Yina Huang

Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway

Methamphetamine (METH), a commonly abused psychostimulant, has been shown to induce neuronal damage by causing reactive oxygen species (ROS) formation, apoptosis and autophagy. Taurine (2-aminoethanesulfonic acid) is involved in several physiological actions in the brain, including neuroprotection, osmoregulation and neurotransmission. In this study, we investigate the protective effect of taurine against METH-induced neurotoxicity in PC12 cells and the underlying mechanism. The results showed that taurine significantly increased the cell viability inhibited by METH. LC3-II expression was elevated by METH treatment, whereas such increase was obviously attenuated by taurine. Co-treatment of taurine strongly reversed the decline of antioxidase activities induced by METH. Moreover, phosphorylated mammalian target of rapamycin (p-mTOR) was significantly inhibited by METH, whereas complementation of taurine markedly increased the expression of p-mTOR in PC12 cells, rather than phosphorylated Erk. Interestingly, taurine-induced decreasing expression of LC3-II was partially blocked by pretreatment of RAD001, an mTOR inhibitor. These results indicated that taurine inhibits METH-induced autophagic process through activating mTOR rather than Erk signaling. Collectively, our study shows that taurine protects METH-induced PC12 cells damage by attenuating ROS production, apoptosis and autophagy, at least in part, via mTOR signaling pathway.

Zinc oxide nanoparticles cause nephrotoxicity and kidney metabolism alterations in rats

Although zinc oxide nanoparticles (ZnO NPs) have been widely used, their potential hazards on mammalian and human remain largely unknown. In this study, the biochemical compositions of urine and kidney from the rats treated with ZnO NPs (100, 300 and 1000 mg/kg, respectively) were investigated using 1H nuclear magnetic resonance (NMR) technique with the pattern recognition of partial least squares-discriminant analysis. Hematology, clinical biochemistry and kidney histopathological examinations were also performed. Metabolic profiles from rats treated with ZnO NPS exhibited increases in the levels of taurine, lactate, acetate, creatine, phosphocholine, trimethylamine-N-oxide, α-glucose, and 3-D-hydroxybutyrate, as well as decreases in lipid, succinate, citrate, α-ketoglutarate, hippurate and 4-hydroxyphenylacetic acid in urine after ZnO NPs treatment for 14 days. A similar alteration pattern was also identified in kidney. Urine choline and phosphocholine increased significantly shortly after ZnO NPs treatment, moreover, some amino acids and glucose also increased during the experimental period. However, succinate, citrate and α-ketoglutarate in urine exhibited a different alteration trend, which showed increases on the first day after ZnO NPs treatment, but decreases gradually until the termination of the study. A similar alteration pattern of urinary 1H NMR spectra was also detected in kidney. Moreover, ZnO NPs (1000 mg/kg) resulted in significant increases in serum creatine and blood urea nitrogen, decreases in hemoglobin, haematocrit and mean corpuscular hemoglobin concentration, and overt tubular epithelial cell necrosis. These findings show that ZnO NPs can disturb the energy metabolism and cause mitochondria and cell membrane impairment in rat kidney, which may contribute to ZnO NPs-induced nephrotoxicity.

Antibrowning and antimicrobial activities of the water-soluble extract from pine needles of Cedrus deodara.

UNLABELLED The antibrowning and antimicrobial activities of the water-soluble extract from pine needles of Cedrus deodara (CDE), a traditional Chinese medicine and raw materials of pine needle tea, was investigated. Total phenols of CDE were 31.4 ± 0.53 mg gallic acid equivalent/g, and total flavonoids were 23.1 ± 0.79 mg rutin equivalent/g. CDE showed a strong antioxidant activity against ABTS free radicals with IC(50) (the half-inhibitory concentration) of 25.5 ± 0.64 μg/mL. In mushroom tyrosinase inhibitory assay, IC(50) values were 2.1 ± 0.98 and 2.27 ± 0.93 mg/mL for monophenolase and diphenolase, respectively. Evaluated by detecting changes of L* (indicated the darkness of sample), a* (indicated the redness of sample), and b* (indicated the yellowness of sample) values in fresh-cut apple slices model, CDE showed a significant antibrowning effect when compared with ascorbic acid. In addition, it was discovered that CDE in combination with 0.5% ascorbic acid exhibited a synergistic antibrowning effect. Meanwhile, CDE was observed to show a potent antimicrobial effect on all of the tested Gram-positive and Gram-negative bacteria. In conclusion, the results of the present research suggested that pine needles of C. deodara could be used as a natural resource of antibrowning and antimicrobial agents in food preservation. PRACTICAL APPLICATION The present study provides a theoretical basis for the potential application of pine needles of C. deodara to be used as a natural resource of antibrowning and antimicrobial agents in food industry.

