In Vitro Chemosensitivity Using the Histoculture Drug Response Assay in Human Epithelial Ovarian Cancer

The choice of chemotherapeutic drugs to treat patients with epithelial ovarian cancer has not depended on individual patient characteristics. We have investigated the correlation between in vitro chemosensitivity, as determined by the histoculture drug response assay (HDRA), and clinical responses in epithelial ovarian cancer. Fresh tissue samples were obtained from 79 patients with epithelial ovarian cancer. The sensitivity of these samples to 11 chemotherapeutic agents was tested using the HDRA method according to established methods, and we analyzed the results retrospectively. HDRA showed that they were more chemosensitive to carboplatin, topotecan and belotecan, with inhibition rates of 49.2%, 44.7%, and 39.7%, respectively, than to cisplatin, the traditional drug of choice in epithelial ovarian cancer. Among the 37 patients with FIGO stage Ⅲ/Ⅳ serous adenocarcinoma who were receiving carboplatin combined with paclitaxel, those with carboplatin-sensitive samples on HDRA had a significantly longer median disease-free interval than patients with carboplatin- resistant samples (23.2 vs. 13.8 months, p＜0.05), but median overall survival did not differ significantly (60.4 vs. 37.3 months, p＝0.621). In conclusion, this study indicates that HDRA could provide useful information for designing individual treatment strategies in patients with epithelial ovarian cancer

Depression and PTSD in Pashtun Women in Kandahar, Afghanistan

ObjectivesThe objectives were (a) to establish prevalence of depression and post-traumatic stress disorder (PTSD) in Afghanistan and, (b) to investigate sociodemographic and quality of life variables, which predict depression and PTSD.MethodsTranslated versions of the Beck Depression Inventory, Impact of Event Scale-Revised, and Quality of Life Inventory were administered to 125 Pashtun women in Kandahar, and statistically analyzed.ResultsApproximately half of the participants showed moderate to severe levels of depression, and more than half of the participants exhibited symptoms of PTSD. Education and income showed significant associations with PTSD symptoms or depression. The way one spends time, general health status, and general feeling towards life predicted low levels of depression and PTSD.ConclusionsThe high prevalence of depression and PTSD indicate the continuing need for mental health intervention. While education has been found to be a protective factor for mental health in previous studies, the relationship between education and mental health appear to be more complex among Afghan women. Quality of life variables could be further investigated and incorporated into mental health interventions for Afghan women

Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for Glucose Uptake

Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1) activation is required for (14)C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT) stimulates PLD activity, while AMPK-dominant negative (DN) inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14)C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14)C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK) is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA), which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14)C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator) regulate (14)C-glucose uptake and cell surface glucose transport (GLUT) 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14)C-glucose uptake through ERK stimulation. We propose that the AMPK-mediated PLD1 pathway may provide crucial clues to understanding the mechanisms involved in glucose uptake

Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM) of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance

Micro solid oxide fuel cell fabricated on porous stainless steel: a new strategy for enhanced thermal cycling ability

Miniaturized solid oxide fuel cells (micro-SOFCs) are being extensively studied as a promising alternative to Li batteries for next generation portable power. A new micro-SOFC is designed and fabricated which shows enhanced thermal robustness by employing oxide-based thin-film electrode and porous stainless steel (STS) substrate. To deposit gas-tight thin-film electrolyte on STS, nano-porous composite oxide is proposed and applied as a new contact layer on STS. The micro-SOFC fabricated on composite oxide- STS dual layer substrate shows the peak power density of 560 mW cm−2 at 550 °C and maintains this power density during rapid thermal cycles. This cell may be suitable for portable electronic device that requires high power-density and fast thermal cycling.1111Ysciescopu

Structural studies on Helicobacter pylori ATP-dependent protease, FtsH

The crystal structures of the Helicobacter pylori FtsH ATPase domain in the nucleotide-free state and complexed with ADP have been determined

Crescimento reduzido por salinidade, fotoquímica PS2 e conteúdo de clorofila em rabanete

When plants are grown under saline conditions, photosynthetic activity decreases leading to reduced plant growth, leaf area, chlorophyll content and chlorophyll fluorescence. Seeds and seedlings of radish (Raphanus sativus L.) were grown in NaCl solutions under controlled greenhouse conditions. The NaCl concentrations in complete nutrient solutions were 0 (control), 4.7, 9.4 and 14.1 dS m-1. The salinity reduced germination percentage and also delayed the germination rate as the salt level increased. Lengths and fresh weights of root and shoot decreased with the increasing salt concentration. Furthermore, photochemical efficiency of PS2 (Fv/Fm), photochemical quenching coefficient (qP), non photochemical quenching coefficient (qN), leaf area and chlorophyll content (SPAD value) were also reduced (P < 0.001) by salt stress. In contrast, the Fo/Fm ratio increased with increasing salt concentration while salinity showed no effect on the efficiency of excitation captured by open PS2 (Fv'/Fm'), electron transport rate (ETR), and leaf water content. Linear regression shows that the photochemical efficiency of PS2 (Fv/Fm) had a positive relationship with the photochemical quenching coefficient (qP), leaf area and chlorophyll content but had no relation with Fv'/Fm', Fo/Fm, and qN.Quando plantas crescem sob condições de salinidade, sua atividade fotossintética diminui levando a um crescimento reduzido, menor área foliar, conteúdo de clorofila e fluorescência de clorofila. Sementes e plântulas de rabanete (Raphanus sativus L.) foram germinadas e conduzidas em soluções de NaCl sob condições controladas de casa de vegetação. As concentrações de NaCl adicionado a solução nutritiva completa foram 0 (Controle), 4,7; 9,4 e 14,1 dS m-1. A salinidade diminui a percentagem de germinação e também atrasou a taxa de germinação com o aumento do nível de sal. Comprimento e peso fresco da parte aérea e da raiz decresceram com o aumento da concentração salina. Além disso, a eficiência fotoquímica de PS2 (Fv/Fm), o coeficiente fotoquímico de 'quenchin" (q p), o coeficiente não fotoquímico de "quenching" (q n), a área foliar e o teor de clorofila (valor SPAD) também foram reduzidos (P < 0,001) por estresse de sal. Ao contrário, a relação Fo/Fm aumentou com a concentração salina, ao passo que a salinidade não teve efeito sobre a eficiência de excitação capturada pelo PS2 aberto (Fv'/Fm'), taxa de transporte eletrônico (ETR) e conteúdo de água na folha. Através de regressão linear mostrou-se que a eficiência fotossintética de PS2 (Fv/Fm) teve uma relação positiva com o coeficiente fotoquímico de "quenching" (q p), área foliar e conteúdo de clorofila, mas nenhuma relação com (Fv/Fm), (Fo/Fm), e q n