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Protective lung strategy

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https://www.readbyqxmd.com/read/29232398/remote-ischemic-preconditioning-attenuates-cardiopulmonary-bypass-induced-lung-injury
#1
Xiaona Zhou, Runzhu Jiang, Yucai Dong, Lifeng Wang
The use of cardiopulmonary bypass (CPB) in cardiac surgeries is known to induce pathological changes in vital organs such as lungs. Remote ischemic preconditioning (RIPC) is a protective strategy that has shown to be able to reduce tissue damage related to ischemia-reperfusion injury (IRI). The current study seeks to evaluate the beneficial effects of limb RIPC on lung tissues and function in a rat CPB model. RIPC, which consisted of three cycles of 5-min ischemia and subsequently 5-min reperfusion, was induced in the hind limbs of the animals via a tourniquet...
2017: PloS One
https://www.readbyqxmd.com/read/29230061/boosting-with-recombinant-mva-expressing-m-tuberculosis-%C3%AE-crystallin-antigen-augments-the-protection-imparted-by-bcg-against-tuberculosis-in-guinea-pigs
#2
Prachi Nangpal, Ritika Kar Bahal, Anil K Tyagi
Tuberculosis (TB) is one of the major causes of mortality all over the globe. BCG, the only vaccine available against this disease has been successful in preventing the severe forms of childhood TB. However, the unsatisfactory performance of BCG in controlling the adult pulmonary tuberculosis has made the development of an effective vaccine against M. tuberculosis a prime objective of the TB research. In this study, a genetically stable, marker-free recombinant MVA expressing α-crystallin of M. tuberculosis (rMVA...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29226313/model-based-assessments-of-cyp-mediated-drug-drug-interaction-risk-of-alectinib-physiologically-based-pharmacokinetic-modeling-supported-clinical-development
#3
Yumi Cleary, Michael Gertz, Peter N Morcos, Li Yu, Kuresh Youdim, Alex Phipps, Stephen Fowler, Neil Parrott
Alectinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. Alectinib and its major active metabolite M4 exhibited drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8 in vitro. Clinical relevance of the DDI risk was investigated as part of a rapid development program to fulfil the breakthrough therapy designation. Therefore, a strategy with a combination of physiologically based pharmacokinetic (PBPK) modeling and limited clinical trials focused on generating informative data for modeling was taken to ensure extrapolation ability of DDI risk...
December 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29221302/the-society-for-translational-medicine-clinical-practice-guidelines-for-mechanical-ventilation-management-for-patients-undergoing-lobectomy
#4
REVIEW
Shugeng Gao, Zhongheng Zhang, Alessandro Brunelli, Chang Chen, Chun Chen, Gang Chen, Haiquan Chen, Jin-Shing Chen, Stephen Cassivi, Ying Chai, John B Downs, Wentao Fang, Xiangning Fu, Martínez I Garutti, Jianxing He, Jie He, Jian Hu, Yunchao Huang, Gening Jiang, Hongjing Jiang, Zhongmin Jiang, Danqing Li, Gaofeng Li, Hui Li, Qiang Li, Xiaofei Li, Yin Li, Zhijun Li, Chia-Chuan Liu, Deruo Liu, Lunxu Liu, Yongyi Liu, Haitao Ma, Weimin Mao, Yousheng Mao, Juwei Mou, Calvin Sze Hang Ng, René H Petersen, Guibin Qiao, Gaetano Rocco, Erico Ruffini, Lijie Tan, Qunyou Tan, Tang Tong, Haidong Wang, Qun Wang, Ruwen Wang, Shumin Wang, Deyao Xie, Qi Xue, Tao Xue, Lin Xu, Shidong Xu, Songtao Xu, Tiansheng Yan, Fenglei Yu, Zhentao Yu, Chunfang Zhang, Lanjun Zhang, Tao Zhang, Xun Zhang, Xiaojing Zhao, Xuewei Zhao, Xiuyi Zhi, Qinghua Zhou
Patients undergoing lobectomy are at significantly increased risk of lung injury. One-lung ventilation is the most commonly used technique to maintain ventilation and oxygenation during the operation. It is a challenge to choose an appropriate mechanical ventilation strategy to minimize the lung injury and other adverse clinical outcomes. In order to understand the available evidence, a systematic review was conducted including the following topics: (I) protective ventilation (PV); (II) mode of mechanical ventilation [e...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29217176/a-strong-adjuvant-based-on-glycol-chitosan-coated-lipid-polymer-hybrid-nanoparticles-potentiates-mucosal-immune-responses-against-the-recombinant-chlamydia-trachomatis-fusion-antigen-cth522
#5
Fabrice Rose, Jeanette Erbo Wern, Francesca Gavins, Peter Andersen, Frank Follmann, Camilla Foged
Induction of mucosal immunity with vaccines is attractive for the immunological protection against pathogen entrance directly at the site of infection. An example is infection with Chlamydia trachomatis (Ct), which is the most common sexually transmitted infection in the world, and there is an unmet medical need for an effective vaccine. A vaccine against Ct should elicit protective humoral and cell-mediated immune (CMI) responses in the genital tract mucosa. We previously designed an antibody- and CMI-inducing adjuvant based on poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles modified with the cationic surfactant dimethyldioctadecylammonium bromide and the immunopotentiator trehalose-6,6'-dibehenate...
