35 results about "Nod mouse" patented technology

AS-oligonucleotides are delivered in microsphere form in order to induce dendritic cell tolerance, particularly in the non-obese-diabetic (NOD) mouse model. The microspheres incorporate antisense (AS) oligonucleotides. A process includes using an antisense approach to prevent an autoimmune diabetes condition in NOD mice in vivo and in situ. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.

Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of blood glucose levels and may reducing insulin resistance, the compositions, methods and cells described herein can also be used for treating Type 2 diabetes (T2D).

The invention relates to novel I-type diabetes resisting recombination lactic acid bacteria and application thereof, belongs to the field of biological medicine, and discloses an I-type diabetes resisting vaccine with lactococcus lactics as a carrier and a preparing method and application of I-type diabetes resisting vaccine. A micro genetic technology platform of a laboratory is used, the recombination lactococcus lactics vaccine with lactococcus lactics as the carrier, and the recombination lactococcus lactics vaccine expresses fusion protein HSP65-6IA2P2 after induction. The correct expression of the fusion protein vaccine is detected through Western blot authentication. It is proved through in-vivo animal experiments that the vaccine can remarkably reduce the occurrence of NOD mouse diabetes through an oral administration way, can perform the function of controlling I-type diabetes and has good clinical application prospects on preventing diabetes.

AS-oligonucleotides are delivered in microsphere form in order to induce dendritic cell tolerance, particularly in the non-obese-diabetic (NOD) mouse model. The microspheres incorporate antisense (AS) oligonucleotides. A process includes using an antisense approach to prevent an autoimmune diabetes condition in NOD mice in vivo and in situ. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.

Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of fasting blood glucose levels and may ameliorate (e.g., reduce, eliminate) insulin resistance, the compositions, methods and cells described herein can also be used for treating Type 2 diabetes (T2D).

The invention discloses a VSIG4 (V-set and Ig domain containing 4) and IGRP (glucose-6-phosphatase catalytic subunit-related protein) dual-gene coexpression recombinant adenovirus as well as a preparation method and an application thereof. The recombinant adenovirus genome contains a VSIG4 and IGRP dual-gene expression cassette which sequentially comprises a CMV (cytomegalovirus) promoter, a VSIG4 full length coding gene, a terminator, an internal ribosome entry site (IRES), an IGRP full length coding gene and a terminator from the upstream to the downstream. The preparation method of the recombinant adenovirus is simple. Dendritic cells of the recombinant adenovirus, which are transfected in vitro, are fed back in vivo, which can reduce the multiplication capacity of lymphocytes of NOD (Nonobese Diabetic) mice with diabete liability and the secretion capacity of cell factors, moreover, the onset time of the diabetes of the NOD mice is delayed, and the morbidity is reduced. The recombinant adenovirus is proved to be capable of effectively inducing the tolerance of specific T-cells and effectively inhibiting the breakage of pancreas islet beta cells and can be used for preparing dendritic cell vaccines for resisting type-1 diabetes.

The invention discloses a linear 33 peptide molecule which consists of a B epitope (10 peptide) of human dipeptidyl peptidase 4 and 23 peptide containing a Th2 epitope; serum of an animal immunized by33 peptide contains an antibody which has high price and can be specifically combined with DPP4; the antibody can inhibit the activity of the DPP4 and regulate immune rebalance trending to Th2; the 33 peptide is utilized to carry out subcutaneous immunological control or treat type 1 diabetic NOD mice and treat STZ-induced diabetic mice every 2 weeks, so that blood glucose is significantly controlled or reversed; the blood glucoses of the NOD mice are basically normal, GLP-1 and Th2 cytokines are significantly increased and glucagon and Th1 cytokines are significantly reduced, so that morbidity, death rate, multiple immune balances as well as uric acid, creatinine, blood lipid and oxidative stress indicators are remarkably improved, pancreatic inflammation is relieved, and the ability ofpancreas secreting insulin is significantly strengthened. The 33 peptide as well as vaccines and drugs prepared by using microorganisms, animals, plants and cell expression based on the 33 peptide areof great value in preventing and treating diabetes, especially in type 1 diabetes and complications and other diseases.

The invention relates to a novel non-obese diabetic (NOD) mouse and its application. Particularly, the invention relates to a NOD mouse specifically expressing anti-polyethylene glycol membrane antibody reporter (anti-PEG reporter) in the NOD mouse.

