Exploring the shared mechanism of fatigue between [lupus] and [ME/CFS]: monocytic dysregulation..., 2024, Zheng et al

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing

Daisi Zheng, Xiaolong Li, Qingmiao Zhu, Zhiyan Huang, Peicheng Wang, Ting Zhao

[Provisionally accepted]
Edit: Now published, abstract unchanged

Background: SLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.

Methods: Genes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.

Results: Fifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.

Conclusion: SLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies.

Link | PDF (Frontiers in Immunology) [Open Access]

 

To me this is a nice example of the problems of bioinformatic, 'systems biology' or AI approaches to disease. As far as I can see it is devoid of any biological meaning. They don't even mean genes when they say genes, they mean proteins. There aren't any findings associated with ME/CFS so how can they describe shared mechanisms? It's barmy.

 

AI seems to have acquired the unfortunate human trait of sounding extremely confident even when obviously wrong.

 

well it is taught by humans .so not unexpected for A I to have human flaws error correction needs significant work.

 

Full text has now been published:
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1440922/full