ORCID Profile
0000-0001-9270-2437
Current Organisations
Griffith University
,
Griffith University Griffith Health Institute
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Oxford University Press (OUP)
Date: 16-12-2013
Abstract: Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood s les were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.
Publisher: Springer Science and Business Media LLC
Date: 15-07-2021
DOI: 10.1186/S12967-021-02974-4
Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious multifactorial disorder. The origin remains ambiguous, however reduced natural killer (NK) cell cytotoxicity is a consistent immunological feature of ME/CFS. Impaired transient receptor potential melastatin 3 (TRPM3), a phosphatidylinositol dependent channel, and impaired calcium mobilisation have been implicated in ME/CFS pathology. This investigation aimed to examine the localisation of TRPM3 at the NK cell plasma membrane and co-localisation with phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The effect of IL-2 priming and treatment using pregnenolone sulfate (PregS) and ononetin on TRPM3 co-localisation and NK cell cytotoxicity in ME/CFS patients and healthy controls (HC) was also investigated. NK cells were isolated from 15 ME/CFS patients and 15 age- and sex-matched HC. Immunofluorescent technique was used to determine co-localisation of TRPM3 with the NK cell membrane and with PIP 2 of ME/CFS patients and HC. Flow cytometry was used to determine NK cell cytotoxicity. Following IL-2 stimulation and treatment with PregS and ononetin changes in co-localisation and NK cell cytotoxicity were measured. Overnight treatment of NK cells with PregS and ononetin resulted in reduced co-localisation of TRPM3 with PIP 2 and actin in HC. Co-localisation of TRPM3 with PIP 2 in NK cells was significantly reduced in ME/CFS patients compared with HC following priming with IL-2. A significant increase in co-localisation of TRPM3 with PIP 2 was reported following overnight treatment with ononetin within ME/CFS patients and between groups. Baseline NK cell cytotoxicity was significantly reduced in ME/CFS patients however, no changes were observed following overnight incubation with IL-2, PregS and ononetin between HC and ME/CFS patients. IL-2 stimulation significantly enhanced NK cell cytotoxicity in HC and ME/CFS patients. Significant changes in co-localisation suggest PIP 2 -dependent TRPM3 function may be impaired in ME/CFS patients. Stimulation of NK cells with IL-2 significantly enhanced cytotoxic function in ME/CFS patients demonstrating normal function compared with HC. A crosstalk exists between IL-2 and TRPM3 intracellular signalling pathways which are dependent on Ca 2+ influx and PIP 2 . While IL-2R responds to IL-2 binding in vitro, Ca 2+ dysregulation and impaired intracellular signalling pathways impede NK cell function in ME/CFS patients.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2020
DOI: 10.1007/S11136-019-02411-6
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS. Self-reported data collected from 480 in iduals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL. Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties. This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.
Publisher: Hikari, Ltd.
Date: 2014
Publisher: MDPI AG
Date: 11-10-2021
Abstract: (1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multifaceted illness. The pathomechanism, severity and progression of this illness is still being investigated. Stressors have been implicated in symptom exacerbation for ME/CFS, however, there is limited information for an Australian ME/CFS cohort. The aim of this study was to assess the potential effect of life stressors including changes in work, income, or family scenario on symptom severity in an Australian ME/CFS cohort over five months (2) Methods: Australian residents with ME/CFS responded to questions relating to work, income, living arrangement, access to healthcare and support services as well as symptoms experienced (3) Results: thirty-six ME/CFS patients (age: 41.25 ± 12.14) completed all questionnaires (response rate 83.7%). Muscle pain and weakness, orthostatic intolerance and intolerance to extreme temperatures were experienced and fluctuated over time. Sleep disturbances were likely to present as severe. Work and household income were associated with worsened cognitive, gastrointestinal, body pain and sleep symptoms. Increased access to healthcare services was associated with improved symptom presentation (4) Conclusions: life stressors such as work and financial disruptions may significantly contribute to exacerbation of ME/CFS symptoms. Access to support services correlates with lower symptom scores.
Publisher: MDPI AG
Date: 13-10-2021
Abstract: Chronic fatigue syndrome (CFS) is a heterogenous disorder of multiple disabling symptoms with complex manifestations. Network analysis is a statistical and interrogative methodology to investigate the prevalence of symptoms (nodes) and their inter-dependent (inter-nodal) relationships. In the present study, we explored the co-occurrence of symptoms in a cohort of Polish CFS patients using network analysis. A total of 110 patients with CFS were examined (75 females). The mean age of the total s le was 37.93 (8.5) years old while the mean duration of symptoms in years was 4.4 (4). Post-exertional malaise (PEM) was present in 75.45% of patients, unrefreshing sleep was noted in 89.09% and impaired memory or concentration was observed in 87.27% of patients. The least prevalent symptom was tender cervical or axillary lymph nodes, noted in 34.55% of the total s le. Three of the most densely connected nodes were the total number of symptoms, sore throat and PEM. PEM was positively related with impairment in memory or concentration. Both PEM and impairment in memory or concentration presence are related to more severe fatigue measured by CFQ and FIS. PEM presence was positively related with the presence of multi-joint pain and negatively with tender lymph nodes and muscle pain. Sore throat was related with objective and subjective autonomic nervous system impairment. This study helps define symptom presentation of CFS with the pathophysiology of specific systems and links with multidisciplinary contemporary molecular pathology, including comparative MRI.
Publisher: Wiley
Date: 29-06-2017
DOI: 10.1002/NBM.3757
Abstract: Unrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS). This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T
Publisher: Springer Science and Business Media LLC
Date: 21-04-2016
Publisher: Springer Science and Business Media LLC
Date: 31-05-2016
Publisher: Informa UK Limited
Date: 03-2016
DOI: 10.2147/TACG.S99405
Publisher: Oxford University Press (OUP)
Date: 23-11-2016
DOI: 10.1111/CEI.12882
Abstract: Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56dimCD16+NK cells and CD56brightCD16dim/– NK cells. Ca2+ flux and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2-aminoethoxydiphenyl borate (2APB) and ionomycin. Unstimulated CD56brightCD16dim/– NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). Ca2+ flux showed no significant difference between groups. Moreover, PregS-stimulated CD56brightCD16dim/–NK cells showed a significant increase in Ca2+ flux in CFS/ME patients compared with HC. By comparison, unstimulated CD56dimCD16+ NK cells showed no significant difference in both Ca2+ flux and TRPM3 expression. PregS-stimulated CD56dimCD16+ NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca2+ flux. Furthermore, TG-stimulated CD56dimCD16+ NK cells increased K562 cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca2+ flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.
Publisher: MDPI AG
Date: 26-06-2023
DOI: 10.3390/BIOM13071039
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystemic condition. The pathomechanism of ME/CFS remains unestablished however, impaired natural killer (NK) cell cytotoxicity is a consistent feature of this condition. Calcium (Ca2+) is crucial for NK cell effector functions. Growing research recognises Ca2+ signalling dysregulation in ME/CFS patients and implicates transient receptor potential ion channel dysfunction. TRPM7 (melastatin) was recently considered in the pathoaetiology of ME/CFS as it participates in several Ca2+-dependent processes that are central to NK cell cytotoxicity which may be compromised in ME/CFS. TRPM7-dependent Ca2+ influx was assessed in NK cells isolated from n = 9 ME/CFS patients and n = 9 age- and sex-matched healthy controls (HCs) using live cell fluorescent imaging techniques. Slope (p 0.05) was significantly reduced in ME/CFS patients compared with HCs following TRPM7 activation. Half-time of maximal response (p 0.05) and litude (p 0.001) were significantly reduced in the HCs compared with the ME/CFS patients following TRPM7 desensitisation. Findings from this investigation suggest that TRPM7-dependent Ca2+ influx is reduced with agonism and increased with antagonism in ME/CFS patients relative to the age- and sex-matched HCs. The outcomes reported here potentially reflect TRPM3 dysfunction identified in this condition suggesting that ME/CFS is a TRP ion channelopathy.
