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https://www.readbyqxmd.com/read/28440792/an-extra-uterine-system-to-physiologically-support-the-extreme-premature-lamb
#1
Emily A Partridge, Marcus G Davey, Matthew A Hornick, Patrick E McGovern, Ali Y Mejaddam, Jesse D Vrecenak, Carmen Mesas-Burgos, Aliza Olive, Robert C Caskey, Theodore R Weiland, Jiancheng Han, Alexander J Schupper, James T Connelly, Kevin C Dysart, Jack Rychik, Holly L Hedrick, William H Peranteau, Alan W Flake
In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed 'amniotic fluid' circuit that closely reproduces the environment of the womb...
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#2
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28429504/induced-pluripotent-stem-cells-reduce-neutrophil-chemotaxis-via-activating-grk2-in-endotoxin-induced-acute-lung-injury
#3
Vincent Yi-Fong Su, Shih-Hwa Chiou, Chi-Shiuan Lin, Wei-Chih Chen, Wen-Kuang Yu, Yen-Wen Chen, Cheng-Yu Chen, Kuang-Yao Yang
BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathological findings, neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF), bone marrow (BM) cell distribution, expression of chemokine receptors and regulatory signalling pathways were analysed after 24 h...
April 21, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28426693/influence-of-prenatal-hypoxia-and-postnatal-hyperoxia-on-morphologic-lung-maturation-in-mice
#4
Andreas Schmiedl, Torge Roolfs, Erol Tutdibi, Ludwig Gortner, Dominik Monz
BACKGROUND: Oxygen supply as a lifesaving intervention is frequently used to treat preterm infants suffering additionally from possible prenatal or perinatal pathogen features. The impact of oxygen and/or physical lung injury may influence the morphological lung development, leading to a chronic postnatal lung disease called bronchopulmonary dysplasia (BPD). At present different experimental BPD models are used. However, there are no systematic comparative studies regarding different influences of oxygen on morphological lung maturation...
2017: PloS One
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#5
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28421817/sequential-gm-csf-inhalation-after-whole-lung-lavage-for-pulmonary-alveolar-proteinosis-a-report-of-five-intractable-cases
#6
Shinya Ohkouchi, Keiichi Akasaka, Toshio Ichiwata, Shu Hisata, Hideya Iijima, Toshinori Takada, Hiroki Tsukada, Hideaki Nakayama, Jun-Ichi Machiya, Toshiya Irokawa, Hiromasa Ogawa, Yoko Shibata, Masakazu Ichinose, Masahito Ebina, Toshihiro Nukiwa, Hajime Kurosawa, Koh Nakata, Ryushi Tazawa
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte/macrophage colony stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid (BALF). The antibodies inhibit the maturation and phagocytosis of alveolar macrophages (AMs). Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years...
April 19, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28409646/intravitreal-bevacizumab-alters-type-iv-collagenases-and-exacerbates-arrested-alveologenesis-in-the-neonatal-rat-lungs
#7
Arwin M Valencia, Charles L Cai, Jeffrey Tan, Thomas J Duggan, Gloria B Valencia, Jacob V Aranda, Kay D Beharry
Purpose/Aim: Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used off-label to treat severe retinopathy of prematurity in extremely low gestational age neonates. VEGF and matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) participate in lung maturation. We tested the hypothesis that intravitreal bevacizumab enters the systemic circulation and has long-lasting effects on lung MMPs. MATERIALS AND METHODS: Neonatal rats were exposed to: (1) hyperoxia (50% O2); (2) intermittent hypoxia (IH) (50% O2 with brief episodes of 12% O2); or (3) room air (RA) from birth (P0) to P14...
April 14, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#8
REVIEW
Lalita Sharma, Hridayesh Prakash
Sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. Sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. Out of several sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central molecules and decisive for sphingolipid signaling. These are produced by enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either biological or physiological stresses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396322/camp-elevating-capacity-of-the-adenylate-cyclase-toxin-hemolysin-is-sufficient-for-lung-infection-but-not-for-full-virulence-of-bordetella-pertussis
#9
Karolina Skopova, Barbora Tomalova, Ivan Kanchev, Pavel Rossmann, Martina Svedova, Irena Adkins, Ilona Bibova, Jakub Tomala, Jiri Masin, Nicole Guiso, Radim Osicka, Radislav Sedlacek, Marek Kovar, Peter Sebo
The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cAMP, a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes...
