance of the highest fitness score to output the Pareto optimal sequence index, and recording the hotspot residue distribution and the site mutation frequency at the same time. On the basis of keeping the biological activity of the original sequence, the key drug properties are improved in a breakthrough manner.

The present application relates to a kind of pharmaceutical composition for treating type 2 diabetes and its application.The pharmaceutical composition includes icariin, hydroxymethyl coumarin and cinnamaldehyde, by three-component synergistic effect, simultaneously act on insulin resistance, pancreatic beta cell apoptosis and systemic metabolic inflammation three type 2 diabetes core pathological links, auxiliary reduce serum lipid level, and reduce drug-related liver injury risk, good safety.Animal experiment results show that three-drug combination group can effectively reduce blood sugar (decrease about 50%), significantly improve islet structure atrophy, restore hepatocyte index arrangement, reduce glomerular hypertrophy, significantly reduce serum TG and CHOL level (P<0.05) and inflammatory factor IL-6 and TNF-alpha level (P<0.05), and avoid the hepatotoxicity risk (ALT / AST restores to close to normal level) of hydroxymethyl coumarin.The present application is composed of three kinds of natural monomers with clear structure, and has clear components and controllable quality, which provides a more optimal comprehensive treatment strategy for the treatment of type 2 diabetes and its complications.

The invention relates to the technical field of gene vectors, and discloses a multi-target multi-gene stable silencing vector and an application thereof in treating diabetes mellitus, and a multi-gene multi-target gene modification combined element is safely and efficiently integrated at a gene safety parking point of a second intron region of a CCR5 gene in a genome in a reverse fixed point manner by using a non-viral vector system; therefore, the effect of continuously silencing expression of a plurality of target genes such as MSTN, GRB10 and PTBP1 for a long time is achieved, and aging of mesenchymal stem cells cultured in vitro is remarkably inhibited. When the mesenchymal stem cells modified by the multi-target multi-gene stable silencing vector are infused, the activity is high, the chronic inflammatory microenvironment is effectively inhibited, and the senescence process is delayed; moreover, proliferation and differentiation of pancreatic beta cells are promoted, insulin secretion is enhanced, insulin resistance is effectively resisted, and diseases such as diabetes mellitus are prevented.

The present disclosure relates to a method of generating pancreatic lineage cells, e.g. islet-like cell aggregates comprising pancreatic beta cells, comprising the steps of providing a single cell suspension of a population of endocrine progenitor cells (EP), allowing the EP cells in the single cell suspension to form 3D structures, and culturing the cells under conditions allowing differentiation into pancreatic mono-hormonal beta cells. The present disclosure also relates to islet-like cell aggregates obtainable by said method and their medical use.

The invention discloses nutrition-balanced flour assisting in pancreas islet repair as well as a preparation method and application of the nutrition-balanced flour. The nutrition-balanced flour is prepared from the following raw materials in parts by mass: 40-60 parts of whole grains, 10-15 parts of beans, 5-15 parts of vital gluten, 7-10 parts of potatoes, 7-10 parts of vegetables, 5-8 parts of bacteria and algae, 5-8 parts of nut seeds, 3-5 parts of medicinal and edible food and 3-5 parts of beer yeast. The invention provides more comprehensive nutrition powder containing whole grains, beans, potatoes, nuts and the like, and further comprises common food with the effect of reducing blood sugar and medicinal and edible food which has the effect of reducing blood sugar and can prevent diabetic complications, and the nutrition flour has the following functions: balanced nutrition is provided for the body; blood sugar reduction is assisted; the islet cells are assisted to repair; and diabetic complications are prevented. The invention relates to an application of nutrition-balanced flour assisting in pancreas islet repair. The flour is used for making steamed buns, dumplings, steamed stuffed buns, wontons, noodles, cakes, biscuits or other flour products.

