Efficacy of parthenolide on lung histopathology in a murine model of asthma

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Bedolla-Barajas, F. Valdez-López, G. Alcalá-Padilla, T.I. Bedolla-Pulido, V. Rivera-Mejia, J. Morales-Romero" "autores" => array:6 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Bedolla-Barajas" ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Valdez-López" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Alcalá-Padilla" ] 3 => array:2 [ "nombre" => "T.I." "apellidos" => "Bedolla-Pulido" ] 4 => array:2 [ "nombre" => "V." "apellidos" => "Rivera-Mejia" ] 5 => array:2 [ "nombre" => "J." 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Simão-Gurge, B.T. Costa-Carvalho, F.A. Nobre, I.G.S. Gonzalez, M.I. de Moraes-Pinto" "autores" => array:5 [ 0 => array:2 [ "nombre" => "R.M." "apellidos" => "Simão-Gurge" ] 1 => array:2 [ "nombre" => "B.T." "apellidos" => "Costa-Carvalho" ] 2 => array:2 [ "nombre" => "F.A." "apellidos" => "Nobre" ] 3 => array:2 [ "nombre" => "I.G.S." "apellidos" => "Gonzalez" ] 4 => array:2 [ "nombre" => "M.I." "apellidos" => "de Moraes-Pinto" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054616300763?idApp=UINPBA00004N" "url" => "/03010546/0000004500000001/v1_201612300037/S0301054616300763/v1_201612300037/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Efficacy of parthenolide on lung histopathology in a murine model of asthma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "63" "paginaFinal" => "68" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Z. Arıkan-Ayyıldız, M. Karaman, S. Özbal, A. Bağrıyanık, O. Yilmaz, Ö. Karaman, N. Uzuner" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Z." "apellidos" => "Arıkan-Ayyıldız" "email" => array:2 [ 0 => "zarikanayyildiz@gmail.com" 1 => "zeynep.ayyildiz@deu.edu.tr" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Karaman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "S." "apellidos" => "Özbal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Bağrıyanık" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "O." "apellidos" => "Yilmaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Ö." "apellidos" => "Karaman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "N." "apellidos" => "Uzuner" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Pediatric Allergy, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Experimental Animal Laboratory, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Histology and Embryology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2148 "Ancho" => 3295 "Tamanyo" => 1413667 ] ] "descripcion" => array:1 [ "en" => "Light and electron microscopic findings of study groups. I; control (n:7), II; placebo (n:7), III; dexamethasone (n:7), IV; parthenolide (n:7), V; parthenolide and dexamethasone (n:7), A; H&E, B; PAS, C; Toluidine staining. (A) Arrow with two heads; sub-epithelial smooth muscle thickening, * peribronchial mononuclear cell infiltration. (B) arrows; goblet cells (C) arrows; mast cells. (D) Electron microscopic views. Increased goblet cells in placebo group (Gc), smooth muscle thickening (Sm)." ] ] ] "textoCompleto" => "IntroductionAsthma is a chronic inflammatory disease of the airways characterised by airway hyperresponsiveness, airflow obstruction and remodelling. Airway inflammation is the principal factor in the pathogenesis of asthma in which numerous cell types and mediators released from these cells have been demonstrated to play significant roles. The transcription factor, nuclear factor κB (NF-κB) is known to be a critical modulator of inflammation in the pathogenesis of asthma. It is expressed in many cell types, which plays a key role in the expression of many pro-inflammatory genes, leading to synthesis of cytokines, adhesion molecules, chemokines, growth factors and enzymes.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Nuclear factor κB pathway is known to be active in asthma. In previous studies it has been demonstrated that levels of NF-κB p65 and NF-κB p50 were increased in asthmatic patients, while in mice lacking NF-κB p50, diminished eosinophilic infiltration was observed in response to an aerolised allergen in a model of allergic asthma.<a class="elsevierStyleCrossRefs" href="#bib0165">2–5</a>Current strategies for the management of asthma focus mainly on suppressing airway inflammation, and steroids are the most effective anti-inflammatory drugs in asthma.<a class="elsevierStyleCrossRef" href="#bib0185">6</a> Inhaled steroids are currently the mainstay of asthma therapy but they also have several systemic and local side effects when used at high doses for a long time. Research for the use of alternative and complementary treatments that reverse histopathological changes and have fewer side effects is continuously increasing.Sesquiterpene lactones are the active constituents of medicinal plants from the Asteraceae family which have been used for centuries as a folk remedy in inflammatory conditions such as migraine, inflammation and arthritis.<a class="elsevierStyleCrossRefs" href="#bib0190">7,8</a> Parthenolide is one of the important sesquiterpene lactones found in plant Tanacetum Parthenium (feverfew) and the active constituent of this plant is responsible for its inflammatory effects.<a class="elsevierStyleCrossRefs" href="#bib0190">7,8</a> Previous studies suggest that anti-inflammatory effects of parthenolide are related to inhibition of NF-κB pathway. As this pathway is also known to be active in asthma pathogenesis, it may be speculated that parthenolide may be beneficial in the treatment of asthma. To our knowledge there is no study in the medical literature evaluating the efficacy of parthenolide on chronic airway changes of asthma. The aim of the present study was to investigate the effects of parthenolide on chronic changes of lung in a murine model of asthma for the first time.Materials and methodsAnimalsConventionally raised, 6- to 8-week-old, 35 female BALB/c mice weighing 20–25g were used in the experiment. The animals were fed a commercial diet ad libitum and housed in an air-conditioned facility on a 12-h light/12-h dark cycle. The studies adhered to the National Institutes of Health guidelines for the experimental use of animals. The Local Animal Care and Use Committee granted approval for the study.Experimental protocolMice were sensitised by an intraperitoneal (ip) injection of ovalbumin (10μg/0.1ml, two weeks apart, i.e. on day 0 and day 14) consisting of a chicken egg albumin (ovalbumin, grade V, ≥98 pure, Sigma, St. Louis, MO, USA) with alum adjuvant as described by Temelkovski et al.<a class="elsevierStyleCrossRef" href="#bib0200">9</a>. Mice in study groups II, III, IV, V and VI were then challenged with an aerosol of 5ml 2.5% ovalbumin (OVA) in saline for 30min per day on three days of the week for eight weeks beginning from the 21st day of the study. The mice in the control group (group I) received normal saline with alum intraperitoneally on days 0 and 14 of the experiment and aerosolised saline without alum for 30min per day on three days of the week for eight weeks beginning from the 21st day of the study. Exposures were carried out in a whole body inhalation exposure system in a plexiglass chamber with 40×60×120 diameters designed for placement of cages. Temperature and relative humidity were maintained at 20–25°C and 40–60%, respectively. A solution of 2.5% ovalbumin in normal saline was aerosolised by delivery of compressed air to a sidestream jet nebuliser with a flow rate of 6L/min (Medicair, UK) and injected into a chamber. The aerosol generated by this nebuliser comprised >80% particles with a diameter of <4μm. Particle concentration was maintained in the range of 10–20mg/mm3 in the chamber.<a class="elsevierStyleCrossRef" href="#bib0205">10</a>Study drugsMice in group III received dexamethasone 1mg/kg;<a class="elsevierStyleCrossRef" href="#bib0210">11</a> group IV received parthenolide 3μg/g;<a class="elsevierStyleCrossRef" href="#bib0215">12</a> group V received both dexamethasone 1mg/kg and parthenolide 3μg/g; and group II received DMSO (solvent of parthenolide) 50μL<a class="elsevierStyleCrossRef" href="#bib0220">13</a> once a day in the last seven days of the challenge period. Parthenolide was obtained from Calbiochem (Merck Millipore, Darmstadt, Germany). Animals were sacrificed by an overdose of ketamin 24h after the last drug administration. Experimental protocol and study drugs are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Preparations of lung homogenatesAnimals were sacrificed by an overdose of ketamin 24h after the last drug administration. Lungs were removed and washed with cold PBS three times in order to remove blood. Lung tissues were taken into 2ml microcentrifuge tubes and stored at −80°C until analysis. On the study day, frozen lungs were thawed, weighed (60–80mg), transferred into different tubes on ice containing 5ml of stainless beads, 0.1% SDS, protease inhibitor cocktail (Sigma–Aldrich, St. Louis, MO, USA) and 0.1mg/ml phenylmethanesulfonyl fluoride (PMSF) in PBS. Microcentrifuge tubes were transferred to precooled Tissuelyser LT racks and placed into TissueLyser (Qiagen, Germany) homogenisator. Frequency and time were set to 50 and 5min, respectively. The homogenates were then centrifugated at 15,000×g for 1h at 4°C. The supernatants were stored at −80°C.Measurement of cytokinesLevels of IL-4 and IL-5 were quantified in the supernatants of the lung tissue by standard ELISA protocols using commercial mouse IL-4 and IL-5 (Bender MedSystems, MedSystems Diagnostics GmbH, Vienna, Australia). Detection levels were 2.0pg/ml for IL-4 and 3.3pg/ml for IL-5.Histologic evaluationExaminations were conducted blinded by two of the investigators. Tissue specimens were obtained from the mid zone of the left lung of mice. Samples were fixed in 10% formalin for light microscopic evaluation. Some tissue samples of 1–2mm3 taken from adjacent regions were stocked in 2% gluteraldehyde for electron microscopic evaluation. After fixation, samples were embedded in paraffin for light microscopic evaluation. Paraffin blocks were placed in Leica RM2125 rotary microtome (Germany) and serial sections of 5μm thickness were obtained. After choosing the first section randomly, 10 sections in each mouse were selected by skipping over 10 sections and proceeded to the staining process. For light microscopic evaluation, four different staining processes were used. The first 10 samples were stained with haematoxylin and eosin (H&E). In these samples general tissue features were examined and thicknesses of epithelium and subepithelial smooth muscle layers of the medium and small airways were measured. In order to evaluate the thicknesses of epithelium and subepithelial smooth muscle layers, measurements were performed