Nox4 promotes endothelial differentiation through chromatin remodeling.

RATIONALE: Nox4 is a constitutively active NADPH oxidase that constantly produces low levels of H2O2. Thereby, Nox4 contributes to cell homeostasis and long-term processes, such as differentiation. The high expression of Nox4 seen in endothelial cells contrasts with the low abundance of Nox4 in stem cells, which are accordingly characterized by low levels of H2O2. We hypothesize that Nox4 is a major contributor to endothelial differentiation, is induced during the process of differentiation, and facilitates homeostasis of the resulting endothelial cells. OBJECTIVE: To determine the role of No×4 in differentiation of murine inducible pluripotent stem cells (miPSC) into endothelial cells (ECs). METHODS AND RESULTS: miPSC, generated from mouse embryonic wildtype (WT) and Nox4-/- fibroblasts, were differentiated into endothelial cells (miPSC-EC) by stimulation with BMP4 and VEGF. During this process, Nox4 expression increased and knockout of Nox4 prolonged the abundance of pluripotency markers, while expression of endothelial markers was delayed in differentiating Nox4-depleted iPSCs. Eventually, angiogenic capacity of iPSC-ECs is reduced in Nox4 deficient cells, indicating that an absence of Nox4 diminishes stability of the reached phenotype. As an underlying mechanism, we identified JmjD3 as a redox target of Nox4. iPSC-ECs lacking Nox4 display a lower nuclear abundance of the histone demethylase JmjD3, resulting in an increased triple methylation of histone 3 (H3K27me3), which serves as a repressive mark for several genes involved in differentiation. CONCLUSIONS: Nox4 promotes differentiation of miPSCs into ECs by oxidation of JmjD3 and subsequent demethylation of H3K27me3, which forced endothelial differentiation and stability.

[Scanning electron microscopic studies on the efficacy of irrigated, hand root canal preparation]. / Rasterelektronenmikroskopische Untersuchungen zur Effektivität der feuchten manuellen Wurzelkanalaufbereitung.

The effectiveness of hand preparation and irrigation of 48 root canals of upper anterior teeth was evaluated by scanning electron microscopy. Independently of instrument (K reamer or combination K reamer and H file), irrigating solution (sodium chloride) and root canal dressing a similar degree of preparing and cleaning effectiveness of root canals was detected. In all groups a homogeneous or inhomogeneous smear layer of different thickness and extent dominated. A scale of preparing and cleaning effectiveness is recommended.

[Transparent dentinal sclerosis and its clinical significance]. / Uber transparente Dentinsklerose und ihre klinische Bedeutung.

Localisation, extension, age dependence and permeability of the translucent zones in different progression stages of the dentine caries were examined by light microscopy, histochemical methods and dye penetration on ground sections, thin-ground sections and decalcified material of extracted human teeth. This phenomenon is observed in every age and more interpreted as a passive chemical precipitation than a protective activity of the pulp-dentine-system. As it is developed incompletely, it represents at most a relative, but not a proof protection from penetrating noxious actions.

Electroconvulsive therapy and intracranial aneurysm. Prevention of blood pressure elevation in a normotensive patient by hydralazine and propranolol.

A 42-year-old normotensive woman developed a severe mental depression 6 months after an operation for intracranial aneurysm. The use of electroconvulsive therapy (ECT) was judged to be of vital importance. By concurrent administration of intravenous hydralazine and propranolol before induction of anaesthesia the normally occurring ECT-induced blood pressure elevation was completely prevented, and the patient received a series of ten ECTs without complications.