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Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 89664

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Special Issue Editor

Prof. Dr. Daniela Caccamo

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Guest Editor

Department of Biomedical Sciences, Polyclinic Hospital University, Messina, Italy
Interests: environmental sensitivity disorders; oxidative stress; genotype/phenotype relationships; neuroinflammation; immune activation; hyperhomocysteinemia-related disorders; hypovitaminosis D-related disorders; pathological role of transglutaminase 2 aberrant expression; neurological disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2019 Special Issue, “Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures”.

This Special Issue aims to be a state-of-the-art review of environmental sensitivity illnesses (ESI), namely, multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and electro-hypersensitivity, to cite only the most relevant ones. Although these pathological conditions have recently gained great interest due to concerns about potential health risks raised by continuously increasing daily exposure to toxic xenobiotics, i.e., chemicals, drugs, artificial food components, heavy metals, and electromagnetic fields, a nosologic classification of ESI is still lacking in a large number of countries worldwide.

This Special Issue aims to gather high-quality research papers, as well as systematic reviews and meta-analyses, that focus on the following:

Molecular mechanisms underlying shared and distinct features of different disorders arising from toxicant-induced loss of tolerance;
Genetic and epigenetic alterations playing a role as risk factors, i.e., DNA (genomic, mitochondrial) sequence alterations, changes in either site-specific DNA methylation status or in circulating levels of microRNAs, and long noncoding RNAs;
Distinctive alterations in the transcriptome and/or the proteome of peripheral blood cells, as well as in serum metabolome;
Changes in gut microbiome and/or microbiota metabolites;
Molecular tracers for neuroimaging.

I hope you will take the opportunity to share knowledge and new perspectives on these intriguing pathologies.

Prof. Dr. Daniela Caccamo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

multiple chemical sensitivity
fibromyalgia
electromagnetic hypersensitivity
toxicant-induced loss of tolerance
chronic fatigue syndrome
total allergy syndrome
chronic pain disorder
circulating biomarkers
genetic susceptibility factors
changes in DNA methylation status
miRNA
lncRNA
transcriptomics
proteomics
neuroimaging biomarkers

Published Papers (7 papers)

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Research

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36 pages, 5531 KiB

Open AccessArticle

Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts

by Daniel Missailidis, Oana Sanislav, Claire Y. Allan, Paige K. Smith, Sarah J. Annesley and Paul R. Fisher

Int. J. Mol. Sci. 2021, 22(4), 2046; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042046 - 19 Feb 2021

Cited by 21 | Viewed by 9040

Abstract

Although understanding of the biomedical basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is growing, the underlying pathological mechanisms remain uncertain. We recently reported a reduction in the proportion of basal oxygen consumption due to ATP synthesis by Complex V in ME/CFS patient-derived lymphoblast cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied by elevated respiratory capacity, elevated mammalian target of rapamycin complex 1 (mTORC1) signaling activity and elevated expression of enzymes involved in the TCA cycle, fatty acid β-oxidation and mitochondrial transport. These and other observations led us to hypothesise the dysregulation of pathways providing the mitochondria with oxidisable substrates. In our current study, we aimed to revisit this hypothesis by applying a combination of whole-cell transcriptomics, proteomics and energy stress signaling activity measures using subsets of up to 34 ME/CFS and 31 healthy control lymphoblast cell lines from our growing library. While levels of glycolytic enzymes were unchanged in accordance with our previous observations of unaltered glycolytic rates, the whole-cell proteomes of ME/CFS lymphoblasts contained elevated levels of enzymes involved in the TCA cycle (p = 1.03 × 10⁻⁴), the pentose phosphate pathway (p = 0.034, G6PD p = 5.5 × 10⁻⁴), mitochondrial fatty acid β-oxidation (p = 9.2 × 10⁻³), and degradation of amino acids including glutamine/glutamate (GLS p = 0.034, GLUD1 p = 0.048, GOT2 p = 0.026), branched-chain amino acids (BCKDHA p = 0.028, BCKDHB p = 0.031) and essential amino acids (FAH p = 0.036, GCDH p = 0.006). The activity of the major cellular energy stress sensor, AMPK, was elevated but the increase did not reach statistical significance. The results suggest that ME/CFS metabolism is dysregulated such that alternatives to glycolysis are more heavily utilised than in controls to provide the mitochondria with oxidisable substrates. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