Publisher: Informa UK Limited
Date: 03-2013
DOI: 10.2147/CLEP.S39876
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.ANNEPIDEM.2013.04.003
Abstract: Prevalence estimates have been based on several case definitions of chronic fatigue syndrome (CFS). The purpose of this work is to provide a rigorous overview of their application in prevalence research. A systematic review of primary studies reporting the prevalence of CFS since 1990 was conducted. Studies were summarized according to study design, prevalence estimates, and case definition used to ascertain cases. Thirty-one studies were retrieved, and eight different case definitions were found. Early estimates of CFS prevalence were based on the 1988 Centers for Disease Control and Prevention, Australian, and Oxford. The 1994 Centers for Disease Control and Prevention, however, has been adopted internationally, as a general standard. Only one study has reported prevalence according to the more recent, Canadian Consensus Criteria. Additional estimates were also found according to definitions by Ho-Yen, the 2005 Centers for Disease Control and Prevention empirical definition, and an epidemiological case definition. Advances in clinical case definitions during the past 10 years such as the Canadian Consensus Criteria have received little attention in prevalence research. Future assessments of prevalence should consider adopting more recent developments, such as the newly available International Consensus Criteria. This move could improve the surveillance of more specific cases found within CFS.
Publisher: SAGE Publications
Date: 11-11-2016
Abstract: The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca 2+ ) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients. A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software. Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3′ untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group. This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca 2+ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.
Publisher: Public Library of Science (PLoS)
Date: 30-04-2020
Publisher: Elsevier BV
Date: 2018
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.2147/CLEP.S96797
Publisher: Allergy, Asthma, and Immunology Association of Thailand
Date: 2017
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.JAD.2012.03.037
Abstract: Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME. Natural Killer (NK) and CD8(+)T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n=28 mean age=41.8±9.6 years and controls, n=28 mean age=45.3±11.7 years), via negative cell enrichment. Following total RNA extraction and subsequent synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of nineteen miRNAs. There was a significant reduction in the expression levels of miR-21, in both the NK and CD8(+)T cells in the CFS/ME sufferers. Additionally, the expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 was significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls. The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required. Collectively these miRNAs have been associated with apoptosis, cell cycle, development and immune function. Changes in miRNAs in cytotoxic cells may reduce the functional capacity of these cells and disrupt effective cytotoxic activity along with other immune functions in CFS/ME patients.
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 28-04-2016
DOI: 10.1002/JMRI.25283
Publisher: Springer Science and Business Media LLC
Date: 10-05-2019
Publisher: Public Library of Science (PLoS)
Date: 19-09-2014
Publisher: Informa UK Limited
Date: 03-2009
DOI: 10.2147/OPTH.S5356
Publisher: Wiley
Date: 11-2006
DOI: 10.1111/J.1365-3083.2006.01805.X
Abstract: Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2022
DOI: 10.1186/S10020-022-00528-Y
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic condition associated with post-infectious onset, impaired natural killer (NK) cell cytotoxicity and impaired ion channel function, namely Transient Receptor Potential Melastatin 3 (TRPM3). Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has resulted in neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations recently recognised as post coronavirus disease 2019 (COVID-19) condition. The symptomatology of ME/CFS overlaps significantly with post COVID-19 therefore, this research aimed to investigate TRPM3 ion channel function in post COVID-19 condition patients. Whole-cell patch-cl technique was used to measure TRPM3 ion channel activity in isolated NK cells of N = 5 ME/CFS patients, N = 5 post COVID-19 patients, and N = 5 healthy controls (HC). The TRPM3 agonist, pregnenolone sulfate (PregS) was used to activate TRPM3 function, while ononetin was used as a TRPM3 antagonist. As reported in previous research, PregS-induced TRPM3 currents were significantly reduced in ME/CFS patients compared with HC (p = 0.0048). PregS-induced TRPM3 litude was significantly reduced in post COVID-19 condition compared with HC (p = 0.0039). Importantly, no significant difference was reported in ME/CFS patients compared with post COVID-19 condition as PregS-induced TRPM3 currents of post COVID-19 condition patients were similar of ME/CFS patients currents (p 0.9999). Isolated NK cells from post COVID-19 condition and ME/CFS patients were resistant to ononetin and differed significantly with HC (p 0.0001). The results of this investigation suggest that post COVID-19 condition patients may have impaired TRPM3 ion channel function and provide further evidence regarding the similarities between post COVID-19 condition and ME/CFS. Impaired TRPM3 channel activity in post COVID-19 condition patients suggest impaired ion mobilisation which may consequently impede cell function resulting in chronic post-infectious symptoms. Further investigation into TRPM3 function may elucidate the pathomechanism, provide a diagnostic and therapeutic target for post COVID-19 condition patients and commonalities with ME/CFS patients.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2018
Publisher: Scientific Research Publishing, Inc.
Date: 2018
Publisher: Elsevier BV
Date: 2020
Publisher: Allergy, Asthma, and Immunology Association of Thailand
Date: 2016
DOI: 10.12932/AP0733
Publisher: Bentham Science Publishers Ltd.
Date: 06-01-2014
DOI: 10.2174/2211536604666141218154252
Abstract: MicroRNAs (miRNA) are small (~22 nucleotide] non-coding RNA molecules originally characterised as nonsense or junk DNA. Emerging research suggests that these molecules have erse regulatory roles in an array of molecular, cellular and physiological processes. MiRNAs are versatile and highly stable molecules, therefore, they are able to exist as intracellular or extracellular miRNAs. The purpose of this paper is to review the function and role of miRNAs in the intracellular space with specific focus on the interactions between miRNAs and organelles such as the mitochondria and the rough endoplasmic reticulum. Understanding the role of miRNAs in the intracellular space may be vital in understanding the mechanism of certain diseases.
Publisher: Frontiers Media SA
Date: 31-10-2019
Publisher: Ivyspring International Publisher
Date: 2015
DOI: 10.7150/IJMS.12399
Publisher: Springer Science and Business Media LLC
Date: 24-08-2019
Publisher: Frontiers Media SA
Date: 02-03-2023
DOI: 10.3389/FNINS.2023.1125208
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla. Group comparisons with HC detected significantly larger volumes in ME/CFS for pons ( p = 0.004) and whole brainstem ( p = 0.01), and in long COVID for pons ( p = 0.003), superior cerebellar peduncle ( p = 0.009), and whole brainstem ( p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.” In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.
Publisher: Frontiers Media SA
Date: 22-06-2023
DOI: 10.3389/FNINS.2023.1182607
Abstract: Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection. Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippoc us and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores. Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI. Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep–wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2020
DOI: 10.1186/S12967-020-02452-3
Abstract: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls. Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes. Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.
Publisher: Informa UK Limited
Date: 19-11-2014
Publisher: Wiley
Date: 15-08-2021
DOI: 10.1111/EJN.15413
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a variety of physical and neurological complaints indicating the central nervous system plays a role in ME/CFS pathophysiology. Diffusion tensor imaging (DTI) has been used to study microstructural changes in neurodegenerative diseases. In this study, we evaluated DTI parameters to investigate microstructural abnormalities in ME/CFS patients. We estimated DTI parameters in 25 ME/CFS patients who met Fukuda criteria (ME/CFS Fukuda ), 18 ME/CFS patients who met International Consensus Criteria (ICC) (ME/CFS ICC ) only and 26 healthy control (HC) subjects. In addition to voxel‐based DTI‐parameter group comparisons, we performed voxel‐based DTI‐parameter interaction‐with‐group regressions with clinical and autonomic measures to test for abnormal regressions. Group comparisons between ME/CFS ICC and HC detected significant clusters (a) with decreased axial diffusivity ( p = .001) and mean diffusivity ( p = .01) in the descending cortico‐cerebellar tract in the midbrain and pons and (b) with increased transverse diffusivity in the medulla. The mode of anisotropy was significantly decreased ( p = .001) in a cluster in the superior longitudinal fasciculus region. Voxel‐based group comparisons between ME/CFS Fukuda and HC did not detect significant clusters. For ME/CFS ICC and HC, DTI parameter interaction‐with‐group regressions were abnormal for the clinical measures of information processing score, SF36 physical, sleep disturbance score and respiration rate in both grey and white matter regions. Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFS ICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS.
