Selenium inhibits ferroptosis in hyperglycemic cerebral ischemia/reperfusion injury by stimulating the Hippo pathway.

Hyperglycemia can exacerbate cerebral ischemia/reperfusion (I/R) injury, and the mechanism involves oxidative stress, apoptosis, autophagy and mitochondrial function. Our previous research showed that selenium (Se) could alleviate this injury. The aim of this study was to examine how selenium alleviates hyperglycemia-mediated exacerbation of cerebral I/R injury by regulating ferroptosis. Middle cerebral artery occlusion (MCAO) and reperfusion models were established in rats under hyperglycemic conditions. An in vitro model of hyperglycemic cerebral I/R injury was created with oxygen-glucose deprivation and reoxygenation (OGD/R) and high glucose was employed. The results showed that hyperglycemia exacerbated cerebral I/R injury, and sodium selenite pretreatment decreased infarct volume, edema and neuronal damage in the cortical penumbra. Moreover, sodium selenite pretreatment increased the survival rate of HT22 cells under OGD/R and high glucose conditions. Pretreatment with sodium selenite reduced the hyperglycemia mediated enhancement of ferroptosis. Furthermore, we observed that pretreatment with sodium selenite increased YAP and TAZ levels in the cytoplasm while decreasing YAP and TAZ levels in the nucleus. The Hippo pathway inhibitor XMU-MP-1 eliminated the inhibitory effect of sodium selenite on ferroptosis. The findings suggest that pretreatment with sodium selenite can regulate ferroptosis by activating the Hippo pathway, and minimize hyperglycemia-mediated exacerbation of cerebral I/R injury.

Glutamine potentiates gentamicin to kill lab-evolved gentamicin-resistant and clinically isolated multidrug-resistant Escherichia coli.

Introduction: Gentamicin is a conventional antibiotic in clinic. However, with the wide use of antibiotics, gentamicin-resistant Escherichia coli (E. coli) is an ever-increasing problem that causes infection in both humans and animals. Thus, it is especially important to restore gentamicin-mediated killing efficacy. Method: E. coli K12 BW25113 cells were passaged in medium with and without gentamicin and obtain gentamicin-resistant (K12-R GEN ) and control (K12-S) strains, respectively. Then, the metabonomics of the two strains were analyzed by GC-MS approach. Results: K12-R GEN metabolome was characterized as more decreased metabolites than increased metabolites. Meantime, in the most enriched metabolic pathways, almost all of the metabolites were depressed. Alanine, aspartate and glutamate metabolism and glutamine within the metabolic pathway were identified as the most key metabolic pathways and the most crucial biomarkers, respectively. Exogenous glutamine potentiated gentamicin-mediated killing efficacy in glutamine and gentamicin dose-and time-dependent manners in K12-R GEN . Further experiments showed that glutamine-enabled killing by gentamicin was effective to clinically isolated multidrug-resistant E. coli. Discussion: These results suggest that glutamine provides an ideal metabolic environment to restore gentamicin-mediated killing, which not only indicates that glutamine is a broad-spectrum antibiotic synergist, but also expands the range of metabolites that contribute to the bactericidal efficiency of aminoglycosides.

Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel.

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.

Effect of hyperglycemia on microglial polarization after cerebral ischemia-reperfusion injury in rats.

Hyperglycemia has been shown to aggravate ischemic brain damage, in which the inflammatory reaction induced by hyperglycemia is involved in the worsening of cerebral ischemia-reperfusion injury. However, the role of microglial polarization in hyperglycemia-aggravating cerebral ischemia-reperfusion injury remains unknown. The present study investigated whether diabetic hyperglycemia inhibited or activated microglia, as well as microglial subtypes 1 and 2. Rats were used to establish the diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) model. The markers CD11b, CD16, CD32, CD86, CD206, and Arg1 were used to show M1 or M2 microglia. The results revealed increased neurological deficits, infarct volume, and neural apoptosis in rats with hyperglycemia subjected to MCAO for 30 min and reperfused at 1, 3, and 7 days compared with the normoglycemic rats. Microglia and astrocyte activation and proliferation were inhibited in hyperglycemic rats. Furthermore, M1 microglia polarization was promoted, while that of M2 microglia was inhibited in hyperglycemic rats. These findings suggested that the polarization of M1 and M2 microglia is activated and inhibited, respectively, in hyperglycemic rats and may be involved in the aggravated brain damage caused by ischemia-reperfusion in diabetic hyperglycemia.

