Purpose Signal Transducers and Activators of Transcription (STATs) activate transcription in response to numerous cytokines, controlling proliferation, gene expression and apoptosis. Aberrant activation of STAT proteins, particularly STAT-3, is implicated in the pathogenesis of many cancers, including Globlastoma Multiforme (GBM), by promoting cell cycle progression, stimulating angiogenesis, and impairing tumor immune surveillance. Little is known about the endogenous STAT inhibitors, the Protein Inhibitors of Activated STATs (PIAS) proteins, in human malignancies. The objective of this study was to examine the expression of STAT-3 and its negative regulator, PIAS3, in human tissue samples from control and GBM brains. Experimental Design Control and GBM human tissues were analyzed by immunoblotting and immunohistochemistry to determine the activation status of STAT-3 and expression of the PIAS3 protein. The functional consequence of PIAS3 inhibition by siRNA or PIAS3 over-expression in GBM cells was determined by examining cell proliferation, STAT-3 transcriptional activity and STAT-3 target gene expression. This was accomplished using 3H-TdR incorporation, STAT-3 dominant-negative constructs, RT-PCR and immunoblotting. Results and Conclusions STAT-3 activation, as assessed by tyrosine and serine phosphorylation, was elevated in GBM tissue compared to control tissue. Interestingly, we observed expression of PIAS3 in control tissue, while PIAS3 protein expression in GBM tissue was greatly reduced. Inhibition of PIAS3 resulted in enhanced glioblastoma cellular proliferation. Conversely, PIAS3 over-expression inhibited STAT-3 transcriptional activity, expression of STAT-3 regulated genes, and cell proliferation. We propose that the loss of PIAS3 in GBM contributes to enhanced STAT-3 transcriptional activity and subsequent cell proliferation.
The significant increase in life expectancy is closely related to the growing interest in the impact of aging on the function and appearance of the skin. Skin aging is influenced by several factors, and solar ultraviolet (UV) irradiation is considered one of the most important causes of skin photoaging. The aim of this study was to examine the anti-photoaging role of porphyra-334 from Porphyra (P.) yezoensis, a mycosporine-like amino acid (MAA), using high-performance liquid chromatography (HPLC), and electrospray ionization-mass spectrometry (ESI-MS). In the present study, extracted UV-absorbing compounds from P. yezoensis included palythine, asterina-330 and porphyra-334. Porphyra-334 was the most abundant MAA in P. yezoensis, and it was therefore used for conducting antiphotoaging experiments. The effect of porphyra-334 on the prevention of photoaging was investigated by measuring reactive oxygen species (ROS) production and matrix metalloproteinase (MMP) levels, as well as extracellular matrix (ECM) components and protein expression in UVA-irradiated human skin fibroblasts. Porphyra-334 suppressed ROS production and the expression of MMPs following UVA irradiation, while increasing levels of ECM components, such as procollagen, type I collagen, elastin. These results suggest that porphyra-334 has various applications in cosmetics and toiletries because of its anti-photoaging activities and may serve as a novel anti-aging agent.
OBJECTIVEMany studies have reported that periodontal disease is associated with diabetes, but its relation with impaired fasting glucose (IFG) has been understudied. This study investigated the relationship between chronic periodontitis, IFG, and diabetes in the U.S. population.RESEARCH DESIGN AND METHODSParticipants in the National Health and Nutrition Examination Survey III, aged ≥20 years, who received periodontal examinations and provided blood samples (n = 12,254) were grouped into quintiles of mean clinical attachment loss (CAL) and pocket depth, with the lowest category being the reference. Plasma fasting glucose was categorized into three groups (normal, <100 mg/dL; IFG, ≥100 but <126 mg/dL; and diabetic, ≥126 mg/dL). Sociodemographic factors and other potential risk factors were obtained by interview or examination. SAS 9.1 was used for statistical analysis accounting for the complex weighted sampling.RESULTSParticipants in the top quintile category of CAL had higher prevalence odds of IFG (odds ratio [OR] 1.55 [95% CI 1.16–2.07]) and diabetes (4.77 [2.69–8.46]) after adjustment for related confounders, compared with those in the bottom quintile. The highest quintile of pocket depth was positively associated with IFG (1.39 [1.00–1.92]) and diabetes (1.63 [1.10–2.42]) compared with the lowest quintile. ORs for CAL increased from the lowest to the highest quintile (P value test for trend <0.01) for all outcomes. The ORs for pocket depth also tended to rise across quintiles.CONCLUSIONSChronic periodontitis measured by CAL and pocket depth was positively associated in a linear relation with IFG and diabetes in U.S. adults.
Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.
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