Prolonged sleep increases the risk of intracerebral haemorrhage: a nationwide case-control study.

BACKGROUND AND PURPOSE: Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study. METHODS: A nationwide, multicentre matched case-control study was performed to investigate the risk factors for haemorrhagic stroke, using patients from 33 hospitals in Korea. In all, 490 patients with ICH and 980 age- and sex-matched controls were enrolled. Detailed information regarding sleep, sociodemographic factors, lifestyle and medical history before ICH onset was obtained using qualified structured questionnaires. Sleep duration was categorized and the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression with 7 h as the reference duration. RESULTS: The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). After controlling for relevant confounding factors, longer sleep duration was found to be independently associated with the risk of ICH in a dose-response manner (8 h, OR 1.57, 95% CI 1.00-2.47; ≥9 h, OR 5.00, 95% CI 2.18-11.47). CONCLUSIONS: Our study suggested that long sleep duration is positively associated with an increased ICH risk in a dose-dependent manner. Further studies on the relationship linking long sleep duration with increased risk of ICH are required.

Self-consolidation mechanism of nanostructured Ti5Si3 compact induced by electrical discharge.

Electrical discharge using a capacitance of 450 µF at 7.0 and 8.0 kJ input energies was applied to mechanical alloyed Ti5Si3 powder without applying any external pressure. A solid bulk of nanostructured Ti5Si3 with no compositional deviation was obtained in times as short as 159 µsec by the discharge. During an electrical discharge, the heat generated is the required parameter possibly to melt the Ti5Si3 particles and the pinch force can pressurize the melted powder without allowing the formation of pores. Followed rapid cooling preserved the nanostructure of consolidated Ti5Si3 compact. Three stepped processes during an electrical discharge for the formation of nanostructured Ti5Si3 compact are proposed: (a) a physical breakdown of the surface oxide of Ti5Si3 powder particles, (b) melting and condensation of Ti5Si3 powder by the heat and pinch pressure, respectively, and (c) rapid cooling for the preservation of nanostructure. Complete conversion yielding a single phase Ti5Si3 is primarily dominated by the solid-liquid mechanism.

Berberine reduce allergic inflammation in a house dust mite allergic rhinitis mouse model.

BACKGROUND: Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitis mouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti-CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-γ), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4⁺ CD25⁺ Foxp3⁺ T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4⁺ CD25⁺ Foxp3⁺ T cells was increased versus the Derf group. The percentage of CD4⁺ CD25⁺ Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4⁺ CD25⁺ Foxp3⁺ Treg cells, possibly through not only by increasing their numbers but also altering their function.

Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.

Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have anti-tumor activities; however, the mechanism underlying its anti-tumorigenic effects is poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse resting macrophages. We found that UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex. These results demonstrate that UA stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappaB transactivation in the resting macrophages.

Expression of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P4501A1 in human splenic lymphocyte cultures.

The induction of cytochrome P4501A1 (P4501A1) and P4501A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in human splenic lymphocytes cultures. EROD activity was induced by TCDD in mitogen (phytohemagglutinin and pokeweed mitogen) stimulated blast cells but not in the resting cells. TCDD markedly induced EROD activity in a dose- and time-dependent manner. The expression of P4501A1 mRNA was increased by TCDD in mitogen-stimulated cells as detected by Northern blot analysis. These findings support the conclusion that TCDD induced the expression of P4501A1 gene, resulting in increased EROD activity in mitogen-stimulated human splenic lymphocytes cultures.

Suppressive effects of alpha-Hederin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated murine Cyp1a-1 expression in the mouse hepatoma Hepa-1c1c7 cells.

Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with alpha-Hederin to assess the role of alpha-Hederin in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and Cyp1a-1 protein. When alpha-Hederin and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by alpha-Hederin in a dose-dependent manner. TCDD-induced Cyp1a-1 protein and mRNA levels were markedly reduced in the concomitant treatment of TCDD and alpha-Hederin consistent with EROD activity. Electrophoretic mobility shift assay using nuclear extraction of cells revealed that alpha-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene. These results suggest that the suppressive effect of alpha-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor.

Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice.

Diallyl sulfide (DAS), a flavor component of garlic that has been used as a food additive, exerts chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens possibly by inhibiting carcinogen activation via cytochrome P450-mediated oxidative metabolism. In this study, we investigated the protective effect of DAS on the N-nitrosodimethylamine (NDMA)-induced immunosuppression of humoral and cellular responses in BALB/c mice and the possible mechanisms involved in this protection. We observed that oral administration of DAS prior to NDMA treatment for 14 consecutive days blocked the NDMA-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes, and the lymphoproliferative response to the T-cell and the B-cell mitogens in dose-dependent manners. Treatment of mice with DAS resulted in a significant decrease of cytochrome P450 2E1-dependent p-nitrophenol hydroxylase and NDMA demethylase activities. The results show that the protective effects of DAS against the NDMA-induced immunotoxicity may, at least in part, be due to its ability to block bioactivation of NDMA mainly by the inhibition of cytochrome P450 2E1.

Suppressive effects of estradiol on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated transcriptional activation of murine Cyp1a-1 in mouse hepatoma Hepa 1c1c7 cells.

Cultured mouse hepatoma Hepa lclc7 cells were treated with either estradiol or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or in combination to assess the role of estradiol in the process of Cypla-1 induction. Estradiol at a concentration as high as 1 microM slightly increased the activity of Cypla-1-specific 7-ethoxyresorufin O-deethylase (EROD); in contrast, TCDD-induced EROD activity and Cypla-1 mRNA levels were markedly reduced in the concomitant treatment of TCDD and estradiol in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen which acts through the estrogen receptor, did not affect the suppressive effects of estradiol on TCDD-induced EROD activity. Electrophoretic mobility shift assay using nuclear extract of cells revealed that estradiol reduced transformation of the Ah receptor to the form capable of specifically binding to an oligonucleotide containing dioxin-response element (DRE) sequence. Consistent with this, estradiol decreased TCDD-induced increased chloramphenicol acetyltransferase (CAT) activity from a DRE-containing CAT reporter plasmid after transient transfection into the cells. The levels of the cytosolic [3H]TCDD-Ah receptor complex were reduced by estradiol in competitive Ah receptor binding assay using [3H]TCDD. This study demonstrated that estradiol acts as an antagonist to TCDD and can regulate Cyp1a-1 expression in an Ah receptor-dependent manner but not through estradiol receptor in Hepa 1c1c7 cells.

Suppression of CYP1A1 expression by 4-nonylphenol in murine Hepa-1c1c7 cells.

This study investigated the effects that 4-nonylphenol (NP) has on CYP1A1 expression in Hepa-1c1c7 cell cultures. NP alone did not affect CYP1A1-specific 7-ethoxyresorufin-O-deethylase (EROD) activity. In contrast, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and NP in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen that acts through the estrogen receptor, did not affect the suppressive effects that NP has on TCDD-inducible EROD activity. The TCDD-inducible CYP1A1 mRNA levels were markedly suppressed upon concomitant treatment with TCDD and NP that is consistent with their effects on EROD activity. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that NP reduced the transformation of the aryl hydrocarbon (Ah) receptor to a form capable of binding specifically to the DRE sequence of the CYP1A1 gene promoter. These results suggest that the down-regulation of CYP1A1 gene expression by NP in Hepa-1c1c7 cells might be an antagonism of the DRE-binding potential of the nuclear Ah receptor, but is not mediated through the estradiol receptor.

Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice.