April 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28394330/thymosin-%C3%AE-1-represents-a-potential-potent-single-molecule-based-therapy-for-cystic-fibrosis
#10
Luigina Romani, Vasilis Oikonomou, Silvia Moretti, Rossana G Iannitti, Maria Cristina D'Adamo, Valeria R Villella, Marilena Pariano, Luigi Sforna, Monica Borghi, Marina M Bellet, Francesca Fallarino, Maria Teresa Pallotta, Giuseppe Servillo, Eleonora Ferrari, Paolo Puccetti, Guido Kroemer, Mauro Pessia, Luigi Maiuri, Allan L Goldstein, Enrico Garaci
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28389622/il-4r%C3%AE-on-dendritic-cells-in-neonates-and-th2-immunopathology-in-respiratory-syncytial-virus-infection
#11
Bishwas Shrestha, Dahui You, Jordy Saravia, David T Siefker, Sridhar Jaligama, Greg I Lee, Asmaa A Sallam, Jeffrey N Harding, Stephania A Cormier
Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children, and severe RSV infection early in life has been associated with asthma development. Using a neonatal mouse model, we have shown that down-regulation of IL-4 receptor α (IL-4Rα) with antisense oligonucleotides in the lung during neonatal infection protected from RSV immunopathophysiology. Significant down-regulation of IL-4Rα was observed on pulmonary CD11b(+) myeloid dendritic cells (mDCs) suggesting a role for IL-4Rα on mDCs in the immunopathogenesis of neonatal RSV infection...
April 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28388600/influence-of-antenatal-glucocorticoid-on-preterm-lamb-diaphragm
#12
Tanzila Mahzabin, J Jane Pillow, Gavin J Pinniger, Anthony J Bakker, Peter B Noble, Robert B White, Kanakeswary Karisnan, Yong Song
BACKGROUND: Pregnant women at high risk of preterm delivery receive glucocorticoids to accelerate fetal lung maturation and surfactant synthesis. However, the effect of antenatal steroids on the developing diaphragm remains unclear. We hypothesized that maternal betamethasone impairs the fetal diaphragm, and the magnitude of the detrimental effect increases with longer duration of exposure. We aimed to determine how different durations of fetal exposure to maternal betamethasone treatment influence the fetal diaphragm at the functional and molecular levels...
April 7, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28382037/influenza-infection-in-mice-induces-accumulation-of-lung-mast-cells-through-the-recruitment-and-maturation-of-mast-cell-progenitors
#13
Behdad Zarnegar, Erika Mendez-Enriquez, Annika Westin, Cecilia Söderberg, Joakim S Dahlin, Kjell-Olov Grönvik, Jenny Hallgren
Mast cells (MCs) are powerful immune cells that mature in the peripheral tissues from bone marrow (BM)-derived mast cell progenitors (MCp). Accumulation of MCs in lung compartments where they are normally absent is thought to enhance symptoms in asthma. The enrichment of lung MCs is also observed in mice subjected to models of allergic airway inflammation. However, whether other types of lung inflammation trigger increased number of MCp, which give rise to MCs, is unknown. Here, mouse-adapted H1N1 influenza A was used as a model of respiratory virus infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28379718/sonic-hedgehog-signaling-regulates-myofibroblast-function-during-alveolar-septum-formation-in-murine-postnatal-lung
#14
Matthias C Kugler, Cynthia A Loomis, Zhicheng Zhao, Jennifer C Cushman, Li Liu, John S Munger
Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh signaling maintains mesenchymal quiescence and is dysregulated in diseases such as IPF and COPD. Our previous data implicated a role for Shh in postnatal lung development. Here we report a detailed analysis of Shh signaling during murine postnatal lung development. We show that Shh pathway expression and activity during alveolarization (P0-P14) are distinct from those during maturation (P14-P24)...
