Cms regulations

HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiated from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiated from control hiPSCs...

BACKGROUND: Psychosocial evaluation for transplant suitability is required by the Centers for Medicare and Medicaid Services (CMS) as a condition of participation for transplant programs. There are no regulations regarding follow-up reassessment for transplant readiness after waitlisting. OBJECTIVES: An evidence-based pilot project was developed and implemented to evaluate the feasibility of psychosocial readiness assessments for waitlisted heart transplantation candidates...

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a promising cell source for cardiac regenerative medicine and in vitro modeling. However, hPSC-CMs exhibit immature structural and functional properties compared with adult cardiomyocytes. Various electrical, mechanical, and biochemical cues have been applied to enhance hPSC-CM maturation but with limited success. In this work, we investigated the potential application of the semiconducting polymer poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (P(NDI2OD-T2)) as a light-sensitive material to stimulate hPSC-CMs optically...

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively...

Induced pluripotent stem cells (iPSCs) are obtained by introducing exogenous genes or adding chemicals to the culture medium to induce somatic cell differentiation. iPSCs have the ability to differentiate into all three embryonic cell lines, similar to embryonic stem cells. iPSCs can differentiate into cardiac muscle cells through two-dimensional differentiation methods such as monolayer cell culture and co-culture, or through embryoid body and scaffold-based three-dimensional differentiation methods. In addition, the process of iPSCs differentiation into cardiac muscle cells also requires activation or inhibition of specific signaling pathways,such as Wnt, BMP, Notch signaling pathways to mimic the development of the heart in vivo ...

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line...

OBJECTIVE: Long QT syndrome type 7 (Andersen-Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism. METHODS AND RESULTS: We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs...

We show that zinc finger imprinted 3 (Zim3), when used as Zim3-KRAB-dCas9 effector in interference CRISPR, without any guide RNAs, paradoxically up-regulates key cardiac ion channel genes in human-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), responsible for healthy resting membrane potential, repolarization of the action potential, and electrical transmission of signals. These were found to yield expected functional enhancements consistent with a more mature iPSC-CM phenotype, with potentially desirable properties...

Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis...

In vitro cellular models provide valuable insights into the adaptive biochemical mechanisms triggered by cells to cope with the stress situation induced by hypoxia and reoxygenation cycles. The first biological data generated in studies based on this micrometric life-scale has the potential to provide us a global overview about the main biochemical phenomena presented in some reported preconditioning therapies in life-scale of higher dimensions. Thus, in this study, a cell incubator was designed and manufactured to produce a cellular model of heart hypoxia followed by reoxygenation (HfR) through consecutive repetitions of hypoxia-normoxia gas exchange...

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma...

BACKGROUND: Acute cardiac injury caused by coronavirus disease 2019 (COVID-19) increases mortality. Acute cardiac injury caused by COVID-19 requires understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects cardiomyocytes. This study provides a solid foundation for related studies by using a model of SARS-CoV-2 infection in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at the transcriptome level, highlighting the relevance of this study to related studies...

INTRODUCTION: In native heart tissue, functions of cardiac fibroblasts (CFs) include synthesis, remodeling, and degradation of the extracellular matrix (ECM) as well as secreting factors that regulate cardiomyocyte (CM) function. The influence of direct co-culture and CF-derived ECM on CM mechanical function are not fully understood. METHODS: Here we use an engineered culture platform that provides control over ECM geometry and substrate stiffness to evaluate the influence of iPSC-CFs, and the ECM they produce, on the mechanical function of iPSC-CMs...

BACKGROUND: As of 2021, the Centers for Medicare and Medicaid Services (CMS) requires all hospitals to publish their commercially negotiated prices. To our knowledge, price variation of spine oncology diagnosis and treatments has not been previously investigated. PURPOSE: The aim of this study is to characterize the availability and variation of prices for spinal oncology services among National Cancer Institute-Designated Cancer Centers (NCI-DCC). STUDY DESIGN: Cross-sectional analysis...

Maydis leaf blight is a significant disease of maize caused by Bipolaris maydis race T, O and C . Molecular mechanisms regulating defense responses in non-CMS maize towards race O fungus are not fully known. In the present investigation, comparative transcriptome profiling was conducted on a highly resistant maize genotype SC-7-2-1-2-6-1 against a standard susceptible variety CM 119 at 48 h post inoculation (h PI) along with non-infected control. mRNA sequencing generated 38.4 Gb data, where 9349602 reads were mapped uniquely in SC-7, whereas 2714725 reads were mapped uniquely in CM-119...

In the initial hours following the application of the calcium channel blocker (CCB) nifedipine to microtissues consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we observe notable variations in the drug's efficacy. Here, we investigate the possibility that these temporal changes in CCB effects are associated with adaptations in the expression of calcium ion channels in cardiomyocyte membranes. To explore this, we employ a recently developed mathematical model that delineates the regulation of calcium ion channel expression by intracellular calcium concentrations...

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo ...

Calcium carbonate (CaCO3), which exhibits excellent biocompatibility and bioactivity, is a well-established bone filling material for bone defects. Here, we synthesized CaCO3 microspheres (CMs) to use as an intelligent carrier to load bone morphogenetic protein-2 (BMP-2). Subsequently, drug-loaded CMs and catalase (CAT) were added to methacrylated gelatin (GelMA) hydrogels to prepare a composite hydrogel for differential release of the drugs. CAT inside hydrogels was released with a fast rate to eliminate H2O2 and generate oxygen...

TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the anthraquinone Mitoxantrone (MTX). It is unclear whether women would experience the same adverse effects from all drugs in this class, or if specific drugs would be preferable for certain individuals based on their cardiotoxicity risk profile. To investigate this, we studied the effects of treatment of DOX, DNR, EPI, MTX, and an unrelated monoclonal antibody Trastuzumab (TRZ) on iPSC-derived cardiomyocytes (iPSC-CMs) from six healthy females...

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury...