Tag: pathophysiology

Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group

Abstract:

Background: Muscle-related symptoms are among the most disabling manifestations of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), yet their position within the broader symptom architecture of the disease remains unclear. We hypothesized that muscle symptoms may represent a candidate integrative symptom within a broader shared symptom-dysregulation structure and their symptom associations differ according to sex and menopausal status.

Methods: Cross-sectional data from 736 individuals with physician-diagnosed ME/CFS enrolled in the APAV-ME/CFS registry were analysed. Muscle problems served as the primary outcome variable. Associations with 14 symptom domains were examined using multivariable logistic regression. Pearson and tetrachoric correlations, exploratory factor analysis, and structural equation modeling (SEM) were used to identify latent symptom structures. Exploratory analyses were stratified by sex, menopausal status, and disease duration.

Results: In the full multivariable model (non-robust estimates), breathing problems (OR 2.49 [95% Conf. Interval: 1.42-4.38], p = 0.001), flu-like symptoms (OR 1.97 [1.14-3.42], p = 0.015), and temperature-regulation disorders (OR 1.97 [1.10-3.51], p = 0.021) independently predicted muscle problems. A reduced physiological model (not-robust estimates) additionally identified cardiovascular symptoms (OR 1.87 [1.09-3.24], p = 0.024) as a significant predictor. Tetrachoric correlations demonstrated substantial latent associations between muscle problems and breathing difficulties (ρ = 0.52), cardiovascular symptoms (ρ = 0.49), temperature-regulation disorders (ρ = 0.49), visual disturbances (ρ = 0.39), and flu-like symptoms (ρ = 0.39). Factor analysis and SEM supported a single latent physiological dysregulation factor with good model fit (RMSEA = 0.046, CFI = 0.971, TLI = 0.952, SRMR = 0.026).

The sex-stratified analyses revealed differences in the pattern of statistically significant symptom associations across the subgroups. However, the overall test of the symptom-by-sex interaction terms did not provide evidence for a statistically established difference in the symptom associations by sex. Thus, the subgroup-specific patterns should primarily be interpreted as descriptive and exploratory. At the individual symptom level, the association between breathing-related symptoms and muscle problems showed a statistically significant interaction with sex, suggesting that this association may differ between women and men. However, this finding should be interpreted cautiously given the non-significant overall interaction test and the wide confidence interval of the interaction estimate.

In women, all five physiological symptoms independently predicted muscle problems, whereas in men only breathing problems and temperature-regulation disorders remained significant. Women classified as premenopausal and postmenopausal based on an age-defined proxy showed different patterns of symptom associations with muscle problems in subgroup-specific analyses. Women in the premenopausal age-proxy group showed significant associations with cardiovascular symptoms, visual disturbances, and temperature-regulation disorders, whereas women classified as postmenopausal showed significant associations with breathing difficulties and flu-like symptoms. However, the overall menopausal-by-symptom interaction was not statistically significant (Wald χ2 (5)=5.96, p = 0.310).

The specified latent physiological factor showed statistical comparability across the cross-sectional disease-duration groups. Gastrointestinal complaints loaded substantially on the latent factor despite lacking an independent association with muscle problems in multivariable regression. Urogenital symptoms also showed a smaller but significant association with the latent factor and substantial item-specific variance.

Conclusions: Muscle symptoms may represent a candidate integrative symptom within a latent physiological symptom-dysregulation factor encompassing respiratory, cardiovascular, thermoregulatory, visual, and flu-like symptoms in this ME/CFS sample. Secondary analyses suggested that gastrointestinal complaints were also part of the broader physiological symptom pattern, although they were not independently associated with muscle problems. The specified latent physiological factor showed no overall statistical evidence of measurement differences across the cross-sectional disease-duration groups. However, subgroup-specific symptom patterns differed descriptively by sex and age-defined menopausal-status proxy group.

Women classified as premenopausal were characterized primarily by cardiovascular, visual, and thermoregulatory symptom associations, whereas women classified as postmenopausal and men showed greater prominence of breathing-related symptoms. Flu-like symptoms were independently associated with muscle problems in the postmenopausal subgroup but not in the premenopausal subgroup. Because the corresponding interaction term was not statistically significant, this subgroup contrast should be interpreted as an exploratory difference in association rather than as evidence of a menopause-specific effect. More broadly, the findings are compatible with the hypothesis that the latent symptom-dysregulation factor may reflect a chronic PEM-associated multisystem response.

Whether this symptom-dysregulation factor corresponds to interacting autonomic, vascular, immunological, and metabolic processes remains to be determined by longitudinal and biomarker-based studies. ME/CFS phenotyping may improve patient stratification and facilitate the development of mechanism-based therapeutic approaches.

Source: Habermann-Horstmeier L, Horstmeier LM. Muscle symptoms and a latent physiological symptom-dysregulation factor in ME/CFS: exploratory analyses by sex and age-defined menopausal-status proxy group. J Transl Med. 2026 Sep 28;24(1):1216. doi: 10.1186/s12967-026-09018-9. PMID: 42806383. https://link.springer.com/article/10.1186/s12967-026-09018-9 (Full text)

Postural orthostatic tachycardia syndrome in adolescents with ME/CFS – a case control study

Abstract:

Introduction: Postural orthostatic tachycardia syndrome (PoTS) can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Pediatric PoTS requires a “sustained” rise in orthostatic heart rate ≥40 bpm above supine heart rate (relative limit), often >120 bpm (absolute limit). However, the diagnostic criteria for PoTS in adolescents remain underexplored, particularly regarding the definition of “sustained” tachycardia, which poses challenges in clinical and research settings. This study examined orthostatic intolerance criteria, including PoTS, in adolescents with ME/CFS and healthy controls.

Methods: Medical history of orthostatic intolerance was assessed by a semi-structured interview with 18 ME/CFS patients and 18 matched healthy controls (14-17 years). A passive 10-min standing test with minute-by-minute heart rate and blood pressure registration was performed. PoTS was diagnosed by a clinical expert based on current consensus criteria. Data were analyzed using Fisher’s exact test and receiver operating characteristic analysis.

Results: Although history of orthostatic intolerance was positive in 15/18 ME/CFS [83%, 0.95 CI (61; 94)] and 3/18 healthy controls [17%, 0.95 CI (5.9; 39)], PoTS was diagnosed in only 7/18 ME/CFS [39%, 0.95 CI (20; 61)] vs. no healthy controls [0%, 0.95 CI (0; 18)]. Subgroups were identified, e.g., positive history of orthostatic intolerance yet physiological passive 10-min standing test, or negative history of orthostatic intolerance yet tachycardia in passive 10-minute standing test. PoTS diagnosis by the clinical expert matched best with the passive 10-min standing test alone when at least 60% of upright heart rate values were above one or both limits. The absolute limit was superior to the relative limit in distinguishing adolescents with and without PoTS.

Discussion: PoTS was observed only in ME/CFS. In adolescents with ME/CFS, positive history of orthostatic intolerance, along with at least 60% of heart rate values above published upright-position limits, may allow non-experts to make a valid diagnosis, facilitating clinical care and future studies. Further research will show if these results can be generalized.

Source: Leone A, Gerrer K, Viereck A, Grabbe A, Kircher A, Behrends U, Maier A. Postural orthostatic tachycardia syndrome in adolescents with ME/CFS – a case control study. Front Pediatr. 2026 Sep 1;14:1836407. doi: 10.3389/fped.2026.1836407. PMID: 42746015; PMCID: PMC13574936. https://pmc.ncbi.nlm.nih.gov/articles/PMC13574936/ (Full text)

Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest

Abstract:

Patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from post-exertional malaise. The accompanying physical inactivity may contribute to a lower aerobic capacity and may explain skeletal muscle adaptations in these patients. Here, we compare whole-body exercise responses and skeletal muscle adaptations after strict 60-day bed rest in healthy people with those in long COVID and ME/CFS patients, and healthy age- and sex-matched controls.

Bed rest alters respiratory and cardiovascular responses to maximal exercise, which are dissimilar in patients. Bed rest causes muscle atrophy without altering fiber type. Both patient groups have more glycolytic fibers, and ME/CFS patients display type I-specific atrophy. Only after bed rest is oxidative phosphorylation capacity associated with maximal oxygen uptake.

As skeletal muscle characteristics differ between patients and healthy individuals after bed rest, physical inactivity cannot solely explain the lower exercise capacity and skeletal muscle adaptations in long COVID and ME/CFS patients.

Source: Charlton BT, Slaghekke A, Appelman B, Eggelbusch M, Huijts JY, Noort W, Hendrickse PW, Bloemers FW, Posthuma JJ, van Amstel P, Goulding RP, Degens H, Jaspers RT, van Vugt M, Wüst RCI. Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest. Nat Commun. 2026 Jul 28;17(1):9125. doi: 10.1038/s41467-026-75725-y. PMID: 42649155. https://www.nature.com/articles/s41467-026-75725-y (Full text)

Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating, multi-systemic condition that has gained renewed global attention due to its clinical overlap with the growing population of long COVID patients. Despite ongoing efforts to characterize the disease, definitive diagnostic molecular markers are yet to be fully established, posing challenges in clinically differentiating from idiopathic chronic fatigue (ICF) and depression (Dep). This study aimed to identify circulating extracellular vesicles (EVs)-associated microRNAs (miRNAs) that serve as both diagnostic signatures and windows into the disease’s underlying pathophysiology.

Methods: Circulating EVs from ME/CFS (n = 6), ICF (n = 6), and depression (n = 8) patients were analyzed using flow cytometry, nano-tracking analysis, and comprehensive miRNA analysis. Differentially expressed miRNAs were analyzed using KEGG pathway enrichment to identify ME/CFS-specific signatures. Key candidate biomarkers were further validated in an additional healthy control (HC) cohort (n = 4).

Results: ME/CFS-EVs exhibited a unique subpopulation with high calcein intensity and larger diameters. Initial global miRNA profiling (Volcano plot) identified miR-21-5p, let-7f-5p, miR-26b-5p, and miR-20a-5p as significantly dysregulated EV-miRNAs in ME/CFS compared to ICF and Dep. To explore systemic pathophysiology, we identified a 114 EV-miRNA signature that achieved 87.0 ± 4.8% sensitivity and 93.7 ± 2.4% specificity within repeated cross-validation of the discovery cohort. After adjusting for covariates, 91 miRNAs remained significant; pathway analysis of the 62 up-regulated EV-miRNAs revealed significant enrichment in neuro-systemic axes, encompassing cellular structural integrity (focal adhesion), core signaling hubs (PI3K-Akt), and systemic homeostasis (such as insulin signaling and endocrine functions). Preliminary evaluation confirmed that these target EV-miRNAs remained at minimal or undetectable levels in the HC group.

Conclusions: A 62 EV-miRNA signature provides insight into the interconnected neuro-systemic pathways disrupted in ME/CFS, particularly those governing neuronal connectivity and cellular scaffolding. Within this candidate EV-miRNA signature, the top-ranked miRNAs-miR-21-5p, let-7f-5p, miR-26b-5p, and miR-20a-5p-emerge as potential candidate biomarkers whose specific elevation was not shared by HC. These findings establish a valuable framework for targeted diagnosis and enhance our understanding of the molecular pathways involved in synaptic and structural alterations in ME/CFS.

Source: Eguchi A, Kuratsune H, Nakatomi Y, Yasui T, Nakagawa R, Watanabe Y, Fukuda S. Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions. J Transl Med. 2026 Jul 27;24(1):979. doi: 10.1186/s12967-026-08695-w. PMID: 42533331. https://link.springer.com/article/10.1186/s12967-026-08695-w (Full text)

Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterised by post-exertional malaise, non-restorative sleep, and cognitive impairment, yet no objective diagnostic biomarkers have been established. Untargeted plasma metabolomics provides a broad view of the biochemical disturbances underlying ME/CFS; however, the high dimensionality of omics datasets and the limited interpretability of conventional classifiers nevertheless hinder translation into clinical practice. This study evaluates three ensemble classifiers-Explainable Boosting Machine (EBM), XGBoost, and LightGBM-for binary ME/CFS classification using plasma metabolomic and lipidomic profiles from 197 participants (106 ME/CFS; 91 healthy controls; 888 features).

Feature dimensionality was reduced using a Pareto-Guided Recursive Neural Network (PRNN) pipeline. Model performance was assessed via 50-repeat stratified hold-out validation. EBM achieved the highest accuracy (0.909; 95% CI: 0.868-0.949) and area under the receiver operating characteristic curve (AUC: 0.940; 95% CI: 0.909-0.983), with XGBoost and LightGBM performing comparably. Interpretability analyses revealed that pairwise metabolite interaction terms-particularly proline & indole-3-lactate, tyrosine & N-acetylornithine, and maleic acid & arachidic acid-contributed the greatest discriminative signal.

An ablation analysis comparing the full interaction-augmented EBM (AUC = 0.940) with a main-effects-only EBM (AUC = 0.882) confirmed that pairwise metabolite co-variation contributes additional discriminative value beyond individual metabolite levels, implicating amino acid catabolism, tryptophan-kynurenine pathway dysregulation, mitochondrial energy impairment, and lipid remodelling as central pathophysiological features. Global and instance-level explanations jointly demonstrated population-level metabolic signatures alongside individual heterogeneity, highlighting the added clinical value of explainable artificial intelligence (XAI) in metabolomics.

These findings support EBM-based metabolomic profiling as an internally validated approach for ME/CFS classification, subject to external validation, calibration assessment, and prospective testing.

Source: Yagin FH, Korkmaz Y, Colak C, Alzakari SA, Alkhalifa AK, Al-Hashem F, Aghaei M. Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection. Int J Mol Sci. 2026 Jun 30;27(13):5920. doi: 10.3390/ijms27135920. PMID: 42450188. https://www.mdpi.com/1422-0067/27/13/5920 (Full text)

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS

Abstract:

The glymphatic system is a recently discovered brain waste clearance system that is mostly active during sleep and disengaged during wakefulness. Impaired glymphatic function leads to the deposition of metabolic waste products in the brain potentially causing inflammation leading to various symptoms in ME/CFS. While the glymphatic function has been assessed in other neurodegenerative diseases using ‘diffusion tensor imaging along the perivascular space’ (DTI-ALPS), it has not been studied in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

This preliminary study investigates glymphatic function in 58 participants (ME/CFS = 31 and healthy controls = 27) using the DTI-ALPS index derived from DTI data acquired with 3 T MRI. The bilateral hemispheric DTI-ALPS index was estimated to assess glymphatic function, and an asymmetry index was calculated to determine interhemispheric asymmetry in glymphatic function.

We found that the global DTI-ALPS index was significantly lower in ME/CFS patients compared to healthy controls (ME/CFS: 1.44 ± 0.086; healthy controls: 1.51 ± 0.11, p = 0.014), indicating reduced glymphatic function in ME/CFS. Examining the hemispheres separately, showed the right hemisphere DTI-ALPS index was lower in ME/CFS than healthy controls (ME/CFS = 1.41 ± 0.097; healthy controls = 1.49 ± 0.12; p = 0.009) but not different on the left. Additionally, we did not find any significant difference in asymmetry index between ME/CFS and healthy controls. We observed an association between the global DTI-ALPS index and severity of ‘sleep disturbance’ (p = 0.013, r = -0.47) and “impaired concentration” (p = 0.026, r = -0.43).

This study demonstrated impaired glymphatic function in ME/CFS which may lead to symptoms such as cognitive dysfunction and sleep disturbance experienced by ME/CFS.

Source: Thapaliya K, Marshall-Gradisnik S, Inderyas M, Barnden L. Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS. Front Neurosci. 2026 Jun 19;20:1875420. doi: 10.3389/fnins.2026.1875420. PMID: 42403482; PMCID: PMC13329448. https://pmc.ncbi.nlm.nih.gov/articles/PMC13329448/ (Full text)

Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by post-exertional malaise, fatigue and pain. Yet, its underlying biological mechanisms remain poorly understood. Extracellular vesicles (EVs) are nanoparticles carrying biological cargo and are involved in cell-cell communication. Plasma EVs reflect several disease states and may serve as minimally invasive biomarkers. In this exploratory study, we characterized the plasma EV profiles of ME/CFS patients (N = 49) and healthy controls (N = 50), by enriching for EVs by size-exclusion chromatography coupled to high-resolution quantitative proteomics.

The ME/CFS patients had significantly higher concentrations of EVs than healthy controls. Among the 424 detected proteins included for analyses, 11 had different levels in EVs from ME/CFS patients. The ME/CFS associated EV proteins appear to mainly originate from erythroid cells, hepatocytes and plasma B cells, based on their tissue expression. Albeit differences in EV protein levels did not withstand correction for multiple testing, our study is the largest to date, thereby encouraging future investigations on the role of EV and its cargo in ME/CFS.

Source: Rydland A, Yran ES, Nyman TA, Strand EB, Trøseid AS, Øvstebø R, Heinicke F, Lie BA, Viken MK. Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls. Biochem Biophys Rep. 2026 Jun 20;47:102679. doi: 10.1016/j.bbrep.2026.102679. PMID: 42375682; PMCID: PMC13312568. https://pmc.ncbi.nlm.nih.gov/articles/PMC13312568/ (Full text)

Tryptophan Metabolism and Aryl-Hydrocarbon Receptor Agonists in the Gut Microbiome of People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease with unknown biological basis and no cure. Microbiome dysbiosis has been reported in people with ME/CFS but its relevance to pathophysiology is unknown. Gut microbes are an important source of tryptophan metabolites that activate the aryl hydrocarbon receptor (AHR), a regulator of homeostatic and inflammatory genes. Dysregulated activation of AHR contributes to pathophysiology of several neuroimmune and chronic diseases but its role in ME/CFS has not been investigated. The purpose of this study was to investigate the production of tryptophan metabolites and AHR agonists by gut microbes of people with ME/CFS.

