39 results about "Myocyte" patented technology

The application provides an active exosome stent coating, a vascular stent and a preparation method and application, and belongs to the technical field of biomedical intervention instruments. The active exosome stent coating of the application adopts stem cell-derived myocardial cell active exosomes which are strengthened by active components of traditional Chinese medicine. Compared with commercial myocardial cells, the stem cell-derived myocardial cells have more significant effects of promoting blood vessels and tissue repair and regeneration, and stronger cytokine secretion capacity. The preparation method of the active exosome stent coating of the application adjusts the introduction sequence and premixing mode of active components such as exosomes and drugs, and enhances the homogeneity and stability. The vascular stent prepared by using the active exosome stent coating of the application has reasonable sequential release kinetics design, can realize precise targeted regulation on human coronary artery smooth muscle cells (HCASMC) in vitro, does not affect the repair potential of endothelial cells, and solves the contradiction between traditional stents in terms of "anti-proliferation and promotion of healing".

This invention discloses the application of alismazone B acetate in the preparation of drugs for the prevention or treatment of hypertrophic cardiomyopathy and its related symptoms. This invention is the first to propose the use of alismazone B acetate (AB23a) for the prevention or treatment of hypertrophic cardiomyopathy. The invention utilizes AB23a to directly treat cardiomyocytes obtained from directed differentiation of human embryonic stem cells in vitro, finding that AB23a treatment significantly inhibits the hypertrophic phenotype of human embryonic stem cell-cardiomyocytes. Feeding mice with hereditary hypertrophic cardiomyopathy caused by gene mutations to a diet containing AB23a showed that AB23a significantly alleviated pathological myocardial hypertrophy and improved cardiac function in mice. AB23a can be used to prepare drugs against hereditary hypertrophic cardiomyopathy, providing a new approach and method for treating hypertrophic cardiomyopathy. AB23a is the most important medicinal component of the traditional Chinese medicine Alisma plantago-aquatica, is safe for organisms, and has good clinical application prospects.

This invention discloses the application of lipoic acid analog formulations in the preparation of anti-cardiomyocyte senescence products. The lipoic acid analog DMAE-LA is N-(2-(dimethylamino)ethyl)-5-(1,2-dithiopentane-3-yl)pentanamide, with a concentration of 2-25 μM. DMAE-LA pretreatment effectively reduces intracellular ROS, improves mitochondrial function, inhibits the overexpression of p21 and HMGB1, and restores Lamin B1 levels, thereby alleviating the senescent manifestations of cardiomyocytes. DMAE-LA reduces H₂S oxidative depletion by inhibiting ROS generation and may promote H₂S synthase activity, increasing endogenous H₂S levels and further enhancing cellular antioxidant capacity. In summary, DMAE-LA can significantly inhibit cardiomyocyte senescence through multiple antioxidant mechanisms and organelle function protection, providing a potential intervention strategy for targeting cellular senescence in cardiovascular diseases.

Provided herein are novel reprogrammed smooth muscle cells (rSMCs) and methods of making and using the cells for the treatment of ischemia. The rSMCs are produced by culturing a fibroblast with an all-trans-retinoic acid (ATRA) under conditions that produce the rSMC from the fibroblast, wherein the fibroblasts are genetically modified to overexpress myocardin. The rSMCs offer advantages over currently available regenerative vascular therapies by promoting vascular perfusion in a recipient subject. In particular, the rSMCs can increase neovascularization of both small and large vessels.

The application belongs to the technical field of biological medicine, and particularly relates to application of a GCN2 kinase inhibitor in preparation of a drug for treating heart failure with preserved ejection fraction. 18 H 12 ClF2N5O3S, the inhibitor can inhibit the activity of GCN2 kinase, and exhibits significant therapeutic effect in a disease model: can obviously improve ventricular diastolic function (E / E' ratio is reduced), reduce the level of heart failure markers, reduce cardiomyocyte hypertrophy and interstitial fibrosis, inhibit the expression of oxidative stress level and inflammatory factors, reduce the accumulation of triglyceride and total cholesterol in myocardium and serum, and improve obesity-related insulin resistance and metabolic disorder. The application provides a novel targeted treatment strategy and candidate drug for heart failure with preserved ejection fraction.

