33 results about "Cardiac fibroblast" patented technology

Compositions and methods for aptamer-mediated delivery of therapeutic agents. RNA aptamers identified via SELEX specifically bind and are internalized by cardiomyocytes or cardiac fibroblasts, delivering antisense oligonucleotides or other therapeutics intracellularly. This strategy offers a non-viral, targeted approach for treating cardiac diseases and may be extended to other tissues or therapeutic modalities.

Relates to the field of biomedicine, in particular to the field of regenerative medicine. Specifically, the invention relates to a compound for preparing myocardial cells and application thereof, and a method for differentiating pluripotent stem cells such as induced pluripotent stem cells into myocardial cells by using the compound.

The invention provides a method of promoting reprogramming of a cardiac fibroblast into a cardiomyocyte by contacting the cardiac fibroblast with an isolated polynucleotide molecule comprising at least two functional miRNA sequences using a multicistronic expression system for reprogramming of fibroblasts into functional mature cardiomyocytes.

The invention belongs to the technical field of biological medicines, and relates to application of histone demethylase KDM4A as a target spot, in particular to application of the histone demethylase KDM4A as the target spot in preparation of medicines for treating myocardial fibrosis and heart failure. The KDM4A is determined to be capable of mediating myocardial fibroblast aging so as to promote fibrosis of myocardial tissues and lead to heart failure. The invention provides a method for screening the medicine for treating myocardial fibrosis and heart failure by taking KDM4A as a target spot for the first time, and provides the medicine for treating myocardial fibrosis and heart failure, namely the medicine for regulating and controlling cardiac muscle fiber cell senescence to inhibit myocardial fibrosis.

The disclosure generally relates to methods, cells, and compositions for preparing cardiac extracellular matrix. In particular, provided herein are methods for preparing a cardiac extracellular matrix using SUSD2 High fibroblasts and SUSD2 High myofibroblasts.

The invention belongs to the technical field of biology, and particularly relates to a CFTSR gene, a CFTSR gene simulant and application of the CFTSR gene simulant. The nucleic acid sequence of the CFTSR gene is as shown in SEO ID NO. 1. The nucleic acid sequence of the CFTSR gene simulant is as shown in SEO ID NO. 2. The CFTSR gene provided by the invention can be used as a marker for fibroblast activation, and is used for a kit for detecting cardiac fibroblast activation. The CFTSR gene simulant can be used as a therapeutic drug for myocardial infarction injury, and the overexpression of the CFTSR gene can significantly inhibit the proliferation of fibroblasts and activate the repair of damaged myocardial tissues. Based on CFTSR mimics, a simulant of the CFTSR gene is constructed, and the simulant can be conveyed to the position of a heart lesion and can be used as a medicine for treating myocardial infarction injury, so that effective treatment of the lesion is realized.

The application discloses application of a composition containing tanshinone extract and muscone, and belongs to the technical field of medicines. The compatibility and ratio control of the tanshinone extract and the muscone can inhibit expression and / or secretion of FSTL1 of cardiac fibroblasts at a molecular level, regulate related fibrosis signal pathways, thereby inhibiting a myocardial fibrosis process, and producing a synergistic effect with anti-myocardial injury, improving ventricular structure and function abnormalities after myocardial infarction, and being used for treating cardiovascular diseases such as myocardial infarction, myocardial fibrosis and heart failure after myocardial infarction. The composition of the application comprises the tanshinone extract and the muscone, and can be used for preparing a medicine for preventing and treating cardiovascular diseases with better effects.

A system and method for distinguishing non-failing from failing cardiac fibroblasts (CFs) using advanced imaging techniques and machine learning (ML). The method involves staining CFs with fluorescent dyes to highlight key cellular components, such as nuclei and actin fibers. Images are analyzed to extract morphological features, which are then processed and normalized. A supervised ML system, trained on labeled CF data, classifies CFs based on phenotypic differences. The system enables accurate diagnosis of heart failure (HF), facilitates screening for therapeutic efficacy, and identifies antifibrotic agents by evaluating changes in CF phenotypes pre- and post-treatment.

