110 results about "Beta cell" patented technology

The invention discloses a human pancreas islet function digital evaluation method and system based on an AI algorithm, and relates to the technical field of artificial intelligence medical evaluation, and the method comprises the steps: collecting and preprocessing multi-modal physiological data; extracting multi-source features to generate a low-dimensional input vector; performing dynamic weighted fusion based on a space-time attention mechanism; constructing a neural differential equation model in which a beta cell two-phase secretion mechanism is introduced, and outputting pancreas islet function evaluation indexes; and a dynamic evaluation report is generated through a visualization and early warning module. According to the method, the modeling accuracy of the pancreas islet function under the interference of complex behaviors can be improved, the individualized quantitative evaluation of function decline trend prediction and sensitivity scoring is realized, the clinical staging reference value and the model interpretation ability are enhanced, and the technical problems of low fusion precision, poor dynamic nature and lack of physiological constraints in the existing method are solved.

The invention relates to a lactic acid bacterium capable of reducing fat, resisting inflammation and reducing blood sugar, which is classified and named as pediococcus acidilactici XJ335, and is preserved in the China General Microbiological Culture Collection Center (CGMCC), the preservation number is CGMCC No.30093, the preservation date is March 22, 2024, and the preservation address is No.3, Yard 1, Beichen West Road, Chaoyang District, Beijing. The strain can achieve the fat reducing effect by adjusting the abundance of intestinal flora; the levels of IL-6 and TNF-alpha in serum of diabetic mice are remarkably improved through regulation, so that the anti-inflammatory effect is achieved; various cardiovascular diseases of atherosclerosis are prevented by adjusting the levels of TC, TG, HDL-C and LDL-C; by reducing FINS and HOMA-IR levels and improving HOMA-IS, HOMA-beta and QUICKI value levels, insulin resistance of a body is reduced, insulin sensitivity and pancreas islet beta cell functions of the body are improved, gene expression related to blood sugar regulation is regulated, and an excellent blood sugar reducing effect is achieved in the body.

The invention relates to an electrochemical sensor for monitoring beta cell insulin secretion in real time and a preparation method and application thereof, the sensor is an electrochemical chip modified by a multi-dimensional nano material, and the multi-dimensional nano material on the electrochemical chip is used for capturing dopamine released by beta cells; and determining the release quantity of dopamine according to the electrochemical signal. According to the method, the insulin secretion condition of the beta cells is monitored in real time by taking dopamine as a tracer agent, and the exocytosis process of the beta cells can be researched under natural and normal conditions. According to the invention, only a common Faraday cage and a basic electrochemical workstation are needed for detection, one or more beta cells can be detected, the operation is simple, and the research efficiency of insulin secretion is greatly improved. In addition, the medicine for regulating beta cell insulin secretion can be efficiently screened, and a foundation is laid for research of diabetes treatment medicine.

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 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.

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 formula of a composition capable of assisting in reducing blood sugar and preventing diabetes, and relates to the field of health food, the composition has the effects of reducing blood sugar and preventing diabetes, and the composition comprises the following composition components: 0.25 to 0.37% of bitter gourd peptide, 0.018 to 0.026% of corosolic acid, 0.39 to 0.48% of mulberry leaf extract, 0.083 to 0.095% of pseudo-ginseng extract, 0.115 to 0.132% of radix polygonati officinalis extract, and 0.00003 to 0.00005% of chromium-enriched yeast. By adopting the composition formula for assisting in reducing blood sugar and preventing diabetes, the formula composition has the effects of assisting in reducing the blood sugar level and treating. Meanwhile, the composition also has a synergistic effect on prevention of diabetes caused by hyperglycemia symptoms, the components of the composition are equal-part compositions formed by physical stirring and uniform mixing, and the increase of postprandial blood sugar level can be effectively inhibited, so that the effects of assisting beta cells of a body to secrete insulin and improving the blood sugar level are achieved. And insulin can promote the utilization of sugar by cells, the synthesis of hepatic glycogen and the improvement of the metabolism of sugar, so that the effect of reducing blood sugar is finally achieved. The raw materials of the composition can be purchased and obtained in the market, the raw materials are simple and easy to obtain, the production benefit is high, and the composition is suitable for being widely used.

