46 results about "Pancreatic beta Cells" patented technology

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 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 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.

Disclosed herein include methods, compositions, and kits suitable for use in cell therapy. In some embodiments, there are provided methods and compositions for differentiating stem cells into pancreatic beta cells capable of producing insulin.

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 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 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.

The invention provides a high-stress-tolerance pancreas islet organ as well as a preparation method and application thereof. Specifically, the invention provides a method for preparing pancreas islet organs. The invention also provides a use of a reagent combination comprising (a) a pancreatic islet organ and (b) a compound of formula I or a pharmaceutically acceptable salt thereof. In the presence of the compound shown in the formula I or the pharmaceutically acceptable salt thereof, pancreatic endocrine progenitor cells are cultured, so that the increase of the differentiation proportion of pancreatic beta cells is promoted, and pancreatic islet organs with high stress tolerance are obtained; according to the present invention, the combination of the pancreatic islet organ and the compound represented by the formula I or the pharmaceutically acceptable salt thereof can significantly improve and alleviate the integration stress reaction generated during the pancreatic islet organ transplantation compared to the only transplantation treatment, such that the pancreatic islet beta cell identity loss is resisted, and the stress tolerance of the pancreatic islet organ is significantly improved; therefore, the invention provides a new strategy for the treatment of diabetes, and has a wide application prospect.

The invention relates to a preparation method and application of ganoderma lucidum and coix seed mycoplasm, and belongs to the technical field of traditional Chinese medicine and health food processing. According to the preparation method of the lucid ganoderma and coix seed mycoplasm, the lucid ganoderma and coix seed mycoplasm is obtained through liquid fermentation by taking coix seeds as a fermentation substrate and lucid ganoderma as a fermentation strain. The ganoderma lucidum and coix seed mycoplasm composition is obtained through a ganoderma lucidum and coix seed two-way fermentation technology, functional ingredients are increased, and the ganoderma lucidum and coix seed mycoplasm composition has the effects of enhancing immunity, protecting pancreas islet beta cells and improving glycolipid metabolism. The invention develops the application of the traditional Chinese medicine composition in the fields of food and health care products.

The present application relates to the technical field of mRNA vaccine, and specifically discloses a proinsulin mRNA vaccine for protecting the function and quantity of pancreatic beta cells. The vaccine is composed of a lipid nanoparticle (LNP) and an mRNA wrapped by the LNP; the mRNA is an mRNA sequence encoding proinsulin, and all uridines in the mRNA sequence are replaced by N1-methyl pseudouridine. The mRNA vaccine of the present application realizes the dual protection of the quantity and function of pancreatic beta cells, compared with the existing intervention means which only focus on blood glucose control or immune regulation, the present application delays the occurrence process of type 1 diabetes from the root, and provides a new technical scheme and drug selection for the prevention and early intervention of type 1 diabetes.

The invention discloses a synthesis method of a fullerene nano material with glycolipid metabolism regulation capability, and belongs to the technical field of material science and biomedical engineering. The fullerene and the metformin are combined through chemical bonds, the strong oxidation resistance of the fullerene and the hypoglycemic effect of the metformin are exerted at the same time, the synergistic treatment effect is formed, and the drug composition is superior to a single drug; active oxygen in cells can be efficiently removed, oxidative stress is effectively relieved, and the functions of pancreatic beta cells are protected; through structural modification, the problem of low bioavailability caused by hydrophobicity of fullerene and hydrophilicity of metformin is solved, and the solubility and absorption efficiency of the medicine are improved; in conclusion, through chemical combination of the fullerene and the metformin, a dual-mechanism synergistic effect of oxidation resistance and blood sugar reduction is achieved, the treatment effect is remarkably improved, meanwhile, good safety and biocompatibility are achieved, and important application value is achieved in the field of treatment of the type II diabetes mellitus.

The invention discloses a type 2 diabetes mellitus mouse model construction method combining artificial intelligence prediction and multi-target knockout. Acquiring and standardizing mouse multi-omics data and phenotype baseline data to form a standardized modeling data set; constructing an interaction map covering the functions of the pancreatic beta cells on the basis of the data; screening to obtain a target combination and a target phenotype prediction result, generating a construction instruction, and submitting the construction instruction to a controlled facility to execute multi-gene knockout transformation, so as to obtain a transformed mouse and a transformation receipt; acquiring actual measurement phenotype data of the transformed mouse based on the transformation receipt, and comparing the actual measurement phenotype data with a target phenotype prediction result to generate phenotype deviation measurement and a phenotype judgment result; and when the phenotype determination result is satisfied, registering the target combination, the prediction result, the actually measured phenotype data and the transformation receipt to form the type-2 diabetes mellitus composite mouse model. According to the method, AI-driven multi-target genetic modification closed-loop optimization is realized, and the efficiency and accuracy of complex metabolic disease animal model construction are improved.

