bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of interferon-α signaling by hepatitis E virus
Authors: Dong Chen , Zafrullah Mohammad , Mixson-Hayden Tonya , Dai Xing , Liang Jiuhong , Meng Jihong , Kamili Saleem 
Published: December 2011

Abstract

The interferon (IFN) system is integral to the host response against viruses, and many viruses have developed strategies to overcome its antiviral effects. The effects of hepatitis E virus (HEV), the causative agent of hepatitis E, on IFN signaling have not been investigated primarily because of the nonavailability of an efficient

in vitro

culture system or small animal models of infection. We report here the generation of A549 cell lines persistently infected with genotype 3 HEV, designated as HEV-A549 cells and the effects HEV has on IFN-α–mediated Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling. Treatment of HEV-A549 cells with 250, 500, and 1000 U/mL of IFN-α for 72 hours showed a dose-dependent reduction in HEV RNA levels by 10%, 20%, and 50%, respectively. IFN-α–stimulated genes coding for the antiviral proteins dsRNA-activated protein kinase (PKR) and 2′,5′-oligoadenylate synthetase (2′,5′-OAS) were down-regulated in IFN-α–treated HEV-A549 cells. HEV infection also prevented IFN-α–induced phosphorylation of STAT1. Regulation of STAT1 by HEV was specific, as phosphorylation of STAT2, tyrosine kinase (Tyk) 2, and Jak1 by IFN-α was unaltered. Additionally, STAT1 levels were markedly increased in HEV-A549 cells compared with naive A549 cells. Furthermore, binding of HEV open reading frame (ORF)3 protein to STAT1 in HEV-A549 cells was observed. HEV ORF3 protein alone inhibited IFN-α–induced phosphorylation of STAT1 and down-regulated the IFN-α–stimulated genes encoding PKR, 2′,5′-OAS, and myxovirus resistance A.

Conclusion:

HEV inhibits IFN-α signaling through the regulation of STAT1 phosphorylation in A549 cells. These findings have implications for the development of new strategies against hepatitis E. (Hepatology 2012 )
Ursodeoxycholyl lysophosphatidylethanolamide improves steatosis and inflammation in murine models of nonalcoholic fatty liver disease
Authors: Pathil Anita , Mueller Jan , Warth Arne , Chamulitrat Walee , Stremmel Wolfgang 
Published: December 2011

Abstract

Hepatic fat accumulation and changes in lipid composition are hallmarks of nonalcoholic fatty liver disease (NAFLD). As an experimental approach for treatment of NAFLD, we synthesized the bile acid–phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). Previous work demonstrated profound hepatoprotective properties of the conjugate

in vitro

and

in vivo

. Here we investigated the effects of UDCA-LPE in two nutritional mouse models of NAFLD. C57BL/6 mice were fed a high-fat diet (HFD) for 28 weeks, resulting in steatosis with hyperlipidemia. In a second model, mice received a methionin–choline-deficient (MCD) diet for up to 11 weeks, which induced advanced nonalcoholic steatohepatitis (NASH). Establishment of liver injury was followed by intraperitoneal injections of 30 mg/kg UDCA-LPE three times a week for different time periods. UDCA-LPE ameliorated both HFD- and MCD-induced increases in alanine aminotransferase (ALT) values near to normalization. As for metabolic parameters, UDCA-LPE reduced elevated serum triglyceride and cholesterol values in HFD mice. Liver histology showed improvement of steatosis in HFD and MCD mice concomitant with reductions in hepatic triglyceride and cholesterol levels. Additionally, the conjugate lowered serum caspase-8 activity in both models and decreased lipid hydroperoxides in MCD mice. Abundance of proinflammatory lysophosphatidylcholine (LPC), which was detectable in both HFD and MCD mice, was reduced by UDCA-LPE. Quantitative reverse transcriptase-polymerase chain reaction qRT-PCR of liver specimens revealed that UDCA-LPE strongly down-regulated inflammatory genes and modified the expression of genes involved in lipid metabolism.

Conclusion:

The current study demonstrates that UDCA-LPE improves hepatic injury at different stages of NAFLD. By concurrently lowering hepatic lipid overloading as well as susceptibility of hepatocytes toward inflammatory stimuli, the conjugate may be able to ameliorate disease progression. Thus, UDCA-LPE represents a promising compound suitable for the treatment of NAFLD. (Hepatology 2012 )
Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease
Authors: Lomonaco Romina , Ortiz-Lopez Carolina , Orsak Beverly , Webb Amy , Hardies Jean , Darland Celia , Finch Joan , Gastaldelli Amalia , Harrison Stephen , Tio Fermin , Cusi Kenneth 
Published: December 2011

Abstract

The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 ± 1, body mass index = 34.1 ± 0.3 kg/m2) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IRi = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IRi quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[3H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all

P

< 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all

P

< 0.01).

