30 results about "Heart dysfunction" patented technology

The present invention relates to neukinase, a downstream protein kinase in the neuregulin signaling pathway. In certain aspects, the present invention provides isolated neukinase-encoding nucleic acids, neukinase polypeptides, oligonucleotides that hybridize to neukinase nucleic acids, and expression vectors containing neukinase-encoding sequences. The present invention further provides isolated host cells, antibodies, transgenic non-human animals, compositions, and kits relating to neukinase. In other aspects, the present invention further provides methods of identifying predisposition to cardiac dysfunction, methods of detecting the presence of neukinase, neukinase nucleic acid, methods of screening for agents which affect neukinase activity, and methods of modulating neukinase activity.

A method for treatment of cardiac dysfunction comprising administering to a subject in need thereof a therapeutically effective amount of at least one of ANAVEX 2-73 or ANAVEX 19-144 or pharmaceutically acceptable salt thereof or combination thereof.

The present invention provides for methods and compositions for treating, reducing and / or preventing cardiac dysfunction by administering to subject a therapeutically effective amount of a bisphosphonate, prodrug thereof, functional analog or a pharmaceutically effective salt thereof in an amount sufficient to increase activity of at least one kinase in heart tissue of the subject.

The disclosure provides a system for screening compounds for therapeutic cardiac effects in the cells, tissues and organoids of patients having diseases such as neurological diseases or disorders withsignificant cardiac comorbidities. The system comprises a medical device apparatus that can be suitable for a single-tier screen for cardio-active compounds that comprises a human ventricular cardiacanisotropic sheet (hvCAS) and human ventricular cardiac tissue strip (hvCTS), a two-tier system further comprising human ventricular cardiac organoid chamber (hvCOC), or a three-tier system still further comprising a medical device comprising multiple organoids, which include tissues or organoids of the same or different type (e.g., heart, liver, pancreas, kidney). Another aspect of the disclosure is the methods suitable for use with the systems, comprising screens for identifying compounds having cardiac effects on cells, tissues or organoids of patients having a non-cardiac disease exhibiting a cardiac effect, such as neurological diseases. The methods are further useful in assessing the toxicity of compounds to various cells, tissues or organoids of such patients.

The invention provides methods for reducing the incidence and / or severity and / or delaying the onset of heart dysfunction / failure and improving overall survival through the use of remote ischemic per-conditioning and post-conditioning.

The invention discloses a medicine for treating sepsis myocardial dysfunction. The medicine consists of an active ingredient and a pharmaceutically acceptable excipient, wherein the active ingredient is prepared from the following raw materials: cassia twig, radix salviae miltiorrhizae, radix pseudostellariae, styrax ester, calculus bovis factitius and radix et rhizoma rhei. The traditional Chinese medicinal composition disclosed by the invention, which is prepared from the active ingredient and the excipient together, is capable of effectively improving the cardiac function of patients with sepsis myocardial dysfunction and reducing a death rate, a myocardial injury marker and an inflammatory mediator, and the traditional Chinese medicinal composition is free from an adverse reaction. The medicine fills a gap in the therapeutic field.

The present invention provides a method for establishing a mouse model of autoimmune myocarditis (Experimental Autoimmune Myocarditis, EAM) induced by an autoantigen epitope. The relationship between AchR and autoimmune myocarditis is determined for the first time. Injection of AchR-Freund's complete adjuvant solution, AchR-Freund's incomplete adjuvant solution and immune booster to produce antibodies against cardiomyocyte M2 cholinergic receptors to induce autoimmune myocarditis, and the established model has cardiomyocyte hypertrophy , myocardial fibrosis and cardiac dysfunction. At the same time, with 18 F-FDG PET / CT myocardial metabolic imaging is the core, combined with echocardiography, HE staining of myocardial tissue sections, myocardial Mason staining and myocardial tissue immune antibody special staining to verify the characteristic changes related to the mouse model. Provide a new mouse model for further research on autoimmune myocarditis.

The invention provides compositions and methods for treating cardiac dysfunction, particularly cachexia-associated or RAGE-associated cardiac dysfunction, using an anti-RAGE agent. The invention also provides compositions and methods for identifying therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing). The methods comprise designing or identifying agents that bind to functional sites identified on the RAGE polypeptide, wherein binding of agents to the functional site(s) inhibit RAGE-mediated cachetogenic signaling.

