Exercise and mitochondrial health.

Mitochondrial health is an important mediator of cellular function across a range of tissues, and as a result contributes to whole-body vitality in health and disease. Our understanding of the regulation and function of these organelles is of great interest to scientists and clinicians across many disciplines within our healthcare system. Skeletal muscle is a useful model tissue for the study of mitochondrial adaptations because of its mass and contribution to whole body metabolism. The remarkable plasticity of mitochondria allows them to adjust their volume, structure and capacity under conditions such as exercise, which is useful or improving metabolic health in individuals with various diseases and/or advancing age. Mitochondria exist within muscle as a functional reticulum which is maintained by dynamic processes of biogenesis and fusion, and is balanced by opposing processes of fission and mitophagy. The sophisticated coordination of these events is incompletely understood, but is imperative for organelle function and essential for the maintenance of an interconnected organelle network that is finely tuned to the metabolic needs of the cell. Further elucidation of the mechanisms of mitochondrial turnover in muscle could offer potential therapeutic targets for the advancement of health and longevity among our ageing populations. As well, investigating exercise modalities that are both convenient and capable of inducing robust mitochondrial adaptations are useful in fostering more widespread global adherence. To this point, exercise remains the most potent behavioural therapeutic approach for the improvement of mitochondrial health, not only in muscle, but potentially also in other tissues.

Restoration of Polyamine Metabolic Patterns in In Vivo and In Vitro Model of Ischemic Stroke following Human Mesenchymal Stem Cell Treatment.

We investigated changes in PA levels by the treatment of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS-treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM-MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In the in vivo MCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In the in vitro OGD system, N (1)-acetylspermidine, spermidine, N (1)-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group.

Microfluidic assessment of mechanical cell damage by extensional stress.

Mammalian cells have been widely used in bioreactors to produce biological products such as pharmaceutical materials. The productivity of such bioreactors is vastly affected by flow-induced cell damage in complicated flow environments, such as agitation-driven turbulence and oxygen bubble bursting at the interface between the culturing medium and air. However, there is no systematic approach to diagnose the cell damage caused by the hydrodynamic stress. In this work, we propose a novel microfluidic method to accurately assess the mechanical cell damage under a controlled extensional stress field, generated in a microfluidic cross-slot geometry. The cell damage in the extensional field is related to the oxygen bubble bursting process. We employed viscoelasticity-induced particle focusing to align the cells along the shear-free channel centerline, so that all the cells experience a similar extensional stress field, which also precludes the cell damage due to wall shear stress. We applied our novel microfluidic sensor to find the critical extensional stress to damage Chinese hamster ovary (CHO) cells; the critical stress is found to be ∼250 Pa. Our current results are relevant in the design of practical bioreactors, as our results clearly demonstrate that the control of the bubble bursting process is critical in minimizing cell damage in bioreactor applications. Further, our results will provide useful information on the biophysical cell properties under fluid flow environments.

Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro.

The potential toxicity of nanoparticles, particularly to neurons, is a major concern. In this study, we assessed the cytotoxicity of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye (MNPs@SiO2(RITC)) in HEK293 cells, SH-SY5Y cells, and rat primary cortical and dopaminergic neurons. In cells treated with 1.0 µg/µl MNPs@SiO2(RITC), the expression of several genes related to the proteasome pathway was altered, and proteasome activity was significantly reduced, compared with control and with 0.1 µg/µl MNPs@SiO2(RITC)-treated cells. Due to the reduction of proteasome activity, formation of cytoplasmic inclusions increased significantly in HEK293 cells over-expressing the α-synuclein interacting protein synphilin-1 as well as in primary cortical and dopaminergic neurons. Primary neurons, particularly dopaminergic neurons, were more vulnerable to MNPs@SiO2(RITC) than SH-SY5Y cells. Cellular polyamines, which are associated with protein aggregation, were significantly altered in SH-SY5Y cells treated with MNPs@SiO2(RITC). These findings highlight the mechanisms of neurotoxicity incurred by nanoparticles.