Region-specific changes in aquaporin 4 induced by hyperglycemia underlie the differences in cell swelling in the cortex and striatum after cerebral ischemia-reperfusion.

Brain edema is a major cause of death in patients who suffer an ischemic stroke. Diabetes has been shown to aggravate brain edema after cerebral ischemia-reperfusion, but few studies have focused on the heterogeneity of this response across different brain regions. Aquaporin 4 plays an important role in the formation and regression of brain edema. Here, we report that hyperglycemia mainly affects the continuity of aquaporin 4 distribution around blood vessels in the cortical penumbra after ischemia-reperfusion; however, in the striatal penumbra, in addition to affecting the continuity of distribution, it also substantially affects the fluorescence intensity and the polarity distribution in astrocytes. Accordingly, hyperglycemia induces a more significant increase in the number of swelling cells in the striatal penumbra than in the cortical penumbra. These results can improve our understanding of the mechanism underlying the effects of diabetes in cerebral ischemic injury and provide a theoretical foundation for identification of appropriate therapeutic modalities.

The Involvement of Mitochondrial Biogenesis in Selenium Reduced Hyperglycemia-Aggravated Cerebral Ischemia Injury.

Selenium has been shown to possess antioxidant and neuroprotective effects by modulating mitochondrial function and activating mitochondrial biogenesis. Our previous study has also suggested that selenium protected neurons against glutamate toxicity and hyperglycemia-induced damage by regulating mitochondrial fission and fusion. However, it is still not known whether the mitochondrial biogenesis is involved in selenium alleviating hyperglycemia-aggravated cerebral ischemia reperfusion (I/R) injury. The object of this study is to define whether selenium protects neurons against hyperglycemia-aggravated cerebral I/R injury by promoting mitochondrial biogenesis. In vitro oxygen deprivation plus high glucose model decreased cell viability, enhanced reactive oxygen species production, and meanwhile stimulated mitochondrial biogenesis signaling. Pretreated with selenium significantly decreased cell death and further activated the mitochondrial biogenesis signaling. In vivo 30 min of middle cerebral artery occlusion in the rats under hyperglycemic condition enhanced neurological deficits, enlarged infarct volume, exacerbated neuronal damage and oxidative stress compared with normoglycemic ischemic rats after 24 h reperfusion. Consistent to the in vitro results, selenium treatment alleviated ischemic damage in hyperglycemic ischemic animals. Furthermore, selenium reduced the structural changes of mitochondria caused by hyperglycemic ischemia and further promoted the mitochondrial biogenesis signaling. Selenium activates mitochondrial biogenesis signaling, protects mitochondrial structure integrity and ameliorates cerebral I/R injury in hyperglycemic rats.

Synaptic remodeling and reduced expression of the transcription factors, HES1 and HES5, in the cortex neurons of cognitively impaired hyperhomocysteinemic mice.

Hyperhomocysteinemia (HHcy) is associated with cognitive impairment and neurodegenerative diseases. The synaptic ultrastructure and the expression of hairy enhancer of split (HES) genes are involved in cognitive impairment induced by HHcy, but their precise role remains unclear. The present study aimed to measure synaptic remodeling and the expression of HES1 and HES5 in the cortex neurons of mice with HHcy to clarify their role in cognitive impairment. Mild HHcy was induced in ApoE-/- mice receiving a high-methionine diet. The correct response percentage, latency, and distance traveled in the mice with HHcy decreased compared with those of non-HHcy control mice (P < 0.05). There was no difference in the neuronal counts and the mean optical density of Nissl bodies in the frontal cortex of HHcy and non-HHcy mice. Increased apoptosis rates and numbers of autophagosomes were observed in the HHcy mice by TUNEL staining and electron microscopy, respectively, compared to those in the control group (P < 0.05). There was a significant increase in the area of postsynaptic density and size variation of synaptic vesicles in the HHcy group compared to that in the control (P < 0.05). Decreased expression of HES1 and HES5 was observed by western blotting and immunostaining in the HHcy group compared to that in the control (P < 0.05). Collectively, these results suggest that increased autophagy, apoptosis, synaptic remodeling, and downregulation of hes1 and hes5 are involved in the cognitive impairment induced by hyperhomocysteinemia.

