bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dax1 Up-Regulates Oct4 Expression in Mouse Embryonic Stem Cells via LRH-1 and SRA
Authors: Kelly Victoria R. , Xu Bin , Kuick Rork , Koenig Ronald J. , Hammer Gary D. 
Published: October 2010

Abstract
Dax1 (Nr0b1) is an atypical orphan nuclear receptor that has recently been shown to play a role in mouse embryonic stem (mES) cell pluripotency. Here we describe a mechanism by which Dax1 maintains pluripotency. In steroidogenic cells, Dax1 protein interacts with the NR5A nuclear receptor steroidogenic factor 1 (Nr5a1) to inhibit transcription of target genes. In mES cells, liver receptor homolog 1 (LRH-1, Nr5a2), the other NR5A family member, is expressed, and LRH-1 has been shown to interact with Dax1. We demonstrate by coimmunoprecipitation that Dax1 is, indeed, able to form a complex with LRH-1 in mES cells. Because Dax1 was historically characterized as an inhibitor of steroidogenic factor 1-mediated transcriptional activation, we hypothesized that Dax1 would inhibit LRH-1 action in mES cells. Therefore, we examined the effect of Dax1 on the LRH-1-mediated activation of the critical ES cell factor Oct4 (Pou5f1). Chromatin immunoprecipitation localized Dax1 to the Oct4 promoter at the LRH-1 binding site, and luciferase assays together with Dax1 overexpression and knockdown experiments revealed that, rather than repress, Dax1 accentuated LRH-1-mediated activation of the Oct4 gene. Similar to our previously published studies that defined the RNA coactivator steroid receptor RNA activator as the critical mediator of Dax1 coactivation function, Dax1 augmentation of LRH-1-mediated Oct4 activation is dependent upon steroid receptor RNA activator. Finally, utilizing published chromatin immunoprecipitation data of whole-genome binding sites of LRH-1 and Dax1, we show that LRH-1 and Dax1 commonly colocalize at 288 genes (43% of LRH-1 target genes), many of which are involved in mES cell pluripotency. Thus, our results indicate that Dax1 plays an important role in the maintenance of pluripotency in mES cells through interaction with LRH-1 and transcriptional activation of Oct4 and other genes.
Suppressive potencies of calcineurin inhibitors against the mitogen-induced blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis patients
Authors: Tanaka Sachiko , Nakajima Kanako , Hirano Toshihiko , Oka Kitaro , Saito Toyokazu , Wakata Nobuo 
Published: October 2010

Abstract
The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. The median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of PBMCs of MG patients were 0.06 (0.001–100) and 0.41 (0.09–83.0) ng mL−1, respectively. In contrast, the median (range) IC50 values of tacrolimus and ciclosporin on healthy PBMCs were 0.16 (0.001–0.33) and 5.59 (1.4–31.3), respectively, and thus ciclosporin potencies against PBMCs of MG patients were significantly higher than those against PBMCs of healthy subjects (P &lt; 0.0001). The differences in tacrolimus IC50 values between the patients and healthy subjects were not significant. There was a correlation between ciclosporin IC50 values against the blastogenesis of PBMCs of MG patients and the duration of the disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.
Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats
Authors: Yuan Li-ping , Chen Fei-hu , Ling Lu , Bo Hu , Chen Zhi-wu , Li Fan , Zhong Ming-mei , Xia Li-juan 
Published: October 2010

Abstract
Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg−1) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg−1) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg−1) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kB, α-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-β1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kB on hepatic stellate cell activation and the expression of TGF-β1.
Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of β-cyclodextrin derivatives
Authors: Alexanian Christina , Papademou Helen , Vertzoni Maria , Archontaki Helen , Valsami Georgia 
Published: October 2010

Abstract
The aqueous solubility of nimesulide in the absence and presence of β-cyclodextrin (β-CD) and its alkyl derivatives hydroxypropyl-β-CD and methyl-β-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinyl- pyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25°C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. β-CDs increased the aqueous solubility of nimesulide in the following order: methyl-β-CD &gt; β-CD &gt; hydroxypropyl-β-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three β-CDs with nimesulide, while preheating of the polymer at 70°C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium- carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus β-CD, hydroxypropyl-β-CD and methyl-β-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl- cellulose in order to enhance its oral bioavailability.
Cirsilineol inhibits proliferation of cancer cells by inducing apoptosis via mitochondrial pathway
Authors: Sheng Xia , Sun Yang , Yin Ye , Chen Ting , Xu Qiang 
Published: October 2010

Abstract
Cirsilineol (4′,5-dihydroxy-3′,6,7-trimethoxyflavone) is a compound isolated from the herb of Artemisia vestita Wall (Compositae). In this study, we aimed at examining the anti-proliferative activity of cirsilineol against multiple types of cancer cells and the underlying mechanisms. Cirsilineol significantly inhibited proliferation of Caov-3, Skov-3, PC3 and Hela cells in a concentration-dependent manner. The compound also dose-dependently induced apoptosis in Caov-3 cells, as determined by annexin V/propidium iodide staining. Besides, cirsilineol induced a remarkable change in mitochondrial membrane potential and caused release of cytochrome c to cytosol. Furthermore, the compound caused a marked activation of capase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP). These results suggested that the induction of apoptosis via the mitochondrial pathway was involved in the anti-proliferative activity of cirsilineol against cancer cells.
Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: Critical roles of ERK2 and cAMP
Authors: Lee Whi Min , Kim Sung Dae , Park Myung Hwan , Cho Jae Youl , Park Hwa Jin , Seo Geon Sik , Rhee Man Hee 
Published: October 2010

Abstract
Ginsenoside Rg3, a single ginseng saponin, is known to be a major anti-platelet component of protopanaxadiol that is isolated from Korean red ginseng. In this study, we investigated whether dihydroginsenoside Rg3, a stable chemical derivative of ginsenoside Rg3, also demonstrated anti-platelet activity. Dihydroginsenoside Rg3 inhibited thrombin-induced platelet aggregation in a concentration-dependent manner with an IC50 (concentration producing 50% inhibition) of 18.8 ± 0.4 μM. Ginsenoside Rg3 inhibited platelet aggregation which was induced by thrombin (0.1 U mL−1) with an IC50 of 40.2 ± 0.9 μM. We next determined whether dihydroginsenoside Rg3 affected different types of ligand-induced platelet aggregation. We found that dihydroginsenoside Rg3 inhibited collagen-induced platelet aggregation with an IC50 of 20.0 ± 0.9 μM. To elucidate the inhibitory mechanism of dihydroginsenoside Rg3 on aggregation, we analysed its downstream signalling pathway. It was interesting to note that dihydroginsenoside Rg3 elevated cyclic AMP production in resting platelets, but did not affect cyclic GMP production. In addition, we found that dihydroginsenoside Rg3 potently suppressed phosphorylation of extracellular signal-regulated kinase 2 (ERK2), which was stimulated by collagen (2.5 μg mL−1), but not of p38 mitogen-activated protein kinase. Taken together, our results indicate that dihydroginsenoside Rg3 potently inhibited platelet aggregation via the modulation of downstream signalling components such as cAMP and ERK2.
Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive and thymidine-kinase-negative herpesviruses
Authors: Koch Christine , Reichling Jürgen , Kehm Roland , Sharaf Mona M , Zentgraf Hanswalter , Schneele Jürgen , Schnitzler Paul 
Published: October 2010