Acute toxicity and genotoxicity studies on poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) nanomaterials

In the present study, we prepared poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanomaterials by solvent-extraction method. The obtained PCEC nanomaterials were studied extensively for acute toxicity and genotoxicity using bacterial reverse mutation test (Ames test), chromosomal aberration test and mouse micronucleus test. All of the Sprague-Dawley rats did not show any mortality and clinical signs of toxicity after intravenous injection at the level of 2.4g/kg body weight. Thus, the LD(50) of PCEC nanomaterials was determined to be greater than 2.4g/kg. In Ames test, PCEC nanomaterials were negative in Salmonellatyphimurium strains TA97, TA98, TA100, TA102, and TA1535 with or without metabolic activation. PCEC nanomaterials did not induce chromosomal aberrations in cultured Chinese hamster lung cells up to 5000mug/mL with or without metabolic activation. Micronucleus assay demonstrated that PCEC nanomaterials did not significantly increase micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of ICR mice or suppress bone marrow, indicating they did not cause chromosome aberrations. In conclusion, our results indicated that PCEC nanomaterials did not cause any acute toxicity and genotoxicity in our experimental conditions. Its potential to be a candidate of drug carrier is worth being further investigated.

Metabolomics: A Revolution for Novel Cancer Marker Identification

The repertoire of small-molecular-weight substances present in cells, tissue and body fluids are known as the metabolites. The global analysis of metabolites, such as by high-resolution ¹H nuclear magnetic resonance spectroscopy and mass spectrometry, is integral to the rapidly expanding field of metabolomics, which is making progress in various diseases. In the area of cancer and metabolic phenotype, the integrated analysis of metabolites may provide a powerful platform for detecting changes related to cancer diagnosis and discovering novel biomarkers. In this review, metabolomics including the technologies in metabolomics research and extracting information from metabolomics datasets are described. Then we discuss the challenges and opportunities in metabolomics for finding metabolic processes in cancer and discovering novel cancer biomarkers. Finally, we assess the clinical applicability of metabolomics.

Cytokines induced by long-term potentiation (LTP) recording: A potential explanation for the lack of correspondence between learning/memory performance and LTP

The relationship between learning/memory performance and long-term potentiation (LTP) induction is ambiguous. Although a large body of data supports a strong correspondence between learning/memory performance and LTP, many studies have also provided evidence to the contrary. In this study, we found that 2-month-old senescence-accelerated mice/prone 8 (SAMP8 mice) displayed both impaired performance in a Morris Water Maze (MWM) and enhanced LTP compared to senescence-accelerated mice/resistance 1 (SAMR1). BALB/c mice challenged with Complete Freunds Adjuvant (CFA) performed better in the shuttle-box test but displayed impaired LTP compared to intact animals. It is interesting that BALB/c mice challenged with Incomplete Freunds Adjuvant (IFA) performed better than intact animals, with no LTP impairment. Cytokine analysis showed no significant differences between the interleukin-6 (IL-6), interleukin-10 (IL-10) or TNF-α content in the intact hippocampal tissues of either the SAMR1 and SAMP8 mice or the immune-challenged BALB/c and intact animals. Further analysis demonstrated that the increase in cytokine content was higher in the hippocampal tissues used for LTP recording in the SAMR1 and CFA-challenged animals compared to the SAMP8 and intact BALB/c mice. A correlation analysis demonstrated that pro-inflammatory cytokines (IL-6 and TNF-α) displayed a negative correlation with LTP, while an anti-inflammatory cytokine (IL-10) displayed a positive correlation with LTP. These results suggest that pro-inflammatory cytokines induced by LTP manipulation in experiments (e.g., via tissue injury caused by electrode insertion) may be one of the factors contributing to the observed lack of correspondence between memory/learning ability and LTP.

