33 results about "Sarcomere" patented technology

Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.

Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.

Methods for treating heart failure are described herein. Treatment methods include administering a cardiac sarcomere activator (e.g., omecamtiv mecarbil, or a pharmaceutically acceptable salt and / or hydrate thereof) to a subject in need thereof. Treatment methods also include adjusting a dose level of the CSA, for example, to increase, decrease, or maintain a dose level, based on the subject's plasma concentration of the CSA determined after administration of the first dose level of the CSA has started. Provided herein are also treatment methods effective to achieve a target concentration range of the CSA and dose in a single step following a single plasma concentration determination.

The invention discloses application of functional protein STEAP3 in preparation of drugs for preventing, diagnosing and / or treating heart failure and medical inspection products, and belongs to the technical field of medicines. The invention discloses application of targeted regulation of STEAP3 in preparation of drugs for prevention, diagnosis and / or treatment of heart failure and medical inspection products. Experiments prove that targeted regulation of the protein can significantly improve the activity of cardiac muscle cells and enhance the ability of the protein to resist stress injury, and the protein also has the following five significant activities in DOX-induced heart failure model mouse in-vivo experiments: 1) improving cardiac dysfunction; the traditional Chinese medicine composition has the effects of clearing away heat and toxic materials, reversing myocardial tissue fibrosis, improving myocardial tissue sarcoma disorder, relieving myocardial cell apoptosis and reducing myocardial cell mitochondria damage.

Provided herein are compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein Z1, Z2, Z3, R1, R2, R3, and n are as defined herein. Also provided herein is a pharmaceutically acceptable composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof. Also provided herein are methods of using a compound of formula (I), or a pharmaceutically acceptable salt thereof, to treat various diseases, disorders, and conditions responsive to the modulation of the contractility of the skeletal sarcomere.

To provide a method for treating a subject having cardiac failure.SOLUTION: A method includes administering an initial dose of cardiac sarcomere activator (CSA) to a subject for a first period, and subsequently, administering a dose of CSA based on the plasma concentration of CSA in the subject at the end of the first period to the subject.SELECTED DRAWING: None

The present invention relates to a method, device and storage medium for automatically detecting the sarcomere region of cardiomyocytes, and is applied to the technical field of cardiomyocyte detection. Specifically, it includes: fusing the original video data into an image to represent the region of cells during rhythmic contraction and relaxation; calculating the structural strength of the image based on the fused and sharpened image, and generating a high-structural-strength region mask according to the structural strength, which represents the region where sarcomeres exist; finally, iteratively optimizing the high-structural-strength region mask image by the centroid-driven polar ray method to obtain the sarcomere region map inside the cardiomyocyte; by calculating the structural features of the image after fusing multiple frames of images, the present application obtains the general sarcomere region, and through the centroid-driven polar ray method, obtains a smooth inscribed contour of the sarcomere region. Compared with the prior art, it does not need to locate cardiomyocytes, directly locates sarcomeres through the structural strength, and the obtained sarcomere ROI is more suitable for subsequent calculation of sarcomere motion parameters and is not affected by human subjective factors.

The invention discloses a method for evaluating the quality of surimi on the basis of muscle tissue microstructure and endogenous enzyme activity, which comprises the following steps: acquiring the muscle joint length of raw material fish muscle tissue and the activity data of muscle fiber-bound cathepsin L, and constructing a correlation model between the muscle joint length and the activity data of muscle fiber-bound cathepsin L and the gel strength of surimi; and predicting to obtain the gel strength after the raw material fish is processed into the gel, so that the special raw material fish for surimi is classified and screened. According to the method disclosed by the invention, the sarcomedo length and the activity of the muscle fiber-bound cathepsin L are selected to have significant correlation with the quality of the minced fillet gel, and the parameter combination provides objective and reliable data support and decision basis for raw material screening and quality control; besides, the method can realize rapid prediction of the gel quality based on the raw material fish without preparing the minced fillet gel, greatly simplifies the process, saves time, cost, raw materials and the like, has important application value and wide popularization prospect, and can provide reliable quality prediction technical support for the minced fillet product industry.