The protective effects of an aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), on acetaminophen (APAP)-induced hepatotoxicities and the possible protective mechanisms involved were investigated in mice. Pretreatment with CK prior to the administration of APAP significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. APAP-induced hepatotoxicity was also essentially prevented as evidenced by liver histopathology. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by treatment with CK alone, but pretreatment with CK protected the APAP-induced depletion of hepatic glutathione levels. The effects of CK on cytochrome P450 (P450) 1A2 and 2E1, the major isozymes involved in APAP bioactivation, were investigated. In microsomal incubations, CK effectively inhibited P450 lA2-dependent methoxyresorufin O-deethylase activities and the P450 2E1-dependent p-nitrophenol and aniline hydroxylase. The results suggest that the protective effects of CK against the APAP-induced hepatotoxicity may, at least in part, be due to its ability to block P450-mediated APAP bioactivation.

Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum.

Platycodon grandiflorum has been claimed to have a wide range of health benefits, which include immunostimulation and antitumor activity. The associated biological mechanisms are unclear; however, of the wide diversity of effects, it is believed that their activities may be exerted through several potent effector cells such as macrophages. Therefore, the effects of an aqueous extract from the root of P. grandiflorum (Changkil: CK) on mouse peritoneal macrophage function were investigated. It was found that CK stimulated macrophage proliferation, spreading ability, phagocytosis, cytostatic activity, and nitric oxide production in a dose-dependent manner, and that the production of cytokines such as TNF-alpha, IL-1beta and IL-6 were similarly increased. CK significantly affected secretion at concentrations greater than 10 microg/ml; its maximal effects were at the concentration of 100 microg/ml. Reverse transcription-polymerase chain reaction showed that CK increased the appropriate cytokine mRNAs. These results suggest that CK is a potent enhancer of macrophage function.

Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-alpha from murine macrophages.

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. Aqueous extract from the root of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), is reported to have antitumor and immunomodulatory activities; however, the mechanism underlying its therapeutic effect is not known. In the present study we examined the effects of CK on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the gene expression of iNOS and TNF-alpha in mouse macrophages. CK elicited a dose-dependent increase in NO and TNF-alpha production in cultured macrophages. CK significantly affected secretion at concentrations of more than 5 micrograms/ml, and its maximum effect was at concentration of 100 micrograms/ml. Reverse transcription polymerase chain reaction showed that increases in NO and TNF-alpha secretion were due to an increase in inducible NO synthase mRNA and TNF-alpha mRNA, respectively. Transient expression assays with NF-kappa B binding sites linked to the luciferase gene revealed that CK-induced increase of inducible NO synthase mRNA and TNF-alpha mRNA were mediated by the NF-kappa B transcription factor complex. These results demonstrate that CK stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappa B transactivation and this may be a mechanism whereby this herbal medicine elicits its therapeutic effects.

Direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human tonsillar lymphocytes.

Murine lymphocyte function is quite sensitive to TCDD. However, in contrast to the murine model, the corresponding functional studies have not been undertaken with human lymphocytes. One laboratory has recently demonstrated that human tonsillar lymphocytes (HTL) possess the aryl hydrocarbon (Ah) receptor which mediates many of the effects of TCDD. This observation suggested that HTL may be sensitive to TCDD. In mitogen stimulated HTL, TCDD induced a dose-dependent increase in 7-ethoxyresorufin-O-deethylase (EROD) synthesis. Because we recently demonstrated that background proliferation in HTL and murine splenocytes was suppressed by TCDD, we purified human and murine B-cells into high density and low density populations. In low density human B-cells, TCDD suppressed background proliferation and IgM secretion from 0.3 to 30 nM. Interestingly, TCDD produced comparable effects on background proliferation and IgM secretion in purified low density murine B-cells. When low density human B-cells were stimulated with LPS and TRF, TCDD suppressed both proliferation and IgG secretion in a dose-dependent manner from 0.3 to 30 nM, although the suppression was modest when compared to the magnitude of suppression of the background responses. In contrast, TCDD did not alter background or stimulated proliferation in high density human B-cells. These results indicate that TCDD has a direct effect on human tonsillar lymphocyte activity and suggest that low density B-cells are a sensitive cellular target.

