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21677085, 21537001 and 81472986) and the Project funded by China Postdoctoral Science Foundation (No 2016 M590071)

At the genetic level, two common functional polymorphisms, C677T (rs1801133) and A1298C (rs1801131), are widely studied for their effects on enzyme thermolability and folate/homocysteine status

These molecules can further induce various transcription factors, like NF-B, STAT, p53, and activator protein-1 (AP-1) [9]

More importantly, by restoring mitochondrial integrity via overexpressing hHsp27, the development of mechanical and cold allodynia was completely prevented in paclitaxel-treated or vincristine-treated hHsp27 overexpressing mice (Chine et al., 2019a,b)

Interestingly, there is emerging evidence that TCAs may improve liver fibrosis and reduce portal hypertensive complications, a potential dual benefit that warrants further investigation [55, 56]