from four points of each airway at levels of 3, 6, 9, and 12 O’clock. Considering that each section contained two to three airways, nearly 20 or more airways were evaluated in each mouse.Photomicrographs were taken by Olympus DP25 (Japan) camera, which was adapted on Olympus CX-41 model microscope (Olympus Optical, Tokyo, Japan). The histological analysis was carried out with a computer-assisted image analyser system (DP2-BSW).The consecutive 10 sections were stained with Toluidine Blue and the other 10 sections with periodic acid–Shiff (PAS). The last sections were stained with Masson Trichrome stain for demonstration of collagen deposition. Photomicrographs were taken randomly from five fields of each section which were stained with Toluidine Blue. For mast cell enumeration, a standard transparent counting frame representing an area of 20,000μm2 was used manually and 10 fields in each photograph were examined for each mouse. Goblet cells stained with PAS were enumerated in 10 sections of each mouse. In each section, three to five randomly selected airways were photographed. Circumferences of all airways were measured and goblet cell numbers in these areas were recorded. For standardisation, goblet cell numbers in 100μm were analysed by division of total goblet cell number to the total length of airway circumferences and multiplying the result by 100.For ultrastructural investigations, the tissues were postfixed with osmium tetroxide (OsO4), dehydrated in a graded series of alcohol, and then embedded in Araldite® CY212. The thin (60–90nm) sections were obtained with ultra-microtome (Leica) and stained with uranyl acetate and lead citrate, examined on a transmission electron microscope (Carl Zeiss Libra 120 EFTEM, Germany), and digitally photographed. In each mouse, five to seven ultrathin sections were taken from each two blocks and epithelium of the airway, the surrounding structures, and the intercellular connections were evaluated. Thicknesses of the basement membrane of the respiratory epithelium were measured from 20 points that were at equal distances to each other and the data were recorded.Statistical analysisSPSS 15.0 package programme was used in the statistical analysis. Data were presented as mean±standard deviation (SD) in each group. All data were analysed by Kruskal–Wallis and then Mann–Whitney test for dual comparisons. p<0.05 was considered statistically significant.ResultsEach group consisted of seven mice at the beginning of the experiment and all of the mice completed the study. We compared the control group with the placebo in order to show that the model of asthma was established. In the placebo group, all histologic parameters, namely thickness of basal membrane, epithelium and subepithelial smooth muscle layer and the number of mast cells and goblet cells were significantly higher than the control group (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). These results showed that the model of chronic asthma was established.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>In Group III (Dexamethasone) all histologic parameters were improved when compared with placebo (p<0.05, <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). In Group IV (Parthenolide), basal membrane thickness, subepithelial smooth muscle thickness and epithelial thickness were significantly lower when compared to placebo group (p<0.05) while the number of mast and goblet cells were similar with the placebo group (p<0.05). When histological parameters of Group IV were compared with Group III, dexamethasone seems to be superior in lowering subepithelial smooth muscle thickness, epithelial thickness and the number of goblet cells (p<0.05) but the effect of two drugs was similar in basal membrane thickness and the number of mast cells (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).In Group V in which the study drugs were parthenolide and dexamethasone combination, all histologic parameters were significantly better compared to placebo and improvement was similar to dexamethasone in all parameters except epithelial thickness and the number of goblet cells (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This showed that this combination did not add any improvement on administration of dexamethasone alone.Interleukin 4 and 5 levels were significantly higher in placebo group compared to control group, as expected. Only significant decreases of IL-4 levels were detected in study groups when compared with placebo. Interleukin-5 levels of the groups III, IV and V were all similar with the placebo group (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionParthenolide, a naturally occurring molecule derived from feverfew (T. Parthenium) exhibits its anti-inflammatory properties by inhibition of NF-κB and resulting decreased signal induction of pro-inflammatory cytokines.<a class="elsevierStyleCrossRefs" href="#bib0225">14–16</a> Anti-inflammatory effects of parthenolide are also mediated by inhibition of prostoglandin synthesis.<a class="elsevierStyleCrossRefs" href="#bib0240">17–19</a> Although parthenolide has been used for asthma therapy for many centuries, there is no study investigating the role of parthenolide in asthma therapy. We firstly demonstrated that parthenolide was partially effective in reversing abnormal histological findings of asthma in a murine model of asthma.Nuclear factor-κB which is the target of parthenolide, has a critical role in the pathogenesis of lung diseases.<a class="elsevierStyleCrossRef" href="#bib0255">20</a> Nuclear factor-κB activation has been shown to be robust and prolonged in airway epithelium of asthmatics.<a class="elsevierStyleCrossRef" href="#bib0260">21</a> Activation of NF-κB in airways of allergen sensitised mice also resulted in enhancement of the inflammation and airway hyperesponsiveness<a class="elsevierStyleCrossRef" href="#bib0265">22</a>. On the contrary, it has been shown that mucus secretion, Th2 cytokines and cellular infiltration were diminished when NF-κB activation was inhibited in a murine model of asthma.<a class="elsevierStyleCrossRef" href="#bib0270">23</a> In another study with OVA-sensitised mice having Clara cell specific IKK-β deletions, peribronchial fibrosis, airway eosinophilia, eotaxin and TARC chemokine were diminished when compared with mice having functional IKK-β.<a class="elsevierStyleCrossRef" href="#bib0275">24</a> All these studies highlighted the importance of NF-κB pathway in asthma and paved the way for studies about therapeutics inhibiting NF-κB pathway and effects of existing therapeutics on NF-κB pathway.<a class="elsevierStyleCrossRef" href="#bib0280">25</a> Decoy oligonucleotides and small molecules inhibiting NF-κB were studied in animal models of asthma and it is concluded that inhibition of NF-κB resulted in a decrease in inflammatory cytokines, mucus secretion and airway hyperresponsiveness.<a class="elsevierStyleCrossRefs" href="#bib0285">26,27</a>Parthenolide, a naturally occurring inhibitor of NF-κB, is used in only a few studies involving respiratory cell lines. A study investigating the role of parthenolide in cultured human respiratory epithelial cells showed that parthenolide inhibited NF-κB activity by IL-8 gene expression in these human respiratory epithelial cell lines.<a class="elsevierStyleCrossRef" href="#bib0295">28</a> In a study using defective cystic fibrosis transmembrane conductance regulator (CFTR) cell lines and CFTR- knockout mice, it is also shown that parthenolide inhibited IL-8 secretion and prevented NF-κB activation, IκBα degradation and IκB kinase activity. Inhibiting NF-κB translocation resulted in attenuation of subsequent inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0300">29</a>In our study, parthenolide has been shown to improve most of the histopathological parameters in a murine model of asthma when compared with placebo. Histological parameters except the number of goblet cells and mast cells significantly improved in the group receiving parthenolide while in the group receiving dexamethasone, all histological parameters improved significantly compared to placebo. Dexamethasone was superior to parthenolide in most of the parameters except basal membrane thickness and number of mast cells. Combination of parthenolide and dexamethasone also had no additional benefit over dexamethasone therapy. We only detected decrease of IL-4 levels in the study groups (receiving either dexamethasone or parthenolide) suggesting that parthenolide may exert its anti-inflammatory properties by IL-4 similar to dexamethasone. This seems different from a previous study investigating the consequences of NF-κB inhibition by decoy oligonucleotides in experimental asthma.<a class="elsevierStyleCrossRef" href="#bib0285">26</a> Nuclear factor-κB decoys inhibited IL-5, IL-13 and eotaxin but did not change IL-4 production in the airways of OVA-challenged mice.<a class="elsevierStyleCrossRef" href="#bib0285">26</a> Although it is known that typical Th2 cytokines are often coordinately expressed, selective production of IL-4 or IL-5 has been reported in several situations and this may be attributed to differential transcription factor activation or inhibition.