Induction of inducible nitric oxide synthase gene expression by Pokeweed mitogen.

The present study has characterized the expression of iNOS gene in Pokeweed mitogen (PWM)-driven murine macrophage RAW 264.7 cells. PWM significantly induced nitric oxide production in a dose-dependent manner. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that the inducible nitric oxide synthase gene expression is increased by PWM treatment. Since iNOS transcription has recently been shown to be under the control of the nuclear factor (NF)-kappaB/Rel family of transcription factors, the effects of PWM on NF-kappaB/Rel activation were examined using a transient transfection assay and an electrophoretic mobility shift assay (EMSA). Transient expression assays with NF-kappaB/Rel binding sites linked to the chloramphenicol acetyltransferase gene suggest that the PWM-induced increase in transcription is mediated by the NF-kappaB/Rel transcription factor complex. Using DNA fragments containing the NF-kappaB/Rel binding sequence, PWM was shown to activate the protein/DNA binding of NF-KB/Rel to its cognate site as measured by EMSA. Supershift EMSA showed the presence of p50 and c-Rel protein in the complex at the kappaB site. Western blot analysis of isolated nuclear fractions, using p65 and c-Rel-specific antibodies, provided further evidence that c-Rel is increased by PWM treatment. N-Tosyl-1-phenylalanine chloromethyl ketone, a potent inhibitor of NF-kappaB/Rel activation, inhibited PWM-induced nitrite generation in a dose-dependent manner. Collectively, the results of these experiments indicate that c-Rel is positively regulated by PWM to assist in the initiation of iNOS gene expression.

Inhibition of cytochrome P450 2E1 expression by oleanolic acid: hepatoprotective effects against carbon tetrachloride-induced hepatic injury.

The protective effects of oleanolic acid on carbon tetrachloride-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with oleanolic acid prior to the administration of carbon tetrachloride significantly prevented the increase in serum alanine aminotransferase and lactate dehydrogenase activity and liver lipid peroxidation in a dose-dependent manner. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by treatment with oleanolic acid alone but pretreatment with oleanolic acid protects carbon tetrachloride-induced depletion of hepatic glutathione levels. The effects of oleanolic acid on the cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were investigated. Treatment of mice with oleanolic acid resulted in a significant decrease of P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. These results show that the protective effects of oleanolic acid against the carbon tetrachloride-induced hepatotoxicity may, at least in part, be due to its ability to block bioactivation of carbon tetrachloride mainly by the inhibition of expression and activities of P450 2E1.

Differential effects of B- and T-lymphocyte mitogens on cytochrome P450 in mice.

Lipopolysaccharide (LPS) is widely used as a B-lymphocyte mitogen and is known to depress expression of the cytochrome P450 (P450). However, there have been no studies regarding to the effects of the other mitogens on the expression of P450. This study investigated the effects of mitogens on the constitutive and inducible expression of mouse hepatic P450. Following treatment with B-lymphocyte mitogens, such as LPS and pokeweed mitogen (PWM), hepatic P450 content was reduced. LPS and PWM also suppressed activities of microsomal ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase and aniline hydroxylase, a representative activity of P4501A1/2, P4502B1/2 and P4502E1, respectively, in both constitutive and P450 induced mice. However, there was no effect when treated with T-lymphocyte mitogens, such as concanavalin A and phytohemagglutinin. Suppression of P450 expression in the LPS- or PWM-treated mice occurred and was shown to involve a decrease in P450 protein and mRNA levels in liver. These results suggest that suppressive effects of mitogens on the expression of P450 might be different and that B-lymphocyte mitogens selectively depress the expression of P450.

Cytokine-mediated suppression of cytochrome P450 1A1 in Hepa-1c1c7 cells by pokeweed mitogen.

