Depression is a serious condition that occurs more frequently in women and is often associated with treatment resistance. The main hypotheses of this study are that (a) aldosterone is an early marker of depression onset and (b) a tryptophan (TRP) depletion model of depression previously validated in male rats is treatment resistant in females. To explore possible underlying mechanisms, we have focused on factors shown to be altered in patients with treatment-resistant depression. Female Sprague-Dawley rats were treated with a control or low-TRP-containing diet for various time periods up to 21 days. The results show that aldosterone secretion increased after 4 days of TRP depletion and prior to corticosterone. Optimal effects of TRP depletion occurred at 14 days. In addition to neurochemical and behavioural changes observed previously in males, TRP depletion in females was associated with a significant decline in serum magnesium concentrations, increased serum interleukin-6, enhanced gene expression of orexin A in the frontal cortex and induced a rise in N-methyl-D-aspartate (NMDA) receptor B_max in the amygdala. Depression-like behaviour, NMDA receptor upregulation, enhancement of the kynurenine-to-kynurenic acid ratio and magnesium were resistant to paroxetine treatment (10 mg/kg/day in drinking water for 14 days). In conclusion, aldosterone may represent an important early marker for the onset of depression-like behaviour. With respect to treatment resistance, the underlying mechanisms may involve pro-inflammatory cytokines, the kynurenine pathway, magnesium, glutamate neurotransmission and the orexin pathway. This model of treatment-resistant depression may be useful for the future development of new compounds with novel antidepressant properties.

Parkinson's disease (PD) is most commonly manifested by the presence of motor symptoms. However, non-motor symptoms occur several years before the onset of motor symptoms themselves. Hallmarks of dysfunction of the respiratory system are still outside the main focus of interest, whether by clinicians or scientists, despite their indisputable contribution to the morbidity and mortality of patients suffering from PD. In addition, many of the respiratory symptoms are already present in the early stages of the disease and efforts to utilize these parameters in the early diagnosis of PD are now intensifying. Mechanisms that lead to the development and progression of respiratory symptoms are only partially understood. This review focuses mainly on the comparison of respiratory problems observed in clinical studies with available findings obtained from experimental animal models. It also explains pathological changes observed in non-neuronal tissues in subjects with PD.

Dental pulp stem cells (DPSCs) have excellent proliferative properties, mineralization potential and can be easily obtained from third molar teeth. Recently, many studies have focused on isolation and differentiation of DPSCs. In our study, we focused on biological properties of non-differentiated DPSCs in comparison with osteogenic differentiated cells from DPSCs. We analyzed morphology as well as mineralization potential using three varied osteogenic differentiation media. After fifteen days of differentiation, calcium deposit production was observed in all three osteogenic differentiation media. However, only one osteogenic medium, without animal serum supplement, showed rapid and strong calcification—OsteoMAX-XF™ Differentiation Medium. Therefore, we examined specific surface markers, and gene and protein expression of cells differentiated in this osteogenic medium, and compared them to non-differentiated DPSCs. We proved a decrease in expression of CD9 and CD90 mesenchymal stem cell surface markers, as well as downregulation in the expression of pluripotency genes (NANOG and OCT-4) and increased levels of expression in osteogenic genes (ALP, BSP, OCN and RUNX2). Moreover, osteogenic proteins, such as BSP and OCN, were only produced in differentiated cells. Our findings confirm that carefully selected differentiation conditions for stem cells are essential for their translation into future clinical applications.

Traditionally, oxidative stress as a biological aspect is defined as an imbalance between the free radical generation and antioxidant capacity of living systems. The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic conditions, and dysregulation of gene expression are all molecular pathogenic mechanisms closely associated with oxidative stress and underpin systemic changes in the body. These also include aspects such as chronic immune system activation, the impairment of cellular structure renewal, and alterations in the character of the endocrine secretion of diverse tissues. All of these mentioned features are crucial for the correct function of the various tissue types in the body. In the present review, we summarize current knowledge about the common roots of metabolic and neurodegenerative disorders induced by oxidative stress. We discuss these common roots with regard to the way that (1) the respective metal ions are involved in the maintenance of oxidative balance and (2) the metabolic and signaling disturbances of the most important biometals, such as Mg2+, Zn2+, Se2+, Fe2+, or Cu2+, can be considered as the central connection point between the pathogenesis of both types of disorders and oxidative stress.