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Lung Repair

Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
Chung-I Lin, Chin-Hung Tsai, Yu-Ling Sun, Wen-Yeh Hsieh, Yi-Chang Lin, Cheng-Yi Chen, Chih-Sheng Lin
Inhaled particulate matter 2.5 (PM2.5 ) can cause lung injury by inducing serious inflammation in lung tissue. Renin-angiotensin system (RAS) is involved in the pathogenesis of inflammatory lung diseases and regulates inflammatory response. Angiotensin-converting enzyme II (ACE2), which is produced through the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II) axis, protects against lung disease. However, few studies have focused on the relationships between PM2.5 and ACE2. Therefore, we aimed to explore the role of ACE2 in PM2...
2018: International Journal of Biological Sciences
Bon-Hee Gu, Matthew C Madison, David Corry, Farrah Kheradmand
Multicellular organisms synthesize and renew components of their subcellular and scaffolding proteins, collectively known as the extracellular matrix molecules (ECMs). In the lung, ECMs maintain tensile strength, elasticity, and dictate the specialized function of multiple cell lineages. These functions are critical in lung homeostatic processes including cellular migration and proliferation during morphogenesis or in response to repair. Alterations in lung ECMs that expose cells to new cryptic fragments, generated in response to endogenous proteinases or exogenous toxins, are associated with the development of several common respiratory diseases...
March 17, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Tudor Borza, Mary K Oerline, Ted A Skolarus, Edward C Norton, Justin B Dimick, Bruce L Jacobs, Lindsey A Herrel, Chad Ellimoottil, John M Hollingsworth, Andrew M Ryan, David C Miller, Vahakn B Shahinian, Brent K Hollenbeck
OBJECTIVE: To evaluate the effect of Medicare Shared Savings Program accountable care organizations (ACOs) on hospital readmission after common surgical procedures. SUMMARY BACKGROUND DATA: Hospital readmissions following surgery lead to worse patient outcomes and wasteful spending. ACOs, and their associated hospitals, have strong incentives to reduce readmissions from 2 distinct Centers for Medicare and Medicaid Services policies. METHODS: We performed a retrospective cohort study using a 20% national Medicare sample to identify beneficiaries undergoing 1 of 7 common surgical procedures-abdominal aortic aneurysm repair, colectomy, cystectomy, prostatectomy, lung resection, total knee arthroplasty, and total hip arthroplasty-between 2010 and 2014...
March 19, 2018: Annals of Surgery
Katerina M Antoniou, Konstantinos Karagiannis, Eliza Tsitoura, Eleni Bibaki, Ismini Lasithiotaki, Athanasia Proklou, Demetrios A Spandidos, Nikos Tzanakis
Mesenchymal stem (stromal) cells (MSCs) are multipotent stromal cells that have the ability to modulate immune response to tissue injury and promote repair in vivo . The therapeutic potential of ex vivo expanded MSCs are currently under investigation for a variety of chronic and acute lung diseases. This review summarizes the encouraging results regarding the safety of MSCs administration from recent and current clinical trials for idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and chronic obstructive pulmonary disease...
April 2018: Biomedical Reports
Jiang-Kai Dong, Hui-Min Lei, Qian Liang, Ya-Bin Tang, Ye Zhou, Yang Wang, Shengzhe Zhang, Wen-Bin Li, Yunguang Tong, Guanglei Zhuang, Liang Zhang, Hong-Zhuan Chen, Liang Zhu, Ying Shen
How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients...
2018: Theranostics
Lehui Du, Wei Yu, Xiang Huang, Nana Zhao, Fang Liu, Fang Tong, Sujing Zhang, Baolong Niu, Xiaoliang Liu, Shouping Xu, Yurong Huang, Xiangkun Dai, Chuanbin Xie, Gaoxiang Chen, Xiaohu Cong, Baolin Qu
Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP. Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT)...
2018: Journal of Cancer
Ding Qian-Shan, Zhang Li, Wang Bi-Cheng, Zeng Zhi, Zou Xian-Qiong, Cao Peng-Bo, M S Zhou Guang-Ming, Tang Meng, Wu Lu, B S Wu Lian-Lian, Yu Hong-Gang, Guo Yong, Zhou Fu-Xiang
Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types employing immunohistochemical staining and analysis of mRNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, oesophagus and bladder)...
March 16, 2018: Human Pathology
Adriana Correa Melo, Isabella Cattani-Cavalieri, Marina Valente Barroso, Nicolas Quesnot, Lycia Brito Gitirana, Manuella Lanzetti, Samuel Santos Valença
Emphysema results in a proteinase - antiproteinase imbalance, inflammation and oxidative stress. Our objective was to investigate whether atorvastatin could repair mouse lungs after elastase-induced emphysema. Vehicle (50 μL) or porcine pancreatic elastase (PPE) was administered on day 1, 3, 5 and 7 at 0.6 U intranasally. Male mice were divided into a control group (sham), PPE 32d (sacrificed 24 h after 32 days), PPE 64d (sacrificed 24 h after 64 days), and atorvastatin 1, 5 and 20 mg treated from day 33 until day 64 and sacrificed 24 h later (A1 mg, A5 mg and A20 mg, respectively)...
March 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Elizabeth A Middleton, Matthew T Rondina, Hansjorg Schwertz, Guy A Zimmerman
Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions, and are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, some of these newly-discovered activities of platelets appear to contribute to tissue injury based on clinical investigations and animal models of disease...