April 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28378805/neonatal-mice-possess-two-phenotypically-and-functionally-distinct-lung-migratory-cd103-dendritic-cell-populations-following-respiratory-infection
#15
T J Ruckwardt, K M Morabito, E Bar-Haim, D Nair, B S Graham
The CD103(+) subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8(+) T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103(+) DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103(+) DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103(+) DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28372944/histone-demethylases-kdm6ba-and-kdm6bb-redundantly-promote-cardiomyocyte-proliferation-during-zebrafish-heart-ventricle-maturation
#16
Alexander A Akerberg, Astra Henner, Scott Stewart, Kryn Stankunas
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development...
March 31, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28365931/the-effect-of-granulocyte-and-granulocyte-macrophage-colony-stimulating-factors-on-tumor-promotion
#17
Qiqi Liu, Lili Qiao, Pingping Hu, Guodong Deng, Jingxin Zhang, Ning Liang, Jian Xie, Jiandong Zhang
GM-CSF and G-CSF are capable to regulate the maturation of undifferentiated multipotent stem cells into mature granulocytes, macrophages and T cells in the bone marrow. Thereby, clinicians correct neutropenia induced by chemotherapy or radiation routinely with recombinant G- or GM-CSFs in clinical practice. However, relevant studies found that treatment for cancer patients with adjuvant G-/GM-CSF would occasionally enhance the progression of tumors. Besides, constitutive production of G-CSF or GM-CSF by lung cancer cells could stimulate the growth or the invasion of tumor and result in protecting the tumor against unfavorable environment...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28365781/the-lung-cancer-surgical-study-group-of-the-japan-clinical-oncology-group-past-activities-current-status-and-future-direction
#18
Kazuo Nakagawa, Shun-Ichi Watanabe, Hideo Kunitoh, Hisao Asamura
The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group was organized in 1986. Initially, 26 collaborative institutions participated. In the early period, the Lung Cancer Surgical Study Group focused on combined modality therapies and conducted nine trials, including JCOG9101: adjuvant chemotherapy for resected small-cell lung cancer, and JCOG9806: induction chemoradiotherapy followed by surgery for superior sulcus tumor, which greatly impacted the treatment strategies for some special kinds of lung cancer...
March 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28360114/ror%C3%AE-dependent-type-2-innate-lymphoid-cells-are-required-and-sufficient-for-mucous-metaplasia-in-immature-mice
#19
Charu Rajput, Tracy X Cui, Mingyuan Han, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life wheezing associated respiratory tract infection by rhinovirus (RV) is considered a risk factor for asthma development. We have shown that RV infection of 6 day-old BALB/c mice, but not mature mice, induces an asthma-like phenotype which is associated with an increase in the population of type 2 innate lymphoid cells (ILC2s) and dependent on IL-13 and IL-25. We hypothesize that ILC2s are required and sufficient for development of the asthma-like phenotype in immature mice. Mice were infected with RV1B on day 6 of life and treated with vehicle or a chemical inhibitor of retinoic acid receptor-related orphan receptor (ROR)-α, SR3335 (15 mg/kg/day intraperitoneally for 7 days)...
March 30, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28359838/graphene-oxide-nanosheets-induced-genotoxicity-and-pulmonary-injury-in-mice
#20
Nabil A El-Yamany, Faten F Mohamed, Taher A Salaheldin, Amany A Tohamy, Walaa N Abd El-Mohsen, Adel S Amin
Graphene and graphene-related materials have broadly applied in biomedical purposes due to their unique properties, thus safety evaluation of them is crucial. This study was performed to explore the genotoxic and pulmonary toxic potential of different doses of graphene oxide nanosheets' (GOs) in mice.A total of 90 male mature mice were randomly divided into six groups of fifteen mice per each, five groups were intraperitoneally injected by GO at doses of 10, 50, 100, 250 and 500μg/kg b.w once weekly in addition to the control group that was injected intraperitoneally with 0...
March 27, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
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