<a class="elsevierStyleCrossRefs" href="#bib0305">30,31</a>In conclusion, administration of parthenolide partially alleviated airway inflammation and remodelling in a murine model of asthma and combination therapy with dexamethasone did not have additive effects. Parthenolide as a naturally occurring NF-κB inhibitor exhibiting anti-inflammatory properties is still a prominent candidate for further studies and drug development. But specific mechanisms regarding its effects in asthma should be elucidated in oncoming studies of parthenolide.Ethical disclosuresConfidentiality of dataThe authors declare that no patient data appears in this article.Right to privacy and informed consentThe authors declare that no patient data appears in this article.Protection of human subjects and animals in researchThe authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.Authors’ contributionsZAA and NU contributed in design of the study, OY and MK participated in animal study of the work, SO carried out conventional histological work, AB carried out electron microscopy, OK participated in design and coordination of the work. ZAA wrote the manuscript. All authors read and approved the manuscript.Conflict of interestThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres783848" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aim of the study" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec782735" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Animals" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Experimental protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Study drugs" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Preparations of lung homogenates" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Measurement of cytokines" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Histologic evaluation" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0060" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Confidentiality of data" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Protection of human subjects and animals in research" ] ] ] 7 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors’ contributions" ] 8 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-16" "fechaAceptado" => "2016-06-22" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec782735" "palabras" => array:5 [ 0 => "Asthma" 1 => "Lung histology" 2 => "Murine model" 3 => "Parthenolide" 4 => "Tanacetum Parthenium" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundParthenolide is the active constituent of the plant ‘Tanacetum parthenium’ (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. Aim of the studyIn this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. Materials and methodsThirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. ResultsHistologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. ConclusionWe demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aim of the study" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2148 "Ancho" => 3295 "Tamanyo" => 1413667 ] ] "descripcion" => array:1 [ "en" => "Light and electron microscopic findings of study groups. I; control (n:7), II; placebo (n:7), III; dexamethasone (n:7), IV; parthenolide (n:7), V; parthenolide and dexamethasone (n:7), A; H&E, B; PAS, C; Toluidine staining. (A) Arrow with two heads; sub-epithelial smooth muscle thickening, * peribronchial mononuclear cell infiltration. (B) arrows; goblet cells (C) arrows; mast cells. (D) Electron microscopic views. Increased goblet cells in placebo group (Gc), smooth muscle thickening (Sm)." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "fx1.jpeg" "imagenAlto" => 1645 "imagenAncho" => 1961 "imagenTamanyo" => 195846 ] ] ] ] ] "descripcion" => array:1 [ "en" => "Schematic presentation of the experimental drugs and study drugs." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "n:7 in each group." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group I \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Placebo group II \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dexamethasone group III (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parthenolide group IV \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dexamethasone and parthenolide group V \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subepithelial smooth muscle thickness (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">322.94±16.15<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">653.83±18.36<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">508.89±11.61<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">553.93±15.86<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">511.02±10.99 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epithelial thickness (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.40±0.05<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.93±0.12<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.75±0.06<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5±0.13<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.68±0.15<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of goblet cells/100 (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.55±0.18<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.69±0.31<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.96±0.12<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.6±0.17<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.88±0.16<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of mast cells/16,400 (μm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5±0.04<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.45±0.05<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.96±0.07<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.21±0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.41±0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal membrane thickness (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4±0.02<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.44±0.05<a class="elsevierStyleCrossRef" href="#tblfn0010">¥</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.17±0.04<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.15±0.11<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.3±0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1302789.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p<0.05 compared with placebo." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "¥" "nota" => "p<0.05 compared with dexamethasone." ] ] ] "descripcion" => array:1 [ "en" => "Histological comparison of the study groups." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "n:7 in each group." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-5 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.84±32.46<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.44±32.26<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">133.26±74.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">179.39±92.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dexamethasone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.67±46.61<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">163.39±59.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Parthenolide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.52±34.04<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">191.17±106.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Parthenolide and dexamethasone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.30±16.88<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">143.12±56.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1302788.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "p<0.05 when compared with placebo." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of IL-4 and IL-5 between study groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0160" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inflammatory mediators of asthma: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.J. Barnes" 1 => "K.F. Chung" 2 => "C.P. Page" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pharmacol Rev" "fecha" => "1998" "volumen" => "50" "paginaInicial" => "515" "paginaFinal" => "596" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9860804" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0165" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Persistent activation of nuclear factor-kappa B signaling pathway in severe uncontrolled asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Gagliardo" 1 => "P. Chanez" 2 => "M. Mathieu" 3 => "A. Bruno" 4 => "G. Costanzo" 5 => "C. Gougat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200205-479OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2003" "volumen" => "168" "paginaInicial" => "1190" "paginaFinal" => "1198" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12893643" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0170" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation of NF-kappa B in bronchial epithelial cells from children with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Zhao" 1 => "Y. Qi" 2 => "X. Liu" 3 => "Q. Jiang" 4 => "S. Liu" 5 => "Y. Jiang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin Med J" "fecha" => "2001" "volumen" => "114" "paginaInicial" => "909" "paginaFinal" => "911" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11780379" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0175" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A critical role for NF-kappa B in GATA3 expression and Th2 differentiation in allergic airway inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Das" 1 => "C.H. Chen" 2 => "L. Yang" 3 => "L. Chon" 4 => "P. Ray" 5 => "A. Ray" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Nat Immunol" "fecha" => "2001" "volumen" => "2" "paginaInicial" => "45" "paginaFinal" => "50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11135577" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0180" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Essential role of nuclear factor kappa B in the induction of eosinophilia in allergic airway inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Yang" 1 => "L. Chon" 2 => "D.H. Zhang" 3 => "R. Homer" 4 => "A. Ray" 5 => "P. Ray" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Exp Med" "fecha" => "1998" "volumen" => "188" "paginaInicial" => "1739" "paginaFinal" => "1750" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9802985" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0185" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of inhaled corticosteroids in asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.J. Barnes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1998" "volumen" => "102" "paginaInicial" => "531" "paginaFinal" => "538" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9802359" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0190" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the Ikappa B kinase complex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.P. Hehner" 1 => "T.G. Hofman" 2 => "W. Droge" 3 => "M.L. Schmitz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "1998" "volumen" => "163" "paginaInicial" => "5617" "paginaFinal" => "5623" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10553091" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0195" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of transcription factor NF-kappa B by sesquiterpene lactones: a proposed molecular mechanism of action" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Rüngeler" 1 => "V. Castro" 2 => "G. Mora" 3 => "N. Gören" 4 => "W. Vichnewski" 5 => "H.L. Pahl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bioorg Med Chem" "fecha" => "1999" "volumen" => "7" "paginaInicial" => "2343" "paginaFinal" => "2352" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10632044" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0200" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Temelkovski" 1 => "S.P. Hogan" 2 => "D.P. Shepherd" 3 => "P.S. Foster" 4 => "R.K. Kumar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1998" "volumen" => "53" "paginaInicial" => "849" "paginaFinal" => "856" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10193371" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0205" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of curcumin on