Article
Medicine, Research & Experimental
Natalie Eaton-Fitch, Helene Cabanas, Stanley du Preez, Donald Staines, Sonya Marshall-Gradisnik
Summary: The study found that co-localization of TRPM3 with PIP2 was significantly reduced in ME/CFS patients, leading to decreased NK cell cytotoxicity. IL-2 stimulation enhanced NK cell cytotoxic function, indicating a normal response in ME/CFS patients. This suggests a crosstalk between IL-2 and TRPM3 signaling pathways.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Etianne Martini Sasso, Katsuhiko Muraki, Natalie Eaton-Fitch, Peter Smith, Olivia Ly Lesslar, Gary Deed, Sonya Marshall-Gradisnik
Summary: This study found that patients with post COVID-19 condition may have impaired TRPM3 ion channel function and similarities with ME/CFS.
MOLECULAR MEDICINE
(2022)
Article
Immunology
Helene Cabanas, Katsuhiko Muraki, Natalie Eaton-Fitch, Donald Ross Staines, Sonya Marshall-Gradisnik
Summary: The study found that ME/CFS patients taking LDN had restored TRPM3-like ionic currents in NK cells, suggesting LDN may be a potential treatment for ME/CFS. The therapeutic effect of LDN in regulating the underlying mechanisms involving TRPM3 and opioid receptors in NK cells was highlighted. This study may lead to the repurpose of marketed drugs and support prospective randomized clinical studies on the role and dose of NTX in treating ME/CFS patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Environmental Sciences
Stanley Du Preez, Helene Cabanas, Donald Staines, Sonya Marshall-Gradisnik
Summary: The TRP superfamily of ion channels plays a crucial role in neuroimmune interactions and is implicated in various neuroimmune disorders. TRPM7 is identified as a potential candidate in the pathomechanism of ME/CFS due to its key roles in multiple organ systems and limited literature on its role in the disorder. This review discusses TRPM7's biochemistry, its role in neurological and immunological systems, and its potential involvement in the pathophysiology of ME/CFS.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Biochemistry & Molecular Biology
Stanley Du Preez, Natalie Eaton-Fitch, Peter K. Smith, Sonya Marshall-Gradisnik
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystemic condition characterized by impaired natural killer (NK) cell cytotoxicity. This study investigated the role of TRPM7-dependent calcium (Ca2+) influx in ME/CFS patients. The results showed that TRPM7 activation resulted in reduced Ca2+ influx in ME/CFS patients compared to healthy controls, while TRPM7 desensitization led to increased Ca2+ influx in healthy controls compared to ME/CFS patients. These findings suggest that ME/CFS may be a TRP ion channelopathy.
Article
Biochemistry & Molecular Biology
Jessica Maya, Sabrina M. Leddy, C. Gunnar Gottschalk, Daniel L. Peterson, Maureen R. Hanson
Summary: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness characterized by fatigue, inflammatory symptoms, cognitive dysfunction, and post-exertional malaise. This study found that ME/CFS patients have altered fatty acid metabolism in immune cells, specifically Natural Killer cells, CD4+ T cells, and CD8+ T cells. These metabolic shifts may impact T and NK cell effector function and shed light on the mechanism of action of the illness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Natalie Eaton-Fitch, Stanley Du Preez, Helene Cabanas, Katsuhiko Muraki, Donald Staines, Sonya Marshall-Gradisnik
Summary: This study found that the calcium influx in NK cells of ME/CFS patients was impaired. However, the overnight treatment of isolated NK cells with NTX restored the TRPM3-dependent calcium influx. These findings suggest that ME/CFS may be a TRP ion channel disorder and that NTX could be a potential therapeutic intervention.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Xiao-Yu Cheng, Shu-Fang Li, Yong Chen, Ying-Jie Zhao, Wei Hu, Chao Lu, Ren-Peng Zhou
Summary: TRPM7 is a channel protein located on the cell membrane that regulates the balance of intracellular Mg2+. It plays an important role in cell proliferation, adhesion, migration, and is directly related to disease occurrence and development.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Troy Querec, Jin-Mann S. Lin, Yang Chen, Britany Helton, Andreas Kogelnik, Nancy Klimas, Daniel Peterson, Lucinda Bateman, Charles Lapp, Richard Podell, Benjamin Natelson, Elizabeth Unger
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by reduced function and unexplained fatigue. The study found that reduced natural killer (NK) cell count and cytotoxicity, which have been investigated as potential biomarkers for ME/CFS, do not show statistically significant differences between patients with ME/CFS and healthy controls. The results suggest that more studies are needed to explore other immune parameters that may be involved in the pathophysiology of ME/CFS.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Bindu D. Paul, Marian D. Lemle, Anthony L. Komaroff, Solomon H. Snyder
Summary: The review summarizes evidence of biological abnormalities in patients with acute COVID-19 and ME/CFS, including redox imbalance, systemic inflammation, neuroinflammation, impaired ATP generation, and general hypometabolism. Although these phenomena have not been extensively studied in individuals with long COVID-19, understanding these abnormalities may lead to the development of novel therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, General & Internal
Rebekah Maksoud, Chandi Magawa, Natalie Eaton-Fitch, Kiran Thapaliya, Sonya Marshall-Gradisnik
Summary: This systematic review aimed to evaluate potential biomarkers that could effectively differentiate ME/CFS patients from healthy controls. A total of 101 studies were included, and potential biomarkers ranged from genetic/epigenetic, immunological, metabolomics/mitochondrial/microbiome, endovascular/circulatory, neurological, ion channel, to physical dysfunction biomarkers. The findings indicated evidence of immune dysfunction in ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of the illness.
