bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tangeretin and its metabolite 4′‐hydroxytetramethoxyflavone attenuate EGF‐stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K
Authors: Cheng Z , Surichan S , Ruparelia K , Arroo R , Boarder MR 
Published: December 2010

BACKGROUND AND PURPOSE The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′‐hydroxy‐5,6,7,8‐tetramethoxyflavone (4′‐OH‐TMF) in this effect.EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)‐stimulated rat hepatocytes, with [3H]‐thymidine incorporation into DNA as an index of progression to S‐phase of the cell cycle, and Western blots for phospho‐proteins involved in the cell signalling cascade.KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′‐OH‐TMF. Low micromolar concentrations of tangeretin or 4′‐OH‐TMF gave a concentration‐dependent inhibition of EGF‐stimulated progression to S‐phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre‐incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF‐stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′‐OH‐TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR.CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′‐OH‐TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′‐OH‐TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid‐rich diet.
The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL‐10 expression in cutaneous T‐cell lymphoma cells
Authors: Tiffon CE , Adams JE , van der Fits L , Wen S , Townsend PA , Ganesan A , Hodges E , Vermeer MH , Packham G 
Published: December 2010

BACKGROUND AND PURPOSEVorinostat and romidepsin are histone deacetylase inhibitors (HDI), approved for the treatment of cutaneous T‐cell lymphoma (CTCL). However, the mechanism(s) by which these drugs exert their anti‐cancer effects are not fully understood. Since CTCL is associated with immune dysregulation, we investigated whether these HDI modulated cytokine expression in CTCL cells.EXPERIMENTAL APPROACHCTCL cell lines and primary CTCL cells were treated in vitro with vorinostat or romidepsin, or with STAT3 pathway inhibitors. Cell cycle parameters and apoptosis were analysed by propidium iodide and annexin V/propidium iodide staining respectively. Cytokine expression was analysed using QRT‐PCR and elisa assays. STAT3 expression/phosphorylation and transcriptional activity were analysed using immunoblotting and transfection/reporter assays respectively.KEY RESULTSVorinostat and romidepsin strongly down‐regulated expression of the immunosuppressive cytokine, interleukin (IL)‐10, frequently overexpressed in CTCL, at both the RNA and protein level in CTCL cell lines and at the RNA level in primary CTCL cells. Vorinostat and romidepsin also increased expression of IFNG RNA and decreased expression of IL‐2 and IL‐4 RNA, although to a lesser extent compared to IL‐10. Transient exposure to vorinostat was sufficient to suppress IL‐10 secretion but was not sufficient to irreversibly commit cells to undergo cell death. STAT3 pathway inhibitors decreased production of IL‐10 and vorinostat/romidepsin partially decreased STAT3‐dependent transcription without effects on STAT3 expression or phosphorylation.CONCLUSIONS AND IMPLICATIONSThese results demonstrate that HDI modulate cytokine expression in CTCL cells, potentially via effects on STAT3. Immunomodulation may contribute to the clinical activity of HDI in this disease.
Ectopic overexpression of haem oxygenase‐1 protects kidneys from carboplatin‐mediated apoptosis
Authors: Sue Yuh‐Mou , Cheng Ching‐Feng , Chou Ying , Chang Chih‐Cheng , Lee Pei‐Shan , Juan Shu‐Hui 
Published: December 2010