The invention discloses a method for efficiently and directionally inducing IPS to be differentiated into pancreatic beta cells. According to the method, through staged signal regulation and strict cell screening, the directionality and the overall efficiency of differentiation are remarkably improved. The whole process pays attention to cell quality control from the initial stage, and a stable foundation is laid for subsequent differentiation by screening iPS cells with uniform morphology and high expression of pluripotent markers. Progressive signal molecule regulation is adopted in each stage, and an accurate differentiation path is formed from Activin A gradient adjustment during endoderm induction, synergistic effect of FGF10 and retinoic acid in pancreatic precursor cell differentiation and Wnt signal inhibition during endocrine precursor cell induction, so that the non-specific differentiation tendency is effectively reduced. Meanwhile, cell enrichment steps of key nodes, such as SOX17 positive cell screening in an endoderm stage and Ngn3 magnetic bead sorting of endocrine precursor cells, further improve the purity of a target cell population and avoid interference of parenchyma cells on subsequent function maturation.

The invention discloses an application of a jerusalem artichoke tuber alcohol extract in preparation of a medicine for treating type 2 diabetes mellitus, and belongs to the technical field of medicines, the chemical components of the jerusalem artichoke tuber alcohol extract are mainly flavonoid substances, and the jerusalem artichoke tuber alcohol extract can remarkably recover the weight of a mouse with the type 2 diabetes mellitus and improve glucose metabolism indexes such as fasting blood-glucose and oral glucose tolerance; meanwhile, insulin sensitivity is stimulated to secrete insulin, and the functions of pancreatic beta cells are recovered; in addition, the concentration of biochemical indexes such as total cholesterol and triglyceride in the liver is reduced, lipid metabolism of the liver is improved, and a new direction is provided for research and development of natural plant source hypoglycemic products.

The present application provides compositions of induced pluripotent stem cells (iPSCs) or pancreatic beta cells and poxviruses, as well as methods of making the compositions and methods of using the compositions to treat diseases.

The invention discloses an application of WBSCR16 protein as a target spot in preparation of a medicine for treating diabetes, and provides an application in research and development of related medicines. By constructing a mouse model of Wbscr16 with pancreatic beta cells specifically knocked out, the action mechanism of WBSCR16 in diabetes mellitus attack is deeply researched, and it is found that WBSCR16 participates in regulating the mitochondrial function of the pancreatic beta cells, and then insulin secretion is affected. On the basis, the invention provides a reagent for regulating the expression of the WBSCR16 protein for treating diabetes mellitus. Meanwhile, a construction method of the Wbscr16 pancreatic beta cell specific knockout mouse model is described in detail, and an important tool is provided for related research. Meanwhile, candidate drugs capable of acting on a WBSCR16 target spot are screened out through drug prediction, and a new strategy and a potential intervention direction are provided for treatment of diabetes mellitus.

The invention discloses a fusion protein for regulating and controlling functions of pancreatic beta cells based on an optogenetics technology and application of the fusion protein, and relates to the technical field of biology. The fusion protein Opto LOVTRAP disclosed by the invention has very high temporal-spatial resolution, and rapid and accurate control on a single cell can be realized by adjusting blue light; opto LOVTRAP has reversibility, can effectively inhibit a pancreatic beta cell Ca < 2 + > channel under a dark condition, and can quickly stop playing a role after being stimulated by blue light, so that the purpose of reversibly and accurately regulating insulin secretion is achieved. Opto LOVTRAP is targeted to regulate the concentration of Ca < 2 + > in cells, and is a final triggering factor for release of pancreas islet vesicles, so that the opto LOVTRAP is not influenced by the KATP function, and the purpose of breaking through the bottleneck of a traditional clinical treatment mode is achieved.

The present disclosure provides novel methods for increasing β-cell viability in islets by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to the islets. The disclosure also provides novel methods for treating a disease or condition in a subject, such as type 1 diabetes mellitus, by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to islets and transplanting the islets into the subject to treat the disease or condition. Kits and compositions including RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, are also provided to increase β-cell viability.

