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Open Access
October 21, 2021
Abstract
Cardiovascular disease is the leading cause of morbidity in patients with diabetes mellitus. In 2019, the American Heart Association and the American Diabetes Association (along with industry leaders) launched the groundbreaking collaborative initiative “Know Diabetes by Heart™” to reduce cardiovascular deaths in type 2 diabetic patients. The molecular basis linking diabetes with cardiovascular complications has not yet been fully defined. Recent clinical and experimental studies strongly suggest that adipocyte dysfunction and subsequent pathological communications between adipocyte and cardiomyocytes play important roles in diabetic cardiac injury. This perspective article will review recent development concerning adipocyte-cardiomyocyte communications, and identify the most critical questions remain to be answered in this filed.
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Open Access
October 21, 2021
Abstract
Caveolae, the specialized cell-surface plasma membrane invaginations which are abundant in endothelial cells, play critical roles in regulating various cellular processes, including cholesterol homeostasis, nitric oxide production, and signal transduction. Endothelial caveolae serve as a membrane platform for compartmentalization, modulation, and integration of signal events associated with endothelial nitric oxide synthase, ATP synthase β, and integrins, which are involved in the regulation of endothelial dysfunction and related cardiovascular diseases, such as atherosclerosis and hypertension. Furthermore, these dynamic microdomains on cell membrane are modulated by various extracellular stimuli, including cholesterol and flow shear stress. In this brief review, we summarize the critical roles of caveolae in the orchestration of endothelial function based on recent findings as well as our work over the past two decades.
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Open Access
October 21, 2021
Abstract
Gene editing nucleases (GENs), represented by CRISPR/Cas9, have become major tools in biomedical research and offer potential cures for many human diseases. Gene editing therapy (GETx) studies in animal models targeting genes such as proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C3 (APOC3), angiopoietin Like 3 (ANGPTL3) and inducible degrader of the low-density lipoprotein receptor (IDOL) have demonstrated the benefits and advantages of GETx in managing atherosclerosis. Here we present our views on this brand new therapeutic option for cardiovascular diseases (CVD).
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Open Access
October 21, 2021
Abstract
Cardiovascular disease is the leading cause of mobility and morality worldwide, in which the ischemic heart disease is the most common type of the diseases. During last decade, a major progress in the study of the pathogenesis of heart disease has been achieved. For example, the discovery of adult stem/progenitor cells in the heart and vessel tissues may play a role in tissue regeneration. However, the issue of 31 retractions for cardiac stem cell work has caused a “storm of trust” in the heart stem cell field, in which both founders and scientists have become cautious and conservative in stem cell research of the heart. Despite that the existence of adult cardiac stem cells has been denied, recent studies confirmed that there are many other resident stem/progenitor cells in adult heart. Although these cells cannot differentiate into cardiomyocytes, the role they played in heart repair after injury should not be ignored. The purpose of this short article is to briefly review the current research progress in resident stem/progenitor cells in the heart, to discuss how they function during cardiac repair and to point out unanswered questions in the research field.
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Open Access
October 21, 2021
Abstract
Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries, in which atherosclerosis triggered by dyslipidemia is the major pathological basis. Over the past 40 years, small rodent animals, such as mice, have been widely used for understanding of human atherosclerosis-related cardiovascular disease (ASCVD) with the advantages of low cost and ease of maintenance and manipulation. However, based on the concept of precision medicine and high demand of translational research, the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field, indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future. With the development and breakthrough of novel gene editing technology, Syrian golden hamster, a small rodent animal replicating the metabolic characteristics of humans, has been genetically modified, suggesting that gene-targeted hamster models will provide new insights into the precision medicine and translational research of ASCVD. The purpose of this review is aimed to summarize the genetically-modified hamster models with dyslipidemia to date, and their potential applications and perspective for ASCVD.
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Open Access
October 21, 2021
Abstract
Despite continual progress in the technologies and regimens for cancer therapy, the treatment outcome of fatal metastatic breast cancer is far from satisfactory. Encouragingly, nanotechnology has emerged as a valuable tool to optimize drug delivery process in cancer therapy via preventing the cargos from degradation, improving the tumor-targeting efficiency, enhancing therapeutic agents’ retention in specific sites, and controlling drug release. In the last decade, several mechanisms of suppressing tumor metastasis by functional nano drug delivery systems (NDDSs) have been revealed and a guidance for the rational design of anti-metastasis NDDSs is summarized, which consist of three aspects: optimization of physiochemical properties, tumor microenvironment remodeling, and biomimetic strategies. A series of medicinal functional biomaterials and anti-metastatic breast cancer NDDSs constructed by our team are introduced in this review. It is hoped that better anti-metastasis strategies can be inspired and applied in clinic.
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Open Access
October 21, 2021
Abstract
The sympathetic nervous system is activated in the setting of heart failure (HF) to compensate for hemodynamic instability. However, acute sympathetic surge or sustained high neuronal firing rates activates β-adrenergic receptor (βAR) signaling contributing to myocardial remodeling, dysfunction and electrical instability. Thus, sympatho-βAR activation is regarded as a hallmark of HF and forms pathophysiological basis for β-blocking therapy. Building upon earlier research findings, studies conducted in the recent decades have significantly advanced our understanding on the sympatho-adrenergic mechanism in HF, which forms the focus of this article. This review notes recent research progress regarding the roles of cardiac β 2 AR or α 1 AR in the failing heart, significance of β 1 AR-autoantibodies, and βAR signaling through G-protein independent signaling pathways. Sympatho-βAR regulation of immune cells or fibroblasts is specifically discussed. On the neuronal aspects, knowledge is assembled on the remodeling of sympathetic nerves of the failing heart, regulation by presynaptic α 2 AR of NE release, and findings on device-based neuromodulation of the sympathetic nervous system. The review ends with highlighting areas where significant knowledge gaps exist but hold promise for new breakthroughs.
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Open Access
October 21, 2021
Abstract
Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.
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Open Access
October 21, 2021
Abstract
In the past several years, nanopore sequencing technology from Oxford Nanopore Technologies (ONT) and single-molecule real-time (SMRT) sequencing technology from Pacific BioSciences (PacBio) have become available to researchers and are currently being tested for cancer research. These methods offer many advantages over most widely used high-throughput short-read sequencing approaches and allow the comprehensive analysis of transcriptomes by identifying full-length splice isoforms and several other posttranscriptional events. In addition, these platforms enable structural variation characterization at a previously unparalleled resolution and direct detection of epigenetic marks in native DNA and RNA. Here, we present a comprehensive summary of important applications of these technologies in cancer research, including the identification of complex structure variants, alternatively spliced isoforms, fusion transcript events, and exogenous RNA. Furthermore, we discuss the impact of the newly developed nanopore direct RNA sequencing (RNA-Seq) approach in advancing epitranscriptome research in cancer. Although the unique challenges still present for these new single-molecule long-read methods, they will unravel many aspects of cancer genome complexity in unprecedented ways and present an encouraging outlook for continued application in an increasing number of different cancer research settings.