scholarly journals GASOMEDIATOR H2S IN THROMBOSIS AND HEMOSTASIS

2020 ◽  
Vol 13 (6) ◽  
pp. 24-29
Author(s):  
Nadiya Druzhyna ◽  
Keyword(s):  
Hydrogen Sulfide ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Blood Platelet ◽  
Cell Physiology ◽  
Biologically Relevant ◽  
And Function

This review was aimed to briefly summarize current knowledge of the biological roles of gasomediator H2S in hemostasis and cardiovascular diseases. Since the discovery that mammalian cells are enzymatically producing H2S, this molecule underwent a dramatic metamorphosis from dangerous pollutant to a biologically relevant mediator. As a gasomediator, hydrogen sulfide plays a role of signaling molecule, which is involved in a number of processes in health and disease, including pathogenesis of cardiovascular abnormalities, mainly through modulating different patterns of vasculature functions and thrombotic events. Recently, several studies have provided unequivocal evidence that H2S reduces blood platelet reactivity by inhibiting different stages of platelet activation (platelet adhesion, secretion and aggregation) and thrombus formation. Moreover, H2S changes the structure and function of fibrinogen and proteins associated with fibrinolysis. Hydrogen sulfide regulates proliferation and apoptosis of vascular smooth muscle cells, thus modulating angiogenesis and vessel function. Undoubtedly, H2S is also involved in a multitude of other physiological functions. For example, it exhibits anti-inflammatory effects by inhibiting ROS production and increasing expression of antioxidant enzymes. Some studies have demonstrated the role of hydrogen sulfide as a therapeutic agent in various diseases, including cardiovascular pathologies. Further studies are required to evaluate its importance as a regulator of cell physiology and associated cardiovascular pathological conditions such as myocardial infarction and stroke.

scholarly journals How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Wenyi Zhou ◽  
Mingyi Zhao
Keyword(s):  
Cardiovascular Disease ◽  
Tumor Suppressor ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Cardiovascular Development ◽  
Molecular Therapeutic ◽  
And Function

Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the nucleus and initiate transcriptional activity if the pathway is inhibited. The role of Hippo signaling has been widely investigated in organ development and cancers. A heart of normal size and function which is critical for survival could not be generated without the proper regulation of the Hippo tumor suppressor pathway. Recent research has demonstrated a novel role of Hippo signaling in cardiovascular disease in the context of development, hypertrophy, angiogenesis, regeneration, apoptosis, and autophagy. In this review, we summarize the current knowledge of how Hippo signaling modulates pathological processes in cardiovascular disease and discuss potential molecular therapeutic targets.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska
Keyword(s):  
Current Knowledge ◽  
Stress Factors ◽  
Oxygenic Photosynthesis ◽  
Ros Generation ◽  
Main Site ◽  
Storage Lipids ◽  
Abiotic Stress Factors ◽  
Cell Components ◽  
And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

scholarly journals Non-Coding RNA in Pancreas and β-Cell Development

2018 ◽  
Vol 4 (4) ◽  
pp. 41 ◽  
Author(s):  
Wilson K. M. Wong ◽  
Anja E. Sørensen ◽  
Mugdha V. Joglekar ◽  
Anand A. Hardikar ◽  
Louise T. Dalgaard
Keyword(s):  
Cell Function ◽  
Islet Cells ◽  
Current Knowledge ◽  
Cell Development ◽  
Pancreas Development ◽  
Β Cell ◽  
Neighboring Gene ◽  
Non Coding Rnas ◽  
And Function

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

scholarly journals T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Kiekens ◽  
Wouter Van Loocke ◽  
Sylvie Taveirne ◽  
Sigrid Wahlen ◽  
Eva Persyn ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Current Knowledge ◽  
Functional Differentiation ◽  
Cell Maturation ◽  
Hematopoietic Stem ◽  
And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

scholarly journals Extracellular Vesicles and Thrombosis: Update on the Clinical and Experimental Evidence

2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer
Keyword(s):  
Experimental Evidence ◽  
Extracellular Vesicles ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Cell Types ◽  
Heterogenous Group ◽  
Clearance Mechanism ◽  
And Function ◽  
Role And Function

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.

