bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a water-immiscible ionic liquid to improve asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one catalyzed by immobilized Candida parapsilosis CCTCC M203011 cells
Authors: Lou Wen-Yong , Chen Lei , Zhang Bo-Bo , Smith Thomas J , Zong Min-Hua 
Published: October 2009

Abstract

Background
Whole cells are usually employed for biocatalytic reduction reactions to ensure efficient coenzyme regeneration and to avoid problems with enzyme purification and stability. The efficiency of whole cell-catalyzed bioreduction is frequently restricted by pronounced toxicity of substrate and/or product to the microbial cells and in many instances the use of two-phase reaction systems can solve such problems. Therefore, we developed new, biphasic reaction systems with biocompatible water-immiscible ionic liquids (ILs) as alternatives to conventional organic solvents, in order to improve the asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one (TMSB) to (S)-4-(trimethylsilyl)-3-butyn-2-ol {(S)-TMSBOL}, a key intermediate for synthesis of 5-lipoxygenase inhibitors, using immobilized Candida parapsilosis CCTCC M203011 cells as the biocatalyst.

Results
Various ILs exerted significant but different effects on the bioreduction. Of all the tested water-immiscible ILs, the best results were observed with 1-butyl-3-methylimidazolium hexafluorophosphate (C4MIM·PF6), which exhibited not only good biocompatibility with the cells but also excellent solvent properties for the toxic substrate and product, thus markedly improving the efficiency of the bioreduction and the operational stability of the cells as compared to the IL-free aqueous system. 2-Propanol was shown to be the most suitable co-substrate for coenzyme regeneration, and it was found that the optimum volume ratio of buffer to C4MIM·PF6, substrate concentration, buffer pH, 2-propanol concentration and reaction temperature were 4/1 (v/v), 24 mM, 5.5, 130 mM and 30°C, respectively. Under these optimized conditions, the maximum yield and the product e.e. wer 97.7% and >99%, respectively, which are much higher than the corresponding values previously reported. The efficient whole-cell biocatalytic process was shown to be feasible on a 250-mL scale.

Conclusion
The whole cell-catalyzed asymmetric reduction of TMSB to (S)-TMSBOL can be substantially improved by using a C4MIM·PF6/buffer biphasic system instead of a single-phase aqueous system and the resulting biocatalytic process appears to be effective and competitive on a preparative scale.
Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells
Authors: Yuzugullu Haluk , Benhaj Khemais , Ozturk Nuri , Senturk Serif , Celik Emine , Toylu Asli , Tasdemir Nilgun , Yilmaz Mustafa , Erdal Esra , Akcali Kamil Can , Atabey Nese , Ozturk Mehmet 
Published: October 2009

Abstract

Background
β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling.

Results
We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines.

Conclusion
Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.
Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system
Authors: Desai Nisarg R , Kesari Kavindra K , Agarwal Ashok 
Published: October 2009

Abstract
Hazardous health effects stemming from exposure to radiofrequency electromagnetic waves (RF-EMW) emitted from cell phones have been reported in the literature. However, the cellular target of RF-EMW is still controversial. This review identifies the plasma membrane as a target of RF-EMW. In addition, the effects of RF-EMW on plasma membrane structures (i.e. NADH oxidase, phosphatidylserine, ornithine decarboxylase) and voltage-gated calcium channels are discussed. We explore the disturbance in reactive oxygen species (ROS) metabolism caused by RF-EMW and delineate NADH oxidase mediated ROS formation as playing a central role in oxidative stress (OS) due to cell phone radiation (with a focus on the male reproductive system). This review also addresses: 1) the controversial effects of RF-EMW on mammalian cells and sperm DNA as well as its effect on apoptosis, 2) epidemiological, in vivo animal and in vitro studies on the effect of RF-EMW on male reproductive system, and 3) finally, exposure assessment and dosimetry by computational biomodeling.
Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP) signaling to inhibit steroidogenesis in human granulosa cells
Authors: Lin Qing , Poon Song Ling , Chen Junling , Cheng Linan , HoYuen Basil , Leung Peter CK 
Published: October 2009

Abstract

Background
Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells.

Methods
The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG) cells was examined by Enzyme linked immunosorbent assay (ELISA). The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD) in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner.

Results and Conclusion
In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR) protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059) and p38 (SB203580) inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone production, suggesting that the effect of leptin on steroidogenesis in granulosa cells is receptor dependent. In summary, leptin acts through the MAPK pathway to downregulate cAMP-induced StAR protein expression and progesterone production in immortalized human granulosa cells. These results suggest a possible mechanism by which gonadal steroidogenesis could be suppressed in obese women.
Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function
Authors: Kmieciak Maciej , Gowda Madhu , Graham Laura , Godder Kamar , Bear Harry D , Marincola Francesco M , Manjili Masoud H 
Published: October 2009

AbstractBackgroundFoxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation.MethodsT cell activation was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte reaction (MLR), and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells.ResultsBoth CD4+ and CD8+ T cells expressed Foxp3 upon activationin vitro. Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing their effector and memory phenotypes. Both FoxP3- responder T cells and CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation.ConclusionExpression of Foxp3 does not necessarily convey regulatory function in human CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T cells upon stimulation suggest the activation-induced regulation of FoxP3 expression.
Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immue systems towards a TH2-dominated response
Authors: Gilles Stefanie , Mariani Valentina , Bryce Martina , Mueller Martin J , Ring Johannes , Behrendt Heidrun , Jakob Thilo , Traidl-Hoffmann Claudia 
Published: October 2009

AbstractPollen allergy is characterized by a TH2-biased immune response to pollen-derived allergens. However, pollen-exposed epithelia do not encounter pure allergen but rather a plethora of protein and non-protein substances. We demonstrated that pollen liberate lipids with chemical and functional similarities to leukotriens and prostaglandins - the pollen associated lipid mediators (PALMs). To date, two main groups of PALMs have been characterized: The immunostimulatory PALMs activating innate immune cells such as neutrophils and eosinophils, and the immunomodulatory E1-phytoprostanes blocking IL-12 production of dendritic cells, resulting in the preferential induction of TH2 responses. This article reviews our work in the field of PALMs and their effects on cells of the innate and adoptive immune system. From recent results a general picture starts to emerge in which PALMs (and possibly other pollen-associated substances) may - independently from protein allergens - propagate an overall TH2 favoring micromilieu in pollen exposed tissue of predisposed individuals.
Ginseng leaf-stem: bioactive constituents and pharmacological functions
Authors: Wang Hongwei , Peng Dacheng , Xie Jingtian 
Published: October 2009

Abstract
Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.
RETRACTED ARTICLE: Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report
Authors: Tsalis Konstantinos , Blouhos Konstantinos , Kapetanos Dimitrios , Kontakiotis Theodore , Lazaridis Charalampos 
Published: October 2009

Abstract

Background
Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma.

Case report
A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax.

Conclusion
The patient was successfully treated using conservative measures.
Evidence that Corticotropin-Releasing Hormone Modulates Myometrial Contractility during Human Pregnancy
Authors: Tyson Elisa K. , Smith Roger , Read Mark 
Published: October 2009

AbstractAs human pregnancy advances, CRH increases exponentially and is hypothesized to trigger the transition from myometrial quiescence to active contractions at labor. Paradoxically, CRH stimulates cAMP production, suggesting it should cause relaxation. To evaluate CRH as a mediator of quiescence, the effect of CRH on contractions in preterm and term myometria with concurrent progesterone (P4) was determined. In late gestation, we hypothesized that high concentrations of CRH down-regulate agonist-activated-cAMP relaxatory pathways and that increased phosphodiesterase (PDE) activity induces heterologous down-regulation of agonist-activated-cAMP pathways. CRH caused dose-dependent relaxation of spontaneously contracting myometrial strips of 31 ± 8% (mean ± sem; n = 12) and 35 ± 20% (n = 3) in term and preterm samples, respectively. CRH with P4 pretreatment caused a 40 ± 13% (n = 4) reduction in contractility, whereas in matched samples, CRH alone exerted a 26 ± 6% (n = 4) reduction, with a shift of CRH dose-response curves (P &lt; 0.01, ANOVA). Pretreatment of strips with 10−7m CRH did not attenuate relaxation induced by subsequent CRH (n = 3) or salbutamol (β2-agonist) treatment (n = 9). PDE inhibition by rolipram showed a 2.2- and 1.5-fold increase in maximal relaxation induced by CRH and salbutamol, respectively, with a shift of both dose-response curves (P &lt; 0.05 and P &lt; 0.01, ANOVA). In conclusion, CRH at physiological concentrations acts synergistically with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH-mediated relaxation. Our functional model does not support homologous or heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation. Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a mechanism for down-regulation of agonist-stimulated-cAMP pathways at term.
The Spontaneous Ala147Thr Amino Acid Substitution within the Translocator Protein Influences Pregnenolone Production in Lymphomonocytes of Healthy Individuals
Authors: Costa Barbara , Pini Stefano , Gabelloni Pamela , Da Pozzo Eleonora , Abelli Marianna , Lari Lisa , Preve Matteo , Lucacchini Antonio , Cassano Giovanni B. , Martini Claudia 
Published: October 2009