Abstract
The effect of anise oil, dwarf-pine oil and chamomile oil against different thymidine-kinase-positive (aciclovir-sensitive) and thymidine-kinase-negative (aciclovir-resistant) herpes simplex virus type 1 (HSV-1) strains was examined. Clinical HSV-1 isolates containing frameshift mutations in the thymidine kinase (TK) gene, an insertion or a deletion, yield a non-functional thymidine kinase enzyme resulting in phenotypical resistance against aciclovir. The inhibitory activity of three different essential oils against herpes simplex virus isolates was tested in-vitro using a plaque reduction assay. All essential oils exhibited high levels of antiviral activity against aciclovir-sensitive HSV strain KOS and aciclovir-resistant clinical HSV isolates as well as aciclovir-resistant strain Angelotti. At maximum noncytotoxic concentrations of the plant oils, plaque formation was significantly reduced by 96.6–99.9%, when herpesviruses were preincubated with drugs before attachment to host cells. No significant effect on viral infectivity could be achieved by adding these compounds during the replication phase. These results indicate that anise oil, dwarf-pine oil and chamomile oil affected the virus by interrupting adsorption of herpesviruses and in a different manner than aciclovir, which is effective after attachment inside the infected cells. Thus the investigated essential oils are capable of exerting a direct effect on HSV and might be useful in the treatment of drug-resistant viruses. Chamomile oil did not reveal any irritating potential on hen's egg chorioallantoic membrane, demonstrated the highest selectivity index among the oils tested and was highly active against clinically relevant aciclovir-resistant HSV-1 strains.
Staphylococcus epidermidis device-related infections: pathogenesis and clinical management
Authors: McCann Maureen T , Gilmore Brendan F , Gorman Sean P 
Published: October 2010

Abstract
Staphylococcus epidermidis, the most frequently isolated coagulase-negative staphylococcus, is the leading cause of infection related to implanted medical devices (IMDs). This is directly related to its capability to establish multilayered, highly structured biofilms on artificial surfaces. At present, conventional systemic therapies using standard antimicrobial agents represent the main strategy to treat and prevent medical device-associated infections. However, device-related infections are notoriously difficult to treat and bacteria within biofilm communities on the surface of IMDs frequently outlive treatment, and removal of the medical device is often required for successful therapy. Importantly, major advances in this research area have been made, leading to a greater understanding of the complexities of biofilm formation of S. epidermidis and resulting in significant developments in the treatment and prevention of infections related to this member of the coagulase-negative group of staphylococci. This review will examine the pathogenesis of the clinically significant S. epidermidis and provide an overview of the conventional and emerging antibiofilm approaches in the management of medical device-associated infections related to this important nosocomial pathogen.
Depressant-like effects of parthenolide in a rodent behavioural antidepressant test battery
Authors: Pandey Dilip Kumar , Rajkumar Ramamoorthy , Mahesh Radhakrishnan , Radha Raghuraman 
Published: October 2010

AbstractThe anti-serotonergic effects of parthenolide (PTL) demonstrated in platelets inspired the present psychopharmacological investigation, which employs a battery of rodent behavioural assays of depression. In mice, PTL (0.5-2 mg kg−1) exhibited dose-dependent depressant-like effects in a forced swim test and a tail suspension test, without affecting the baseline locomotor status. The doses (1 and 2 mg kg−1) that induced depressant-like effects were found to significantly reduce 5-hydroxytrypto-phan-induced head twitch response. Interaction studies revealed that the depressant-like effects of PTL (1 mg kg−1) were reversed more efficiently by serotonergic antidepressants (venlafaxine, escitalopram, citalopram, fluoxetine) than by others (desipramine, bupropion) tested. Chronic treatment of PTL (1 and 2 mg kg−1) augmented the hyper-emotionality of olfactory bulbectomized rats, when compared with sham rats, as observed in modified open field, elevated plus maze and social interaction paradigms. This study depicts the severe depressogenic potential of PTL (in its pure form) plausibly mediated by platelet/neuronal hypo-serotonergic effects.
Effects of isorhynchophylline on angiotensin II-induced proliferation in rat vascular smooth muscle cells
Authors: Zhang Feng , Sun An-Sheng , Yu Li-Mei , Wu Qin , Gong Qi-Hai 
Published: October 2010

AbstractProliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with α-smooth muscle actin. Isorhynchophylline (0.1–10.0 μM) was not toxic to VSMCs, but markedly decreased Ang II (1.0 μm)-enhanced cell number and MTT intensity, and blocked cell transition from G0/G1 to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation.
Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells
Authors: Gao Ying , Xue Jing , Li Xiaoyu , Jia Yongqian , Hu Jing 
Published: October 2010