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15 pages, 892 KiB

Open AccessArticle

Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects

by Renata Risi, Simonetta Masieri, Eleonora Poggiogalle, Mikiko Watanabe, Alessandra Caputi, Rossella Tozzi, Elena Gangitano, Davide Masi, Stefania Mariani, Lucio Gnessi and Carla Lubrano

Int. J. Mol. Sci. 2020, 21(24), 9733; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249733 - 20 Dec 2020

Cited by 9 | Viewed by 2488

Abstract

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

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Review

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19 pages, 743 KiB

Open AccessReview

The Critical Importance of Molecular Biomarkers and Imaging in the Study of Electrohypersensitivity. A Scientific Consensus International Report

by Dominique Belpomme, George L. Carlo, Philippe Irigaray, David O. Carpenter, Lennart Hardell, Michael Kundi, Igor Belyaev, Magda Havas, Franz Adlkofer, Gunnar Heuser, Anthony B. Miller, Daniela Caccamo, Chiara De Luca, Lebrecht von Klitzing, Martin L. Pall, Priyanka Bandara, Yael Stein, Cindy Sage, Morando Soffritti, Devra Davis, Joel M. Moskowitz, S. M. J. Mortazavi, Martha R. Herbert, Hanns Moshammer, Gerard Ledoigt, Robert Turner, Anthony Tweedale, Pilar Muñoz-Calero, Iris Udasin, Tarmo Koppel, Ernesto Burgio and André Vander Vorst Show full author list Hide full author list

Int. J. Mol. Sci. 2021, 22(14), 7321; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147321 - 07 Jul 2021

Cited by 12 | Viewed by 12460

Abstract

Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called “provocation tests”, which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF). However, because those tests depend on multiple EMF-associated physical and biological parameters and have been conducted in patients without having first defined EHS objectively and/or endpoints adequately, they cannot presently be considered to be valid pathogenesis research methodologies. Consequently, the negative results obtained by these tests do not preclude a role of EMF exposure as a symptomatic trigger in EHS patients. Moreover, there is no proof that EHS symptoms or EHS itself are caused by psychosomatic or nocebo effects. This international consensus report pleads for the acknowledgement of EHS as a distinct neuropathological disorder and for its inclusion in the WHO International Classification of Diseases. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

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31 pages, 1075 KiB

Open AccessReview

Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update

by Rosalba Siracusa, Rosanna Di Paola, Salvatore Cuzzocrea and Daniela Impellizzeri

Int. J. Mol. Sci. 2021, 22(8), 3891; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083891 - 09 Apr 2021

Cited by 176 | Viewed by 37628

Abstract

Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

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11 pages, 242 KiB

Open AccessReview

Insights into Metabolite Diagnostic Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

by Emi Yamano, Yasuyoshi Watanabe and Yosky Kataoka

Int. J. Mol. Sci. 2021, 22(7), 3423; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073423 - 26 Mar 2021

Cited by 8 | Viewed by 4008

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. Its pathogenesis is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of ME/CFS and diagnostic uncertainty. Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

27 pages, 2688 KiB

Open AccessReview

Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies

by Massimo E. Maffei

Int. J. Mol. Sci. 2020, 21(21), 7877; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217877 - 23 Oct 2020

Cited by 68 | Viewed by 20741

Abstract

Fibromyalgia (FM) is a syndrome that does not present a well-defined underlying organic disease. FM is a condition which has been associated with diseases such as infections, diabetes, psychiatric or neurological disorders, rheumatic pathologies, and is a disorder that rather than diagnosis of exclusion requires positive diagnosis. A multidimensional approach is required for the management of FM, including pain management, pharmacological therapies, behavioral therapy, patient education, and exercise. The purpose of this review is to summarize the recent advances in classification criteria and diagnostic criteria for FM as well as to explore pharmacotherapy and the use of alternative therapies including the use of plant bioactive molecules. Full article

(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

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