Secretory Clusterin Inhibits Dopamine Neuron Apoptosis in MPTP Mice by Preserving Autophagy Activity.

Secretory clusterin (sCLU) plays an important role in the research progress of nervous system diseases. However, the physiological function of sCLU in Parkinson's disease (PD) are unclear. The purpose of this study was to examine the effects of sCLU-mediated autophagy on cell survival and apoptosis inhibition in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We found that MPTP administration induced prolonged pole-climbing time, shortened traction time and rotarod time, significantly decreased TH protein expression in the SN tissue of mice. In contrast, sCLU -treated mice took less time to climb the pole and had an extended traction time and rotating rod time. Meanwhile, sCLU intervention induced increased expression of the TH protein in the SN of mice. These results indicated that sCLU intervention could reduce the loss of dopamine neurons in the SN area and alleviate dyskinesia in mice. Furthermore, MPTP led to suppressed viability, enhanced apoptosis, an increased Bax/Bcl-2 ratio, and cleaved caspase-3 in the SN of mice, and these effects were abrogated by sCLU intervention. In addition, MPTP increased the levels of P62 protein, decreased Beclin1 protein, decreased the ratio of LC3B-II/LC3B-I, and decreased the numbers of autophagosomes and autophagolysosomes in the SN tissues of mice. These effects were also abrogated by sCLU intervention. Activation of PI3K/AKT/mTOR signaling with MPTP inhibited autophagy in the SN of MPTP mice; however, sCLU treatment activated autophagy in MPTP-induced PD mice by inhibiting PI3K/AKT/mTOR signaling. These data indicated that sCLU treatment had a neuroprotective effect in an MPTP-induced model of PD.

Widely targeted metabolomics analysis reveals new biomarkers and mechanistic insights on chestnut (Castanea mollissima Bl.) calcification process.

Chestnut calcification is a quality deterioration due to fast water loss, which has been of deep concern for chestnut quality control because its mechanism is unclear. In order to find out the different key metabolites and metabolic pathways related to the occurrence of chestnut calcification, in this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) based widely targeted metabolomics analysis was performed on chestnuts that were stored at 50%-55% (low relative humidity, LRH) at 25 °C and 85%-90% (high relative humidity, HRH) at 25 °C. A total of 611 metabolites were detected, and 55 differentially accumulated metabolites were identified as key metabolites involved in chestnut calcification process. The decrease in some monosaccharides accompanied with the increase in some unsaturated fatty acids indicated the degradation of chestnut cell wall and cell membrane during calcification process. As a stress response, amino acid metabolism related to membrane stability was significantly activated. In addition, the enhancement of phenylpropanoid biosynthesis pathway and flavonoid biosynthesis pathway characterized by the accumulation of lignin precursors and antioxidants suggested that lignification process was triggered in calcified chestnut. Therefore, the degradation and hardening of the cell wall and membrane damage were proposed to be associated with the calcification occurrence of chestnut. The metabolic profile of chestnut characterized in this study provided new insights into chestnut calcification process and laid a foundation for further chestnut quality control.

Development and characterization of an edible chitosan-whey protein nano composite film for chestnut (Castanea mollissima Bl.) preservation.

Chitosan (CHI) and whey protein are usually used to prepare edible films for food preservation. However, the composite film composed of the two components does not yield satisfactory properties for chestnut preservation. In this study, nano-cellulose and cinnamaldehyde (CMA) were added to CHI and whey protein, creating a new composite film with strong water retention, bacteriostatic, and mechanical properties. The water vapor permeability (WVP) of the film decreased by 21.61% with the addition of 0.5% (w/v) nano-cellulose, and 23.02% with the addition of 0.3% (w/v) CMA. Furthermore, water solubility (WS) decreased 22.05%, and the density of the film was significantly improved with the addition of 0.3% (w/v) CMA. The optimized formula of the film was CHI 2.5% (w/v), whey protein 3.0% (w/v), nano-cellulose 0.5% (w/v), CMA 0.3% (w/v), and pH 3.8, as determined by orthogonal testing L9(34 ), with fuzzy comprehensive assessment, of WVP, WS, tensile strength, and elongation at break. The film clearly inhibited the growth of E. coli, S. aureus, and Chinese chestnut fungus, destroying the mycelial structure of the fungus. In addition, coating effectively reduced the weight loss, mildew rate, and calcification index during 16 days of storage of chestnuts at 25 °C.