Publisher: OMICS Publishing Group
Date: 2015
Publisher: SAGE Publications
Date: 2015
DOI: 10.4137/III.S25147
Abstract: The transient receptor potential (TRP) superfamily in humans comprises 27 cation channels with permeability to monovalent and alent cations. These channels are widely expressed within humans on cells and tissues and have significant sensory and regulatory roles on most physiological functions. Chronic fatigue syndrome (CFS) is an unexplained disorder with multiple physiological impairments. The purpose of this study was to determine the role of TRPs in CFS. The study comprised 115 CFS patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years). CFS patients were defined according to the 1994 Center for Disease Prevention and Control criteria for CFS. A total of 240 single nucleotide polymorphisms (SNPs) for 21 mammalian TRP ion channel genes ( TRPA1, TRPC1, TRPC2, TRPC3, TRPC4, TRPC6, TRPC7, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Thirteen SNPs were significantly associated with CFS patients compared with the controls. Nine of these SNPs were associated with TRPM3 (rs12682832 P 0.003, rs11142508 P 0.004, rs1160742 P 0.08, rs4454352 P 0.013, rs1328153 P 0.013, rs3763619 P 0.014, rs7865858 P ≤ 0.021, rs1504401 P ≤ 0041, rs10115622 P ≤ 0.050), while the remainder were associated with TRPA1 (rs2383844 P ≤ 0.040, rs4738202 P ≤ 0.018) and TRPC4 (rs6650469 P ≤ 0.016, rs655207 P ≤ 0.018). The data from this pilot study suggest an association between TRP ion channels, predominantly TRPM3 and CFS. This and other TRPs identified may contribute to the etiology and pathomechanism of CFS.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2023
DOI: 10.1186/S12967-023-04295-0
Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is currently no universal diagnostic marker or targeted treatment for ME/CFS. Urine is a non-invasive s le that provides biomarkers that may have the potential to be used in a diagnostic capacity for ME/CFS. While there are several studies investigating urine-based biomarkers for ME/CFS, there are no published systematic reviews to summarise existing evidence of these markers. The aim of this systematic review was to compile and appraise literature on urinary-based biomarkers in ME/CFS patients compared with healthy controls. Three databases: Embase, PubMed, and Scopus were searched for articles pertaining to urinary biomarkers for ME/CFS compared with healthy controls published between December 1994 to December 2022. The final articles included in this review were determined through application of specific inclusion and exclusion criteria. Quality and bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A meta-analysis according to Cochrane guidelines was conducted on select studies, in particular, those that investigate urinary free cortisol levels in ME/CFS patients compared to healthy controls using the program STATA 17. Twenty-one studies were included in this review. All of the studies investigated urinary-based markers in ME/CFS patients compared with healthy controls. The reported changes in urinary outputs include urinary free cortisol (38.10%), carnitine (28.6%), iodine (4.76%), and the metabolome (42.86%). In most cases, there was minimal overlap in the main outcomes measured across the studies, however, differences in urinary free cortisol between ME/CFS patients and healthy controls were commonly reported. Seven studies investigating urinary free cortisol were included in the meta-analysis. While there were significant differences found in urinary free cortisol levels in ME/CFS patients, there was also substantial heterogeneity across the included studies that makes drawing conclusions difficult. There is limited evidence suggesting a consistent and specific potential urinary-based biomarker for ME/CFS. Further investigations using more standardised methodologies and more stringent case criteria may be able to identify pathophysiological differences with diagnostic potential in ME/CFS patients compared with healthy controls.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2012
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: Frontiers Media SA
Date: 13-07-2021
DOI: 10.3389/FIMMU.2021.687806
Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-systemic chronic condition of unknown aetiology classified as an immune dysfunction syndrome and neurological disorder. The discovery of the widely expressed Transient Receptor Potential Melastatin 3 (TRPM3) as a nociceptor channel substantially targeted by certain opioid receptors, and its implication in calcium (Ca 2+ )-dependent Natural Killer (NK) cell immune functions has raised the possibility that TRPM3 may be pharmacologically targeted to treat characteristic symptoms of ME/CFS. Naltrexone hydrochloride (NTX) acts as an antagonist to the mu (μ)-opioid receptor thus negating its inhibitory function on TRPM3. Based on the benefits reported by patients on their symptoms, low dose NTX (LDN, 3.0–5.0 mg/day) treatment seems to offer some potential benefit suggesting that its effect may be targeted towards the pathomechanism of ME/CFS. As there is no literature confirming the efficacy of LDN for ME/CFS patients in vitro , this study investigates the potential therapeutic effect of LDN in ME/CFS patients. TRPM3 ion channel activity was measured after modulation with Pregnenolone sulfate (PregS) and ononetin in NK cells on 9 ME/CFS patients taking LDN and 9 age- and sex-matched healthy controls using whole-cell patch-cl technique. We report that ME/CFS patients taking LDN have restored TRPM3-like ionic currents in NK cells. Small ionic currents with a typical TRPM3-like outward rectification were measured after application of PregS, a TRPM3-agonist, in NK cells from patients taking LDN. Additionally, PregS-evoked ionic currents through TRPM3 were significantly modulated by ononetin, a TRPM3-antagonist, in NK cells from ME/CFS patients taking LDN. These data support the hypothesis that LDN may have potential as a treatment for ME/CFS by characterising the underlying regulatory mechanisms of LDN treatment involving TRPM3 and opioid receptors in NK cells. Finally, this study may serve for the repurpose of marketed drugs, as well as support the approval of prospective randomized clinical studies on the role and dose of NTX in treating ME/CFS patients.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.CLINTHERA.2016.04.038
Abstract: The pathogenesis of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is complex and remains poorly understood. Evidence regarding the use of drug therapies in CFS/ME is currently limited and conflicting. The aim of this systematic review was to examine the existing evidence on the efficacy of drug therapies and determine whether any can be recommended for patients with CFS/ME. MEDLINE, EMBASE, and PubMed databases were searched from the start of their records to March 2016 to identify relevant studies. Randomized controlled trials focusing solely on drug therapy to alleviate and/or eliminate chronic fatigue symptoms were included in the review. Any trials that considered graded exercise therapy, cognitive behavior therapy, adaptive pacing, or any other nonpharmaceutical treatment plans were excluded. The inclusion criteria were examined to ensure that study participants met specific CFS/ME diagnostic criteria. Study size, intervention, and end point outcome domains were summarized. A total of 1039 studies were identified with the search terms 26 studies met all the criteria and were considered suitable for review. Three different diagnostic criteria were identified: the Holmes criteria, International Consensus Criteria, and the Fukuda criteria. Primary outcomes were identified as fatigue, pain, mood, neurocognitive dysfunction and sleep quality, symptom severity, functional status, and well-being or overall health status. Twenty pharmaceutical classes were trialed. Ten medications were shown to be slightly to moderately effective in their respective study groups (P < 0.05). These findings indicate that no universal pharmaceutical treatment can be recommended. The unknown etiology of CFS/ME, and complications arising from its heterogeneous nature, contributes to the lack of clear evidence for pharmaceutical interventions. However, patients report using a large number and variety of medications. This finding highlights the need for trials with clearly defined CFS/ME cohorts. Trials based on more specific criteria such as the International Consensus Criteria are recommended to identify specific subgroups of patients in whom treatments may be beneficial.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2018
Publisher: S. Karger AG
Date: 24-09-2009
DOI: 10.1159/000242461
Abstract: There are limited investigations which have examined the relationship between neutrophil activation and erythrocyte aggregation in older persons. The purpose of the present study was to investigate the relationship between neutrophil activation and erythrocyte aggregation (EA) in an aging population. Twenty-eight male and female subjects were allocated into one of four groups with 7 participants in each group (group 1, 20–29 years group 2, 30–39 years group 3, 40–49 years group 4, 50–59 years). EA was determined using the Myrenne aggregometer. Neutrophil function (respiratory burst and phagocytic activity) was assessed using flow cytometry. EA was found to increase with age. An ANOVA showed a significant (p 0.05) increase for EA in autologous plasma in group 4 compared to groups 1 and 2. An ANOVA and Pearson’s correlation showed that phagocytic activity decreased with age. Furthermore, a positive correlation between stimulated phagocytic activity and erythrocyte aggregability at low shear in 3% dextran-70 solution was observed. The current investigation suggests a decrease in neutrophil phagocytic activity with age and EA was increased with age. Additionally, the current study is novel as it suggests a possible relationship between neutrophil phagocytic activity and erythrocyte aggregability.