BACKGROUND AND PURPOSE We previously reported that the activation of the nuclear factor of activated T‐lymphocyte‐3 (NFAT3) by carboplatin leads to renal apoptosis as a result of oxidative stress, which is reversed by N‐acetylcysteine. Herein, we extend our previous work to provide evidence of the molecular mechanisms of haem oxygenase (HO)‐1 in protecting against injury.EXPERIMENTAL APPROACH Protective mechanisms of HO‐1 in carboplatin‐mediated renal apoptosis were examined in C57BL/6 mice and rat renal tubular cells (RTC) with HO‐1 induction or inactivation/knockdown.KEY RESULTS The HO‐1, induced by cobalt protoporphyrin, protected against carboplatin‐induced renal injury in vivo. This protection was decreased by an inhibitor of HO‐1 action, tin protoporphyrin. In cultures of RTC, carboplatin‐induced apoptosis was similarly affected by HO‐1 overexpression or knockdown. Carboplatin‐mediated NFAT3 activation and apoptosis involve activation of the signalling kinases, extracellular signal regulated kinase, Jun N‐terminal kinase and protein kinase C, and such activation was reversed in cells overexpressing HO‐1. Both products of the HO‐1 reaction, CO and bilirubin, inhibited (by 30–40%) NFAT3 activation and production of the pro‐apoptotic proteins Bcl‐XS/Bax. Additionally, the activation of NFκB was markedly decreased by HO‐1 induction.CONCLUSION AND IMPLICATIONS HO‐1 and its reaction products show anti‐apoptotic effects in carboplatin‐mediated renal injury. A novel functional NFAT3 binding site identified in the rat HO‐1 promoter region was involved in producing a 1.5‐fold to 2.5‐fold increase in HO‐1 induction by carboplatin. Nevertheless, only HO‐1 overexpression and activation prior to the carboplatin challenge provided protection against carboplatin‐induced injury.
Muscarinic receptor antagonists, from folklore to pharmacology; finding drugs that actually work in asthma and COPD
Authors: Moulton Bart C , Fryer Allison D 
Published: December 2010

In the lungs, parasympathetic nerves provide the dominant control of airway smooth muscle with release of acetylcholine onto M3 muscarinic receptors. Treatment of airway disease with anticholinergic drugs that block muscarinic receptors began over 2000 years ago. Pharmacologic data all indicated that antimuscarinic drugs should be highly effective in asthma but clinical results were mixed. Thus, with the discovery of effective β‐adrenergic receptor agonists the use of muscarinic antagonists declined. Lack of effectiveness of muscarinic antagonists is due to a variety of factors including unwanted side effects (ranging from dry mouth to coma) and the discovery of additional muscarinic receptor subtypes in the lungs with sometimes competing effects. Perhaps the most important problem is ineffective dosing due to poorly understood differences between routes of administration and no effective way of testing whether antagonists block receptors stimulated physiologically by acetylcholine. Newer muscarinic receptor antagonists are being developed that address the problems of side effects and receptor selectivity that appear to be quite promising in the treatment of asthma and chronic obstructive pulmonary disease.LINKED ARTICLESThis article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.163.issue‐1
Hydrogen sulphide and angiogenesis: mechanisms and applications
Authors: Szabó Csaba , Papapetropoulos Andreas 
Published: December 2010

In vascular tissues, hydrogen sulphide (H2S) is mainly produced from L‐cysteine by the cystathionine gamma‐lyase (CSE) enzyme. Recent studies show that administration of H2S to endothelial cells in culture stimulates cell proliferation, migration and tube formation. In addition, administration of H2S to chicken chorioallantoic membranes stimulates blood vessel growth and branching. Furthermore, in vivo administration of H2S to mice stimulates angiogenesis, as demonstrated in the Matrigel plug assay. Pathways involved in the angiogenic response of H2S include the PI‐3K/Akt pathway, the mitogen activated protein kinase pathway, as well as ATP‐sensitive potassium channels. Indirect evidence also suggests that the recently demonstrated role of H2S as an inhibitor of phosphodiesterases may play an additional role in its pro‐angiogenic effect. The endogenous role of H2S in the angiogenic response has been demonstrated in the chicken chorioallantoic membranes, in endothelial cells in vitro and ex vivo. Importantly, the pro‐angiogenic effect of vascular endothelial growth factor (but not of fibroblast growth factor) involves the endogenous production of H2S. The pro‐angiogenic effects of H2S are also apparent in vivo: in a model of hindlimb ischaemia‐induced angiogenesis, H2S induces a marked pro‐angiogenic response; similarly, in a model of coronary ischaemia, H2S exerts angiogenic effects. Angiogenesis is crucial in the early stage of wound healing. Accordingly, topical administration of H2S promotes wound healing, whereas genetic ablation of CSE attenuates it. Pharmacological modulation of H2S‐mediated angiogenic pathways may open the door for novel therapeutic approaches.LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐3
Antagonist interaction with the human 5‐HT7receptor mediates the rapid and potent inhibition of non‐G‐protein‐stimulated adenylate cyclase activity: a novel GPCR effect
Authors: Klein MT , Teitler M 
Published: December 2010

BACKGROUND AND PURPOSEThe human 5‐hydroxytryptamine7(h5‐HT7) receptor is Gs‐coupled and stimulates the production of the intracellular signalling molecule cAMP. Previously, we reported a novel property of the h5‐HT7receptor: pseudo‐irreversible antagonists irreversibly inhibit forskolin‐stimulated (non‐receptor‐mediated) cAMP production. Herein, we sought to determine if competitive antagonists also affect forskolin‐stimulated activity and if this effect is common among other Gs‐coupled receptors.EXPERIMENTAL APPROACHRecombinant cell lines expressing h5‐HT7receptors or other receptors of interest were briefly exposed to antagonists; cAMP production was then stimulated by forskolin and quantified by an immunocompetitive assay.KEY RESULTSIn human embryonic kidney 293 cells stably expressing h5‐HT7receptors, all competitive antagonists inhibited nearly 100% of forskolin‐stimulated cAMP production. This effect was insensitive to pertussis toxin, that is, not Gi/o‐mediated. Potency to inhibit forskolin‐stimulated activity strongly correlated with h5‐HT7binding affinity (r2= 0.91), indicating that the antagonists acted through h5‐HT7receptors to inhibit forskolin. Potency and maximal effects of clozapine, a prototypical competitive h5‐HT7antagonist, were unaffected by varying forskolin concentration. Antagonist interaction with h5‐HT6, human β1, β2, and β3adrenoceptors did not inhibit forskolin's activity.CONCLUSIONS AND IMPLICATIONSThe inhibition of adenylate cyclase, as measured by forskolin's activity, is an underlying property of antagonist interaction with h5‐HT7receptors; however, this is not a common property of other Gs‐coupled receptors. This phenomenon may be involved in the roles played by h5‐HT7receptors in human physiology. Development of h5‐HT7antagonists that do not elicit this effect would aid in the elucidation of its mechanisms and shed light on its possible physiological relevance.
Quasi-periodic oscillations in XTE J1550−564: the rms–flux relation
Authors: Heil L. M. , Vaughan S. , Uttley P. 
Published: December 2010

Abstract
We present an analysis of the short time-scale variations in the properties of the strong (type ‘C’) quasi-periodic oscillation (QPO) observed in XTE J1550−564 during its 1998 outburst. In particular, the QPO shows a correlation between absolute rms amplitude and mean source flux over time-scales shorter than ∼3 ks. A linear rms–flux relation has been observed to be a common property of broad-band noise, but here we report the first detection of rms–flux dependence in a QPO. The gradient of the rms–flux relation is correlated with the QPO peak frequency: from a strong positive correlation when the QPO peak frequency is below ∼4 Hz, through no correlation, to a strong negative correlation when the peak frequency is above 6 Hz. This is the first time a negative short term rms–flux relation has been observed in any component of the power spectrum. Previous work on both the broad-band noise and QPOs in a range of sources have suggested the presence of a filter reducing the amplitude of QPOs with increasing frequency. We attempt to remove the possible effects of this filter and find that the previously negative rms–flux relations above ∼5 Hz become constant.
Upstream thinking and health promotion planning for older adults at risk of social isolation
Authors: Wilson Donna M. , Harris Ashley , Hollis Vivien , Mohankumar Deepthi 
Published: December 2010

wilson d.m., harris a., hollis v. & mohankumar d. (2010) Upstream thinking and health promotion planning for older adults at risk of social isolation. International Journal of Older People Nursing6, 282–288 doi: 10.1111/j.1748‐3743.2010.00259.xAims and objectives.  To raise awareness of social isolation, and provide an approach to first conceptualise and then prevent social isolation among older community‐dwelling persons.Background.  Older adults comprise a vulnerable population for social isolation and its associated health risks.Design.  Literature review.Methods.  Canada’s Population Health Promotion Model was chosen as a comprehensive tool to understand and prevent social isolation. Research studies were sought to identify key health determinants and evidence‐based options for preventing social isolation.Results.  Around 1 out of 6 older persons are socially isolated and three health determinants are of prime importance: (i) income and social status; (ii) personal health practices and coping skills and (iii) social support networks. Evidence‐based interventions targeted to these health determinants are suggested.Conclusion.  Nurses are a key group to advocate for actions needed to prevent social isolation.Implications for practice.  Nurses can play a vital role in minimising social isolation through a variety of educational, prevention and political lobbying activities.
A New Eusauropod Dinosaur from the Lower Cretaceous of Guangxi Province, Southern China
Authors: Jinyou MO , Xing XU , BUFFETAUT Eric 
Published: December 2010

Abstract:A new sauropod dinosaur,Liubangosaurus heigen. et sp. nov., is erected based on a specimen represented by five articulated middle‐caudal dorsal vertebrae, which was discovered in the Lower Cretaceous Napai Formation of Guangxi Province, southern China. This new taxon is diagnosed by a unique combination of derived features: prezygapophysis closely contacts with parapophysis, with the prdl and prpl absent; presence of cavity on the dorsal surface of the diapophysis; neural spine very low, with its distal end level with that of diapophysis; distal end of the neural spine strongly expanded laterally to form a platform; marked fossa formed between the infradiapophyseal lamina and the parapophysis; broad, flat area of featureless bone on lateral surface of neural arch; vertically directed infradiapophyseal lamina expands or bifurcates ventrally to form a inverted “Y”; highly positioned parapophyses large and tear‐drop in shape. The discovery of this new taxon increases the diversity of sauropods in China during the Early Cretaceous.
A New Basal Sauropod Dinosaur from the Lufeng Basin, Yunnan Province, Southwestern China
Authors: Junchang LÜ , KOBAYASHI Yoshitsugu , Tianguang LI , Shimin ZHONG 
Published: December 2010

Abstract:A new dinosaur Chuxiongosaurus lufengensis gen. et sp. nov. is erected based on a nearly complete skull. The taxon is characterized by the lacrimal perpendicular to the ventral margin of the upper jaw, which is similar to that of Thecodontosaurus; a depression present on the dorsal profile of the snout behind the naris; the rostral profile of the maxilla slopes continuously towards the rostral tip; and the presence of 25 dentary teeth. It also displays prosauropod characters such as a relatively long skull, the slope of the maxillary rostral profile, and teeth that do not have basically constricted crowns. The new specimen is more basal than Anchisaurus and represents the first basal sauropod dinosaur from the Early Jurassic of China.
Late Tremadoc and Early Floian Graptolites from Central Hunan, China
Authors: Ming LI , Hongzhen FENG , Xinxin JI , Lixia LI 
Published: December 2010

Abstract:Fourteen graptolite species of the Late Tremadoc and Early Floian are described from the Nanba section in the Yiyang area, Hunan Province. Among them, Paradelograptus onubensis, Kiaerograptus bulmani, K. kutchini and Paratemnograptus isolatus of the Late Tremadoc are first found in China. Based on the current graptolite materials, the correspondingly complete graptolite zones of Upper Tremadocian in China are recognized as follows (in ascending order): the Adelograptus tenellus Zone, the Aorograptus victoriae Zone, the Araneograptus murrayi Zone and the Hunnegraptus copiosus Zone. In the Nanba section, the Hunnegraptus copiosus Zone is overlain directly by the Tetragraptus approximates Zone, there is no hiatus below the base of Floian.
Bayan Obo Carbonatites: Texture Evidence from Polyphase Intrusive and Extrusive Carbonatites
Authors: Kaiyi WANG , Hongrui FAN , Kuifeng YANG , Fangfang HU , Yuguang MA 
Published: December 2010

Abstract:Most of the so‐called Bayan Obo fine‐grained dolomite marbles collected from the main and east orebodies show a microporphyritic texture, namely the microphenocrysts are set in a very finegrained matrix, although nearly all of them have undergone recrystallization caused either by deformation or alteration. The texture seems likely to have maintained the original features. It is known that one of the most characteristic textures of volcanic rocks is the porphyritic texture, and the microporphyritic texture is a variety in which both the phenocrysts and the matrix are only distinguishable with the microscope. Therefore, the dolomite marbles in the main and east orebodies may be related to the extrusive carbonatites. In addition, there also occur some carbonatite sills and dykes with different textures at Bayan Obo. Thus, the Bayan Obo carbonatites are polyphase intrusive and extrusive carbonatites.
Regional Metallogenesis of the Chang'an Gold Ore Deposit in Western Yunnan: Evidences from Fluid Inclusions and Stable Isotopes
Authors: Yue CHEN , Junlai LIU , Dung TRAN My , Yongchao LI , Mingming BING 
Published: December 2010