Conclusion :

Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. (Hepatology 2012)
Patient safety and reprocessing: A usability test of the endoscope reprocessing procedure
Authors: Jolly Jonathan D. , Hildebrand Emily A. , Branaghan Russell J. , Garland T. B. , Epstein Dana , Babcock‐Parziale Judith , Brown Victoria 
Published: December 2011

AbstractWhen endoscopes are reprocessed correctly, endoscopy is a safe procedure. Recent incidents of insufficient reprocessing, however, have resulted in public concern. Results of a usability test of the reprocessing procedure identified that none of 24 users, naïve to the procedure, could reprocess endoscopes correctly, nor could they correctly complete any of the component tasks in the procedure. Five of the 76 subtasks were identified as particularly critical. These were 1) brushing the instrument channel, 2) attaching the channel plug and injection tube, 3) identifying leaks, 4) blowing water out of the endoscope's internal channels during high‐level disinfection, and 5) aspirating solution through the endoscope to remove debris loosened by brushing. Additionally, three themes were identified as causes of the majority of problems: 1) lack of visibility, 2) high memory demands, and 3) insufficient user feedback. Design recommendations for these problems are discussed. © 2011 Wiley Periodicals, Inc.
Assessment of future stream flow over the Sesan catchment of the Lower Mekong Basin in Vietnam
Authors: Raghavan Srivatsan V. , Vu Minh Tue , Liong Shie‐Yui 
Published: December 2011

AbstractThis study used a regional climate model, driven at a resolution of 30 km, to derive climate estimates that were used as input to a hydrological model to determine stream flow in a changing climate. This regional climate model output was derived using the Weather Research and Forecasting model, which was used to downscale the general circulation model ECHAM5 T63 under the A2 greenhouse gas emission scenario for the future. Two river basins, Dakbla and Poko, over the Sesan catchment of the Lower Mekong region were considered for runoff modeling. A 10‐year climatology of the recent past, 1991–2000, was used as the baseline for the present‐day climate, and another 10‐year climate over the period 2091–2100 was chosen for the future time slice. The results from the simulation of future stream flow indicate that, over both Dakbla and Poko river basins, the stream flow is likely to increase, especially during the peak rainfall season. The Dakbla River Basin shows a substantial increase in stream flow when compared with the Poko River Basin. Copyright © 2011 John Wiley & Sons, Ltd.
A synthetic compound, 1,5‐bis(2‐methoxyphenyl)penta‐ 1,4‐dien‐3‐one (B63), induces apoptosis and activates endoplasmic reticulum stress in non‐small cell lung cancer cells
Authors: Xiao Jian , Wang Yi , Peng Jing , Guo Lu , Hu Jie , Cao Menghua , Zhang Xie , Zhang Hanqing , Wang Zhouguang , Li Xiaokun , Yang Shulin , Yang Huiling , Liang Guang 
Published: December 2011

AbstractEndoplasmic reticulum (ER) stress‐induced cancer cell apoptosis has become a novel signaling target for the development of therapeutic drugs for cancer treatment. Curcumin, a dietary phytochemical, exhibits growth‐suppressive activity against cancer cells via multitarget mechanisms. However, the low stability and poor pharmacokinetics significantly limit its clinical applications. Thus, we designed and synthesized a novel monocarbonyl analog of curcumin, 1,5‐bis(2‐methoxyphenyl) penta‐1,4‐dien‐3‐one (B63). This compound exhibited a higher chemical stability in cultural medium and a better intracellular profile than curcumin. Treatment with B63 potently induced apoptosis of human non‐small cell lung cancer (NSCLC) cells in a dose‐responsive manner, while exhibiting no cytotoxicity in normal lung fibroblast cells. Its antitumor effect was associated with the ER stress‐mediated apoptotic pathway and, ultimately, the activation of the caspase cascades. However, curcumin at the same concentrations did not cause ER stress in H460 cells. Further, C/EBP homologous protein knockdown by siRNA attenuated B63‐induced cell apoptosis, indicating that the apoptotic pathway is ER stress‐dependent. In vivo, the volume and weight of the tumor were reduced significantly by pretreating the H460 tumor cells with B63 before implantation. Taken together, these insights on the novel compound B63, from both chemical and biological perspectives, may provide a novel anticancer candidate for the treatment of NSCLC.
Coffee consumption and risk of endometrial cancer: Findings from a large up‐to‐date meta‐analysis
Authors: Je Youjin , Giovannucci Edward 
Published: December 2011