Publisher: MDPI AG
Date: 12-06-2026
Abstract: The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS. In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.
Publisher: Scientific Research Publishing, Inc.
Date: 2018
Publisher: Informa UK Limited
Date: 20-12-2014
DOI: 10.1080/07399332.2014.962139
Abstract: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a physical and cognitive disabling illness, characterized by severe fatigue and a range of physiological symptoms, that primarily affects women. The immense variation in clinical presentation suggests differences in severity based on symptomology and physical and cognitive functional capacities. In this article, we examine a number of severity scales used in assessing severity of patients with CFS/ME and the clinical aspects of CFS/ME severity subgroups. The use of severity scales may be important in CFS/ME because it permits the establishment of subgroups that may improve accuracy in both clinical and research settings.
Publisher: Bentham Science Publishers Ltd.
Date: 05-2011
DOI: 10.2174/138955711795445907
Abstract: Anabolic androgenic steroids (AAS) are artificial substances, acting through androgen receptors and were primarily developed for the treatment of hypogonadism, tumors, hypercalcemia, hypercalcuria and other chronic diseases. The discovery, in the early 1930s that these substances may have other benefits related to improvement in physique and athletic performance, has encouraged extensive use of these substances by amateur and professional athletes and members of the general public. The range of AAS used can be classified as either endogenous or exogenous. When used for ergogenic or recreational purposes the dosage is more often higher than the recommended dosage, and at supraphysiological levels, AAS can cause a number of serious side effects including liver dysfunction, myocardial infarction and potentially stroke, due to its ability to increase platelet and platelet aggregation. Furthermore, these high dosages may or can affect other physiological systems including the immune system. Hence, this paper reviews the current research on the effects of a number of specific AAS in the immune system.
Publisher: SNF Swedish Nutrition Foundation
Date: 07-06-2021
Publisher: Wiley
Date: 22-08-2011
Publisher: Wiley
Date: 22-01-2017
DOI: 10.1111/JHN.12435
Publisher: Mary Ann Liebert Inc
Date: 04-2023
Abstract: Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with unknown pathophysiology. Functional MRI (fMRI) studies in ME/CFS have reported disparate connectivities for the brain salience (SA) and default mode (DMN) networks. In this study, we acquired resting state and task fMRI with an advanced scanner for improved subject numbers: 24 healthy controls (HC) and 42 ME/CFS patients, 18 meeting International Consensus Criteria (ICC) and 24 meeting Fukuda criteria. We evaluated mean FC between SA and DMN network hub, and subcortical regions known to be involved in ME/CFS. We tested the hypothesis that ME/CFS connectivity differed from HC and the ICC and Fukuda classes are distinguished by different connectivities with HC for different pairs of SA, DMN or subcortical hubs. During resting state fMRI only two connections differed from HC, both for Fukuda ME/CFS and both with an SA hub. During task fMRI 10 ME/CFS connections differed from HC, 5 for ICC and 5 for Fukuda. None were common to both classes. Eight of the 10 different connections involved an SA hub, six of 10 were weaker in ME/CFS, 4 stronger. SA connections to the hippoc us and brainstem reticular activation system (RAS) differed from and were stronger than HC. The SA mediates the relative activity of the DMN and executive networks and imbalance will have functional consequences. The RAS and hippoc us modulate cortical activation. Different regulatory connections are consistent with the impaired cognitive performance and sleep-wake cycle of ME/CFS. Different neuropathology is involved in ICC and Fukuda classes.
Publisher: Wiley
Date: 15-12-2016
DOI: 10.1111/SJI.12388
Abstract: Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56(dim) CD16(+) and CD56(bright) CD16(+/-) NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56(bright) CD16(+/-) NK cells and expression of CD94 was significantly increased on CD56(dim) CD16(+) NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56(dim) CD16(+) NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2019
DOI: 10.1186/S13643-019-1202-6
Abstract: Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS. Medline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells’ features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist. Seventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies. A consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.
Publisher: Hindawi Limited
Date: 2008
DOI: 10.1155/2008/792428
Abstract: Vasoactive neuropeptides (VNs) such as pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) have critical roles as neurotransmitters, vasodilators including perfusion and hypoxia regulators, as well as immune and nociception modulators. They have key roles in blood vessels in the central nervous system (CNS) including maintaining functional integrity of the blood brain barrier (BBB) and blood spinal barrier (BSB). VNs are potent activators of adenylate cyclase and thus also have a key role in cyclic AMP production affecting regulatory T cell and other immune functions. Virchow-Robin spaces (VRSs) are perivascular compartments surrounding small vessels within the CNS and contain VNs. Autoimmunity of VNs or VN receptors may affect BBB and VRS function and, therefore, may contribute to the aetiology of neurological-related conditions including multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. VN autoimmunity will likely affect CNS and immunological homeostasis. Various pharmacological and immunological treatments including phosphodiesterase inhibitors and plasmapheresis may be indicated.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-09-2022
Abstract: Myalgic encephalomyelitis and Long Covid have overlapping presentation
Publisher: Scientific Research Publishing, Inc.
Date: 2012
Publisher: Elsevier BV
Date: 03-2010
Publisher: Springer Science and Business Media LLC
Date: 16-02-2022
DOI: 10.1186/S12967-022-03297-8
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious disorder of unknown aetiology. While the pathomechanism of ME/CFS remains elusive, reduced natural killer (NK) cell cytotoxic function is a consistent immunological feature. NK cell effector functions rely on long-term sustained calcium (Ca 2+ ) influx. In recent years evidence of transient receptor potential melastatin 3 (TRPM3) dysfunction supports the hypothesis that ME/CFS is potentially an ion channel disorder. Specifically, reports of single nucleotide polymorphisms, low surface expression and impaired function of TRPM3 have been reported in NK cells of ME/CFS patients. It has been reported that mu (µ)-opioid receptor (µOR) agonists, known collectively as opioids, inhibit TRPM3. Naltrexone hydrochloride (NTX), a µOR antagonist, negates the inhibitory action of µOR on TRPM3 function. Importantly, it has recently been reported that NTX restores impaired TRPM3 function in NK cells of ME/CFS patients. Live cell immunofluorescent imaging was used to measure TRPM3-dependent Ca 2+ influx in NK cells isolated from n = 10 ME/CFS patients and n = 10 age- and sex-matched healthy controls (HC) following modulation with TRPM3-agonist, pregnenolone sulfate (PregS) and TRPM3-antaognist, ononetin. The effect of overnight (24 h) NTX in vitro treatment on TRPM3-dependent Ca 2+ influx was determined. The litude (p 0.0001) and half-time of Ca 2+ response (p 0.0001) was significantly reduced at baseline in NK cells of ME/CFS patients compared with HC. Overnight treatment of NK cells with NTX significantly improved TRPM3-dependent Ca 2+ influx in ME/CFS patients. Specifically, there was no significance between HC and ME/CFS patients for half-time response, and the litude of Ca 2+ influx was significantly increased in ME/CFS patients (p 0.0001). TRPM3-dependent Ca 2+ influx was restored in ME/CFS patients following overnight treatment of isolated NK cells with NTX in vitro. Collectively, these findings validate that TRPM3 loss of function results in altered Ca 2+ influx supporting the growing evidence that ME/CFS is a TRP ion channel disorder and that NTX provides a potential therapeutic intervention for ME/CFS.