The invention provides a viral vector based on adeno-associated virus serotype 2 (AAV2,) which preferentially targets and transduces activated cardiac fibroblasts in vivo, the viral vector comprising a nucleic acid construct for an effector molecule as a transgene, the viral vector being characterized by comprising a capsid protein (CAP) which C-terminally and directly adjacent to amino acid No. 587 of the wild-type amino acid sequence of CAP contains an inserted amino acid section.

The present invention relates to the field of biomedicine, and discloses use of a PD1 inhibitor in preparation of an inhibitor for cardiac fibroblast transdifferentiation. The present invention found through cell and animal experiments that the PD1 inhibitor can reduce the transdifferentiation level of cardiac fibroblasts after myocardial infarction. The present invention not only provides a therapeutic drug or strategy for myocardial infarction, but also provides a tool drug for the study of transdifferentiation of cardiac fibroblasts.

The invention relates to the method of generating immortalized cardiac fibroblasts with knockout Fhl1 gene. The cells are useful in therapy as a model for finding new strategies to treat cardiomyopathy.

The invention relates to the field of biological medicine, in particular to a si-RNA composition for inducing cardiac fibroblasts to transdifferentiate into endothelial cells and application of the si-RNA composition. The si-RNA composition comprises a si-RNA (Ribonucleic Acid) aiming at a gene Huwe1, a si-RNA aiming at a gene Ltbp3, a si-RNA aiming at a gene Dysf and a si-RNA aiming at a gene Hivep3. The HLDH (Huwe1, Ltbp3, Dysf and Hive3) combined knockout can be used for successfully inducing the transformation of fibroblasts into endothelial cells in an in-vitro ischemia and hypoxia state. A carrier containing shRNA capable of expressing and generating the si-RNA composition is delivered into the heart, so that cardiac fibroblasts undergo transdifferentiation in vivo and participate in angiogenesis, and therefore, increase of fibrosis area and adverse ventricular remodeling after myocardial ischemia are limited through ways such as fibrosis remodeling, the heart function is retained, and myocardial ischemia is improved and repaired.

Activated cardiac fibroblasts are essential for the production of extracellular matrix proteins that accumulate during cardiac fibrosis, and PW1+ cardiac adult stem cells were recently proposed as a cellular source of fibroblasts in the ischemic hearts. Here the inventors identify αV-integrin (or CD51) as an essential regulator of PW1+ cardiac adult stem cells fibrogenic behavior. Inhibition of αV-integrin reduce the profibrotic gene expression profile and the ability to differentiate into fibroblasts of cardiac PW1+ cells. The pharmacological blockade of αV-containing integrins improved cardiac function and survival after MI by reducing infarct size and attenuating the extension of reactive cardiac fibrosis. Notably, the total cardiac fibrotic area as well as interstitial fibrosis in the remote myocardial area are significantly reduced after pharmacological blockade of αV-containing integrins. These data identify a new mechanism that regulates cardiac fibrosis in response to an ischemic injury and suggest that pharmacological targeting of αV-integrin may provide clinical benefit in the treatment of cardiac fibrosis.

Providing gene vector regulation using microRNAs expressed in cardiomyocytes. [Solution] This disclosure provides vectors and methods of using them for cell-type-specific repression of the expression of transgenes (e.g., cardiomyocyte reprogramming factors) using microRNA binding sites. The present invention generally relates to vectors and methods of using them for cell-type-specific repression of the expression of transgenes (e.g., cardiomyocyte reprogramming factors). This disclosure provides vectors comprising microRNA binding sites configured to promote specific repression of the expression of transgenes (e.g., cardiomyocyte reprogramming factors) in cardiomyocytes and cardiomyocyte progenitor cells compared to cardiac fibroblasts.

