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https://www.readbyqxmd.com/read/28923883/microtubules-associated-rac-regulation-of-endothelial-barrier-a-role-of-asef-in-acute-lung-injury
#1
Pratap Karki, Anna A Birukova
The endothelial barrier function regulated by the cytoskeletal reorganizations has been implicated in the pathogenesis of multiple lung diseases including asthma, sepsis, edema, and acute respiratory distress syndrome. The extensive studies have established that activation of small GTPase Rac is a key mechanism in endothelial barrier protection but the role of microtubules-associated Rac in the endothelial functions remains poorly understood. With the emerging evidences that microtubules disassembly also plays a critical role in actin cytoskeleton remodeling leading to endothelial permeability, the knowledge on microtubules-mediated regulation of endothelial barrier is imperative to better understand the etiology of lung injuries as well as to develop novel therapeutics against these disorders...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28922731/shikonin-suppresses-pulmonary-fibroblasts-proliferation-and-activation-by-regulating-akt-and-p38-mapk-signaling-pathways
#2
Yunjuan Nie, Yaoyao Yang, Jian Zhang, Guowei Cai, Yanhua Chang, Gaoshang Chai, Chongyong Guo
Fibroblast is believed to be the primary effector in idiopathic pulmonary fibrosis (IPF), a progressive lung disorder characterized by aberrant tissue remodeling and the formation of fibroblastic foci. Due to the complicated etiology and mechanism, there are few effective drugs for this fatal disease. Shikonin (SHI), which is the major ingredient isolated from the plant Lithospermum Erythrorhizon, has long been used as traditional medicine for many diseases including inflammation and cancer. The roles of SHI in attenuating skin scar and renal fibrosis by reducing TGFβ1-stimulated fibroblast activation are also reported...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28919014/regulation-and-function-of-endothelial-glycocalyx-layer-in-vascular-diseases
#3
REVIEW
Irina Sieve, Anja Münster-Kühnel, Denise Hilfiker-Kleiner
In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i...
September 12, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28918442/the-role-of-periostin-in-lung-fibrosis-and-airway-remodeling
#4
REVIEW
David N O'Dwyer, Bethany B Moore
Periostin is a protein that plays a key role in development and repair within the biological matrix of the lung. As a matricellular protein that does not contribute to extracellular matrix structure, periostin interacts with other extracellular matrix proteins to regulate the composition of the matrix in the lung and other organs. In this review, we discuss the studies exploring the role of periostin to date in chronic respiratory diseases, namely asthma and idiopathic pulmonary fibrosis. Asthma is a major health problem globally affecting millions of people worldwide with significant associated morbidity and mortality...
September 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28916766/stimulatory-secretions-of-airway-epithelial-cells-accelerate-early-repair-of-tracheal-epithelium
#5
Egi Kardia, Rafeezul Mohamed, Badrul Hisham Yahaya
Airway stem/progenitor epithelial cells (AECs) are notable for their differentiation capacities in response to lung injury. Our previous finding highlighted the regenerative capacity of AECs following transplantation in repairing tracheal injury and reducing the severity of alveolar damage associated acute lung injury in a rabbit model. The goal of this study is to further investigate the potential of AECs to re-populate the tracheal epithelium and to study their stimulatory effect on inhibiting pro-inflammatory cytokines, epithelial cell migration and proliferation, and epithelial-to-mesenchymal transition (EMT) process following tracheal injury...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916165/muc1-deficiency-exacerbates-pulmonary-fibrosis-in-a-mouse-model-of-silicosis
#6
Kosuke Kato, Marina A Zemskova, Alec D Hanss, Marianne M Kim, Sandra J Gendler, Ross Summer, Kwang Chul Kim
BACKGROUND: MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown...
September 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28914424/new-perspectives-in-nanotherapeutics-for-chronic-respiratory-diseases
#7
Adriana Lopes da Silva, Fernanda Ferreira Cruz, Patricia Rieken Macedo Roccco, Marcelo Marcos Morales
According to the World Health Organization (WHO), hundreds of millions of people of all ages and in all countries suffer from chronic respiratory diseases, with particular negative consequences such as poor health-related quality of life, impaired work productivity, and limitations in the activities of daily living. Chronic obstructive pulmonary disease, asthma, occupational lung diseases (such as silicosis), cystic fibrosis, and pulmonary arterial hypertension are the most common of these diseases, and none of them are curable with current therapies...
September 15, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28912466/using-a-novel-microfabricated-model-of-the-alveolar-capillary-barrier-to-investigate-the-effect-of-matrix-structure-on-atelectrauma
#8
N Higuita-Castro, M T Nelson, V Shukla, P A Agudelo-Garcia, W Zhang, S M Duarte-Sanmiguel, J A Englert, J J Lannutti, D J Hansford, S N Ghadiali
The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling of the ECM occurs during several lung disorders, it is not known how fiber structure and mechanics influences cell injury during cyclic airway reopening as occurs during mechanical ventilation (atelectrauma). We have developed a novel in vitro platform that mimics the micro/nano-scale architecture of the alveolar microenvironment and have used this system to investigate how ECM microstructural properties influence epithelial cell injury during airway reopening...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911970/mesenchymal-stem-cells-alleviate-oxidative-stress-induced-mitochondrial-dysfunction-in-the-airways
#9
Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H Wiegman, Ian M Adcock, Qizhou Lian, Judith C W Mak, Pankaj K Bhavsar, Kian Fan Chung
BACKGROUND: Oxidative stress-induced mitochondrial dysfunction may contribute to inflammation and remodeling in chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells (MSCs) protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. OBJECTIVE: To examine the effect of induced-pluripotent stem cell-derived MSCs (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo...
