CircRNA SCAR Improves High-Glucose-Induced Mitochondrial Dysfunction and Permeability Damage in Retinal Microvascular Endothelial Cells.

This study was designed to assess the role and mechanism of circRNA SCAR in human retinal microvascular endothelial cells (hRMVECs) treated with high glucose. Quantitative real-time polymerase chain reaction (qRT-PCR) and cell counting kit 8 (CCK-8) were used to detect the effects of different concentrations of glucose on circRNA SCAR expression and cell proliferation in hRMVECs. Cell viability, levels of oxygen species (ROS), malondialdehyde (MDA) and adenosine triphosphate (ATP), as well as activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the transfected hRMVECs in each group were detected using CCK-8 and their corresponding detection kits. Changes in mtDNA copy number in high-glucose-induced hRMVECs were observed by qRT-PCR. Additionally, western blot was applied to detect effect of overexpressing circRNA SCAR on the expression levels of mitochondrial function-related proteins (Drp1 and Fis1) and cell permeability-related proteins (claudin-5, occludin and ZO-1) in hRMVECs under high-glucose concentration. According to experimental results, high glucose significantly downregulated circRNA SCAR expression and inhibited cell proliferation in hRMVECs. Instead, overexpression of this circRNA SCAR promoted cell proliferation, reduced levels of ROS, MDA and ATP, and increased SOD and CAT activities in hRMVECs under high-glucose concentration. Also, circRNA SCAR overexpression reversed the high-glucose-induced decrease in mtDNA copy number as well as, high-glucose-induced upregulation of Drp1 and Fis1 protein expression and downregulation of claudin-5, occludin and ZO-1 protein expression in hRMVECs. In summary, circRNA SCAR promotes the proliferation of hRMVECs under high-glucose concentration, alleviates oxidative stress induced by high glucose, and improves mitochondrial function and permeability damage.

Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models.

We have previously shown that roflupram (ROF) protects against MPP+-induced neuronal damage in models of Parkinson's disease (PD). Since impaired degradation of α-synuclein (α-syn) is one of the key factors that lead to PD, here we investigated whether and how ROF affects the degradation of α-syn in rotenone (ROT)-induced PD models in vivo and in vitro. We showed that pretreatment with ROF (10 µM) significantly attenuated cell apoptosis and reduced the level of α-syn in ROT-treated SH-SY5Y cells. Furthermore, ROF significantly enhanced the lysosomal function, as evidenced by the increased levels of mature cathepsin D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1) through increasing NAD+/NADH and the expression of sirtuin 1 (SIRT1). Pretreatment with an SIRT1 inhibitor selisistat (SELI, 10 µM) attenuated the neuroprotection of ROF, ROF-reduced expression of α-syn, and ROF-increased expression levels of LAMP1 and mature CTSD. Moreover, inhibition of CTSD by pepstatin A (20 µM) attenuated ROF-reduced expression of α-syn. In vivo study was conducted in mice exposed to ROT (10 mg·kg-1·d-1, i.g.) for 6 weeks; then, ROT-treated mice received ROF (0.5, 1, or 2 mg·kg-1·d-1; i.g.) for four weeks. ROF significantly ameliorated motor deficits, which was accompanied by increased expression levels of tyrosine hydroxylase, SIRT1, mature CTSD, and LAMP1, and a reduced level of α-syn in the substantia nigra pars compacta. Taken together, these results demonstrate that ROF exerts a neuroprotective action and reduces the α-syn level in PD models. The mechanisms underlying ROF neuroprotective effects appear to be associated with NAD+/SIRT1-dependent activation of lysosomal function.

[Regulatory roles of microRNAs in sarcopenia and exercise intervention].

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.

Fabrication of Si Nanoparticles Encapsulated into Porous N-Doped Carbon for Superior Lithium Storage Performances.

To improve lithium storage performances of Si anode for lithium-ion batteries, Si nanoparticles encapsulated into porous N-doped carbon (Si@PNC) was devised and prepared by metal nitrate accelerated polymer blowing process. The Si@PNC composites have large specific surface area of 221.7 m² g-1 and possess a great deal of mesopores and micropores, which are attributed to the carbonization of PVP and etching metallic nanoparticles. As anode for lithium ion battery, the initial discharge capacity of Si@PNC composites is high to 1626 mA h g-1, and the specific capacity still retains 1030 mA h g-1 after 200 cycles at 200 mA g-1. Meanwhile, remarkably improved rate capability is achieved with an excellent reversible specific capacity of 375 mA h g-1 at 5.0 A g-1. The excellent lithium storage performances benefit from the unique porous core-shell structure of Si@PNC composites, which improve electroconductivity, reduce volume dilatation and accelerate lithium ion transmission.

