PAF Physiology in Target Organ Systems—A Deep Dive to Understand the PAF Mystery in Pathogenesis of Disease

The purpose of this literature review is to gain an overview of the role of platelet-activating factor (PAF) within each of the body systems and how it contributes to normal and pathophysiological states. The review showed that there are multiple functions of PAF that are common to several body systems; however, there is little evidence to explain why PAF has this affect across multiple systems. Interestingly, there seems to be conflicting research as to whether PAF is an overall protective or pathogenic pathway. Within this research, it was found that there are different pathways depending on the specific body system, as well as between body systems. However, one universal function reported in the literature is of PAF as a pro-inflammatory molecule. Overall, this review identified five major functions of PAF: vasoconstriction, increased inflammation, vascular remodeling, increased edema, and endothelial permeability.

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The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models

Biomolecules ◽

10.3390/biom11050667 ◽

2021 ◽

Vol 11 (5) ◽

pp. 667

Author(s):

Meera Krishnan ◽

Sahil Kumar ◽

Luis Johnson Kangale ◽

Eric Ghigo ◽

Prasad Abnave

Keyword(s):

Stem Cells ◽

Animal Models ◽

Adult Stem Cells ◽

The Body ◽

In Vivo Studies ◽

Self Renewal ◽

Hematopoietic Stem ◽

Organ Systems

Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differentiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. intestinal stem cells (ISCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs), and epidermal stem cells (Ep-SCs).

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Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

Journal of Clinical Medicine ◽

10.3390/jcm9010264 ◽

2020 ◽

Vol 9 (1) ◽

pp. 264 ◽

Cited By ~ 2

Author(s):

Laura Governini ◽

Bianca Semplici ◽

Valentina Pavone ◽

Laura Crifasi ◽

Camilla Marrocco ◽

...

Keyword(s):

Taste Receptor ◽

Receptor Activation ◽

Taste Buds ◽

The Body ◽

Semen Parameters ◽

Human Testis ◽

Taste Receptors ◽

Organ Systems

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.

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Role of collecting duct endothelin in control of renal function and blood pressure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00345.2013 ◽

2013 ◽

Vol 305 (7) ◽

pp. R659-R668 ◽

Cited By ~ 28

Author(s):

Donald E. Kohan

Keyword(s):

Arterial Pressure ◽

Collecting Duct ◽

Extracellular Fluid ◽

Multiple Organ ◽

The Body ◽

Water Reabsorption ◽

Organ Systems ◽

Key Issues ◽

Salt Sensitive Hypertension

Over 26,000 manuscripts have been published dealing with endothelins since their discovery 25 years ago. These peptides, and particularly endothelin-1 (ET-1), are expressed by, bind to, and act on virtually every cell type in the body, influencing multiple biological functions. Among these actions, the effects of ET-1 on arterial pressure and volume homeostasis have been most extensively studied. While ET-1 modulates arterial pressure through regulation of multiple organ systems, the peptide's actions in the kidney in general, and the collecting duct in particular, are of unique importance. The collecting duct produces large amounts of ET-1 that bind in an autocrine manner to endothelin A and B receptors, causing inhibition of Na+ and water reabsorption; absence of collecting duct ET-1 or its receptors is associated with marked salt-sensitive hypertension. Collecting duct ET-1 production is stimulated by Na+ and water loading through local mechanisms that include sensing of salt and other solute delivery as well as shear stress. Thus the collecting duct ET-1 system exists, at least in part, to detect alterations in, and maintain homeostasis for, extracellular fluid volume. Derangements in collecting duct ET-1 production may contribute to the pathogenesis of genetic hypertension. Blockade of endothelin receptors causes fluid retention due, in large part, to inhibition of the action of ET-1 in the collecting duct; this side effect has substantially limited the clinical utility of this class of drugs. Herein, the biology of the collecting duct ET-1 system is reviewed, with particular emphasis on key issues and questions that need addressing.