Article
Multidisciplinary Sciences
Andras Szollosi, Janos Almassy
Summary: The TRPM2 cation channel plays a critical role in insulin secretion, immune cell activation, and body heat control. This study demonstrates that the purified nvTRPM2 protein is fully functional when reconstituted into lipid bilayers, and its activation is co-dependent on cytosolic Ca2+ and either ADPR or ADPRP. The results also suggest a high affinity binding of PIP2 or some other activating phosphoinositol lipid to nvTRPM2 under physiological conditions.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Irene Soffritti, Sabine Gravelsina, Maria D'Accolti, Francesca Bini, Eleonora Mazziga, Anda Vilmane, Santa Rasa-Dzelzkaleja, Zaiga Nora-Krukle, Angelika Krumina, Modra Murovska, Elisabetta Caselli
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease without diagnostic biomarkers, but there is evidence supporting a role of herpesviruses and microRNAs in its development. This study found that six out of eight selected microRNAs were differently expressed in ME/CFS patients compared to healthy controls. The levels of these microRNAs correlated with disease severity but not with pro-inflammatory cytokines or HHV-6A/6B genome levels. These results suggest that microRNAs could serve as potential biomarkers and provide insights into ME/CFS pathogenic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Rebekah Maksoud, Cassandra Balinas, Sean Holden, Helene Cabanas, Donald Staines, Sonya Marshall-Gradisnik
Summary: There is currently insufficient evidence on the effectiveness of mitochondrial-targeting nutraceuticals in treating ME/CFS patients. Future well-designed studies are needed to clarify the involvement of mitochondria in the pathomechanism of ME/CFS and the impact of mitochondrial-modifying agents on illness severity.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Varvara A. A. Ryabkova, Natalia Y. Y. Gavrilova, Alina A. A. Poletaeva, Alexander I. I. Pukhalenko, Irina A. A. Koshkina, Leonid P. P. Churilov, Yehuda Shoenfeld
Summary: Recent studies suggest that antibody-mediated autoimmune mechanisms may play a role in fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), specifically in relation to G protein-coupled receptors. However, the full extent of the natural antibody network and its implications in these disorders has not been fully explored.
Article
Medicine, Research & Experimental
Natalie Eaton-Fitch, Stanley Du Preez, Helene Cabanas, Katsuhiko Muraki, Donald Staines, Sonya Marshall-Gradisnik
Summary: This study found that the calcium influx in NK cells of ME/CFS patients was impaired. However, the overnight treatment of isolated NK cells with NTX restored the TRPM3-dependent calcium influx. These findings suggest that ME/CFS may be a TRP ion channel disorder and that NTX could be a potential therapeutic intervention.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Multidisciplinary Sciences
Olga A. Sukocheva, Rebekah Maksoud, Narasimha M. Beeraka, SabbaRao V. Madhunapantula, Mikhail Sinelnikov, Vladimir N. Nikolenko, Margarita E. Neganova, Sergey G. Klochkov, Mohammad Amjad Kamal, Donald R. Staines, Sonya Marshall-Gradisnik
Summary: COVID-19 infection can lead to various pathologies and complications, exacerbating existing conditions in multiple body systems. Besides the respiratory organs, adverse effects of COVID-19 have been observed in the nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems. The post-COVID-19 condition shows overlapping symptoms with ME/CFS.