Publisher: MDPI AG
Date: 12-11-2021
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder. Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca2+) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP2 and participates in Ca2+ signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown. This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP2 and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger s le size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2011
DOI: 10.1186/S12967-021-02742-4
Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS. A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale. Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters. There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.
Publisher: Wiley
Date: 31-03-2022
DOI: 10.1002/JNR.25048
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippoc us plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippoc us in ME/CFS. We estimated hippoc al subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFS Fukuda ), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFS ICC ), and 25 healthy controls (HC). Group comparisons with HC detected extensive differences in subfield volumes in ME/CFS ICC but not in ME/CFS Fukuda . ME/CFS ICC patients had significantly larger volume in the left subiculum head ( p 0.001), left presubiculum head ( p = 0.0020), and left fimbria ( p = 0.004). Correlations of hippoc us subfield volumes with clinical measures were stronger in ME/CFS ICC than in ME/CFS Fukuda patients. In ME/CFS Fukuda patients, we detected positive correlations between fatigue and hippoc us subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume. In ME/CFS ICC patients, we detected a strong negative relationship between fatigue and left hippoc us tail volume. Strong negative relationships were also detected between pain and SF36 physical scores and two hippoc al subfield volumes (left: GC‐ML‐DG head and CA4 head). Our study demonstrated that volumetric differences in hippoc al subfields have strong statistical inference for patients meeting the ME/CFS ICC case definition and confirms hippoc al involvement in the cognitive and memory problems of ME/CFS ICC patients.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2013
Publisher: Springer Science and Business Media LLC
Date: 14-09-2015
Publisher: Wiley
Date: 08-2003
Publisher: Springer Science and Business Media LLC
Date: 20-02-2018
DOI: 10.1007/S12602-018-9397-8
Abstract: Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use. Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms). The level of evidence identified for the use of probiotics in IBS was excellent in quality however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.
Publisher: Walter de Gruyter GmbH
Date: 03-03-2009
DOI: 10.2478/S11535-008-0058-X
Abstract: Androgenic anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. AAS are used by athletes and recreational users of all ages to enhance their athletic performance and/or physical appearance. While several adverse effects of AAS abuse have been described, their effect on the immune system has not been clearly elucidated. The literature generally indicates that supraphysiologic doses of AAS with an intact steroid nucleus are immunosuppressive, that is they reduce immune cell number and function. While those with alterations to the steroid nucleus are immunostimulatory as they induce the proliferation of T cells and other immune cells. Specifically, several common AAS have been shown to adversely influence lymphocyte differentiation and proliferation, antibody production, Natural Killer Cytotoxic activity and the production of certain cytokines, thereby altering the immune reaction. These effects may be profound and long lasting depending on the dosing regime, types or combinations of AAS used and the extent and duration of AAS abuse. Nevertheless, the effects of long term use of supraphysiologic doses of AAS on the immune system remain uncertain.
Publisher: OMICS Publishing Group
Date: 2014
Publisher: American Physiological Society
Date: 10-2008
DOI: 10.1152/JAPPLPHYSIOL.01281.2007
Abstract: The purpose of this study was to elucidate the effect of normal fluctuating [non-monophasic oral contraceptive pill (MOCP) users] and low, consistent (MOCP users) endogenous plasma estrogen levels on the strain behavior of the Achilles tendon in vivo. Twenty women (age 28.0 ± 4.2 yr, height 1.67 ± 0.07 m, mass 61.6 ± 6.8 kg) who had been using the MOCP for at least 12 mo together with 20 matched women who were non-MOCP users (age 31.9 ± 7.3 yr, height 1.63 ± 0.05 m, mass 62.5 ± 5.9 kg) participated in this study. Non-MOCP users were tested at the time of lowest (menstruation) and highest (≈ovulation) estrogen, whereas MOCP users, who exhibited constant and attenuated endogenous estrogen levels, were tested at day 1 and day 14 of their cycle. At each test session, maximal isometric plantarflexion efforts were performed on a calf-raise apparatus while synchronous real-time ultrasonography of the triceps surae aponeurosis was recorded. Achilles tendon strain (%) was calculated by iding tendon displacement during plantarflexion by resting tendon length. Repeated-measures ANOVA revealed a significant ( P 0.05) main effect of subject group with significantly lower Achilles strain (25.5%) in the MOCP users compared with the non-MOCP users. In conclusion, acute fluctuations in plasma estrogen across the menstrual cycle in non-MOCP users did not alter the strain behavior of the Achilles tendon. Conversely, long-term exposure to attenuated estrogen in MOCP users resulted in a decrease in Achilles tendon strain, which is thought to be attributed to the effects of endogenous estrogen on collagen synthesis. These findings have a number of important functional and clinical implications.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
DOI: 10.1519/R-18395.1
Publisher: SAGE Publications
Date: 2016
DOI: 10.4137/GRSB.S40036
Abstract: The etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME. Messenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT) NanoString Technologies) from moderate ( n = 11 age, 54.9 ± 10.3 years) and severe ( n = 12 age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls ( n = 11 age, 50.0 ± 12.3 years). The expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls. In severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.
Publisher: BMJ
Date: 23-02-2019
DOI: 10.1136/ARCHDISCHILD-2018-316450
Abstract: To estimate the paediatrician-diagnosed incidence of chronic fatigue syndrome (CFS) in Australia, and describe demographic and clinical features, as well as approaches to diagnosis and management. The Australian Paediatric Surveillance Unit facilitates monthly national surveillance of uncommon conditions seen by paediatricians. Data from young people aged years diagnosed with CFS were collected. Incidence was estimated based on new cases reported from April 2015 to April 2016. A total of 164 cases of newly diagnosed CFS in young people aged 4–17 years were identified for inclusion. The estimated national incidence for children aged 4–9 years was 0.25 per 100 000 per annum. In children aged 10–17 years, the estimated incidence of paediatrician-diagnosed cases for Victoria (17.48 per 100 000) was substantially greater than other Australian states (range 1.31–5.51 per 100 000). Most cases were female and Caucasian, most commonly presenting after an infectious illness with symptoms gradual in onset. The majority were diagnosed at least 13 months after symptom onset. Symptoms, associations, investigations and management strategies were highly variable. Current findings suggest that, consistent with other countries, the Australian incidence of CFS in children aged years is very low. In contrast, the national incidence of CFS in older children and adolescents (aged 10–17 years) is more unclear, with marked variability between geographical regions apparent. This may be due to variation in service accessibility and clinician understanding of CFS. Accordingly, national initiatives to improve equity of care for children with CFS may be required.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2010
DOI: 10.1007/S00421-010-1756-4
Abstract: Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4(+) (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4(+)/CD8(+) ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74 ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4(+)/CD8(+) ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.
Publisher: Scientific Research Publishing, Inc.