A novel diabetes-related immunoloregulation vaccine peptide VP is designed which can effectively prevent T1DM attack and is free of an atherosclerotic side effect. The VP peptide does not cause lipid disorders in serum of mice, sharp hs-CRP level increases or atherosclerosis side effects. The VP peptide can control blood glucose of NOD mice, maintain normal body weights of mice and reduce the incidence of T1DM. In addition, the VP peptide can maintain normal secretion functions of islet beta cells and can allow the cells to exert normal blood sugar adjusting functions.

The invention relates to the application of recombinant lactic acid bacteria and SNase in the preparation of drugs for preventing or treating type 1 diabetes. The purpose of the present invention is to provide the new application of the vaccine with recombinant lactic acid bacteria L.lactisNZ9000 pCYT:SNase as carrier in anti-type 1 diabetes. The recombinant bacteria can express the target protein Staphylococcal nuclease, SNase after being induced by lactose. L.lactisNZ9000 pCYT:SNase live bacterial vaccine was immunized to 4-week-old female NOD / LtJ mice by oral administration, and a series of pharmacodynamic indicators were evaluated. It was found that: compared with the control group, L.lactisNZ9000 pCYT:SNase can significantly reduce the incidence of diabetes in NOD mice, better control the blood sugar and body weight of NOD mice, and significantly improve the survival rate of NOD mice. It can be seen that the recombinant Lactococcus lactis L. lactisNZ9000 pCYT:SNase can significantly inhibit the development of diabetes in NOD mice, and can be used for the development of type 1 diabetes drugs.

The invention provides an expression method of recombinant human insulin, a special expression vector, engineering bacteria and application. This expression method can induce the expression of recombinant human insulin gene in food-grade lactic acid bacteria and display recombinant human insulin on the surface of lactic acid bacteria. The engineering bacteria, expression vector and inducer used in this expression method all meet the requirements of food grade, avoiding the The presence of resistance genes on vectors and the potential harm caused by non-food-grade inducers, etc. The lactic acid bacteria engineering bacteria containing cell wall display insulin obtained by the present invention can stimulate NOD mice to produce recombinant human insulin-specific antibodies, significantly increase the level of cytokine IL-4 related to immune tolerance, and induce immune tolerance. The induced lactic acid bacteria engineered bacteria can be used as an oral vaccine for type 1 diabetes after being made into bacterial preparations, without the need for tedious post-processing such as purification, and has broad application prospects.

Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

The present invention provides one kind of restructuring protein and its restructuring gene for preventing and treating type-1 diabetes. Connecting heat shock protein HSP60 originated Mycobacterium bovine to a piece of antigen epitope P277 from human HSP60; restructuring protein produced can be used for immunity directly with no adjuvant. The restructuring protein can stimulate body to produce antigen for P277 both by ways of injection and mucous membrane immunity, decreases marked NOD mouse diabetes occur, can contribute to preventing and caring type-1 diabetes. Meantime, the restructuring gene produced in this invention can also be used to transgene animals or plants and restructuring microorganism as the factory for producing restructuring protein or preparing oral vaccine.

The invention discloses an insulin chain A human leukocyte antigen (HLA)-A*0201 restrictive cytotoxic T lymphocyte (CTL) epitope altered peptide ligand (APL) which is obtained by replacing sixth amino acid L-Cys in insulin chain A HLA-A*0201 restrictive natural CTL epitope mInsA2-10 of humanized non-obese diabetic (NOD) mice with D-Cys. The amino acid sequence of the APL is shown as SECIDNo.1L; the natural CTL epitope has high cross reactivity with human epitope, and the APL has an obvious characteristic of inhibiting natural epitope specificity CTL response in the extracorporal cellar immunefunction experiment of the humanized NOD mice and the peptide has the characteristics that the peptide is easy to prepare and purify in a large scale and can be used safely, so that the APL can be independently applied to the development of I-type diabetes mellitus therapeutic antagonist peptide vaccine or is combined with other immunodominance autoantigen epitopes or APL to be applied to the development of I-type diabetes mellitus therapeutic antagonist peptide vaccine, and has potential and good development and application prospect in the field of human I-type diabetes mellitus treatment.

The invention discloses a miR-29 sponge, and further provides a nucleic acid construct comprising the miR-29 sponge. The present invention finds that the miR-29 sponge can absorb miR-29a-3p and miR-29b-3p in the body and close its function, inhibit the secretion of pro-inflammatory cytokines, thereby alleviating the occurrence of insulitis in NOD mice, increasing serum insulin levels, maintaining The blood sugar tends to normal level, finally significantly reduces the incidence of type 1 diabetes in NOD mice, and improves the survival rate of NOD mice.

Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of blood glucose levels and may reducing insulin resistance, the compositions, methods and cells described herein can also be used for treating Type 2 diabetes (T2D).