Differentiation of Wharton's jelly mesenchymal stem cells into neurons in alginate scaffold

Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton's jelly mesenchymal stem cells(WJMSCs) and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin(marker for WJMSCs-differentiated neuron) and CD271(motor neuron marker). β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.     

Synthesis and Structure-Driven Acid-Catalyzed Degradation of Benzoic Cyclic Acetal-Labeled PEG Precursors toward Shell-Sheddable PLA Block Copolymer Synthesis

The synthesis of acid-degradable poly(ethylene glycol) (PEG) precursors labeled with benzoic cyclic acetal (BzCA) is reported. To get an insight into their acid-catalyzed hydrolysis, three precursors are designed with spacers exhibiting different inductive effects between PEG and BzCA linkage. The ¹H-NMR analysis confirms the order of increasing acid-catalyzed hydrolysis to be ether > ester oxygen > ester carbonyl, which can be attributed to their ability to stabilize benzylic carbocation intermediates formed during hydrolysis. The formed precursors tend to be stable under a tin-catalyzed condition for ring opening polymerization of lactide (LA), thus enabling the synthesis of well-controlled acid-degradable PEG-based PLA block copolymers labeled with BzCA linkage at the block junction. When being exposed to acidic pH, the copolymers degrade through the cleavage of the junction BzCA linkages. These results guide the design principle of acid-degradable shell-sheddable BzCA-bearing block copolymers for control over their acid-catalyzed degradation and potentially drug release kinetics.     

Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice

Restenosis remains a major cause of morbidity and mortality after coronary angioplasty. Injury-induced inflammation, thrombosis, smooth muscle cell (SMC) proliferation, and neointimal formation contribute to restenosis. These events are linked to circulating glucose-derived advanced gycation endproducts (AGE), known to promote cell proliferation, lipid glycoxidation and oxidant stress. This study evaluates the association between dietary AGE content and neointimal formation after arterial injury in genetically hypercholesterolemic mice. Male, 12-week-old, apolipoprotein E-deficient (apoE(-/-)) mice were randomly assigned to receive either a high AGE diet (HAD; AGE=15000 U/mg), or a similar diet with ten-fold lower AGE (LAD; AGE=1500 U/mg). These mice underwent femoral artery injury 1 week later, and were maintained on their diets for an additional 4 weeks. At 4 weeks after injury, significant decrease in neointimal formation was noted in LAD-fed mice. Neointimal area, intima/media ratio, and stenotic luminal area (LA) were less pronounced in the LAD group than the HAD group (P<0.05). These quantitative differences were associated with a marked reduction ( approximately 56%) of macrophages in the neointimal lesions, as well as an obvious reduction of SMC content of LAD-fed mice. The reduction of neointimal formation in the LAD mice correlated with a approximately 40% decrease in circulating AGE levels (P<0.0005). Immunohistochemistry also showed a reduced ( approximately 1.5-fold) deposition of AGE in the endothelia, SMC, and macrophages in neointimal lesions of LAD-fed mice. These results represent the first evidence in vivo for a causal relationship between dietary AGE and the vessel wall response to acute injury, suggesting a significant potential for dietary AGE restriction in the prevention of restenosis after angioplasty.     

Adherence to the Dietary Approaches to Stop Hypertension (DASH) and risk of Nonalcoholic Fatty Liver Disease

This case–control study was conducted to examine the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of Nonalcoholic Fatty Liver Disease (NAFLD) development in 102 patients with newly diagnosed NAFLD and 204 controls. Adherence to DASH-style diet was assessed using a validated food frequency questionnaire, and a DASH diet score based on food and nutrients emphasized or minimized in the DASH diet. Participants in the top quartile of DASH diet score were 30% less likely to have NAFLD (OR: 0.0.70; 95%?CI: 0.61, 0.80); however, more adjustment for dyslipidemia and body mass index changed the association to non-significant (OR: 0.92; 95%?CI: 0.73, 1.12). In conclusion, we found an inverse relationship between the DASH-style diet and risk of NAFLD. Prospective studies are needed to confirm this association.     

Habitual Physical Activity Levels Are Associated with Performance in Measures of Physical Function and Mobility in Older Men

OBJECTIVES: To determine whether objectively measured physical activity levels are associated with physical function and mobility in older men. DESIGN: Cross‐sectional. SETTING: Academic research center. PARTICIPANTS: Eighty‐two community‐dwelling men aged 65 and older with self‐reported mobility limitations were divided into a low‐activity and a high‐activity group based on the median average daily physical activity counts of the whole sample. MEASUREMENTS: Physical activity according to triaxial accelerometers; physical function and mobility according to the Short Physical Performance Battery (SPPB), gait speed, stair climb time, and a lift‐and‐lower task; aerobic capacity according to maximum oxygen consumption (VO₂max); and leg press and chest press maximal strength and peak power. RESULTS: Older men with higher physical activity levels had a 1.4‐point higher mean SPPB score and a 0.35‐m/s faster walking speed than those with lower physical activity levels. They also climbed a standard flight of stairs 1.85 seconds faster and completed 60% more shelves in a lift‐and‐lower task (all P<.01); muscle strength and power measures were not significantly different between the low‐ and high‐activity groups. Correlation analyses and multiple linear regression models showed that physical activity is positively associated with all physical function and mobility measures, leg press strength, and VO₂max. CONCLUSION: Older men with higher physical activity levels demonstrate better physical function and mobility than their less‐active peers. Moreover, physical activity levels are predictive of performance in measures of physical function and mobility in older men. Future work is needed to determine whether modifications in physical activity levels can improve or preserve physical performance in later life.