The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells.

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase inhibitors, p16(INK4A) and p21(CIP1), but not Rb phosphorylation and E2F1 expression, indicating that AR has a specific role in the pathway-mediated differentiation and growth inhibitory signaling. However, despite the sufficient role of Raf/MEK/ERK, its inhibition using U0126 or ERK1/2 knockdown could not block androgen deprivation-induced AR downregulation in an LNCaP neuroendocrine differentiation model, suggesting that additional signaling pathways are involved in the regulation. We additionally report that sustained Raf/MEK/ERK activity can downregulate full length as well as hormone binding domain-deficient AR isoforms in androgen-refractory C4-2 and CWR22Rv1, but not in LAPC4 and MDA-PCa-2b. Our study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation

(2R)-N-(2-Benzoyl­phen­yl)-1-benzyl­pyrrolidine-2-carboxamide

In the title compound, C25H24N2O2, the dihedral angle between the two benzene rings of the benzophenone moiety is 59.10 (6)°. An intra­molecular, bifurcated N—H⋯(O,N) hydrogen bond, which generates S(6) and S(5) rings, respectively, helps to establish the overall conformation of the mol­ecule

Tracing the historical origin of Joseon mummies considering the structural similarities between the burial systems of Korean and Chinese dynasties

Joseon mummies have proved to be excellent subjects for scientific research on the health and disease statuses of pre-modern Korean peoples. Despite its academic significance, the origins of the Hoegwakmyo tomb in which the Joseon mummy was discovered have not yet been entirely revealed. Meanwhile, over the past several decades, there have been some reports on mummies and cultural artifacts preserved very well in the tombs of several Chinese dynasties (especially Song, Yuan, Ming and Qing). Although the Chinese tombs were very diverse in structure, we note that some graves among them were structurally very similar to Joseon Hoegwakmyo tombs. Before the Hoegwakmyo tomb in Korea, there were already similar tombs in China, inside which dead persons were mummified like the Joseon mummies. Considering that the Hoegwakmyo tomb of the Joseon Dynasty was established by the influence of the Confucian ideology, the Korean and Chinese mummies might share common cultural origins in history

Auxin response factor 2 (ARF2) plays a major role in regulating auxin-mediated leaf longevity

Auxin regulates a variety of physiological and developmental processes in plants. Although auxin acts as a suppressor of leaf senescence, its exact role in this respect has not been clearly defined, aside from circumstantial evidence. It was found here that ARF2 functions in the auxin-mediated control of Arabidopsis leaf longevity, as discovered by screening EMS mutant pools for a delayed leaf senescence phenotype. Two allelic mutations, ore14-1 and 14-2, caused a highly significant delay in all senescence parameters examined, including chlorophyll content, the photochemical efficiency of photosystem II, membrane ion leakage, and the expression of senescence-associated genes. A delay of senescence symptoms was also observed under various senescence-accelerating conditions, where detached leaves were treated with darkness, phytohormones, or oxidative stress. These results indicate that the gene defined by these mutations might be a key regulatory genetic component controlling functional leaf senescence. Map-based cloning of ORE14 revealed that it encodes ARF2, a member of the auxin response factor (ARF) protein family, which modulates early auxin-induced gene expression in plants. The ore14/arf2 mutation also conferred an increased sensitivity to exogenous auxin in hypocotyl growth inhibition, thereby demonstrating that ARF2 is a repressor of auxin signalling. Therefore, the ore14/arf2 lesion appears to cause reduced repression of auxin signalling with increased auxin sensitivity, leading to delayed senescence. Altogether, our data suggest that ARF2 positively regulates leaf senescence in Arabidopsis

Successful Resection of a Giant Left Ventricular Pseudoaneurysm Developed Later after Mitral Valve Replacement

We present a case of successful surgical resection of a giant left ventricular (LV) pseudoaneurysm that developed 5 yr after mitral valve replacement (MVR). A 59-yr-old female was admitted with exertional chest pain radiating to left arm and back. 64-slice multidetector computed tomography (MDCT) revealed significant stenosis on the ostium of the first diagonal branch of the left anterior descending coronary artery and also a huge pseudoaneurysm compressing the right atrium and the inferior vena cava. She underwent resection of the pseudoaneurysm, and the pseudoaneurysm tunnel was repaired from the inside of LV cavity by removing the previously inserted prosthetic valve, followed by redo MVR together with coronary arterial bypass grafting (CABG) for a single-vessel disease. At the 6-month follow-up, the patient continued to do well without any complications

Effects of Preoperative Anxiety on Gastric Fluid Acidity and Volume

The aim of this study was to evaluate the effect of preoperative anxiety on the gastric pH and volume. We studied 96 female patients aged 16-60 yr who underwent elective gynecological surgery. We classified the subjects into 2 groups, those presenting preoperative anxiety scores using visual analogue scale (VAS, 0-10) less than 5 (L-group, n=59), and those with 5 and more (H-group, n=37). Immediately after tracheal intubation, gastric contents were aspirated using a 14-F multiorifice nasogastric tube. The gastric acidity and volume of the two groups were not statistically different. Mean pH were 3.0±1.8 and 3.0±2.0 in each group (L-group and H-group) and mean gastric volume (mL) were 15.3±11.7 and 11.8±11.8, respectively. Nine (15.3%) patients in the L-group were considered to be 'at risk i.e. gastric pH <2.5 and volume >25 mL' and one patient (2.7%) in the H-group (p<0.05). The mean serum gastrin concentrations in both groups were similar (21.6±9.8 vs. 20.2±11.0 pg/mL). The pH and volume of preoperative gastric contents were not correlated with the preoperative anxiety. The results suggest that a low level of preoperative anxiety can be considered a risk factor for aspiration pneumonitis

Changes in the Reflux Symptom Index After Multilevel Surgery for Obstructive Sleep Apnea

Objectives This study evaluated whether the symptoms of laryngopharyngeal reflux (LPR) change after multilevel surgery for obstructive sleep apnea (OSA). Methods Patients who underwent multilevel surgery for OSA between April 2009 and September 2014 were enrolled in this study. All patients underwent preoperative polysomnography prior to surgery and were asked to complete the reflux symptom index (RSI) questionnaire before and after surgery. Results Of 73 enrolled patients, 24 (33%) reported an RSI score >13 and were thus classified as having reflux. The mean RSI score before surgery was 11.48±7.95; this number decreased to 4.95±6.19 after surgery (P<0.001). The rate of positive RSI responses was 33% before surgery and 9% after surgery. Each variable that comprised the RSI improved significantly after surgery, except for difficulty with swallowing. Regarding the degree of RSI improvement after surgery, there were no significant differences between subgroups according to sex, age, body mass index, OSA severity, or surgical outcome. Conclusion LPR symptoms are prevalent in OSA patients. Treatment for OSA using multilevel surgery potentially reduces the symptoms of LPR

Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin

AbstractEndothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp–EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage