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Table 2 MAFLD-related programmed cell death markers and targets

From: Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy

Name

Contents

Refs.

Cytokeratin-18

It alone is not enough as a valuable biomarker, but it may have clinical significance when combined with other non-invasive methods of invasion, such as with serum adiponectin, serum resistin, uric acid (NCT01068444)

[18, 164, 165]

Fas/TNF-α

Inhibitor of death receptor-associated protein, including pentoxifylline, YLGA(Try-Leu-Gly-Ala) peptides

[35, 166]

Caspase enzymes

Inhibitor of apoptosis-related caspase enzymes, including VX-166, GS-9450 (NCT00740610), PF-03491390 (NCT02077374), and emricasan (NCT02686762, NCT02077374)

[34, 156, 157, 167]

R-3032

A ctsb inhibitor

[168]

Aramchol

Aramchol inhibits the liver enzyme stearoyl coenzyme A desaturase (SCD)

[25]

Selonsertib

ASK1 inhibitor

[169]

The farnesoid X-activated receptor (FXR)

Its agonist (NCT01265498) can improve serum transaminase levels in patients with MAFLD

[170]

Thioredoxin (TRX)

Oxidative stress can lead to a variety of PCD. TRX is induced by oxidative stress. Compared with healthy controls, the level of TRX rises significantly, but whether it can be used as a biomarker still needs further research

[171]

XIAP

XIAP antisense oligonucleotide (AEG35156) increases progression-free survival and overall survival

[172]

RIPK1/3

Although RIPK1/3 currently has inhibitors (GSKʹ840, GSKʹ843, GSKʹ872), according to different preclinical studies, it seems that directly targeting RIPK1/3 is not a better treatment for MAFLD, and further studies are needed

[173]

MLKL

Theoretically, the MLKL inhibitor (necrosulfonamide) may improve MAFLD, but evidence from well-designed clinical studies is still needed

[173]

NLRP3 inflammasome

Inhibiting the activation of the MAFLD inflammasome is an innovative treatment method, including an inhibitor of the NALP3 inflammasome (glyburide), a caspase 1 inhibitor (Pralnacasan), and an IL-1β antibody (canakinumab) or endogenous IL-1β inhibitor (anakinra)

[174]