scholarly journals Blood Platelets as an Important but Underrated Circulating Source of TGFβ

2021 ◽  
Vol 22 (9) ◽  
pp. 4492
Author(s):  
Kamil Karolczak ◽  
Cezary Watala
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Cell ◽  
Current Knowledge ◽  
Blood Platelets ◽  
Biological Effects ◽  
Cell Functions ◽  
Tumour Metastasis ◽  
Peripheral Blood Plasma ◽  
Important Regulator ◽  
Dependent Processes

When treating diseases related primarily to tissue remodeling and fibrosis, it is desirable to regulate TGFβ concentration and modulate its biological effects. The highest cellular concentrations of TGFβ are found in platelets, with about 40% of all TGFβ found in peripheral blood plasma being secreted by them. Therefore, an understanding of the mechanisms of TGFβ secretion from platelets may be of key importance for medicine. Unfortunately, despite the finding that platelets are an important regulator of TGFβ levels, little research has been carried out into the development of platelet-directed therapies that might modulate the TGFβ-dependent processes. Nevertheless, there are some very encouraging reports suggesting that platelet TGFβ may be specifically involved in cardiovascular diseases, liver fibrosis, tumour metastasis, cerebral malaria and in the regulation of inflammatory cell functions. The purpose of this review is to briefly summarize these few, extremely encouraging reports to indicate the state of current knowledge in this topic. It also attempts to better characterize the influence of TGFβ on platelet activation and reactivity, and its shaping of the roles of blood platelets in haemostasis and thrombosis.

Protective Effects of Phenylpropanoids and Phenylpropanoid-rich Essential Oils on the Cardiovascular System

2019 ◽  
Vol 19 (17) ◽  
pp. 1459-1471 ◽  
Author(s):  
Jorge M. Alves-Silva ◽  
Mónica Zuzarte ◽  
Carla Marques ◽  
Henrique Girão ◽  
Lígia Salgueiro
Keyword(s):  
Cardiovascular Diseases ◽  
Essential Oils ◽  
Cardiovascular System ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Biological Effects ◽  
Ischemia Reperfusion ◽  
Future Research ◽  
Protective Effects ◽  
Plant Metabolites

Background: Cardiovascular diseases are the leading cause of global mortality with a tendency to increase due to population ageing as well as an increase in associated risk factors. Although current therapies improve survival rates, they are associated with several side effects, thus justifying the development of novel preventive and/or therapeutic approaches. In this way, plant metabolites such as essential oils have emerged as promising agents due to their biological effects. Objective: Bearing in mind that several essential oils are characterized by high amounts of phenylpropanoids, which may play a crucial role in the activity of these volatile extracts, a comprehensive and systematic review focusing on the cardiovascular effects of phenylpropanoid-rich essential oils is presented. Methods: Popular search engines including PubMed, Science Direct, Scopus and Google Scholar were consulted and papers from 2000 onwards were selected. Non-volatile phenylpropanoids were not considered in this review. Results: A compilation of the current knowledge on this thematic pointed out beneficial effects for volatile phenylpropanoids namely hypotensive, vasorelaxant, antiplatelet aggregation, antidyslipidaemic and antidiabetic, as well as protective properties against ischemia/reperfusion injury and heart hypertrophy. Conclusion: A better understanding of the protective effects of phenylpropanoids on the cardiovascular system is presented, thus paving the way towards future research on plant-based therapies for cardiovascular diseases.

scholarly journals Role of TRP channels in the cardiovascular system

2015 ◽  
Vol 308 (3) ◽  
pp. H157-H182 ◽  
Author(s):  
Zhichao Yue ◽  
Jia Xie ◽  
Albert S. Yu ◽  
Jonathan Stock ◽  
Jianyang Du ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Mechanical Stretch ◽  
Signal Pathways ◽  
Variable Degree ◽  
Cell Functions

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca2+-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases.

scholarly journals The role of orexin in controlling the activity of the adipo-pancreatic axis

2018 ◽  
Vol 238 (2) ◽  
pp. R95-R108 ◽  
Author(s):  
M Skrzypski ◽  
M Billert ◽  
K W Nowak ◽  
M Z Strowski
Keyword(s):  
Energy Homeostasis ◽  
Current Knowledge ◽  
Biological Effects ◽  
Peripheral Tissues ◽  
Cell Functions ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Regulate Body Weight ◽  
G Protein Coupled

Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep–wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeostasis. Since both organs are crucially important in the context of pathophysiology of obesity and diabetes, we summarize the current knowledge regarding the role of orexins and their receptors in controlling adipocytes as well as the endocrine pancreatic functions. Particularly, we discuss studies evaluating the effects of orexins in controlling brown and white adipocytes as well as pancreatic alpha and beta cell functions.

