20 results about "Cardiotoxicity" patented technology

The invention discloses a construction method and application of an animal model for evaluating cardiotoxicity of antitumor drugs, sodium carboxymethyl cellulose (CMC-Na) with extremely low cost is adopted to replace matrigel, a tumor-bearing mouse model with high stability can be constructed at low cost, and experimental verification shows that 4T1 cells are resuspended by using a 0.7% CMC-Na solution, and the tumor formation rate of subcutaneous inoculation reaches gt; 95%. The tumor microenvironment-mediated cardiac injury critical period is accurately captured, and the constructed tumor-bearing mouse model is the optimal tumor-bearing mouse model for evaluating the cardiotoxicity of an antitumor drug (adriamycin) in the tumor microenvironment in the third week after the mouse has a 50mm < 3 > tumor.

The invention belongs to the field of traditional Chinese medicines, and provides astragalus membranaceus and jujube heart-protecting granules as well as a preparation method and application thereof, and the astragalus membranaceus and jujube heart-protecting granules are prepared from the following medicinal materials: raw astragalus membranaceus, codonopsis pilosula, semen ziziphi spinosae, salvia miltiorrhiza, angelica sinensis, ligusticum wallichii and cassia twig. The astragalus membranaceus and jujube heart-protecting granules are convenient to carry and take, experiments prove that the astragalus membranaceus and jujube heart-protecting granules are helpful for preventing or treating cardiotoxicity of targeted drugs and / or immune examination inhibitors, and a new solution is provided for expanding the application of astragalus membranaceus and jujube heart-protecting prescriptions and solving the problem of cardiotoxicity of traditional Chinese medicines for tumor treatment.

The invention provides a composition, cell culture and application of the composition in differentiation of human pluripotent stem cells to myocardial cells and / or construction of human-derived heart organoid, and belongs to the technical field of cell engineering. The invention provides a composition. The composition comprises a fatty acid receptor antagonist, a fatty acid synthetase inhibitor and a fatty acid oxidation activator. The composition provided by the invention can regulate cell metabolism, breaks through the contradiction that the proliferation capacity and the cell maturity cannot be obtained at the same time in the traditional technology, can maintain the myocardial cells in a proliferation stage, and obtains the myocardial cells with relatively mature structures and functions, and the contractility of 3D heart organs constructed by the myocardial cells is greatly improved. The invention provides a high-quality cell source for myocardial regeneration treatment, high-throughput drug cardiotoxicity screening and heart disease mechanism research, and has remarkable clinical application value and industrialization prospect.

The invention relates to application of S-adenosylmethionine or salt thereof in preparation of a medicine for preventing and treating ATO cardiotoxicity, and belongs to the field of biological medicine. In order to solve the problem that a general ferroptosis inhibitor cannot prevent and treat ATO cardiotoxicity from the source, the invention provides application of S-adenosylmethionine or salt thereof in preparation of drugs for preventing and treating ATO cardiotoxicity. The invention discloses a key molecular pathway of cardiac toxicity caused by ATO: ATO methylation metabolism exhausts endogenous methyl donors of myocardial cells, causes methylation imbalance of histone H3K9me3, and causes abnormal high expression of ferroptosis key protein HO-1 and mitochondrial iron overload. On the basis, the invention creatively provides a targeted intervention strategy of exogenous supplementation of S-adenosylmethionine, methylation imbalance and ferroptosis pathway activation are blocked from the upstream, root prevention and treatment of ATO cardiotoxicity are realized, and cardiac insufficiency is improved. The targeted intervention strategy is good in safety and has the advantages of clinical transformation and long-term application.

The invention relates to the technical field of medicine, in particular to application of parishin E in preparation of medicine for preventing and / or treating mitochondrial dysfunction heart failure, and the heart failure particularly refers to chronic heart failure induced by anthracycline antitumor drugs and related to mitochondrial dysfunction. In-vitro experiments prove that the parishin E can remarkably improve the mitochondrial function of myocardial cells damaged by adriamycin and improve basic respiration, ATP (adenosine triphosphate) synthesis and maximum respiration capacity of the myocardial cells. In an animal model, the parishin E effectively improves heart function indexes and relieves pathological injuries such as myocardial fiber arrangement disorder and cavity enlargement. The invention provides a natural small molecule which is novel in mechanism and has development potential for clinically preventing and treating anthracycline cardiotoxicity.