1H NMR-based metabonomics in brain nucleus accumbens and striatum following repeated cocaine treatment in rats

Studies have shown a few cerebral metabolites modified by cocaine in brain regions; however, endogenous metabolic profiling has been lacking. Ex vivo (1)H NMR (hydrogen-1 nuclear magnetic resonance) spectroscopy-based metabonomic approach coupled with partial least squares was applied to investigate the changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats subjected to cocaine treatment. Our results showed that both single and repeated cocaine treatment can induce significant changes in a couple of cerebral metabolites. The increase of neurotransmitters glutamate and gamma-amino butyric acid (GABA) were observed in NAc and striatum from the rats repeatedly treated with cocaine. Creatine and taurine increased in NAc whereas taurine increased and creatine decreased in striatum after repeated cocaine treatment. Elevation of N-acetylaspartate in NAc and striatum and decrease of lactate in striatum were observed, which may reflect the mitochondria dysregulation caused by cocaine; moreover, alterations of choline, phosphocholine and glycerol in NAc and striatum could be related to membrane disruption. Moreover, groups of rats with and without conditioned place preference (CPP) apparatus are presenting difference in metabolites. Collectively, our results provide the first evidence of metabonomic profiling of NAc and striatum in response to cocaine, exhibiting a regionally-specific alteration patterns. We find that repeated cocaine administration leads to significant metabolite alterations, which are involved in neurotransmitter disturbance, oxidative stress, mitochondria dysregulation and membrane disruption in brain.

Intestinal α-glucosidase inhibitory activity and toxicological evaluation of Nymphaea stellata flowers extract.

AIM OF THE STUDY Nymphaea stellata willd. flowers (NSF) are used as a traditional medicine in India and Nepal to treat diabetic disease. Different works have demonstrated that NSF extract showed antihyperglycemic effect on alloxan-induced diabetic rats. In the present work we evaluated in vitro intestinal alpha-glucosidase inhibition as the possible mode of action of NSF extract on suppressing postprandial hyperglycemia for curing diabetic mellitus. In addition, NSF extract was studied to assess its possible acute oral toxicity and genotoxicity. MATERIALS AND METHODS Rat intestinal crude enzyme preparation and Caco-2 monolayer were used to evaluate alpha-glucosidase inhibitory activity of NSF extract. The main alpha-glucosidase inhibitors were detected by HPLC. For acute toxicity test, NSF extract was administered at doses of 2000, 5000 and 10,000 mg/kg body to three groups of 10 ICR mice each, and then clinical symptoms including mortality, clinical sign and gross findings were observed once a day for 14 days. In Ames test, histidine-dependent auxotrophic mutants of Salmonella typhimurium (strains TA97, TA98, TA100, TA102 and TA1535) were used and incubated in the presence and absence of S9 metabolic activation using NSF extract with concentrations of 150-5000 microg/plate. The chromosome aberration test was conducted with Chinese hamster lung (CHL) cells treated with NSF extract at doses of 150-5000 microg/ml in the presence and absence of S9 metabolic activation. In the in vivo mouse micronucleus assay, 9-week-old male and female ICR mice (n=90, 25-30 g) were administered daily by oral gavage at doses of 2.5, 5.0 and 10.0 g/kg body for 1 or 2 days. Bone marrow smears were prepared from each treatment group 24h after last administration and then polychromatic erythrocytes (PCEs) and normochromatic erythrocytes (NCEs) were identified. RESULTS NSF extract showed potent rat intestinal alpha-glucosidase inhibitory activity for maltose hydrolysis with ED(50) value of 0.1 mg/ml. In Caco-2 monolayer, alpha-glucosidase activity for the maltose hydrolysis was down-regulated by NSF extract at a concentration of 0.05 mg/well level, showing 74% inhibition compared to the saline treated control. NSF was rich in phenol contents and the main alpha-glucosidase inhibitor, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, was identified together with two phenolic compounds of gallic acid and corilagin. In acute toxicity test, NSF extract did not produce any toxic signs or deaths and the LD(50) value of this extract could be greater than 10,000 mg/kg body weight. These results of genotoxicity assessment showed that NSF extract did not cause genotoxic effects in Ames test, in the in vitro chromosomal aberration assay and in the in vivo micronucleus assay. CONCLUSION The current study shows that the extract from Nymphaea stellata flowers exhibits significant intestinal alpha-glucosidase inhibitory activity, without showing any acute toxicity or genotoxicity, which may be useful in suppressing postprandial hyperglycemia in diabetics. The results presented here suggest that the use of NSF in folk medicine as a natural antidiabetic treatment could be safe as well as beneficial.