scholarly journals Adenosine and Inflammation: Here, There and Everywhere

2021 ◽  
Vol 22 (14) ◽  
pp. 7685
Author(s):  
Silvia Pasquini ◽  
Chiara Contri ◽  
Pier Andrea Borea ◽  
Fabrizio Vincenzi ◽  
Katia Varani
Keyword(s):  
Protective Factor ◽  
Therapeutic Strategies ◽  
The Body ◽  
Main Function ◽  
Pathogenetic Mechanism ◽  
Pharmacological Profile ◽  
Endogenous Modulator ◽  
Almost All ◽  
G Protein Coupled

Adenosine is a ubiquitous endogenous modulator with the main function of maintaining cellular and tissue homeostasis in pathological and stress conditions. It exerts its effect through the interaction with four G protein-coupled receptor (GPCR) subtypes referred as A1, A2A, A2B, and A3 adenosine receptors (ARs), each of which has a unique pharmacological profile and tissue distribution. Adenosine is a potent modulator of inflammation, and for this reason the adenosinergic system represents an excellent pharmacological target for the myriad of diseases in which inflammation represents a cause, a pathogenetic mechanism, a consequence, a manifestation, or a protective factor. The omnipresence of ARs in every cell of the immune system as well as in almost all cells in the body represents both an opportunity and an obstacle to the clinical use of AR ligands. This review offers an overview of the cardinal role of adenosine in the modulation of inflammation, showing how the stimulation or blocking of its receptors or agents capable of regulating its extracellular concentration can represent promising therapeutic strategies for the treatment of chronic inflammatory pathologies, neurodegenerative diseases, and cancer.

scholarly journals Normal red blood cells’ shape stabilized by membrane’s in-plane ordering

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
L. Mesarec ◽  
W. Góźdź ◽  
A. Iglič ◽  
V. Kralj-Iglič ◽  
E. G. Virga ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Extrinsic Curvature ◽  
The Body ◽  
Main Function ◽  
Disorder Phase Transition ◽  
Body Tissues ◽  
Almost All ◽  
Membrane Shape

AbstractRed blood cells (RBCs) are present in almost all vertebrates and their main function is to transport oxygen to the body tissues. RBCs’ shape plays a significant role in their functionality. In almost all mammals in normal conditions, RBCs adopt a disk-like (discocyte) shape, which optimizes their flow properties in vessels and capillaries. Experimentally measured values of the reduced volume (v) of stable discocyte shapes range in a relatively broad window between v ~ 0.58 and 0.8. However, these observations are not supported by existing theoretical membrane-shape models, which predict that discocytic RBC shape is stable only in a very narrow interval of v values, ranging between v ~ 0.59 and 0.65. In this study, we demonstrate that this interval is broadened if a membrane’s in-plane ordering is taken into account. We model RBC structures by using a hybrid Helfrich-Landau mesoscopic approach. We show that an extrinsic (deviatoric) curvature free energy term stabilizes the RBC discocyte shapes. In particular, we show on symmetry grounds that the role of extrinsic curvature is anomalously increased just below the nematic in-plane order-disorder phase transition temperature.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

“Mindfulness Makes You a Way Better Lover”

2017 ◽  
Author(s):  
Jeff Wilson
Keyword(s):  
The Body ◽  
Buddhist Meditation ◽  
Self Help ◽  
Key Concepts ◽  
Almost All ◽  
New Applications ◽  
Ted Talks

American self-help authors, coaches, and sexologists selectively adopt and apply Buddhist meditation techniques to meet their goals and sell products. This chapter draws upon books, articles, podcasts, TED talks, and other sources to demonstrate how these new applications of mindfulness are touted to enhance the sex act, delivering greater pleasure or effectively managing dysfunction. Key concepts include analysis of the economics involved in the appropriation of Buddhist practices, the role of gender in the “secular” use of meditation (almost all books recommend mindful sex for women, but few focus on men), the mixed Asian and Western frameworks for understanding the body and the meaning of sex, and the alternate uses to which elements of Buddhism may be put in different cultural settings. A specific genre of the use of meditation serves as a means to explore secular developments that draw upon Buddhist sources in a sometimes uneasy relationship.