Date: 2018
Publisher: OMICS Publishing Group
Date: 2014
Publisher: MDPI AG
Date: 11-05-2021
DOI: 10.3390/HEALTHCARE9050568
Abstract: (1) Background—Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifaceted illness characterized by profound and persistent fatigue unrelieved by rest along with a range of other debilitating symptoms. Experiences of unrefreshing and disturbed sleep are frequently described by ME/CFS patients. This is the first systematic review assessing sleep characteristics in ME/CFS. The aim of this review is to determine whether there are clinical characteristics of sleep in ME/CFS patients compared to healthy controls using objective measures such as polysomnography and multiple sleep latency testing. (2) Methods—the following databases—Pubmed, Embase, Medline (EBSCO host) and Web of Science, were systematically searched for journal articles published between January 1994 to 19 February 2021. Articles that referred to polysomnography or multiple sleep latency testing and ME/CFS patients were selected, and further refined through use of specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute checklist. (3) Results—twenty observational studies were included in this review. The studies investigated objective measures of sleep quality in ME/CFS. Subjective measures including perceived sleep quality and other quality of life factors were also described. (4) Conclusions—Many of the parameters measured including slow- wave sleep, apnea- hypopnea index, spectral activity and multiple sleep latency testing were inconsistent across the studies. The available research on sleep quality in ME/CFS was also limited by recruitment decisions, confounding factors, small s le sizes and non-replicated findings. Future well-designed studies are required to understand sleep quality in ME/CFS patients.
Publisher: Scientific Research Publishing, Inc.
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 28-05-2011
Abstract: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients. We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8 + T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4 + T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56 bright and CD56 dim ) and regulatory T cells expressing FoxP3 transcription factor. Compared to healthy in iduals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4 + CD25 + T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8 + T cells and NK phenotypes, in particular the CD56 bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.
Publisher: Mary Ann Liebert Inc
Date: 02-2018
Abstract: The chronic fatigue syndrome (CFS)/myalgic encephalomyelitis is a debilitating disease with unknown pathophysiology and no diagnostic test. This study investigated the default mode network (DMN) to understand the pathophysiology of CFS and to identify potential biomarkers. Using functional MRI (fMRI) collected from 72 subjects (45 CFS and 27 controls) with a temporal resolution of 0.798 sec, we evaluated the DMN using static functional connectivity (FC), dynamic functional connectivity (DFC) and DFC complexity, blood oxygenation level dependent (BOLD) activation maps, and complexity of activity. General linear model univariate analysis was used for intergroup comparison to account for age and gender differences. Hierarchical regression analysis was used to test whether fMRI measures could be used to explain variances of health scores. BOLD signals in the posterior cingulate cortex (PCC), the driving hub in the DMN, were more complex in CFS in both resting state and task (p < 0.05). The FCs between medial prefrontal cortex (mPFC) and both inferior parietal lobules (IPLs) were weaker (p < 0.05) during resting state, whereas during task mPFC-left IPL and mPFC-PCC were weaker (p < 0.05). The DFCs between the DMN hubs were more complex in CFS (p < 0.05) during task. Each of these differences accounted for 7-11% variability of health scores. This study showed that DMN activity is more complex and less coordinated in CFS, suggesting brain network analysis could be potentially used as a diagnostic biomarker for CFS.
Publisher: Elsevier BV
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 11-11-2016
Publisher: Springer Science and Business Media LLC
Date: 24-05-2023
DOI: 10.1186/S12916-023-02893-9
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems. There is currently no known diagnostic biomarker instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated. The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing “biomarker” and “ME/CFS” keywords in the abstract or title and if they included the following criteria: (1) were observational studies published between December 1994 and April 2022 (2) involved adult human participants (3) full text is available in English (4) original research (5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015) (6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A total of 101 publications were included in this systematic review. Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%). Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers. Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment. All potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker. Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness. The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.
Publisher: OMICS Publishing Group
Date: 2013
Publisher: Frontiers Media SA
Date: 23-09-2022
DOI: 10.3389/FPHYS.2022.947723
Abstract: Introduction: Mutations and misfolding of membrane proteins are associated with various disorders, hence they make suitable targets in proteomic studies. However, extraction of membrane proteins is challenging due to their low abundance, stability, and susceptibility to protease degradation. Given the limitations in existing protocols for membrane protein extraction, the aim of this investigation was to develop a protocol for a high yield of membrane proteins for isolated Natural Killer (NK) cells. This will facilitate genetic analysis of membrane proteins known as transient receptor potential melastatin 3 (TRPM3) ion channels in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research. Methods: Two protocols, internally identified as Protocol 1 and 2, were adapted and optimized for high yield protein extraction. Protocol 1 utilized ultrasonic and salt precipitation, while Protocol 2 implemented a detergent and chloroform/methanol approach. Protein concentrations were determined by the Pierce Bicinchoninic Acid (BCA) and the Bio-Rad DC (detergent compatible) protein assays according to manufacturer’s recommendation. Using Protocol 2, protein s les were extracted from NK cells of n = 6 healthy controls (HC) and n = 4 ME/CFS patients. In silico tryptic digest and enhanced signature peptide (ESP) predictor were used to predict high-responding TRPM3 tryptic peptides. Trypsin in-gel digestion was performed on protein s les loaded on SDS-PAGE gels (excised at 150–200 kDa). A liquid chromatography-multiple reaction monitoring (LC-MRM) method was optimized and used to evaluate the detectability of TRPM3 n = 5 proteotypic peptides in extracted protein s les. Results: The detergent-based protocol protein yield was significantly higher ( p & 0.05) compared with the ultrasonic-based protocol. The Pierce BCA protein assay showed more reproducibility and compatibility compared to the Bio-Rad DC protein assay. Two high-responding tryptic peptides (GANASAPDQLSLALAWNR and QAILFPNEEPSWK) for TRPM3 were detectable in n = 10 extracted protein s les from NK cells isolated from HC and ME/CFS patients. Conclusion: A method was optimized for high yield protein extraction from human NK cells and for the first time TRPM3 proteotypic peptides were detected using LC-MRM. This new method provides for future research to assess membrane protein structural and functional relationships, particularly to facilitate proteomic investigation of TRPM3 ion channel isoforms in NK cells in both health and disease states, such as ME/CFS.
Publisher: Allergy, Asthma, and Immunology Association of Thailand
Date: 2017
DOI: 10.12932/AP0771
Abstract: Mast cells (MCs) mediate inflammation through neuropeptides and cytokines, along with histamine and reactive oxygen species (ROS). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an illness characterized by an unexplained disabling fatigue with multiple physiological impairments as well as dysregulated cytokine profiles. To determine mast cell phenotypes in isolated human PBMCs, in healthy controls and in CFS/ME patients. Second, determine receptor expression of RAGE and its ligand high mobility group box 1 protein (HMGB1). Moderately severe CFS/ME patients (n=12, mean age 39.25 ± SD3.52 years), severe CFS/ME patients (n=6, mean age 43.00 ± SD4.02 years) and healthy controls (n=13, mean age 42.69 ± SD3.87 years) were included in this study. CFS/ME patients were classified according to the 2011 International Consensus Criteria. LSRFortessa X-20 Flow cytometry was used for the identification of phenotypic peripheral mast cell population in PBMCs using an exclusion marker Lin2 cocktail (anti-CD3, anti-CD14, anti-CD19, anti-CD20 and anti-CD56) and inclusion markers (CD117, CD34, FCεRI, chymase, HLA-DR and CD154) following comparative investigation. HMGB1 and soluble RAGE expression in plasma was measured by sandwich ELISA assay. There was a significant increase in CD117⁺CD34⁺FCεRI-chymase- mast cell populations in moderate and severe CFS/ME patients compared with healthy controls. There was a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cell populations in the severe CFS/ME compared with healthy controls and moderate CFS/ME. There were no significant differences between groups for HMGB1 and sRAGE. This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naïve MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required.
