Novel Quinolone CHM-1 Induces Apoptosis and Inhibits Metastasis in a Human Osterogenic Sarcoma Cell Line

[[abstract]]Novel 2-phenyl-4-quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20-fluoro-6,7-methylenedioxy-2-phenyl-4-quinol one (CHM-1) in human osterogenic sarcoma U-2 OS cells. CHM-1-induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM-1-inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM-1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM-1 induced G2/M arrest and apoptosis at an IC50 (3 mu M) in U-2 OS cells and caspase-3, -8, and -9 were activated. Caspase inhibitors increased cell viability after exposure to CHM-1. CHM-1-induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased Delta Psi(m), levels, and promotion of mitochondrial cytochrome c release. CHM-1 stimulated mRNA expression of caspase-3, -8, and -9, AIF, and Endo G. In addition, CHM-1 inhibited cell metastasis at a low concentration (<3 mu M). CHM-1. inhibited the cell metastasis through the inhibition of MMP-2, -7, and -9. CHM-1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM-1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM-1. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1.637-1644, 200

Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer

The risk of dementia after androgen deprivation therapy (ADT) in patients with advanced prostate cancer (PCa) remains controversial. This study aimed to evaluate the association between ADT and the incidence of dementia in patients with PCa. We identified patients newly diagnosed with PCa in the National Health Insurance Database of Taiwan from 1 January 2002 to 30 June 2016 and in The Health Improvement Network of the United Kingdom (UK) from 1 January 1998 to 31 March 2018. We classified patients with PCa into ADT and ADT-naïve groups. Propensity score (PS) methods were used to minimize the differences in characteristics between the groups. We performed a Cox proportional hazard model to obtain the adjusted hazard ratio (HR) to compare the incidence of dementia between the groups. Our ADT group comprised 8743 and 73,816 patients in Taiwan and the UK, respectively, which were matched 1:1 to ADT-naïve patients by PS. The incidence rates of dementia in the ADT group were 2.74 versus 3.03 per 1000 person-years in the ADT naïve groups in Taiwan, and 2.81 versus 2.79 per 1000 person-years in the UK. There was no statistical difference between ADT and ADT-naïve groups (adjusted HR: 1.12; 95% confidence interval (CI): 0.87–1.43 in Taiwan and adjusted HR: 1.02; 95% CI: 0.85–1.23 in the UK). We found no association between the incidence of dementia and ADT in patients with advanced PCa in either database. Further studies are warranted to evaluate other possible triggers of incident dementia in patients receiving ADT for advanced PCa

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

Pregnancy in women with pulmonary hypertension

Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced therapies for pulmonary hypertension decrease the risk, though some promising results have been reported. However, pregnancy should still be regarded as contraindicated in women with pulmonary hypertension. When pregnancy occurs and termination is declined, pregnancy and delivery should be managed by multidisciplinary services with experience in the management of both pulmonary hypertension and high-risk pregnancies

The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds

The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds

Electronic structure and bonding properties of Si-doped hydrogenated amorphous carbon films

[[abstract]]This work investigates the C K-edge x-ray absorption near-edge structure (XANES), valence-band photoelectron spectroscopy (PES), and Fourier transform infrared (FTIR) spectra of Si-doped hydrogenated amorphous carbon films. The C K-edge XANES and valence-band PES spectra indicate that the sp2/sp3 population ratio decreases as the amount of tetramethylsilane vapor precursor increases during deposition, which suggest that Si doping% enhances sp3 and reduces sp2-bonding configurations. FTIR spectra show the formation of a polymeric sp3 C–Hn structure and Si–Hn bonds, which causes the Young’s modulus and hardness of the films to decrease with the increase of the Si content.[[incitationindex]]SCI[[booktype]]紙

Applying the selective Cu electroplating technique to light-emitting diodes

[[abstract]]We successfully fabricated a predefined patterned copper (Cu) substrate for thin GaN light-emitting diodes without barriers by the selective electroplating technique. The contours of Cu bumps fabricated using different electroplating modes and parameters were measured. We observed that the average thickness diminished with increasing current density. The current density conditions to obtain the best upright structure in the process were 40 and 80 mA/cm2.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Women's preference for cesarean delivery and differences between Taiwanese women undergoing different modes of delivery

<p>Abstract</p> <p>Background</p> <p>The rate of cesarean delivery was 35% in 2007 in Taiwan. It is unclear how many of the cesarean deliveries were without medical indications. Women's preference for cesarean delivery during their course of pregnancy has rarely been studied and therefore our objectives were to examine rate of cesarean deliveries without medical indications, to explore women's preference for cesarean delivery as their gestation advances, and to compare background and perinatal factors among women who underwent different modes of delivery in Taiwan.</p> <p>Methods</p> <p>This prospective study applied a longitudinal design. The study participants were 473 women who received prenatal care at four hospitals in Taipei and answered structured questionnaires at 20 to 24 weeks of pregnancy, 34 to 36 weeks of pregnancy, and 5 to 7 weeks after delivery.</p> <p>Results</p> <p>Of the 151 women (31.9%) who had cesarean deliveries, 19.9% were without medical indication. Three indications: malpresentation, prior cesarean section, and dysfunctional labor together accounted for 82.6% of cesarean section with medical indications. The prevalence of maternal preference for cesarean delivery was found to be 12.5% and 17.5% during the second and third trimester, respectively. Of the women who preferred cesarean delivery during the second trimester, 93.2% eventually had a cesarean delivery. Women who were older, with older spouses, and who had health problems before or during pregnancy were more likely to have cesarean deliveries.</p> <p>Conclusions</p> <p>About 20% of cesarean deliveries were without medical indications. Women's preference for cesarean delivery during the second trimester predicts subsequent cesarean delivery. Counseling regarding mode of delivery should be offered early in pregnancy, especially for women who are older or with older spouses, have health problems, or had a prior cesarean section.</p