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Purpose Hepatitis B virus (HBV) reactivation can occur after radiotherapy (RT) for hepatobiliary malignancies. Our previous in vitro culture study identified interleukin-6 (IL-6) as the main bystander mediator of RT-induced HBV replication. We attempted to examine the molecular mechanism in HBV-transgenic mice. Methods and materials HBV transgenic mice were treated with whole liver RT (4 Gy daily for 5 days) with or without administration of IL-6 (400 ng twice daily for 15 days). The serum level of HBV DNA was measured using real-time polymerase chain reaction, and the IL-6 concentration was measured using enzyme-linked immunosorbent assay. The intensity of immunostaining with antibodies to HBV core protein and phosphorylated signal transducer and activator of transcription (STAT)3 in the mouse liver was qualitatively analyzed. HepG2.2.15 cells (a human hepatoblastoma cell line that persistently produces HBV DNA) were used to investigate the molecular role of IL-6 plus RT in HBV reactivation. Results HBV reactivation was induced in vivo with IL-6 plus RT (5.58-fold) compared with RT alone (1.31-fold, p = .005), IL-6 alone (1.31-fold, p = .005), or sham treatment (1.22-fold, p = .004). HBV core protein staining confirmed augmentation of intrahepatic HBV replication. IL-6 plus RT-induced HBV DNA replication in HepG2.2.15 cells was suppressed by the STAT3 inhibitor AG490 and by transfection with dominant-negative STAT3 plasmid. Phosphorylated STAT3 staining was strongest in liver tissue from mice treated with IL-6 plus RT. The mobility shift assay demonstrated that reactivation was mediated through the interaction of phosphorylated STAT3/hepatocyte nuclear factor-3 complex with HBV enhancer 1. Conclusion RT to the liver and longer sustained IL-6 induced HBV reactivation through the STAT3 signal transduction pathway.

Summary Objective The human endometrium manifests different and distinct morphologies and physiologies during the different phases of the menstrual cycle. We aimed to determine which candidate genes demonstrate differential expression patterns in the endometrium during different phases of the menstrual cycle. Materials and Methods Using differential display reverse transcription polymerase chain reaction to compare day 5 and day 18 human glandular endometrium obtained by laser capture microdissection, we identified a specific gene, NUDT9 (nucleoside diphosphate-linked moiety X motif 9). NUDT9 is known to function as a highly specific adenosine diphosphate ribose pyrophosphatase and has been mapped to chromosome 4q22.1. It gives rise to two alternatively spliced messenger RNAs, NUDT9α and NUDT9β, encoding a member of the Nudix hydrolase family. In this study, we purified NUDT9 protein and produced an antibody, which we then used for immunohistochemical studies. Results Using this anti-NUDT9 antibody, we successfully demonstrated that NUDT9 protein was differentially expressed in endometrial glandular cells at different phases of the menstrual cycle. NUDT9 was also found to be expressed more prominently in the epithelial glandular component than in the stromal component of human endometrial carcinomas. Conclusion We suggest that NUDT9 may be involved in the regulation of the menstrual cycle and may be related to the proliferation of glandular cells in the human endometrium.

Since both the parents need to work and look after their babies/infants simultaneously, the families bear more workload. Thus, this paper presents an innovative infant monitoring system consisting of an embedded system platform with a Linux kernel embedded operation system using the TCP/IP protocol, a CMOS image sensor, and peripheral control systems. The key feature of the system is that it can be used to monitor the living environment and the activities of the babies and/or infants through a web browser at any time from any place in the world. In order to increase the accuracy of the temperature sensor, the measured values from the digital temperature sensor were calibrated using regression analysis methods, resulting in an accuracy of ± 0.1°C, a correlation coefficient of 0.996, and a standard deviation of 0.124. The experimental results show that the proposed concept and the resulting system are feasible.

By using brewery yeast waste and microflora from rice straw compost, an anaerobic semi-solid bio-hydrogen-producing system has been established. For the purpose of industrialization, the major players of both aerobic and anaerobic bacterial strains in the system were isolated and their combination for an effective production of bio-hydrogen and other bio-fuels was examined in this study. The phylogenetic analysis found that four anaerobic isolates (Clostridium beijerinckii L9, Clostridium diolis Z2, Clostridium roseum Z5-1, and C. roseum W8) were highly related with each other and belongs to the cluster I clostridia family, the family that many of solvent-producing strains included. On the other hand, one of the aerobic isolates, the Bacillus thermoamylovorans strain I, shown multiple extracellular enzyme activities including lipase, protease, α-amylase, pectinase and cellulase, was suggested as a good partner for creating an anaerobic environment and pre-saccharification of substrate for those co-cultured solventogenic clostridial strain. Among these clostridial strains, though C. beijerinckii L9 do not show as many extracellular enzyme activities as Bacillus, but it performs the highest hydrogen-producing ability. The original microflora can be updated to a syntrophic bacterial co-culture system contended only with B. thermoamylovorans I and C. beijerinckii L9. The combination of aerobic Bacillus and anaerobic Clostridium may play the key role for developing the industrialized bio-fuels and bio-hydrogen-producing system from biomass.

Lysophosphatidic acid (LPA) is a pleiotropic phospholipid molecule involved in inflammation, angiogenesis, would healing,andcancerinvasion.WhereasserumlysophospholipaseD activity increases in women with pregnancy, the role of LPA inpregnancyremainsunclear.Weinvestigatedtheexpression of LPA receptors and function of LPA in endometrial stromal cells. Histologically normal endometrium was obtained from surgical specimens of women undergoing hysterectomy for leiomyoma. First-trimester decidua was obtained from women receiving elective termination of pregnancy. We examined the expressions of LPA1, LPA2, and LPA3 receptors in endometrial stromal cells. The effects of LPA on the expression of vascular endothelial growth factor, IL-6, and IL-8 were examined. Signal pathways of LPA were delineated. Functions of secretory angiogenic factors were tested using human endometrial microvascular endothelial cells. Immunoreactivity and mRNA of LPA1 receptors were identified in endometrial stromal cells. LPA enhanced IL-8 expression in a dose- and time-dependent manner, whereas vascular endothelial growth factor or IL-6 expression was not affected by LPA treatment. Mechanistic dissection disclosed that LPA functioned via the Gi protein, MAPK/p38 and nuclear factor-B pathway. LPA-induced IL-8 enhanced migration, permeability, capillary tube formation, and proliferation of human endometrial microvascular endothelial cells. Endometrial stromal cells express LPA1 receptors. Through the LPA1 receptor, LPA induces IL-8 expression via a nuclear factor-B-dependent signal pathway. These results could suggest that LPA may play a role in angiogenesis of endometrium and placenta through induction of IL-8 in endometrial stromal cells during pregnancy. (Endocrinology 149: 5888–5896, 2008)

Ten and 100 L bioreactors were utilized to evaluate the effect of stirring and pH on anaerobes converting spent brewery grains to hydrogen. Experimental results of 10-L bioreactor demonstrated that both stirring speed and pH significantly affected the hydrogen conversion and the chemical oxygen demand reduction of the spent grains. Highly reproducible metabolic data confirmed that the anaerobes from grass compost could convert the spent grains to fatty acids and alcohols as well as hydrogen. Multiple analyses indicated that stirring mainly affected the hydrogen production rate. pH level was a more important factor than the stirring on shortening hydrogen production lag and increasing hydrogen yield. Optimum conditions of pH = 6.0 and stirring speed=120 rpm were obtained for 10-L bioreactor converting 3% grains to hydrogen by observing its production rate together with yield, found to be 161 mL H 2 / gTVS / d and 13 mL H 2 / g TVS , respectively. However, the rate and the yield decreased along with stirring speeds increased above 120 rpm. When the stirring speeds of 10-L bioreactor were greater than this value, its mixing condition changed from laminar flow to turbulent flow. The 100-L experiment with a sequencing batch mode operation confirmed that the hydrogen production rate obtained with laminar flow was significantly more stable and reproducible than with turbulent flow.

Through in situ reduction of a gold precursor, we have tethered gold nanoparticles (Au NPs) to the side chains of poly{2,7-(9,9' -dioctylfluorene)-co-4-diphenylamino-4' -bipenylmethylsulfide) (PF-DBMS) through its ArSCH 3 anchor groups. The presence of 1 wt % of the tethered Au NPs led to a reduction in the degree of aggregation of the polymer chains, resulting in a 50 % increase in its quantum yield. The electroluminescence of a 1 wt % Au/PF-DBMS device was almost four times higher in terms of its maximum brightness and its full-width-at-half-maximum emission peak was much narrower than that of a pure PF-DBMS device; the presence of a small amount of Au NPs significantly enhances the electron injection and transport and suppresses the photo-oxidation of PF-DBMS.

By using hydrogenase gene-targeted polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR), the predominant clostridial hydrogenase that may have contributed to biohydrogen production in an anaerobic semi-solid fermentation system has been monitored. The results revealed that a Clostridium pasteurianum-like hydrogenase gene sequence can be detected by both PCR and RT-PCR and suggested that the bacterial strain possessing this specific hydrogenase gene was dominant in hydrogenase activity and population. Whereas another Clostridium saccharobutylicum-like hydrogenase gene can be detected only by RT-PCR and suggest that the bacterial strain possessing this specific hydrogenase gene may be less dominant in population. In this study, hydrogenase gene-targeted fluorescence in situ hybridization (FISH) and flow cytometry analysis confirmed that only 6.6% of the total eubacterial cells in a hydrogen-producing culture were detected to express the C. saccharobutylicum-like hydrogenase, whereas the eubacteria that expressed the C. pasteurianum-like hydrogenase was 25.6%. A clostridial strain M1 possessing the identical nucleotide sequences of the C. saccharobutylicum-like hydrogenase gene was then isolated and identified as Clostridium butyricum based on 16S rRNA sequence. Comparing to the original inoculum with mixed microflora, either using C. butyricum M1 as the only inoculum or co-culturing with a Bacillus thermoamylovorans isolate will guarantee an effective and even better production of hydrogen from brewery yeast waste.

Objectives To study the role of selected cytokines and growth factors involved in the pathogenesis of fetal chylous pleural effusion. Methods Seventeen fetuses with prenatal chylothorax at gestational age (GA) 17–29 weeks were enrolled as the study group during the period 2003–2005. Their pleural effusion (n = 17) and amniotic fluid (n = 17) were drawn when disease set in. Eleven fetuses received cordocentesis because of suspected fetal anemia. Forty-one normal fetuses without adverse perinatal outcome at GA 17-29 weeks received amniocentesis and were enrolled in the reference group. Levels of hepatocyte growth factor (HGF), stromal-derived factor-1(SDF-1), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), macrophage migratory inhibition factor (MIF), and interleukin-6 (IL-6) were determined in the samples from both groups (amniotic fluid, pleural fluid, and cord blood from the study group and amniotic fluid from the reference group) by enzyme-linked immunoassay (EIA). Results No significant differences were observed in the amniotic fluids between the study group and the reference group regarding levels of IL-6, IL-8, MIF, SDF-1, HGF and VEGF. In the study group, levels of IL-8, VEGF and SDF-1 (all pro-angiogenic) showed no significant differences between the amniotic fluid, cord blood and pleural effusion. The level of HGF (proangiogenic) was significantly higher in the amniotic fluid than in the cord blood or the pleural effusion, but there were no significant differences between the levels in the pleural fluid and in the cord blood. Interestingly, the levels of MIF and IL-6 (both are proinflammatory) in the amniotic fluid and in the pleural effusion were much higher than the levels in the cord blood. Conclusion Our study demonstrated that the levels of pro-inflammatory proteins (MIF and IL-6) that we tested were higher in the fetal pleural effusion than in the fetal circulation, a phenomenon not observed in the levels of proangiogenic proteins (HGF, SDF-1, VEGF, IL-8). This result implies that inflammation-related proteins may be more relevant than the angiogenesis-related proteins in the local environment of accumulating pleural effusion, a prominent feature of prenatal chylothorax. Copyright © 2007 John Wiley & Sons, Ltd.

Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells.

Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity.

An adjustable output power ratio branch line coupler design is proposed. The mixed transmission line and shunted capacitor T-type equivalent circuit replaced the arms of the general branch line forms the tuning mechanism. By changing the shunted capacitors values, the power at output ports could shift to the desired ratio. A prototype circuit designed at 925MHz has been simulated and fabricated on FR4 substrate. The simulated experimental results show that the output power ratio changing is in a good agreement at the design frequency.

OBJECTIVE To test if collagen markers are associated with aldosterone-induced diastolic dysfunction. BACKGROUND Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction. METHODS We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group. RESULTS The baseline plasma TIMP-1 level (88.4 ± 38.7 vs. 63.6 ± 32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ± 2.9 vs. 9.0 ± 2.1; P

We have prepared highly luminescent dendron-substituted copolyfluorenes that incorporate surface-modified cadmium sulfide nanoparticles. Both the photoluminescence and electroluminescence efficiencies of the polymer nanocomposites are dramatically enhanced relative to the values of the pure polymer.

We demonstrated that in a nanocrystalline TiO2/poly(2-methoxy-5-(2 0 -ethylhexyloxy)-1,4-phenylene vinylene) (MEHPPV) composite, electroluminescence of this composite is enhanced via addition of TiO2 nanoneedles. The TiO2 nanoneedles enhance the partial crystallization of MEH-PPV around TiO2, which in turn causes a decrease in the hole barrier height and an increase in hole mobility. The IYV measurement was established on an indium tin oxide/MEHPPV:TiO2/Al device to identify the electrical properties of the composites.

We have synthesized a thermally stable and high molecular weight fluorescent poly(phenylenevinylene) (PPV) incorporating side-chain-tethered dendritic phenyl groups (DENPPV) through Gilch route; this DENPPV has a low abundance of tolane-bisbenzyl defects. Intramolecular energy transfer from the dendritic phenyl side group to the PPV backbone was evidenced from UV−vis and photoluminescence spectra of the DENPPV polymer and its model compound. Copolymers of DENPPV with 2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene (MEHPPV) display excellent photoluminescence both in solution and in the solid state; the highest quantum yield we observed was 82%. The electroluminescence of the copolymer MEHPPV/DENPPV (molar ratio: 25/75) was 70% higher than that of MEHPPV (0.12 lm/W vs 0.07).

We have synthesized, using the Gilch polymerization method, a new series of high- brightness, soluble copolymers (POSS-PPV-co-MEHPPV) of poly(p-phenylenevinylene) (PPV) containing side-chain-tethered polyhedral oligomeric silsesquioxane (POSS) pendent units and poly(2-methoxy-5- (2-ethylhexyloxy)-1,4-phenylenevinylene) (MEHPPV). This particular molecular architecture of POSS- PPV-co-MEHPPV copolymers possesses not only a larger quantum yield (0.85 vs 0.19) but also higher degradation and glass transition temperatures relative to those of pure MEHPPV. The maximum brightness of a double-layered-configured light-emitting diode (ITO/PEDOT/emissive polymer/Ca/Al) incorporating a copolymer of MEHPPV and 10 mol % PPV-POSS was 5 times as large as that of a similar light-emitting diode incorporating pure MEHPPV (2196 vs 473 cd/m 2 ).

To convert high-solids organic wastes (3% w./w.) to high-value hydrogen, a full factorial experimental design was employed in planning the experiments for learning the effects of pH and hydraulic retention time (HRT) on the hydrogen production in a chemostat reactor using waste yeast obtained from beer processing wastes. For determining which experimental variable settings affect hydrogen production, predictive polynomial quadratic equation and response surface methodology were employed to determine and explain the conditions required for high-value hydrogen production. Experimental results indicate that a maximum hydrogen production rate of 460 mL/gVSS/d was obtained at pH=5.8 and HRT=32 hours. Moreover, hydrogenase targeted RT-PCR results indicate that Clostridium thermocellum and Klebsiella pneumoniae predominated.

Using Suzuki polycondensation, we have synthesized polyhedral silsesquioxane-tethered polyfluorene copolymers, poly(9,9‘-dioctylfluorene-co-9,9‘-bis[4-(N,N-dipolysilsesquioxane)aminophenyl]fluorene) (PFO–POSS), that have well-defined architectures. This particular PFO–POSS molecular architecture increases the quantum yield of polyfluorene significantly by reducing the degree of interchain aggregation; in addition, these copolymers exhibit a purer and stronger blue light by preventing the formation of keto defects.