Abstract:The Chang'an gold ore deposit in western Yunnan is located at the southern segment of the Ailaoshan metallogenic belt. The ore bodies are preserved in fractured Ordovician sedimentary clastic rocks. The gold‐bearing minerals occur dominantly in sulfide‐quartz veins. Fluid inclusion analysis shows that the Chang'an gold ore deposit is characterized by epithermal gold mineralization at temperatures between 200°C and 280°C at a shallow crustal level. The mineralizing fluids have intermediate to low salinity (6%–18%) and low densities (0.72–1.27 g/cm3). The ore minerals have δ34S in a range from −13‰ to 3.57‰, concentrated from −2.06‰ to 3.57‰ with an average of 1.55‰. The 206Pb/204Pb, 207Pb/204pb and 208pb/204pb values are 18.9977–19.5748, 15.7093–15.784, 39.3814–40.2004 respectively. These isotope data suggest that the ore‐forming elements were mainly derived from mixed crustal and mantle sources. The Chang'an gold ore deposit and Tongchang Cu‐Mo deposit are closely related to each other in their spatial distribution and age of formation. They have similar sources of mineralizing elements and identical ore‐forming metal elements, and show a close relationship in physical and chemical conditions of mineralization. The two deposits constitute an epithermal‐porphyry‐skarn type Cu‐Mo‐Au mineralization system in the Tongchang‐Chang'an area, which is related to the Cenozoic high‐K alkaline magmatism.
Red Clay Type Gold Deposits in China
Authors: Xiang SUN , Jun DENG , Qingfei WANG , Qingjie GONG , Liqiang YANG , Changming WANG 
Published: December 2010

Abstract:Red clay type gold deposits, located in the south of China, are situated not only in orogenic belts, but also in inner cratons, where climate is tropical‐subtropical with clear arid and humid. The lateritic weathering crust often can be divided into five zones, including topsoil, siliceous duricrust zone, multi‐color zone (or red clay zone in some deposits), pallid zone and saprolite zone from surface to the base rock, several of which are absent in some deposits. The base rocks are composed mainly of carbonate rocks with minor clastic rocks, intermediate‐basic volcanic rocks and intermediate‐acid and alkalic intrusions. The orebodies are mainly located in the multi‐color zone with part of them in the pallid and saprolite zones. The ore sources include orebodies of Carlin‐type gold deposits and porphyry gold deposits, as well as gold‐rich base rocks. The red clay type gold deposits experienced early‐stage endogenic gold mineralization and laterization during the Tertiary and Quaternary. The areas with endogenic gold deposits, especially Carlin‐type gold deposits and porphyry gold deposits in karst depressions on the plateau, structual erosional platforms in the middle‐lower mountains, and intermountain basins in southern China are well worth studying to trace red clay type gold deposits.
Geochemistry of the Eocene Felsic Porphyric Rocks and High‐Mg Potassic Rocks along JARSZ: Implication for the Tectonic Evolution in Eastern Tibet
Authors: Jianlin CHEN , Jifeng XU , Baodi WANG , Zhiqiang KANG 
Published: December 2010

Abstract:Eocene felsic porphyric rocks and the high‐Mg potassic volcanic rocks (HMPR) occur along the Jinshajiang‐Ailao Shan‐Red River shear zone (JARSZ) in eastern Tibet. Compared with the HMPR, which are generally believed to be sourced from an enriched mantle, the felsic porphyric rocks show similar K2O contents, enrichment in LREE and LILE, particularly radiogenic isotope (e.g. Sr and Nd) features much similar to the former, implying generation of the felsic porphyric rocks most likely related to the HMPR, although they both have clearly different major and trace element compositions. The close relationship in spatial‐temporal distribution and similar Sr‐Nd characteristics between the felsic porphyric rocks and HMPR in eastern Tibet indicate that both of them were possibly formed by a similar tectonic process (event). Combining the basic dikes in southern and eastern Tibet, we suggest that the break‐off of north‐dipping Neo‐Tethyan slab in southern Tibet during 50–40 Ma, triggered formation of high‐Mg potassic magma. This led to developing felsic porphyric magma production by partial melting of underplating HMPR in the lower crust, or fractionation crystallization of the high‐Mg potassic magmas. The break‐off of slab in the Eocene may also have contributed to the abundant ore‐forming material related to earlier subduction events, resulting in formation of the porphyric deposits along JARSZ in eastern Tibet.