Methods and compositions for rapidly replacing cMyBP-C in sarcomeres featuring the creation of Spy-C mice, which are mice genetically engineered to express cMyBP-C with a protease recognition site and SpyTag peptide introduced into the cMyBP-C gene. In permeabilized myocytes from the Spy-C mice, the cMyBP-C protein can be cleaved at the protease recognition site, and the N-Terminus of cMyBP-C can be removed while the C-terminus remains anchored to the thick filament. A new peptide featuring the SpyCatcher sequence can be covalently bonded to the remaining portion of cMyBP-C, thereby creating a modified cMyBP-C protein. The methods and compositions of the present invention allow for the reconstitution of full-length cMyBP-C at the precise position of native cMyBP-C in the sarcomere and allow for a variety of modifications to be introduced to cMyBP-C in situ.

The present disclosure relates to the treatment and prevention of diseases and conditions (e.g., cardiomyopathy) by LINC complex inhibition. LINC complex inhibitors are provided for use in methods of treating or preventing a disease or condition characterized by microtubule dysfunction and / or a disease or condition characterized by sarcomere defects or dysfunction.

Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.

The present invention provides expression cassettes and methods that reduce expression of an endogenous TNNT2 gene while providing a non-mutant TNNT2 transgene (tTNNT2), resulting in greatly increased TNNT2 transgene incorporation in the sarcomere than from delivery of the TNNT2 transgene alone.

The present disclosure relates to the treatment and prevention of diseases and conditions (eg. cardiomyopathy) through LINC complex inhibition. A LINC complex inhibitor is provided for use in a method of treating or preventing a disease or condition characterised by microtubule dysfunction and / or a disease or condition characterised by sarcomere deficiency or dysfunction.

The invention discloses a high-frequency mechanical stimulation and sarcoplasmic reticulum calcium activity combined imaging device and method conjugated with sarcoplasmic systole and application. The high-frequency mechanical stimulation and sarcoplasmic reticulum calcium activity combined imaging method conjugated with sarcoplasmic systole comprises the steps that muscle cells are provided; carrying out calcium ion dyeing treatment on the muscle cells; and applying mechanical stimulation which is conjugated with the systolic length of the sarcometre of the muscle cell and is vertical to the direction of the sarcometre to the muscle cell subjected to the calcium ion dyeing treatment, and observing by using a high-speed turntable confocal microscope. The monitoring method provided by the invention can better simulate the physiological conditions of the cells and monitor the calcium ions on the myoplasmon of the muscle cells, and is of great significance to the research of cell mechanics.

Disclosed are an apparatus and method for the joint imaging of high-frequency mechanical stimulation conjugated with sarcomere contraction and sarcoplasmic reticulum calcium activity, and an application. The method for the joint imaging of high-frequency mechanical stimulation conjugated with sarcomere contraction and sarcoplasmic reticulum calcium activity comprises: providing muscle cells; performing calcium ion staining on the muscle cells; and applying, to the muscle cells, which have been subjected to calcium ion staining, mechanical stimulation conjugated with the sarcomere contraction length of the muscle cells and oriented perpendicular to a sarcomere direction, and using a high-speed spinning disk confocal microscope to perform observation.

Provided herein are compounds of formula (I):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X1, X2, Ry, Rz, R1, R2, R3, and R4 are as defined herein.Also provided herein is a pharmaceutically acceptable composition comprising a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.Also provided herein are methods of using a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, to treat various diseases, disorders, and conditions responsive to the modulation of the contractility of the skeletal sarcomere.

Here, we describe an infant with congenital dilated cardiomyopathy (cDCM) whose impaired cardiac function and disrupted sarcomere and mitochondria structures were modeled using induced pluripotent stem cells (iPSCs). The causal gene encodes the centrosomal protein rotatin (RTTN), representing the first time a centrosome defect has been found to cause nonsyndromic dilated cardiomyopathy (DCM) in humans. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. The small molecule, C19, restored initiation of the perinuclear MTOC, and significantly improved the structure and function of cardiomyocytes. In summary, this study provides a new therapeutic strategy for infantile or congenital DCM.

Provided are compounds of Formula (I):or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1, R2, R3, and R4 are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Also provided are methods of using a compound of Formula (I), or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

Compounds of formula (i) are provided: formula (i) or a pharmaceutically acceptable salt thereof, wherein a, z, b, r1, r2, r3, g1, g2 and g3 are as defined herein. A pharmaceutically acceptable composition comprising a compound of formula (i), or a pharmaceutically acceptable salt thereof, is also provided. Methods for using a compound of formula (i), or a pharmaceutically acceptable salt thereof, for use in methods of treating heart disease by inhibiting the cardiac sarcomere are also provided.