Coenzyme Q10 Protects Astrocytes from Ultraviolet B-Induced Damage Through Inhibition of ERK 1/2 Pathway Overexpression.

Overexpression of extracellular signal-regulated kinase ½ (ERK ½) signaling pathway leads to overproduction of reactive oxygen species (ROS) which induces oxidative stress. Coenzyme Q10 (CoQ10) scavenges ROS and protects cells against oxidative stress. The present study was designed to examine whether the protection of Coenzyme Q10 against oxidative damage in astrocytes is through regulating ERK 1/2 pathway. Ultraviolet B (UVB) irradiation was chosen as a tool to induce oxidative stress. Murine astrocytes were treated with 10 µg/ml and 25 µg/ml of CoQ10 for 24 h prior to UVB and maintained during UVB and 24 h post-UVB. Cell viability was evaluated by counting viable cells and MTT conversion assay. ROS production was measured using fluorescent probes. Levels of p-ERK 1/2, ERK 1/2, p-PKA, PKA were detected using immunocytochemistry and/or Western blotting. The results showed that UVB irradiation decreased the number of viable cells. This damaging effect was associated with accumulation of ROS and elevations of p-ERK 1/2 and p-PKA. Treatment with CoQ10 at 25 µg/ml significantly increased the number of viable cells and prevented the UVB-induced increases of ROS, p-ERK 1/2, and p-PKA. It is concluded that suppression of the PKA-ERK 1/2 signaling pathway may be one of the important mechanisms by which CoQ10 protects astrocytes from UVB-induced oxidative damage.

Selenium suppresses glutamate-induced cell death and prevents mitochondrial morphological dynamic alterations in hippocampal HT22 neuronal cells.

BACKGROUND: Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage. RESULTS: We find that glutamate-induced cytotoxicity was associated with enhancement of superoxide production, activation of caspase-9 and -3, increases of mitochondrial fission marker and mitochondrial morphological changes. Selenium significantly resolved the glutamate-induced mitochondria structural damage, alleviated oxidative stress, decreased Apaf-1, caspases-9 and -3 contents, and altered the autophagy process as observed by a decline in the ratio of the autophagy markers LC3-I and LC3-II. CONCLUSION: These findings suggest that the protection of selenium against glutamate stimulated cell damage of HT22 cells is associated with amelioration of mitochondrial dynamic imbalance.

Overexpression of selenoprotein H prevents mitochondrial dynamic imbalance induced by glutamate exposure.

Selenium and selenoproteins play important roles in neuroprotection against glutamate­induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. Recent studies have revealed that mitochondrial fission could activates mitochondrial initiated cell death pathway. The objectives of the study are to determine whether glutamate induced cell death is mediated through mitochondrial initiated cell death pathway and activation of autophagy, and whether overexpression of selenoprotein H can protect cells from glutamate toxicity by preserving mitochondrial morphology and suppressing autophagy. Vector- or human selenoprotein H (SelH)-transfected HT22 cells (V-HT22 and SelH-HT22, respectively) were exposed to glutamate. The results showed that glutamate-induced cytotoxicity was associated with increased ROS production and imbalance in mitochondrial dynamics and autophagy. These alterations were reversed and cellular integrity restored by overexpression of SelH in HT22 cells.

Interleukin-17A promotes the formation of inflammation in the lung tissues of rats with pulmonary fibrosis.