lung histology and fungal burden in a mouse model of chronic asthma and oropharyngeal candidiasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Karaman" 1 => "Z. Arıkan Ayyıldız" 2 => "F. Fırıncı" 3 => "M. Kiray" 4 => "A. Bağrıyanık" 5 => "O. Yilmaz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arcmed.2011.01.011" "Revista" => array:6 [ "tituloSerie" => "Arch Med Res" "fecha" => "2011" "volumen" => "42" "paginaInicial" => "79" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21565619" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0210" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W.R. Henderson Jr." 1 => "G.K. Chiang" 2 => "Y.T. Tien" 3 => "E.Y. Chi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200501-088OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2006" "volumen" => "173" "paginaInicial" => "718" "paginaFinal" => "728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16387808" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0215" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parthenolide inhibits IκB kinase, NF-κB activation, and inflammatory response in cystic fibrosis cells and mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Saadane" 1 => "S. Masters" 2 => "J. DiDonato" 3 => "J. Li" 4 => "M. Berger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/rcmb.2006-0323OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2007" "volumen" => "36" "paginaInicial" => "728" "paginaFinal" => "736" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17272824" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0220" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparative effects of the herbal constituent parthenolide (feverfew) on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.T. Smolinski" 1 => "J.J. Pestka" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Inflamm (Lond)" "fecha" => "2005" "volumen" => "29" "paginaInicial" => "2" "paginaFinal" => "6" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0225" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B.H. Kwok" 1 => "B. Koh" 2 => "M.I. Ndubuisi" 3 => "M. Elofsson" 4 => "C.M. Crews" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chem Biol" "fecha" => "2001" "volumen" => "8" "paginaInicial" => "759" "paginaFinal" => "766" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11514225" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0230" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-inflammatory activity of parthenolide-depleted feverfew (Tanacetum parthenium)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Sur" 1 => "K. Martin" 2 => "F. Liebel" 3 => "P. Lyte" 4 => "S. Shapiro" 5 => "M. Southall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10787-008-8040-9" "Revista" => array:6 [ "tituloSerie" => "Inflammopharmacology" "fecha" => "2009" "volumen" => "17" "paginaInicial" => "42" "paginaFinal" => "49" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19112586" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0235" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "V.B. Mathema" 1 => "Y.S. Koh" 2 => "B.C. Thakuri" 3 => "M. Silanpää" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10753-011-9346-0" "Revista" => array:6 [ "tituloSerie" => "Inflammation" "fecha" => "2012" "volumen" => "35" "paginaInicial" => "560" "paginaFinal" => "565" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21603970" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0240" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Feverfew (Tanacetum parthenium L.): a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Pareek" 1 => "M. Suthar" 2 => "G.S. Rathore" 3 => "V. Bansal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0973-7847.79105" "Revista" => array:6 [ "tituloSerie" => "Pharmacogn Rev" "fecha" => "2011" "volumen" => "5" "paginaInicial" => "103" "paginaFinal" => "110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22096324" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0245" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.N. Makheja" 1 => "J.M. Bailey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Prostoglandins Leukot Med" "fecha" => "1982" "volumen" => "8" "paginaInicial" => "653" "paginaFinal" => "660" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0250" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prostoglandin synthetase inhibitors in feverfew" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.J. Pugh" 1 => "K. Sambo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Pharmacol" "fecha" => "1998" "volumen" => "40" "paginaInicial" => "743" "paginaFinal" => "745" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0255" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.G. Wright" 1 => "J.W. Christman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Respir Med" "fecha" => "2003" "volumen" => "2" "paginaInicial" => "211" "paginaFinal" => "219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14720003" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0260" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Kato" 1 => "R.P. Schleimer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.coi.2007.08.004" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Immunol" "fecha" => "2007" "volumen" => "19" "paginaInicial" => "711" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17928212" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0265" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nuclear factor kappa B induction in airway epithelium increases lung inflammation in allergen- challenged mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.R. Scheller" 1 => "V.V. Polosukhin" 2 => "D. Mitchell" 3 => "D.S. Cheng" 4 => "R.S. Peebles" 5 => "T.S. Blackwell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/01902140903019710" "Revista" => array:6 [ "tituloSerie" => "Exp Lung Res" "fecha" => "2009" "volumen" => "35" "paginaInicial" => "883" "paginaFinal" => "895" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19995280" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0270" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nf-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.E. Poynter" 1 => "R. Cloots" 2 => "T. van Woerkom" 3 => "K.J. Butnor" 4 => "P. Vacek" 5 => "D.J. Taatjes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "2004" "volumen" => "173" "paginaInicial" => "7003" "paginaFinal" => "7009" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15557197" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0275" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in the airway epithelium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.H. Broide" 1 => "T. Lawrence" 2 => "T. Doherty" 3 => "J.Y. Cho" 4 => "M. Miller" 5 => "K. McElwain" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2005" "volumen" => "102" "paginaInicial" => "177723" "paginaFinal" => "177728" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0280" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.R. Edwards" 1 => "N.W. Bartlett" 2 => "D. Clarke" 3 => "M.A. Birrell" 4 => "M. Belvisi" 5 => "S.L. Johnston" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pharmthera.2008.09.003" "Revista" => array:6 [ "tituloSerie" => "Pharmacol Ther" "fecha" => "2009" "volumen" => "121" "paginaInicial" => "1" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18950657" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0285" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IkappaB kinase-2 inhibitor blocks inflammation in human airway smooth muscle and a rat model of asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Birrell" 1 => "E. Hardaker" 2 => "S. Wong" 3 => "K. McCluskie" 4 => "M. Catley" 5 => "J. De Alba" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200412-1647OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2005" "volumen" => "172" "paginaInicial" => "962" "paginaFinal" => "971" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16002568" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0290" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Desmet" 1 => "P. Gosset" 2 => "B. Pajak" 3 => "D. Cataldo" 4 => "M. Bentires-Alj" 5 => "P. Lekeux" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "2004" "volumen" => "173" "paginaInicial" => "5766" "paginaFinal" => "5775" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15494529" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0295" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sesquiterpene lactones are potent inhibitors of interleukin 8 gene expression in cultured human respiratory epithelium" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.L. Mazor" 1 => "I.Y. Menendez" 2 => "M.A. Ryan" 3 => "M.A. Fiedler" 4 => "H.R. Wong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/cyto.1999.0526" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2000" "volumen" => "12" "paginaInicial" => "239" "paginaFinal" => "245" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10704251" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0300" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parthenolide inhibits ERK and AP-1 which are dysregulated and contribute to excessive IL-8 expression and secretion in cystic fibrosis cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Saadane" 1 => "J. Eastman" 2 => "M. Berger" 3 => "T.L. Bonfield" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Inflamm (Lond)" "fecha" => "2011" "volumen" => "8" "paginaInicial" => "26" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0305" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Ray" 1 => "L. Chon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI8204" "Revista" => array:5 [ "tituloSerie" => "J Clin Invest" "fecha" => "1999" "volumen" => "104" "paginaInicial" => "985" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10525032" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0310" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dissociation of production of IL-4 and IL-5" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.A. Sewell" 1 => "H.H. Mu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/icb.1996.48" "Revista" => array:5 [ "tituloSerie" => "Immunol Cell Biol" "fecha" => "1996" "volumen" => "74" "paginaInicial" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8799728" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004500000001/v1_201612300037/S0301054616301057/v1_201612300037/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004500000001/v1_201612300037/S0301054616301057/v1_201612300037/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054616301057?idApp=UINPBA00004N"]

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Original Article

Z. Arıkan-Ayyıldıza,

Corresponding author

zarikanayyildiz@gmail.com
zeynep.ayyildiz@deu.edu.tr

Corresponding author.

