NanoTiO2 Sunscreen Does Not Prevent Systemic Oxidative Stress Caused by UV Radiation and a Minor Amount of NanoTiO2 is Absorbed in Humans.

The present pilot study tested the efficiency of nanoTiO2 sunscreen to prevent the oxidative stress/inflammation caused by ultraviolet (UV) radiation using biomarkers in subjects' blood, urine, and exhaled breath condensate (EBC). In addition, the skin absorption of nanoTiO2 was studied. Six identical subjects participated in three tests: (A) nanoTiO2 sunscreen, (B) UV radiation, and (C) sunscreen + UV. The first samples were collected before the test and the second after sunscreen application and/or UV exposure. On day 4, the third samples were collected, and the sunscreen was washed off, and the fourth samples were collected on day 11. The following biomarkers were measured: malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, aldehydes C6-C12, 8-iso-Prostaglandin F2α, o-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-hydroxymethyl uracil, and leukotrienes, using liquid chromatography-electrospray ionisation-tandem mass spectrometry. Titania was measured using inductively coupled plasma mass spectrometry and TiO2 nanoparticles by transmission and scanning electron microscopy. Sunscreen alone did not elevate the markers, but UV increased the biomarkers in the plasma, urine, and EBC. The sunscreen prevented skin redness, however it did not inhibit the elevation of oxidative stress/inflammatory markers. Titania and nanoTiO2 particles were found in the plasma and urine (but not in the EBC) in all sunscreen users, suggesting their skin absorption.

N-terminal domain of nuclear IL-1α shows structural similarity to the C-terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.

Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly.

HOX gene expression in phenotypic and genotypic subgroups and low HOXA gene expression as an adverse prognostic factor in pediatric ALL.

BACKGROUND: HOX genes play an important role in both normal lymphopoiesis and leukemogenesis. However, HOX expression patterns in leukemia cells compared to normal lymphoid progenitors have not been systematically studied in acute lymphoblastic leukemia (ALL) subtypes. PROCEDURE: The RNA expression levels of HOXA, HOXB, and CDX1/2 genes were analyzed by qRT-PCR in a cohort of 61 diagnostic pediatric ALL samples and FACS-sorted subpopulations of normal lymphoid progenitors. RESULTS: The RNA expression of HOXA7-10, HOXA13, and HOXB2-4 genes was exclusively detected in leukemic cells and immature progenitors. The RNA expression of HOXB6 and CDX2 genes was exclusively detected in leukemic cells but not in B-lineage cells at any of the studied developmental stages. HOXA3-4, HOXA7, and HOXB3-4 genes were differentially expressed between BCP-ALL and T-ALL subgroups, and among genotypically defined MLL/AF4, TEL/AML1, BCR/ABL, hyperdiploid and normal karyotype subgroups. However, this differential expression did not define specific clusters in hierarchical cluster analysis. HOXA7 gene was low expressed at the RNA level in patients with hyperdiploid leukemia, whereas HOXB7 and CDX2 genes were low expressed in TEL/AML1-positive and BCR/ABL-positive cases, respectively. In contrast to previous findings in acute myeloid leukemia, high HOXA RNA expression was associated with an excellent prognosis in Cox's regression model (P = 0.03). In MLL/AF4-positive ALL, lower HOXA RNA expression correlated with the methylation status of their promoters. CONCLUSIONS: HOX gene RNA expression cannot discriminate leukemia subgroups or relative maturity of leukemic cells. However, HOXA RNA expression correlates with prognosis, and particular HOX genes are expressed in specific genotypically characterized subgroups.