Inflammatory Monocyte/Macrophage Modulation by Liposome-Entrapped Spironolactone Ameliorates Acute Lung Injury in Mice

Ji, Wen; Qiang, Ya‐Wei; Zhang, Xin; Zhang, Li; Zhang, Yi Dan; Su, Cheng; Xiang, Guo An; Zhang, Mei Ping; Lin, Zhi Chun; Wei, Lü; Wang, Peter; Zhang, Zhuoli; Li, Yu Ming; Zhou, Xin

doi:10.2217/nnm-2016-0006

Cited by 23 publications

(14 citation statements)

References 52 publications

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“…Moreover, neotuberostemonine (NTS), one of the traditional Chinese medicines included in all versions of the Chinese Pharmacopoeia, can effectively attenuate BLM-induced lung fibrosis via suppressing the recruitment and polarization of M2 macrophages [ 122 ]. Intriguingly, Ji et al demonstrated that mineralocorticoid receptor (MR) antagonism by liposome-encapsulated spironolactone (Lipo-SP) could alleviate bleomycin-induced acute pulmonary injury and fibrosis, partially by reducing circulating inflammatory Ly6C high monocyte expansion and repressing alternatively activated mononuclear phagocytes in the alveolar compartment [ 123 , 124 ].…”

Section: Discussionmentioning

confidence: 99%

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a prototype of lethal, chronic, progressive interstitial lung disease of unknown etiology. Over the past decade, macrophage has been recognized to play a significant role in IPF pathogenesis. Depending on the local microenvironments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) phenotypes. In general, M1 macrophages are responsible for wound healing after alveolar epithelial injury, while M2 macrophages are designated to resolve wound healing processes or terminate inflammatory responses in the lung. IPF is a pathological consequence resulted from altered wound healing in response to persistent lung injury. In this review, we intend to summarize the current state of knowledge regarding the process of macrophage polarization and its mediators in the pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, we expect to provide help for developing effective therapeutic strategies in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

et al. 2018

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“…Flow cytometry (FCM) analysis was performed using a Cytomics FC500 cytometer (Beckman-Coulter, Miami, FL) according to previous work [ 59 ]. Fifty microliters of EDTA-anticoagulated whole blood was stained with antibody mix containing 10 μL PerCP-Cy5.5 (clone 1A8), 10 μL FITC-Ly6C (clone HK1.4), and 10 μL PE-CD11b antibodies, incubated for 15 min at room temperature in the dark.…”

Section: Methodsmentioning

confidence: 99%

Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction

et al. 2018

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BackgroundPost-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge.ResultsHere, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and d-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated.ConclusionsOur results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0441-4) contains supplementary material, which is available to authorized users.

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“…In addition to the protection reported to be provided by spironolactone, specific actions against SARS-CoV-2 actions have been proposed, including increased availability of free circulating ACE2 in response to a hyperreninemic state induced by MR antagonism [98][99][100][101][102][103][104], reduction of TMPRSS2 expression due to antagonism of AR [105][106][107], reversal of RAAS abnormalities induced by obesity [108,109], and possible direct antiinflammatory and anti-viral actions that hamper lung injuries [110][111][112][113][114][115][116][117][118][119][120][121]. There are currently three ongoing clinical trials with spironolactone [122][123][124].…”

Section: Of Moderate Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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Inflammatory Monocyte/Macrophage Modulation by Liposome-Entrapped Spironolactone Ameliorates Acute Lung Injury in Mice

Cited by 23 publications

References 52 publications

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction

Repurposing existing drugs for COVID-19: an endocrinology perspective

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