Perfluorooctanoic acid and perfluorooctane sulfonate co-exposure induced changes of metabolites and defense pathways in lettuce leaves.

Growing evidence shows plants are at risks of exposure to various per- and polyfluoroalkyl substances (PFASs), however the phytotoxicity induced by these compounds remains largely unknown on the molecular scale. Here, lettuce exposed to both perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) at different concentrations (500, 1000, 2000 and 5000 ng/L) in hydroponic media was investigated via metabolomics. Under the co-exposure conditions, the growth and biomass were not affected by PFOA and PFOS, but metabolic profiles of mineral elements and organic compounds in lettuce leaves were significantly altered. The contents of Na, Mg, Cu, Fe, Ca and Mo were decreased 1.8%-47.8%, but Zn was increased 7.4%-24.2%. The metabolisms of amino acids and peptides, fatty acids and lipids were down-regulated in a dose-dependent manner, while purine and purine nucleosides were up-regulated, exhibiting the stress response to PFOA and PFOS co-exposure. The reduced amounts of phytol (14.8%-77.0%) and abscisic acid (60.7%-73.8%) indicated the alterations in photosynthesis and signal transduction. The metabolism of (poly)phenol, involved in shikimate-phenylpropanoid pathway and flavonoid branch pathway, was strengthened, to cope with the stress of PFASs. As the final metabolites of (poly)phenol biosynthesis, the abundance of various antioxidants was changed. This study offers comprehensive insight of plant response to PFAS co-exposure and enhances the understanding in detoxifying mechanisms.

Low Density Lipoprotein Peptide-Conjugated Gold Nanorods for Combating Gastric Cancer.

As a potential drug carrier, the toxicity of gold nanorods (AuNRs) has been extensively studied to ensure their safety. Some of these studies reported that AuNRs caused a series of toxic cell responses and inspired the hypothesis that AuNRs may act as anti-cancer agents. In the present study, we synthesized AuNRs (72× 17 nm) and low density lipoprotein (LDL) peptide-RLT modified AuNRs to test this hypothesis. A tumor cell inhibition assay was conducted in five cell lines, and RLT-AuNRs demonstrated the most efficient inhibition of SGC-7901 cells. RLT-AuNRs inhibited SGC-7901 cells and increased SGC-7901 cell apoptosis more effectively than did AuNRs and DOX in vitro. Treatment with RLT-AuNRs reduced the tumor volume, decreased the tumor weight, and enhanced the tumor inhibition rates. RLT-AuNRs showed comparable anti-tumor efficacy with DOX but possessed higher in vivo safety than did DOX. Nude mice treated with RLT-AuNRs showed good health and gained weight during the ten-day anti-tumor therapy. Histological results showed no tissue toxicity of RLT-AuNRs. Therefore, RLT-AuNRs may be a viable anti-tumor agent for gastric cancer.

Ethosomes as delivery system for transdermal administration of vinpocetine.

The purpose of the present study was to develop a novel transdermal vinpocetine patch containing a stable formulation and with good entrapment efficiency, and percutaneous absorption which via ethosome. Ethosome was found to be a more efficient delivery carrier with high encapsulation capacities (79.5% +/- 1.8%) and nanometric size (180.7 +/- 1.5 nm). In vitro percutaneous permeation experiments demonstrated that the permeation of vinpocetine through abdominal skin of Sprague Dawley was significantly increased when ethosome was used. The vinpocetine transdermal fluxes from ethosome gel (3.56 +/- 0.13 microg/cm2/h) were 6.72 and 3.10 times higher than that of vinpocetine gel solution and vinpocetine aueous solution, respectively. Furthermore, the AUC(0 --> infinity), and eliminiation half-life by the transdermal administration were significantly higher than those by the intragastric administration (P < 0.01). The study demonstrated that ethosome is a promising vesicular carrier for enhancing percutaneous absorption of vinpocetine.