A convenient and efficient precursor transformation route to well-dispersed, stable, and highly accessible supported Au nanocatalysts with excellent catalytic hydrogenation performances.

A new, convenient, and efficient precursor transformation route for the synthesis of supported Au nanocatalysts was reported. In this strategy, [Au(en)2]3+-riched titanate nanospheres (en: ethylenediamine) with hierarchical flower-like architecture were pre-synthesized via "ammonia etching-ion exchange" processes and then used as the precursors of the objective catalysts. Direct pyrolysis of these precursors, varying in amount of [Au(en)2]3+, led to the formation of Au nanoparticles (AuNPs) with different contents uniformly supported on highly crystalline titania nanoflowers (fTiO2). The fTiO2-supported AuNPs nanocomposites possessed highly open porous structures with large surface areas (142.3-149.3 m2 g-1), which could allow guest molecules to diffuse in and out easily. More interestingly, the formed AuNPs with small size (∼3.8 nm) were well-dispersed and partially embedded into the nanosheets of fTiO2, which was beneficial for achieving high activity while avoiding their detachment from the support during application. Accordingly, the AuNPs/TiO2 catalysts exhibited superior catalytic properties for 4-nitrophenol hydrogenation with significantly higher catalytic efficiencies than many previously reported heterogeneous catalysts. Moreover, the catalytic activity could remain almost unchanged after being recycled several times, demonstrating their high stability. These findings open up a new possibility for rational design and synthesis of supported catalysts for diverse catalytic applications.

Comparison of Posteromedial Versus Posterolateral Approach for Posterior Malleolus Fixation in Trimalleolar Ankle Fractures.

OBJECTIVE: To compare clinical and radiographic outcomes of posterior malleolar fractures (PMF) treated with lag screws from anterior to posterior versus posterior to anterior approach. METHODS: We retrospectively analyzed 48 patients with trimalleolar fractures who underwent open reduction and internal fixation (ORIF) with either posteromedial (PM) or posterolateral (PL) approaches between January 2012 and December 2014. Fixation of the posterior malleolus was made with anteroposterior screws in 20 patients using the PM approach and posteroanterior screws in 28 patients using the PL approach. The American Orthopedic Foot and Ankle Society (AOFAS) scores and range of motion (ROM) of the ankle were used as the main outcome measurements, and results were evaluated at the 6-month, 12-month and final follow-up. Postoperative radiographs and computed tomography scans were used to evaluate the residual gap/step-off. The degree of arthritis was evaluated on final follow-up using Bargon criteria. Other complications were also recorded to compare the clinical outcomes of the two approaches. RESULT: The mean duration of follow-up regardless of the approaches was 21.1 months (range, 15-54 months). None of the patients developed delayed union or nonunion. Functional bone healing was obtained in all patients at 10.7 weeks (range, 8-16 weeks). The mean AOFAS scores of the PM group at the postoperative 6-mouth, 12-month, and final follow-up were 91.4 (range, 82-100), 92.5 (range, 84-100), and 92.9 (range, 86-100), respectively. In the PL group, the mean AOFAS scores were 89.9 (range, 72-100), 91.4 (range, 77-100), and 91.9 (range, 77-100), respectively. At the final follow-up, the median loss of range of motion (ROM) for dorsiflexion and plantaflexion were 0°(0°, 5°) and 0°(0°, 0°), respectively, in both groups. There were no significant differences between the two approaches in AOFAS scores and ROM of the ankle in each period postoperatively (P > 0.05). Two patients in the PL group and 1 in the PM group developed Bargon grade 2 or 3 arthritis. We detected a 2-mm and 3-mm step-off in 1 patient in the PM and PL groups, respectively. CONCLUSION: Satisfactory results were obtained by using the two approaches for fixation of posterior malleolus, and the approaches have similar clinical and radiographic outcomes. Surgeons should choose the appropriate approach based on their experience.