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Wenguang Li
Strain energy-based constitutive laws with damage effect were proposed by using existing both uniaxial tensile test and tubular biaxial inflation test data on the human great saphenous vein (GSV) segments. These laws were applied into GSV coronary artery bypass grafts (CABG) by employing a thin-walled vessel model to evaluate their passive biomechanical performance under coronary artery physiological conditions at a fixed axial pre-stretch. At a peak systolic pressure in 100-150 mmHg, a 20-33% GSV diameter dilation was predicted with the law based on tubular biaxial inflation test data and agreed well with 25% dilation in clinical observation in comparison with as small as 2-4% dilation estimated with the law based on uniaxial tensile test data...
February 23, 2018: Journal of the Mechanical Behavior of Biomedical Materials
Jia Zhou, Jiaqi Li, Rodolfo B Serafim, Steven Ketchum, Catarina G Ferreira, Jessica C Liu, Kathryn A Coe, Brendan D Price, Timur Yusufzai
CHD1 is a conserved chromatin remodeling enzyme required for development and linked to prostate cancer in adults, yet its role in human cells is poorly understood. Here, we show that targeted disruption of the CHD1 gene in human cells leads to a defect in early double-strand break (DSB) repair via homologous recombination (HR), resulting in hypersensitivity to ionizing radiation as well as PARP and PTEN inhibition. CHD1 knockout cells show reduced H2AX phosphorylation (γH2AX) and foci formation as well as impairments in CtIP recruitment to the damaged sites...
February 26, 2018: Nucleic Acids Research
Nydia Ávila-Vanzzini, Hector I Michelena, Juan Francisco Fritche Salazar, Héctor Herrera-Bello, Silvia Siu Moguel, Rubén Rafael Rodríguez Ocampo, Diego Javier Oregel Camacho, Nilda Espínola Zavaleta
Aims: Ischaemic mitral regurgitation (IMR) is consequence of left ventricular (LV) remodelling after myocardial infarction. In some cases, the mitral valve enlarges to compensate for LV remodelling and tenting, improving its coaptation; a process termed 'plasticity'. We sought to identify clinical and echocardiographic factors associated with plasticity in patients with chronic inferior myocardial infarction (CII). Methods and results: This study included 91 revascularized CII patients and 46 controls...
February 26, 2018: European Heart Journal Cardiovascular Imaging
Elda Favari, Michael J Thomas, Mary G Sorci-Thomas
The formation of the atherosclerotic plaque that is characterized by the accumulation of abnormal amounts of cholesterol-loaded macrophages in the artery wall is mediated by both inflammatory events and alterations of lipid/lipoprotein metabolism. Reverse transport of cholesterol (RCT) opposes the formation and development of atherosclerotic plaque through high density lipoprotein (HDL) metabolism, promoting the removal of cholesterol from peripheral macrophages and its delivery back to the liver for excretion into the bile...
March 8, 2018: Journal of Cardiovascular Pharmacology
Karolina Nemes, Michael C Frühwald
Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches...
March 12, 2018: Expert Opinion on Therapeutic Targets
Irina Kramerova, Jorge A Torres, Ascia Eskin, Stanley F Nelson, Melissa J Spencer
Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise...
March 8, 2018: Human Molecular Genetics
Pravin Bhattarai, Sadaf Hameed, Zhifei Dai
Angiogenesis is a normal physiological remodeling process initiated at the time of embryonic development and lessened with the progress of time. Nevertheless, continuous activation of stringent signaling pathways and proangiogenic factors during tumorigenesis (a pathological condition) instigates serious vessel abnormalities eliciting severe therapeutic inefficiency. In principle, systemic delivery of robust antiangiogenic drugs often fails to reach these abnormal tumor vessels depicting poor pharmacokinetics, biodistribution profiles and adverse side effects in vivo...
March 12, 2018: Nanoscale
Min Jiang, Qiang Lyu, Yun-Gang Bai, Huan Liu, Jing Yang, Jiu-Hua Cheng, Ming Zheng, Jin Ma
Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated microgravity-induced basilar and femoral arterial remodelling...
March 11, 2018: Canadian Journal of Physiology and Pharmacology
M Piasecki, A Ireland, J Piasecki, D W Stashuk, A Swiecicka, M K Rutter, D A Jones, J S McPhee
Sarcopenia results from the progressive loss of skeletal muscle mass and reduced function in older age. It is likely to be associated with the well-documented reduction of motor unit numbers innervating limb muscles and the increase in size of surviving motor units via reinnervation of denervated fibres. However no evidence currently exists to confirm the extent of motor unit remodelling in sarcopenic individuals. The aim of the present study was to compare motor unit size and number between young (n = 48), non-sarcopenic old (n = 13), pre-sarcopenic (n = 53) and sarcopenic (n = 29) men...