The invention discloses application of a serine protease inhibitor A3 in preparation of a medicine for preventing and / or treating heart failure diseases. Experimental results show that the SERPINA3 can improve cardiac function reduction, improve ventricular remodeling, reduce myocardial fibrosis, inhibit proliferation and migration ability of cardiac fibroblasts, inhibit differentiation of the cardiac fibroblasts to myofibroblasts and inhibit extracellular matrix proteins. The serine protease inhibitor A3 can inhibit cardiac fibroblast activation and myocardial fibrosis, and provides a new treatment strategy and means for clinical treatment of intractable heart failure.

The invention relates to the field of cell engineering, and particularly discloses a preparation method and application of a conditionally immortalized human myocardial fibroblast model. According to the method, a Tet-on system driven by a cardiac fibroblast specific promoter is constructed to regulate and control a lentiviral vector of an SV40LT-tsA58 temperature-sensitive mutant gene, and after primary human cardiac fibroblasts are transduced, conditional immortalization of the cells is realized in the presence of an inducer doxycycline. The model can be stably amplified under an induction condition, the immortalized gene expression is closed after an inducer is removed, the primary physiological state of cells is recovered, and the high-fidelity response capability to fibrosis promoting and anti-fibrosis drugs is reserved. According to the method, the in-vitro proliferation limit of primary cells is broken through, the problems of species difference and ethics are avoided, and a humanized, high-fidelity and high-controllability standardized tool is provided for myocardial fibrosis pathological mechanism research and drug screening.

The invention discloses application of GANT61 in preparation of a medicine for preventing and / or treating sleep apnea complicated with heart failure. Experiments show that the GANT61 can improve cardiac function reduction induced by intermittent hypoxia combined with angiotensin II, reduce ventricular remodeling and myocardial fibrosis induced by intermittent hypoxia combined with angiotensin II, inhibit the multiplication capacity of cardiac fibroblasts, inhibit differentiation of cardiac fibroblasts induced by intermittent hypoxia to myofibroblasts, improve the cardiac function reduction induced by intermittent hypoxia combined with angiotensin II, and improve the cardiac function reduction induced by intermittent hypoxia combined with angiotensin II. Intermittent hypoxia-induced cardiac fibroblasts are inhibited from secreting extracellular matrixes, and the weight, blood pressure, heart rate and renal functions are not affected.

The present invention provides a polypeptide, whose amino acid sequence is shown in SEQ ID NO.1. The present invention also provides a DNA molecule encoding the above polypeptide. The present invention also provides a recombinant vector containing the above DNA molecule. The present invention also provides the use of the above polypeptide in the preparation of a drug for treating myocardial fibrosis. Compared with the existing polypeptides for treating myocardial fibrosis, the polypeptide of the present invention is secreted in large quantities under physiological conditions after exercise, so the polypeptide has no obvious adverse reactions to the organism. In normal organisms and organisms in the early stages of the disease, myocardial fibrosis can be alleviated by increasing the amount of exercise. In the middle and late stages, myocardial fibrosis can be alleviated by administering the polypeptide in vitro, especially under conditions of restricted exercise. Therefore, the present invention can inhibit the transformation of cardiac fibroblasts into myofibroblasts and alleviate myocardial fibrosis.

Provided herein are methods for producing quiescent cardiac fibroblast cells from pluripotent stem cells. Further provided herein are microtissue compositions comprising the cardiac fibroblast cells with endothelial cells and cardiomyocytes.

The invention discloses a construction method and application of a heart organoid model capable of inducing gene overexpression in fibroblasts, and belongs to the field of biomedicine. The construction method comprises the following steps: constructing an iPSCs stable cell line capable of inducing gene overexpression in fibroblasts on the basis of a PiggyBac transposon system; directionally differentiating the iPSCs stable cell line into cardiac fibroblasts to obtain the cardiac fibroblasts from the iPSCs; and co-culturing the heart fibroblasts from the iPSCs and the myocardial cell spheres from the iPSCs to form heart organoid, and inducing the heart organoid by using doxycycline to obtain the heart organoid model capable of inducing the overexpression of the specific gene in the fibroblasts. The heart organ-like model constructed by the invention provides a powerful tool for research on a myocardial fibrosis pathological mechanism.