Abstract
Metformin is widely used for the treatment of type 2 diabetes mellitus. In this study, we evaluated the effects of metformin on the osteoblast and adipocyte differentiation of rat marrow mesenchymal stem cells (MSCs) in culture. Treatment of MSCs in osteoblastic or adipogenic medium with 100 μM metformin for 21 days led to an increased mRNA expression of the osteoblast markers but a decreased mRNA expression of the adipocyte markers in the MSCs. Metformin markedly stimulated deposition of mineralized nodules and blocked the formation of cytoplasmic lipid droplets. In addition, alkaline phosphate activity and Western blot analysis for core binding factor a1 (Cbfa 1) and peroxisome proliferator-activated receptor gamma 2 (PPARγ2) proteins also confirmed that metformin inhibited adipocyte differentiation and promoted osteoblast differentiation. The reciprocal relationship between osteoblastic and adipogenic differentiation suggests that metformin may regulate osteoblastic and adipogenic differentiation through inhibition of PPARγ.
Ozone oxidative post-conditioning in acute renal failure
Authors: Calunga José Luis , Trujillo Yanelis , Menéndez Silvia , Zamora Zullyt , Alonso Yaima , Merino Nelson , Montero Teresa 
Published: October 2010

Abstract

Objectives
The ischaemia–reperfusion process is largely mediated by reactive oxygen species. Taking into account that a transient and controlled administration of ozone is able to upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing warm renal ischaemia.

Methods
Rats were divided into four groups. All except the negative controls underwent 60 min' bilateral renal ischaemia followed by 10 days' reperfusion. The positive control group received no further treatment. The ozone group received an ozone/oxygen mixture (ozone dose 0.5 mg/kg) immediately after the ischaemia and daily for the 10 days' reperfusion; the oxygen group were given the same concentration of oxygen alone (13 mg/kg). Biochemical parameters fructosamine, phospholipase A2, catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured, as well as renal plasma flow and glomerular filtration rate.

Key findings
Renal plasma flow and glomerular filtration rate decreased significantly in the positive controls and the oxygen group whereas values in the ozone group were similar to those in the negative control group. With respect to the biochemical parameters, ozone maintained a homeostasis redox, with significant increases in catalase and superoxide dismutase activities and similar values for phospholipase A2 and fructosamine compared with the negative control group. Fewer morphological alterations were seen in kidneys from the ozone group. No advantages were obtained in the positive control and oxygen groups.

Conclusions
The protective effect of ozone may be explained by upregulation of the antioxidant defence system and beneficial effects on blood circulation and in oxygen metabolism. Ozone treatment may represent a therapeutic approach for minimising renal damage after transplantation.
In-vitro respiratory drug absorption models possess nominal functional P-glycoprotein activity
Authors: Madlova Michaela , Bosquillon Cynthia , Asker Dan , Dolezal Pavel , Forbes Ben 
Published: October 2010

AbstractObjectivesThe P-glycoprotein (P-gp) efflux pump is known to be present within several major physiological barriers including the brain, kidney, intestine and placenta. However, the function of P-gp in the airways of the lung is unclear. The purpose of this study was to use the highly specific P-gp inhibitor GF120918A to investigate the activity of the P-gp transporter in the airways to determine whether P-gp could influence inhaled drug disposition.MethodsP-gp activity was measured as a change in digoxin transport in the presence of GF120918A in normal human bronchial epithelial (NHBE) cells, Calu-3 cell layers and the ex-vivo rat lung.Key findingsThe efflux ratios (ERs) in NHBE and Calu-3 cells were between 0.5 and 2, in contrast to 10.7 in the Caco-2 cell control. These low levels of GF120918A-sensitive polarised digoxin transport were measured in the absorptive direction in NHBE cells (ER = 0.5) and in the secretory direction in Calu-3 cells (ER = 2), but only after 21 days in culture for both cell systems and only in Calu-3 cells at passage &gt;50. The airspace to perfusate transfer kinetics of digoxin in the ex-vivo rat lung were unchanged in the presence of GF120918A.ConclusionsThese results demonstrated that although low levels of highly culture-dependent P-gp activity could be measured in cell-lines, these should not be interpreted to mean that P-gp is a major determinant of drug disposition in the airways of the lung.