The invention discloses a co-culture method of cell culture meat and application of the co-culture method in improving meat quality and flavor. According to the invention, through two-stage differentiation, muscle precursor cells and fat precursor cells are respectively subjected to proliferation culture, then are separately subjected to primary differentiation, and are mixed together for co-culture, and meanwhile, second-stage continuous differentiation is carried out; the problem that differentiation of muscle cells and fat cells cannot be effectively and simultaneously differentiated under the co-culture condition due to different requirements of differentiation of muscle cells and fat cells on the serum environment is solved. In addition, the invention also provides an objective standard for evaluating the flavor quality of cell culture meat generated by co-culture. The cell culture meat with different flavors can be obtained by adjusting the proportion of the co-culture cells through the co-culture method, and the flavor quality of the cell culture meat from other sources can be evaluated and detected through the amino acid detection means.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mespl, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mespl, Mesp2, Gata4, Gata6, Baf60c, SRF, Isll, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mespl, Mesp2, Tbx5, Tbx20, Isll, Gata4, Gata6, Irx4, Nkx2.5, Handl, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mespl, Mesp2, Tbx5, Tbx20, Isll, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

The application relates to application of miRNA and / or a miRNA agonist in preparation of a medicine for preventing and / or treating myocardial ischemia-reperfusion injury, and belongs to the technical field of biological medicine. The medicine is administered through skeletal muscle injection, is secreted to a circulation system after expression on the skeletal muscle, is delivered to heart tissue by taking extracellular vesicles as carriers, and thus regulates myocardial cell functions. According to the animal model verification result, the miRNA can be delivered to the heart by the extracellular vesicles secreted by the skeletal muscle through injection of the medicine into the skeletal muscle, the expression level of the miRNA in the I / RI heart is significantly increased, the myocardial infarction area is effectively reduced, myocardial cell apoptosis is inhibited, myocardial fibrosis is reduced, and heart function is improved, a brand-new intervention strategy is provided for treatment of myocardial ischemia-reperfusion injury and related heart diseases, and a brand-new idea is opened up for research and development of heart failure treatment medicines.

The application discloses application of recombinant human USP13 protein in preparation of a drug for treating diabetic cardiomyopathy, and belongs to the technical field of biological medicines.The application first proves that the expression of USP13 in myocardial tissue and serum is significantly reduced under the condition of diabetic cardiomyopathy (DCM); the recombinant human USP13 protein can obviously reduce the level of myocardial cell active oxygen, reduce the expression of NLRP3 inflammasome and active Caspase3 protein in a DCM in-vitro model induced by high sugar / palmitic acid; in a DCM mouse model injected with the recombinant human USP13 protein through a tail vein, myocardial cell apoptosis is inhibited, and the expression of NLRP3 inflammasome and the synthesis of TNF-alpha in the heart of the animal are reduced.USP13 is a human protein, has no obvious toxic side effects, is high in safety, is small in immunological rejection in theory, provides a new effective drug for the clinical treatment of DCM, and has important clinical application value and industrialization prospect.

The invention relates to the technical field of biomedicine and cardiovascular disease treatment, and discloses application of an Aralar myocardial overexpression virus in preparation of a medicine for treating heart failure. The related product is a gene therapy preparation containing an effective amount of AAV9-cTnT-Aralar, and can be matched with pharmaceutically acceptable carriers, diluents and other auxiliary materials, and the preparation is an injection type. The preparation method comprises the following steps: firstly, constructing a cardiac troponin T-carrying promoter and an AAV9 carrier of an Aralar coding nucleic acid to form a recombinant adeno-associated virus, and then matching the virus with proper auxiliary materials to prepare the preparation. The product can be used for treating heart failure accompanied with mitochondrial dysfunction, can realize heart targeted delivery and myocardial cell specific overexpression of Aralr, relieves the heart failure course by improving the myocardial cell mitochondrial function and dynamic balance, and is good in preparation stability, convenient in administration and adaptive to clinical application requirements.

The application discloses application of papyriquinone in treatment of muscular dystrophy. The inventors find that papyriquinone can be combined with ERRa, activate ERRa and downstream signal pathways, promote muscle cell differentiation, improve muscle function, promote skeletal muscle regeneration, and finally plays a therapeutic role on Duchenne muscular dystrophy.

The present application mainly relates to the application of small molecule compound TA in the preparation of drugs and inhibitors. The application discloses the application of tannic acid, a GSDMD specific inhibitor obtained by designing computer virtual auxiliary screening, in the preparation of drugs for inhibiting myocardial cell pyroptosis inflammation to prevent or treat myocardial ischemia reperfusion injury. The role of GSDMD mediated myocardial cell pyroptosis in promoting myocardial ischemia reperfusion injury is clear, the drug active ingredient tannic acid (TA) in the application is easy to obtain, can directly inhibit the activity of GSDMD protein, resist myocardial cell pyroptosis, and play an anti-inflammatory effect to prevent or treat myocardial ischemia reperfusion injury, and the effect is remarkable. Tannic acid (TA) provides a new drug target strategy for myocardial ischemia reperfusion injury, and has a wide application prospect.

