Mitohormesis and mitochondrial dynamics in the regulation of stem cell fate.

The ability of stem cells for self-renewing, differentiation, and regeneration of injured tissues is believed to occur via the hormetic modulation of nuclear/mitochondrial signal transductions. The evidence now indicates that in damaged tissues, the mitochondria set off the alarm under oxidative stress conditions, hence they are the central regulators of stem cell fate decisions. This review aimed to provide an update to a broader concept of stem cell fate in stress conditions of damaged tissues, and insights for the mitochondrial hormesis (mitohormesis), including the integrated stress response (ISR), mitochondrial dynamics, mitochondria uncoupling, unfolded protein response, and mitokines, with implications for the control of stem cells programing in a successful clinical cell therapy.

Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications.

Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic ß-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary.

The protective effect of N-acetylcysteine on antimycin A-induced respiratory chain deficiency in mesenchymal stem cells.

Transplantation of mesenchymal stem cells (MSCs) is an effective treatment in tissue injuries though it is limited due to the early death of stem cells within the first few days. The main reason could be a deficiency in the respiratory chain of injured tissues which is linked to the oxidative stress (OS) and disruption of energy metabolism. The disruption in energy metabolism and OS both inhibit the homing of stem cells in the hypoxic micro-environment, however on other hand, the key functions of stem cells are mainly regulated by their cellular redox status and energy metabolism. Because of that, strategies are being developed to improve the bio-functional properties of MSCs, including preconditioning of the stem cells in hypoxic conditions and pretreatment of antioxidants. To achieve this purpose, in this study N-acetylcysteine (NAC) was used for the protection of cells from oxidative stress and the disruption in energy metabolism was induced by Antimycin A (AMA) via blocking the cytochrome C complex. Then several parameters were analyzed, including cell viability/apoptosis, mitochondrial membrane potential, and redox molecular homeostasis. Based on our findings, upon the exposure of the MSCs to the conditions of deficient respiratory chain, the cells failed to scavenge the free radicals, and energy metabolism was disrupted. The use of NAC was found to alleviate the DNA damage, cell apoptosis, and oxidative stress via Nrf2/Sirt3 pathway though without any effect on the mitochondrial membrane potential. It means that antioxidants protect the cells from OS but the problem of ATP metabolism yet remains unresolved in the hypoxic conditions.

Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells.

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

Optimizing the Radiology Experience through Radiologist-Patient Interaction.

Objective The goal of this survey-based study is to explore patients' knowledge of and expectations for radiologists in the outpatient setting.  Materials and Methods A comprehensive survey was distributed to adult patients undergoing knee magnetic resonance imaging (MRI) over a one-year period from September 2015 through August 2016 at an urban, quaternary care academic medical center. Results The survey results demonstrate that only a subset of patients undergoing knee MRI at the institution during the survey period are aware of the role of the radiologist, which is a well-documented fact described in the literature. Approximately one-third of patients expected to meet the radiologist during their visit to the department of radiology to undergo a knee MRI. The vast majority of patients surveyed wanted to be able to contact the person who read their exam, but only one patient actually contacted the radiologist during the study period.  Conclusion While the vast majority of surveyed patients wanted to be able to contact the person who read their knee MRI, only one patient actually did reach out to the radiologist to discuss findings. However, six of 36 follow-up respondents reported that they had contacted the person "who interpreted/read your exam:" two in person, one by email, three by phone, and one by other. Survey results demonstrated that only a subset of patients correctly understood the role of the radiologist (46% in the 1st survey and 63% in the 2nd survey, which does not represent a statistically significant difference), which suggests that perhaps the patients did have a conversation with a member of the radiology department staff whom they believed was actually the radiologist. The fact that patients expressed a desire to communicate with the person reading their reports, but then did not take advantage of the opportunity to contact the radiologist, suggests that the issue is more complicated than just a lack of a pathway for communication between patients and radiologists. Perhaps the lack of a clear understanding of the role of the radiologist hinders patients from contacting radiologists, as they feel uncertain as to whom they are actually attempting to reach. Or perhaps patients are sufficiently reassured by having a means through which they could contact the radiologist and do not require the actual communication in order to feel comfortable. There remains a significant amount of work to be done in understanding the barriers in patient-radiologist communications.