Synergistic effects ofα-Fe2O3nanoparticles and Fe-doping on gas-sensing performance of NiO nanowires and interface mechanism.

High surface area nickel oxide nanowires (NiO NWs), Fe-doped NiO NWs andα-Fe2O3/Fe-doped NiO NWs were synthesized with nanocasting pathway, and then the morphology, microstructure and components of all samples were characterized with XRD, TEM, EDS, UV-vis spectra and nitrogen adsorption-desorption isotherms. Owing to the uniform mesoporous template, all samples with the same diameter exhibit the similar mesoporous-structures. The loadedα-Fe2O3nanoparticles should exist in mesoporous channels between Fe-doped NiO NWs to form heterogeneous contact at the interface of n-typeα-Fe2O3nanoparticles and p-type NiO NWs. The gas-sensing results indicate that Fe-dopant andα-Fe2O3-loading both improve the gas-sensing performance of NiO NWs sensors.α-Fe2O3/Fe-doped NiO NWs sensors presented the highest response to 100 ppm ethanol gas (55.264) compared with Fe-doped NiO NWs (24.617) and NiO NWs sensors (3.189). The donor Fe-dopant increases the ground state resistance and the absorbed oxygen content in air.α-Fe2O3nanoparticles in electron depletion region result in the increasing resistance in ethanol gas and decreasing resistance in air. In this way,α-Fe2O3/Fe-doped NiO NWs sensor presents the excellent gas-sensing performance due to the formation of heterogeneous contact at the interface.

Human dCTP pyrophosphatase 1 promotes breast cancer cell growth and stemness through the modulation on 5-methyl-dCTP metabolism and global hypomethylation.

Human DCTPP1 (dCTP pyrophosphatase 1), also known as XTP3-transactivated protein A, belongs to MazG-like nucleoside triphosphate pyrophosphatase (NTP-PPase) superfamily. Being a newly identified pyrophosphatase, its relevance to tumorigenesis and the mechanisms are not well investigated. In the present study, we have confirmed our previous study that DCTPP1 was significantly hyperexpressed in breast cancer and further demonstrated its strong association with tumor progression and poor prognosis in breast cancer. Knockdown of DCTPP1 in breast cancer cell line MCF-7 cells remarkably retarded proliferation and colony formation in vitro. The capacity of mammosphere formation of MCF-7 was suppressed with the silence of DCTPP1, which was consistent with the enhanced mammosphere-forming ability in DCTPP1-overexpressed MDA-MB-231 cells. To further dissect the mechanisms of DCTPP1 in promoting tumor cell growth and stemness maintenance, its biochemical properties and biological functions were investigated. DCTPP1 displayed bioactive form with tetrameric structure similar to other MazG domain-containing pyrophosphatases based on structure simulation. A substrate preference for dCTP and its methylated or halogen-modified derivatives over the other canonical (deoxy-) NTPs was demonstrated from enzymatic assay. This substrate preference was also proved in breast cancer cells that the intracellular 5-methyl-dCTP level increased in DCTPP1-deficient MCF-7 cells but decreased in DCTPP1-overexpressed MDA-MB-231 cells. Moreover, global methylation level was elevated in DCTPP1-knockdown MCF-7 cells or mammosphere-forming MCF-7 cells but decreased significantly in DCTPP1-overexpressed MDA-MB-231 cells and its mammospheres. Our results thus indicated that human DCTPP1 was capable of modulating the concentration of intracellular 5-methyl-dCTP. This in turn affected global methylation, contributing to a known phenomenon of hypomethylation related to the cancer cell growth and stemness maintenance. Our current investigations point to the pathological functions of DCTPP1 overexpression in breast cancer cells with aberrant dCTP metabolism and epigenetic modification.

dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas.

Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) functions as one of the mechanisms to guarantee the fidelity of DNA replication through the cleavage of non-canonical nucleotides into di- or monophosphates. Human NTP-PPase is poorly understood and investigated. In the present study, by using tissue microassays with the paired cancer and adjacent regions, we found that with the prevalent expression of dCTP pyrophosphohydrase (DCTPP1) in the cytosol and nucleus in tumors investigated, DCTPP1 was inclined to accumulate in the nucleus of cancer cells compared to the paired adjacent tissue cells in multiple carcinoma including lung, breast, liver, cervical, gastric and esophagus cancer. More significantly, the higher DCTPP1 expression in the nucleus of lung, gastric and esophagus cancer cells was associated with histological subtypes. The nucleic accumulation of DCTPP1 was apparently observed as well when cancer cell line MCF-7 was treated with H2O2 in vitro. Considering the roles of DCTPP1 on restricting the concentration of non-canonical nucleotides in the nucleotide pool, accumulation of DCTPP1 in the nucleus of cancer cells might suffice for maintaining the proper DNA replication in order to fulfill the requirement for the survival and proliferation of tumor cells.

Magnetic stability of SnO2 nanosheets.

Room temperature ferromagnetism has been observed in freshly synthesized and post-annealed SnO2 nanosheets. The results of x-ray diffraction and x-ray photoelectron spectroscopy reveal that the newly synthesized samples and those annealed at 400 °C under either an O2 or Ar atmosphere possess rutile structure and no other impurity phases are observed. The fitting results of the O 1s and Sn 3d spectra from SnO2 samples annealed at 400 °C under an O2 or Ar atmosphere both indicate that oxygen vacancies inevitably exist in these samples. It is found that the saturation magnetization of all the annealed samples does not feature mono-dependence on oxygen vacancies, whereas an Sn vacancy related origin seems more plausible to account for variations in the magnetization of samples studied. This finding corresponds to first-principle calculation results from our previous work. Furthermore, the Curie temperature of SnO2 nanosheets was estimated to be around 300 °C, rendering it a very good option for the next generation of spintronics.

The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A.

The prevalence of inhibitors in Chinese haemophiliacs has not yet been reported. The aim of this study was to identify the prevalence of factor VIII (FVIII) inhibitors among haemophiliacs who are treated only with plasma-derived FVIII (pdFVIII), cryoprecipitate or fresh frozen plasma (FFP), and tried to explore the relationship between the generation of inhibitors and particular FVIII deficiency genotypes. Clinical information and blood samples of 1435 patients with haemophilia A (HA) were collected by six haemophilia centres in China. The Nijmegen modification of the Bethesda assay was used to detect inhibitors. Multiplex PCR, long-range PCR and direct sequencing were performed for genotyping. The overall prevalence of inhibitors in Chinese HA patients was 3.9% and the prevalence of severe haemophiliacs was 4.3%; 18 of the 56 patients with inhibitors had high titres. A total of 38 different mutations were identified in the 55 patients with inhibitors, including 15 intron 22 and 3 intron 1 inversions, seven large deletions, 14 small deletion/insertions, seven nonsense mutations, one splice site mutations and eight missense mutations. Of 38 mutations, 28 were novel. Patients with large deletions and nonsense mutations were prone to have high titre inhibitors, with incidence rates of 57.1% (4/7) and 42.9% (3/7), respectively. In conclusion, the prevalence of inhibitors in Chinese HA patients is much lower than that reported for other ethnic groups and the large deletion and nonsense mutations are high risk factors for high titre inhibitor development.

