27 results about "Endometrial Stromal Cell" patented technology

The present invention provides: a drug which can improve the implantation rate of an embryo and can be used in conjunction with conventional drugs for infertility treatment; and a screening method and the like with which it is possible to reliably evaluate such a drug. Specifically, the integrin activator comprises: (1) a peptide composed of KFEERMRCKWMT, and (2) a peptide composed of KFEERMRCKWMT. (2) a peptide which is composed of KFEEERSRCKWMT; (3) a peptide comprising an amino acid sequence obtained by deleting, substituting and / or adding 1-3 amino acids in (1) or (2); or (4) a peptide obtained by binding any one of (1) to (3) to a membrane-permeable molecule. Provided are an artificial uterus and a screening method based on an implantation reproduction test system using a fertilized egg (for example, an embryo developed to an implanted blastocyst), the artificial uterus comprising: a hydrogel containing endometrial stromal cells and having an extracellular matrix as a main component; and a uterine epithelial organoid configured to be surrounded by the hydrogel.

The invention provides an application of a composition containing cryopreserved prp in treatment of gynecological diseases. The invention also provides a reproduction promoting peptide which can obviously promote the proliferation and migration activity of human endometrial stromal cells, can reduce the apoptosis level of the cells, and has a better promoting effect. In addition, the cryopreserved prp is also prepared, after the cryopreserved prp is combined with the reproduction promoting peptide, the repair of the endometrial injury of the rat can be remarkably promoted, and a relatively good treatment effect is achieved.

The invention discloses a Nur77 methylation site mutation peptide based on structural modification design and application of the Nur77 methylation site mutation peptide in promoting embryo implantation, according to the mutation peptide, arginine at the 346th site of Nur77 is mutated into lysine, and methylation modification of Nur77 is reserved while phosphorylation of Nur77 is inhibited, so that the transcriptional activity of Nur77 is enhanced. It is found that the mutant peptide can promote deciduation of endometrial interstitial cells, remarkably improve deciduation disorder of infertility mice in in-vivo experiments and improve the embryo planting rate of low-fertility mice. Therefore, the mutant peptide is expected to become a new medicine for treating the uterine-derived infertility and has important clinical application value. The invention also relates to a preparation method of the mutant peptide and application of the mutant peptide in a pharmaceutical composition and a treatment method.

The invention provides application of injectable bioactive hydrogel in treatment of recurrent abortion, and relates to the technical field of biomedicine, and the technical key points are as follows: aldehydic hyaluronic acid and chitosan are connected in parallel, the injectable bioactive hydrogel is developed, and the hydrogel is loaded with LIF, VEGF, IL-11 and valproic acid to enhance regeneration activity. According to the application, the effect is evaluated in vitro through a specific verification experiment. Results show that the hydrogel prepared by the application shows rapid gelation, good biocompatibility and factor loading capacity, and enhances the proliferation of human endometrial stromal cells and the vascularization capacity of human umbilical vein endothelial cells. In macrophages, the expression of a proinflammatory cytokine is down-regulated, and the expression of an anti-inflammatory cytokine IL-10 is up-regulated. In conclusion, the HA-CHO / chitosan hydrogel in the application supports endometrial regeneration by synergistically promoting proliferation, angiogenesis, immune regulation and receptivity.

The invention relates to a medicine for recurrent abortion endometrial cell senescence and a preparation process thereof, and belongs to the technical field of traditional Chinese medicine preparations. The medicine is prepared from the following traditional Chinese medicine components: 10 to 30 parts of semen cuscutae, 5 to 15 parts of herba taxilli, 5 to 15 parts of radix dipsaci, 5 to 15 parts of radix angelicae sinensis, 5 to 15 parts of radix scutellariae, 5 to 15 parts of radix paeoniae alba, 5 to 15 parts of rhizoma chuanxiong, 1 to 9 parts of rhizoma atractylodis macrocephalae and 6 to 16 parts of colla corii asini. The medicine has a remarkable curative effect on endometrial cell senescence in an implantation window phase of recurrent abortion. The traditional Chinese medicine preparation is used for treating endometrial interstitial cell senescence in an implantation window phase of unexplained recurrent abortion. The dosage form of the medicine can be any one of clinically acceptable dosage forms such as granules, capsules and tablets, pharmacodynamic experiments prove that the same technical effect can be achieved, and the medicine is suitable for further popularization and application.