The application discloses a kind of based on sarcomere's bionic flexible driver, belong to soft robot technical field.The driver includes external pneumatic artificial muscle driving unit group, internal bionic tension integral framework and upper and lower connecting disc buckle group.External pneumatic artificial muscle driving unit group is made of four external pneumatic artificial muscle driving units distributed in cross shape, as active driving source;Internal tension integral framework realizes self-balancing and self-stabilization by prestress.By differentiating pressure to each external pneumatic artificial muscle driving unit, control its generation non-uniform axial contraction, to drive the whole realization controllable bending movement.The application fuses sarcomere bionic principle and tension integral structure, while maintaining good compliance, significantly improves stiffness and stability, effectively solves the problem of weak rigidity, slow response and insufficient deformation control precision of traditional flexible driver, and is suitable for robot operation scene needing high flexibility and environmental adaptability.

The application discloses a gene therapy vector for promoting myocardial maturation and improving dilated cardiomyopathy and application thereof, and belongs to the technical field of gene therapy. The gene therapy system provided by the application can promote myocardial maturation and enhance contractility. In the NRVM and hiPSC-CM / EHT models, low expression of caMRTFA can significantly increase the Myh6 / Myh7 expression ratio, increase the order degree of sarcomere arrangement, and greatly enhance the contractility of engineered myocardial tissue. The application significantly improves LMNA dilated cardiomyopathy. In the DCM model mice, the left ventricular ejection fraction (EF%) and the fractional shortening (FS%) of the administration group are significantly restored, the ventricular dilation is improved, the myocardial fibrosis area is significantly reduced, and the survival period is greatly prolonged. The gene therapy vector provided by the application shows extremely high safety under the precise regulation of Risdiplam and does not cause myocardial hypertrophy and abnormal activation of pro-inflammatory / pro-fibrotic genes.

The invention discloses a bionic flexible driver based on sarcomels, and belongs to the technical field of soft robots. The driver comprises an external pneumatic artificial muscle driving unit group, an internal bionic stretch-draw integral framework, an upper connecting disc buckle group and a lower connecting disc buckle group. The external pneumatic artificial muscle driving unit set is composed of four external pneumatic artificial muscle driving units distributed in a cross shape and serves as an active driving source. The internal tensioning integral framework achieves self-balance and self-stabilization through prestress. Differential air pressure is applied to all the external pneumatic artificial muscle driving units, the external pneumatic artificial muscle driving units are controlled to generate non-uniform axial contraction, and therefore the whole body is driven to achieve controllable bending movement. According to the flexible actuator, the sarcomedo bionic principle and the tensegrity structure are fused, the rigidity and stability are remarkably improved while good flexibility is kept, the problems that a traditional flexible actuator is low in rigidity, slow in response and insufficient in deformation control precision are effectively solved, and the flexible actuator is suitable for robot operation scenes needing high flexibility and environmental adaptability.

Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.

The invention discloses a differentiation method of hiPSCs-derived myocardial cells based on 3D suspension culture, belongs to the technical field of differentiation culture of human induced pluripotent stem cells, and realizes the effects of improvement of cell differentiation efficiency, improvement of cell function maturity, enrichment of cell purity, enhancement of clinical application suitability and the like by adopting staged directional induction based on 3D suspension culture. The problems that a two-dimensional adherent culture method is low in differentiation efficiency, poor in repeatability, difficult to scale and insufficient in physiological correlation of obtained myocardial cells are solved. Meanwhile, the 3D environment can induce cytoskeleton reconstruction, promote orderly arrangement of sarcoglyphs and improve the contraction strength, rhythm stability and cell sphere size uniformity of the myocardial cells, and the problems that the myocardial cells obtained through existing three-dimensional suspension culture are uneven in cell sphere size, low in purity and difficult to meet the requirements are solved.

This document describes an image analysis method for characterizing muscle cells or their substructures. The method includes: - Analyze (102) at least one image (602; 1702) representing at least one muscle cell to identify a plurality of Z-bands (302; 604; 1704); - Identification (104) of a multitude of sarcomeres (306) as segments between two adjacent Z-bands; - Represent (106) each of the sarcomeres by a set of a plurality of distance lines (402), wherein each distance line is characterized by at least one length, one orientation and one position, wherein at least the position of the distance lines of each set is different, and wherein the distance lines are oriented perpendicular to the Z-bands that define the sarcomere; - Calculate (108), for each of the sarcomeres, at least one sarcomere feature (902-910) as a function of the set of distance lines of that sarcomere; and - Characterization (110) of the at least one muscle cell or its substructures depending on the at least one sarcomere feature of the plurality of sarcomeres