Understanding Cytokines Part I: Physiology and Mechanism of Action

This is the first of a 2-part article on understanding cytokines. Cytokines are intercellular signaling proteins released from virtually all nucleated cells that influence growth and cellular proliferation in a wide range of tissues. Cytokines have immune modulating effects and are understood to control most of the physical and psychological symptoms associated with infection and inflammation. Cytokines also influence reproduction and bone remodeling. Dysregulation of the cytokine cellular system has significant implications in the development of a variety of illnesses, including most autoimmune disorders, many diseases of the cardiovascular system, osteoporosis, asthma, and depression. For nurses to be adequately informed when caring for clients with chronic illnesses and to be sufficiently knowledgeable when evaluating client outcomes, an understanding of the physiology of cytokines, the occurrences of dysregulation, and the role of cytokines in health and illness is essential. In Part I of this review, cytokine physiology is presented, with an emphasis on characteristics, categories, and mechanism of action. Specific instances of cytokine function in health and disease and implications for nursing research and practice are presented in Part II.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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The GCN5: its biological functions and therapeutic potentials

Clinical Science ◽

10.1042/cs20200986 ◽

2021 ◽

Vol 135 (1) ◽

pp. 231-257

Author(s):

Md. Ezazul Haque ◽

Md. Jakaria ◽

Mahbuba Akther ◽

Duk-Yeon Cho ◽

In-Su Kim ◽

...

Keyword(s):

Neurological Disorders ◽

Cellular Proliferation ◽

Chromatin Modification ◽

Structural Features ◽

Histone Acetyltransferases ◽

Epigenetic Landscape ◽

General Control ◽

Wide Range ◽

Lysine Acetyltransferase

Abstract General control non-depressible 5 (GCN5) or lysine acetyltransferase 2A (KAT2A) is one of the most highly studied histone acetyltransferases. It acts as both histone acetyltransferase (HAT) and lysine acetyltransferase (KAT). As an HAT it plays a pivotal role in the epigenetic landscape and chromatin modification. Besides, GCN5 regulates a wide range of biological events such as gene regulation, cellular proliferation, metabolism and inflammation. Imbalance in the GCN5 activity has been reported in many disorders such as cancer, metabolic disorders, autoimmune disorders and neurological disorders. Therefore, unravelling the role of GCN5 in different diseases progression is a prerequisite for both understanding and developing novel therapeutic agents of these diseases. In this review, we have discussed the structural features, the biological function of GCN5 and the mechanical link with the diseases associated with its imbalance. Moreover, the present GCN5 modulators and their limitations will be presented in a medicinal chemistry perspective.

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Tunneling Nanotubes and the Eye: Intercellular Communication and Implications for Ocular Health and Disease

BioMed Research International ◽

10.1155/2020/7246785 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Holly R. Chinnery ◽

Kate E. Keller

Keyword(s):

Eye Diseases ◽

Cellular Communication ◽

Tunneling Nanotubes ◽

Extracellular Milieu ◽

Wide Range ◽

Aqueous Environments ◽

Health And Disease ◽

Ocular Health

Cellular communication is an essential process for the development and maintenance of all tissues including the eye. Recently, a new method of cellular communication has been described, which relies on formation of tubules, called tunneling nanotubes (TNTs). These structures connect the cytoplasm of adjacent cells and allow the direct transport of cellular cargo between cells without the need for secretion into the extracellular milieu. TNTs may be an important mechanism for signaling between cells that reside long distances from each other or for cells in aqueous environments, where diffusion-based signaling is challenging. Given the wide range of cargoes transported, such as lysosomes, endosomes, mitochondria, viruses, and miRNAs, TNTs may play a role in normal homeostatic processes in the eye as well as function in ocular disease. This review will describe TNT cellular communication in ocular cell cultures and the mammalian eye in vivo, the role of TNTs in mitochondrial transport with an emphasis on mitochondrial eye diseases, and molecules involved in TNT biogenesis and their function in eyes, and finally, we will describe TNT formation in inflammation, cancer, and stem cells, focusing on pathological processes of particular interest to vision scientists.

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Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

Biochemical Journal ◽

10.1042/bj20110949 ◽

2011 ◽

Vol 439 (3) ◽

pp. 349-378 ◽

Cited By ~ 212

Author(s):

Anthony J. Morgan ◽

Frances M. Platt ◽

Emyr Lloyd-Evans ◽

Antony Galione

Keyword(s):

Molecular Mechanisms ◽

Cellular Processes ◽

Late Endosomes ◽

Wide Range ◽

Health And Disease ◽

Lysosome Related Organelles ◽

Cellular Compartments ◽

Endosomal Vesicles ◽

Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

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The role of Galactose in human health and disease

Open Medicine ◽

10.2478/s11536-012-0022-z ◽

2012 ◽

Vol 7 (4) ◽

pp. 409-419 ◽

Cited By ~ 4

Author(s):

Muhammad Manwar Hussain ◽

Mukhtarul Hassan ◽

Noor Shaik ◽

Zeeshan Iqbal

Keyword(s):

Human Health ◽

Cellular Signaling ◽

Biological Processes ◽

Microbial Adhesion ◽

Wide Range ◽

Health And Disease ◽

Stereochemical Properties ◽

Specific Sugar

AbstractAccording to the universal biological findings, cellular bodies are covered with an intense coating of glycans. Diversity of glycan chains, linked to lipids and proteins is due to isomeric and conformational modifications of various sugar residues, giving rise to unique carbohydrate structures with a wide range of sequences and anomeric configurations. Proteins and lipids, carrying specific sugar residues (like Galactose) with particular stereochemical properties (sequence, anomery and linkages) are involved in broad spectrums of biological processes, including intercellular and intracellular interactions, microbial adhesion and cellular signaling. By studying the role of specific seterochemical features of galactose (Gal), we have improved our understanding about the normal physiology and diseases in human bodies.

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Early Life Inflammation and the Developing Hematopoietic and Immune Systems: The Cochlea as a Sensitive Indicator of Disruption

Cells ◽

10.3390/cells10123596 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3596

Author(s):

Kelly S. Otsuka ◽

Christopher Nielson ◽

Matthew A. Firpo ◽

Albert H. Park ◽

Anna E. Beaudin

Keyword(s):

Immune Cells ◽

Early Life ◽

Congenital Infection ◽

Perinatal Infection ◽

Hematopoietic Stem ◽

Wide Range ◽

Infection And Inflammation ◽

Health And Disease ◽

And Function ◽

Future Work

Emerging evidence indicates that perinatal infection and inflammation can influence the developing immune system and may ultimately affect long-term health and disease outcomes in offspring by perturbing tissue and immune homeostasis. We posit that perinatal inflammation influences immune outcomes in offspring by perturbing (1) the development and function of fetal-derived immune cells that regulate tissue development and homeostasis, and (2) the establishment and function of developing hematopoietic stem cells (HSCs) that continually generate immune cells across the lifespan. To disentangle the complexities of these interlinked systems, we propose the cochlea as an ideal model tissue to investigate how perinatal infection affects immune, tissue, and stem cell development. The cochlea contains complex tissue architecture and a rich immune milieu that is established during early life. A wide range of congenital infections cause cochlea dysfunction and sensorineural hearing loss (SNHL), likely attributable to early life inflammation. Furthermore, we show that both immune cells and bone marrow hematopoietic progenitors can be simultaneously analyzed within neonatal cochlear samples. Future work investigating the pathogenesis of SNHL in the context of congenital infection will therefore provide critical information on how perinatal inflammation drives disease susceptibility in offspring.

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Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

Clinical Science ◽

10.1042/cs20160940 ◽

2017 ◽

Vol 131 (15) ◽

pp. 1919-1922 ◽

Cited By ~ 3

Author(s):

Gareth A. Nye ◽

Giorgos K. Sakellariou ◽

Hans Degens ◽

Adam P. Lightfoot

Keyword(s):

Skeletal Muscle ◽

Sexual Dimorphism ◽

Mitochondrial Function ◽

Nutraceuticals against Oxidative Stress in Autoimmune Disorders

Antioxidants ◽

10.3390/antiox10020261 ◽

2021 ◽

Vol 10 (2) ◽

pp. 261

Author(s):

Carmen Mannucci ◽

Marco Casciaro ◽

Emanuela Elisa Sorbara ◽

Fabrizio Calapai ◽

Eleonora Di Salvo ◽

...

Keyword(s):

Oxidative Stress ◽

Fruits And Vegetables ◽

Autoimmune Disorders ◽

Chronic Illnesses ◽

Antioxidant Systems ◽

Oxidative Stress Biomarkers ◽

Positive Effects ◽

Dietary Antioxidant ◽

Wide Range

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called “phytochemicals”. Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers.

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Lysosome function in glomerular health and disease

Cell and Tissue Research ◽

10.1007/s00441-020-03375-7 ◽

2021 ◽

Author(s):

Catherine Meyer-Schwesinger

Keyword(s):

Current Knowledge ◽

Lysosomal Storage Diseases ◽

Cell Types ◽

Lysosomal Storage ◽

Membrane Repair ◽

Glomerular Cell ◽

Wide Range ◽

Center Position ◽

Health And Disease

AbstractThe lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

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METALLOTHIONEINS AS SENSORS AND CONTROLS EXCHANGE OF METALS IN THE CELLS

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2014-3-91-99 ◽

2014 ◽

Vol 13 (3) ◽

pp. 91-99 ◽

Cited By ~ 1

Author(s):

V. A. Kutyakov ◽

A. V. Salmina

Keyword(s):

Stress Factors ◽

Special Role ◽

Cellular Functions ◽

Regulation Of Expression ◽

Wide Range ◽

Health And Disease ◽

Pharmacology And Toxicology ◽

Regulatory Functions ◽

The Impact

The basic information on the classification, structure, induction and degradation, functions of the protein family – metallothionein (MT), including CNS in health and disease are presented in this review. It was found that four major isoforms of metallothionein perform different biological roles, are localized in dif- ferent tissues. Induction of MT is a universal reaction to the impact of a variety of stress factors. In recent years, understanding of the role of metallothioneins in metal homeostasis in the tissues in normal and pathological conditions have changed significantly. Notes polyfunctionality metallothioneins (transport of metal ions, maintaining redox reactions, tread, signal, modulated and regulatory functions) and their im- pact on basic cellular functions such as proliferation, differentiation, programmed cell death. Further- more, a special role is shown MT in the pathogenesis of cardiovascular, neurodegenerative and neoplastic disorders.Currently, these molecules are increasingly considered as potential targets for therapy of a wide range of diseases and the development of targeted approaches to the regulation of expression of MT – one of the promising areas of pharmacology and toxicology. Stressed the safety of metallothioneins as therapeutic agents.

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