Arsenic trioxide (ATO) has been implicated as a promising anticancer agent by inhibiting cell growth and inducing apoptosis in certain types of cancer cells. This study explored the antimetastasis property of arsenic, drew potential link between arsenic use and radiotherapy, and uncovered the specific mechanisms underlying these remarkable responses. Using gelatin invasion assay and intravasation assay, we report the novel finding that low-dose ATO (1 muM) reduced the intrinsic migration ability of HeLa cells and significantly inhibited radiation-promoted tumor invasive potential of CaSki cells without inducing apoptotic cell death. Using the murine Lewis lung carcinoma model, the control animals and ATO treatment animals (1 mg/kg i.p., twice weekly) displayed similar in vivo growth kinetics, whereas the radiation (30 Gy in one fraction) and concurrent treatment groups showed considerable growth inhibition. Importantly, although concurrent treatment did not enhance the effectiveness of radiation therapy to the primary tumor, further examination of the lungs revealed that all animals succumbed to radiation-accelerated lung metastases could be effectively treated by combination of ATO and radiation. Radiation-induced matrix metalloproteinase-9 (MMP-9) expression was significantly inhibited by ATO using sequential analysis of the expression of MMPs in xenografts. Supporting this observation, ATO directly downregulates radiation-induced MMP-9 mRNA expression by inhibiting nuclear factor kappaB activity in human cervical cancer cells. In sum, concurrent arsenic-radiation therapy not only achieves local tumor control but also inhibits distant metastasis. Experimental results of this study highlight a novel strategy in cancer treatment.

Polystyrene-block-poly(ethylene oxide) (SEO) block copolymer thin films, in which CdS clusters have been sequestered into the PEO domains of the SEO block copolymers, are found to induce the morphological transformation of PEO from cylinders to spheres, as shown by using atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). This transformation is caused by the presence of hydrogen-bonding interactions between surface-hydroxylated CdS and PEO, as confirmed by nuclear magnetic resonance (NMR) studies.

Bioactive lysophospholipid, lysophosphatidic acid (LPA), is consistently raised in the ascites of patients with ovarian cancer. Interleukin-6 (IL-6) is a pleiotropic cytokine, which is assumed to be involved in ovarian carcinogenesis. However, the regulation of IL-6 in ovarian cancer remains largely unknown. To elucidate the pathogenesis of ovarian cancer, this study investigated how LPA affects IL-6 production in ovarian cancer cells. Experimental results indicated that LPA stimulates IL-6 expression in all ovarian cancer cell lines tested, but not in normal ovarian surface epithelial (NOSE) cells, owing to the lack of LPA-specific Edg4 and/or Edg7 receptors in NOSE cells. This work demonstrated that LPA transcriptionally activates IL-6 expression, which can be totally blocked by the pertussis toxin, indicating that Gi-mediated signaling is critically involved in inducing IL-6 by LPA. Pharmacological and genetic inhibition assays revealed that Gi-mediated PI3K activation phosphorylated downstream Akt and subsequently induced NF-kappaB activation causes the induction of IL-6 by LPA in SK-OV-3 cells. In summary, data presented here demonstrate that LPA is an important inducer of IL-6 and LPA-regulated IL-6 expression via a Gi/PI3K-Akt/NF-kappaB pathway in ovarian cancer cells, providing molecular therapeutic targets for treating ovarian cancer.

Vascular endothelial growth factor C (VEGF-C) is an important growth factor that governs lymphatic spread and the development of intraperitoneal tumors associated with epithelial ovarian cancer; however, its regulation is not yet understood. Overexpression of Her-2/NEU is related to poor survival in advanced epithelial ovarian carcinoma patients. Accordingly, this study attempted to analyze the association between the Her-2/NEU oncogene and VEGF-C in ovarian carcinoma and to elucidate the molecular mechanism of VEGF-C induction by Her-2/NEU. Immunohistochemistry was used to determine the expression of Her-2/NEU and VEGF-C in tissues from 41 patients with epithelial ovarian carcinoma. Several Her-2/NEU-stably-transfected Caov-3 ovarian carcinoma cells were used to evaluate the effect of Her-2/NEU on VEGF-C, the possible regulation mechanism, and the biological function of VEGF-C. Our experimental results identified a significant association between the Her-2/NEU oncogene and VEGF-C expression in both epithelial ovarian cancer patients (p0.05; Fisher's exact test) and in vitro cell lines. The overexpression of Her-2/NEU in Caov-3 ovarian cancer cells resulted in induction of a considerable amount of VEGF-C mRNA and protein; this process was dose-dependently inhibited by herceptin. The generation of VEGF-C significantly increased endothelial permeability. Pharmacological and genetic inhibition assays revealed that the cytoplasmic signaling molecule, p38 MAPK, and the transcriptional factor, NF-kappa B, are critically involved in the transcriptional activation of the VEGF-C gene by Her-2/NEU. In conclusion, this work clearly establishes that the Her-2/NEU oncogene is essential for the regulation of VEGF-C in ovarian carcinoma. It may be possible to use the monoclonal antibody targeting Her-2/NEU receptor to limit the formation of malignant ascites and lymphatic spread in ovarian carcinoma.

2,2′-dipyridylamine substituted poly(fluorene-co-phenylene) copolymers with different concentrations of dipyridylamine have been synthesized by Suzuki polycondensation. These polymers were found to be soluble in organic solvents such as tetrahydrofuran, chloroform, and dimethylformamide. The photoluminescence of the copolymer was slightly blueshifted as the concentration of dipridylamine was increased. The introduction of dipyridylamine and the ruthenium complex into the polymer significantly improved the photoluminescence efficiency. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4838–4846, 2004

Interleukin-6 (IL-6) has received particular attention in the pathogenesis of cervical cancer, although the underlying mechanism remains elusive. This study revealed that IL-6 promotes in vivo tumor growth of human cervical cancer C33A cells, but does not substantially alter their in vitro growth kinetics. The in vivo angiogenic assays showed that IL-6 increases angiogenic activity in human cervical cancer cells, an effect that is specifically associated with upregulation of vascular endothelial growth factor (VEGF). Also, using anti-VEGF antibody to block VEGF function significantly inhibited IL-6-mediated angiogenesis and tumor growth in nude mice, strongly supporting the critical role of VEGF in the IL-6-mediated cervical tumorigenesis. Accordingly, the signaling pathway downstream of IL-6/IL-6R responsible for the regulation of VEGF was investigated. Notably, pharmacological inhibition of PI3-K or MAPK failed to inhibit IL-6-mediated transcriptional upregulation of VEGF. Meanwhile, blocking STAT3 pathway with dominant-negative mutant STAT3D effectively abolished IL-6-induced VEGF mRNA. In transient transfections, a luciferase reporter construct containing the full-length 1.5-kb VEGF promoter or a 1.2-kb fragment lacking the known hypoxic-response element also exhibited the same degree of response to IL-6. Additionally, transient transfection of STAT3D downregulated the 1.2-kb VEGF promoter luciferase reporter stimulated by IL-6. Based on the above phenomenon combined with the concomitant increased tumor expression of IL-6 and VEGF in cervical cancer tissues, we conclude that IL-6 may promote cervical tumorigenesis by activating VEGF-mediated angiogenesis via a STAT3 pathway.

A series of aromatic poly(ether imide)s containing 9,9′-spirobifluorene moieties in the main chain have been synthesized via the polycondensation of 2,2′-bis(4-aminophenoxy)-9,9′-spirobifluorene with a variety of aromatic dianhydrides. In the diamine monomer, the two aminophenoxyfluorene entities are orthogonally arranged and are connected through an sp3 carbon atom (the spiro center). The resulting poly(ether imide)s have a polymer backbone which is periodically twisted with an angle of 90° at each spiro center. This structural feature, which restricts the close packing of the polymer chains and reduces inter-chain interactions, leads to amorphous poly(ether imide)s with good solubility in common organic solvents. In addition, the rigidity of the main chain of these polymers appears to be preserved due to the spiro-structure. As a result, these poly(ether imide)s exhibit a high Tg and excellent thermal stability.

A series of polyfluorenes containing pendant poly(benzyl ether) dendritic wedges of different generations was synthesized via the macromonomer approach, and then they were characterized by their st...

The synthesis and properties of organosoluble aromatic polyimides, containing spiro-skeletal units in the polymer backbone on the basis of the spiro-diamine monomer, 2,2'-diamino-9,9'-spirobifluorene, are described. In the case of the spiro segment, the two fluorene rings are orthogonally arranged and connected through a tetrahedral bonding carbon atom, the spiro center. As a consequence, the polymer chain is periodically zigzagged with a 90° angle at each spiro center. This structural feature minimizes interchain interactions and restricts the close packing of the polymer chains, resulting in amorphous polyimides that have good solubility in organic solvents. Compared with their fluorene-based cardo analogues, the spirobifluorene-based polyimides have an improved solubility. Furthermore, the main-chain rigidity of the polyimide appears to be preserved because of the presence of the spiro structure, which restricts the free segmental mobility. As a result, these polyimides exhibit a high glass-transition temperature (T g 's) and good thermal stability. The T g 's of these polyimides were in the range of 287-374 °C, and the decomposition temperatures in nitrogen for a 10% weight loss occurred at temperatures above 570 °C.

Childhood nephrotic syndrome is mainly caused by minimal change disease which is named because only subtle ultrastructural alteration could be observed at electron microscopic level in the pathological kidney. Glomerular podocytes are presumed to be the target cells whose protein sieving capability is compromised by a yet unidentified permeability perturbing factor. In a cohort of children with non-hereditary idiopathic nephrotic syndrome, we found the complement fragment C5a was elevated in their sera during active disease. Administration of recombinant C5a induced profound proteinuria and minimal change nephrotic syndrome in mice. Purified glomerular endothelial cells, instead of podocytes, were demonstrated to be responsible for the proteinuric effect elicited by C5a. Further studies depicted a signaling pathway involving Rho/Rho-associated kinase/myosin activation leading to endothelial cell contraction and cell adhesion complex breakdown. Significantly, application of Rho-associated kinase inhibitor, Y27632, prevented the protein leaking effects observed in both C5a-treated purified endothelial cells and mice. Taken together, our study identifies a previously unknown mechanism underlying nephrotic syndrome and provides a new insight toward identifying Rho-associated kinase inhibition as an alternative therapeutic option for nephrotic syndrome.

High serum estradiol (E2) concentrations result in adverse reproductive outcome in in vitro fertilization cycles, and the detrimental effects are probably due to impaired endometrial receptivity.Endometrial glandular cells (EGCs) are the cells that embryos first interact with during implantation. Our objective is to examine the in vitro EGC alterations after high E2 treatment.This was a prospective study.The study was conducted at a tertiary university hospital.Six women in the follicular phase participated in the study.EGCs were purified from human endometrium and cultured with different concentrations (0, 10(-9), 10(-8), 10(-7), 10(-5), 10(-4) M) of E2.EGC apoptosis and its underlying mechanism were measured.In vitro BeWo spheroid-EGC implantation assay demonstrated that the stimulation with 10(-5) and 10(-4) M E2 for 2 days decreased embryo implantation potentials. Presence of apoptotic bodies and DNA fragmentation and an increased percentage of sub-G1 phase were found in EGCs treated with high E2 concentrations. The high E2-treated EGCs could be rescued from apoptosis after the addition of estrogen receptor antagonist ICI 182 780. Western blot revealed increased inhibitory-κB (IκB)-α expression and decreased nuclear factor-κB (NF-κB) expression in high E2-treated EGCs, and NF-κB binding site-driven luciferase activity was decreased as well. When EGCs were pretreated with IκB-α small interfering RNA, high E2-induced B cell lymphoma 2 (Bcl-2) down-regulation did not occur and EGCs apoptosis was reduced. Bcl-2 overexpression also rescued high E2-induced EGCs from apoptosis.High E2 concentrations induced EGCs apoptosis through enhancing IκB-α expression, which in turn suppressed NF-κB expression. The decreased nuclear NF-κB subsequently inhibited Bcl-2 expression and accordingly enhanced EGC apoptosis.

BackgroundAngiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiotensinogen during liver regeneration is still unclear.AimsTo investigate the regulation of angiotensinogen during liver regeneration for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.MethodsA mouse in vitro partial hepatectomy animal model was used to evaluate the expression of interleukin-6 (IL-6) and angiotensinogen during liver regeneration. Serum IL-6 and angiotensinogen were detected by enzyme immunoassay (EIA). Angiotensinogen mRNA was detected by RT-PCR. Tissue levels of angiotensinogen protein were detected by Western blot analysis. Primary cultures of mouse hepatocytes were used to investigate IL-6-induced angiotensinogen. Chemical inhibitors were used to perturb signal transduction pathways. Synthetic double-stranded oligodeoxynucleotides (ODNs) were used as 'decoy' cis-elements to investigate transcription. Ki 67 staining and quantification were used to verify liver regeneration.ResultsIn the in vivo model, the levels of serum IL-6 and angiotensinogen correlated. In the in vitro model, IL-6 transcriptionally regulated angiotensinogen expression. Additionally, IL-6 mediated angiotensinogen expression through the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and JAK/p38 signaling. Decoy ODN analyses revealed that STAT3 and nuclear factor-kB (NF-kB) also played critical roles in the transcriptional regulation of angiotensinogen by IL-6. IL-6-mediated signaling, JAK2, STAT3 and p38 inhibitors reduced angiotensinogen expression in the partially hepatectomized mice.ConclusionDuring liver regeneration, IL-6-enhanced angiotensinogen expression is dependent on the JAK/STAT3 and JAK/p38/NF-kB signaling pathways. Interruption of the molecular mechanisms of angiotensinogen regulation may be applied as the basis of therapeutic strategies for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.

The high serum estradiol (E2) concentrations induced during in vitro fertilization are detrimental to endometrial receptivity and may result in lower embryo implantation rates. We have previously found that high E2 concentrations inhibit the activation of nuclear factor kappa B (NF-κB), leading to endometrial epithelial cell (EEC) apoptosis. The objective of this study is to investigate the signaling pathways through which high E2 results in NF-κB downregulation in EECs. Isolated human EECs were cultured in different concentrations of E2 (10−10, 10−9, 10−8, 10−7 M). The expression of heat shock protein 70 (Hsp70) and heat shock factor 1 (HSF-1) were upregulated under supraphysiological E2 (10−7 M) concentration, whereas phosphorylated inhibitory kappa B-alpha (pI κB-α) and NF-κB p65 subunits were downregulated. Immunohistochemistry of C57BL/6 mouse EECs that were exposed in vivo to high serum E2 from the administration of 20 IU of equine chorionic gonadotropin also demonstrated the same increase ...

Recently, there are many researches on the design of RF probes. Usually the materials of RF probe are tungsten and copper beryllium. They employed fabrication process of soldering and drawing of metal wire, which are not compatible with MEMS or IC fabrication process. Precise and high skill assembly is needed to finish the final probe module therefore results in high cost. This paper presents a novel RF probe module design which can be fabricated by Micro Electro Mechanical (MEM) fabrication process to reduce the cost. We use microwave simulation software, such as IE3D, Microwave Office, and Fidelity for design and analysis, and to know what kind of probe can reach the optimal impedance match and S-parameter. The design flow chart is coaxial cable to transform square coaxial cable, finally, in order to match up CPW standard pitches, therefore, design rectangular coaxial transition and success suitable ratio. Probe can match 50?.

The aim of this study was to describe the characteristics of electronic medication-related information (e-MRI) via Internet offered by the hospital settings in Taiwan.The structured Internet search and comprehensive review were performed on the most commonly used search engines in Taiwan. The assessment checklists were developed to describe the characteristics of general, e-MRI in the years 2008 and 2010, and specific digoxin information in 2011 based on the operational definitions derived from other studies. The descriptive analyses and chi-square tests for the retrieved data were performed.With approximately 15% of hospital settings providing general, e-MRI on their websites, their content varied but was not statistically significant, and different among the providers from different levels of hospitals and in different years. More medical centres provided the information with the updated dates and contact approaches than the smaller scale hospitals. Little was found about reference citation and authorships for those general, e-MRI websites. More medical centres created the accesses to search for the individual prescription in the corresponding settings and the specific information about digoxin storage. However, more district hospitals provided the precaution and dosage form information about digoxin.The providers to offer the e-MRI via hospital websites in Taiwan could be more responsible for its update, authorship and evidence. Further, the provision of electronic medication-related information via the Internet should be regularly examined or audited by the neutral personnel or organizations to ensure its quality.

Objective We recently characterized the molecular linkage that directs both BCL10 overexpression and nuclear translocation in response to inflammation-related NF-κB signaling pathway. Since NF-κB activation has been shown to occur in the pathogenesis of cervical cancer, we sought to investigate whether BCL10 possesses clinical significance in relation to cervical cancer. Methods Four cervical cancer cell lines (C33A, SiHa, HeLa, and CaSki) were used in this study. The DNA-binding activity of NF-κB was determined by the luciferase assay. The expression of BCL10, NF-κB, and cyclin D1 in tumor cells from an array of 182 tissue samples was examined using immunohistochemical staining. Results We transfected four cervical cancer cell lines with BCL10 small interfering RNA (siRNA), and discovered that the down-regulation of BCL10 inhibited the viability of these cervical cancer cells through G1 arrest. BCL10 siRNA treatment inhibited the expression of p-IKKβ and p-IκB, and also down-regulated both NF-κB activation cyclin D1, its downstream cell cycle protein. Our results reveal that cervical cancer had a higher rate of positive cytoplasmic staining (74.1%, 123/166) than either carcinoma in situ (50.0%, 3/6) or normal cervix (0.0%, 0/10); and that poorly differentiated cancer had a higher rate of cytoplasm staining (80.7%, 71/88) than moderately differentiated (75.4%, 43/57) and well differentiated (40%, 4/10) carcinoma. Furthermore, nuclear expression of BCL10 was closely associated with NF-κB activation (p Conclusions Our findings indicate that BCL10 plays an important role in controlling the growth of cervical cancer cells through NF-κB dependent cyclin D1 regulation.

Matrix metalloproteinases (MMPs) associate with tumor progression and metastasis. We sought to investigate the role of MMP-9 from sublethally irradiated tumor in accelerated pulmonary metastasis of Lewis lung carcinoma (LLC-LM) and the corresponding anti-metastasis strategies in C57BL/6 mice. We used Matrigel-coated Boyden chamber assays and chicken chorioallantoic membrane assays to evaluate the invasion capability of irradiated LLC-LM cells (7.5 Gy), reverse transcription–polymerase chain reaction and the western blot assay to investigate the expression of MMPs by irradiated cells, and small interfering RNA duplexes to inhibit MMP-9 expression. LLC-LM cells differing in MMP-2 or -9 expression were subcutaneously injected into right thighs and the resulting tumors were irradiated (10 Gy × 5) to induce pulmonary metastasis. Radiation significantly enhanced MMP-9 at both the transcriptional and translational levels. MMP-9 siRNA significantly inhibited in vitro radiation-enhanced invasiveness. The number of radiation-accelerated pulmonary metastases was significantly reduced by MMP-9 knockdown and MMP-2/9 knockdown. Reverse transcription–polymerase chain reaction of LLC-LM cells in the blood and lung tissue revealed MMP-9 involvement in radiation-enhanced intravasation. Either higher-dose irradiation (30 Gy × 2) or pretreatment with prototypical MMP-9 inhibitor, zoledronic acid, significantly reduced the number of pulmonary metastases. The viability of irradiated tumor was seen on both positron emission tomography and magnetic resonance imaging, and tumor/serum MMP-9 levels suggested the association of local control of primary tumor and inhibition of time-dependent MMP-9 activities. Our results demonstrate that MMP-9 is crucially involved in radiation-enhanced LLC-LM cell invasiveness in vitro and in pulmonary metastasis from inadequately irradiated primary tumor in vivo.

Purpose Radiotherapy is integrated into the multimodal treatment of localized hepatocellular carcinoma (HCC) refractory to conventional treatment. Tumor control remains unsatisfactory and the sublethal effect associates with secondary spread. The use of an effective molecularly targeted agent in combination with radiotherapy is a potential therapeutic approach. Our aim was to assess the effect of combining a phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, AR-42, with radiotherapy in in vitro and in vivo models of human HCC. Methods and Materials Human HCC cell lines (Huh-7 and PLC-5) were used to evaluate the in vitro synergism of combining AR-42 with irradiation. Flow cytometry analyzed the cell cycle changes, whereas Western blot investigated the protein expressions after the combined treatment. Severe combined immunodeficient (SCID) mice bearing ectopic and orthotopic HCC xenografts were treated with AR-42 and/or radiotherapy for the in vivo response. Results AR-42 significantly enhanced radiation-induced cell death by the inhibition of the DNA end-binding activity of Ku70, a highly versatile regulatory protein for DNA repair, telomere maintenance, and apoptosis. In ectopic xenografts of Huh-7 and PLC-5, pretreatment with AR-42 significantly enhanced the tumor-suppressive effect of radiotherapy by 48% and 66%, respectively. A similar combinatorial effect of AR-42 (10 and 25 mg/kg) and radiotherapy was observed in Huh-7 orthotopic model of tumor growth by 52% and 82%, respectively. This tumor suppression was associated with inhibition of intratumoral Ku70 activity as well as reductions in markers of HDAC activity and proliferation, and increased apoptosis. Conclusion AR-42 is a potent, orally bioavailable inhibitor of HDAC with therapeutic value as a radiosensitizer of HCC.

The corpus luteum is a dynamic endocrine structure with periodic development and regression during menstrual cycles. Its lifespan can be prolonged by human chorionic gonadotropin (hCG). However, the signal mechanisms of this phenomenon remain unclear.Our objective was to investigate the molecular mechanisms of hCG in the maintenance of the viability of granulosa-lutein cells.Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the effects of hCG on the survival of cultured granulosa-lutein cells. The signal pathway inducing antiapoptotic protein was investigated.hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased. Myeloid cell leukemia-1 (Mcl-1) protein, but not B-cell lymphoma protein-2 or B-cell lymphoma protein-xL, was significantly induced by hCG and LH. The granulosa-lutein cells secreted vascular endothelial growth factor that induced endothelial permeability. Mcl-1 small interfering RNA increased DNA fragmentation and diminished the antiapoptotic effect of hCG. hCG induced Mcl-1 expression through the LH/hCG receptor, adenylate cyclase, protein kinase A, and cAMP response element-binding protein signal pathway. Flavopiridol inhibited Mcl-1 production, released cytochrome c, and induced apoptosis of granulosa-lutein cells.We first demonstrate that hCG prevents apoptosis of granulosa-lutein cells through the induction of Mcl-1 protein via the LH/hCG receptor and a cAMP response element-binding protein-dependent pathway. We may have found the molecular mechanism for luteal rescue during early pregnancy. Mcl-1 prevents apoptosis and increases cell viability but not proliferation as mechanisms for luteal rescue. Mcl-1 is a key molecule of hCG signaling.