The invention relates to application of MEIS1 in preparation of an endometriosis therapeutic agent and the therapeutic agent prepared by the MEIS1. According to the invention, the influence of MEIS1 on an endometrial stromal cell apoptosis pathway is studied, endometrial stromal cell apoptosis is induced by overexpression of MEIS1 in endometrial stromal cells, and an MEIS1 lentivirus overexpression vector is used for administration to an endometriosis mouse model, so that the size and weight of a mouse endometriosis focus are remarkably reduced, and the application of MEIS1 in the endometriosis mouse model is realized. Liver and kidney biochemical indexes show that the LV-MEIS1 does not damage main organ functions and brings a new potential hope for treatment of endometriosis.

This invention discloses the application of platelet-reactive protein-4 (THBS4) in the diagnosis and treatment of endometriosis. Through bioinformatics integration analysis, clinical sample validation, and in vitro and in vivo experiments, this invention confirms that THBS4 is significantly highly expressed in both ectopic lesions and peripheral blood of patients with endometriosis, and its expression level is positively correlated with disease severity. The area under the receiver operating characteristic (AUC) curve for THBS4 alone in diagnosing endometriosis is 0.930, significantly superior to cancer antigen 125 (CA125); the AUC for the combined diagnosis of THBS4 and CA125 reaches 0.968. Simultaneously, silencing the THBS4 gene effectively inhibits the proliferation, migration, and invasion of human endometrial stromal cells, and significantly reduces the volume and fibrosis area of ​​ectopic lesions in a mouse model of endometriosis. This invention provides a highly sensitive and specific new biomarker for the non-invasive or minimally invasive early diagnosis of endometriosis, and provides new targets and candidate drugs for non-hormone-dependent targeted therapy.

The invention relates to application of arachidonic acid (ARA) in preparation of a medicine for treating sleep disorder related spontaneous abortion. Peripheral blood lipid metabolism sequencing analysis finds that the ARA content in peripheral blood serum of a patient suffering from sleep disorder and repeated pregnancy loss is most obviously reduced compared with that of a patient suffering from normal sleep and normal pregnancy; an enzyme-linked immunosorbent assay test shows that the content of ARA in decidua stromal cells (DSCs) of a patient with sleep disorder and repeated pregnancy loss is remarkably reduced compared with that of a pregnant person with normal sleep; after the endometrial stromal cells (ESCs) are subjected to ARA treatment, the in-vitro decidualization level is increased; the ARA inhibitor can be used for inhibiting the in-vitro deciduation level of the ESCs; compared with a mouse with normal sleep, the content of ARA in peripheral blood and DSCs of a mouse with sleep disorder is remarkably reduced, decidua is poor, and the abortion rate is increased; supplementing ARA can improve decidua disorder and high abortion rate caused by sleep disorder. Therefore, a potential target and a new idea are provided for diagnosis and treatment of repeated pregnancy loss related to sleep disorder.

The invention discloses an application of miR-2355-3p in endometriosis. The research discovers that the RNA transcriptional level of miR-2355-3p in an ectopic endometrial tissue sample is obviously reduced for the first time; the mimics RNA overexpressed by miR-2355-3p is cloned to a lentiviral vector, lentiviral packaging is carried out, the miR-2355-3p mimic lentivirus is obtained, then the miR-2355-3p mimic lentivirus is used for transfecting ectopic endometrial interstitial cells, proliferation of the ectopic endometrial interstitial cells can be inhibited, apoptosis of the ectopic endometrial interstitial cells can be promoted, growth of ectopic endometrial tissues is inhibited, and the mimic RNA-mimic lentivirus can be used for treating the endometrial interstitial cells. And a new possibility is provided for developing the medicine for treating the endometriosis.

The application discloses a preparation method of a 3D model of a maternal-fetal interface constructed by an endometrial organoid in vitro, and the method comprises the following steps: establishing a primary endometrial epithelial organoid and an endometrial stromal cell line in vitro; improving an extracellular matrix for assembling endometrial gland-like organoids and stromal cells; the constructed endometrial organoid model comprises gland cells and stromal cells; the endometrial organoid model is cultured by using a gas-liquid interface, so that the endometrial organoid model has a cavity epithelium and a gland structure; the endometrial organoid model simulates a menstrual cycle of the endometrium and performs function identification. The endometrial organoid model has the cavity epithelium and the gland epithelium for the first time, the tissue structure, the cell composition, the hormone-induced change, the gene expression characteristics of the organoid are similar to those in the body, and the organoid can reproduce the receptivity genes and the dynamicity of cilia which are necessary for embryo implantation in the body; the organoid can be used as a model for studying embryo implantation regulation, endometrial diseases and regeneration mechanisms.

