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This deacetylation leads to chromatin compaction and transcriptional silencing of these tumor suppressors, thereby promoting uncontrolled proliferation and resistance to apoptosis (Zheng et al., 2024)

When acutely administered in the perfusate at non-necrotic concentrations, tBOOH impaired bile salt excretion and increased the bile/perfusate ratio of [14C]- sucrose, a tight-junctional-integrity marker that enters the bile canaliculus via the paracellular pathway.70 The impairment in bile salt excretion and the disruption of the tight-junctional barrier function may be causally associated, since the latter induces leakage of bile salts (or other osmotically-active biliary solutes) from the canalicular space via the paracellular pathway, leading to dissipation of the osmotic gradients involved in bile formation.112 These functional alterations to secrete and retain bile salts in the biliary space seem to have a structural correlate

Evaluation: Body fat (DXA scanning) Lean mass Insulin sensitivity Energy expenditure What they found: The combination showed an additive effect on fat reduction vs monotherapy AOD-9604 partially protected lean mass during GLP-1-induced weight reduction Increased energy expenditure in combination (~3 % vs GLP-1 alone) No new safety signals Why it matters: It validates the concept of combination , the idea that AOD-9604 may not work on its own, but can add value in combination with incretin agonists

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