The invention provides an application and a method of GSH in promoting mature differentiation of hiPSC-CMs, and the method is characterized in that in the process of directionally differentiating the hiPSC-CMs into the hiPSC-CMs, an effective dose of GSH is added into a differential medium, and the optimal concentration is 20-100 [mu] M. According to the invention, through simple and economical exogenous supplement of GSH, maturation of hiPSC-CMs is systematically promoted from multiple dimensions, including enhancement of intracellular anti-oxidation defense capability; energy metabolism is promoted to be converted from glycolysis to oxidative phosphorylation; up-regulating expression of cardiac muscle cell specific structural protein and calcium ion channel related genes; mitochondrial biological generation and functions are promoted; and the cell morphological structure is induced to develop to a mature phenotype. The method is simple and convenient to operate and high in biocompatibility, the hiPSC-CMs with mature functions can be stably obtained, and a high-quality cell source is provided for application of the hiPSC-CMs in the fields of heart disease modeling, drug cardiotoxicity screening and the like.

The invention discloses an anti-fibrillation organ chip state monitoring system and method based on electrophysiological signal analysis, and relates to the field of micro-physiological systems and bio-electricity signal monitoring. The problem that the myocardial tissue tremor risk cannot be dynamically and quantitatively evaluated through existing organ chip monitoring is solved. The method comprises the following steps: acquiring a myocardial electrophysiological signal in real time through a reconfigurable probe array, and calculating a signal quality index; dynamically inverting key parameters of the ion channel by using a data assimilation algorithm, and constructing an observation noise covariance matrix; constructing a tremor critical curved surface in a myocardial electrophysiological model parameter space, and calculating a geometric distance from a current parameter point to the critical curved surface to generate a critical distance index; calculating a dynamic curvature tensor based on the tiny disturbance response function and generating a curvature early warning index; and finally, fusing the two to generate a comprehensive early warning index, and outputting an early warning signal when a threshold value is exceeded. Real-time quantitative early warning of the myocardial tissue tremor risk is realized, and the accuracy and reliability of anti-tremor drug screening and cardiotoxicity assessment are remarkably improved.

The invention relates to the technical field of traditional Chinese medicine preparations, and particularly discloses a traditional Chinese medicine preparation for treating heart failure and diuretic resistance and a preparation method of the traditional Chinese medicine preparation. The active extract is prepared from the following raw material medicines: astragalus membranaceus, ginseng, cinnamon, salvia miltiorrhiza, red paeony root, radix rehmanniae recen, cassia twig, ligusticum wallichii and pseudo-ginseng. On the basis of a traditional qi-tonifying and blood-activating treatment method, a treatment method for enhancing the effect of dredging collaterals and the effect of nourishing yin is combined, the cinnamon serves as a core monarch drug to warm and tonify yang of the heart and the kidney, and compatibility is scientific; the cortex cinnamomi is used for completely replacing radix aconiti lateralis preparata, so that potential cardiotoxicity and neurotoxicity risks caused by aconitum alkaloids are fundamentally eliminated; the traditional Chinese medicine preparation disclosed by the invention provides a solid guarantee for long-term and safe medication of patients with heart failure, is more suitable for treating intractable and complicated heart failure, and has a good clinical application value.

In certain embodiments, the present disclosure is directed to methods and uses for treating a mammal having an epileptic seizure disorder or being at risk for having an epileptic seizure disorder, comprising administering certain herein disclosed isolated fenfluramine enantiomers that are surprisingly effective as anti-epilepsy drugs (AEDs), despite having lower anti-seizure potency than fenfluramine racemate, by virtue of also being less cardiotoxic than fenfluramine racemate. Preferred embodiments contemplate treatment of Dravet syndrome; other preferred embodiments contemplate treatment of other epileptic seizure disorders.