The aim of the present study was to investigate the effects of interleukin (IL)-17A in a rat model of pulmonary fibrosis. In total, 20 female Wistar rats were randomly divided into a normal saline (NS group) and a bleomycin group (BLM group). The BLM group rats were intratracheally instilled with BLM, while the NS group rats were intratracheally instilled with saline. In each group, half the rats were sacrificed at day 7 and day 28, respectively, following intratracheal instillation. Subsequently, hematoxylin and eosin and Masson's trichrome staining were performed to observe the pathological changes in the lung tissue, while the expression of IL-17A in the lung tissue was detected by immunohistochemistry. In addition, the bronchoalveolar lavage fluid (BALF) was collected and divided into two sections. One section was used for cell counting and classification, and an ELISA was performed to detect the concentration of IL-17A in the BALF. The additional section was used to separate, purify and cultivate alveolar macrophages (AMs). The concentration of IL-17A in the cultivating supernatant was detected by ELISA, and the mRNA expression levels of IL-17A in the AMs were detected using reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that a considerable number of inflammatory cells had infiltrated into the alveolar cavity in the BLM group at day 7, and less alveolitis and more serious fibrosis were observed at day 28, as compared with the NS group. Furthermore, when compared with the NS group, the protein expression levels of IL-17A in the lung tissue were markedly higher in the BLM group at days 7 and 28 (higher at day 7; P<0.05). In addition, the total number of BALF cells in the BLM group was clearly higher at day 7 when compared with the NS group (P<0.05), although a normal level was re-established by day 28. The level of IL-17A in the BALF increased significantly at days 7 and 28 in the BLM group; however, when compared with the level at day 7, the concentration had decreased at day 28. When compared with the NS group, the protein expression levels of IL-17A in the BLM group were notably higher after 12, 24 and 48 h. In addition, the results of the RT-PCR assay revealed that the mRNA expression levels of IL-17A increased significantly at days 7 and 28 in the BLM group when compared with the NS group (P<0.05). Therefore, IL-17A was demonstrated to promote the development of pulmonary inflammation, which may be involved in the development of pulmonary fibrosis.

Metabolome strategy against Edwardsiella tarda infection through glucose-enhanced metabolic modulation in tilapias.

Edwardsiella tarda causes fish disease and great economic loss. However, metabolic strategy against the pathogen remains unexplored. In the present study, GC-MS based metabolomics was used to investigate the metabolic profile from tilapias infected by sublethal dose of E. tarda. The metabolic differences between the dying group and survival group allow the identification of key pathways and crucial metabolites during infections. More importantly, those metabolites may modulate the survival-related metabolome to enhance the anti-infective ability. Our data showed that tilapias generated two different strategies, survival-metabolome and death-metabolome, to encounter EIB202 infection, leading to differential outputs of the survival and dying. Glucose was the most crucial biomarker, which was upregulated and downregulated in the survival and dying groups, respectively. Exogenous glucose by injection or oral administration enhanced hosts' ability against EIB202 infection and increased the chances of survival. These findings highlight that host mounts the metabolic strategy to cope with bacterial infection, from which crucial biomarkers may be identified to enhance the metabolic strategy.

One-Pot Synthesis of Mesoporous TiO2 Micropheres and Its Application for High-Efficiency Dye-Sensitized Solar Cells.

TiO2 microspheres are of great interest for a great deal of applications, especially in the solar cell field. Because of their unique microstructure and light-scattering effect, TiO2 microsphere-based solar cells often exhibit superior photovoltaic performance. Hence, exploring new suitable TiO2 microspheres for high-efficiency solar cells is essential. In this work, we demonstrate a facile one-pot solvothermal approach for synthesis of TiO2 microspheres using acetone as solvent. The as-prepared TiO2 microspheres are composed of densely interconnected nanocrystals and possess a high specific surface area up to 138.47 m(2) g(-1). As the photoanode, the TiO2 microsphere-based DSSC gives higher dye loading and light adsorption ability as well as longer electron lifetime, resulting in higher short-circuit current value and superior power conversion efficiency (PCE) compared with Dyesol 18 nm TiO2 nanoparticle paste. Finally, the TiO2 microsphere-based DSSC were optimized by adding a TiO2 nanocrystal underlayer and TiCl4 post-treatment, giving a high PCE of 10.32%.

Liver functional metabolomics discloses an action of L-leucine against Streptococcus iniae infection in tilapias.

Streptococcus iniae seriously affects the intensive farming of tilapias. Much work has been conducted on prevention and control of S. iniae infection, but little published information on the metabolic response is available in tilapias against the bacterial infection, and no metabolic modulation way may be adopted to control this disease. The present study used GC/MS based metabolomics to characterize the metabolic profiling of tilapias infected by a lethal dose (LD50) of S. iniae and determined two characteristic metabolomes separately responsible for the survival and dying fishes. A reversal changed metabolite, decreased and increased l-leucine in the dying and survival groups, respectively, was identified as a biomarker which featured the difference between the two metabolomes. More importantly, exogenous l-leucine could be used as a metabolic modulator to elevate survival ability of tilapias infected by S. iniae. These results indicate that tilapias mount metabolic strategies to deal with bacterial infection, which can be regulated by exogenous metabolites such as l-leucine. The present study establishes an alternative way, metabolic modulation, to cope with bacterial infections.

L-proline increases survival of tilapias infected by Streptococcus agalactiae in higher water temperature.

Streptococcosis causes massive tilapia kills, which results in heavy economic losses of tilapia farming industry. Out of the Streptococcosis, Streptococcus agalactiae is the major pathogen. The bacterium causes higher mortality of tilapias in higher than lower temperatures. However, effect of temperature on metabolic regulation which is related to the mortality is largely unknown. The present study showed 50% and 70% mortality of tilapias cultured in 25 °C and 30 °C, respectively, in comparison with no death in 20 °C following infection caused by S. agalactiae. Then, GC/MS based metabolomics was used to investigate a global metabolic response of tilapia liver to the two higher water temperatures compared to 20 °C. Thirty-six and forty-five varied abundance of metabolites were identified in livers of tilapias cultured at 25 °C and 30 °C, respectively. More decreasing abundance of amino acids and increasing abundance of carbohydrates were detected in 30 °C than 25 °C groups. On the other hand, out of the pathways enriched, the first five biggest impact pathways belong to amino acid metabolism. Decreasing abundance of l-proline was identified as a crucial biomarker for indexing higher water temperature and a potential modulator to reduce the high death. This was validated by engineering injection or oral addition of l-proline. Exogenous l-proline led to elevated amino acid metabolism, which contributes to the elevated survivals. Our findings provide a potential metabolic modulator for controlling the disease, and shed some light on host metabolic prevention to infectious diseases.

N-acetylglucosamine enhances survival ability of tilapias infected by Streptococcus iniae.

Streptococcus iniae infection has emerged as a serious fish health and economic problem in the global aquaculture operations. Current antibiotic options are few and possess severe practical limitations and potential adverse environmental impacts. The major factor contributing to the large burden of S. iniae disease in aquaculture is the lack of fundamental knowledge of innate immunity against the pathogen. In the present study, we use a tilapia model to explore which metabolites are crucial for the defense against the infection caused by S. iniae. We establish GC/MS based metabolic profile of tilapia liver and then compare the metabolic difference between survivals and the dying fish post the bacterial infection. We identify elevating N-acetylglucosamine in survival group as the most crucial metabolite differentiating the survivals from the dying in these fish infected by S. iniae. Exogenous N-acetylglucosamine significantly elevates survival ability of tilapia against the infection caused by S. iniae. Our findings highlight the importance of metabolic strategy against bacterial infections.

Effect of matrine on transforming growth factor ß1 and hepatocyte growth factor in rat liver fibrosis model.