The present disclosure provides a use of a substance targeting BRD4 in the preparation of a product related to diabetes. In the present disclosure, it is found that the expression of BRD4 in human diabetic beta cells is significantly reduced, and BRD4 plays an important role in maintaining beta cell maturation and differentiation, and long-term and acute BRD4 deficiency can lead to reduced insulin secretion and down-regulation of differentiation markers, highlighting the key role of BRD4 in pancreatic beta cells, providing a target BRD4 that has a significant impact on diabetes, so that substances targeting BRD4 can help to assess the susceptibility of diabetes, screening, prevention, intervention and treatment of diabetes.

The invention relates to the technical field of microorganisms, and particularly discloses lactobacillus crispatus and application thereof in regulating blood sugar, improving cognitive impairment of diabetes and treating vaginitis. In the invention, the lactobacillus crispatus A21013 and the lactobacillus crispatus A21033 are found to have multiple effects for the first time, can reduce blood sugar, maintain forms and functions of pancreatic beta cells, improve cognitive impairment of diabetes, and inhibit growth and reproduction of vaginal harmful pathogens and oral pathogenic bacteria, so that the lactobacillus crispatus A21013 and the lactobacillus crispatus A21033 can be used for treating diabetes mellitus. A dual prevention and treatment means is provided for patients with diabetes, cognitive impairment and vaginitis.

The invention discloses a pancreatic beta cell precursor cell transplantation chip based on human-derived iPSC (induced pluripotent stem cell) as well as a preparation method and application of the pancreatic beta cell precursor cell transplantation chip. The chip is composed of beta cell precursor cells (expressing Pdx1, Nkx6.1 and NeuroD1) and a porous degradable bracket (PCL / hyaluronic acid composite material), wherein the beta cell precursor cells (expressing Pdx1, Nkx6.1 and NeuroD1) are obtained by performing four-stage induction on autologous iPSC. The preparation method comprises the steps of autologous iPSC acquisition, beta cell precursor cell induction, three-dimensional bracket preparation and chip assembly. After the chip is implanted into the pancreas of a patient through minimally invasive surgery, precursor cells are differentiated into mature beta cells in vivo, insulin is secreted, the stent is gradually degraded, the pancreas islet function can be fundamentally improved, and the chip is used for treating type I and type II diabetes mellitus. The invention avoids immunological rejection, improves cell survival and functional stability, and has significant clinical transformation value.

The invention provides application of a lobular formosan lattuce herb extract with a function of regulating insulin secretion of pancreatic beta cells in preparation of a hypoglycemic drug, and relates to the technical field of natural product extracts. A preparation method of the lobular broadleaf holly leaf extract comprises the following steps: taking high-quality and dry lobular broadleaf holly leaves, crushing, carrying out microwave treatment, and carrying out enzyme treatment; and carrying out water extraction and alcohol extraction, and separating the product. Compared with the prior art, the preparation method has the advantages that the dual advantages of microwave and enzyme treatment are ingeniously fused, the efficiency of the extract is greatly improved, the extract has a remarkable effect in the aspect of improving type 2 diabetes symptoms of model mice, the broadleaf holly leaf component is highly utilized, the loss of precious components is effectively reduced, and the preparation method is suitable for industrial production. The yield is obviously improved. Besides, the preparation method disclosed by the invention is comprehensively optimized in process, is simple and convenient to operate, is stable and reliable, and brings unprecedented development potential and broad prospects for the market.

The application discloses a sea cucumber active peptide, a preparation method and a blood glucose reduction application, belongs to the field of biological medicines, and the amino acid sequence of the active peptide is Thr-Ser-Pro-Gly-Leu-Gly-Lys-Gly-Phe. The preparation method comprises the following steps: putting chopped sea cucumbers into a reaction container, adding a compound protease for enzyme hydrolysis; enzyme inactivation and centrifugation are performed, and the supernatant is taken; the supernatant is subjected to ultrafiltration through an ultrafiltration membrane with a molecular weight cut-off of 1000 Da, the obtained filtrate is dried to obtain a sea cucumber oligopeptide powder, and Sephadex G25F gel chromatography column separation and purification and C18 reverse phase chromatography column further purification are performed. Experiments show that the active peptide can relieve STZ-induced pancreatic beta cell damage.