The present disclosure provides methods of amplifying tissue samples derived from humans for purposes of treating certain diseases. The method comprises: isolating a small amount of associated tissue by biopsy or other tissue acquisition methods; the tissue is amplified in vitro, and meanwhile, natural functions are reserved; and re-implanting the amplified tissue to alleviate human disease. One example includes ex vivo expansion of human pancreatic islet tissue and reimplantation of the expanded cells into an individual with Type 1 diabetes for treatment and long term relief or cure of disease.

This invention discloses a traditional Chinese medicine composition for reversing type 2 diabetes and its preparation method, belonging to the field of traditional Chinese medicine technology. It comprises the following raw materials in parts by weight: Astragalus membranaceus 25-35 parts, Rehmannia glutinosa 20-30 parts, Trichosanthes kirilowii 15-25 parts, Anemarrhena asphodeloides 10-20 parts, Coptis chinensis 8-15 parts, Salvia miltiorrhiza 15-25 parts, Ligusticum chuanxiong 8-15 parts, Paeonia lactiflora 10-20 parts, Pueraria lobata 20-30 parts, Atractylodes lancea 10-20 parts, Poria cocos 15-25 parts, Alisma plantago-aquatica 10-20 parts, Ophiopogon japonicus 15-25 parts, Schisandra chinensis 5-15 parts, and Glycyrrhiza uralensis 3-10 parts. This invention strictly follows the principles of traditional Chinese medicine's principal, assistant, adjuvant, and guide herb combination, comprehensively addressing the four methods of invigorating qi and nourishing yin, clearing heat, resolving blood stasis, and eliminating turbidity. It regulates the body's metabolism from the root cause, significantly controlling blood sugar and improving insulin resistance, while also protecting pancreatic function, thus solving the problems of single herb combinations and limited efficacy in traditional Chinese medicine.

The application provides an islet-vascular co-culture system based on a microfluidic chip, a building method and application, and the building method of the islet-vascular co-culture system comprises the following steps: S1, preparing microfibers loaded with islets; S2, preparing an assembled chip, the assembled chip comprises a containing cavity, first microchannel networks and second microchannel networks are symmetrically arranged on two sides of the containing cavity, and the first microchannel networks and the second microchannel networks are respectively communicated with a liquid inlet and a liquid outlet at an end away from the containing cavity; S3, controlling the flow of the liquid inlet to be 6-8 muL / min to carry out dynamic culture. The application can simulate the key structure and characteristics of islet tissue, can evaluate a diabetes treatment drug in vitro, can bridge the gap between in vitro and in vivo models, and can provide new tools and methods for the fields of drug development, disease model construction and personalized medical treatment.

The invention provides a microfiber for loading pancreas islet, a preparation method and application, the preparation method comprises the following steps: S1, preparing a micro-fluidic chip and building a pneumatic control micro-fluidic spinning device, the micro-fluidic chip is provided with channels for conveying a core flow, a sample flow and a sheath flow, the micro-fluidic chip further comprises a PDMS chamber, and the PDMS chamber is provided with a PDMS cavity; a channel for periodically pressurizing to expand so as to squeeze and close the core flow; s2, adding collagen into the core flow, then adding beta-TC6 cells to enable the cell density of the core flow to be 4 * 10 < 6 > mL <-1 > to 8 * 10 < 6 > mL <-1 >, respectively controlling the flow rates of the core flow, the sample flow and the sheath flow to be 0.8-1.2 [mu] L / min, 18-22 [mu] L / min and 80-120 [mu] L / min, and carrying out preparation under the frequency of 0.8-1.2 Hz; according to the method, a pneumatic control droplet generation method is combined with microfluidics, so that the high-flux islet-like can be prepared more simply and quickly, and the difference between the islet-like and an in-vivo complex microenvironment is small; the prepared microfiber is continuous and complete, and a large number of water-phase liquid drops containing beta-TC6 cells are uniformly distributed in the microfiber.