AbstractThe de novo production of steroids and neurosteroids begins in mitochondria by the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain cleavage (CYP11A1) enzymatic activity. The C-terminal amino acid domain of the translocator protein (TSPO) has been demonstrated to bind cholesterol, thereby determining its mitochondrial translocation. The goal of the present study was to investigate the effect of the Ala147Thr single-nucleotide polymorphism localized in this TSPO region on pregnenolone production in healthy volunteers. Pregnenolone production was evaluated in a peripheral cell model, represented by circulating lymphomonocytes. First, CYP11A1 expression, both at mRNA and protein level, was demonstrated. Pregnenolone production varied among genotype groups. Comparison of pregnenolone mean values revealed that Thr147 homozygous or heterozygous individuals had significantly lower pregnenolone levels compared with Ala147 homozygous individuals. These findings suggested a dominant effect of the minor allelic variant Thr147 to produce this first metabolite of the steroidogenesis pathway. Interestingly, Ala147 homozygous individuals exhibited significant higher levels of circulating cholesterol-rich low-density lipoproteins with respect to heterozygous individuals. In conclusion, our results demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is able to affect pregnenolone production; this should encourage further studies to investigate its potential role in polygenic dyslipidemias.
Circulating and Adipose Tissue Gene Expression of Zinc-α2-Glycoprotein in Obesity: Its Relationship with Adipokine and Lipolytic Gene Markers in Subcutaneous and Visceral Fat
Authors: Ceperuelo-Mallafré V. , Näf S. , Escoté X. , Caubet E. , Gomez J. M. , Miranda M. , Chacon M. R. , Gonzalez-Clemente J. M. , Gallart L. , Gutierrez C. , Vendrell J. 
Published: October 2009

Context: Zinc-α2-glycoprotein (ZAG) is a soluble protein similar to the class I major histocompatibility complex heavy chain, which has been implicated in lipid catabolism. We hypothesized that ZAG mRNA expression in adipose tissue may be linked with lipolytic and adipokine gene expression and have a close relationship with clinical phenotype.Objectives: The objective of the study was to analyze ZAG gene expression in human adipose tissue from lean and obese subjects. ZAG circulating plasma levels and its relationship with cardiometabolic risk factors were also studied.Design: Seventy-three Caucasian (43 male and 30 female) subjects were included. Plasma and adipose tissue [sc (SAT) and visceral (VAT)] from the same patient were studied. mRNA of PPARγ, hormone-sensitive lipase (HSL), adipose triglyceride lipase, adiponectin, omentin, visfatin, and ZAG were quantified. Plasma concentrations of ZAG were determined with ELISA.Results: ZAG plasma levels showed a negative correlation with insulin (r = −0.39; P = 0.008) and the homeostasis model assessment for insulin resistance index (r = −0.36; P = 0.016). No differences in ZAG circulating levels according to body mass index classification were observed.ZAG expression in SAT was significantly reduced in overweight and obese individuals compared with lean subjects (P &lt; 0.001 and P = 0.007, respectively). ZAG mRNA expression in both SAT and VAT depots were negatively correlated with many clinical and metabolic cardiovascular risk factors. After multiple linear regression analysis, SAT ZAG was mainly predicted by adiponectin mRNA expression (B = 0.993; P &lt; 0.0001) and plasma triglyceride levels (B = −0.565; P = 0.006). VAT ZAG expression was predicted by adiponectin expression (B = 0.449; P &lt; 0.0001), and HSL VAT expression (B = 0.180; P = 0.023).Conclusions: The present study provides evidence of a role of ZAG gene in adipose tissue metabolism, with a close association with adiponectin gene expression in sc and visceral fat.
Prenatal Determinants of Uterine Volume and Ovarian Reserve in Adolescence
Authors: Hart Roger , Sloboda Deborah M. , Doherty Dorota A. , Norman Robert J. , Atkinson Helen C. , Newnham John P. , Dickinson Jan E. , Hickey Martha 
Published: October 2009

Context: Adequate uterine volume and ovarian reserve are essential for reproductive health. Antenatal events such as restricted fetal growth and maternal tobacco smoking are hypothesized to impact on reproductive function in later life, although not studied in a large prospective normal pregnancy population to date.
Objective: The objective of the study was to determine the relationship between intrauterine growth, birth weight, and maternal tobacco smoking on uterine volume and ovarian reserve in adolescence.
Design and Setting: This was a prospective study in which half the cohort underwent intensive ultrasound monitoring in utero.
Participants: Intrauterine growth was measured using ultrasound at 18, 24, 28, and 34/36 wk gestation (n = 115 girls). Maternal smoking data were prospectively collected at 18 and 34/36 wk from the whole cohort. Uterine (n = 229) and early follicular ovarian volume and antral follicle count (n = 225) were measured using transabdominal ultrasound (n = 230). Ovarian reserve was estimated using early follicular phase anti-Mullerian hormone, inhibin B, and FSH (n = 213).
Main Outcome Measures: The relationship between maternal tobacco smoking, intrauterine growth trajectories, and markers of ovarian reserve and uterine size in adolescence was measured.
Results: Linear regression showed that daughters of mothers who smoked had a significantly smaller uterus compared with nonsmokers (P = 0.019). No significant relationship between maternal tobacco smoking and ovarian volume (P = 0.164) or markers of ovarian reserve (antral follicle count, plasma FSH, anti-Mullerian hormone, and inhibin B) in adolescence was determined.
Conclusions: Our findings indicate that maternal smoking, but not variations in fetal growth, may lead to a reduction in uterine volume and does not appear to impact ovarian reserve.