The invention discloses a diazaspiro compound as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The diazaspiro compound is shown as a formula I, is a CCK-BR small-molecule agonist, has excellent agonistic activity, has good selectivity in CCK-AR and CCK-BR, can reduce side effects caused by off-target effects, and has no potential side effects such as cardiotoxicity. The molecules have potential treatment capacity on epilepsy, depression, dementia, anxiety, Alzheimer's disease, tinnitus, amblyopia, schizophrenia, neuropathic pain, memory loss, gastric acid, obesity, pancreatic cancer and gallbladder cancer.

The present application relates to a breast cancer cardiotoxicity risk prediction system based on multi-modal data fusion. The system collects multi-source heterogeneous medical data such as electronic health records, dynamic electrocardio monitoring, echocardiogram video stream, chemotherapy medication time series data and pathological section images in real time through a distributed architecture, and optimizes storage efficiency by adopting a hierarchical compression strategy. The system maps the risk index to a three-dimensional heart heat map, displays the key feature contribution degree, and establishes a dynamic risk knowledge graph to reveal the toxicity occurrence path. The system deploys an incremental learning mechanism to realize continuous optimization of the model, ensures data security through differential privacy and federated learning, sets up a real-time early warning feedback loop, triggers clinical intervention when the risk exceeds the threshold, and dynamically adjusts the model weight according to the feedback of the physician, thereby significantly improving the prediction accuracy and clinical applicability.

A method for evaluating the cardiotoxicity of a drug by using a multiple in silico biomarkers-based logistic regression model, according to the present invention, comprises: generating a multi-input scenario for biomarkers and inputting same into ordinal logistic regression models (OLR) to predict a risk of arrhythmia (TdP) caused by a drug; and evaluating performance to rank and analyze the ordinal logistic regression models (OLR).

This invention discloses a copper dicyclopentyl dithiocarbamate compound and its applications, relating to the field of pharmaceutical chemistry, with the molecular formula C0. 22 H 36 CuN2S4, with a central copper ion and two dicyclopentyl dithiocarbamate ligands coordinated via sulfur atoms to form a four-coordinate planar square structure, or its pharmaceutically acceptable salts, solvates, crystal forms, or hydrates. This invention utilizes a novel chemical entity of dicyclopentyl-substituted copper dithiocarbamate, leveraging the greater steric hindrance and lipophilicity advantages of its cyclopentyl structure, as well as its selective response to the high-copper microenvironment of cholangiocarcinoma. Furthermore, it exhibits strong targeting, achieving high enrichment in liver and cholangiocarcinoma tissues, broadening the therapeutic index. Simultaneously, by avoiding the inhibition of systemic ALDH2 activity, it eliminates the alcohol-like toxicity caused by acetaldehyde accumulation. Moreover, it does not cross the blood-brain barrier, exhibits no significant neurotoxicity or cardiotoxicity, is patient-friendly for those with renal insufficiency, and demonstrates high safety.

The embodiment of the invention provides an immune cardiotoxicity assessment system and method based on autonomic nerve axis response, and relates to the technical field of immune cardiotoxicity assessment technologies. The method comprises the steps that the peak value of real current flowing through a patient is obtained, a first physiological signal and a second physiological signal concurrent with a nerve stimulation probe are synchronously collected, and the real current is generated by applying the nerve stimulation probe to the patient; and based on the true current peak value, the first physiological signal and the second physiological signal, generating a comprehensive nerve-heart conduction efficacy index representing the conduction state of the autonomic nerve axis. According to the invention, the problem of low toxicity assessment precision is solved, and the effect of improving the toxicity assessment precision is achieved.