March 11, 2018: Journal of Physiology
Michelle D Tallquist
The cardiac fibroblast has essential roles in production and maintenance of extracellular matrix. While its role in maladaptive myocardial remodeling has been a focus of many studies, the cardiac fibroblast has become a topic of great interest as a contributor to heart physiology and as a therapeutic target. Recent reports are changing how we view and study the cardiac fibroblast by providing greater insights into fibroblast biology using refined techniques for fibroblast identification and manipulation. Here, we briefly summarize some of these fundamental recent findings...
February 2018: Current Opinion in Physiology
Soumaya Kouidhi, Farhat Ben Ayed, Amel Benammar Elgaaied
Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains a major challenge for more effective antitumor immunity. There is a growing evidence that the TME supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the antitumor immune response and tumor progression...
2018: Frontiers in Immunology
Martine C Morrison, Robert Kleemann, Arianne van Koppen, Roeland Hanemaaijer, Lars Verschuren
Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical models, for instance for time-resolved studies. Such models must reflect molecular disease processes of importance in patients. Herein we characterized inflammation in NASH patients on the molecular level by transcriptomics and investigated whether key human disease pathways can be recapitulated experimentally in Ldlr-/- ...
2018: Frontiers in Physiology
Kelsey H Collins, Walter Herzog, Graham Z MacDonald, Raylene A Reimer, Jaqueline L Rios, Ian C Smith, Ronald F Zernicke, David A Hart
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i...
2018: Frontiers in Physiology
Alexandre Lewalle, Sander Land, Eric Carruth, Lawrence R Frank, Pablo Lamata, Jeffrey H Omens, Andrew D McCulloch, Steven A Niederer, Nicolas P Smith
The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems...
2018: Frontiers in Physiology
Tamara Roitbak
Stroke-induced endothelial cell injury leads to destruction of cerebral microvasculature and significant damage to the brain tissue. A subacute phase of cerebral ischemia is associated with regeneration involving the activation of vascular remodeling, neuroplasticity, neurogenesis, and neuroinflammation processes. Effective restoration and improvement of blood supply to the damaged brain tissue offers a potential therapy for stroke. microRNAs (miRNAs) are recently identified small RNA molecules that regulate gene expression and significantly influence the essential cellular processes associated with brain repair following stroke...
2018: Frontiers in Molecular Neuroscience
Hyojung Kang, Rachel L Orlowsky, Gregory J Gerling
In mammals, touch is encoded by sensory receptors embedded in the skin. For one class of receptors in the mouse, the architecture of its Merkel cells, unmyelinated neurites, and heminodes follow particular renewal and remodeling trends over hair cycle stages from ages 4 to 10 weeks. As it is currently impossible to observe such trends across a single animal's hair cycle, this work employs discrete event simulation to identify and evaluate policies of Merkel cell and heminode dynamics. Well matching the observed data, the results show that the baseline model replicates dynamic remodeling behaviors between stages of the hair cycle - based on particular addition and removal polices and estimated probabilities tied to constituent parts of Merkel cells, terminal branch neurites and heminodes...
December 2017: Proceedings of the Winter Simulation Conference
Tongliang Ma, Decai Zhu, Duoxue Chen, Qiaoyun Zhang, Huifang Dong, Wenwu Wu, Huihe Lu, Guangfu Wu
BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts...
March 12, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yasuhiro Maejima
Autophagy is an evolutionarily conserved process for degradation of long-lived proteins and organelles that govern a number of cardiac pathologies which cause heart failure. Indeed, recent investigations have uncovered pathways that regulate autophagy in the heart and underlying mechanisms by which alterations in this process affect cardiac function and structure. One of the major roles of autophagy in cardiomyocytes is the intracellular protein quality control (PQC). Impairment of autophagy causes aggregation of damaged and/or misfolded proteins in cardiomyocytes, thereby damaging the cells which, in turn leads to pathological cardiac remodeling...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Mao Li, Xi Chen, Jinku Yan, Long Zhou, Yifan Wang, Fan He, Jun Lin, Caihong Zhu, Guoqing Pan, Jia Yu, Ming Pei, Huilin Yang, Tao Liu
Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. In this study, ECM was deposited by MSCs and, after decellularization, the effect of ECM on osteoclastogenesis of bone marrow monocytes (BMMs) was investigated in comparison to standard tissue culture polystyrene...
March 8, 2018: Acta Biomaterialia
Christine L Monteleon, Tanvir Agnihotri, Ankit Dahal, Mingen Liu, Vito W Rebecca, Gregory L Beatty, Ravi K Amavaradi, Todd W Ridky
Keratinocytes undergo significant structural remodeling during epidermal differentiation, including a broad transformation of the proteome coupled with a reduction in total cellular biomass. This suggests that intracellular digestion of proteins and organelles is necessary for keratinocyte differentiation. Here, we use both genetic and pharmacologic approaches to demonstrate that autophagy and lysosomal functions are required for keratinocyte differentiation in organotypic human skin. Lysosomal activity was required for mTOR signaling and mitochondrial oxidative metabolism...
March 8, 2018: Journal of Investigative Dermatology
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