Oxidative-damage effect of Fe3O4 nanoparticles on mouse hepatic and brain cells in vivo

To assess the biological safety of Fe3O4 nanoparticles （NPs）, the oxidative-damage effect of these NPs was studied. Twenty-five Kunming mice were exposed to Fe3O4 NPs by intraperitoneai injection daily for 1 week at doses of 0, 10, 20, and 40 mg.kg1. Five Kunming mice were also injected with 40 mg.kg 1 ordinary Fe3O4 particles under the same physiological conditions. Biomarkers of reactive oxygen species （ROS）, glutathione （GSH）, and malondialdehyde （MDA） in the hepatic and brain tissues were detected. Results showed that no significant difference in oxidative damage existed at concentrations lower than 10 mg.kg i for NPs compared with the control group. Fe3O4 NP concentration had obvious dose-effect relationships （P〈 0.05 or P 〈 0.01） with ROS level, GSH content, and MDA content in mouse hepatic and brain tissues at〉20 mg.kg 1 concentrations. To some extent, ordinary Fe3O4 particles with 40mg.kg -1 concentration also affected hepatic and brain tissues in mice. The biological effect was similar to Fe3O4 NPs at 10 mg. kg-1 concentration. Thus, Fe3O4 NPs had significant damage effects on the antioxidant defense system in the hepatic and brain tissues of mice, whereas ordinary Fe3O4 had less influence than Fe3O4 NPs at the same concentration.     

Insecticidal activity of the chitinase from the Spodoptera litura nucleopolyhedrovirus

Baculovirus chitinase gene (chiA) is a late gene essential for liquefying the host insect at a late stage of infection for its hydrolyzing chitin function. In a previous report, baculovirus ChiA has been shown to offer many interesting new opportunities for pest control. Recently, a putative chiA gene was identified in the Korean isolate of the Spodoptera litura nucleopolyhedorvirus (SpliMNPV‐K1) genome. The open reading frame (ORF) contains 1692 nucelotides and encodes a protein of 563 amino acids with a predicted molecular weight of about 62.6 kDa. To study the insecticidal activity of ChiA from SpliMNPV‐K1, we constructed a recombinant AcMNPV, Ap‐SlChiA, which is designed to express the ChiA under the control of a polyhedrin promoter. Western blot analysis indicated that ChiA was successfully expressed by this recombinant virus. Chitinase assay revealed that the chitobiosidase and endochitinase activity of the recombinant virus was 2.5‐ and 3.9‐flods higher than those of wild‐type AcMNPV, respectively. In addition, the recombinant virus showed higher evident insecticidal activity against 3rd instar larvae of Spodotera exigua than that of the AcMNPV. These results suggest that the chiA gene from SpliMNPV‐K1 could be successfully applied to improve pathogenicity of baculoviruses.     

Expression of the Arabidopsis vacuolar H+-pyrophosphatase gene AVP1 in peanut to improve drought and salt tolerance

The Arabidopsis gene AVP1 encodes an H⁺-pyrophosphatase that functions as a proton pump at the vacuolar membranes, generating a proton gradient across vacuolar membranes, which serves as the driving force for many secondary transporters on vacuolar membranes such as Na⁺/H⁺-antiporters. Overexpression of AVP1 could improve drought tolerance and salt tolerance in transgenic plants, suggesting a possible way in improving drought and salt tolerance in crops. The AVP1 was therefore introduced into peanut by Agrobacterium-mediated transformation. Analysis of AVP1-expressing peanut indicated that AVP1-overexpression in peanut could improve both drought and salt tolerance in greenhouse and growth chamber conditions, as AVP1-overexpressing peanuts produced more biomass and maintained higher photosynthetic rates under both drought and salt conditions. In the field, AVP1-overexpressing peanuts also outperformed wild-type plants by having higher photosynthetic rates and producing higher yields under low irrigation conditions.     

Comparative Analysis of CpG Islands among HBV Genotypes

DNA methylation is being increasingly recognized to play a role in regulation of hepatitis B virus (HBV) gene expression. The aim of this study was to compare the CpG island distribution among different HBV genotypes. We analyzed 176 full-length HBV genomic sequences obtained from the GenBank database, belonging to genotypes A through J, to identify the CpG islands in the HBV genomes. Our results showed that while 79 out of 176 sequences contained three conventional CpG islands (I–III) as previously described, 83 HBV sequences harbored only two of the three known islands. Novel CpG islands were identified in the remaining 14 HBV isolates and named as CpG island IV, V, and VI. Among the eight known HBV genotypes and two putative genotypes, while HBV genomes containing three CpG islands were predominant in genotypes A, B, D, E, and I; genotypes C, F, G, and H tended to contain only two CpG islands (II and III). In conclusion, the CpG islands, which are potential targets for DNA methylation mediated by the host functions, differ among HBV genotypes, and these genotype-specific differences in CpG island distribution could provide new insights into the understanding of epigenetic regulation of HBV gene expression and hepatitis B disease outcome.     

Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

Background

Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated.

Methods and Findings

Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers.

Conclusion

This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.     

Optimization of Substituted 6-Salicyl-4-Anilinoquinazoline Derivatives as Dual EGFR/HER2 Tyrosine Kinase Inhibitors

4-Anilinoquinazolines as an important class of protein kinase inhibitor are widely investigated for epidermal growth factor receptor (EGFR) tyrosine kinase or epidermal growth factor receptor 2 (HER2) inhibition. A series of novel 6-salicyl-4-anilinoquinazoline derivatives 9–27 were prepared and evaluated for their EGFR/HER2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on three variant cancer cell lines (A431, MCF-7, and A549). The bioassay results showed most of the designed compounds exhibited moderate to potent in vitro inhibitory activity in the enzymatic and cellular assays, of which compound 21 revealed the most potent dual EGFR/HER2 inhibitory activity, with IC₅₀ values of 0.12 µM and 0.096 µM, respectively, comparable to the control compounds Erlotinib and Lapatinib. Furthermore, the kinase selectivity profile of 21 was accessed and demonstrated its good selectivity over the majority of the close kinase targets. Docking simulation was performed to position compound 21 into the EGFR/HER2 active site to determine the probable binding pose. These new findings along with molecular docking observations could provide an important basis for further development of compound 21 as a potent EGFR/HER2 dual kinase inhibitor.     

Complete Chloroplast Genome Sequence of Holoparasite Cistanche deserticola (Orobanchaceae) Reveals Gene Loss and Horizontal Gene Transfer from Its Host Haloxylon ammodendron (Chenopodiaceae)

Background

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants.

Principal Findings/Significance

Here we report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae. The cp genome of C. deserticola is greatly reduced both in size (102,657 bp) and in gene content, indicating that all genes required for photosynthesis suffer from gene loss and pseudogenization, except for psbM. The striking difference from other holoparasitic plants is that it retains almost a full set of tRNA genes, and it has lower dN/dS for most genes than another close holoparasitic plant, E. virginiana, suggesting that Cistanche deserticola has undergone fewer losses, either due to a reduced level of holoparasitism, or to a recent switch to this life history. We also found that the rpoC2 gene was present in two copies within C. deserticola. Its own copy has much shortened and turned out to be a pseudogene. Another copy, which was not located in its cp genome, was a homolog of the host plant, Haloxylon ammodendron (Chenopodiaceae), suggesting that it was acquired from its host via a horizontal gene transfer.     

A retrospective analysis of 140 patients with giant cell tumor in the extremity: A multicenter study based on four hospitals in South China

Background: Update reports are rarely available regarding the bone giant cell tumors (GCTs) in the extremity in Chinese people. The aim of this study was to review the epidemiological characteristics of bone GCT in the extremity based on the clinical data from four hospitals in South China. Methods: We searched medical electronic records from January 2001 to December 2011 in four hospitals in South China to identify patients with definite diagnosis of extremity GCT. Epidemiological data including gender, tumor site, age at the time of first diagnosis, local recurrence and pulmonary metastasis were collected and analyzed statistically. Differences between-genders were particularly analyzed regarding first diagnosis age, tumor site, local recurrence and pulmonary metastasis. T-test and Chi-square test were used for continuous and dichotomous variables, respectively. Results: A total of 140 GCT patients (87 males and 53 females) were identified. The gender ratio was 1.64 for a male predominance. GCTs were mostly located around the knee (67 cases). 92 patients were in their 20s to 40s upon first diagnosis. The average age at the time of first diagnosis for all was 30.49 years, 30.76 years for males and 30.06 years for females (P = 0.757). GCT recurred locally in 50 patients (26 males and 24 females) with no gender difference (P = 0.065). The average interval from first surgery to local recurrence was 21.42 months. Pulmonary metastasis was found in 11 patients (8 males and 3 females) also with no gender difference (P = 0.667). The average interval from first diagnosis to metastasis was 36.45 months. Conclusions: Extremity GCT may have a male predominance in Chinese population and mostly occur at 20–40 years of age and around the knee. Follow-ups for GCT patients should be carried on for at least 3 years after primary surgery according to the average intervals for possible local recurrence and pulmonary metastasis.     

Cancer incidence and mortality in people aged less than 75 years: Changes in Australia over the period 1987–2007

BackgroundAustralia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified.MethodsWe used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age–sex specific rates (average of 1986–1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006–2008). We limited the analyses to people aged less than 75 years.ResultsThere was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (?2259), bowel (?1797), breast (?773) and stomach (?577). Other notable falls were for cancers of the prostate (?295), cervix (?242) and non-Hodgkin lymphoma (?240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (?1705), bladder (?1110) and unknown primary (?904).ConclusionsThe reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.