OBJECTIVE: To observe the preventive and control effect of matrine on transforming growth factor (TGF-ß1) and hepatocyte growth factor (HGF) of liver fibrosis tissue in rats. METHODS: A total of 48 SD rats were randomly divided into A, B, C, D groups with 12 in each, group A as the normal control group and groups B, C, D as liver fibrosis models using composite modulus method with carbon tetrachloride (CCL4). Group B was the model group, group C adopted γ-interferon lavage therapy in the second day of modeling, and group D adopted matrine lavage treatment, at 4 and 8 weeks after treatment. Six rats were executed for detection of TGF-ß1 and HGF, liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups. RESULTS: Groups B, C, D showed a more significantly increased TGF-ß1 at each time point compared with group A (P<0.05); Group B showed a more significantly increased TGF-ß1 than groups C and D at weeks 4 and 8 (P<0.05); group D showed a lowest level of TGF-ß1, followed by groups C and B. HGF of group B decreased more significantly than A group at weeks 4 and 8 (P<0.05); HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B (P<0.05), in which the group D showed the highest level of HGF. According to tissue histologic observation, rat liver tissue structure of group A was clear and normal, tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells; groups C and D showed a slighter liver tissue damage, cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement. CONCLUSIONS: Matrine can reduce TGF-ß1 expression and enhance the activity of HGF, so as to realize the inhibition effect on liver fibrosis in rats.

Analysis of factors affecting the life quality of the patients with late stomach cancer.

AIMS AND OBJECTIVES: To provide a theoretical basis for the clinical care of patients with late stomach cancer, we investigated the life quality and analysed its related factor in the patients with late stomach cancer. BACKGROUND: Due to the lack of effective screening methods, stomach cancer usually has been in the advanced stage when patients are diagnosed. However, the treatment for late stomach cancer is a tough problem in today's medicine. Chemotherapy or radiotherapy brings patients physiological and psychological distress and heavy financial burden, affecting patients' therapeutic effects, prognosis and life quality. DESIGN: The patients with late stomach cancer were included, and then, questionnaires about the life quality were completed. METHODS: Questionnaires including European Organisation for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30, Social Support Rating Scale, Medical Coping Modes Questionnaire and Self-rating Anxiety Scale were completed by 173 patients with late stomach cancer who received treatment in our hospital between May 2010 and May 2011. Correlation analyses were performed. RESULTS: The overall score of the life quality of the patients with late stomach cancer was only 29·54 ± 12·21. The social support, medical coping modes, anxiety and patients' clinical data (except radiotherapy) markedly affected the overall life quality of the patients with late stomach cancer (p < 0·05). CONCLUSION: The life quality of the patients with late stomach cancer is poor and is associated with many factors. RELEVANCE TO CLINICAL PRACTICE: This study provides a theoretical basis for better nursing the patients with late stomach cancer and improving their life quality.

[Raman characterization of high-pressure phase transition in AlN nanowires].

High-pressure phase transition of AlN nanowires was investigated in the range of 0-33.1 GPa by in situ Raman spectrum method in diamond anvil cell (DAC). The A1 (LO) vibration mode exhibits considerably asymmetry and broadening, indicating the occurrence of wurtzite-to-rocksalt phase transition. The Raman signal of high-pressure phase can be assigned to the disorder activated Raman scattering of rocksalt AlN. After fully releasing pressure, the Raman characterization of high-pressure phase was quenched. According to the pressure dependence of phonon frequency of AlN nanowires, the difference of transiton path between AlN nanowires and bulk materials was discussed and the mode Grüneisen parameters were determined.

Iron loading inhibits ferroportin1 expression in PC12 cells.

Ferroportin1 (FP1 or MTP1/IREG1), the product of the SLC40A1 gene, is a main iron export protein in mammals. Its mRNA contains an iron response element (IRE) in its 5' untranslated region, but the way this gene is regulated by iron is still unclear. The existence of FP1 in the brain has been recently confirmed. To better understand the role of this important transmembrane iron exporter in brain iron homeostasis, we investigated the effects of iron and nitric oxide (NO) on FP1 expression and that of a FP1 antibody on iron release in nerve growth factor-treated rat PC12 cells. We found that FP1 expression was down-regulated by iron loading but stimulated by iron chelation and treatment with a NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In addition, a significant decrease in iron release was found in cells treated with a FP1 antibody. Our findings imply that regulation of FP1 by iron in the cells is at the transcriptional level, rather than by an IRE/IRP-mediated pathway. Based on our results and published data, it is suggested that the transcriptional and translational (IRP/IRE pathway) mechanisms of FP1 expression might both operate in a tissue-specific manner and that FP1 might have a role in iron export from PC12 cells.