scholarly journals Molecular Basis of Atrial Fibrillation Initiation and Maintenance

Hearts ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 170-187
Author(s):  
Kira Beneke ◽  
Cristina E. Molina
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Basis ◽  
Genetic Factors ◽  
Transcriptional Regulators ◽  
Genetic Changes ◽  
Therapeutic Implications ◽  
The Past ◽  
Risk Variants ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

Atrial fibrillation (AF) is the most common cardiac arrhythmia, largely associated to morbidity and mortality. Over the past decades, research in appearance and progression of this arrhythmia have turned into significant advances in its management. However, the incidence of AF continues to increase with the aging of the population and many important fundamental and translational underlaying mechanisms remain elusive. Here, we review recent advances in molecular and cellular basis for AF initiation, maintenance and progression. We first provide an overview of the basic molecular and electrophysiological mechanisms that lead and characterize AF. Next, we discuss the upstream regulatory factors conducting the underlying mechanisms which drive electrical and structural AF-associated remodeling, including genetic factors (risk variants associated to AF as transcriptional regulators and genetic changes associated to AF), neurohormonal regulation (i.e., cAMP) and oxidative stress imbalance (cGMP and mitochondrial dysfunction). Finally, we discuss the potential therapeutic implications of those findings, the knowledge gaps and consider future approaches to improve clinical management.

scholarly journals Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy

2020 ◽  
Vol 127 (1) ◽  
pp. 51-72 ◽  
Author(s):  
Stanley Nattel ◽  
Jordi Heijman ◽  
Liping Zhou ◽  
Dobromir Dobrev
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Basis ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Critical Discussion ◽  
Inflammatory Signaling ◽  
Molecular Control ◽  
Therapeutic Implications ◽  
Impulse Generation ◽  
Dependent Protein

Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innovation is a better understanding of underlying fundamental mechanisms. This article reviews recent advances in understanding the molecular basis for AF, with a particular emphasis on relating these new insights to opportunities for clinical translation. We first review the evidence relating basic electrophysiological mechanisms to the characteristics of clinical AF. We then discuss the molecular control of factors leading to some of the principal determinants, including abnormalities in impulse conduction (such as tissue fibrosis and other extra-cardiomyocyte alterations, connexin dysregulation and Na + -channel dysfunction), electrical refractoriness, and impulse generation. We then consider the molecular drivers of AF progression, including a range of Ca 2+ -dependent intracellular processes, microRNA changes, and inflammatory signaling. The concept of key interactome-related nodal points is then evaluated, dealing with systems like those associated with CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II), NLRP3 (NACHT, LRR, and PYD domains-containing protein-3), and transcription-factors like TBX5 and PitX2c. We conclude with a critical discussion of therapeutic implications, knowledge gaps and future directions, dealing with such aspects as drug repurposing, biologicals, multispecific drugs, the targeting of cardiomyocyte inflammatory signaling and potential considerations in intervening at the level of interactomes and gene-regulation. The area of molecular intervention for AF management presents exciting new opportunities, along with substantial challenges.

scholarly journals Design, challenges, and the potential of transcriptomics to understand social behavior

2020 ◽  
Vol 66 (3) ◽  
pp. 321-330 ◽  
Author(s):  
Wen Kin Lim ◽  
Ajay S Mathuru
Keyword(s):  
Social Behavior ◽  
Molecular Basis ◽  
Behavioral Plasticity ◽  
Single Cells ◽  
Rna Seq ◽  
Tissue Samples ◽  
Design Considerations ◽  
The Past ◽  
Underlying Mechanisms ◽  
Design Challenges

Abstract Rapid advances in Ribonucleic Acid sequencing (or RNA-seq) technology for analyzing entire transcriptomes of desired tissue samples, or even of single cells at scale, have revolutionized biology in the past decade. Increasing accessibility and falling costs are making it possible to address many problems in biology that were once considered intractable, including the study of various social behaviors. RNA-seq is opening new avenues to understand long-standing questions on the molecular basis of behavioral plasticity and individual variation in the expression of a behavior. As whole transcriptomes are examined, it has become possible to make unbiased discoveries of underlying mechanisms with little or no necessity to predict genes involved in advance. However, researchers need to be aware of technical limitations and have to make specific decisions when applying RNA-seq to study social behavior. Here, we provide a perspective on the applications of RNA-seq and experimental design considerations for behavioral scientists who are unfamiliar with the technology but are considering using it in their research.

scholarly journals Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications

2022 ◽  
Vol 12 ◽  
Author(s):  
Wanyue Dan ◽  
Lihua Peng ◽  
Bin Yan ◽  
Zhengpeng Li ◽  
Fei Pan
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Genetic Factors ◽  
Survival Rates ◽  
Relative Survival ◽  
Therapeutic Implications ◽  
The Past ◽  
Human Microbiota ◽  
Current State ◽  
Esophageal Carcinogenesis ◽  
The Relationship

Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.

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