scholarly journals Structural and Functional Features of the P2X4 Receptor: An Immunological Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean M. Kanellopoulos ◽  
Cássio Luiz Coutinho Almeida-da-Silva ◽  
Sirje Rüütel Boudinot ◽  
David M. Ojcius
Keyword(s):  
Plasma Membrane ◽  
P2y Receptors ◽  
Potential Interaction ◽  
The Body ◽  
Extracellular Nucleotides ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Features ◽  
G Protein Coupled

Extracellular nucleotides are important mediators of activation, triggering various responses through plasma membrane P2 and P1 receptors. P2 receptors are further subdivided into ionotropic P2X receptors and G protein-coupled P2Y receptors. P2X4 is an ATP-gated cation channel broadly expressed in most tissues of the body. Within the P2X family, P2X4 has a unique subcellular distribution, being preferentially localized in lysosomes. In these organelles, high ATP concentrations do not trigger P2X4 because of the low pH. However, when the pH increases to 7.4, P2X4 can be stimulated by intra-lysosomal ATP, which is in its active, tetra-anionic form. Elucidation of P2X4, P2X3 and P2X7 structures has shed some light on the functional differences between these purinergic receptors. The potential interaction between P2X4 and P2X7 has been extensively studied. Despite intensive effort, it has not been possible yet to determine whether P2X4 and P2X7 interact as heterotrimers or homotrimers at the plasma membrane. However, several publications have shown that functional interactions between P2X4 and P2X7 do occur. Importantly, these studies indicate that P2X4 potentiates P2X7-dependent activation of inflammasomes, leading to increased release of IL-1β and IL-18. The role of P2X4 in various diseases could be beneficial or deleterious even though the pathophysiological mechanisms involved are still poorly defined. However, in diseases whose physiopathology involves activation of the NLRP3 inflammasome, P2X4 was found to exacerbate severity of disease. The recent production of monoclonal antibodies specific for the human and mouse P2X4, some of which are endowed with agonist or antagonist properties, raises the possibility that they could be used therapeutically. Analysis of single nucleotide polymorphisms of the human P2RX4 gene has uncovered the association of P2RX4 gene variants with susceptibility to several human diseases.

scholarly journals Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

2021 ◽  
Vol 9 ◽  
Author(s):  
Dianne M. Perez
Keyword(s):  
Adrenergic Receptors ◽  
Smooth Muscle Contraction ◽  
The Body ◽  
Whole Body ◽  
Selective Ligands ◽  
Recent Developments ◽  
Vascular Smooth Muscle Contraction ◽  
G Protein Coupled ◽  
Similar Affinity

The α1-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with β and α2-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While α1-AR subtypes (α1A, α1B, α1C) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

scholarly journals The role of the lymphatic system in the homeostasis of the interstitial fluid in the lung and pleural liquid

2019 ◽  
Vol 18 (1) ◽  
pp. 104-112 ◽  
Author(s):  
G. I. Lobov
Keyword(s):  
Endothelial Cells ◽  
Respiratory System ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Current Data ◽  
The Body ◽  
Almost All ◽  
Preclinical And Clinical Studies

Accomplishments in the identifcation of lymphatic endothelial cells and the ability to differentiate them from the endothelial cells of blood vessels have contributed to progress in recent decades in studying the role of the lymphatic system in the body. Preclinical and clinical studies of the last decade have shown that changes in the lymphatic vascular network are observed in almost all lung diseases. At the same time, it remains unclear whether the lymphatic vessels and lung nodes are being part of the overall process of lung remodeling or they make a defnite contribution to the pathogenesis of diseases of the respiratory system. This review presents current data on the morphology and physiology of lymphatic vessels and nodes, their role in the regulation of interstitial fluid homeostasis, lipid transportation and immune responses as well as describes the mechanisms of regulation of the transport function of lymphatic vessels. Data on the role of the lymphatic system of the lungs in the exchange of fluid in the interstitial space of the lungs are presented in the review. The results of studies of the last two decades on the formation and reabsorption of pleural fluid and the role of various lymphatic networks in regulating its volume are described. Finally, modern ideas on the mechanisms of pulmonary edema are outlined and important questions of the lymphatic biology of the respiratory system are identifed, still remaining unanswered today.