Signalling functions of coenzyme A and its derivatives in mammalian cells

2014 ◽  
Vol 42 (4) ◽  
pp. 1056-1062 ◽  
Author(s):  
Hongorzul Davaapil ◽  
Yugo Tsuchiya ◽  
Ivan Gout
Keyword(s):  
Mammalian Cells ◽  
Coenzyme A ◽  
Current Knowledge ◽  
Pantothenic Acid ◽  
Future Developments ◽  
Malonyl Coa ◽  
Vitamin B5 ◽  
Coa Thioesters ◽  
Living Organisms

In all living organisms, CoA (coenzyme A) is synthesized in a highly conserved process that requires pantothenic acid (vitamin B5), cysteine and ATP. CoA is uniquely designed to function as an acyl group carrier and a carbonyl-activating group in diverse biochemical reactions. The role of CoA and its thioester derivatives, including acetyl-CoA, malonyl-CoA and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA), in the regulation of cellular metabolism has been extensively studied and documented. The main purpose of the present review is to summarize current knowledge on extracellular and intracellular signalling functions of CoA/CoA thioesters and to speculate on future developments in this area of research.

scholarly journals Role of microRNAs in Venous Thromboembolism

2020 ◽  
Vol 21 (7) ◽  
pp. 2602 ◽  
Author(s):  
Vânia M. Morelli ◽  
Sigrid K. Brækkan ◽  
John-Bjarne Hansen
Keyword(s):  
Venous Thromboembolism ◽  
Animal Models ◽  
Statistical Power ◽  
Current Knowledge ◽  
Thrombus Formation ◽  
Therapeutic Targets ◽  
Small Sample ◽  
Future Research ◽  
Gene Expressions

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

scholarly journals The Urothelium: Life in a Liquid Environment

2020 ◽  
Vol 100 (4) ◽  
pp. 1621-1705 ◽  
Author(s):  
Marianela G. Dalghi ◽  
Nicolas Montalbetti ◽  
Marcelo D. Carattino ◽  
Gerard Apodaca
Keyword(s):  
Current Knowledge ◽  
Nerve Fibers ◽  
Liquid Environment ◽  
Afferent Nerve Fibers ◽  
Proximal Urethra ◽  
Key Aspects ◽  
And Function ◽  
Solute Composition ◽  
Extended Discussion

The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment and communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the past decade. After familiarizing the reader with key aspects of urothelial histology, we describe new insights into urothelial development and regeneration. This is followed by an extended discussion of urothelial barrier function, including information about the roles of the glycocalyx, ion and water transport, tight junctions, and the cellular and tissue shape changes and other adaptations that accompany expansion and contraction of the lower urinary tract. We also explore evidence that the urothelium can alter the water and solute composition of urine during normal physiology and in response to overdistension. We complete the review by providing an overview of our current knowledge about the urothelial environment, discussing the sensor and transducer functions of the urothelium, exploring the role of circadian rhythms in urothelial gene expression, and describing novel research tools that are likely to further advance our understanding of urothelial biology.

scholarly journals Primary Cilium in Cancer Hallmarks

2019 ◽  
Vol 20 (6) ◽  
pp. 1336 ◽  
Author(s):  
Lucilla Fabbri ◽  
Frédéric Bost ◽  
Nathalie Mazure
Keyword(s):  
Cancer Progression ◽  
Primary Cilium ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Cancer Hallmarks ◽  
Mutual Regulation ◽  
Ultrastructure And Function ◽  
And Function ◽  
External Stimuli

The primary cilium is a solitary, nonmotile and transitory appendage that is present in virtually all mammalian cells. Our knowledge of its ultrastructure and function is the result of more than fifty years of research that has dramatically changed our perspectives on the primary cilium. The mutual regulation between ciliogenesis and the cell cycle is now well-recognized, as well as the function of the primary cilium as a cellular “antenna” for perceiving external stimuli, such as light, odorants, and fluids. By displaying receptors and signaling molecules, the primary cilium is also a key coordinator of signaling pathways that converts extracellular cues into cellular responses. Given its critical tasks, any defects in primary cilium formation or function lead to a wide spectrum of diseases collectively called “ciliopathies”. An emerging role of primary cilium is in the regulation of cancer development. In this review, we seek to describe the current knowledge about the influence of the primary cilium in cancer progression, with a focus on some of the events that cancers need to face to sustain survival and growth in hypoxic microenvironment: the cancer hallmarks.

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