{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:01Z","timestamp":1792793821712,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Professor Manfred von Ardenne Forschungsf\u00f6rderungsgesellschaft e.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aetiology and pathophysiology of myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) have not yet been clarified. Its exact diagnosis is also difficult because it has no biomarkers. This lack of knowledge leads to difficulties in treating the disease. In our work, we are attempting to counteract this problem by analysing the central cellular mechanisms in ME\/CFS patients and comparing them with those of healthy individuals. This pilot study provides a small glimpse into the journey of nine people with ME\/CFS\u2014more specifically, how their peripheral blood mononuclear cells (PBMCs) responded immediately after a session of whole-body hyperthermia (WBH). The clinical effect of WBH has already been investigated in other studies on the treatment of ME\/CFS, and these studies have provided valuable insights into its potential benefits. The present study is concerned with the investigation of cellular parameters, namely autophagy, mitochondrial function and mRNA expression, before and after WBH. The results suggest that ME\/CFS patients may have higher autophagy-related protein light chain 3 (LC3)-II levels and increased mitochondrial function compared with healthy individuals. A whole-body hyperthermia session could lead to a reduction in LC3-II levels, resulting in a reversion to the levels observed in healthy donors. In the case of mitochondrial parameters, hyperthermia could lead to an increase in the measured parameters. This pilot study is a continuation of a previously published study in which only the isolated cells of ME\/CFS patients and a healthy control group were treated with hyperthermia.<\/jats:p>","DOI":"10.3390\/ijms26115339","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heat vs. Fatigue: Hyperthermia as a Possible Treatment Option for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-6091","authenticated-orcid":false,"given":"Barbara","family":"Hochecker","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton-G\u00fcnther-Strasse 51, 72488 Sigmaringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Matt","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton-G\u00fcnther-Strasse 51, 72488 Sigmaringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0115-4549","authenticated-orcid":false,"given":"Melanie","family":"Scherer","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton-G\u00fcnther-Strasse 51, 72488 Sigmaringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alica","family":"Me\u00dfmer","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton-G\u00fcnther-Strasse 51, 72488 Sigmaringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"von Ardenne","sequence":"additional","affiliation":[{"name":"Von Ardenne Institute of Applied Medical Research GmbH, 01324 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Bergemann","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton-G\u00fcnther-Strasse 51, 72488 Sigmaringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1515\/reveh-2015-0026","article-title":"Review of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: An evidence-based approach to diagnosis and management by clinicians","volume":"30","author":"Bested","year":"2015","journal-title":"Rev. Environ. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1001\/jama.2015.1346","article-title":"Beyond myalgic encephalomyelitis\/chronic fatigue syndrome: An IOM report on redefining an illness","volume":"313","author":"Clayton","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cortes Rivera, M., Mastronardi, C., Silva-Aldana, C.T., Arcos-Burgos, M., and Lidbury, B.A. (2019). Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030091"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Almenar-P\u00e9rez, E., S\u00e1nchez-Fito, T., Ovejero, T., Nathanson, L., and Oltra, E. (2019). Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Striking Back on Treatments. Pharmaceutics, 11.","DOI":"10.20944\/preprints201902.0134.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3109\/09638288.2011.635746","article-title":"Pacing as a strategy to improve energy management in myalgic encephalomyelitis\/chronic fatigue syndrome: A consensus document","volume":"34","author":"Goudsmit","year":"2012","journal-title":"Disabil. Rehabil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/0360-3016(96)00154-X","article-title":"Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: Results from five randomized controlled trials. International Collaborative Hyperthermia Group","volume":"35","author":"Vernon","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S0140-6736(95)90463-8","article-title":"Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology","volume":"345","author":"Overgaard","year":"1995","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"492","DOI":"10.4103\/0973-1482.77101","article-title":"Hyperthermia with radiation in the treatment of locally advanced head and neck cancer: A report of randomized trial","volume":"6","author":"Huilgol","year":"2010","journal-title":"J. Cancer Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/j.1464-410X.2010.09654.x","article-title":"Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC)","volume":"107","author":"Colombo","year":"2011","journal-title":"BJU Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1080\/02656730903092018","article-title":"A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma","volume":"25","author":"Harima","year":"2009","journal-title":"nt. J. Hyperth."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.critrevonc.2015.08.003","article-title":"Therapeutic hyperthermia: The old, the new, and the upcoming","volume":"97","author":"Mallory","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.2169\/internalmedicine.56.8001","article-title":"Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study","volume":"56","author":"Munemoto","year":"2017","journal-title":"Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2169\/internalmedicine.54.3042","article-title":"Effects of Waon therapy on chronic fatigue syndrome: A pilot study","volume":"54","author":"Soejima","year":"2015","journal-title":"Intern. Med."},{"key":"ref_14","first-page":"767","article-title":"Brainstem perfusion is impaired in chronic fatigue syndrome","volume":"88","author":"Costa","year":"1995","journal-title":"QJM Int. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cnp.2020.01.003","article-title":"Cerebral blood flow is reduced in ME\/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography","volume":"5","author":"Verheugt","year":"2020","journal-title":"Clin. Neurophysiol. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ijcard.2011.10.030","article-title":"Large and small artery endothelial dysfunction in chronic fatigue syndrome","volume":"154","author":"Newton","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hochecker, B., Molinski, N., Matt, K., Me\u00dfmer, A., Scherer, M., von Ardenne, A., and Bergemann, J. (2024). Heat treatment in health and disease: How water-filtered infrared-A (wIRA) irradiation affects key cellular mechanisms in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) patients compared to healthy donors. J. Therm. Biol., 120.","DOI":"10.1016\/j.jtherbio.2024.103813"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.1193497","article-title":"Autophagy and metabolism","volume":"330","author":"Rabinowitz","year":"2010","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.15252\/embj.201796697","article-title":"Molecular definitions of autophagy and related processes","volume":"36","author":"Galluzzi","year":"2017","journal-title":"EMBO J."},{"key":"ref_20","first-page":"e221","article-title":"Elevated Energy Production in Chronic Fatigue Syndrome Patients","volume":"2","author":"Lawson","year":"2016","journal-title":"J. Nat. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e6500","DOI":"10.7717\/peerj.6500","article-title":"Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types","volume":"7","author":"Tomas","year":"2019","journal-title":"PeerJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103731","DOI":"10.1016\/j.mcn.2022.103731","article-title":"Elevated ATG13 in serum of patients with ME\/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE)","volume":"120","author":"Gottschalk","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nunes, J.M., Kruger, A., Proal, A., Kell, D.B., and Pretorius, E. (2022). The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). Pharmaceuticals, 15.","DOI":"10.21203\/rs.3.rs-1727226\/v2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0003-9861(66)90036-1","article-title":"The mitochondrial electron transfer chain","volume":"116","author":"Green","year":"1966","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/ehf2.12633","article-title":"Peripheral endothelial dysfunction in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"7","author":"Scherbakov","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_26","first-page":"Doc54","article-title":"Principles and working mechanisms of water-filtered infrared-A (wIRA) in relation to wound healing","volume":"2","author":"Hoffmann","year":"2007","journal-title":"GMS Krankenhaushygiene Interdiszip."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/MCB.00166-09","article-title":"Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains","volume":"29","author":"Bellot","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"McCormick, J.J., King, K.E., C\u00f4t\u00e9, M.D., McManus, M.K., Topshee, S.M., Hsu, H., Fujii, N., and Kenny, G.P. (2020). Regulation of autophagy following ex vivo heating in peripheral blood mononuclear cells from young adults. J. Therm. Biol., 91.","DOI":"10.1016\/j.jtherbio.2020.102643"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Amirkavei, M., Plastino, F., Kvanta, A., Kaarniranta, K., Andr\u00e9, H., and Koskelainen, A. (2022). Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells. Cells, 11.","DOI":"10.3390\/cells11111778"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Faheem, M.S., Ghanem, N., Gad, A., Proch\u00e1zka, R., and Dessouki, S.M. (2021). Adaptive and Biological Responses of Buffalo Granulosa Cells Exposed to Heat Stress under In Vitro Condition. Animals, 11.","DOI":"10.3390\/ani11030794"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3109\/02656736.2014.956810","article-title":"Whole body hyperthermia treatment increases interleukin 10 and toll-like receptor 4 expression in patients with ankylosing spondylitis: A pilot study","volume":"30","author":"Zauner","year":"2014","journal-title":"Int. J. Hyperth."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2216899","DOI":"10.1080\/02656736.2023.2216899","article-title":"Fever-range whole body hyperthermia leads to changes in immune-related genes and miRNA machinery in Wistar rats","volume":"40","author":"Maciejewski","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2010.01.028","article-title":"Methods in mammalian autophagy research","volume":"140","author":"Mizushima","year":"2010","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3844\/ajbbsp.2010.120.135","article-title":"The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition","volume":"6","author":"Jason","year":"2010","journal-title":"Am. J. Biochem. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The chronic fatigue syndrome: A comprehensive approach to its definition and study","volume":"121","author":"Fukuda","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_36","unstructured":"Bell, D.S. (1995). The Doctor\u2019s Guide to Chronic Fatigue Syndrome: Understanding, Treating, and Living with CFIDS, Da Capo Press."},{"key":"ref_37","unstructured":"Hochecker, B., and Scherer, M. (2025, May 27). LC3-II Fluorescence Intensity in PBMCs from Healthy Donors and ME\/CFS Patients (CTRL + Whole-Body Hyperthermia). Available online: https:\/\/data.mendeley.com\/datasets\/vy5z29r5pg\/1."},{"key":"ref_38","unstructured":"Vaupel, P., and Kr\u00fcger, W. (1995). Physikalische Grundlagen der wassergefilterten Infrarot-A-Strahlung. W\u00e4rmetherapie Mit Wassergefilterter Infrarot-A-Strahlung. Grundlagen und Anwendungsm\u00f6glichkeiten, Stuttgart."},{"key":"ref_39","unstructured":"Vaupel, P., and Kr\u00fcger, W. (1995). W\u00e4rmetherapie Mit Wassergefilterter Infrarot-A-Strahlung. Grundlagen und Anwendungsm\u00f6glichkeiten, Stuttgart."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sch\u00f6ller-Mann, A., Matt, K., Hochecker, B., and Bergemann, J. (2021). Ex vivo Assessment of Mitochondrial Function in Human Peripheral Blood Mononuclear Cells Using XF Analyzer. Bio-Protoc., 11.","DOI":"10.21769\/BioProtoc.3980"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:45:47Z","timestamp":1760031947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115339"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115339","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,1]]}}}