JOURNAL OF ADVANCED RESEARCH
(2022)
Article
Neurosciences
Kiran Thapaliya, Donald Staines, Sonya Marshall-Gradisnik, Jiasheng Su, Leighton Barnden
Summary: This study found that hippocampal subfield volumes are associated with cognitive and memory problems in ME/CFSICC patients, but not in ME/CFSFukuda patients. ME/CFSICC patients have larger subfield volumes, which are strongly correlated with clinical measures.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Etianne Martini Sasso, Katsuhiko Muraki, Natalie Eaton-Fitch, Peter Smith, Olivia Ly Lesslar, Gary Deed, Sonya Marshall-Gradisnik
Summary: This study found that patients with post COVID-19 condition may have impaired TRPM3 ion channel function and similarities with ME/CFS.
MOLECULAR MEDICINE
(2022)
Editorial Material
Multidisciplinary Sciences
Sonya Marshall-Gradisnik, Natalie Eaton-Fitch
Article
Physiology
Chandi T. T. Magawa, Natalie Eaton-Fitch, Cassandra Balinas, Etianne Martini Sasso, Kiran Thapaliya, Leighton Barnden, Rebekah Maksoud, Breanna Weigel, Penny A. Rudd, Lara J. J. Herrero, Sonya Marshall-Gradisnik
Summary: The study aimed to optimize a high-yield protein extraction method for membrane proteins from NK cells, successfully detecting proteotypic peptides of TRPM3 for future investigations.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Jiasheng Su, Kiran Thapaliya, Natalie Eaton-Fitch, Sonya Marshall-Gradisnik, Leighton Barnden
Summary: This study used functional magnetic resonance imaging to compare the connectivity patterns in the brains of healthy individuals and patients with chronic fatigue syndrome. The results showed significant differences in connectivity between the two groups, indicating that these differences may play a role in the development of chronic fatigue syndrome.
BRAIN CONNECTIVITY
(2023)
Review
Medicine, General & Internal
Rebekah Maksoud, Chandi Magawa, Natalie Eaton-Fitch, Kiran Thapaliya, Sonya Marshall-Gradisnik
Summary: This systematic review aimed to evaluate potential biomarkers that could effectively differentiate ME/CFS patients from healthy controls. A total of 101 studies were included, and potential biomarkers ranged from genetic/epigenetic, immunological, metabolomics/mitochondrial/microbiome, endovascular/circulatory, neurological, ion channel, to physical dysfunction biomarkers. The findings indicated evidence of immune dysfunction in ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of the illness.
Article
Neurosciences
Kiran Thapaliya, Sonya Marshall-Gradisnik, Markus Barth, Natalie Eaton-Fitch, Leighton Barnden
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients share similar neurological, autonomic, pain, and post-exertional symptoms. Comparing brainstem volumes in ME/CFS, long COVID, and healthy control subjects, the study found enlarged volumes in pons and whole brainstem for both ME/CFS and long COVID patients. Positive correlations were found between pons and whole brainstem volumes with pain in ME/CFS, while a strong negative relationship was detected between midbrain volume and breathing difficulty in long COVID patients. The study demonstrated abnormal brainstem volumes consistent with overlapping symptoms in both ME/CFS and long COVID.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Leighton Barnden, Kiran Thapaliya, Natalie Eaton-Fitch, Markus Barth, Sonya Marshall-Gradisnik
Summary: This study compared the brain connectivity in Long-Covid patients and healthy controls using functional magnetic resonance imaging (fMRI). It found differences in connectivity in the brainstem regions of Long-Covid patients, which may be related to their clinical symptoms.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Medicine, Research & Experimental
Asher Taccori, Rebekah Maksoud, Natalie Eaton-Fitch, Maharshi Patel, Sonya Marshall-Gradisnik
Summary: This systematic review aimed to evaluate and summarize the use of urinary biomarkers in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared to healthy controls. The study found significant differences in urinary free cortisol levels between ME/CFS patients and healthy controls, although there was considerable heterogeneity in the results. There is limited evidence suggesting a consistent and specific urinary-based biomarker for ME/CFS, and further standardized research is needed to identify potential diagnostic differences.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Stanley Du Preez, Natalie Eaton-Fitch, Peter K. Smith, Sonya Marshall-Gradisnik
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystemic condition characterized by impaired natural killer (NK) cell cytotoxicity. This study investigated the role of TRPM7-dependent calcium (Ca2+) influx in ME/CFS patients. The results showed that TRPM7 activation resulted in reduced Ca2+ influx in ME/CFS patients compared to healthy controls, while TRPM7 desensitization led to increased Ca2+ influx in healthy controls compared to ME/CFS patients. These findings suggest that ME/CFS may be a TRP ion channelopathy.