The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

scholarly journals Lysosomal Calcium Channels in Autophagy and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1299
Author(s):  
Yi Wu ◽  
Peng Huang ◽  
Xian-Ping Dong
Keyword(s):  
Calcium Channels ◽  
Cancer Progression ◽  
Human Cancer ◽  
Human Diseases ◽  
Cellular Processes ◽  
Cell Functions ◽  
Multiple Cell ◽  
Dependent Processes ◽  
Intracellular Messenger

Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.

scholarly journals Meat and Human Health—Current Knowledge and Research Gaps

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1556
Author(s):  
Nina Rica Wium Geiker ◽  
Hanne Christine Bertram ◽  
Heddie Mejborn ◽  
Lars O. Dragsted ◽  
Lars Kristensen ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Biological Effects ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Meat Consumption ◽  
Metabolic Effects ◽  
Food Sources ◽  
Current Evidence ◽  
Processed Meat ◽  
Total Energy Consumption

Meat is highly nutritious and contributes with several essential nutrients which are difficult to obtain in the right amounts from other food sources. Industrially processed meat contains preservatives including salts, possibly exerting negative effects on health. During maturation, some processed meat products develop a specific microbiota, forming probiotic metabolites with physiological and biological effects yet unidentified, while the concentration of nutrients also increases. Meat is a source of saturated fatty acids, and current WHO nutrition recommendations advise limiting saturated fat to less than ten percent of total energy consumption. Recent meta-analyses of both observational and randomized controlled trials do not support any effect of saturated fat on cardiovascular disease or diabetes. The current evidence regarding the effect of meat consumption on health is potentially confounded, and there is a need for sufficiently powered high-quality trials assessing the health effects of meat consumption. Future studies should include biomarkers of meat intake, identify metabolic pathways and include detailed study of fermented and other processed meats and their potential of increasing nutrient availability and metabolic effects of compounds.

scholarly journals Efforts to emulate human milk oligosaccharides

2007 ◽  
Vol 98 (S1) ◽  
pp. S74-S79 ◽  
Author(s):  
Rosa María Espinosa ◽  
Martha Taméz ◽  
Pedro Prieto
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Current Knowledge ◽  
Biological Effects ◽  
Historical Context ◽  
Published Data ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Fast Analysis ◽  
Chemical Structures

Research on human milk oligosaccharides (HMO) began with the characterisation of their chemical structures and is now focused on the elucidation of their biological roles. Previously, biological effects could only be investigated with fractions or structures isolated from breast milk; consequently, clinical observations were limited to comparisons between outcomes from breast-fed infants and their formula-fed counterparts. In some cases, it was inferred that the observed differences were caused by the presence of HMO in breast milk. Presently, analytical techniques allow for the fast analysis of milk samples, thus providing insights on the inherent variability of specimens. In addition, methods for the synthesis of HMO have provided single structures in sufficient quantities to perform clinical studies with oligosaccharide-supplemented formulae. Furthermore, studies have been conducted with non-mammalian oligosaccharides with the purpose of assessing the suitability of these structures to functionally emulate HMO. Taken together, these developments justify summarising current knowledge on HMO to further discussions on efforts to emulate human milk in regard to its oligosaccharide content. The present account summarises published data and intends to provide an historical context and to illustrate the state of the field.

scholarly journals What we need to know about lipid-associated injury in case of renal ischemia-reperfusion

2018 ◽  
Vol 315 (6) ◽  
pp. F1714-F1719 ◽  
Author(s):  
Pauline Erpicum ◽  
Pascal Rowart ◽  
Jean-Olivier Defraigne ◽  
Jean-Marie Krzesinski ◽  
François Jouret
Keyword(s):  
Energy Demand ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Cell Functions ◽  
Associated Injury ◽  
Cortex Area

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises

2021 ◽  
Vol 23 (1) ◽  
pp. 430
Author(s):  
Ángel Ortega ◽  
Ivana Vera ◽  
Maria P. Diaz ◽  
Carla Navarro ◽  
Milagros Rojas ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Growth Regulation ◽  
Current Knowledge ◽  
Biological Effects ◽  
Critical Role ◽  
Binding Motif ◽  
Hippo Signaling ◽  
Tumor Resistance ◽  
Therapeutic Alternatives

The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways’ role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.

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