The application belongs to the technical field of biotechnology and medicine, and specifically discloses a single-domain antibody-exosome compound (Nb-EMX2-Exos) targeting EMX2 as well as a preparation method and application thereof. The compound is prepared by covalently coupling a single-domain antibody (Nb-EMX2) specifically binding to EMX2 protein to the surface of endometrial stem cell-derived exosomes (ESC-Exos). In-vitro experiments show that the compound can specifically recognize and efficiently internalize into damaged endometrial stromal cells with high expression of EMX2, and significantly promote the migration and proliferation of the cells. In-vivo experiments further prove that the compound can precisely target and enrich in damaged endometrial tissue, effectively promote the structural repair (thicken the endometrium and reduce fibrosis) of the endometrium, and completely restore the fertility function. The application provides a novel targeted treatment preparation for solving the problems of poor targeting of natural exosomes and limited treatment effect, and has important application value in the treatment of endometrial injury repair and related infertility.

The invention discloses an engineered extracellular vesicle for targeted uterus delivery of Hand2siRNA and a preparation method and application thereof, and belongs to the technical field of biomedicine. The invention provides an engineered extracellular vesicle for targeted delivery of Hand2siRNA (small interfering Ribonucleic Acid) in a uterus. The engineered extracellular vesicle comprises the engineered extracellular vesicle for targeted delivery of the uterus and the Hand2siRNA entrapped in the engineered extracellular vesicle. The engineered extracellular vesicle for contraception has the characteristic of targeting endometrial stromal cells, and because the Hand2 transcription factor plays a key role in establishing endometrial receptivity, the engineered extracellular vesicle can target the endometrial stromal cells and interfere with Hand2 gene expression, the endometrial receptivity is interfered, and the engineered extracellular vesicle can be used for contraception. Therefore, the contraception effect is realized.

The invention provides a pharmaceutical preparation for repairing endometrial injury, and belongs to the technical field of biomedicine. The pharmaceutical preparation takes improved polypeptide as an active ingredient, and the amino acid sequence of the improved polypeptide is shown as SEQ ID NO.5. Experimental results show that the polypeptide can significantly promote proliferation and migration of human endometrial stromal cells, still maintains low cytotoxicity under high concentration, and shows excellent safety. Furthermore, in a rat endometrial mechanical injury model, the preparation can obviously increase the endometrial thickness, improve the Ki-67 positive cell rate, enhance the proliferation activity of endometrial cells and promote the repair of damaged tissues. Compared with the original polypeptide, the preparation disclosed by the invention shows unexpected technical effects in the aspects of repairing activity and safety, and has a good application prospect.

The invention discloses a co-culture model based on endometrial stromal cell organoid and follicle organoid as well as a construction method and application of the co-culture model, and belongs to the technical field of reproductive medicine and cell engineering. The invention discloses a construction method of a co-culture model based on an endometrial stromal cell organ and a follicle organ. The construction method comprises a culture method of the follicle organ, a culture method of the endometrial stromal cell organ and co-culture of the follicle organ and the endometrial stromal cell organ. The 3D follicle-like organ and endometrial stromal cell-like organ co-culture system provided by the invention can reproduce in-vivo physiological conditions more truly, can be used for exploring a deciduous molecular mechanism, and also has the potential of constructing a high-throughput detection platform for drugs and environmental toxicants.

The present invention provides the use of a composition containing cryopreserved PRP in the treatment of gynecological diseases. It is also provided that the reproductive promoting peptide can significantly promote the proliferation and migration activities of human endometrial stromal cells, and can reduce the apoptosis level of cells, showing a good promoting effect. In addition, the present invention has also prepared cryopreserved PRP, and after combining it with the reproductive promoting peptide, it can significantly promote the repair of rat endometrial injury, showing a good therapeutic effect.

The invention provides application of hsacirc0069443 in preparation of a medicine for treating early pregnancy loss, and belongs to the technical field of molecular biology. The invention finds that the hsacirc0069443 is an important circRNA (Ribonucleic Acid) which causes the loss of early pregnancy. The hsacirc0069443 is down-regulated in a patient with early pregnancy loss, and the hsacirc0069443 is knocked down to inhibit proliferation, migration and invasion of trophoblast cells. The research finds that hsacirc0069443 can be secreted from trophoblast cells in an exosome form, migration and invasion of endometrial interstitial cells are promoted, and the endometrial gland epithelial cell EMT process is promoted by the exosome secreted by the trophoblast cells. The invention provides a new target for early pregnancy loss treatment.

