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Our findings indicate that the medical staff exposed to low IR levels were under risk of significant oxidative stress that was enhanced by their glutathione S-transferase (GST) polymorphisms.

Disruption of the daily (i.e., circadian) rhythms of cell metabolism, proliferation and blood perfusion is a hallmark of many cancer types, perhaps most clearly exemplified by the rare but detrimental pheochromocytomas. These tumors arise from genetic disruption of genes critical for hypoxia signaling, such as von Hippel-Lindau and hypoxia-inducible factor-2 or cellular metabolism, such as succinate dehydrogenase, which in turn impacts on the cellular circadian clock function by interfering with the Bmal1 and/or Clock transcription factors. While pheochromocytomas are often non-malignant, the resulting changes in cellular physiology are coupled to de-regulated production of catecholamines, which in turn disrupt circadian blood pressure variation and therefore circadian entrainment of other tissues. In this review we thoroughly discuss the molecular and physiological interplay between hypoxia signaling and the circadian clock in pheochromocytoma, and how this underlies endocrine disruption leading to loss of circadian blood pressure variation in the affected patients. We furthermore discuss potential avenues for targeting these tumor-specific pathophysiological mechanisms therapeutically in the future.

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BackgroundMitochondrial diabetes (MD) is a rare monogenic form of diabetes and divided into type l and type 2. It is characterized by a strong familial clustering of diabetes with the presence of maternal transmission in conjunction with bilateral hearing impairment in most of the carriers. The most common form of MD is associated with the m.3243A>G mutation in the mitochondrial MT‐TL1, but there are also association with a range of other point mutations, deletion, and depletion in mtDNA.MethodsThe mitochondrial genome anomalies were investigated in a family with clinical features of MD, which includes a proband presenting severe MD conditions including cardiomyopathy, retinopathy, and psychomotor retardation.ResultsBy investigating the patient's blood leukocytes and skeletal muscle, we identified the m.3243A>G mutation in heteroplasmic state. This mutation was absent in the rest of the family members. In addition, our analysis revealed in the proband a large mtDNA heteroplasmic deletion (~1 kb) and a reduction in mtDNA copy number.ConclusionOur study points out, for the first time, a severe phenotypic expression of the m.3243A>G point mutation in association with mtDNA deletion and depletion in MD.

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