, M. Karamanb, S. Özbalc, A. Bağrıyanıkc, O. Yilmazb, Ö. Karamana, N. Uzunera

a Department of Pediatric Allergy, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey

b Department of Experimental Animal Laboratory, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey

c Department of Histology and Embryology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey

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In previous studies it has been demonstrated that levels of NF-&#954;B p65 and NF-&#954;B p50 were increased in asthmatic patients&#44; while in mice lacking NF-&#954;B p50&#44; diminished eosinophilic infiltration was observed in response to an aerolised allergen in a model of allergic asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#8211;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Current strategies for the management of asthma focus mainly on suppressing airway inflammation&#44; and steroids are the most effective anti-inflammatory drugs in asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> Inhaled steroids are currently the mainstay of asthma therapy but they also have several systemic and local side effects when used at high doses for a long time&#46; Research for the use of alternative and complementary treatments that reverse histopathological changes and have fewer side effects is continuously increasing&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Sesquiterpene lactones are the active constituents of medicinal plants from the Asteraceae family which have been used for centuries as a folk remedy in inflammatory conditions such as migraine&#44; inflammation and arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">7&#44;8</span></a> Parthenolide is one of the important sesquiterpene lactones found in plant <span class="elsevierStyleItalic">Tanacetum Parthenium &#40;feverfew&#41;</span> and the active constituent of this plant is responsible for its inflammatory effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">7&#44;8</span></a> Previous studies suggest that anti-inflammatory effects of parthenolide are related to inhibition of NF-&#954;B pathway&#46; As this pathway is also known to be active in asthma pathogenesis&#44; it may be speculated that parthenolide may be beneficial in the treatment of asthma&#46; To our knowledge there is no study in the medical literature evaluating the efficacy of parthenolide on chronic airway changes of asthma&#46; The aim of the present study was to investigate the effects of parthenolide on chronic changes of lung in a murine model of asthma for the first time&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Animals</span><p id="par0020" class="elsevierStylePara elsevierViewall">Conventionally raised&#44; 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Temperature and relative humidity were maintained at 20&#8211;25<span class="elsevierStyleHsp" style=""></span>&#176;C and 40&#8211;60&#37;&#44; respectively&#46; A solution of 2&#46;5&#37; ovalbumin in normal saline was aerosolised by delivery of compressed air to a sidestream jet nebuliser with a flow rate of 6<span class="elsevierStyleHsp" style=""></span>L&#47;min &#40;Medicair&#44; UK&#41; and injected into a chamber&#46; The aerosol generated by this nebuliser comprised &#62;80&#37; particles with a diameter of &#60;4<span class="elsevierStyleHsp" style=""></span>&#956;m&#46; Particle concentration was maintained in the range of 10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;mm<span class="elsevierStyleSup">3</span> in the chamber&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Study drugs</span><p id="par0030" class="elsevierStylePara elsevierViewall">Mice in group III received dexamethasone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">11</span></a> group IV received parthenolide 3<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#59;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">12</span></a> group V received both dexamethasone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and parthenolide 3<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#59; and group II received DMSO &#40;solvent of parthenolide&#41; 50<span class="elsevierStyleHsp" style=""></span>&#956;L<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> once a day in the last seven days of the challenge period&#46; Parthenolide was obtained from Calbiochem &#40;Merck Millipore&#44; Darmstadt&#44; Germany&#41;&#46; Animals were sacrificed by an overdose of ketamin 24<span class="elsevierStyleHsp" style=""></span>h after the last drug administration&#46; Experimental protocol and study drugs are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Preparations of lung homogenates</span><p id="par0035" class="elsevierStylePara elsevierViewall">Animals were sacrificed by an overdose of ketamin 24<span class="elsevierStyleHsp" style=""></span>h after the last drug administration&#46; Lungs were removed and washed with cold PBS three times in order to remove blood&#46; Lung tissues were taken into 2<span class="elsevierStyleHsp" style=""></span>ml microcentrifuge tubes and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until analysis&#46; On the study day&#44; frozen lungs were thawed&#44; weighed &#40;60&#8211;80<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; transferred into different tubes on ice containing 5<span class="elsevierStyleHsp" style=""></span>ml of stainless beads&#44; 0&#46;1&#37; SDS&#44; protease inhibitor cocktail &#40;Sigma&#8211;Aldrich&#44; St&#46; Louis&#44; MO&#44; USA&#41; and 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;ml phenylmethanesulfonyl fluoride &#40;PMSF&#41; in PBS&#46; Microcentrifuge tubes were transferred to precooled Tissuelyser LT racks and placed into TissueLyser &#40;Qiagen&#44; Germany&#41; homogenisator&#46; Frequency and time were set to 50 and 5<span class="elsevierStyleHsp" style=""></span>min&#44; respectively&#46; The homogenates were then centrifugated at 15&#44;000<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span> for 1<span class="elsevierStyleHsp" style=""></span>h at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The supernatants were stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Measurement of cytokines</span><p id="par0040" class="elsevierStylePara elsevierViewall">Levels of IL-4 and IL-5 were quantified in the supernatants of the lung tissue by standard ELISA protocols using commercial mouse IL-4 and IL-5 &#40;Bender MedSystems&#44; MedSystems Diagnostics GmbH&#44; Vienna&#44; Australia&#41;&#46; Detection levels were 2&#46;0<span class="elsevierStyleHsp" style=""></span>pg&#47;ml for IL-4 and 3&#46;3<span class="elsevierStyleHsp" style=""></span>pg&#47;ml for IL-5&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Histologic evaluation</span><p id="par0045" class="elsevierStylePara elsevierViewall">Examinations were conducted blinded by two of the investigators&#46; Tissue specimens were obtained from the mid zone of the left lung of mice&#46; Samples were fixed in 10&#37; formalin for light microscopic evaluation&#46; Some tissue samples of 1&#8211;2<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">3</span> taken from adjacent regions were stocked in 2&#37; gluteraldehyde for electron microscopic evaluation&#46; After fixation&#44; samples were embedded in paraffin for light microscopic evaluation&#46; Paraffin blocks were placed in Leica RM2125 rotary microtome &#40;Germany&#41; and serial sections of 5<span class="elsevierStyleHsp" style=""></span>&#956;m thickness were obtained&#46; After choosing the first section randomly&#44; 10 sections in each mouse were selected by skipping over 10 sections and proceeded to the staining process&#46; For light microscopic evaluation&#44; four different staining processes were used&#46; The first 10 samples were stained with haematoxylin and eosin &#40;H&#38;E&#41;&#46; In these samples general tissue features were examined and thicknesses of epithelium and subepithelial smooth muscle layers of the medium and small airways were measured&#46; In order to evaluate the thicknesses of epithelium and subepithelial smooth muscle layers&#44; measurements were performed from four points of each airway at levels of 3&#44; 6&#44; 9&#44; and 12 O&#8217;clock&#46; Considering that each section contained two to three airways&#44; nearly 20 or more airways were evaluated in each mouse&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Photomicrographs were taken by Olympus DP25 &#40;Japan&#41; camera&#44; which was adapted on Olympus CX-41 model microscope &#40;Olympus Optical&#44; Tokyo&#44; Japan&#41;&#46; The histological analysis was carried out with a computer-assisted image analyser system &#40;DP2-BSW&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The consecutive 10 sections were stained with Toluidine Blue and the other 10 sections with periodic acid&#8211;Shiff &#40;PAS&#41;&#46; The last sections were stained with Masson Trichrome stain for demonstration of collagen deposition&#46; Photomicrographs were taken randomly from five fields of each section which were stained with Toluidine Blue&#46; For mast cell enumeration&#44; a standard transparent counting frame representing an area of 20&#44;000<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> was used manually and 10 fields in each photograph were examined for each mouse&#46; Goblet cells stained with PAS were enumerated in 10 sections of each mouse&#46; In each section&#44; three to five randomly selected airways were photographed&#46; Circumferences of all airways were measured and goblet cell numbers in these areas were recorded&#46; For standardisation&#44; goblet cell numbers in 100<span class="elsevierStyleHsp" style=""></span>&#956;m were analysed by division of total goblet cell number to the total length of airway circumferences and multiplying the result by 100&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">For ultrastructural investigations&#44; the tissues were postfixed with osmium tetroxide &#40;OsO<span class="elsevierStyleInf">4</span>&#41;&#44; dehydrated in a graded series of alcohol&#44; and then embedded in Araldite<span class="elsevierStyleSup">&#174;</span> CY212&#46; The thin &#40;60&#8211;90<span class="elsevierStyleHsp" style=""></span>nm&#41; sections were obtained with ultra-microtome &#40;Leica&#41; and stained with uranyl acetate and lead citrate&#44; examined on a transmission electron microscope &#40;Carl Zeiss Libra 120 EFTEM&#44; Germany&#41;&#44; and digitally photographed&#46; In each mouse&#44; five to seven ultrathin sections were taken from each two blocks and epithelium of the airway&#44; the surrounding structures&#44; and the intercellular connections were evaluated&#46; Thicknesses of the basement membrane of the respiratory epithelium were measured from 20 points that were at equal distances to each other and the data were recorded&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">SPSS 15&#46;0 package programme was used in the statistical analysis&#46; Data were presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; in each group&#46; All data were analysed by Kruskal&#8211;Wallis and then Mann&#8211;Whitney test for dual comparisons&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Each group consisted of seven mice at the beginning of the experiment and all of the mice completed the study&#46; We compared the control group with