Multifaceted MRGPRX2: New Insight into the Role of Mast Cells in Health and Disease

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns

Annual Review of Immunology ◽

10.1146/annurev-immunol-071719-094903 ◽

2020 ◽

Vol 38 (1) ◽

pp. 49-77 ◽

Cited By ~ 8

Author(s):

Stephen J. Galli ◽

Nicolas Gaudenzio ◽

Mindy Tsai

Keyword(s):

Mast Cells ◽

Morphological Characteristics ◽

Styela Plicata ◽

Adaptive Immune ◽

Open Questions ◽

Health And Disease ◽

Test Cells ◽

Neutral Proteases ◽

Insight Into ◽

Mast Cell Heterogeneity

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.

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Mast cells in health and disease

Clinical Science ◽

10.1042/cs20100459 ◽

2011 ◽

Vol 120 (11) ◽

pp. 473-484 ◽

Cited By ~ 54

Author(s):

Charlotte L. Weller ◽

Sarah J. Collington ◽

Tim Williams ◽

Jonathan R. Lamb

Keyword(s):

Wound Healing ◽

Mast Cells ◽

Allergic Disease ◽

Effector Functions ◽

Health And Disease ◽

Developing Area ◽

Deficient Mice ◽

Made In

Although MCs (mast cells) were discovered over 100 years ago, for the majority of this time their function was linked almost exclusively to allergy and allergic disease with few other roles in health and disease. The engineering of MC-deficient mice and engraftment of these mice with MCs deficient in receptors or mediators has advanced our knowledge of the role of MCs in vivo. It is now known that MCs have very broad and varied roles in both physiology and disease which will be reviewed here with a focus on some of the most recent discoveries over the last year. MCs can aid in maintaining a healthy physiology by secreting mediators that promote wound healing and homoeostasis as well as interacting with neurons. Major developments have been made in understanding MC function in defence against pathogens, in recognition of pathogens as well as direct effector functions. Probably the most quickly developing area of understanding is the involvement and contribution MCs make in the progression of a variety of diseases from some of the most common diseases to the more obscure.

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Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20153673 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3673 ◽

Cited By ~ 20

Author(s):

Lismont ◽

Revenco ◽

Fransen

Keyword(s):

Hydrogen Peroxide ◽

Molecular Mechanisms ◽

Signaling Network ◽

H2o2 Production ◽

Peroxisomal Enzyme ◽

Pathological Conditions ◽

Health And Disease ◽

Precise Role ◽

Insight Into

Hydrogen peroxide (H2O2), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H2O2 metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.

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The biochemical basis of disease

Essays in Biochemistry ◽

10.1042/ebc20170054 ◽

2018 ◽

Vol 62 (5) ◽

pp. 619-642 ◽

Cited By ~ 8

Author(s):

Alastair J. Barr

Keyword(s):

Liver Disease ◽

Global Health ◽

Cell Biology ◽

Biochemical Basis ◽

New Developments ◽

Biochemical Pathways ◽

Causes Of Disease ◽

Health And Disease ◽

Insight Into

This article gives the reader an insight into the role of biochemistry in some of the current global health and disease problems. It surveys the biochemical causes of disease in an accessible and succinct form while also bringing in aspects of pharmacology, cell biology, pathology and physiology which are closely aligned with biochemistry. The discussion of the selected diseases highlights exciting new developments and illuminates key biochemical pathways and commonalities. The article includes coverage of diabetes, atherosclerosis, cancer, microorganisms and disease, nutrition, liver disease and Alzheimer’s disease, but does not attempt to be comprehensive in its coverage of disease, since this is beyond its remit and scope. Consequently there are many fascinating biochemical aspects of diseases, both common and rare, that are not addressed here that can be explored in the further reading cited. Techniques and biochemical procedures for studying disease are not covered in detail here, but these can be found readily in a range of biochemical methods sources.

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Mitoproteomics: Tackling Mitochondrial Dysfunction in Human Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/1435934 ◽

2018 ◽

Vol 2018 ◽

pp. 1-26 ◽

Cited By ~ 7

Author(s):

María Gómez-Serrano ◽

Emilio Camafeita ◽

Marta Loureiro ◽

Belén Peral

Keyword(s):

Mitochondrial Dysfunction ◽

Cell Metabolism ◽

Mitochondrial Protein ◽

Protein Composition ◽

Interaction Networks ◽

Global View ◽

Health And Disease ◽

Innovative Techniques ◽

Insight Into

Mitochondria are highly dynamic and regulated organelles that historically have been defined based on their crucial role in cell metabolism. However, they are implicated in a variety of other important functions, making mitochondrial dysfunction an important axis in several pathological contexts. Despite that conventional biochemical and molecular biology approaches have provided significant insight into mitochondrial functionality, innovative techniques that provide a global view of the mitochondrion are still necessary. Proteomics fulfils this need by enabling accurate, systems-wide quantitative analysis of protein abundance. More importantly, redox proteomics approaches offer unique opportunities to tackle oxidative stress, a phenomenon that is intimately linked to aging, cardiovascular disease, and cancer. In addition, cutting-edge proteomics approaches reveal how proteins exert their functions in complex interaction networks where even subtle alterations stemming from early pathological states can be monitored. Here, we describe the proteomics approaches that will help to deepen the role of mitochondria in health and disease by assessing not only changes to mitochondrial protein composition but also alterations to their redox state and how protein interaction networks regulate mitochondrial function and dynamics. This review is aimed at showing the reader how the application of proteomics approaches during the last 20 years has revealed crucial mitochondrial roles in the context of aging, neurodegenerative disorders, metabolic disease, and cancer.

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Thyroid Hormone Transporters

Endocrine Reviews ◽

10.1210/endrev/bnz008 ◽

2019 ◽

Vol 41 (2) ◽

pp. 146-201 ◽

Cited By ~ 12

Author(s):

Stefan Groeneweg ◽

Ferdy S van Geest ◽

Robin P Peeters ◽

Heike Heuer ◽

W Edward Visser

Keyword(s):

Thyroid Hormone ◽

Organic Anion ◽

Treatment Strategies ◽

Monocarboxylate Transporter ◽

Organic Anion Transporting Polypeptide ◽

Clinical Disorders ◽

Health And Disease ◽

Mct8 Deficiency ◽

Insight Into

Abstract Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporter (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1, and SLC17A4 are currently known as transporters displaying the highest specificity toward thyroid hormones. Structure-function studies using homology modeling and mutational screens have led to better understanding of the molecular basis of thyroid hormone transport. Mutations in MCT8 and in OATP1C1 have been associated with clinical disorders. Different animal models have provided insight into the functional role of thyroid hormone transporters, in particular MCT8. Different treatment strategies for MCT8 deficiency have been explored, of which thyroid hormone analogue therapy is currently applied in patients. Future studies may reveal the identity of as-yet-undiscovered thyroid hormone transporters. Complementary studies employing animal and human models will provide further insight into the role of transporters in health and disease.

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