Malate dehydrogenase-2 inhibition shields renal tubular epithelial cells from anoxia-reoxygenation injury by reducing reactive oxygen species.

Ischemia-reperfusion (I-R) injury is the most common cause of acute kidney injury. In experiments involving primary human renal proximal tubular epithelial cells (RPTECs) exposed to anoxia-reoxygenation, we explored the hypothesis that mitochondrial malate dehydrogenase-2 (MDH-2) inhibition redirects malate metabolism from the mitochondria to the cytoplasm, towards the malate-pyruvate cycle and reversed malate-aspartate shuttle. Colorimetry, fluorometry, and western blotting showed that MDH2 inhibition accelerates the malate-pyruvate cycle enhancing cytoplasmic NADPH, thereby regenerating the potent antioxidant reduced glutathione. It also reversed the malate-aspartate shuttle and potentially diminished mitochondrial reactive oxygen species (ROS) production by transferring electrons, in the form of NADH, from the mitochondria to the cytoplasm. The excessive ROS production induced by anoxia-reoxygenation led to DNA damage and protein modification, triggering DNA damage and unfolded protein response, ultimately resulting in apoptosis and senescence. Additionally, ROS induced lipid peroxidation, which may contribute to the process of ferroptosis. Inhibiting MDH-2 proved effective in mitigating ROS overproduction during anoxia-reoxygenation, thereby rescuing RPTECs from death or senescence. Thus, targeting MDH-2 holds promise as a pharmaceutical strategy against I-R injury.

Design and evaluation of mobile scenario based learning in the self-management of chronic pain.

Chronic pain is a lifelong issue, being one of the main causes of disability, affecting a great number of people worldwide, many of which often avoid seeking medical advice from pain experts and/or demonstrate poor adherence to their therapeutic plan. One of the most important steps in achieving a manageable course of disease, is the ability of self-management. We aimed at applying a method of systematic patient education and self-management through the use of Virtual Patients (VPs), a well-established method for educating medical doctors and students but never before targeting patients. Two VPs scenarios were designed, tested and evaluated by patients with rheumatic disorders, achieving a SUS score of 88/100 "Best Imaginable", alongside with positive reviews from the participants. The positive feedback from the patients supports the potential of VP educational paradigm to educate these patients and equip them with disease coping skills and strategies.