the placebo in order to show that the model of asthma was established&#46; In the placebo group&#44; all histologic parameters&#44; namely thickness of basal membrane&#44; epithelium and subepithelial smooth muscle layer and the number of mast cells and goblet cells were significantly higher than the control group &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; These results showed that the model of chronic asthma was established&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In Group III &#40;Dexamethasone&#41; all histologic parameters were improved when compared with placebo &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; In Group IV &#40;Parthenolide&#41;&#44; basal membrane thickness&#44; subepithelial smooth muscle thickness and epithelial thickness were significantly lower when compared to placebo group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; while the number of mast and goblet cells were similar with the placebo group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; When histological parameters of Group IV were compared with Group III&#44; dexamethasone seems to be superior in lowering subepithelial smooth muscle thickness&#44; epithelial thickness and the number of goblet cells &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; but the effect of two drugs was similar in basal membrane thickness and the number of mast cells &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In Group V in which the study drugs were parthenolide and dexamethasone combination&#44; all histologic parameters were significantly better compared to placebo and improvement was similar to dexamethasone in all parameters except epithelial thickness and the number of goblet cells &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This showed that this combination did not add any improvement on administration of dexamethasone alone&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Interleukin 4 and 5 levels were significantly higher in placebo group compared to control group&#44; as expected&#46; Only significant decreases of IL-4 levels were detected in study groups when compared with placebo&#46; Interleukin-5 levels of the groups III&#44; IV and V were all similar with the placebo group &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Parthenolide&#44; a naturally occurring molecule derived from feverfew &#40;<span class="elsevierStyleItalic">T&#46; Parthenium</span>&#41; exhibits its anti-inflammatory properties by inhibition of NF-&#954;B and resulting decreased signal induction of pro-inflammatory cytokines&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">14&#8211;16</span></a> Anti-inflammatory effects of parthenolide are also mediated by inhibition of prostoglandin synthesis&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">17&#8211;19</span></a> Although parthenolide has been used for asthma therapy for many centuries&#44; there is no study investigating the role of parthenolide in asthma therapy&#46; We firstly demonstrated that parthenolide was partially effective in reversing abnormal histological findings of asthma in a murine model of asthma&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Nuclear factor-&#954;B which is the target of parthenolide&#44; has a critical role in the pathogenesis of lung diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a> Nuclear factor-&#954;B activation has been shown to be robust and prolonged in airway epithelium of asthmatics&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">21</span></a> Activation of NF-&#954;B in airways of allergen sensitised mice also resulted in enhancement of the inflammation and airway hyperesponsiveness<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">22</span></a>&#46; On the contrary&#44; it has been shown that mucus secretion&#44; Th2 cytokines and cellular infiltration were diminished when NF-&#954;B activation was inhibited in a murine model of asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">23</span></a> In another study with OVA-sensitised mice having Clara cell specific IKK-&#946; deletions&#44; peribronchial fibrosis&#44; airway eosinophilia&#44; eotaxin and TARC chemokine were diminished when compared with mice having functional IKK-&#946;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a> All these studies highlighted the importance of NF-&#954;B pathway in asthma and paved the way for studies about therapeutics inhibiting NF-&#954;B pathway and effects of existing therapeutics on NF-&#954;B pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">25</span></a> Decoy oligonucleotides and small molecules inhibiting NF-&#954;B were studied in animal models of asthma and it is concluded that inhibition of NF-&#954;B resulted in a decrease in inflammatory cytokines&#44; mucus secretion and airway hyperresponsiveness&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Parthenolide&#44; a naturally occurring inhibitor of NF-&#954;B&#44; is used in only a few studies involving respiratory cell lines&#46; A study investigating the role of parthenolide in cultured human respiratory epithelial cells showed that parthenolide inhibited NF-&#954;B activity by IL-8 gene expression in these human respiratory epithelial cell lines&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a> In a study using defective cystic fibrosis transmembrane conductance regulator &#40;CFTR&#41; cell lines and CFTR- knockout mice&#44; it is also shown that parthenolide inhibited IL-8 secretion and prevented NF-&#954;B activation&#44; I&#954;B&#945; degradation and I&#954;B kinase activity&#46; Inhibiting NF-&#954;B translocation resulted in attenuation of subsequent inflammatory response&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In our study&#44; parthenolide has been shown to improve most of the histopathological parameters in a murine model of asthma when compared with placebo&#46; Histological parameters except the number of goblet cells and mast cells significantly improved in the group receiving parthenolide while in the group receiving dexamethasone&#44; all histological parameters improved significantly compared to placebo&#46; Dexamethasone was superior to parthenolide in most of the parameters except basal membrane thickness and number of mast cells&#46; Combination of parthenolide and dexamethasone also had no additional benefit over dexamethasone therapy&#46; We only detected decrease of IL-4 levels in the study groups &#40;receiving either dexamethasone or parthenolide&#41; suggesting that parthenolide may exert its anti-inflammatory properties by IL-4 similar to dexamethasone&#46; This seems different from a previous study investigating the consequences of NF-&#954;B inhibition by decoy oligonucleotides in experimental asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a> Nuclear factor-&#954;B decoys inhibited IL-5&#44; IL-13 and eotaxin but did not change IL-4 production in the airways of OVA-challenged mice&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a> Although it is known that typical Th2 cytokines are often coordinately expressed&#44; selective production of IL-4 or IL-5 has been reported in several situations and this may be attributed to differential transcription factor activation or inhibition&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In conclusion&#44; administration of parthenolide partially alleviated airway inflammation and remodelling in a murine model of asthma and combination therapy with dexamethasone did not have additive effects&#46; Parthenolide as a naturally occurring NF-&#954;B inhibitor exhibiting anti-inflammatory properties is still a prominent candidate for further studies and drug development&#46; But specific mechanisms regarding its effects in asthma should be elucidated in oncoming studies of parthenolide&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical disclosures</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Protection of human subjects and animals in research</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Authors&#8217; contributions</span><p id="par0130" class="elsevierStylePara elsevierViewall">ZAA and NU contributed in design of the study&#44; OY and MK participated in animal study of the work&#44; SO carried out conventional histological work&#44; AB carried out electron microscopy&#44; OK participated in design and coordination of the work&#46; ZAA wrote the manuscript&#46; All authors read and approved the manuscript&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Preparations of lung homogenates"
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              "titulo" => "Measurement of cytokines"
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          "titulo" => "References"
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    "fechaRecibido" => "2016-02-16"
    "fechaAceptado" => "2016-06-22"
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            0 => "Asthma"
            1 => "Lung histology"
            2 => "Murine model"
            3 => "Parthenolide"
            4 => "<span class="elsevierStyleItalic">Tanacetum Parthenium</span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Parthenolide is the active constituent of the plant &#8216;<span class="elsevierStyleItalic">Tanacetum parthenium&#8217;</span> &#40;Feverfew&#41; which has been used for centuries as a folk remedy for inflammatory conditions&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aim of the study</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-five BALB&#47;c mice were divided into five groups&#59; I &#40;control&#41;&#44; II &#40;placebo&#41;&#44; III &#40;dexamethasone&#41;&#44; IV &#40;parthenolide&#41; and V &#40;dexamethasone and parthenolide combination&#41;&#46; Lung histology was evaluated after treatment with the study drugs&#46; Levels of interleukin &#40;IL&#41;-4 and IL-5 were determined by ELISA&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo&#46; All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group&#46; Improvement of most of the histologic parameters was similar in Groups III and V&#46; Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma&#46; But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment&#46;</p></span>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Light and electron microscopic findings of study groups&#46; I&#59; control &#40;n&#58;7&#41;&#44; II&#59; placebo &#40;n&#58;7&#41;&#44; III&#59; dexamethasone &#40;n&#58;7&#41;&#44; IV&#59; parthenolide &#40;n&#58;7&#41;&#44; V&#59; parthenolide and dexamethasone &#40;n&#58;7&#41;&#44; A&#59; H&#38;E&#44; B&#59; PAS&#44; C&#59; Toluidine staining&#46; &#40;A&#41; Arrow with two heads&#59; sub-epithelial smooth muscle thickening&#44; &#42; peribronchial mononuclear cell infiltration&#46; &#40;B&#41; arrows&#59; goblet cells &#40;C&#41; arrows&#59; mast cells&#46; &#40;D&#41; Electron microscopic views&#46; Increased goblet cells in placebo group &#40;Gc&#41;&#44; smooth muscle thickening &#40;Sm&#41;&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control<br>group I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Placebo<br>group II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dexamethasone<br>group III<br>&#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parthenolide<br>group IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dexamethasone and parthenolide<br>group V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subepithelial smooth muscle thickness &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#165;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;13<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#165;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#165;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#165;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;88<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;16<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#165;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of mast cells&#47;16&#44;400 &#40;&#956;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;07<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal membrane thickness &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;02<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Parthenolide and dexamethasone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;88<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">143&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison of IL-4 and IL-5 between study groups&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:31 [