This invention discloses the application of ML-SA5, a highly specific small molecule agonist of TRPML1, for the preparation of drugs against aortic aneurysms or aortic dissections. An aortic aneurysm model was constructed, and an aortic dissection model was established using Fbn1 point mutations. The severity of aortic aneurysms or aortic dissections in control and experimental mice was assessed using small animal ultrasound and aortic morphology staining. Results showed that intraperitoneal injection of ML-SA5 or overexpression of TRPML1 significantly reduced abdominal aortic aneurysm / dissection lesions in mice; it also reduced elastic fiber degradation and smooth muscle cell destruction in abdominal aortic aneurysms, decreased the increase in media thickness and collagen fiber deposition in aortic dissections, further improving the progression and histopathological damage of abdominal aortic aneurysms / dissections. This drug showed good therapeutic effects in animal experiments, with high safety and few toxic side effects, and can be used as a drug to inhibit the progression of aortic aneurysms / dissections.

The application discloses a garden ginseng extract and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The garden ginseng extract contains a large amount of active ingredients, can improve the body's antioxidant, anti-inflammatory, anti-ischemic and anti-apoptotic capacity, protect myocardial cells and blood vessels, reduce damage, stabilize heart rhythm, improve coronary blood supply, and obtain excellent heart-protecting effect; promote intestinal peristalsis, improve intestinal health, improve the body's absorption and utilization capacity of nutrient substances, promote toxin discharge, provide sufficient raw materials and suitable environmental conditions for damaged cell repair and regeneration; assist in reducing blood lipids and cleaning vascular lipids, promote / maintain vascular health; the preparation method has mild conditions, does not use organic reagents, has no safety hidden trouble, can greatly improve the beneficial effect and utilization rate of the garden ginseng, and has definite conditions, can standardize production and popularize on a large scale.

A polynucleotide is provided comprising a nucleotide sequence encoding a biomolecule (e.g., human α-galactosidase A), a nucleotide sequence encoding a promoter (e.g., a hepatocyte-specific promoter or a hepatocyte-myocyte dual-specific promoter), or a nucleotide sequence encoding an expression cassette (e.g., a human α-galactosidase A expression cassette). Furthermore, promoters, expression cassettes, vectors, host cells, gene delivery systems (e.g., recombinant adeno-associated virus (AAV) particles and recombinant viral particles such as nonviral gene delivery systems), related pharmaceutical compositions, and methods for using them are also provided. Such compositions and methods are particularly suitable for gene therapy, and especially for lysosomal storage disorders, including Fabry disease.

The application provides a multifunctional nano-coated stent for preventing and treating in-stent restenosis and a preparation method and application thereof. Based on the multifunctional nano interface of EGCG-Cys, the liposome targeting VCAM-1 is used to deliver MnO2 nanoscale enzyme and FGF21 growth factor, so that the triple treatment effects of active oxygen scavenging, immune regulation and endothelial regeneration can be realized at the vascular lesion site. The EC-MFVL-WE43 stent creates a new paradigm for the design of interventional instruments, realizes the spatiotemporal precise release of drugs through the oxidative stress triggered degradation mechanism, and verifies the excellent anti-restenosis and anti-thrombosis performance in mouse, rabbit and pig models. Mechanism research shows that the nano-coated stent can reprogram macrophages to M2 repair type polarization, and effectively inhibit the abnormal proliferation of smooth muscle cells, providing a biological activity solution to break the vicious cycle of "inflammation-oxidation-restenosis".

This invention relates to the field of cell biology, and discloses a culture medium and method for inducing physiological myocardial hypertrophy based on carnosine. The culture medium for inducing physiological myocardial hypertrophy contains carnosine. By introducing an appropriate concentration of carnosine into a cardiomyocyte system, this invention can induce a series of phenotypic changes in cardiomyocytes related to physiological myocardial hypertrophy, including increased cardiomyocyte area, increased mitochondrial number, enhanced oxidative metabolic capacity, and increased ATP production capacity. These changes can improve the energy metabolism level of cardiomyocytes, thus providing a new technical solution for studying myocardial adaptive remodeling.