The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and / or ameliorate autoimmune diseases.

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 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 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.

Provided herein are systems of modulating gene expression, methods of use thereof, and cells engineered thereof for the purpose of differentiating cells, for example beta cells.

The invention relates to a method of differentiating pancreatic bi-potent progenitor cells into beta cells comprising cultivating pancreatic endocrine precursor cells in a medium that promotes the cAMP signalling pathway that lies downstream of apical-basal polarity in endocrine precursors, which can be used to increase the differentiation of progenitor cells into beta cells. Furthermore, the present invention relates to a method of enriching and / or isolating one or more cells expressing a marker of apical-basal polarity, thereby isolating beta cells, and to a method of producing a population of beta cells from a population of human embryonic stem cells. Furthermore, the present invention relates to a population of beta cells obtainable by the method, a pharmaceutical composition comprising the beta cells, a cell culture of progenitor cells in a medium comprising a cAMP agonist, a complex comprising a beta cell bound by the binding agents specific for CD133 and CD49a, and a use of specific binding partners for isolating beta cells.

This provides an unlimited supply method for human β-cells from stem cells. [Solution] Compositions and methods for promoting the differentiation of stem cells into beta cells using one or more epigenetically modified compounds are disclosed herein. The disclosure also relates to compositions and methods for selecting and enriching differentiated beta cells. The disclosure also relates to compositions and methods for irradiating a cell population to reduce proliferation. In some embodiments, methods are provided herein, comprising the step of contacting a population of pancreatic progenitor cells or their precursors with an epigenetically modified compound, wherein the contact step results in a population of endocrine cells in which the proportion of chromogranin A-positive (CHGA+) cells or C-peptide-positive and NKX6.1-positive (C-PEP+, NKX6.1+) cells is increased compared to a corresponding population of endocrine cells that have not been contacted with the epigenetically modified compound.

The present invention relates to a test kit for performing an assay to detect and measure at least one autoantibody molecule in a subject developing type 1 diabetes (T1D). The invention more specifically relates to a recombinant antigen molecule fused to a bioluminescent reporter protein to detect an autoantibody molecule against a self-antigen. Said self-antigen is preferably expressed by pancreatic islet beta cells and include insulin, proinsulin, Glutamate decarboxylase 65, islet antigen 2, and Zinc transporter 8. More specifically, the present invention relates to an assay comprising a set of at least three recombinant antigen molecules in a single composition, the antigen molecules being selected from the list comprising recombinant human Glutamate decarboxylase 65, recombinant human islet antigen 2, recombinant human Zinc transporter 8, recombinant human insulin, and recombinant human proinsulin. The invention further relates to methods for determining the presence and / or level of at least one autoantibody molecule in a sample from a human subject developing T1D using said recombinant antigen molecules. According to the invention, the presence, absence, or amount of one or more autoantibody molecules against said self-antigens is determined with a luciferase immune precipitation system (LIPS) assay or a modified version of a LIPS assay, i.e., a solid phase capture LIPS (scLIPS) assay.

The invention discloses a stem cell medicine for pancreas islet repair and application, and belongs to the technical field of stem cell biology, and the stem cell medicine for pancreas islet repair is prepared by compounding a carrier, pancreatic progenitor cells and pancreas islet-like cells in proportion. The problems that in the prior art, due to the fact that stem cells are unstable in differentiation efficiency, poor in synergistic effect and poor in biocompatibility, islet injury cannot be repaired, and diabetes cannot be treated are solved. According to the present invention, the dual mechanisms of endogenous beta cell repair and exogenous beta cell supplement are adopted, and the beta cell function recovery and the group structure reconstruction are synchronously achieved through the reasonable ratio, such that the in-vivo blood glucose of the mouse is significantly reduced, the beta cell number and the glucose tolerance dose of the mouse are increased, and the low immunogenicity and the high anti-inflammatory property are simultaneously provided. The compound can be used for treating type I and type II diabetes mellitus, improving the insulin secretion function and relieving local inflammatory response of pancreas by promoting pancreas islet beta cell proliferation, and has application potential in treatment of type I and type II diabetes mellitus and pancreas islet repair.

