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In addition, the loss of SIRT6 reduces the protective effects of CD (cholesterol-lowering drugs) against Ang II-induced podocyte damage in vitro and vivo

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The IRIS 203 trial showed that pioglitazone reduced the incidence of any stroke in nondiabetic patients with IR and stroke, suggesting that pioglitazone has glucose-independent cardiovascular benefits

In summary, neuroprotective capacity is a major differentiator: natural compounds engage pathways (antioxidant responses, antiapoptosis, protein homeostasis, etc.) that maintain neuron health, whereas levodopa largely bypasses these diseasemodifying mechanisms (Figure 5)