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Lung Repair

Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Chun-Hao Li, Sa-Hoe Lim, Hyang-Hwa Ryu, Kyung-Sub Moon, Tae-Young Jung, Shin Jung
Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes...
October 25, 2016: Oncology Reports
Chulananda Goonasekera, Kamal Ali, Ann Hickey, Lekshmi Sasidharan, Malcolm Mathew, Mark Davenport, Anne Greenough
BACKGROUND: Mortality following surgical repair of congenital diaphragmatic hernia (CDH) remains high. The volume and type of perioperative intravenous fluid administered, baro-trauma, oxygen toxicity, and the duration of anesthesia are thought to affect outcome in surgical populations. AIMS: The aim of this retrospective observational study was to determine whether the perioperative volume or type of fluids and/or the duration of anesthesia were associated with postoperative mortality and if mortality was predicted by the oxygenation index (OI) prior to or following CDH surgical repair...
October 25, 2016: Paediatric Anaesthesia
Cheng-Cao Sun, Shu-Jun Li, Zhan-Peng Yuan, De-Jia Li
Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA...
October 18, 2016: Aging
Irsa Tahir, Muhammad Rashid Khan, Naseer Ali Shah, Maryam Aftab
BACKGROUND: In the present study the antioxidant potential of a methanol extract of Phyllanthus emblica leaves (PELE) was determined by in vitro methods as well as by an in vivo animal model, along with HPLC-DAD screening for phyto-constituents. METHODS: The in vitro antioxidant potential of PELE was assessed by scavenging of DPPH, nitric oxide and anti-lipid peroxidation assays. For in vivo evaluation, a 60-day experimental plan was followed in which Sprague Dawley rats were administered with 1 mL/kg of CCl4 (CCl4 : DMSO + Olive oil; 30 % v/v) alone or with different doses of PELE (200, 400 mg/kg p...
October 24, 2016: BMC Complementary and Alternative Medicine
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
Morgan S Schrock, Jenna R Karras, Matthew J Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs...
September 26, 2016: Advances in Biological Regulation
Samriddha Ray, Norika Chiba, Changfu Yao, Xiangrong Guan, Alicia M McConnell, Brian Brockway, Loretta Que, Jonathan L McQualter, Barry R Stripp
Recent studies have implicated keratin 5 (KRT5)(+) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5(+) cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2(+) SCGB1A1(-) KRT5(-) progenitor cells in airways...
October 20, 2016: Stem Cell Reports
Aaron Wilson, Vasily A Yakovlev
Cancer development and progression have been linked to oxidative stress, a condition characterized by unbalanced increase in ROS and RNS production. The main endogenous initiators of the redox imbalance in cancer cells are defective mitochondria, elevated NOX activity, and uncoupled NOS3. Traditionally, most attention has been paid to direct oxidative damage to DNA by certain ROS. However, increase in oxidative DNA lesions does not always lead to malignancy. Hence, additional ROS-dependent, pro-carcinogenic mechanisms must be important...
October 19, 2016: Free Radical Biology & Medicine
Cho-Ming Chao, Faady Yahya, Alena Moiseenko, Caterina Tiozzo, Amit Shrestha, Negah Ahmadvand, Elie El Agha, Jennifer Quantius, Salma Dilai, Vahid Kheirollahi, Matthew Jones, Jochen Wilhem, Gianni Carraro, Harald Ehrhardt, Klaus-Peter Zimmer, Guillermo Barreto, Katrin Ahlbrecht, Rory E Morty, Susanne Herold, Rosanna G Abellar, Werner Seeger, Ralph Schermuly, Jin-San Zhang, Parviz Minoo, Saverio Bellusci
Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model of BPD, the impact of Fgf10 deficiency in Fgf10(+/-) versus Fgf10(+/+) pups was investigated. In normoxia, no lethality of Fgf10(+/+) or Fgf10(+/-) pups was observed...
October 22, 2016: Journal of Pathology
Megan O'Reilly, Bernard Thébaud
Preterm birth occurs in approximately 11 % of all births worldwide. Advances in perinatal care have enabled the survival of preterm infants born as early as 23-24 weeks of gestation. However, many are affected by bronchopulmonary dysplasia (BPD)-a common respiratory complication of preterm birth, which has life-long consequences for lung health. Currently, there is no specific treatment for BPD. Recent advances in stem cell research have opened new therapeutic avenues for prevention/repair of lung damage...