Publisher: OMICS Publishing Group
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 27-10-2020
DOI: 10.1186/S12967-020-02575-7
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
DOI: 10.1519/R-18385.1
Publisher: SAGE Publications
Date: 2016
DOI: 10.4137/III.S37042
Publisher: Allergy, Asthma, and Immunology Association of Thailand
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 13-05-2020
DOI: 10.1186/S12967-020-02356-2
Abstract: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been proposed that metabolomics may contribute to the illness pathogenesis of CFS/ME/SEID. In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID. PubMed, Scopus, EBSCOHost (Medline) and EMBASE were searched using medical subject headings terms for Chronic Fatigue Syndrome, metabolomics and metabolome to source papers published from 1994 to 2020. Inclusion and exclusion criteria were used to identify studies reporting on metabolites measured in blood and urine s les from CFS/ME/SEID patients compared with healthy controls. The Joanna Briggs Institute Checklist was used to complete a quality assessment for all the studies included in this review. 11 observational case control studies met the inclusion criteria for this review. The primary outcome of metabolite measurement in blood s les of CFS/ME/SEID patients was reported in ten studies. The secondary outcome of urine metabolites was measured in three of the included studies. No studies were excluded from this review based on a low-quality assessment score, however there was inconsistency in the scientific research design of the included studies. Metabolites associated with the amino acid pathway were the most commonly impaired with significant results in seven out of the 10 studies. However, no specific metabolite was consistently impaired across all of the studies. Urine metabolite results were also inconsistent. The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.
Publisher: Springer Science and Business Media LLC
Date: 12-2011
Publisher: Springer Science and Business Media LLC
Date: 02-06-2015
Publisher: Frontiers Media SA
Date: 21-08-2020
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: SAGE Publications
Date: 2016
DOI: 10.4137/GRSB.S39861
Abstract: Killer cell immunoglobulin-like receptor (KIR) genes encode for activating and inhibitory surface receptors, which are correlated with the regulation of Natural Killer (NK) cell cytotoxic activity. Reduced NK cell cytotoxic activity has been consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients, and KIR haplotypes and allelic polymorphism remain to be investigated. The aim of this article was to conduct a pilot study to examine KIR genotypes, haplotypes, and allelic polymorphism in CFS/ME patients and nonfatigued controls (NFCs). Comparison of KIR and allelic polymorphism frequencies revealed no significant differences between 20 CFS/ME patients and 20 NFCs. A lower frequency of the telomeric A/B motif ( P 0.05) was observed in CFS/ME patients compared with NFCs. This pilot study is the first to report the differences in the frequency of KIR on the telomeric A/B motif in CFS/ME patients. Further studies with a larger CFS/ME cohort are required to validate these results.
Publisher: SAGE Publications
Date: 2015
DOI: 10.4137/III.S25105
Abstract: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disorder characterized by debilitating fatigue accompanied by pain and impairments in memory, cognition, and concentration. Acetylcholine (ACh) has a plethora of roles in neuronal and neuromuscular transmission. There are two types of ACh receptors, muscarinic and nicotinic, comprising 17 different subunits of the nicotinic ACh receptor (nAChR) and five different subtypes of the muscarinic receptor (mAChR) that have been identified in humans. The purpose of this study was to determine the role of ACh receptor (nAChRs and mAChRs) single nucleotide polymorphisms (SNPs) in CFS/ME patients. One-hundred and fifteen CFS/ME patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years) participated in this study, where CFS/ME patients were defined according to the 1994 Center for Disease Prevention and Control (CDC) criteria. A total of 464 SNPs for nine mammalian ACh receptor genes ( M1, M2, M3, M4, M5, alpha 2, 5, 7, and 10) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Seventeen SNPs were significantly associated with CFS/ME patients compared with the controls. Nine of these SNPs were associated with mAChRM3 (rs4463655 P = 0.00281, rs589962 P = 0.00348, rs1072320 P = 0.00371, rs7543259 P = 0.00513, rs6661621 P = 0.00536 rs7520974 P = 0.0167, rs726169 P = 0.02349, rsrs6669810 P = 0.02361, rsrs6429157 P = 0.0375), while the remainder were associated with nAChR alpha 10 (rs2672211 P = 0.0107, rs2672214 P = 0.0108, rs2741868 P = 0.01185, rs2741870 P = 0.01281, rs2741862 P = 0.03043), alpha 5 (rs951266 P = 0.01153 rs7180002, P = 0.03682), and alpha 2 (rs2565048 P = 0.01403). The data from this pilot study suggest an association between ACh receptors, predominantly M3 and CFS. ACh receptor SNPs may contribute to the pathomechanism of CFS/ME.
Publisher: BMJ
Date: 03-2019
DOI: 10.1136/BMJOPEN-2018-023955
Abstract: The aim of this study was to estimate the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and describe illness characteristics in a community population in Poland. Design: cross-sectional study. Poland. Of the cohort of 1400 who self-presented with fatigue only 69 subsequently were confirmed as having CFS/ME using the Fukuda criteria. Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Hospital Anxiety and Depression Scale (HADS), Epworth Sleepiness Scale (ESS), Composite Autonomic Symptom Score 31 (COMPASS 31), Quality of Life Scale (QOLS). Haemodynamic and autonomic parameters were automatically measured at rest with a Task Force Monitor. In 1308, from 1400 (93%) in iduals who identified themselves as fatigued, recognised chronic conditions were identified, for ex le, neurological (n=280, 21.5%), neurodegenerative (n=200, 15%), psychiatric (n=654, 50%) and immunologic (n=174, 13.5%) disorders. The remaining 69 participants (mean age 38.3±8.5) met the Fukuda defintion for CFS/ME and had baseline objective assessment. The majority had experienced symptoms for over 2 years with 37% having symptoms for 2–5 years and 21.7% for more than 10 years. The COMPASS 31 indicated that 50% have symptoms consistent with orthostatic intolerance. About 43/69 (62%) had Epworth sleepiness scores ≥10, ie, consistent with excessive daytime sleepiness, 26/69 (38%) had significant anxiety and 22/69 (32%) depression measured by HADS A & D. Quality of life is significantly impaired in those with Fukuda criteria CFS (QLS score 64±11) with significant negative relationships between quality of life and fatigue (p .0001), anxiety (p=0.0009), depression (p .0001) and autonomic symptoms (p=0.04). This is the first study to summarise illness characteristics of Polish CFS/ME patients. Our study has confirmed that fatigue is a common and under-recognised symptom affecting the Polish population.