The invention discloses a biomarker related to cardiac fibroblasts. The biomarker is one or a combination of more of CSRP2, POSTN, COL2A1 and THBS4. The invention also provides a kit for diagnosis and prognosis evaluation of acute myocardial infarction. The kit comprises a reagent for detecting the expression level of one or more proteins of CSRP2, POSTN, COL2A1 and THBS4. The biomarker provided by the invention is screened through single cell sequencing, proteome sequencing and clinical sample verification, and has relatively high sensitivity and specificity. The method is easy and convenient to operate and accurate in result, early diagnosis and prognosis evaluation of acute myocardial infarction are facilitated, and the burden of patients and the society is relieved.

The invention discloses application of a composition containing a tanshinone extract and muscone, and belongs to the technical field of medicines. Through compatibility and proportion control of the tanshinone extract and the musk ketone, heart fibroblast expression and / or FSTL1 secretion can be inhibited on the molecular level, related fibrosis signal channels are regulated and controlled, accordingly, the myocardial fibrosis process is inhibited, a synergistic effect with myocardial damage resistance is achieved, ventricular structure and dysfunction after myocardial infarction is improved, and the myocardial infarction treatment effect is improved. The pharmaceutical composition is used for treating cardiovascular diseases such as myocardial infarction, myocardial fibrosis and heart failure after myocardial infarction. The composition disclosed by the invention comprises tanshinone extract and muscone, and can be used for preparing medicines with better effects for preventing and treating cardiovascular diseases.

The invention provides an anoxia response promoter element and application thereof, and belongs to the technical field of biological medicine. The hypoxia response promoter element disclosed by the invention is obtained by transforming a whole sequence of a 1000bp region of an HAND1 gene promoter into a sequence as shown in SEQ ID NO.10 or SEQ ID NO.11. The hypoxia response promoter element disclosed by the invention is a hypoxia response promoter element disclosed by the invention. According to the invention, the HAND1 gene promoter region is analyzed and modified, and the modified promoter shows stronger transcriptional activation ability under an anoxic condition, and is a powerful tool for transcriptional regulation of engineered cardiac fibroblasts.

The invention relates to a circRNA marker and application of the circRNA marker in preparation of a diagnostic kit and a therapeutic drug for myocardial fibrosis after myocardial infarction, and belongs to the technical field of biological medicine. In order to solve the problem that a sensitive circRNA marker for diagnosing myocardial infarction related diseases is lacked, the invention provides a circRNA biomarker circ-CELF1, the nucleotide sequence of the circRNA biomarker circ-CELF1 is as shown in SEQ ID NO.1, and the expression of the circRNA biomarker circ-CELF1 in myocardial infarction mouse heart tissues and human cardiac fibroblasts treated by transforming growth factor-beta1 is remarkably up-regulated. The circ-CELF1 can be used as a novel biomarker for clinical diagnosis of myocardial fibrosis. By knocking down the circ-CELF1, expression of MI and TGF-beta1 induced myocardial fibrosis markers can be remarkably reduced, myocardial fibrosis is improved, and it is prompted that the medicine taking circ-CELF1 as the target spot can inhibit myocardial fibrosis.

The invention belongs to the technical field of molecular stem cell proliferation, and relates to application of miRNA in promoting in-vitro proliferation of human corneal stromal mesenchymal stem cells. The miR-19b-1-5p can be used as a target to screen the culture medium additive capable of promoting the in-vitro proliferation of the human corneal stroma mesenchymal stem cells. The method is expected to realize industrialization, and has important significance for providing'seed 'cells in regenerative medicine. The invention also finds that the co-incubation of the human corneal stromal mesenchymal stem cells with high expression of miR-19b-1-5p and the cardiac fibroblasts can obviously influence the improvement of the expression of PAX6 in the cardiac fibroblasts and inhibit the expression of a profibrosis factor TGF beta; therefore, the human corneal stroma mesenchymal stem cells with high expression of miR-19b-1-5p are expected to be used as a favorable tool for delaying cardiac fibroblast fibrosis in vitro, and a foundation is also laid for exploring a stem cell therapy for treating cardiac fibrosis in the future.