December 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29215723/high-cholesterol-in-lipid-rafts-reduces-the-sensitivity-to-egfr-tki-therapy-in-non-small-cell-lung-cancer
#6
Qiufang Chen, Zhenzhen Pan, Min Zhao, Qin Wang, Chen Qiao, Liyun Miao, Xuansheng Ding
Overcoming EGFR-TKI resistant which has the initial enthusiasm over substantial clinical responses is a formidable challenge on nowadays. In this study, we showed that cholesterol level in lipid rafts in gefitinib resistant non-small cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib sensitive cell line, and depletion of cholesterol increase gefitinib sensitivity. Furthermore, Cholesterol-depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt-1, MEK1/2 and ERK1/2 and these were reversed in cholesterol add-back experiments...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211497/the-rho-kinase-isoforms-rock1-and-rock2-each-contribute-to-the-development-of-experimental-pulmonary-fibrosis
#7
Rachel S Knipe, Clemens K Probst, David Lagares, Alicia Franklin, Jillian J Spinney, Patricia L Brazee, Paula Grasberger, Linlin Zhang, Katharine E Black, Norihiko Sakai, Barry S Shea, James K Liao, Benjamin D Medoff, Andrew M Tager
Pulmonary fibrosis is thought to result from dysregulated wound repair after repetitive lung injury. Many cellular responses to injury involve rearrangements of the actin cytoskeleton mediated by the two isoforms of the Rho-associated coiled coil forming protein kinase, ROCK1 and ROCK2. Additionally, profibrotic mediators such as transforming growth factor-beta (TGF-β), thrombin and lysophosphatidic acid (LPA) act through receptors that activate ROCK. Inhibition of ROCK activation may be a potent therapeutic strategy for human pulmonary fibrosis...
December 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#8
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29207907/implementation-of-a-goal-directed-mechanical-ventilation-order-set-driven-by-respiratory-therapists-improves-compliance-with-best-practices-for-mechanical-ventilation
#9
Misty A Radosevich, Brendan T Wanta, Todd J Meyer, Verlin W Weber, Daniel R Brown, Nathan J Smischney, Daniel A Diedrich
PURPOSE: Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/29205062/microrna-150-protects-against-cigarette-smoke-induced-lung-inflammation-and-airway-epithelial-cell-apoptosis-through-repressing-p53-microrna-150-in-cs-induced-lung-inflammation
#10
H Xue, M X Li
Cigarette smoke (CS) exposure is an important risk factor for chronic obstructive pulmonary disease (COPD). MicroRNA-150 (miR-150) is involved in several inflammatory diseases. However, little is known about the role of miR-150 in the pathogenesis of COPD. In this study, we established a CS-related mouse model of COPD and evaluated the impact of miR-150 on CS-induced lung inflammation. We further investigated the effects of miR-150 overexpression on pro-inflammatory cytokine production and apoptosis in airway epithelial cells exposed to CS extract (CSE)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29204139/mycobacterium-tuberculosis-latent-antigen-rv2029c-from-the-multistage-dna-vaccine-a39-drives-th1-responses-via-tlr-mediated-macrophage-activation
#11
Haibo Su, Shengling Zhu, Lin Zhu, Cong Kong, Qi Huang, Zhi Zhang, Honghai Wang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB) vaccine(s) that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29199874/necrostatin-1-attenuates-lipopolysaccharide-induced-acute-lung-injury-in-mice
#12
Enqin Guan, Yue Wang, Caixia Wang, Ruiyun Zhang, Yiming Zhao, Jiang Hong
AIM OF THE STUDY: Receptor-interacting protein (RIP) kinase family members are involved in several biological processes. However, their role in acute lung injury (ALI) is still unclear. In the present study, we aim to determine the expression and function of RIP kinase family in ALI. MATERIALS AND METHODS: In the present study, ALI was induced in BALB/c male mice by intravenously injecting lipopolysaccharide (LPS). The expression levels of the RIP kinase family in ALI mice were determined using western blotting and immunohistochemical staining...
December 4, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29197105/upper-and-lower-airway-remodelling-mechanisms-in-asthma-allergic-rhinitis-and-chronic-rhinosinusitis-the-one-airway-concept-revisited
#13
REVIEW
Konstantinos Samitas, Alison Carter, Harsha H Kariyawasam, Georgina Xanthou
Allergic rhinitis (AR), chronic rhinosinusitis (CRS) and asthma often co-exist. The one airway model proposes that disease mechanisms occurring in the upper airway may mirror lower airway events. Airway remodelling is the term used to describe tissue structural changes that occur in a disease setting and reflect the dynamic process of tissue restructuring during wound repair. Remodelling has been long identified in the lower airways in asthma and is characterized by epithelial shedding, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, airway smooth muscle hyperplasia and increased angiogenesis...
December 1, 2017: Allergy
https://www.readbyqxmd.com/read/29193684/identification-of-a-novel-compound-targeting-the-nuclear-export-of-influenza-a-virus-nucleoprotein
#14
Feng Huang, Jingliang Chen, Junsong Zhang, Likai Tan, Gui Lu, Yongjie Luo, Ting Pan, Juanran Liang, Qianwen Li, Baohong Luo, Hui Zhang, Gen Lu
Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug-resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti-influenza compound, ZBMD-1, from a library of 20,000 compounds using cell-based influenza A infection assays...
November 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29193276/review-shows-that-using-surfactant-a-number-of-times-or-as-a-vehicle-for-budesonide-may-reduce-the-risk-of-bronchopulmonary-dysplasia
#15
REVIEW
J M Hascoët, J C Picaud, I Ligi, T Blanc, P Daoud, V Zupan, F Moreau, I Guilhoto, M Rouabah, C Alexandre, E Saliba, L Storme, J Patkai, M Pomedio, I Hamon
AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. METHOD: We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources...
November 28, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/29191738/efficacy-and-safety-of-simultaneous-vaccination-with-two-modified-live-virus-vaccines-against-porcine-reproductive-and-respiratory-syndrome-virus-types-1-and-2-in-pigs
#16
Charlotte S Kristensen, L K Kvisgaard, M Pawlowski, S Holmgaard Carlsen, C K Hjulsager, P M H Heegaard, A Bøtner, T Stadejek, S Haugegaard, L E Larsen
The objective of the study was to compare responses of pigs vaccinated with a PRRS MLV vaccine against PRRSV-1 or PRRSV-2 with the responses of pigs vaccinated simultaneously with both vaccines. Furthermore, the efficacy of the two PRRSV MLV vaccination strategies was assessed following challenge. The experimental design included four groups of 4-weeks old SPF-pigs. On day 0 (DPV0), groups 1-3 (N=18 per group) were vaccinated with modified live virus vaccines (MLV) containing PRRSV-1 virus (VAC-T1), PRRSV-2 virus (VAC-T2) or both (VAC-T1T2)...
November 27, 2017: Vaccine
https://www.readbyqxmd.com/read/29190941/associations-between-novel-genetic-variants-in-the-promoter-region-of-malat1-and-risk-of-colorectal-cancer
#17
Yingjun Li, Chengzhen Bao, Simeng Gu, Ding Ye, Fangyuan Jing, Chunhong Fan, Mingjuan Jin, Kun Chen
The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known long non-coding RNA, is involved in pathogenesis and progress of multiple tumors. However, no study has been performed to investigate the relationship between the genetic variants in promoter region of MALAT1 and colorectal cancer risk. In this study, we conducted a two-stage case-control study to evaluate whether MALAT1 genetic variants were associated with colorectal cancer risk. We identified that a single nucleotide polymorphism (SNP) rs1194338 was significantly associated with the decreased colorectal cancer risk with an odds ratio (OR) of 0...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190774/activation-of-the-cholinergic-anti-inflammatory-pathway-by-gts-21-attenuates-cisplatin-induced-acute-kidney-injury-in-mice
#18
Prodyot K Chatterjee, Michael M Yeboah, Malvika H Solanki, Gopal Kumar, Xiangying Xue, Valentin A Pavlov, Yousef Al-Abed, Christine N Metz
Acute kidney injury (AKI) is the most common side effect of cisplatin, a widely used chemotherapy drug. Although AKI occurs in up to one third of cancer patients receiving cisplatin, effective renal protective strategies are lacking. Cisplatin targets renal proximal tubular epithelial cells leading to inflammation, reactive oxygen species, tubular cell injury, and eventually cell death. The cholinergic anti-inflammatory pathway is a vagus nerve-mediated reflex that suppresses inflammation via α7 nicotinic acetylcholine receptors (α7nAChRs)...
2017: PloS One
https://www.readbyqxmd.com/read/29186841/synthetic-secoisolariciresinol-diglucoside-lgm2605-protects-human-lung-in-an-ex-vivo-model-of-proton-radiation-damage
#19
Anastasia Velalopoulou, Shampa Chatterjee, Ralph A Pietrofesa, Cynthia Koziol-White, Reynold A Panettieri, Liyong Lin, Stephen Tuttle, Abigail Berman, Constantinos Koumenis, Melpo Christofidou-Solomidou
Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung...
November 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29180394/redirecting-tgf-%C3%AE-signaling-through-the-%C3%AE-catenin-foxo-complex-prevents-kidney-fibrosis
#20
Xi Qiao, Padmashree Rao, Yun Zhang, Lixin Liu, Min Pang, Hailong Wang, Min Hu, Xinrui Tian, Jianlin Zhang, Ye Zhao, Xin Maggie Wang, Chengshi Wang, Hong Yu, Fei Guo, Qi Cao, Yiping Wang, Yuan Min Wang, Geoff Yu Zhang, Vincent W Lee, Stephen I Alexander, Guoping Zheng, David C H Harris
TGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity...
November 27, 2017: Journal of the American Society of Nephrology: JASN
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