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S-nitrosylation of VASP at cysteine 64 mediates the inflammation-stimulated increase in microvascular permeability

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00135.2017 ◽

2017 ◽

Vol 313 (1) ◽

pp. H66-H71 ◽

Cited By ~ 7

Author(s):

Patricia Zamorano ◽

Natalie Marín ◽

Francisco Córdova ◽

Alejandra Aguilar ◽

Cynthia Meininger ◽

...

Keyword(s):

Endothelial Cells ◽

Platelet Activating Factor ◽

Endothelial Permeability ◽

Subcellular Location ◽

Membrane Reconstitution ◽

Barrier Integrity ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

In Cells

We tested the hypothesis that platelet-activating factor (PAF) induces S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S-nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosylation of VASP in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Reconstitution of VASP knockout myocardial endothelial cells with cysteine mutants of VASP demonstrated that S-nitrosylation of cysteine 64 is associated with PAF-induced hyperpermeability. We propose that regulation of VASP contributes to endothelial cell barrier integrity and to the onset of hyperpermeability. S-nitrosylation of VASP inhibits its function in barrier integrity and leads to endothelial monolayer hyperpermeability in response to PAF, a representative proinflammatory agonist. NEW & NOTEWORTHY Here, we demonstrate that S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) on C64 is a mechanism for the onset of platelet-activating factor-induced hyperpermeability. Our results reveal a dual role of VASP in endothelial permeability. In addition to its well-documented function in barrier integrity, we show that S-nitrosylation of VASP contributes to the onset of endothelial permeability.

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Электродинамическая модель системы «излучатель-корпус объекта»

MORSKIE INTELLEKTUAL`NYE TEHNOLOGII ◽

10.37220/mit.2020.47.1.019 ◽

2020 ◽

Author(s):

A.R. Avdeev ◽

R.Yu. Borodulin ◽

V.P. Chernoles ◽

I.G. Malygin

Keyword(s):

Quality Factor ◽

The Body ◽

Moving Object ◽

Body System ◽

Unified Approach ◽

Arbitrary Type ◽

Excitation Coefficient ◽

Arbitrary Location ◽

The Ideal

В целях выработки единого подхода к оценке роли корпуса подвижного объекта (грунтового, воздушного, корабельного, железнодорожного), на котором установлен малогабаритный излучатель произвольного типа, предложен единый энергетический подход с использованием понятия добротности. Показано, что добротность системы в широких пределах изменяется в зависимости от места установки малогабаритного излучателя. Для оценки вклада корпуса объекта в общую эффективность системы предложен параметр коэффициент возбуждения корпуса объекта, определяемый соотношением идеальной добротности малогабаритного излучателя в свободном пространстве к идеальной добротности излучателя, размещенного на корпусе подвижного объекта. Проанализированы пределы изменения данного коэффициента в зависимости от координат места установки излучателя и его типа (электрического или магнитного). Указанный подход позволяет численно оценить коэффициент полезного действия системы излучатель-корпус объекта при рассмотрении антенны произвольного типа, расположенной в произвольном месте корпуса.In order to develop a unified approach to assessing the role of the body of a moving object (ground, air, ship, or rail) equipped with a small-sized radiator of an arbitrary type, a unified energy approach is proposed using the concept of quality factor. It is shown that the quality factor of the system varies widely depending on the installation location of a small-sized radiator. To assess the contribution of the objects body to the overall system efficiency, a parameter is proposed - the excitation coefficient of the objects body, which is determined by the ratio of the ideal quality factor of a small-sized radiator in free space to the ideal quality factor of a radiator mounted on the body of a moving object. The range of this coefficient is analyzed depending on the location coordinates of the installed radiator and its type (electric or magnetic). This approach allows the numerical evaluation of the efficiency of the radiator objects body system when considering an antenna of an arbitrary type located in an arbitrary location on the body.