The present invention relates to the field of biomedicines. Disclosed are an intervention target for advanced fibrosis of an ischemic heart disease and a use thereof. In the present invention, it was found that a CD248 protein is only specifically and highly expressed in cardiac fibroblasts in an ischemic injury area, and is expressed at lower levels in other normal tissue cells, and therefore, the CD248 protein can be used as an intervention target for advanced fibrosis of an ischemic heart disease to effectively inhibit excessive cardiac fibrosis, and the safety is high. According to the present invention, an RNA fragment, a monoclonal antibody and a CAR-T cell targeting CD248 are prepared; the RNA fragment can inhibit CD248 gene expression; the monoclonal antibody has good affinity to the CD248 protein, and can effectively inhibit the activation of fibroblasts; and the CAR-T cell has better infiltration into a heart ischemia injury area, and can kill CD248+ fibroblasts.

The invention discloses a 3-aryl coumarin derivative as well as a preparation method and application thereof, and the preparation method comprises the following steps: reacting substituted 2-bromobenzaldehyde with a substituted aryl acetic acid compound to obtain a substituted E-2, 3-diaryl acrylic acid compound; and in the presence of cuprous oxide and potassium carbonate, heating and reacting in N, N-dimethylformamide to obtain the 3-aryl coumarin derivative. The 3-aryl coumarin derivative disclosed by the invention can be combined with BRD4, has remarkable inhibitory activity on the BRD4, has a protective effect on primary myocardial cells caused by ischemia reperfusion, can inhibit proliferation, migration and invasion of cardiac fibroblasts, and can inhibit ferroptosis of hypoxia / reperfusion injury myocardial cells; the compound can be used for preparing medicines for treating diseases related to abnormal BRD4 activity.

The invention provides a bovine primary cardiac fibroblast hypoxia model construction method, and belongs to the technical field of cell model construction, trypsin and type II collagenase are adopted for sequentially digesting, differential attachment and the like to obtain bovine primary cardiac fibroblasts, the bovine primary cardiac fibroblasts are treated for 24-72 h under the hypoxia condition of 1% O2, 5% CO2 and 94% N2 at the inoculation cell density of 3.5 * 10 < 5 >-8 * 10 < 5 > / ml, and the bovine primary cardiac fibroblasts are obtained. And constructing the cell hypoxia model. The three-gas incubator hypoxia model based on the primary bovine myocardial fibroblasts can accurately simulate a pathological hypoxia environment, and is suitable for hypoxia stress mechanism research and key molecule screening. The model is high in physiological correlation and simple and convenient to operate, has wide applicability and reference value, and provides a reliable experimental platform for research on the bovine hypoxia myocardial diseases.

The invention relates to the technical field of biomedicine, and provides an application of a long-chain non-coding RNANAV2-AS2 in promotion of Apelin protein expression. The invention further discloses application of the long-chain non-coding RNANAV2-AS2 in preparation of a medicine for promoting expression of Apelin mRNA (messenger ribonucleic acid) or Apelin protein. The expression of Apelin can be promoted by up-regulating the NAV2-AS2 in the human heart fibroblast, and the expression of Apelin can be inhibited by inhibiting the NAV2-AS2; the NAV2-AS2 has an inhibition effect on the expression of the miR-31, the miR-31 has an inhibition effect on the expression of the Apelin, and the effects are confirmed by luciferase reporter gene experiments; after miR-31 is over-expressed in human heart fibroblasts, the miR-31 is found to counteract the promotion effect of NAV2-AS2 on Apelin expression.