The invention belongs to the technical field of biological medicine, and particularly relates to application of beta cell protein in preparation of medicine for preventing and treating abortion. Research finds and verifies for the first time that application of beta cell protein (BTC) promotes invasion and tubulation processes of extravillus trophoblast cell line-HTR8 cells, BTC has an obvious rescue effect on embryo absorption in abortion model mice in early and middle stages of pregnancy, and BTC is injected into the abortion model mice in an intraperitoneal cavity in early and middle stages of pregnancy to increase placenta weight, so that the abortion model mice in early and middle stages of pregnancy have an obvious rescue effect on embryo absorption. Therefore, the BTC has a certain treatment effect on the abortion, so that the BTC has a good practical application value.

Provided are functional modified stem cell-derived beta (β) cells (SC-beta cells) containing one or more modifications, such as genetic modifications, and related methods of their use and generation. In some embodiments, the modified cells are hypoimmunogenic cells. In some embodiments, the modified SC-beta cells are cells differentiated in vitro from a modified or hypoimmunogenic pluripotent stem cell that contains the one or more modifications. In some embodiments, the one or more modifications reduce or eliminate expression of MHC class I and / or MHC class II human leukocyte antigens and also exogenously express one or more tolerogenic factors such as CD47.

The disclosure provides polypeptides that specifically bind to HLA-DQ8 for treating Type 1 Diabetes (TID) and methods using same for reducing autoimmune destruction of pancreatic islet beta cells. In particular, the present disclosure relates to peptides containing at least one D-amino acid that are capable of blocking the presentation of antigenic islet peptides (e.g., lnsB:9-23) by HLA-DQ8, and to their uses, especially as it relates to the prevention and / or treatment of TID.

Disclosed herein are methods for directing the differentiation of stem cells towards a specific cell type.

The invention relates to the technical field of biology, in particular to application of SAFit2 in preparation of a reagent for improving pancreas islet dysfunction. The invention discovers that SAFit2 has a remarkable improvement effect on insulin secretion dysfunction in a high-glucose and high-fat induced islet injury model. Experiments show that in a high glucose (33 mM) combined palmitic acid (500 [mu] M) injury model, the SAFit2 can significantly improve the insulin secretion function of the pancreas islet. Specifically, the SAFit2 is pretreated, the glucose stimulated insulin secretion (GSIS) index of the pancreas islet and the intracellular insulin content are remarkably increased, insulin secretion under high glucose stimulation is promoted, and the SAFit2 is proved to have the effect of promoting the insulin secretion function of the pancreas islet beta cells.

The development of devices for a functional cure for diabetes by mimicking native pancreatic tissue for production of all pancreatic hormones. A physiologically and mechanically biocompatible artificial pancreas, wherein the pancreas comprises a combination of a PVA hydrogel combined with cells selected from the group consisting of islets; clusters of islets; Beta cells, and combinations of islets and Beta cells. The bioartificial pancreas contains vascular grafts therein or thereon a wall of the pancreas so that said grafts are an integral part of the wall of the bioartificial pancreas. The grafts can be anasmotized to living blood vessels in the body.

Disclosed herein are hypoimmunogenic stem cell-derived β cells for use in various applications, such as cell therapy.

The invention provides a preparation method and application of an anti-IL-11 antibody modified Treg cell, and belongs to the technical field of genetic engineering.The preparation method of the anti-IL-11 antibody modified Treg cell comprises the steps that after the Treg cell and umbilical cord blood pluripotent stem cells are co-cultured, the Treg cell is separated and recycled, an anti-IL-11 antibody is adopted for modification, and the anti-IL-11 antibody modified Treg cell is obtained; the nucleotide sequence of the anti-IL-11 antibody is as shown in SEQ ID NO. 2 in the sequence table. In the co-culture process, stem cells are used for providing an immune microenvironment, promoting Treg cell amplification and enhancing the inhibition ability of Treg cells, and obtaining the specific recognition ability of pancreas islet beta cell antigens, so that autoimmune attacks are inhibited more accurately; the nucleotide sequences of the heavy chain and the light chain of the anti-IL-11 antibody are optimized, and the anti-IL-11 antibody has higher efficacy in treatment of diabetic mice.

The invention belongs to the technical field of medicines and health-care foods, and particularly relates to a quercetin-cordyceps militaris polysaccharide solid self-nano emulsification drug delivery system as well as a preparation method and application of the quercetin-cordyceps militaris polysaccharide solid self-nano emulsification drug delivery system. The drug delivery system is prepared by mixing cordyceps militaris polysaccharide and a liquid quercetin self-nano emulsification precursor system, and spray-drying; the solid-to-liquid ratio of the cordyceps militaris polysaccharide to the liquid quercetin self-nano emulsification precursor system is 1 g: 3 mL-3 g: 1 mL. According to the present invention, the QUE-CMP-S-SNEDDS provided by the present invention has characteristics of good slow release ability and high oral bioavailability. Animal experiment results prove that the QUE-CMP-S-SNEDDS can remarkably reduce the fasting blood glucose level of a diabetic model mouse, effectively improve the pancreatic beta cell function of the mouse, and meanwhile, can remarkably relieve the pathological state of liver lipid metabolism disorder of the mouse.

The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to β-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to β-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in β-cells.

The invention discloses an application of miR-100 sponge in preparation of a medicine for treating type 2 diabetes mellitus. The miR-100 sponge can inhibit miR-100 in a targeted manner and close the expression of miR-100 in beta cells. The nucleic acid construct is further prepared from the nucleic acid construct, AAV8-mmu-miR-100 Sponge (AAV-Sponge) is injected into pancreatic ducts of obese diabetes mellitus mice, after treatment is conducted for 4 weeks, it is found that the sugar tolerance of the mice in a treatment group is improved, the GSIS function of beta cells is improved, and the nucleic acid construct is expected to be further applied to preparation of the medicine for treating the type 2 diabetes mellitus. The problems that current treatment methods for type 2 diabetes mellitus are deficient and the treatment cost is high are solved.

The present disclosure is generally directed to the use of biomaterial scaffolds engineered with SA-FasL for the transplantation of stem cell derived β-cells as a treatment for Type I diabetes. Early engraftment post-transplantation and subsequent maturation of these β-cells may be limited by the initial inflammatory response, which impacts the ability to sustain normoglycemia at long times. The survival and development of immature hPSC-derived β-cells transplanted on poly(lactide-co-glycolide) (PLG) microporous scaffolds into the peritoneal fat, a site being considered for clinical translation, was investigated. The scaffolds were modified with biotin for binding of a streptavidin-FasL (SAFasL) chimeric protein to modulate the local inflammatory microenvironment. The presence of FasL impacted infiltration of monocytes and neutrophils and altered their phenotypic response. Conditioned media generated from scaffolds explanted at day 4 did not impact hPSC-derived β-cell survival and maturation in vitro, which was not observed with unmodified scaffolds. Following transplantation, β-cell viability and differentiation were improved with SA-FasL modification. A sustained increase in insulin positive cell ratio was observed with SA-FasL modified relative to unmodified scaffolds. These results demonstrate that SA-FasL-modified scaffolds can mitigate initial inflammatory response and enhance β-cell engraftment and differentiation.