Publisher: Frontiers Media SA
Date: 22-04-2022
DOI: 10.3389/FNINS.2022.848730
Abstract: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) patients suffer from neurocognitive impairment. In this study, we investigated cortical volumetric and thickness changes in ME/CFS patients and healthy controls (HC). We estimated mean surface-based cortical volume and thickness from 18 ME/CFS patients who met International Consensus Criteria (ICC) and 26 HC using FreeSurfer. Vertex-wise analysis showed significant reductions in the caudal middle frontal gyrus ( p = 0.0016) and precuneus ( p = 0.013) thickness in ME/CFS patients compared with HC. Region based analysis of sub-cortical volumes found that amygdala volume ( p = 0.002) was significantly higher in ME/CFS patients compared with HC. We also performed interaction-with-group regressions with clinical measures to test for cortical volume and thickness correlations in ME/CFS with opposite slopes to HC (abnormal). ME/CFS cortical volume and thickness regressions with fatigue, heart-rate variability, heart rate, sleep disturbance score, respiratory rate, and cognitive performance were abnormal. Our study demonstrated different cortical volume and thickness in ME/CFS patients and showed abnormal cortical volume and thickness regressions with key symptoms of ME/CFS patients.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2010
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/ZO10083
Abstract: The blood of two Australian marsupials, the eastern grey kangaroo (Macropus giganteus) and the Tasmanian devil (Sarcophilus harrisii), has been reported to have greater oxygen-carrying capacity (i.e. haemoglobin content) when compared with that of placental mammals. We investigated whether alterations of blood rheological properties are associated with the increased oxygen-carrying capacity of these marsupials. Eastern grey kangaroos (n = 6) and Tasmanian devils (n = 4) were anaesthetised for blood s ling human blood (n = 6) was also s led for comparison. Laboratory measurements included blood and plasma viscosity, red blood cell (RBC) deformability, RBC aggregation and the intrinsic tendency of RBC to aggregate, RBC surface charge and haematological parameters. Scanning electron micrographs of RBC from each species provided morphological information. High-shear blood viscosity at native haematocrit was highest for the Tasmanian devil. When haematocrit was adjusted to 0.4 L L–1, lower-shear blood viscosity was highest for the eastern grey kangaroo. RBC deformability was greatly reduced for the Tasmanian devil. Eastern grey kangaroo blood had the highest RBC aggregation, whereas Tasmanian devil RBC did not aggregate. The surface charge of RBC for marsupials was ~15% lower than that of humans. The dependence of oxygen-delivery effectiveness on haemoglobin concentration (i.e. oxygen content) and blood viscosity was quantitated by calculating the haematocrit to blood viscosity ratio and was 15–25% lower for marsupials compared with humans. Our results suggest that environmental pressures since the marsupial–monotreme ergence have influenced the development of vastly different strategies to maintain a match between oxygen demand and delivery.
Publisher: OMICS Publishing Group
Date: 2018
Publisher: Mary Ann Liebert Inc
Date: 09-2014
Abstract: Endurance exercise can cause immunosuppression and increase the risk of upper respiratory illness. The present study examined changes in the secretion of T helper (Th) cell cytokines after endurance exercise. Ten highly trained road cyclists [mean±SEM: age 24.2±1.7 years height 1.82±0.02 m body mass 73.8±2.0 kg peak oxygen uptake 65.9±2.3 mL/(kg•min)] performed 2 h of cycling exercise at 90% of the second ventilatory threshold. Peripheral blood mononuclear cells were isolated and stimulated with phytohemagglutinin. Plasma cortisol concentrations and the concentration of Th1/Th2/Th17 cell cytokines were examined. Data were analyzed using both traditional statistics and magnitude-based inferences. Results revealed a significant decrease in plasma cortisol at 4-24 h postexercise compared with pre-exercise values. Qualitative analysis revealed postexercise changes in concentrations of plasma cortisol, IL-2, TNF, IL-4, IL-6, IL-10, and IL-17A compared with pre-exercise values. A Th1/Th2 shift was evident immediately postexercise. Furthermore, for multiple cytokines, including IL-2 and TNF (Th1), IL-6 and IL-10 (Th2), and IL-17 (Th17), no meaningful change in concentration occurred until more than 4 h postexercise, highlighting the duration of exercise-induced changes in immune function. These results demonstrate the importance of considering "clinically" significant versus statistically significant changes in immune cell function after exercise.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/813256
Abstract: Heat shock proteins (HSPs) are important molecules required for ideal protein function. Extensive research on the functional properties of HSPs indicates that HSPs may be implicated in a wide range of physiological functions including immune function. In the immune system, HSPs are involved in cell proliferation, differentiation, cytokine release, and apoptosis. Therefore, the ability of the immune system, in particular immune cells, to function optimally and in unison with other physiological systems is in part dependent on signaling transduction processes, including bidirectional communication with HSPs. Regulatory T cells (Tregs) are important T cells with suppressive functions and impairments in their function have been associated with a number of autoimmune disorders. The purpose of this paper is to examine the relationship between HSPs and Tregs. The interrelationship between cells and proteins may be important in cellular functions necessary for cell survival and expansion during diseased state.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S12967-019-02155-4
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is hallmarked by a significant reduction in natural killer (NK) cell cytotoxicity, a mechanism tightly regulated by calcium (Ca 2+ ). Interestingly, interleukin-2 (IL-2) increases NK cell cytotoxicity. Transient receptor potential melastatin 2 (TRPM2) ion channels are fundamental for Ca 2+ signalling in NK cells. This pilot investigation aimed to characterise TRPM2 and CD38 surface expression in vitro on NK cells in ME/CFS patients. This investigation furthermore examined the pharmaceutical effect of 8-bromoadenosine phosphoribose (8-Br-ADPR) and N 6 -Benzoyladenosine-3′,5′-cyclic monophosphate ( N 6 -Bnz-cAMP) on TRPM2 and CD38 surface expression and NK cell cytotoxicity between ME/CFS and healthy control (HC) participants. Ten ME/CFS patients (43.45 ± 12.36) and 10 HCs (43 ± 12.27) were age and sex-matched. Isolated NK cells were labelled with fluorescent antibodies to determine baseline and drug-treated TRPM2 and CD38 surface expression on NK cell subsets. Following IL-2 stimulation, NK cell cytotoxicity was measured following 8-Br-ADPR and N 6 -Bnz-cAMP drug treatments by flow cytometry. Baseline TRPM2 and CD38 surface expression was significantly higher on NK cell subsets in ME/CFS patients compared with HCs. Post IL-2 stimulation, TRPM2 and CD38 surface expression solely decreased on the CD56 Dim CD16 + subset. 8-Br-ADPR treatment significantly reduced TRPM2 surface expression on the CD56 Bright CD16 Dim/− subset within the ME/CFS group. Baseline cell cytotoxicity was significantly reduced in ME/CFS patients, however no changes were observed post drug treatment in either group. Overexpression of TRPM2 on NK cells may function as a compensatory mechanism to alert a dysregulation in Ca 2+ homeostasis to enhance NK cell function in ME/CFS, such as NK cell cytotoxicity. As no improvement in NK cell cytotoxicity was observed within the ME/CFS group, an impairment in the TRPM2 ion channel may be present in ME/CFS patients, resulting in alterations in [Ca 2+ ] i mobilisation and influx, which is fundamental in driving NK cell cytotoxicity. Differential expression of TRPM2 between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in ME/CFS.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/929720
Abstract: Objectives . Previous research has provided evidence for dysregulation in peripheral cytokines in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date only one study has examined cytokines in cerebrospinal fluid (CSF) s les of CFS/ME patients. The purpose of this pilot study was to examine the role of cytokines in CSF of CFS/ME patients. Methods . CSF was collected from 18 CFS/ME patients and 5 healthy controls. The CSF s les were examined for the expression of 27 cytokines (interleukin- (IL-) 1 β , IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN- γ , IP-10, MCP-1 (MCAF), MIP-1 α , MIP-1 β , PDGF-BB, RANTES, TNF- α , and VEGF) using the Bio-Plex Human Cytokine 27-plex Assay. Results . Of the 27 cytokines examined, only IL-10 was significantly reduced in the CFS/ME patients in comparison to the controls. Conclusions . This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME.
Location: No location found
Start Date: 2014
End Date: 2014
Funder: Judith Jane Mason and Harold Stannett Williams Memorial Foundation
View Funded ActivityStart Date: 2014
End Date: 2015
Funder: Griffith University
View Funded ActivityStart Date: 2009
End Date: 2009
Funder: Ramaciotti Foundations
View Funded ActivityStart Date: 2020
End Date: 2021
Funder: McCusker Charitable Foundation
View Funded ActivityStart Date: 2023
End Date: 2025
Funder: Multiple Sclerosis Australia
View Funded ActivityStart Date: 2021
End Date: 2024
Funder: National Health and Medical Research Council
View Funded Activity