RESUMO
In the original publication [...].
RESUMO
Spontaneous senescence of cancer cells remains a puzzling and poorly understood phenomenon. Here we comprehensively characterize this process in primary epithelial ovarian cancer cells (pEOCs). Analysis of tumors from ovarian cancer patients showed an abundance of senescent cells in vivo. Further, serially passaged pEOCs become senescent after a few divisions. These senescent cultures display trace proliferation, high expression of senescence biomarkers (SA--Gal, -H2A.X), growth-arrest in the G1 phase, increased level of cyclins D1, D2, decreased cyclin B1, up-regulated p16, p21, and p53 proteins, eroded telomeres, reduced activity of telomerase, predominantly non-telomeric DNA damage, activated AKT, AP-1, and ERK1/2 signaling, diminished JNK, NF-B, and STAT3 pathways, increased formation of reactive oxygen species, unchanged activity of antioxidants, increased oxidative damage to DNA and proteins, and dysfunctional mitochondria. Moreover, pEOC senescence is inducible by normal peritoneal mesothelium, fibroblasts, and malignant ascites via the paracrine activity of GRO-1, HGF, and TGF-1. Collectively, pEOCs undergo spontaneous senescence in a mosaic, telomere-dependent and telomere-independent manner, plausibly in an oxidative stress-dependent mechanism. The process may also be activated by extracellular stimuli. The biological and clinical significance of pEOC senescence remains to be explored.
RESUMO
Oxidation status of the salivary aldehyde dehydrogenase (ALDH) was measured in healthy human population using two-assay fluorimetric method and compared with antioxidant capacity (ORAC) in non-smoking and heavy smokers group. Influence of high or low antioxidant diet was also examined. Except for the group of smokers, the salivary ALDH oxidation degree in human saliva was not correlated with antioxidant capacity. Simultaneously direct administration of the antioxidant-containing drug, Fluimucil, resulted in short-term, but statistically significant increase of the reduced (active) form of the enzyme, presumably due to a radical-scavenging activity of the drug.
Assuntos
Aldeído Desidrogenase/metabolismo , Antioxidantes/metabolismo , Saliva/enzimologia , Fumar/metabolismo , Acetilcisteína/farmacologia , Adolescente , Adulto , Idoso , Dieta , Feminino , Fluorometria/métodos , Sequestradores de Radicais Livres/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Saliva/metabolismo , Adulto JovemRESUMO
The crystal structures of triethylammonium adenosine cyclic 2',3'-phosphate {systematic name: triethylammonium 4-(6-aminopurin-9-yl)-6-hydroxymethyl-2-oxido-2-oxoperhydrofurano[3,4-c][1,3,2]dioxaphosphole}, Et(3)NH(2',3'-cAMP) or C(6)H(16)N(+).C(10)H(11)N(5)O(6)P(-), (I), and guanosine cyclic 2',3'-phosphate monohydrate {systematic name: triethylammonium 6-hydroxymethyl-2-oxido-2-oxo-4-(6-oxo-1,6-dihydropurin-9-yl)perhydrofurano[3,4-c][1,3,2]dioxaphosphole monohydrate}, [Et(3)NH(2',3'-cGMP)].H(2)O or C(6)H(16)N(+).C(10)H(11)N(5)O(7)P(-).H(2)O, (II), reveal different nucleobase orientations, viz. anti in (I) and syn in (II). These are stabilized by different inter- and intramolecular hydrogen bonds. The structures also exhibit different ribose ring puckering [(4)E in (I) and (3)T(2) in (II)] and slightly different 1,3,2-dioxaphospholane ring conformations, viz. envelope in (I) and puckered in (II). Infinite ribbons of 2',3'-cAMP(-) and helical chains of 2',3'-cGMP(-) ions, both formed by O-H...O, N-H...X and C-H...X (X = O or N) hydrogen-bond contacts, characterize (I) and (II), respectively.
Assuntos
AMP Cíclico/química , GMP Cíclico/química , AMP Cíclico/análogos & derivados , GMP Cíclico/análogos & derivados , Conformação MolecularRESUMO
Efficient and practical large scale synthesis of suitably protected 1',2'-oxetane locked purine and pyrimidine nucleosides for incorporation in oligo-DNA or -RNA by solid-phase synthesis is reported. A high regio and stereoselectivity with preferential formation of the beta-anomer in the glycosylation reaction, using the Vorbrüggen procedure, was achieved by a convergent synthetic procedure with orthogonal protection strategy using either 1,2-di-O-acetyl-3,4-O-isopropylidene-6-O-(4-toluoyl)-d-psicofuranose or 2-O-acetyl-6-O-benzyl-1,3,4-tri-O-(4-toluoyl)-d-psicofuranose as the glycosyl donor.