Obesity and cardiovascular thrombotic events in patients undergoing percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Previous studies have reported conflicting findings regarding the relation of body mass index (BMI) to outcomes following percutaneous coronary interventions (PCI). No study to date has directly examined the effect of obesity on cardiovascular thrombotic events after stent implantation. OBJECTIVE: To evaluate the effect of obesity on cardiovascular thrombotic events in patients undergoing PCI with drug-eluting stents. METHODS: We studied 4972 patients between January 2004 and December 2006. Patients were divided into three groups according to body mass index: normal (BMI <24.9 kg/m(2), n = 1284), overweight (BMI 25-29.9 kg/m(2), n = 2475) and obese (BMI > or =30 kg/m(2), n = 1213). Median follow-up was 26 (interquartile range 20-33) months. RESULTS: Composite cardiovascular thrombotic events, including cardiac death and non-fatal myocardial infarction, were significantly higher in obese patients (5.9%) than in normal (3.2%) and overweight (3.8%) patients (p = 0.001). The incidence of definite or probable stent thrombosis steadily increased with increasing body mass index (0.9% vs 1.0% vs 1.9% in normal, overweight and obese patients, respectively; p = 0.029). Multivariate analyses showed that obesity was an independent predictor of 3-year composite thrombotic events (hazard ratio 1.86; 95% confidence interval 1.25 to 2.75; p = 0.003) and definite or probable stent thrombosis (2.17; 1.04 to 4.55; p = 0.040). CONCLUSIONS: Obese patients have a higher risk for long-term cardiovascular thrombotic events following PCI with drug-eluting stents than patients with normal weight.

Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein.

Cerebral ischemia resulting from a disruption of blood flow to the brain initiates a cascade of events that causes neuron death and leads to neurologic dysfunction. Reactive oxygen species are thought, at least in part, to mediate this disease process. The authors recently cloned and characterized an antioxidant protein, SAG (sensitive to apoptosis gene), that is redox inducible and protects cells from apoptosis induced by redox agents in a number of in vitro cell model systems. This study reports a neuroprotective role of SAG in ischemia/reperfusion-induced brain injury in an in vivo mouse model. SAG was expressed at a low level in brain tissue and was inducible after middle cerebral artery occlusion with peak expression at 6 to 12 hours. At the cellular level, SAG was mainly expressed in the cytoplasm of neurons and astrocytes, revealed by double immunofluorescence. An injection of recombinant adenoviral vector carrying human SAG into mouse brain produced an overexpression of SAG protein in the injected areas. Transduction of AdCMVSAG (wild-type), but not AdCMVmSAG (mutant), nor the AdCMVlacZ control, protected brain cells from ischemic brain injury, as evidenced by significant reduction of the infarct areas where SAG was highly expressed. The result suggests a rather specific protective role of SAG in the current in vivo model. Mechanistically, SAG overexpression decreased reactive oxygen species production and reduced the number of apoptotic cells in the ischemic areas. Thus, antioxidant SAG appears to protect against reactive oxygen species-induced brain damage in mice. Identification of SAG as a neuroprotective molecule could lead to potential stroke therapies.

[Isolation of a gene related to trichosanthin-induced apoptosis (GRETA)].

Disturbance of the apoptosis-related signaling pathway is regarded as one of the critical factors for tumorigenesis. Isolation of the genes involved in the process of apoptosis would be thereby helpful to explore the mechanism of tumor transformation and to develop novel therapeutic approaches. Here we report a gene fragment GRETA, the gene related to trichosanthin-induced apoptosis, isolated from a leukemia cell line U937 undergoing apoptosis induced by a plant protein Trichosanhin (TCS). A 293bp segment of GRETA was revealed to be 78.3% homologous to Bruton's tyrosine kinase at nucleic acid level. And Northern blot analysis showed that three messengers of RNA with the size of about 0.8-kb, 2.0-kb and 7.0-kb, respectively, were detected in TCS-untreated U937 cells when probed with GRETA, but there were only 0.8-kb and 2.0-kb transcripts appeared in apoptotic U937 cells. In addition, the abundance of each transcript changed apparently. The 0.8-kb transcript, for example, was the main band in Northern analysis in apoptotic U937 cells while was only detected marginally in TCS-untreated cells. These data suggested a possible relationship between the alternative splicing patterns of GRETA and the apoptosis.

Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice.

Interleukin-1beta (IL-1beta) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1beta affects ischemic brain are not understood. To investigate the role of IL- 1beta in regulation of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-alpha and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-alpha expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1-positive vessels in the ischemic hemisphere was reduced in ICE KO mice (P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results. The authors' results indicate that TNF-alpha expression is increased in both ICE KO and wild-type mice suggesting that TNF-alpha expression is not related to or upregulated by IL-1beta . ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1beta plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.

Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent focal cerebral ischemic mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist.

Our previous studies have demonstrated that overexpression of recombinant human interleukin-1 receptor antagonist protein (IL-1ra) via gene transfer can reduce ischemic brain injury. However, the mechanism of action of IL-1ra in ischemia is unclear. Since interleukin-1 can up-regulate intercellular adhesion molecules in endothelium, the present study was designed to determine whether overexpression of the IL-1ra can reduce the expression of intercellular adhesion molecule-1 (ICAM-1) after ischemic injury. Normal saline or adenovirus vector (1x109 particles) encoding the human IL-1ra gene (Ad.RSVIL-1ra) or the Escherichia coli LacZ gene (Ad.RSVlacZ) was injected into the right lateral cerebral ventricle of adult CD-1 mice. After five days, permanent middle cerebral artery occlusion (MCAO) was achieved for 24 h using an intraluminal suture. Cerebral blood flow was monitored by transcranial laser Doppler flowmetry to verify the occlusion. ICAM-1 protein was quantified using Western blot analysis and localized using immunohistochemistry. After MCAO, surface blood flow in the ischemic hemisphere was decreased to 9-11% of the baseline. There were fewer ICAM-1 positive vessels in the ischemic cortex of the Ad.RSVIL-1ra transfected mice than in the Ad.RSVlacZ transfected and saline treated mice (138+/-19 vs. 249+/-25, 284+/-22, p<0.05). Western blot analysis shows that ICAM-1 protein decreased 50-60% in the Ad. RSVIL-1ra group compared to the other two groups. There were no significant differences in the numbers of positive vessels in the ischemic basal ganglia and contralateral hemisphere among the three groups. Our studies suggest that IL-1ra overexpression can down-regulate the expression of ICAM-1 in the ipsilateral cortex in ischemic mice. Interleukin-1 may play an important role in the activation of inflammatory reaction during focal cerebral ischemia by promoting leukocyte adhesion on the endothelium cells.

Diagnostic role of gadolinium-DTPA in pediatric neuroradiology. A retrospective review of 655 cases.

We retrospectively reviewed the findings in 655 consecutive young patients who underwent contrast-enhanced MR examinations (1.5T) of the head or spine. Their ages ranged from 4 months to 20 years (mean 10 years). There was a 1.7% incidence of minor adverse reactions to gadolinium (Gd)-DTPA, none of which required treatment; no serious adverse reactions were encountered. Based on the radiologic diagnosis the patients were divided into three groups: (1) normal, (2) CNS neoplasm, (3) abnormal but not neoplasm. There were 178 patients thought to have CNS neoplasms and of these 156 (88%) enhanced. Of 124 histologically confirmed neoplasms 115 (93%) showed enhancement after Gd-DTPA. Eight children had histologically confirmed spinal neoplasms; 5 of 6 neurofibromas and 2 ependymomas enhanced. In the 216 patients with abnormalities thought not to be neoplastic, the enhancement rate was 11%; most of the enhancing lesions were vascular malformations. There were very few examples of inflammatory disease, acute trauma or stroke among our patients.

Immunosuppressive action of Qinghaosu.

Qinghaosu, isolated and purified from the Chinese herb, Artemisia annua Linn, and identified as a sesquiterpene with a peroxide bridge and lactone structure, is a highly potent and non-toxic new antimalaria drug. This paper reports the immunosuppressive action of its water soluble derivative (hemisuccinate NA, QHS). The remarkable suppression by QHS of the in vitro 3HTdR incorporation by mitogen-stimulated mouse spleen cells and human peripheral lymphocytes, as well as the spontaneous incorporation by mouse thymocytes and blood cells from some leukemia patients is presented and its characteristics are described. The in vivo effect as shown by quantitative PFC is studied and the difference between the present in vitro and in vivo effects is investigated. The possible mechanism of inhibition and discrepancy in effects are discussed.