AbstractSeveral epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta‐analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model, and generalized least square trend estimation was used to assess dose–response relationships. A total of 16 studies (10 case–control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta‐analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62–0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55–0.87) for case–control studies and 0.70 (95% CI: 0.61–0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25–0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60–0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63–0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90–0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case–control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk.
Epicatechin‐rich cocoa polyphenol inhibits Kras‐activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model
Authors: Siddique Hifzur Rahman , Liao D. Joshua , Mishra Shrawan Kumar , Schuster Todd , Wang Lei , Matter Brock , Campbell Paul M. , Villalta Peter , Nanda Sanjeev , Deng Yibin , Saleem Mohammad 
Published: December 2011

AbstractActivated Kras gene coupled with activation of Akt and nuclear factor‐kappa B (NF‐κB) triggers the development of pancreatic intraepithelial neoplasia, the precursor lesion for pancreatic ductal adenocarcinoma (PDAC) in humans. Therefore, intervention at premalignant stage of disease is considered as an ideal strategy to delay the tumor development. Pancreatic malignant tumor cell lines are widely used; however, there are not relevant cell‐based models representing premalignant stages of PDAC to test intervention agents. By employing a novel Kras‐driven cell‐based model representing premalignant and malignant stages of PDAC, we investigated the efficacy of ACTICOA‐grade cocoa polyphenol (CP) as a potent chemopreventive agent under in vitro and in vivo conditions. It is noteworthy that several human intervention/clinical trials have successfully established the pharmacological benefits of cocoa‐based foods. The liquid chromatography (LC)–mass spectrometry (MS)/MS data confirmed epicatechin as the major polyphenol of CP. Normal, nontumorigenic and tumorigenic pancreatic ductal epithelial (PDE) cells (exhibiting varying Kras activity) were treated with CP and epicatechin. CP and epicatechin treatments induced no effect on normal PDE cells, however, caused a decrease in the (i) proliferation, (ii) guanosine triphosphate (GTP)‐bound Ras protein, (iii) Akt phosphorylation and (iv) NF‐κB transcriptional activity of premalignant and malignant Kras‐activated PDE cells. Further, oral administration of CP (25 mg/kg) inhibited the growth of Kras‐PDE cell‐originated tumors in a xenograft mouse model. LC–MS/MS analysis of the blood showed epicatechin to be bioavailable to mice after CP consumption. We suggest that (i) Kras‐driven cell‐based model is an excellent model for testing intervention agents and (ii) CP is a promising chemopreventive agent for inhibiting PDAC development.
Tumor‐induced changes in the phenotype of blood‐derived and tumor‐associated T cells of early stage breast cancer patients
Authors: Poschke I. , De Boniface J. , Mao Y. , Kiessling R. 
Published: December 2011

AbstractTumor‐induced immune suppression has mainly been studied in patients with advanced cancer. Despite the fact that they are most likely to benefit from immunotherapy, patients with early stage cancers were under‐represented in these studies. We analyzed blood and tumor‐derived T cells from patients with stage 1 (n = 20), stage 2 (n = 23) or stage 3 (n = 1) breast cancer and found that, even early stage tumors induced T cell differentiation. Breast cancer patients had significantly more circulating CD8+ memory and fewer CD8+ naïve T cells than healthy controls (n = 10). Up‐regulation of CD69 and PD1 on cancer patient T cells suggests previous activation, and increased expression of the chemokine receptors CCR5 and CXCR3 on CD8+ T cells indicates that their homing capacity differs from that of healthy individuals. Comparison of blood‐derived and tumor‐associated T cells from patients with different metastatic status and tumor grades revealed that tumor progression and aggressiveness seem to favor the expansion of memory T cells over naive T cells. We have previously shown that immunosuppression in this patient population is stronger in the tumor than in the blood. Here, we report signs of exhaustion, such as loss of CD28, on tumor‐associated as compared to blood‐derived CD8+ T cells, despite the fact that tumor‐associated T cells are predominantly effector memory cells and express high levels of CD69. The finding that the presence of a tumor potentially induces immunosenescence early during tumorigenesis indicates that efficient immunotherapy might be difficult even in patients with early stage cancer due to T cell exhaustion and tolerance.
Quasicrystal as a Reinforcement Material in Magnesium Alloys
Authors: Chang Hye Jung , Kim Won Tae , Kim Do Hyang 
Published: December 2011

AbstractThe existence of the two‐phase region (icosahedral phase (I‐phase) + α‐Mg) in the Mg‐rich corner of the Mg‐Zn‐Y system indicates that composites consisting of I‐phase and ductile α‐Mg can be fabricated by a simple solidification process. Alloys with a range of combined strength and ductility can be designed by changing the fraction of the I‐phase. Strengthening in proportion with increasing the volume fraction of I‐phase can be explained by the effect of dispersion hardening due to the presence of finely dispersed I‐phase particles. When quasicrystals exist in the α‐Mg matrix as a second phase in Mg‐Zn‐Y alloys, the quasicrystals are stable against coarsening during thermomechanical processes such as hot rolling and high‐temperature forming, due to the low interfacial energy of the quasicrystals with the α‐Mg crystalline matrix, which provides strong bonding properties at the I‐phase/matrix interface. Therefore, quasicrystal‐reinforced Mg‐Zn‐Y alloys exhibit a much better combination of mechanical properties and formability than commercially used alloys such as AZ31 and AZ 61.
OBSERVATIONS OF SALINITY PATTERNS IN SHALLOW GROUNDWATER AND DRAINAGE WATER FROM AGRICULTURAL LAND IN THE NORTHERN PART OF THE NETHERLANDS
Authors: Velstra J. , Groen J. , De Jong K. 
Published: December 2011

ABSTRACTIn studies concerning rainwater lenses on a parcel scale in brackish polder areas it is assumed that infiltrated rainwater flows through the rainwater lens and seeps to the watercourses. This freshwater system is supposed to be superimposed on the brackish diffuse upward seepage system. This study investigates the influence of field drainage on the dynamic behaviour of fresh rainwater lenses and the risk of salinization of the root zone. Observations presented in this paper show that shallow water and salt movements in clayey polders are more complex and more dynamic than previously thought.On 18 parcels 2D geo‐electrical resistivity imaging profiles were measured, which give a good spatial and temporal representation of the salinity distribution of the groundwater. It appears that during wet periods upconing of brackish groundwater appears under pipe drains and ditches, which drain a mixture of fresh meteoric water and deep brackish groundwater. Between drainpipes small rainwater lenses develop. During the dry season, when the groundwater table drops below the drainage level, brackish soil moisture stays behind. Transpiration of the crops rooted in the clayey polder soils result in strong capillary rise of salts, which may even reach the root zone in some places. Copyright © 2011 John Wiley & Sons, Ltd.
Tyrosine phosphorylation and liver regeneration: A glance at intracellular transducers
Authors: Pagano Mario Angelo , Tibaldi Elena , Gringeri Enrico , Brunati Anna Maria 
Published: December 2011

AbstractLiver regeneration (LR) is a compensatory growth that occurs in response to resection or injury of the liver aimed at restoring the liver mass and maintaining body homeostasis. The activation of intracellular signaling pathways due to extracellular stimuli mainly reflects a highly coordinated spatial and temporal organization of phosphotyrosine‐based signals generated by the concerted action of three basic functional modules, namely protein tyrosine kinases, protein tyrosine phosphatases, and the Src homology 2 (SH2) domain. In this review, we have selected a set of signaling proteins downstream of activated cytokine and growth factor receptors that highlight the multifaceted aspects of tyrosine phosphorylation with their impact on the course of LR. Besides being a process of remarkable biological interest, LR has recently emerged as a model for dissecting molecular mechanisms underlying diverse pathophysiological states, offering new perspectives in primarily, but not only, managing life‐threatening liver diseases. © 2011 IUBMB IUBMB Life, 2011
Devastation of adult stem cell pools by irradiation precedes collapse of trabecular bone quality and quantity
Authors: Green Danielle E , Adler Benjamin J , Chan Meilin E , Rubin Clinton T 
Published: December 2011

Abstract
Stem cell depletion and compromised bone marrow resulting from radiation exposure fosters long-term deterioration of numerous physiologic systems, with the degradation of the skeletal system ultimately increasing the risk of fractures. To study the interrelationship of damaged bone marrow cell populations with trabecular microarchitecture, 8- and 16-week-old C57BL/6 male mice were sublethally irradiated with 5 Gy of 137Cs γ-rays, and adult stem cells residing in the bone marrow, as well as bone quantity and quality, were evaluated in the proximal tibia after 2 days, 10 days, and 8 weeks compared with age-matched controls. Total extracted bone marrow cells in the irradiated 8-week, young adult mice, including the hematopoietic cell niches, collapsed by 65% ± 11% after 2 days, remaining at those levels through 10 days, only recovering to age-matched control levels by 8 weeks. As early as 10 days, double-labeled surface was undetectable in the irradiated group, paralleled by a 41% ± 12% and 33% ± 4% decline in bone volume fraction (BV/TV) and trabecular number (Tb.N), respectively, and a 50% ± 10% increase in trabecular separation (Tb.Sp) compared with the age-matched controls, a compromised structure that persisted to 8 weeks postirradiation. Although the overall collapse of the bone marrow population and devastation of bone quality was similar between the “young adult” and “mature” mice, the impact of irradiation—and the speed of recovery—on specific hematopoietic subpopulations was dependent on age, with the older animals slower to restore key progenitor populations. These data indicate that, independent of animal age, complications arising from irradiation extend beyond the collapse of the stem cell population and extend toward damage to key organ systems. It is reasonable to presume that accelerating the recovery of these stem cell pools will enable the prompt repair of the skeletal system and ultimately reduce the susceptibility to fractures. © 2012 American Society for Bone and Mineral Research.