scholarly journals Intrinsically stretchable electrode array enabled in vivo electrophysiological mapping of atrial fibrillation at cellular resolution

2020 ◽  
Vol 117 (26) ◽  
pp. 14769-14778 ◽  
Author(s):  
Jia Liu ◽  
Xinyuan Zhang ◽  
Yuxin Liu ◽  
Miguel Rodrigo ◽  
Patrick D. Loftus ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Spatial Resolution ◽  
Electrode Array ◽  
Chronic Atrial Fibrillation ◽  
Underlying Mechanism ◽  
Cellular Level ◽  
Definitive Treatment ◽  
Comparable Efficacy ◽  
Signal Ratio

Electrophysiological mapping of chronic atrial fibrillation (AF) at high throughput and high resolution is critical for understanding its underlying mechanism and guiding definitive treatment such as cardiac ablation, but current electrophysiological tools are limited by either low spatial resolution or electromechanical uncoupling of the beating heart. To overcome this limitation, we herein introduce a scalable method for fabricating a tissue-like, high-density, fully elastic electrode (elastrode) array capable of achieving real-time, stable, cellular level-resolution electrophysiological mapping in vivo. Testing with acute rabbit and porcine models, the device is proven to have robust and intimate tissue coupling while maintaining its chemical, mechanical, and electrical properties during the cardiac cycle. The elastrode array records epicardial atrial signals with comparable efficacy to currently available endocardial-mapping techniques but with 2 times higher atrial-to-ventricular signal ratio and >100 times higher spatial resolution and can reliably identify electrical local heterogeneity within an area of simultaneously identified rotor-like electrical patterns in a porcine model of chronic AF.

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

Abstract 1362: Degradation of Cardiac Troponins in Atrial Fibrillation is Calpain-dependent

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Lei Ke ◽  
Anne-Jan Dijkhuis ◽  
Robert H Henning ◽  
Harm H Kampinga ◽  
Bianca J Brundel
Keyword(s):  
Atrial Fibrillation ◽  
Western Blotting ◽  
Troponin T ◽  
Cell Model ◽  
Underlying Mechanism ◽  
The Self ◽  
Calpain Inhibitor ◽  
Specific Degradation ◽  
Cardiac Troponins

Background: The self-perpeptuation of atrial fibrillation (AF) is caused by myocyte remodeling including degradation of cardiac troponins. Additionally, we observed enhanced calpain activity in human AF and in the tachypaced cell model for AF. We assessed the hypothesis that calpain plays a role in the degradation of cardiac troponins during AF. Methods: The tachypaced HL-1 atrial myocyte model was used to investigate degradation of endogenous cardiac troponin T, I and C (cTnT, cTnI, cTnC) as well as actin by Western-blotting. To study degradation of human cTnT, myocytes were transfected with V5-C-human cTnT. Inhibitors of calpain, caspase and proteasome were applied to study the underlying mechanism for degradation. In vivo cTn degradation was studied in atrial tissue from AF and sinus rhythm (SR) patients by Western-blotting. Results: Tachypacing (P, 3Hz) significantly and gradually induced the degradation of cTnT (Fig A ), cTnI and cTnC, compared to control (C, 1Hz), while actin were unaffected. The degradation was prevented by calpain inhibitor PD150606 (20μM), whereas caspase (CAS) and proteasome (MG) inhibition was not effective (Fig C ). Tachypacing of V5-C-human cTnT transfected HL-1 myocytes resulted in a specific degradation fragment of 25kDa, which was prevented by PD (Fig B ). In vivo, persistent AF was associated with specific degradation of cTnT, I and C, compared to patients with SR or paroxysmal AF. Actin levels were not changed. Conclusions: AF induces specific degradation of all cTn isoforms, which is mediated by calpain. Activation of calpain may represent a key component in linking cTn degradation, contractile dysfunction and the self-perpetuation of AF.

scholarly journals CXCL12/CXCR4 axis as a key mediator in atrial fibrillation via bioinformatics analysis and functional identification

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Peng Liu ◽  
Hongke Sun ◽  
Xin Zhou ◽  
Qiaozhu Wang ◽  
Feng Gao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Bioinformatics Analysis ◽  
Underlying Mechanism ◽  
Rank Aggregation ◽  
Functional Identification ◽  
Hub Genes ◽  
Cxcr4 Antagonist ◽  
Underlying Mechanisms ◽  
Cxcr4 Axis

AbstractAtrial fibrillation (AF) is an increasingly prevalent arrhythmia with significant health and socioeconomic impact. The underlying mechanism of AF is still not well understood. In this study, we sought to identify hub genes involved in AF, and explored their functions and underlying mechanisms based on bioinformatics analysis. Five microarray datasets in GEO were used to identify the differentially expressed genes (DEGs) by Robust Rank Aggregation (RRA), and hub genes were screened out using protein–protein interaction (PPI) network. AF model was established using a mixture of acetylcholine and calcium chloride (Ach-CaCl2) by tail vein injection. We totally got 35 robust DEGs that mainly involve in extracellular matrix formation, leukocyte transendothelial migration, and chemokine signaling pathway. Among these DEGs, we identified three hub genes involved in AF, of which CXCL12/CXCR4 axis significantly upregulated in AF patients stands out as one of the most potent targets for AF prevention, and its effect on AF pathogenesis and underlying mechanisms were investigated in vivo subsequently with the specific CXCR4 antagonist AMD3100 (6 mg/kg). Our results demonstrated an elevated transcription and translation of CXCL12/CXCR4 axis in AF patients and mice, accompanied with the anabatic atrial inflammation and fibrosis, thereby providing the substrate for AF maintenance. Blocking its signaling via AMD3100 administration in AF model mice reduced AF inducibility and duration, partly ascribed to decreased atrial inflammation and structural remodeling. Mechanistically, these effects were achieved by reducing the recruitment of CD3+ T lymphocytes and F4/80+ macrophages, and suppressing the hyperactivation of ERK1/2 and AKT/mTOR signaling in atria of AF model mice. In conclusion, this study provides new evidence that antagonizing CXCR4 prevents the development of AF, and suggests that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.

Biomedical applications: Pitfalls in the practice

1994 ◽  
Vol 52 ◽  
pp. 378-379
Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey
Keyword(s):  
Operating Room ◽  
Liquid Nitrogen ◽  
Lung Tissue ◽  
Biomedical Applications ◽  
Microprobe Analysis ◽  
Tissue Sample ◽  
Cellular Level ◽  
Tissue Samples ◽  
Asbestos Fibers

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.

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