This study investigated the effects of pokeweed mitogen (PWM) on the regulation of cytochrome P450 (P450) 1A1 expression in an in vitro model, using murine hepatoma cell line Hepa-1c1c7 and murine macrophage cell line RAW 264.7 cell cultures. PWM added directly to Hepa-1c1c7 cells had no effect on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced P450 1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. However, TCDD-induced EROD activity and P450 1A1 mRNA levels were markedly suppressed when Hepa-1c1c7 cells were cultured with PWM-treated conditioned media from RAW 264.7 in a dose-dependent manner. Concomitant treatment with PWM and pentoxifylline, a TNFalpha synthesis inhibitor, to RAW 264.7 cells decreased the suppressive effects of PWM on TCDD-induced EROD activity. In PWM-exposed RAW 264.7 cell cultures, TNFalpha and IL-6 levels increased in a dose-dependent fashion. When antibodies to TNFalpha or/and IL-6 were added to PWM-treated conditioned media from RAW 264.7, the suppression of EROD activity was inhibited. These results suggested the suppression of P450 1A1 by PWM was mediated exclusively by TNFalpha and IL-6, released from macrophages.

Induction of cytochrome P-450 by dimethyl sulfoxide in primary cultures of adult rat hepatocytes.

Treatment of hepatocyte cultures with dimethyl sulfoxide (DMSO) induced P-450IIE1-specific aniline 4-hydroxylase activity and P-450IA1-specific ethoxyresorufin O-deethylase activity at a concentration of 0.1% (v/v). The P-450IIB-specific pentoxyresorufin O-deethylase activity was induced only at the 2% (v/v) level. Dot blot analysis of the total cellular RNA and cycloheximide treatment of the culture suggested that induction of ethoxyresorufin O-deethylase activity by DMSO may be due to the increase of de novo synthesis of the P-450IA1 protein, not to accumulation of mRNA in the hepatocyte culture.

Suppression of IL-2 and IL-4 gene expression by nodularin through the reduced NF-AT binding activity.

Nodularin is a cyclic peptide produced by cyanobacteria. In the present study, the inhibitory effect of nodularin on T lymphocyte functions was demonstrated. Direct addition of nodularin to B6C3F1 mouse splenocyte cultures produced a concentration-dependent inhibition of the lymphoproliferative response to concanavalin A stimulation. Nodularin inhibited PMA plus ionomycin (Io)-induced IL-2 mRNA expression in murine splenocytes and thymocytes as determined by quantitative/competitive RT-PCR. To further characterize the mechanism for the transcriptional regulation of IL-2, the binding activity of transcription factors, NF-AT, AP-1, NF-kappaB, and Oct, was evaluated by electrophoretic mobility shift assays in mouse splenocytes. Nodularin reduced the NF-AT binding activity in PMA/Io-induced splenocytes, but no significant effect was observed on AP-1, NF-kappaB, or Oct binding activity. Nodularin also inhibited IL-4 mRNA expression in PMA/Io-stimulated murine splenocytes. These results suggest that T lymphocyte is a possible cellular target of nodularin, and the inhibitory effect of nodularin on T-cell specific transcription factor NF-AT induces T-cell dysfunction, which leads to a diminution in IL-2 and IL-4 gene transcription.

Mechanical properties and microstructure of AZ31 Mg alloy containing Ca element fabricated by various rolling speeds.

It was reported that the yield strength (YS) of a rolled Mg-3 wt%, Al-1 wt%, Zn-0.3 wt%, Ca alloy reached 340 MPa. The YS value of a rolled Mg-Al-Zn alloy decreases with increasing the rolling speed but that of a rolled Mg-Al-Zn-Ca alloy remains unchanged until the rolling speed of 5 m/min. Static recrystallization behavior in Mg-Al-Zn alloy occurred as a function of rolling speeds; on the other hand, it did not happen in Mg-Al-Zn-Ca alloy. A number of fine precipitates were observed in the grain of the latter alloy, suggesting that they restrain the dislocations from moving during rolling processes and keep the high strength. From the result of boss-forming test, the Mg-Al-Zn-Ca alloy shows more boss-formability than Mg-Al-Zn alloy.