            0 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory mediators of asthma&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46;J&#46; Barnes"
                            1 => "K&#46;F&#46; Chung"
                            2 => "C&#46;P&#46; Page"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacol Rev"
                        "fecha" => "1998"
                        "volumen" => "50"
                        "paginaInicial" => "515"
                        "paginaFinal" => "596"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9860804"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Persistent activation of nuclear factor-kappa B signaling pathway in severe uncontrolled asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Gagliardo"
                            1 => "P&#46; Chanez"
                            2 => "M&#46; Mathieu"
                            3 => "A&#46; Bruno"
                            4 => "G&#46; Costanzo"
                            5 => "C&#46; Gougat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200205-479OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2003"
                        "volumen" => "168"
                        "paginaInicial" => "1190"
                        "paginaFinal" => "1198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12893643"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of NF-kappa B in bronchial epithelial cells from children with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Zhao"
                            1 => "Y&#46; Qi"
                            2 => "X&#46; Liu"
                            3 => "Q&#46; Jiang"
                            4 => "S&#46; Liu"
                            5 => "Y&#46; Jiang"
                          ]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin Med J"
                        "fecha" => "2001"
                        "volumen" => "114"
                        "paginaInicial" => "909"
                        "paginaFinal" => "911"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11780379"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A critical role for NF-kappa B in GATA3 expression and Th2 differentiation in allergic airway inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Das"
                            1 => "C&#46;H&#46; Chen"
                            2 => "L&#46; Yang"
                            3 => "L&#46; Chon"
                            4 => "P&#46; Ray"
                            5 => "A&#46; Ray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Immunol"
                        "fecha" => "2001"
                        "volumen" => "2"
                        "paginaInicial" => "45"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11135577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Essential role of nuclear factor kappa B in the induction of eosinophilia in allergic airway inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Yang"
                            1 => "L&#46; Chon"
                            2 => "D&#46;H&#46; Zhang"
                            3 => "R&#46; Homer"
                            4 => "A&#46; Ray"
                            5 => "P&#46; Ray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "1998"
                        "volumen" => "188"
                        "paginaInicial" => "1739"
                        "paginaFinal" => "1750"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9802985"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of inhaled corticosteroids in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;J&#46; Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1998"
                        "volumen" => "102"
                        "paginaInicial" => "531"
                        "paginaFinal" => "538"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9802359"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the Ikappa B kinase complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;P&#46; Hehner"
                            1 => "T&#46;G&#46; Hofman"
                            2 => "W&#46; Droge"
                            3 => "M&#46;L&#46; Schmitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1998"
                        "volumen" => "163"
                        "paginaInicial" => "5617"
                        "paginaFinal" => "5623"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10553091"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of transcription factor NF-kappa B by sesquiterpene lactones&#58; a proposed molecular mechanism of action"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; R&#252;ngeler"
                            1 => "V&#46; Castro"
                            2 => "G&#46; Mora"
                            3 => "N&#46; G&#246;ren"
                            4 => "W&#46; Vichnewski"
                            5 => "H&#46;L&#46; Pahl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Bioorg Med Chem"
                        "fecha" => "1999"
                        "volumen" => "7"
                        "paginaInicial" => "2343"
                        "paginaFinal" => "2352"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10632044"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An improved murine model of asthma&#58; selective airway inflammation&#44; epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Temelkovski"
                            1 => "S&#46;P&#46; Hogan"
                            2 => "D&#46;P&#46; Shepherd"
                            3 => "P&#46;S&#46; Foster"
                            4 => "R&#46;K&#46; Kumar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "1998"
                        "volumen" => "53"
                        "paginaInicial" => "849"
                        "paginaFinal" => "856"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10193371"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of curcumin on lung histology and fungal burden in a mouse model of chronic asthma and oropharyngeal candidiasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Karaman"
                            1 => "Z&#46; Ar&#305;kan Ayy&#305;ld&#305;z"
                            2 => "F&#46; F&#305;r&#305;nc&#305;"
                            3 => "M&#46; Kiray"
                            4 => "A&#46; Ba&#287;r&#305;yan&#305;k"
                            5 => "O&#46; Yilmaz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arcmed.2011.01.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Med Res"
                        "fecha" => "2011"
                        "volumen" => "42"
                        "paginaInicial" => "79"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21565619"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "W&#46;R&#46; Henderson Jr&#46;"
                            1 => "G&#46;K&#46; Chiang"
                            2 => "Y&#46;T&#46; Tien"
                            3 => "E&#46;Y&#46; Chi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200501-088OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2006"
                        "volumen" => "173"
                        "paginaInicial" => "718"
                        "paginaFinal" => "728"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16387808"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parthenolide inhibits I&#954;B kinase&#44; NF-&#954;B activation&#44; and inflammatory response in cystic fibrosis cells and mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Saadane"
                            1 => "S&#46; Masters"
                            2 => "J&#46; DiDonato"
                            3 => "J&#46; Li"
                            4 => "M&#46; Berger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2006-0323OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2007"
                        "volumen" => "36"
                        "paginaInicial" => "728"
                        "paginaFinal" => "736"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17272824"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparative effects of the herbal constituent parthenolide &#40;feverfew&#41; on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;T&#46; Smolinski"
                            1 => "J&#46;J&#46; Pestka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Inflamm &#40;Lond&#41;"
                        "fecha" => "2005"
                        "volumen" => "29"
                        "paginaInicial" => "2"
                        "paginaFinal" => "6"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46;H&#46; Kwok"
                            1 => "B&#46; Koh"
                            2 => "M&#46;I&#46; Ndubuisi"
                            3 => "M&#46; Elofsson"
                            4 => "C&#46;M&#46; Crews"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chem Biol"
                        "fecha" => "2001"
                        "volumen" => "8"
                        "paginaInicial" => "759"
                        "paginaFinal" => "766"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11514225"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-inflammatory activity of parthenolide-depleted feverfew &#40;<span class="elsevierStyleItalic">Tanacetum parthenium</span>&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Sur"
                            1 => "K&#46; Martin"
                            2 => "F&#46; Liebel"
                            3 => "P&#46; Lyte"
                            4 => "S&#46; Shapiro"
                            5 => "M&#46; Southall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10787-008-8040-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflammopharmacology"
                        "fecha" => "2009"
                        "volumen" => "17"
                        "paginaInicial" => "42"
                        "paginaFinal" => "49"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19112586"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parthenolide&#44; a sesquiterpene lactone&#44; expresses multiple anti-cancer and anti-inflammatory activities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "V&#46;B&#46; Mathema"
                            1 => "Y&#46;S&#46; Koh"