Provided is a class of circular RNAs, comprising mecciND2 and mecciNd2 having nucleotide sequences set forth in SEQ ID No. 1 and SEQ ID No. 2, respectively. The mecciND2 or the mecciNd2 is capable of inhibiting excessive opening of mitochondrial permeability transition pores, thereby significantly reducing ROS levels in myocardial cells, maintaining mitochondrial activity, and further protecting the myocardial cells. Intravenously injecting mecciNd2 into a mouse model of heart failure can effectively protect cardiac function and delay the progression of heart failure. The circular RNA is used as a drug for treating heart failure and exhibits good safety and specificity.

The application belongs to the technical field of genetic engineering and cardiovascular disease treatment, and specifically discloses application of an expression inhibitor of a TSPAN4 gene in preparation of a drug for treating cardiovascular diseases and the drug containing the expression inhibitor of the TSPAN4 gene. The application first constructs a carotid artery injury mouse model, and research finds that the expression absence of TSPAN4 has a significant improvement effect on intimal neogenesis. Further, the expression of the TSPAN4 gene is inhibited through siRNA interference RNA technology targeting the TSPAN4 gene, and it is found that after being treated by human h-siTSPAN4, the phenotype of smooth muscle cells can be changed, and the purpose of treating cardiovascular diseases can be achieved. The method of the application can inhibit the expression of the TSPAN4 gene by delivering siRNA, so as to inhibit the proliferation and migration of abnormal smooth muscle cells and reduce the development of cardiovascular diseases.

The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor member of the immunoglobulin super family which is able to bind Aβ peptide and 3-sheet fibrils. It is expressed in endothelial cells, smooth muscle cells, microglia and neurons, and is implicated in the transport of Aβ through the blood-brain barrier (BBB), oxidative stress-mediated neurotoxicity, and adverse microglia inflammatory responses. The interaction between RAGE and its ligands is thought to result in pro-inflammatory gene activation. Enhanced levels of RAGE ligands in Alzheimer's disease are thought to contribute to the cause of this disorder. Embodiments of the invention use the RAGE multi-ligand site as an anchoring loci for a conversion electron emitting compound rather than as a receptor to intrinsically activate or block inflammation through the RAGE intracellular cascade through activation of the RAGE cytoplasmic tail (ctRAGE) and mammalian diaphanous 1 (DIAPH1).

本发明属于生物医药技术领域，具体涉及一种小分子化合物在制备改善肌肉衰减药物中的应用。本发明使用地塞米松诱导小鼠成肌细胞C2C12产生肌肉衰减模型，通过CCK8活性检测，Western Blot检测肌少症相关蛋白表达情况。通过以上检测指标综合评估小分子化合物在制备改善肌肉衰减的作用。实验结果证明，小分子化合物SY‑4（Syringaresinol，丁香脂素）和 / 或SY‑35（Vomifoliol，吐叶醇）对细胞无明显毒性作用，同时显著降低了肌肉降解蛋白（Murf1）的表达量，并提升了肌肉合成蛋白（MyOD）的表达水平，具有很好的肌肉衰减治疗潜力，可以用于制备改善肌肉衰减药物。

The application discloses application of piRNA-AMIPIR in preparation of a drug for improving heart injury after acute myocardial infarction. The application first discovers that piRNA-AMIPIR is highly expressed in myocardial tissue after acute myocardial infarction (MI), and the expression level is positively correlated with the myocardial injury degree. After administration of the antisense nucleotide Antagomir-AMIPIR designed based on the piRNA-AMIPIR in a mouse acute myocardial infarction model, the myocardial cell apoptosis is reduced, the active oxygen (ROS) accumulation is reduced, the inflammatory cell infiltration is inhibited, the heart contraction function is significantly improved, and the ischemia-induced heart injury is reduced. The application confirms the potential value of the piRNA-AMIPIR as a treatment target for heart injury after acute myocardial infarction, the antisense nucleotide provides a new candidate drug and treatment strategy for clinical treatment of acute myocardial infarction, and has important scientific research significance and clinical application prospect.

This invention discloses a short peptide and its derivatives that mimic the N-terminus of RhoE, and their pharmaceutical applications in the treatment of myocardial hypertrophy, belonging to the field of biomedical technology. This short peptide precisely mimics the amino acid sequence from position 1 to 20 of RhoE, specifically binding to the WW domain of WWP2 and competitively blocking the interaction between the N-Loop and C-Loop of its HECT domain. This causes the WWP2 conformation to change from a self-inhibited "closed" state to an activated "open" state, activating E3 ligase activity. The short peptide retains its binding ability to the cardiomyocyte membrane cavernin CAV3, allowing it to efficiently enter the cardiomyocyte cytoplasm via the cavernin endocytosis pathway, overcoming the deficiency of traditional drugs in clearing intracellular pathogenic proteins. Peptide derivatives constructed by fusing transmembrane peptides such as TAT ​​and T7 further improve intracellular delivery efficiency. Experiments have demonstrated that this short peptide and its derivatives can significantly promote WWP2 self-ubiquitination, enhance cardiomyocyte autophagic flux, clear intracellular pathogenic proteins, and effectively inhibit cardiomyocyte hypertrophy, making it suitable for the preparation of anti-myocardial hypertrophy drugs.

