Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome

[Dolphin]

Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome - Journal of Translational Medicine

Objective This study aimed to investigate differences in protein expression, protein function, and epigenetic modifications related to histone phosphorylation in peripheral blood mononuclear cells among patients with chronic fatigue syndrome (CFS) presenting two common Traditional Chinese...

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Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome​

• Research
• Open access
• Published: 25 December 2025
• article number , (2025)

• Tingting Xu,
• Shuo Gao,
• Xinxin Cheng,
• Wenxuan Man,
• Yanjie Wang &
• Yonghui Yin

Abstract​

Objective​

This study aimed to investigate differences in protein expression, protein function, and epigenetic modifications related to histone phosphorylation in peripheral blood mononuclear cells among patients with chronic fatigue syndrome (CFS) presenting two common Traditional Chinese Medicine (TCM) syndrome types compared with healthy controls.

Methods​

Three groups of participants were selected from the Medical Examination Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2024 and December 2024. The first group consisted of 10 CFS patients with the Qi and Blood Deficiency syndrome pattern; the second group included 10 CFS patients with the Liver Depression and Spleen Deficiency syndrome pattern; and the third group comprised 10 healthy controls. Phosphopeptide enrichment analysis was employed to detect and identify differentially expressed proteins, followed by Gene Ontology (GO) enrichment analysis.

Results​

Differences were observed between both TCM syndrome types of CFS (Qi and Blood Deficiency, Liver Depression and Spleen Deficiency) and the healthy control group in various biological processes and cellular components, including intracellular signal transduction, actin filament bundling, and cortical cytoskeleton organization.

Conclusion​

Multiple processes, structures, and functions—such as intracellular signaling, presynaptic modulation of chemical synaptic transmission, actin filament bundling, cortical cytoskeleton organization, SH3 domain binding, and profilin binding—are associated with the occurrence and development of CFS.

 

[TiredMathematician]

According to the Clinical Research Guidelines for New Chinese Medicines in Treating Chronic Fatigue Syndrome[10], the TCM syndrome diagnostic criteria classify CFS into six patterns: Qi-blood deficiency, spleen-kidney Yang deficiency, marrow vacuity, liver depression-spleen deficiency, liver-kidney Yin deficiency, and liver fire hyperactivity. The diagnostic criteria for syndrome differentiation were established based on the Guiding Principles for Clinical Research of New Chinese Drugs (2002) and The Clinical Research Guidelines for New Chinese Drugs in Treating Chronic Fatigue Syndrome[10], along with our supervisor's clinical expertise in tongue and pulse diagnosis. The four TCM patterns identified were Qi-blood deficiency, liver depression-spleen deficiency, spleen-stomach Yang deficiency, and essence-marrow depletion.

This sounds like complete pseudoscience – is there anything to this that isn't just woo?

 

[hotblack]

Interestingly this paper mentions two genes identified in DecodeME, HTT and ARGEF2. So despite all the questionable TCM discussion and subgrouping, maybe they were heading somewhere in their attempts to look at differentially expressed proteins and use of more Western accepted Gene Ontology (GO) enrichment analysis? Or it could have been chance..

From the results

The comparative GO analysis between healthy controls and patients with CSF and liver depression-spleen deficiency pattern identified distinct functional alterations (Fig. 4a). The most significantly enriched BP was “intracellular signal transduction” (GO:0035556), involving genes, including AKAP11, MAP4K1, and PAK2. “Cortical cytoskeleton” (GO:0030863) revealed the highest differential expression among CC (Fig. 4b), with key genes including CAPZB, FLNA, and ACTB. The top MF was “profilin binding” (GO:0005522), which was mediated by proteins translated from VASP, EVL, CTTN, HTT, and WIPF1 (Fig. 4c)

And the discussion

For BP, the MAST3 gene, associated with the Qi and blood deficiency syndrome, encodes a protein that directly facilitates the NF-κB signaling pathway activation. Elevated MAST3 protein phosphorylation levels were observed in patients with CFS, correlating with enhanced inflammatory responses [55]. Concurrently, MAST3 is closely associated with the intracellular microtubule network. Dysregulation of its role in stabilizing microtubules may lead to cellular morphology and intracellular transport abnormalities [56]. The ARFGEF2 gene encodes a protein that is critically involved in neurodevelopment [57]; however, its downstream effector, ARF1, is vital for inflammasome activation. Studies demonstrate that ARF1 deficiency leads to NLRP3 inflammasome activation, contributing to the low-grade chronic inflammation observed in patients [58].