In this study, we evaluated the effectiveness of using swept-source optical coherence tomography (SS-OCT) to monitor the enhancement of hepatocellular carcinoma (HCC) cell invasiveness by radiation. SS-OCT images were acquired and recorded to obtain three-dimensional datasets at discrete time points of 12, 24 and 48 h after irradiating HepG2 cells with 7.5 Gy. The cell migration distance in three-dimensional tissue models was quantified from images of radiation-induced and sham-irradiated cells, and this method was compared with the conventional Boyden chamber assay conducted at the same time points. SS-OCT measurements show that most cells were found near the gel surface, but a few were much deeper. Among those HCC cells with a high degree of migration capability, the mean migration distances at 24 h and 48 h were significantly greater for irradiated cells than for sham-irradiated cells (0.7 +/- 0.23 mm versus 0.65 +/- 0.26 mm at 24 h, P = 0.019 and 0.84 +/- 0.30 mm versus 0.65 +/- 0.524 mm at 48 h, P = 0.009). The results of radiation-enhanced invasion in HCC cells obtained by the non-invasive, quantitative SS-OCT method were consistent with those obtained using the traditional assay for measuring biological invasion.

It has been previously reported that the pollutant sodium sulfite (Na2SO3) can activate airway epithelial cells; however, there is as yet no evidence of any direct relationship between house dust mite allergen exposure and Na2SO3 with regards to the pathogenesis of airway allergy. This study investigated the effect of sulfite on mite-stimulated human airway epithelial cells.The A549 human lung epithelial cell line was used as an in vitro model. Cells were treated with 10 microg/mL mite crude extract for 8 h and/or Na2SO3 (0, 10, 100, 500, 1000 and 5000 microM) for 16 h, and cell adhesion and dissociation on a cell culture plastic surface were quantitated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Changes in cell adhesion were also analyzed by monitoring the expression of the cell surface of adhesion molecules integrin alpha2 (CD49b) and integrin alpha6 (CD49f) using flow cytometry.A549 cells treated with either mite crude extract only or Na2SO3 only did not show a significant increase in dissociation from the cell culture plastic surface. However, when cells were pretreated with mite extract for 8 h, followed by 16-h incubation with various concentrations of Na2SO3, cell dissociation was enhanced in a dose-dependent manner. A dose-dependent decrease of CD49b and CD49f expression was also seen in cells treated with Na2SO3 only and in mite-pretreated cells. Mite treatment decreased CD49b expression, and a cumulative effect was seen in cells further treated with Na2SO3.Significant dissociation of airway epithelial cells with Na2SO3 stimulation only occurred in cells pretreated with mite extract. Mite pretreatment enhanced Na2SO3-induced CD49f down-regulation; Na2SO3 and/or mite extract down-regulated CD49b expression of A549 cells. These findings indicate that a synergistic effect of mite extract and sulfite can severely disrupt the airway bronchial epithelial barrier.

Context: Lysophosphatidic acid (LPA) was found at significant amounts in follicular fluid of preovulatory follicle. The lysophospholipase D activity of serum from women receiving ovarian stimulation was higher than women with natural cycles. Angiogenic cytokines, including IL-6, IL-8, and vascular endothelial growth factor, increased in plasma and ascites of patients with ovarian hyperstimulation syndrome. The role of LPA in ovarian follicles is unclear. Objective: Our objective was to investigate the expression of LPA receptors and function of LPA in granulosa-lutein cells. Design: Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the expression of LPA receptors using RT-PCR. The effects of LPA on the expression of IL-6, IL-8, and vascular endothelial growth factor were examined. Signal pathways of LPA were delineated. The functions of secretory angiogenic factors were tested using human umbilical vein endothelial cells. Results: The LPA1, LPA2, and LPA3 receptors’ mRNA was identified in granulosa-lutein cells. LPA enhanced IL-8 and IL-6 expressions in a dose- and time-dependent manner. LPA functioned via LPA receptors, Gi protein, MAPK/ERK, p38, phosphatidylinositol 3-kinase/Akt, and nuclear factor-κB, and transactivation of epidermal growth factor receptor. LPA induced IL-8 and IL-6 through different pathways. LPA-induced IL-8 and IL-6 increased permeability of human umbilical vein endothelial cell monolayer. Conclusions: LPA induces IL-8 and IL-6 expressions through LPA receptors and nuclear factor-κB dependent pathways in granulosa-lutein cells. The LPA in preovulatory follicles may play a role in the angiogenesis of corpus luteum. Large amounts of LPA-induced IL-8 and IL-6 from multiple corpora luteae of stimulated ovaries may be one of the pathophysiological causes of ovarian hyperstimulation syndrome.

Printed electronics have attracted increasing attention in recent years due to its flexible format, easy process and potentially low cost features. Achieving good performance organic Schottky diode as the key component of a rectifier for printed RFID applications became a critical task. The electrical performances of an organic Schottky diode can be improved by inserting an intermediate layer between the semiconductor and electrode surfaces. This interface plays an important role in improving rectification ratio and lifetime of a polymer diode. In this work, a 13.56 MHz rectifier based on a polymer Schottky diode will be demonstrated and a wireless energy transmission built on flexible substrates will be proposed.