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Furthermore, IS activates NF-κB signaling, increasing pro-inflammatory factors such as cyclooxygenase-2, ROS, TNF-α, IL-6, and IL-1β, while suppressing antioxidant factors such as heme oxygenase-1 and superoxide dismutase 2, through Nrf2 pathway inhibition, thereby disrupting intestinal homeostasis and promoting systemic inflammation in mice ( Figure 3 ) 116

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Inflammation may even be causing pain all on its own