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Background: Oxidative stress has long been linked to neuronal cell death in many neurodegenerative diseases. Antioxidant conventional supplements are poorly effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Hence the use of molecules extracted from plants and fruits such as phenolics, flavonoids, and terpenoids compounds constitute a new wave of antioxidant therapies to defend against free radicals. Objective: In this study we examined the effects of punicalagin, a ellagitannin isolated from the pomegranate juice, on a rat adrenal pheochromocytoma cell line, treated with hydrogen peroxide, evaluating the viability, oxidation potential, mitochondrial function, and eventual apoptosis. Methods: This study was performed on PC12 cells pretreated with punicalagin (0.5, 1, 5, 10 e 20 µM) 24 hours before of the damage by hydrogen peroxide (H2O2). H2O2 concentration (300 µM) used in our study was determined by preliminary experiments of time course. The cell viability and ROS production were evaluated by MTS assay and cytofluorometry assays, respectively. Subsequently, the number of apoptotic-positive cells and mitochondrial transmembrane potential, were measured by flow cytometry, in the same experimental paradigm. Finally, the expression of Bax and enzymatic activity of Caspase 3, some of the principle actors of programmed cell death, were investigated by semiquantitative PCR and utilizing a colorimetric assay kit, respectively. Results: We found that pretreatment with punicalagin protected the cells from H2O2-induced damage. In particular, the protective effect seemed to be correlated with a control both in radical oxygen species production and in mitochondrial functions. In fact the cells treated with H2O2 showed an altered mitochondrial membrane integrity while the pretreatment with punicalagin retained both the cellular viability and the mitochondrial membrane potential similar to the control. Furthermore, the punicalagin, modulated the apoptotic cascade triggered reducing Bax gene expression and Caspase 3 activity. Discussion: Results of the present study demonstrated a neuroprotective effect of punicalagin on H2O2-induced PC12 cell death, including mitochondria damage and expression of apoptotic gene Bax; therefore we hypothesize a possible prevent role for this molecule in neurodegenerative diseases related to oxidative stress. [ABSTRACT FROM AUTHOR]

Background aims. Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core. Methods. Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR. Results. We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity. Conclusions. Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state. [ABSTRACT FROM AUTHOR]

Bilirubin is the final product of heme metabolism. Until recently, bilirubin was considered as a mere by-product of heme degradation but, in the last 20 years, many papers have appeared in the literature demonstrating that this bile pigment is endowed with a strong antioxidant activity, being able to counteract the cellular damage elicited by reactive oxygen species in many in vitro and in vivo experimental systems. Interestingly, compelling evidence has shown that BR can serve as an endogenous scavenger of both nitric oxide and reactive nitrogen species, thus widening the protective role of bilirubin to other reactive species originating within the cellular milieu. The aim of this paper is to give an overview of the interaction between bilirubin and nitric oxide/reactive nitrogen species; furthermore, the possible pathophysiological and clinical relevance of this interaction will be discussed. [ABSTRACT FROM AUTHOR]