September 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28910321/identification-of-transforming-growth-factor-beta-regulated-micrornas-and-the-microrna-targetomes-in-primary-lung-fibroblasts
#10
Jennie Ong, Wim Timens, Vijay Rajendran, Arjan Algra, Avrum Spira, Marc E Lenburg, Joshua D Campbell, Maarten van den Berge, Dirkje S Postma, Anke van den Berg, Joost Kluiver, Corry-Anke Brandsma
BACKGROUND: Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling. Abnormal repair and remodeling has been observed in lung diseases like COPD. As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function. MATERIALS AND METHODS: We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays...
2017: PloS One
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#11
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28903339/ing5-knockdown-enhances-migration-and-invasion-of-lung-cancer-cells-by-inducing-emt-via-egfr-pi3k-akt-and-il-6-stat3-signaling-pathways
#12
Xin-Li Liu, Xu-Tao Zhang, Jin Meng, Hong-Fei Zhang, Yong Zhao, Chen Li, Yang Sun, Qi-Bing Mei, Feng Zhang, Tao Zhang
ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family, whose functions have been involved in the regulation of chromatin remodeling, cell cycle progression, proliferation and apoptosis. Our previous study has shown that ING5 overexpression inhibits lung cancer aggressiveness via suppressing epithelial to mesenchymal transition (EMT). However, the mechanisms remain largely unknown. In the current study, by Phospho-Kinase array and western blot, we have defined significantly upregulated EGFR/PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways in ING5 knockdown A549 cells, which could be downregulated by ING5 overexpression...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901394/overexpression-of-atp5b-promotes-cell-proliferation-in-asthma
#13
Jianhong Zuo, Mingsheng Lei, Meilin Wen, Yikun Chen, Zhigang Liu
Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper‑responsive-ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2‑3‑fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl β‑D‑1‑thiogalactoside (IPTG) and purified using Ni‑NTA...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28892201/two-brm-promoter-polymorphisms-predict-poor-survival-in-patients-with-hepatocellular-carcinoma
#14
Ivan Pasic, Kit Man Wong, Jonghun John Lee, Osvaldo Espin-Garcia, Yonathan Brhane, Dangxiao Cheng, Zhuo Chen, Devalben Patel, Catherine Brown, Roxana Bucur, David Reisman, Jennifer J Knox, Wei Xu, Rayjean J Hung, Geoffrey Guo, Sean P Cleary
BACKGROUND: Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian-predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. METHODS: HCC cases were recruited in a comprehensive cancer centre while the matched controls were recruited from family practice units from the same catchment area...
September 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28890402/lung-responses-in-murine-models-of-experimental-asthma-value-of-house-dust-mite-over-ovalbumin-sensitization
#15
Camille Doras, Ferenc Petak, Sam Bayat, Aurélie Baudat, Christophe Von Garnier, Philippe Eigenmann, Walid Habre
Ovalbumin (OVA) sensitization has limitations in modelling asthma. Thus, we examined the value of allergic sensitization using a purified natural allergen, house dust mite (HDM), over the sensitization performed with OVA. Mice were sham-treated, or sensitized with OVA- or HDM with identical chronology. Airway resistance, tissue damping and elastance were assessed under control conditions and after challenging the animals with methacholine (MCh) and the specific allergen. Inflammatory profile of the bronchoalveolar lavage fluid was characterized and lung histology was performed...
September 8, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28890197/revisiting-asthma-therapeutics-focus-on-wnt-signal-transduction
#16
REVIEW
Tim Koopmans, Reinoud Gosens
Asthma is a complex disease of the airways that develops as a consequence of both genetic and environmental factors. This interaction has highlighted genes important in early life, particularly those that control lung development, such as the Wingless/Integrase-1 (WNT) signalling pathway. Although aberrant WNT signalling is involved with an array of human conditions, it has received little attention within the context of asthma. Yet it is highly relevant, driving events involved with inflammation, airway remodelling, and airway hyper-responsiveness (AHR)...
September 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28889085/immunosenescence-and-immunecheckpoint-inhibitors-in-non-small-cell-lung-cancer-patients-does-age-really-matter
#17
REVIEW
Roberto Ferrara, Laura Mezquita, Edouard Auclin, Nathalie Chaput, Benjamin Besse
Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients...
August 24, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28886691/impaired-response-of-the-bronchial-epithelium-to-inflammation-characterizes-severe-equine-asthma
#18
Laurence Tessier, Olivier Côté, Mary Ellen Clark, Laurent Viel, Andrés Diaz-Méndez, Simon Anders, Dorothee Bienzle
BACKGROUND: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28886479/high-sensitivity-hplc-method-for-determination-of-the-allysine-concentration-in-tissue-by-use-of-a-naphthol-derivative
#19
Philip A Waghorn, Bruno L Oliveira, Chloe M Jones, Andrew M Tager, Peter Caravan
Common to all fibrotic and metastatic diseases is the uncontrollable remodeling of tissue that leads to the accumulation of fibrous connective tissue components such as collagen and elastin. Build-up of fibrous tissue occurs through the cross-linking of collagen or elastin monomers, which is initiated through the oxidation of lysine residues to form α-aminoadipic-δ-semialdehyde (allysine). To provide a measure of the extent of collagen oxidation in disease models of fibrosis or metastasis, a rapid, sensitive HPLC method was developed to quantify the amount of allysine present in tissue...
August 26, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28884116/the-role-of-pontin-and-reptin-in-cellular-physiology-and-cancer-etiology
#20
REVIEW
Yu-Qian Mao, Walid A Houry
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers...
2017: Frontiers in Molecular Biosciences
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