March 19, 2018: American Journal of Respiratory Cell and Molecular Biology
Julia Krabbe, André Esser, Stephanie Kanzler, Till Braunschweig, Svetlana Kintsler, Jan Spillner, Thomas Schröder, Sebastian Kalverkamp, Galina Balakirski, Benjamin Gerhards, Annette D Rieg, Thomas Kraus, Peter Brand, Christian Martin
Recently, the pro-inflammatory effects of metal inert gas brazing welding fumes containing zinc and copper have been demonstrated in humans. Here, murine, rat and human precision cut lung slices (PCLS) were incubated in welding fume containing media with 0.1, 1, 10 and 100 μg/ml for 24 or 48 h. 24 h incubation were determined either by incubation for the total time or for only 6 h followed by a 18 h post-incubation phase. Cytotoxicity, proliferation and DNA repair rates, and cytokine levels were determined...
March 10, 2018: Journal of Trace Elements in Medicine and Biology
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Justin S Merkow, Erik J Nelson
BACKGROUND Providing anesthesia to immunocompromised patients introduces unique challenges, including difficulty in detecting respiratory infections. Detailed preoperative evaluation and preparation for perioperative complications is crucial. Human metapneumovirus is a common but lesser known respiratory virus that can lead to pneumonia and respiratory compromise and is challenging to detect in the immunocompromised patient. CASE REPORT We present a case of an immunocompromised individual scheduled for umbilical hernia repair who developed severe bronchospasm and intraoperative respiratory failure after induction of general anesthesia...
March 16, 2018: American Journal of Case Reports
Zoel A Quinonez, Laura Downey, Rania K Abbasi, Calvin Kuan, Ritu Asija, Doff B McElhinney, Frank L Hanley, Richard D Mainwaring, Lisa Wise-Faberowski
Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals (TOF/PA/MAPCAs) is a heterogeneous disease with varying degrees of severity, requiring complex anesthetic management. Our institution has adopted the approach of early complete repair with incorporation of all lung segments, extensive lobar and branch segmental pulmonary artery reconstruction, and ventricular septal defect closure. While the surgical management of TOF/PA/MAPCAs has been extensively described and varies depending on the institution, there is a paucity of literature on the anesthetic management for such procedures...
March 2018: World Journal for Pediatric & Congenital Heart Surgery
Ning Zhan, Bin Li, Xiangying Xu, Jianyu Xu, Songliu Hu
Fatty acid synthase (FASN) is the key enzyme required for the de novo synthesis of long-chain fatty acids. FASN has been observed to be overexpressed in the majority of cancer tissues, and its expression is associated with a poor prognosis, potentially mediated by resistance to drug or radiation. The present study investigated whether the downregulation of FASN in non-small cell lung cancer (NSCLC) may increase radiosensitivity. A lentiviral vector containing short hairpin RNA targeted to FASN (pSIH-H1-Puro-shFASN) was successfully constructed and transfected into A549 cells to knockdown the gene by RNA interference...
April 2018: Oncology Letters
Justin Stebbing, Kalpit Shah, Lei Cheng Lit, Teresa Gagliano, Angeliki Ditsiou, Tingting Wang, Franz Wendler, Thomas Simon, Krisztina Sára Szabó, Timothy O'Hanlon, Michael Dean, April Camilla Roslani, Swee Hung Cheah, Soo-Chin Lee, Georgios Giamas
Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment...
March 15, 2018: Oncogene
Triparna Sen, Carl M Gay, Lauren Averett Byers
Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 14% of all lung cancer diagnoses. Despite decades of active research, treatment options for SCLC are limited and resistance to the few Food and Drug Administration (FDA) approved therapies develops rapidly. With no approved targeted agents to date, new therapeutic strategies are desperately needed. SCLC is characterized by high mutation burden, ubiquitous loss of TP53 and RB1, mutually exclusive amplification of MYC family members, thereby, high genomic instability...
February 2018: Translational Lung Cancer Research
Megumi Yazaki, Takehiko Oami, Kazuya Nakanishi, Ryota Hase, Hiroyuki Watanabe
Although vancomycin administration is recommended for the treatment of infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA), it is unclear whether an alternative agent, daptomycin, can be used to treat IE with pulmonary complications. A 26-year-old female who had undergone surgical repair of a ventricular septal defect as an early teenager presented with fever, headache, and vomiting. She was admitted to our hospital and diagnosed with right-sided IE with septic pulmonary embolism caused by MRSA...
March 10, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Peter V Deraska, Colin O'Leary, Hunter D Reavis, Shelby Labe, Tru-Khang Dinh, Jean-Bernard Lazaro, Christopher Sweeney, Alan D D'Andrea, David Kozono
Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization...
December 2018: Cell Death Discovery
Hussein Nassereddine, Nicolas Poté, Pasquale Tammaro, Anne Couvelard
Pulse (hyaline ring) granuloma, a rare entity first described in lung and oral cavity, has been reported under various names before the identification of hyaline rings as fragments of pulses (the edible seeds of legumes). Similar lesions were thereafter described in extra-oral localizations, mainly the gastrointestinal tract, or localizations having potential communication with the gastrointestinal tract. Recently, 2 reports described "spiral bodies" surrounded by foreign body-type multinucleated giant cell reaction in pulse granulomas, corresponding to remnant plant vascular structures (helical xylem elements)...
March 1, 2018: International Journal of Surgical Pathology
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