Idiopathic pulmonary fibrosis is a progressive, life-threatening, interstitial lung disease with no effective therapy. In this study, we evaluated the effects of fluorofenidone (FD), a novel pyridone agent, on a murine model of bleomycin-induced pulmonary inflammation and fibrosis. Institute for Cancer Research mice were intravenously injected with BLM or saline for 14 consecutive days. Fluorofenidone, pirfenidone (500 mg · kg · d, respectively), or vehicle was administered throughout the course of the experiment. Animals were killed on day 28, and various parameters reflecting pulmonary vascular permeability, influx of inflammatory cells, and levels of transforming growth factor β in the bronchoalveolar lavage fluid were assessed. Collagen I, α-smooth muscle actin, and fibronectin were measured by real-time reverse transcriptase-polymerase chain reaction or Western blot. Furthermore, caveolin 1 and activation of P38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase were detected by Western blot. Fluorofenidone treatment significantly attenuated the increased pulmonary damage index score, the levels of proteins, transforming growth factor β, and the influx of cells in bronchoalveolar lavage fluid. Fluorofenidone also markedly reduced the expression of fibronectin, α-smooth muscle actin, and collagen I in mouse lung tissues. Inversely, FD restored caveolin 1 protein and mRNA expression, which was significantly downregulated in BLM-induced lung fibrosis. Fluorofenidone also inhibited phosphorylation of extracellular signal-regulated kinase, P38, and c-Jun N-terminal kinase. These findings collectively suggest that FD is an effective agent with antifibrotic and anti-inflammatory properties, and the mechanisms of its antifibrotic effect include regulating caveolin 1 expression and blocking mitogen-activated protein kinase signaling pathways.

BackgroundAdrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.Methodology/Principal FindingsThis study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3) to postnatal day 60 (P60). Asthmatic pregnant rats (AP), nerve growth factor (NGF)-treated pregnant rats (NP) and NGF antibody-treated pregnant rats (ANP) were sensitized and challenged with ovalbumin (OVA); NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP), offspring from AP (OAP), offspring from NP (ONP), and offspring from ANP (OANP). The expressions of phenylethanolamine N-methyltransferase (PNMT) protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI), corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC) were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Conclusion/SignificanceAsthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

Introduction. Chlamydia psittaci is an important cause of community-acquired pneumonia (CAP). The spectrum of CAP due to Chlamydia psittaci ranges from mild, self-limited to acute respiratory failure and the early identification of this disease can be challenging. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to improve the pathogen identification in severe CAP. Hypothesis/Gap Statement. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to rapidly identify pathogens in severe CAP. The early identification and appropriate use of antibiotics can improve the prognosis of severe CAP caused by Chlamydia psittaci . Aim. The aim of the study is to describe the clinical spectrum of severe psittacosis pneumonia to provide a better understanding of this disease and to demonstrate that mNGS is an effective method for pathogen detection. Methodology. Retrospective case analysis from November 2019 to November 2020 was performed. Sixteen cases of severe psittacosis pneumonia were diagnosed through mNGS. Clinical features, laboratory findings, imaging features, treatment and outcome were summarized. Results. Frequent symptoms included fever (16/16, 100%), dyspnoea (16/16, 100%), cough (12/16, 75%), sputum (11/16, 69%) and headache (9/16, 56%). The median leukocytosis was within the normal range, while C-reactive proteins, CK, LDH, AST, D-Dimer were significantly elevated. The feature of computed tomography included ground-glass opacity with consolidation and multiple lobar distributions. The total number of sequences of Chlamydia psittaci identified from bronchoalveolar lavage by mNGS varied from 58 to 57115. Five patients underwent noninvasive mechanical ventilation, four patients underwent high flow humidified oxygen therapy and one patient underwent invasive mechanical ventilation. Two patients had septic shock needing vasoactive medications. All of the sixteen patients experienced full recoveries. Conclusion. The symptoms of severe CAP caused by Chlamydia psittaci were not typical while laboratory results may have some clues. The mNGS technology can early detect of psittacosis, reduce unnecessary use of antibiotics and short the course of the disease.

BackgroundDecreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous β2-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.Methodology/Principal FindingsThirty-two rats were randomly into four groups (n = 8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).Conclusion/SignificanceCompared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.