This invention relates to the field of cell biotechnology, specifically to a method for large-scale preparation of cultured meat using a pilot-scale standardized bioreactor. The method includes the following steps: preparing photocurable microcarriers using gelatin and a photoinitiator; mixing large yellow croaker myoblasts, large yellow croaker preadipocytes, and the photocurable microcarriers, and then inoculating the mixture into a pilot-scale standardized bioreactor for culture; collecting the cell-bearing microcarriers cultured in the pilot-scale standardized bioreactor; and processing the cell-bearing microcarriers using a mold to prepare cultured meat. This invention uses large yellow croaker myoblasts, large yellow croaker preadipocytes, and photocurable microcarriers as experimental materials. Through a specific culture process, the pilot-scale standardized bioreactor is set up. By utilizing real-time monitoring and control of the culture conditions in the pilot-scale standardized bioreactor, the suspension co-culture of two types of large yellow croaker stem cells on photocurable microcarriers is achieved. Large-sized cultured meat is then prepared through mold processing.

This invention discloses a dihydroquercetin cocrystal, its preparation method, and its applications. The dihydroquercetin cocrystal is prepared by combining dihydroquercetin extracted from species such as Siberian larch with small molecule substances, including betaine, L-proline, benzamide, nicotinamide, or isonicotinine. The dihydroquercetin cocrystal of this invention exhibits high thermal stability and higher apparent solubility and dissolution rate compared to dihydroquercetin itself. This facilitates the full utilization of dihydroquercetin's various pharmacological effects, such as antioxidant, antitumor, anti-apoptotic, anti-inflammatory, cardiomyocyte protection, hypoglycemic, improvement of vascular endothelial cell function, antiplatelet aggregation, and influence on bone metabolism. Furthermore, the preparation method is simple, allowing for large-scale industrial production and offering significant economic benefits.

This invention belongs to the field of biomedical technology, specifically relating to the application of piRNA-45962 inhibitors in the preparation of drugs for preventing and treating myocardial ischemia-reperfusion injury. This invention discovers that piRNA-45962, with the nucleotide sequence shown in SEQ ID No. 1, is specifically highly expressed during myocardial ischemia-reperfusion. Furthermore, specific inhibitors of piRNA-45962 can improve the blockage of autophagic flux during myocardial ischemia-reperfusion through the HNRNPH1 / GATA5 signaling pathway, enhance the clearance of autophagosomes by cardiomyocytes, reduce cardiomyocyte apoptosis, and exert a preventive and therapeutic effect against myocardial ischemia / reperfusion injury. This invention provides a new solution for the prevention and treatment of myocardial ischemia-reperfusion injury and offers new ideas for the development of drugs for the prevention and treatment of myocardial ischemia-reperfusion injury, possessing promising application prospects and clinical value.

This application discloses a composition, preparation method, application, and formulation for improving male sexual dysfunction. The composition includes Salvia miltiorrhiza root extract and Cnidium monnieri fruit extract. The Salvia miltiorrhiza root extract is obtained by hot reflux extraction and amylase hydrolysis of Salvia miltiorrhiza root followed by concentration. The Cnidium monnieri fruit extract is obtained by enzymatic hydrolysis of Cnidium monnieri fruit followed by cellulase and pectinase followed by concentration. This composition can be used as a raw material for topical application to improve male sexual dysfunction. This composition has no toxic effects, effectively improves male sexual dysfunction, and has restorative and nourishing effects on male sexual function. The composition can reverse the phenotypic transformation of penile cavernous smooth muscle cells under pathological conditions and maintain the normal relaxation and contraction function of smooth muscle.

This invention discloses the application of Anemarrhena saponin A-III in the preparation of drugs for treating sarcopenia. This invention is the first to discover that Anemarrhena saponin A-III can significantly promote the growth of C2C12 myocytes into myotubes, improve autophagy function, and reduce lipid deposition; it can strengthen muscle function, alleviate the morphology of the gastrocnemius muscle in sarcopenia model mice, and increase muscle fiber area, thereby effectively combating sarcopenia. This provides an effective approach for the treatment of sarcopenia.