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Role of Bacterial Flora in Oral Cancer- An Insight

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48929.15413 ◽

2021 ◽

Author(s):

R Ananthalakshmi ◽

M Priya ◽

Nadeem Jeddy ◽

LJ Sailakshmi

Keyword(s):

Oral Cavity ◽

Human Body ◽

Bacterial Species ◽

Bacterial Flora ◽

Fungal Species ◽

The Body ◽

Oral Carcinoma ◽

Oral Diseases ◽

Organ Systems

The human body contains about 1014 bacteria which usually colonise different parts of the body. The bacterial flora is important for a person’s health as well as normal functioning of tissue and organ systems. Bacteria are single celled organisms and are found on almost all surfaces of human body. They act in synergy with host immune mechanism and provide protection against various undesirable foreign invasions, especially in the oral cavity, where they exist in a diversified form which survive in a symbiotic relationship with the host. When there is a disturbance in this equilibrium due to various factors like trauma or tobacco smoking, betel nut chewing and alcohol intake, which makes the mucous membrane more permeable to invading microorganisms, these commensal bacterial species can become virulent and give rise to oral diseases ranging from dental caries to oral carcinoma. The effects of these bacteria can be either direct or indirect initiation of chronic inflammation, formation of procarcinogens that contribute to the development of oral carcinoma. This article focuses on the role of oral bacterial flora in initiation and progression of oral carcinogenesis. Various bacterial and fungal species associated with oral carcinoma and predominant bacterial species in oral cavity and oropharyngeal region along with measures to prevent their adverse effects are described.

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The Role of Centres of German Culture in Preserving the Ethnic Identity of Russian Germans

Herald of Omsk University. Series: Historical Studies ◽

10.24147/2312-1300.2020.7(1).180-186 ◽

2020 ◽

Vol 7 (1 (25)) ◽

pp. 180-186

Author(s):

Elena A. Shlegel

Keyword(s):

Ethnic Identity ◽

The Body ◽

Self Organization ◽

Special Role ◽

Body System ◽

Present Stage ◽

German Culture ◽

Ethnic Germans ◽

Russian Germans

The ethnic identity of Russian Germans is formed by various factors. A special role in the self-identification of ethnic Germans are played the body system of self-organization at present stage, most of which is represented by the Centers of German Culture located in different regions of the country. The article analyses the activities of the Centers for German Culture, as well as their contribution of the formation and preservation of the ethnic identity of Russian Germans through project activities implemented in recent years.

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Pathogenic Role of Store-Operated and Receptor-Operated Ca2+ Channels in Pulmonary Arterial Hypertension

Journal of Signal Transduction ◽

10.1155/2012/951497 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 13

Author(s):

Ruby A. Fernandez ◽

Premanand Sundivakkam ◽

Kimberly A. Smith ◽

Amy S. Zeifman ◽

Abigail R. Drennan ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Vascular Remodeling ◽

The Body ◽

Pathogenic Role ◽

Pulmonary Vascular Remodeling ◽

Pulmonary Vasoconstriction ◽

Voltage Dependent ◽

Pulmonary Arterial

Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of Ca2+ signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. [Ca2+]cyt in PASMC is increased by Ca2+ influx through Ca2+ channels in the plasma membrane and by Ca2+ release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two Ca2+ entry pathways, voltage-dependent Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) and voltage-independent Ca2+ influx through store-operated Ca2+ channels (SOC) and receptor-operated Ca2+ channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH.

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Epithelial-Mesenchymal Interactions in Embryogenesis and Head and Neck Tumors

Journal of Surgical Case Reports and Images ◽

10.31579/2690-1897/007 ◽

2019 ◽

Vol 2 (1) ◽

pp. 01-08

Author(s):

Lekshmy Jayan ◽

R. Bharanidharan ◽

Ramya Ramdas

Keyword(s):

Salivary Gland ◽

Epithelial Mesenchymal Transition ◽

Pathological Process ◽

The Body ◽

Important Process ◽

Mesenchymal Transition ◽

Neck Tumors ◽

Pathological Conditions ◽

Organ Systems

Epithelial mesenchymal interactions are one of the most important process taking place in the body. It is an indispensable mechanism that mediates the development of numerous organs and organ systems especially tooth, salivary gland etc. It has been long implicated in the causation of numerous pathogenic processes especially cancer. The mechanism of epithelial mesenchymal interactions are a forerunner for epithelial mesenchymal transition, which is an important pathological process in the development of cancer. In this review, we have highlighted the role of epithelial mesenchymal interactions in normal embryogenesis as well in numerous pathological conditions.

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