This disclosure belongs to the field of pharmaceutical technology, and specifically relates to the application of targeted proline metabolic enzymes in the treatment of endometriosis. This disclosure, through in vitro experiments and EMS animal models, verifies that the proline content in ectopic endometrial stromal cells increases, the expression of proline synthesis metabolic enzymes is elevated, and fibrosis is significantly activated. This disclosure creatively repurposes proline metabolic enzyme inhibitors for EMS treatment. Proline metabolic enzyme inhibitors specifically inhibit the enzyme activity of key proline metabolism enzymes, blocking the synthesis pathway from glutamate to proline, and directly reducing intracellular proline content. Since proline is a major component amino acid of collagen, the inhibition of proline synthesis directly inhibits collagen synthesis and the expression of fibrosis markers in endometrial stromal cells, ultimately achieving the therapeutic effect of inhibiting fibrosis in EMS ectopic lesions and reducing ectopic lesion growth.

This invention belongs to the field of biomedical technology, specifically relating to the application of Danbie capsules in the preparation of products for treating endometriosis. This invention discovers that the combined use of Danbie capsules and progestins has a synergistic effect, with a superior intervention effect on endometrial stromal cells compared to a single component. Furthermore, this invention provides a traditional Chinese medicine-containing serum, the main medicinal components of which are quercetin and luteolin, which can effectively inhibit the growth and migration of endometrial stromal cells and induce apoptosis. This traditional Chinese medicine-containing serum is derived from Danbie capsules. Animal experiments have shown that Danbie capsules can inhibit the expression of AKT1 in endometrial tissue, and cell experiments have shown that the traditional Chinese medicine-containing serum can induce apoptosis of endometrial stromal cells, suggesting that the intervention effect of the traditional Chinese medicine Danbie capsules and its containing serum on endometrial stromal cells is related to AKT1 expression, providing an important insight into the relevant mechanism.

The application provides application of a vitamin-magnesium compound in preparation of a medicine for preventing and treating miscarriage in a pregnant period and an early pregnant period and a preparation, relates to the technical field of biological medicines, and the vitamin-magnesium compound is a magnesium-based coordination chelate with a repairing effect on endometrial tissue. The vitamin-magnesium compound is an organic ligand of the magnesium-based coordination chelate, and the organic matter is any one of vitamin B13, vitamin B3 and vitamin C. The magnesium-based coordination chelate acts on endometrial stromal cells, promotes cell proliferation, and promotes normal implantation of an embryo. The magnesium-based coordination chelate acts on endometrial tissue vascular endothelial cells, promotes cell proliferation, and promotes angiogenesis to meet the nutritional supply of the embryo. The magnesium-based coordination chelate acts on endometrial tissue macrophages, M1 type macrophages are polarized into M2 type macrophages, immune tolerance to the embryo is promoted, and the normal growth and development of the embryo are prevented from being affected by the attack of maternal immune cells.

The application discloses application of prolyl glycine in preparation of a medicine for treating and / or preventing endometriosis, wherein the prolyl glycine can inhibit proliferation of ectopic endometrial stromal cells, inhibit migration of ectopic endometrial stromal cells, inhibit development of a tissue structure of an endometriosis lesion, and reduce fibrosis of the endometriosis lesion, and the application provides a new biological basis and intervention idea for accurate typing and treatment of EMs.

The invention relates to a method of generating an in vitro endometrium assembloid comprising growing endometrial stromal cells inside a hydrogel matrix and layering cells and / or fragments from endometrial epithelial organoids on top, thereby generating a three-dimensional endometrium assembloid comprising a stromal compartment, an outer luminal epithelial layer and a functional secretory glandular endometrium. The invention further relates to an in vitro endometrium assembloid produced according to the methods defined herein. Also provided are methods for determining embryo implantation ability and / or window of receptibility to embryo implantation and for screening for embryo implantation-modulating agents comprising, providing the in vitro endometrium assembloid defined herein. The invention further relates to the use of three sequential human embryo media (HEM) for culturing human stem cell based embryo-like (blastoids) or human blastocysts, and to the compositions of the three media.