                            2 => "B&#46;C&#46; Thakuri"
                            3 => "M&#46; Silanp&#228;&#228;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10753-011-9346-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflammation"
                        "fecha" => "2012"
                        "volumen" => "35"
                        "paginaInicial" => "560"
                        "paginaFinal" => "565"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21603970"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Feverfew &#40;<span class="elsevierStyleItalic">Tanacetum parthenium</span> L&#46;&#41;&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Pareek"
                            1 => "M&#46; Suthar"
                            2 => "G&#46;S&#46; Rathore"
                            3 => "V&#46; Bansal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/0973-7847.79105"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacogn Rev"
                        "fecha" => "2011"
                        "volumen" => "5"
                        "paginaInicial" => "103"
                        "paginaFinal" => "110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22096324"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A platelet phospholipase inhibitor from the medicinal herb feverfew &#40;<span class="elsevierStyleItalic">Tanacetum parthenium</span>&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;N&#46; Makheja"
                            1 => "J&#46;M&#46; Bailey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Prostoglandins Leukot Med"
                        "fecha" => "1982"
                        "volumen" => "8"
                        "paginaInicial" => "653"
                        "paginaFinal" => "660"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostoglandin synthetase inhibitors in feverfew"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46;J&#46; Pugh"
                            1 => "K&#46; Sambo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pharmacol"
                        "fecha" => "1998"
                        "volumen" => "40"
                        "paginaInicial" => "743"
                        "paginaFinal" => "745"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases&#58; implications for therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;G&#46; Wright"
                            1 => "J&#46;W&#46; Christman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Med"
                        "fecha" => "2003"
                        "volumen" => "2"
                        "paginaInicial" => "211"
                        "paginaFinal" => "219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14720003"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Beyond inflammation&#58; airway epithelial cells are at the interface of innate and adaptive immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Kato"
                            1 => "R&#46;P&#46; Schleimer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.coi.2007.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Immunol"
                        "fecha" => "2007"
                        "volumen" => "19"
                        "paginaInicial" => "711"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17928212"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nuclear factor kappa B induction in airway epithelium increases lung inflammation in allergen- challenged mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Scheller"
                            1 => "V&#46;V&#46; Polosukhin"
                            2 => "D&#46; Mitchell"
                            3 => "D&#46;S&#46; Cheng"
                            4 => "R&#46;S&#46; Peebles"
                            5 => "T&#46;S&#46; Blackwell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/01902140903019710"
                      "Revista" => array:6 [
                        "tituloSerie" => "Exp Lung Res"
                        "fecha" => "2009"
                        "volumen" => "35"
                        "paginaInicial" => "883"
                        "paginaFinal" => "895"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19995280"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nf-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;E&#46; Poynter"
                            1 => "R&#46; Cloots"
                            2 => "T&#46; van Woerkom"
                            3 => "K&#46;J&#46; Butnor"
                            4 => "P&#46; Vacek"
                            5 => "D&#46;J&#46; Taatjes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2004"
                        "volumen" => "173"
                        "paginaInicial" => "7003"
                        "paginaFinal" => "7009"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15557197"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in the airway epithelium"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;H&#46; Broide"
                            1 => "T&#46; Lawrence"
                            2 => "T&#46; Doherty"
                            3 => "J&#46;Y&#46; Cho"
                            4 => "M&#46; Miller"
                            5 => "K&#46; McElwain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "2005"
                        "volumen" => "102"
                        "paginaInicial" => "177723"
                        "paginaFinal" => "177728"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeting the NF-&#954;B pathway in asthma and chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Edwards"
                            1 => "N&#46;W&#46; Bartlett"
                            2 => "D&#46; Clarke"
                            3 => "M&#46;A&#46; Birrell"
                            4 => "M&#46; Belvisi"
                            5 => "S&#46;L&#46; Johnston"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pharmthera.2008.09.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacol Ther"
                        "fecha" => "2009"
                        "volumen" => "121"
                        "paginaInicial" => "1"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18950657"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IkappaB kinase-2 inhibitor blocks inflammation in human airway smooth muscle and a rat model of asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Birrell"
                            1 => "E&#46; Hardaker"
                            2 => "S&#46; Wong"
                            3 => "K&#46; McCluskie"
                            4 => "M&#46; Catley"
                            5 => "J&#46; De Alba"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200412-1647OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "172"
                        "paginaInicial" => "962"
                        "paginaFinal" => "971"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16002568"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Desmet"
                            1 => "P&#46; Gosset"
                            2 => "B&#46; Pajak"
                            3 => "D&#46; Cataldo"
                            4 => "M&#46; Bentires-Alj"
                            5 => "P&#46; Lekeux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2004"
                        "volumen" => "173"
                        "paginaInicial" => "5766"
                        "paginaFinal" => "5775"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15494529"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sesquiterpene lactones are potent inhibitors of interleukin 8 gene expression in cultured human respiratory epithelium"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;L&#46; Mazor"
                            1 => "I&#46;Y&#46; Menendez"
                            2 => "M&#46;A&#46; Ryan"
                            3 => "M&#46;A&#46; Fiedler"
                            4 => "H&#46;R&#46; Wong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/cyto.1999.0526"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cytokine"
                        "fecha" => "2000"
                        "volumen" => "12"
                        "paginaInicial" => "239"
                        "paginaFinal" => "245"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10704251"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parthenolide inhibits ERK and AP-1 which are dysregulated and contribute to excessive IL-8 expression and secretion in cystic fibrosis cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Saadane"
                            1 => "J&#46; Eastman"
                            2 => "M&#46; Berger"
                            3 => "T&#46;L&#46; Bonfield"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Inflamm &#40;Lond&#41;"
                        "fecha" => "2011"
                        "volumen" => "8"
                        "paginaInicial" => "26"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Th2 cells and GATA-3 in asthma&#58; new insights into the regulation of airway inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Ray"
                            1 => "L&#46; Chon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI8204"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1999"
                        "volumen" => "104"
                        "paginaInicial" => "985"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10525032"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dissociation of production of IL-4 and IL-5"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46;A&#46; Sewell"
                            1 => "H&#46;H&#46; Mu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/icb.1996.48"
                      "Revista" => array:5 [
                        "tituloSerie" => "Immunol Cell Biol"
                        "fecha" => "1996"
                        "volumen" => "74"
                        "paginaInicial" => "274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8799728"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2016.06.005

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	0	3
2024 October	24	9	33
2024 September	30	8	38
2024 August	45	13	58
2024 July	44	5	49
2024 June	10	3	13
2024 May	17	4	21
2024 April	14	5	19
2024 March	22	9	31
2024 February	25	9	34
2024 January	24	8	32
2023 December	32	8	40
2023 November	25	11	36
2023 October	45	10	55
2023 September	29	7	36
2023 August	25	4	29
2023 July	33	4	37
2023 June	29	4	33
2023 May	67	4	71
2023 April	41	3	44
2023 March	45	10	55
2023 February	48	8	56
2023 January	53	1	54
2022 December	36	8	44
2022 November	42	5	47
2022 October	31	6	37
2022 September	40	24	64
2022 August	45	6	51
2022 July	38	8	46
2022 June	35	12	47
2022 May	24	11	35
2022 April	26	7	33
2022 March	36	10	46
2022 February	36	12	48
2022 January	59	7	66
2021 December	38	14	52
2021 November	50	9	59
2021 October	54	6	60
2021 September	47	15	62
2021 August	43	5	48
2021 July	19	9	28
2021 June	21	14	35
2021 May	17	15	32
2021 April	57	11	68
2021 March	16	11	27
2021 February	25	11	36
2021 January	19	9	28
2020 December	1	0	1
2020 October	1	0	1
2020 July	0	1	1
2018 February	3	1	4
2018 January	1	6	7
2017 December	3	2	5
2017 November	1	0	1
2017 February	1	0	1
2017 January	2	0	2
2016 November	0	1	1

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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