The invention provides a core-shell structure microgel system. The core-shell structure microgel system comprises a core and a shell coating the core, the core is composed of a composite hydrogel of methacrylated gelatin and methacrylated chitosan; the shell is formed by double crosslinking of polyethylene glycol diacrylate and alginate. The core serves as a functional core, provides a highly simulated natural extracellular matrix and maintains pancreas islet activity, and the shell serves as a barrier to protect the core, regulate material exchange and provide mechanical support. The core-shell structure microgel system allows diffusion of glucose, oxygen and insulin and blocks immune globulin, cell factors and immune cells, so that fibrosis wrapping is reduced to the greatest extent.

The invention relates to application of lactobacillus acidophilus LA85 in preparation of a product with a blood sugar reducing effect. The brand new application of the lactobacillus acidophilus LA85 strain is developed, namely the lactobacillus acidophilus LA85 strain is used for inhibiting alpha-glucosidase, reducing blood sugar and improving diabetes mellitus, and tests prove that the food intake, the water intake and the urine volume of a mouse with type II diabetes mellitus can be effectively controlled after intervention of the LA85 strain, and the weight value of the mouse is stabilized; the glucose absorption and metabolism capability of diabetic mice is effectively improved, and continuous damage of pancreatic beta cell functions is retarded; the blood lipid level disorder state of the mouse with the type II diabetes mellitus is improved; the inflammation level of a mouse body with type II diabetes mellitus is reduced, and the immunity is improved; and a very good improvement and recovery effect is achieved on abundance and diversity reduction of intestinal flora of the type II diabetes mellitus mice.

The application relates to a construction method of a Mettl3 transgenic mouse model with specific knockout, enriches the understanding of the function and action mechanism of Mettl3 in mature pancreatic islet beta cells, and provides a new thought and target for the pathogenesis and treatment of diabetes.

The invention belongs to the field of new application of medicines, and particularly relates to application of triptolide in preparation of medicines for treating diabetic vascular obstruction complications. Diabetes vascular obstruction is a common serious complication of diabetes and can cause various tissue injuries such as cardiovascular diseases, nephropathy and retinopathy. Experiments prove that the triptolide can remarkably improve the problems of blood vessel blockage, blood flow slowing, abnormal neovascularization and the like caused in a high-glucose environment, and meanwhile, the expression of blood glucose related indexes (such as Glucose and HbA1c) and inflammatory factors (such as TNF-alpha and IL-1beta) is reduced. In addition, triptolide can also protect pancreas from high glucose damage and improve functions of pancreatic beta cells. According to the invention, the clinical application range of the triptolide is expanded, and a new candidate substance is provided for drug treatment of diabetic vascular complications.

The invention provides a composition for treating diabetes as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: loading berberine on a milk exosome to prepare a berberine-loaded exosome, loading liraglutide on phycobiliprotein to prepare liraglutide-loaded phycobiliprotein, preparing PEG-COOH, reacting with chitosan to prepare a chitosan-polyethylene glycol graft polymer, embedding the berberine-loaded exosome and the liraglutide-loaded phycobiliprotein, and cross-linking to prepare microspheres. And centrifuging, washing and drying to obtain the composition for treating diabetes. According to the prepared composition for treating diabetes, the loading capacity of the medicine is greatly improved, the carrier also has a very good protection effect on islet cells, so that islet cell injury is repaired, normal insulin secretion of islet cells is promoted, the prepared composition can be orally taken, the medicine effect is greatly improved, the compliance of patients is improved, and the preparation method is suitable for clinical application. The bioavailability is high, and safety and non-toxicity are realized.

The invention relates to the technical field of medicines, in particular to application of a recombinant protein DEL-1 in preparation of a medicine for resisting pancreatic beta cell senescence. Within the concentration range of 400-1000 ng / ml, the DEL-1 can reduce the high glucose and high fat induced pancreatic beta cell SA-beta-Gal positive rate by 39.5% or above, and the anti-aging effect is remarkable.