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  1. Article ; Online: Influence of azithromycin and allograft rejection on the post-lung transplant microbiota.

    Spence, Christopher D / Vanaudenaerde, Bart / Einarsson, Gísli G / Mcdonough, John / Lee, Andrew J / Johnston, Elinor / Verleden, Geert M / Elborn, J Stuart / Dupont, Lieven J / Van Herck, Anke / Gilpin, Deirdre F / Vos, Robin / Tunney, Michael M / Verleden, Stijn E

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2019  Volume 39, Issue 2, Page(s) 176–183

    Abstract: Background: Alterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft ... ...

    Abstract Background: Alterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft dysfunction (CLAD). The objective of this study was to determine the association between azithromycin use, CLAD, acute rejection, airway inflammation, and bacterial microbiota composition and structure after LTx.
    Methods: Bronchoalveolar lavage samples (n = 219) from 69 LTx recipients (azithromycin, n = 32; placebo, n = 37) from a previously conducted randomized placebo-controlled trial with azithromycin were analyzed. Samples were collected at discharge, 1, and 2 years following randomization and at CLAD diagnosis. Bacterial microbial community composition and structure was determined using 16S ribosomal RNA gene sequencing and associated with clinically important variables.
    Results: At discharge and following 1 and 2 years of azithromycin therapy, no clear differences in microbial community composition or overall diversity were observed. Moreover, no changes in microbiota composition were observed in CLAD phenotypes. However, acute rejection was associated with a reduction in community diversity (p = 0.0009). Significant correlations were observed between microbiota composition, overall diversity, and levels of inflammatory cytokines in bronchoalveolar lavage, particularly CXCL8.
    Conclusions: Chronic azithromycin usage did not disturb the bacterial microbiota. However, acute rejection episodes were associated with bacterial dysbiosis.
    MeSH term(s) Allografts ; Anti-Bacterial Agents/therapeutic use ; Azithromycin/therapeutic use ; Bronchoalveolar Lavage Fluid/microbiology ; Chronic Disease ; Female ; Graft Rejection/diagnosis ; Graft Rejection/drug therapy ; Graft Rejection/microbiology ; Humans ; Lung/microbiology ; Lung Transplantation ; Male ; Microbiota ; Middle Aged ; Prognosis
    Chemical Substances Anti-Bacterial Agents ; Azithromycin (83905-01-5)
    Language English
    Publishing date 2019-11-21
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2019.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis

    Ahangari, Farida / Price, Nathan L. / Malik, Shipra / Chioccioli, Maurizio / Bärnthaler, Thomas / Adams, Taylor S. / Kim, Jooyoung / Pradeep, Sai Pallavi / Ding, Shuizi / Cosmos, Carlos / Rose, Kadi-Ann S. / Mcdonough, John E. / Aurelien, Nachelle R. / Ibarra-berastegi, Gabriel / Omote, Norihito / Schupp, Jonas C. / Deiuliis, Giuseppe / Villalba, Julian / Sharma, Lokesh /
    Ryu, Changwan / Dela Cruz, Charles S. / Liu, Xinran / Prasse, Antje / Rosas, Ivan O. / Bahal, Raman / Sánchez, Carlos José Hernando / Kaminski, Naftali

    2023  

    Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 ( ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns of sterol regulatory element binding protein (SREBP) genes are master regulators of sterol and fatty acid (FA) metabolism. miR-33 controls macrophage immunometabolic response and enhances mitochondrial biogenesis, FA oxidation, and cholesterol efflux. Here, we show that miR-33 levels are increased in bronchoalveolar lavage (BAL) cells isolated from patients with IPF compared with healthy controls. We demonstrate that specific genetic ablation of miR-33 in macrophages protects against bleomycin-induced pulmonary fibrosis. The absence of miR-33 in macrophages improves mitochondrial homeostasis and increases autophagy while decreasing inflammatory response after bleomycin injury. Notably, pharmacological inhibition of miR-33 in macrophages via administration of anti-miR-33 peptide nucleic acids (PNA-33) attenuates fibrosis in different in vivo and ex vivo mice and human models of pulmonary fibrosis. These studies elucidate a major role of miR-33 in macrophages in the regulation of pulmonary fibrosis and uncover a potentially novel therapeutic approach to treat this disease.

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    Subject code 610
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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