We found lower diversity and altered microbiome community structure in people with ME/CFS and changes in the subcommunity of microbes that correlated with tryptophan metabolites. Using targeted metabolomics we identified nine metabolites elevated in the stool of people with ME/CFS, including three AHR agonists. Stool ex vivo cultures were tested for their capacity to activate AHR in a reporter cell line and by qPCR. AHR activation did not differ between people with ME/CFS and controls, however, we detected elevated agonist activity in people with neurocognitive symptoms, regardless of underlying disease.

These findings are consistent with previous work revealing changes in the gut microbiome of people with ME/CFS and adds further support to alterations in tryptophan metabolism associated with the disease. Altered AHR activity by gut microbial metabolites may be a common mechanism contributing to neurocognitive symptoms in diseases including ME/CFS.

Source: Esteban DJ, Conrad B, Cullinan A, Luong S, Albaum J, Wilk V. Tryptophan Metabolism and Aryl-Hydrocarbon Receptor Agonists in the Gut Microbiome of People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Microbiologyopen. 2026 Jun;15(3):e70333. doi: 10.1002/mbo3.70333. PMID: 42325052. https://onlinelibrary.wiley.com/doi/10.1002/mbo3.70333 (Full text)

Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research

Abstract:

Hormonal dysregulation is increasingly reported in ME/CFS and Long COVID, yet the broader role of neuroendocrine disruption in these conditions remains underexplored. While changes in steroid, peptide, and neuropeptide hormones have been identified, these findings are often considered in isolation and without attention to their timing or integration within broader physiological systems. The hypothalamic-pituitary axes regulate endocrine, immune, autonomic, nervous, and metabolic functions, systems commonly affected in both conditions, yet their circadian and menstrual dynamics are rarely investigated.

In this review, we examine the evidence for neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output, functional assays, receptor expression, and the coordination of endocrine biorhythms. Sex hormone signalling emerges as a key area of vulnerability, particularly given the female predominance in both conditions and the complexity of reproductive hormone regulation.

We argue that accurate hormone measurement and time-structured sampling, including circadian and menstrual rhythms, are essential for detecting meaningful biological differences. By embedding chronobiology-aware, dense-sampling strategies and integrating multi-omic analyses into multi-system study designs, we outline a framework for investigating dynamic endocrine mechanisms underlying symptom variability and multisystem dysfunction, which may ultimately support the development of more targeted, personalised interventions.

Source: Thomas N, Huang K, Schneider-Futschik EK, Pollack B, Tal MC, Fineberg D, Wang X, Gurvich C, Pretorius R, Bergquist J, Armstrong CW. Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research. Front Neuroendocrinol. 2026 Jun 19:101268. doi: 10.1016/j.yfrne.2026.101268. Epub ahead of print. PMID: 42320559. https://www.sciencedirect.com/science/article/abs/pii/S0091302226000385 (Full text)

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis

Abstract:

Myalgic Encephalomyelitis (ME) is a chronic, multisystem disease characterized by systemic metabolic dysfunction and post-exertional malaise (PEM). In this study, we investigated the dysregulation of irisin, an exercise-induced myokine, and its potential antagonism by thrombospondin-1 (TSP-1).

In a cross-sectional study (92 ME patients vs. 44 sedentary healthy controls), plasma irisin and TSP-1 levels were measured at baseline and after a 90 min mechanical stress challenge applied to induce PEM. ME patients exhibited significantly lower baseline irisin (p < 0.05) and a blunted exertional response (p < 0.05). Paradoxically, baseline irisin was an independent predictor of fatigue severity (β = 0.728, p = 0.018), with moderate-to-severe patients showing elevated levels of both irisin and TSP-1 (p < 0.05), suggesting a compensatory but ineffective response. Functional cellular dielectric spectroscopy indicated that TSP-1 inhibits irisin signaling in a concentration-dependent manner. Irisin signaling was markedly reduced by both αvβ5 blockade and HSP90α inhibition in this experimental system, consistent with a diminished ability to counteract TSP-1.

Collectively, these findings support a model in which dysregulation of the irisin-TSP-1 axis contributes to metabolic dysfunction in ME. Elevated circulating TSP-1 levels are associated with symptom severity and are linked to impaired irisin signaling in an HSP90α- and αvβ5-dependent context. This interaction is consistent with defective metabolic adaptation and highlights a potential therapeutic target that warrants further validation to restore energy homeostasis.

Source: Souma B, Elremaly W, Akoume MY, Elbakry M, Godbout C, Moreau A. Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis. Int J Mol Sci. 2026 May 26;27(11):4770. doi: 10.3390/ijms27114770. PMID: 42278300. https://www.mdpi.com/1422-0067/27/11/4770 (Full text)