Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifunctional iron-binding globular glycoprotein, was screened to identify novel neuroprotective pathways against dopaminergic neuronal impairment. We found that Lf substantially ameliorated PD-like motor dysfunction in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We further showed that Lf could alleviate MPTP-triggered apoptosis of DA neurons, neuroinflammation, and histological alterations. As expected, we also found that Lf suppressed MPTP-induced excessive iron accumulation and the upregulation of divalent metal transporter (DMT1) and transferrin receptor (TFR), which is the main intracellular iron regulation protein, and subsequently improved the activity of several antioxidant enzymes. We probed further and determined that the neuroprotection provided by Lf was involved in the upregulated levels of brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor 1α (HIF-1α) and its downstream protein, accompanied by the activation of extracellular regulated protein kinases (ERK) and cAMP response element binding protein (CREB), as well as decreased phosphorylation of c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. Our findings suggest that Lf may be an alternative safe drug in ameliorating MPTP-induced brain abnormalities and movement disorder.
For investigating the relationship between thermal properties and biodegradability of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), several films of PHBV containing different polyhydroxyvalerate (HV) fractions were subjected to degradation in different conditions for up to 49 days. Differential scanning calorimetry (DSC), thermogravimetry (TG), specimen weight loss and scanning electron microscopy (SEM) were performed to characterize the thermal properties and enzymatic biodegradability of PHBV. The experimental results suggest that the degradation rates of PHBV films increase with decreasing crystallinity; the degradability of PHBV occurring from the surface is very significant under enzymatic hydrolysis; the crystallinity of PHBV decreased with the increase of HV fraction in PHBV; and no decrease in molecular weight was observed in the partially-degraded polymer.
A high preoperative plasma fibrinogen level is an independent predictor of distant metastasis and survival prognosis after radical nephrectomy in patients with renal cell carcinoma.
A detailed study has been undertaken on crack healing at high temperatures in a silicon nitride containing 10 wt% additives in order to identify the dominant mechanism responsible for the phenomenon. Fracture toughness increased with annealing time and the crack growth rate decreased until arrest with increasing testing time. Differentiation between possible operating mechanisms was obtained using critical experiments involving detailed compliance measurements, crack wake removal, and crack reinitiation tests and a comprehensive TEM study of healed cracks. It was found that crack healing was not uniform in the crack wake. When the original crack path was either transgranular or intergranular, healing was associated with the appearance of a thin layer of silica glass due to the oxidation of Si 3 N 4 grains. But when the crack went through multigrain junctions, the former crack path was completely obliterated and replaced by a new, crystalline phase formed by diffusion of the preexisting glass phase. It is concluded that the increased crack growth resistance and fracture toughness at high temperature is attributable to the partial recovery of the original strength from the crack segments at multigrain junctions due to vitreous phase flow and subsequent crystallization.
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