Disclosed are antisense oligonucleotide, polynucleotide, and peptide nucleic acid compounds that specifically bind to mammalian mRNA encoding a beta1-adrenoceptor polypeptide and that are useful in the control and / or treatment of cardiac dysfunction, hypertension, hypertrophy, myocardial ischemia, and other cardiovascular diseases in an affected mammal, and preferably, in a human subject. The antisense compounds disclosed herein, and pharmaceutical formulations thereof, provide sustained control of beta1-adrenoceptor expression over prolonged periods, and achieve therapeutic effects from as little as a single dose. Administration of these antisense compositions to approved animal models resulted in a decrease in blood pressure, but no significant change in heart rate. Use of such antisense compositions in the reduction of beta1-adrenoceptor polypeptides in a host cell expressing beta1-adrenoceptor-specific mRNA, and in the preparation of medicaments for treating human and animal diseases, and in particular, hypertension and other cardiac dysfunction is also disclosed.

The present disclosure provides a cDNA, protein sequence, and genomic structure of the human cardiac isoform of myosin light chain kinase (cMLCK), and describes mutations in the cMLCK gene that are associated with cardiac dysfunction. Methods are provided for identifying individuals who can harbor mutations in the cMLCK gene, or carry alleles that can predisposed them to cardiac dysfunction. Disclosed also is a significant role for cMLCK in modulating cardiac contractility. The cMLCK protein is shown herein to reduce the amplitude of stretch activation and increase the tension production, a property of muscle which has heretofore had an unknown role in cardiac contraction. Moreover, the cMLCK protein is shown to be regionally distributed in the heart, thereby having differential effects on contractility and stretch activation. Methods herein are provided to exploit this effect of cMLCK, to treat individuals who have or are prone to cardiac dysfunction. In addition, methods are provided to identify agents that modulate cMLCK activity, thereby having potential therapeutic importance in the treatment of cardiac dysfunction.

Modulation, preferably inhibition, of neurosignaling of a cardiac-related sympathetic nerve in the extracardiac intrathoracic neural circuit is effective in stabilizing cardiac electrical and / or mechanical function, thereby providing ways of treating or preventing cardiac dysfunction such as arrhythmias.

In alternative embodiments, provided are methods for treating, ameliorating or protecting (preventing) congestive heart failure (CHF) or a diabetes-related cardiac dysfunction, comprising: providing a urocortin 2-encoding and / or a urocortin 3-encoding nucleic acid, transcript or message, or gene, operatively linked to a transcriptional regulatory sequence, optionally contained in an expression vehicle or a vector such as an adeno-associated virus (AAV), e.g., an AAV8 serotype; and administering to an individual or a patient in need thereof, such as a type 2 diabetic (T2DM), e.g., by IV administration, thereby treating, ameliorating or protecting against (preventing) the T2DM and / or the diabetes-related cardiac dysfunction in the individual or patient.

The invention discloses application of PEDF gene in treating diabetic myocardial damage. According to the invention, the relationship between the PEDF gene and diabetic myocardial damage is determinedfor the first time, and PEDF gene knockout can lead to a rise in weight and blood sugar, cardiomyocyte hypertrophy, myocardial fibrosis and cardiac dysfunction. It shows that the PEDF gene's functionin diabetic myocardial damage is mainly reflected in the PEDF's effects of improving cardiomyocyte hypertrophy and myocardial fibrosis and improving cardiac function. in allusion to the above functions of the PEDF gene, the PEDF can be used as a medicine for preventing, alleviating or / and treating diabetic myocardial damage; the PEDF can be used as a drug target for screening a medicine for preventing, alleviating or / and treating diabetic myocardial damage; and the PEDF also can be used as a target gene in gene therapy for designing and preparing a medicine for preventing, alleviating or / andtreating diabetic myocardial damage and / or a biological preparation.

Animal models and methods wherein homoplasmic and heteroplasmic mtDNA mutation(s) are induced in an animal (e.g., a mouse) to cause or facilitate the development of a disorder (e.g., disease, malformation, defect, abnormality or other disorder). In at least some embodiments, the mtDNA mutation(s) will cause or facilitate the development of an age-related disorder, such as a cardiac disease, cardiomyopathy, muscle disease, cancer, abnormaly in tissues of high cellular turnover, heart dysfunction, graying of hair, alopecia, auditory function loss, cochlear degeneration, immune cell loss, anemia, male germ cell loss leading to lack of sperm and infertility, skeletal muscle mass loss (sarcopenia), neurodegeneration, increased presence of apoptotic markers, and loss of bone mass.