scholarly journals Gq-Coupled Receptors in Autoimmunity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Lu Zhang ◽  
Guixiu Shi
Keyword(s):  
G Proteins ◽  
Immune Regulation ◽  
Vital Role ◽  
G Protein Coupled Receptors ◽  
Main Function ◽  
Heterotrimeric G Proteins ◽  
Transmembrane Receptors ◽  
Downstream Signaling ◽  
G Protein Coupled

Heterotrimeric G proteins can be divided into Gi, Gs, Gq/11, and G12/13 subfamilies according to theirαsubunits. The main function of G proteins is transducing signals from G protein coupled receptors (GPCRs), a family of seven transmembrane receptors. In recent years, studies have demonstrated that GPCRs interact with Gq, a member of the Gq/11 subfamily of G proteins. This interaction facilitates the vital role of this family of proteins in immune regulation and autoimmunity, particularly for Gαq, which is considered the functionalαsubunit of Gq protein. Therefore, understanding the mechanisms through which Gq-coupled receptors control autoreactive lymphocytes is critical and may provide insights into the treatment of autoimmune disorders. In this review, we summarize recent advances in studies of the role of Gq-coupled receptors in autoimmunity, with a focus on their pathologic role and downstream signaling.

scholarly journals The role of the kidneys in glucose homeostasis

2018 ◽  
Vol 63 (6) ◽  
pp. 385-391
Author(s):  
Ashot M. Mkrtumyan ◽  
Tatyana N. Markova ◽  
Nadezhda K. Mishchenko
Keyword(s):  
Glucose Homeostasis ◽  
The Body ◽  
Main Function ◽  
Energy Needs ◽  
Glucose Reabsorption ◽  
Glomerular Filtrate ◽  
Cortical Substance ◽  
Convoluted Tubules ◽  
Proximal Convoluted Tubules

Until recently, in was believed that degradation of insulin is the main function of the kidneys in maintaining glucose homeostasis. The results of numerous studies showed that the kidneys are involved in filling the energy needs of the body due to the following three key processes: gluconeogenesis, uptake and reabsorption of glucose molecules. The characteristic feature of gluconeogenesis that occurs in the kidneys lies in the fact that it depends on the time elapsed since the last meal. Thus, gluconeogenesis that occurs in the cortical substance of the kidneys provides up to 90% of the glucose entering the blood in the post-absorptive period and up to 60% in the postprandial period. Glucose reabsorption from the glomerular filtrate occurs in the proximal convoluted tubules assisted by sodium-glucose cotransporters, sodium-glucose cotransporters 2 (SGLT2) being the most important of them. It is known that the cells of the proximal convoluted tubules of the kidneys in patients with type 2 diabetes mellitus (DM2) contain significantly more SGLT2 proteins compared to those of healthy individuals. The discovery of the important role of the kidneys in glucose homeostasis led to investigation of the new links in DM2 pathogenesis and the development of a promising approach to its treatment using SGLT2 inhibitors.

scholarly journals Role of Cannabinoid Receptors in Psychological Disorder

2020 ◽  
Vol 3 (4) ◽  
pp. 199-208
Author(s):  
Ambika Nand Jha ◽  
Dhaval M Patel
Keyword(s):  
Cannabinoid Receptors ◽  
Biological Effects ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
The Body ◽  
Psychological Disorder ◽  
Physiological Processes ◽  
Neurochemical Changes ◽  
G Protein Coupled

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

scholarly journals New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Anderson J. Ferreira ◽  
Tatiane M. Murça ◽  
Rodrigo A. Fraga-Silva ◽  
Carlos Henrique Castro ◽  
Mohan K. Raizada ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Therapeutic Strategies ◽  
Biologically Active ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
G Protein Coupled ◽  
Hydrolysis Of

Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1–7). The axis formed by ACE2/Ang-(1–7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT1receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.

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