The invention relates to application of an AQP7 inhibitor in preparation of a medicine for preventing and treating ATO cardiotoxicity, and belongs to the technical field of medicines. In order to relieve ATO cardiotoxicity, the invention provides application of an AQP7 inhibitor in preparation of drugs for preventing and treating ATO cardiotoxicity, and the AQP7 inhibitor is siRNA or valproic acid. The invention proves that the accumulation of ATO in heart tissues is a key factor for inducing cardiotoxicity for the first time, and targeted inhibition of AQP7 can significantly reduce the accumulation level of ATO in the heart and alleviate myocardial structure damage and inflammatory infiltration caused by ATO. The invention finds that valproic acid can be used as an efficient inhibitor of AQP7 for the first time, specifically inhibits AQP7, reduces accumulation of ATO in heart, and effectively relieves cardiotoxicity. By inhibiting the AQP7, the cardiac toxicity of the ATO can be remarkably reduced on the premise of not influencing the anti-tumor curative effect of the ATO.

The invention discloses an application of long-chain non-coding RNA (Ribonucleic Acid) H19 in preparation of a medicine for preventing or treating cardiac adverse reaction caused by sorafenib. The sequence of the long-chain non-coding RNA H19 is a nucleotide sequence as shown in SEQ ID NO.1. The invention further discloses a preparation method of the long-chain non-coding RNA H19. The long-chain non-coding RNA H19 plays a key protection role in sorafenib cardiotoxicity adverse reaction drugs, and the expression level of the long-chain non-coding RNA H19 is in negative correlation with the myocardial injury degree. Therefore, the expression and / or activity of H19 in myocardial cells are / is maintained or improved, and the compound can be used for preventing and treating the adverse cardiotoxic reaction of sorafenib.

The invention discloses an application of a Fe3O4 (at) ZIF-8 nano-enzyme in preparation of a medicine for treating myocardial injury, the Fe3O4 (at) ZIF-8 nano-enzyme is of a core-shell structure which takes Fe3O4 as a nano-enzyme and is externally coated with ZIF-8, the overall average particle size of the nano-enzyme is (12-22) nm, it can be ensured that the ultra-small nano-enzyme has good dispersity and myocardial tissue accessibility, and the nano-enzyme can be used as a medicine for treating myocardial injury. And a ZIF-8 shell layer is utilized to stabilize the enzyme-like activity of Fe3O4 and regulate and control the microenvironment, so that additional oxidative damage caused by free iron is reduced, and the material as a main body plays a multi-dimensional mechanism of oxidation resistance, inflammation resistance and mitochondria protection. According to the invention, the Fe3O4 ZIF-8 nano-enzyme is applied to drug-induced myocardial injury for the first time, and it is found that the nano-enzyme shows a remarkable heart protection effect. The Fe3O4 ZIF-8 nano-enzyme can be prepared on a large scale, is good in biocompatibility, and has a wide application prospect in drug cardiotoxicity intervention and other ROS / inflammation related heart diseases.

The invention relates to organoids, and particularly, although not exclusively, to heart organoids. The invention extends to novel methods for producing heart organoids, to their use in in vitro and ex vivo assays, in screening methods, particularly, although not exclusively, during the evaluation of the efficacy, cardiotoxicity, and teratogenicity of pharmaceuticals, as well as to apparatus for use in such screening. In addition, the invention extends to the use of the heart organoids in the study of heart disease and / or pathology.

The application discloses a low-stimulus and high-safety benzoyl aconine original base temperature-sensitive analgesic gel injection as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The injection takes benzoyl aconine original base as a core analgesic component, constructs a triple heart protection system of'sub-anesthetic dose lidocaine + ammonium glycyrrhizinate + magnesium sulfate', cooperates with a poloxamer 407 temperature-sensitive gel matrix, and is supplemented with a cosolvent and an antioxidant, has a pH value of 5.5-6.5, can be injected at room temperature, and is quickly gelled at body temperature to realize long-acting controlled release. The preparation has high analgesic intensity, no addiction, slight injection pain, controllable cardiotoxicity, and can maintain analgesia for more than 12 hours after single administration, is suitable for local targeted treatment of moderate and severe chronic pain, neuropathic pain and the like, and has significant clinical advantages and popularization value.