Pronounced activation of protein kinase C, ornithine decarboxylase and c-jun proto-oncogene by paraquat-generated active oxygen species in WI-38 human lung cells

AbstractParaquat (methyl viologen, PQ) is a widely used herbicide that produces oxygen-derived free radicals and severely injures human lungs. In this study we examined the effects of PQ on the protein kinase C (PKC), ornithine decarboxylase (ODC) and c-jun oncogene expression in WI-38 human lung cells. Exposure of cells to 25–200 μM PQ resulted in an increase of [3H]phorbol dibutyrate (PDBu) binding and PKC redistribution in a dose-dependent manner. Interestingly, a superoxide dismutase mimic, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 2.5 mM) and catalase (400 μg/ml) could significantly reduce the PQ-stimulated increase of phorbol ester binding and particular PKC phosphorylatiog activity, but dimethylsulfoxide (DMSO, 1.5%), an effective ·OH trapping agent, failed to prevent this stimulation. In addition, an endogenous substrate of PKC, 80 kDa protein, was found to be highly phosphorylated in intact WI-38 cells treated with 50 AM PQ. The increase of phosphorylated proteins could be completely or partly abolished by Tempol or catalase, but only the phosphorylation of 80 kDa protein was diminished by protein kinase C inhibitor, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7). A maximal peak of ODC activity was observed at 6 h of treatment with 50 μM PQ. PQ induced activity was reduced at the following rates, Tempol 85%, DMSO 80% and catalase 45%, but H-7 failed to do so. Furthermore, we found that the level of c-jun mRNA was transiently increased by PQ and the peak appeared at 1 h of treatment. When correlated with the PKC result, Tempol, catalase and H-7 all effectively blocked PQ-elicited c-jun transcript expression, but DMSO only exhibited a weakly inhibitory effect. We therefore propose that superoxide anion (O2− and H2O2 generated by PQ could activate PKC and lead to induction of c-jun gene expression; on the other hand, O2− and ·OH might trigger other kinase pathways to elevate ODC activity. Finally, the sequential expression of c-jun oncogene, and ODC may cooperate to relieve the oxidative damages elicited by PQ

First-order magnetic and structural phase transitions in Fe1+y_{1+y}Sex_xTe1−x_{1-x}

We use bulk magnetic susceptibility, electronic specific heat, and neutron scattering to study structural and magnetic phase transitions in Fe$_{1+y}$Se% $_x$Te$_{1-x}$. Fe$_{1.068}$Te exhibits a first order phase transition near 67 K with a tetragonal to monoclinic structural transition and simultaneously develops a collinear antiferromagnetic (AF) order responsible for the entropy change across the transition. Systematic studies of FeSe$$Te$_x$ system reveal that the AF structure and lattice distortion in these materials are different from those of FeAs-based pnictides. These results call into question the conclusions of present density functional calculations, where FeSe$_{1-x}$Te$_x$ and FeAs-based pnictides are expected to have similar Fermi surfaces and therefore the same spin-density-wave AF order.Comment: 5 pages, 3 figure

Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Selenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population.</p> <p>Methods</p> <p>This was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years) from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders.</p> <p>Results</p> <p>The mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (<it>P </it>< 0.001, <it>P </it>< 0.05 and <it>P </it>< 0.001, respectively) after adjusting for age, gender, anthropometric indices, lifestyle factors, and cardio-vascular risk factors in several linear regression models. Furthermore, there was a significantly positive association between serum selenium and serum fasting glucose concentrations (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Total cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.</p

Dedifferentiated liposarcoma can induce a leukemoid reaction

SummaryLiposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

Dynamics of HBV cccDNA expression and transcription in different cell growth phase

<p>Abstract</p> <p>Background</p> <p>The covalently closed-circular DNA (cccDNA) of hepatitis B virus (HBV) is associated with viral persistence in HBV-infected hepatocytes. However, the regulation of cccDNA and its transcription in the host cells at different growth stages is not well understood.</p> <p>Methods</p> <p>We took advantages of a stably HBV-producing cell line, 1.3ES2, and examine the dynamic changes of HBV cccDNA, viral transcripts, and viral replication intermediates in different cellular growth stages.</p> <p>Results</p> <p>In this study, we showed that cccDNA increased suddenly in the initial proliferation phase of cell growth, probably attributable to its nuclear replenishment by intracellular nucleocapsids. The amount of cccDNA then decreased dramatically in the cells during their exponential proliferation similar to the loss of extrachromosomal plasmid DNA during cell division, after which it accumulated gradually while the host cells grew to confluency. We found that cccDNA was reduced in dividing cells and could be removed when proliferating cells were subjected to long term of lamivudine (3TC) treatment. The amounts of viral replicative intermediates were rapidly reduced in these proliferating cells and were significantly increased after cells reaching confluency. The expression levels of viral transcripts were increased in parallel with the elevated expression of hepatic transcription factors (HNF4α, CEBPα, PPARα, etc.) during cell growth confluency. The HBV transcripts were transcribed from both integrated viral genome and cccDNA, however the transcriptional abilities of cccDNA was less efficient then that from integrated viral genome in all cell growth stages. We also noted increases in the accumulation of intracellular viral particles and the secretion of mature virions as the cells reached confluency and ceased to grow.</p> <p>Conclusions</p> <p>Based on the dynamics of HBV replication, we propose that HBV replication is modulated differently in the different stages of cell growth, and can be divided into three phases (initial proliferation phase, exponential proliferation phase and growth confluency phase) according to the cell growth curve. The regulation of cccDNA in different cell growth phase and its importance regarding HBV replication are discussed.</p

Expression Pattern and Clinicopathological Relevance of the Indoleamine 2,3-Dioxygenase 1/Tryptophan 2,3-Dioxygenase Protein in Colorectal Cancer

Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host&apos;s immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of the APC gene remains unknown. Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci. Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate of APC. Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate of APC, making IDO1 an interesting target for immunotherapy in CRC