Use of an exosome derived from decidual natural killer (dNK) cells or a dNK cell subset in the preparation of a drug and an auxiliary therapeutic agent for infertility-related diseases is provided. Experiments have confirmed that the exosome treats the endometrial growth disorder-related diseases by promoting increase of endometrial thickness, increasing endometrial cell viability, reducing endometrial cell damage, promoting VEGF expression, and maintaining stemness and stimulating proliferation of endometrial stromal cells, such that a conception rate for endometrial injury model mice increases from 20% to 50%-70%; and the exosome treats the maternal-fetal immune tolerance disorder-related diseases by exerting immune tolerance, reducing a spontaneous abortion rate, and increasing a helper T cell level. In addition, the exosome effectively increases the development rate of eggs fertilized in vivo or in vitro in a multiplying way, and improves an implantation rate and a birth rate for in vitro fertilization and embryo transfer.

The application discloses a molecular marker for recurrent spontaneous abortion and a diagnostic application thereof, and relates to the technical field of biological medicine.The application discloses application of a JAZF1 gene in preparation of a product for diagnosis or auxiliary diagnosis of abortion.It is found for the first time that the expression amount of JAZF1 is closely related to recurrent spontaneous abortion, which indicates that the expression of JAZF1 is down-regulated in decidua tissue and endometrial tissue of recurrent spontaneous abortion, and indicates potential possibility of JAZF1 as a diagnostic marker for recurrent spontaneous abortion, which is helpful to clinical diagnosis and prevention of recurrent spontaneous abortion.Furthermore, it is proposed for the first time that JAZF1 can promote survival of endometrial stromal cells and normal decidualization, so as to maintain normal pregnancy.

The invention provides application of a vitamin-magnesium compound in preparation of a medicine for preventing and treating abortion in a pregnancy preparation period and an early pregnancy period and a preparation, and relates to the technical field of biological medicines. The vitamin-magnesium compound takes an organic matter as an organic ligand of the magnesium-based coordination chelate, and the organic matter is any one of vitamin B13, vitamin B3 and vitamin C; the magnesium-based coordination chelate acts on endometrial stromal cells to promote cell proliferation so as to promote normal implantation of embryos; the magnesium-based coordination chelate acts on endometrial tissue vascular endothelial cells to promote cell proliferation so as to promote angiogenesis and meet embryo nutrition supply; the magnesium-based coordination chelate acts on endometrial tissue macrophages, M1 type macrophages are polarized to M2 type macrophages, immune tolerance to embryos is promoted, and the embryos are prevented from being attacked by maternal immune cells to affect normal growth and development.

The invention discloses a construction method of a cadmium ion mediated deciduous damage cell model, and belongs to the technical field of cell model construction. The specific model construction method comprises the following steps: 1) extracting primary endometrial stromal cells from endometrial tissues; 2) culturing primary endometrial stromal cells in vitro; and 3) inducing endometrial stromal cell decidualization in vitro under the cadmium ion exposure condition. The invention finds that the expression of a deciduation related marker can be obviously reduced by cadmium ion treatment, so that the endometrial stromal cell deciduation injury is caused, and the cadmium ion mediated deciduation injury cell model is successfully constructed.

The invention belongs to the technical field of biomedicine, and particularly relates to application of a Dantai capsule in preparation of a product for treating endometriosis. The invention finds that the Dantai capsule and progestational hormone are combined to have a synergistic effect, and the intervention effect on endometrial interstitial cells is superior to that of a single component. Furthermore, the invention provides a traditional Chinese medicine drug serum, the main medicinal components of the traditional Chinese medicine drug serum are quercetin and luteolin, and the traditional Chinese medicine drug serum can effectively inhibit growth and migration of endometrial interstitial cells and induce apoptosis of the endometrial interstitial cells. Animal experiments find that the Dantai capsule can inhibit expression of endometrial tissue AKT1, and cell experiments find that the traditional Chinese medicine drug serum can induce apoptosis of endometrial interstitial cells. It is prompted that the intervention effect of the traditional Chinese medicine Dantai capsule and the traditional Chinese medicine serum thereof on the endometrial interstitial cells is related to AKT1 expression, and an important thought is provided for clarification of related mechanisms.

The application discloses application of miR-2355-3p in endometriosis, and finds that the RNA transcription level of miR-2355-3p in ectopic endometrial tissue samples is significantly decreased for the first time; the mimics RNA of miR-2355-3p overexpression is cloned to a lentivirus vector and lentivirus packaging is carried out, miR-2355-3p mimic lentivirus is obtained, and ectopic endometrial stromal cells are transfected with the lentivirus, so that the proliferation of the ectopic endometrial stromal cells can be inhibited, and apoptosis of the ectopic endometrial stromal cells can be promoted, thereby the growth of ectopic endometrial tissue is inhibited, and a new possibility is provided for development of an endometriosis treatment drug.