Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa

BACKGROUND: Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon. METHODS: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods. RESULTS: Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon. CONCLUSION: The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon

SNAI2/Slug promotes growth and invasion in human gliomas

<p>Abstract</p> <p>Background</p> <p>Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known.</p> <p>Methods</p> <p>To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer.</p> <p>Results</p> <p>Using this approach, we identified the oncogenic transcriptional repressor, <it>SNAI2</it>/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. <it>SNAI2 </it>mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of <it>SNAI2/</it>Slug increased glioblastoma cell proliferation and invasion <it>in vitro </it>and promoted angiogenesis and glioblastoma growth <it>in vivo</it>. Importantly, knockdown of endogenous <it>SNAI2</it>/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model.</p> <p>Conclusion</p> <p>This genome-scale approach has thus identified <it>SNAI2</it>/Slug as a regulator of growth and invasion in human gliomas.</p

Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromsø Staph and Skin Study

Vitamin D induces the expression of antimicrobial peptides with activity against Staphylococcus aureus. Thus, we studied the association between serum 25-hydroxyvitamin D (25(OH)D) and S. aureus nasal colonization and carriage. Nasal swabs, blood samples and clinical data from 2,115 women and 1,674 men, aged 30–87 years, were collected in the Tromsø Staph and Skin Study 2007–08, as part of the population-based sixth Tromsø Study. Multivariate logistic regression analyses were stratified by recognized risk factors for S. aureus carriage: sex, age and smoking. In non-smoking men, we observed a 6.6% and 6.7% decrease in the probability of S. aureus colonization and carriage, respectively, by each 5 nmol/l increase in serum 25(OH)D concentration (P < 0.001 and P = 0.001), and serum 25(OH)D > 59 nmol/l and ≥75 nmol/l as thresholds for ~30% and ~50% reduction in S. aureus colonization and carriage. In non-smoking men aged 44–60 years, the odds ratio for S. aureus colonization was 0.44 (95% confidence interval, 0.28−0.69) in the top tertile of serum 25(OH)D versus the bottom tertile. In women and smokers there were no such associations. Our study supports that serum vitamin D is a determinant of S. aureus colonization and carriage

Crystal structure of tarocystatin–papain complex: implications for the inhibition property of group-2 phytocystatins

Tarocystatin (CeCPI) from taro (Colocasia esculenta cv. Kaohsiung no. 1), a group-2 phytocystatin, shares a conserved N-terminal cystatin domain (NtD) with other phytocystatins but contains a C-terminal cystatin-like extension (CtE). The structure of the tarocystatin–papain complex and the domain interaction between NtD and CtE in tarocystatin have not been determined. We resolved the crystal structure of the phytocystatin–papain complex at resolution 2.03 Å. Surprisingly, the structure of the NtD–papain complex in a stoichiometry of 1:1 could be built, with no CtE observed. Only two remnant residues of CtE could be built in the structure of the CtE–papain complex. Therefore, CtE is easily digested by papain. To further characterize the interaction between NtD and CtE, three segments of tarocystatin, including the full-length (FL), NtD and CtE, were used to analyze the domain–domain interaction and the inhibition ability. The results from glutaraldehyde cross-linking and yeast two-hybrid assay indicated the existence of an intrinsic flexibility in the region linking NtD and CtE for most tarocystatin molecules. In the inhibition activity assay, the glutathione-S-transferase (GST)-fused FL showed the highest inhibition ability without residual peptidase activity, and GST-NtD and FL showed almost the same inhibition ability, which was higher than with NtD alone. On the basis of the structures, the linker flexibility and inhibition activity of tarocystatins, we propose that the overhangs from the cystatin domain may enhance the inhibition ability of the cystatin domain against papain

International recommendations for glucose control in adult non diabetic critically ill patients

The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishedPour la Société Française d'Anesthésie-Réanimation (SFAR); Société de Réanimation de langue Française (SRLF) and the Experts grou