The present application relates to a composition for maintaining healthy blood sugar level and its preparation method and application, and belongs to the technical field of health products. The composition for maintaining healthy blood sugar level comprises mulberry leaf extract, cactus extract, prunus domestica extract, glyceryl tributyrate and capsaicin. The present application has the beneficial effect of providing a composition of active ingredients which can effectively reduce the level of cortisol, significantly reduce the blood sugar level, and protect the activity of pancreatic beta cells. The composition is good for restoring insulin sensitivity and controlling weight. The present combination formula is reasonable, the product performance is stable, the preparation is simple, and the industrialized production is easy to realize.

The application provides a construction method of a zebrafish model of diabetic cerebral hemorrhage sequelae for high-throughput drug screening, and belongs to the technical field of biotechnology.The first zebrafish model capable of comprehensively simulating the complex pathological phenotypes of clinical diabetic cerebral hemorrhage sequelae is successfully constructed, and the blank of the research model in the field is filled.The pathological changes of the model are highly consistent with the symptoms of the patients with clinical diabetic cerebral hemorrhage sequelae, such as glucose metabolism disorder, pancreatic beta cell damage, cerebral vascular injury and hemorrhage, brain cell apoptosis, inflammatory reaction and behavior abnormality, and the limitation that the existing single disease model cannot simulate the synergistic pathogenesis of diabetes and cerebral hemorrhage is overcome, so that a reliable experimental animal model is provided for high-throughput screening of active ingredients against the disease.

The present disclosure provides compositions of stem cell-derived pancreatic islet cells engineered for improved engraftment and methods of use thereof for treating a subject having an insulin deficiency.

The invention provides an efficient and repeatable stem cell-derived pancreatic beta cell preparation method, Wnt and Notch signal channels are regulated and controlled in stages, a culture environment is optimized in combination with bionic matrix stiffness, and differentiation of pluripotent stem cells to functional pancreatic beta cells is promoted. The method specifically comprises the following steps: 1, stage signal regulation: activating a Wnt pathway at the early stage of differentiation to promote endoderm induction, and then inhibiting a Notch pathway to enhance endocrine precursor cell formation; 2, bionic matrix rigidity optimization: adopting hydrogel (-1-5kPa) matched with natural pancreas islet rigidity to simulate an in-vivo microenvironment, and improving beta cell maturity and functions; 3, glucose responsiveness optimization: through later-stage low-glucose / high-glucose alternate culture, the glucose sensitivity of beta cells is enhanced, so that the insulin secretion amount is close to the primary cell level. According to the method, the yield and the function of the beta cells are remarkably improved, and a reliable cell source is provided for diabetes cell therapy.

The invention relates to the technical field of crossing of traditional Chinese medicine and modern transplantation medicine, in particular to application of Xuebijing injection in preparation of a medicine for improving pancreatic beta cell survival in an inflammatory microenvironment. Aiming at a core pathological link of inducing beta cell apoptosis by inflammatory factor storm (IL-1beta / TNF-alpha / IFN-gamma) in pancreatic islet transplantation, the survival rate and the function of beta cells in an inflammatory microenvironment are remarkably improved by inhibiting expression of apoptosis key proteins such as Cleved Caspase-3 / PARP, and an innovative treatment strategy is provided for relieving pancreatic islet inflammatory injury after clinical pancreatic islet transplantation.

The present application relates to the technical field of biological medicine and gene therapy, and particularly relates to a nucleic acid delivery system targeting pancreatic beta cells and application thereof. The nucleic acid delivery system comprises a nanocomplex formed by a cationic polymer modified with a targeting ligand and siRNA; the targeting ligand is a GLP-1 receptor targeting peptide; the cationic polymer is a PEI-PFA polymer; and the siRNA is siRNA targeting DYRK1A. The present application provides a novel pancreatic beta cell targeting delivery platform for gene therapy of type 2 diabetes. The platform realizes beta cell function regeneration by precisely regulating DYRK1A gene expression, and has targeting, safety and high efficiency, thereby providing a new strategy with broad clinical application prospect for diabetes treatment.

A method for generating immuno-free and stress-resistant donor cells comprising editing PRDM1 and FOXP3 genes in T-cells and B-cells with CRISPR-Cas9 and modulating immune responses to reduce inflammation and prevent autoimmunity. Particularly, the present invention discloses a method for treating Type 1 Diabetes, comprising genetically modifying pancreatic beta cells with CRISPR-Cas9, and altering HLA expression, and upregulating immune checkpoint molecules such as PD-L1 to obtain immune-tolerant and stress-resistant pancreatic beta cells.