October 22, 2016: Cell and Tissue Research
Angelo M Dell'Aquila, Francesco Pollari, Khalil Fattouch, Giuseppe Santarpino, Julia Hillebrand, Stefan Schneider, Jan Landwerht, Giuseppe Nasso, Renato Gregorini, Mauro Del Giglio, Elisa Mikus, Alberto Albertini, Heinz Deschka, Theodor Fischlein, Sven Martens, Alina Gallo, Giovanni Concistrè, Giuseppe Speziale, Tommaso Regesta
This study provides early results of re-operations after the prior surgical treatment of acute type A aortic dissection (AAD) and identifies risk factors for mortality. Between May 2003 and January 2014, 117 aortic re-operations after an initial operation for AAD (a mean time from the first procedure was 3.98 years, with a range of 0.1-20.87 years) were performed in 110 patients (a mean age of 59.8 ± 12.6 years) in seven European institutions. The re-operation was indicated due to a proximal aortic pathology in ninety cases: twenty aortic root aneurysms, seventeen root re-dissections, twenty-seven aortic valve insufficiencies and twenty-six proximal anastomotic pseudoaneurysms...
October 21, 2016: Heart and Vessels
Maximilian Bures, Patrick Zardo, Florian Länger, Ruoyu Zhang
BACKGROUND: Albumin-glutaraldehyde glue has gained widespread acceptance for treatment of alveolar air leaks (AAL) in thoracic surgery. As liquid run-off during application is detrimental to its sealing efficacy, we developed a modified technique and assessed it in vitro. METHODS: Caudal lobes of freshly excised swine lungs (n = 20) were intubated and ventilated. A standardized focal superficial parenchymal defect (40 × 25 mm) was created on the inflated lung...
October 21, 2016: Journal of Cardiothoracic Surgery
Sarah-Jayne Edmondson, Saina Attaran, Ulrich P Rosendahl
Wegner's granulomatosis (WG) is an autoimmune systemic vasculitis that results in necrotizing granulomas. We report a WG patient with a lung granuloma and aortic root dilatation, who underwent aortic root replacement on cardiopulmonary bypass (CPB). Intraoperatively, the patient suffered an aortic dissection, which was repaired immediately under deep hypothermic circulatory arrest (DHCA). Follow-up imaging showed complete granuloma resolution, despite absence of immunosuppressive therapy. Immune stimulation following CPB is well described; here, the opposite was observed and DHCA effects are discussed...
February 2016: Aorta (Stamford, Conn.)
Yoonki Hong, You-Sun Kim, Seok-Ho Hong, Yeon-Mok Oh
There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice...
October 21, 2016: Experimental & Molecular Medicine
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
September 28, 2016: Oncotarget
H N Lynch, C T Loftus, J M Cohen, L E Kerper, E M Kennedy, J E Goodman
Research suggests that exposure to ambient particulate matter (PM) may be associated with lung cancer; however, no mode of action (MoA) for this has been established. We applied a weight-of-evidence (WoE) approach to evaluate recent evidence from four realms of research (controlled human exposure, epidemiology, animal, and in vitro) to determine whether the overall evidence supports one or more MoAs by which PM could cause lung cancer. We evaluated three general MoAs: DNA damage and repair; other genotoxic effects, including mutagenicity and clastogenicity; and gene expression, protein expression, and DNA methylation...
October 17, 2016: Regulatory Toxicology and Pharmacology: RTP
Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Kevin K Kim, Thomas H Sisson, Jeffrey C Horowitz
Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells and macrophages responding to an array of soluble and matrix mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF and PDGF receptors can slow the rate of decline in pulmonary function in patients with idiopathic pulmonary fibrosis. However, each of these growth factor families is comprised of multiple ligands and receptors with pleiotropic activities on different cell types such that their broad inhibition might have both pro-fibrotic and anti-fibrotic effects, limiting the potential therapeutic efficacy...
October 19, 2016: Journal of Pathology
Woo Sung Jang, Woong-Han Kim, Sungkyu Cho
BACKGROUND: Left pulmonary artery (LPA) stenosis with acute angulation is a common cause of reoperation after tetralogy of Fallot repair. We therefore investigated surgical outcomes of acute-angle correction angioplasty. METHODS: Between 2005 and 2012, 53 patients underwent operation for LPA stenosis as a concurrent procedure. We divided the patients into two groups according to the LPA ostium angulation: group I (acute angle, acute-angle correction angioplasty, n = 29) and group II (obtuse angle, conventional patch angioplasty, n = 24), encompassing subgroup type I (focal stenosis) and type II (diffuse stenosis)...
October 15, 2016: Annals of Thoracic Surgery
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