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Integrated preclinical to first-in-human to indication-specific randomized clinical trials (RCTs) would be ideal candidates to combine mechanistic readouts (local drug/metabolite concentration, biofilm imaging, single-cell viability) with clinical readouts and, in advanced preclinical studies, local drug/metabolite concentrations

Examples include high-dose vitamin A or retinoids (which can be hepatotoxic in excess), green tea extract catechins (associated with rare cases of liver injury), kava, or high-dose niacin

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Later, pharmacological studies also suggested that TRPM7 mediates apoptotic neuronal death caused by brain ischemia through modulation of CaMKII, calmodulin, and calcineurin (Turlova et al., 2021)