Glandular papilloma in lung parenchyma.

Solitary respiratory papilloma is a rare epithelial tumour that can be categorized into multiple subtypes. The glandular type (Glandular papilloma, GP) is the rarest. Most GP occurs in the proximal airways and is only rarely found in the lung parenchyma. In this article, we reported a case of GP in lung parenchyma.

Computed tomography manifestations of a case of varicella zoster virus (VZV) pneumonia.

Disseminated VZV infections is rare in healthy adults. Several studies have reported VZV reactivation and eruption happens in an immunocompromised host especially after solid organ transplantation. Nonetheless, diffuse bilateral lung VZV infections is also rare. We report a case of disseminated VZV pneumonia after renal transplantation and methylprednisolone treatment. This report highlights the computed tomography manifestations of disseminated VZV pneumonia.

MicroRNA­200c­3p regulates seawater­induced acute lung injury via ANGII and ACE2/ANG1­7 pathways.

Apoptosis is a main characteristic of seawater aspiration-induced acute lung injury (ALI). The local angiotensin (ANG) system angiotensin converting enzyme (ACE)-2/ANG1-7/Mas axis and ANGII/angiotensin II receptor type 1 (AT1) play an important role in apoptosis. MicroRNA (miR)-200c-3p is involved in the regulation of the ACE-2 pathway, but its role and mechanism in seawater-induced ALI remain to be elucidated. In the present study, seawater-ALI lung tissue and cell model was established and apoptosis-related proteins, ACE2, ANGII, ANG1-7 were detected by western blotting following downregulation of miR-200c-3p. In addition, miR-200c-3p was detected by reverse transcription-quantitative PCR. The target relationship between miR-200c-3p and ACE2 was confirmed by dual-luciferase reporter assay. Seawater stimulation increased the expression of miR-200c-3p, ANGII and decreased ACE-2/ANG1-7 expression and induced changes of apoptosis-related protein expression. Apoptosis can be inhibited by AT1 blocker and abrogated by addition of ANG1-7 following seawater stimulation. In addition, inhibition of miR-200c-3p suppressed apoptosis and decreased the expression of ANGII, but increased the ACE-2/ANG1-7 expression. These results suggested that increased expression of miR-200c-3p was an important cause in seawater-induced ALI and this phenomenon was through inhibition of ACE2/ANG1-7 pathway.

A case of tuberculous pleurisy characterized by bleeding and necrosis documented by medical thoracoscope.

Tuberculous pleurisy is a main cause of pleural effusions. The main histological abnormalities in pleural biopsy of tuberculous pleurisy are caseating granulomas and epithelioid cell granuloma. In our case, chronic inflammation of fibrous tissue with bleeding, necrosis, and exudation were observed during a medical thoracoscopy as manifestations of tuberculous pleurisy.

Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE-/- mice.

Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter ≤2.5 µm) exposure is associated with atherosclerosis. Extracellular vesicles (EVs) are messengers between intracellular communications which are important in diseases procession. At present, whether EVs derived from PM2.5-exposed alveolar epithelial cells (P-EVs) involve in atherosclerosis has not been clearly understood. This study is performed to investigate the effects of P-EVs on the development of endothelium adhesion and atherosclerosis. Here, ApoE-/- mice were randomized into different groups receiving one of the following treatments, filtered air (FA), PM2.5, PBS, PBS-treated alveolar epithelial cells-derived EVs (EVs), or P-EVs. Then the atherosclerosis level in aortas or aorta sections was evaluated by oil red O staining. The results indicated that ApoE-/- mice treated with P-EVs or PM2.5 showed more obvious atherosclerosis plaques in aortas and aortic arches than those treated with EVs or PBS. Endothelial cells (ECs) were treated with PBS, EVs, P-EVs, or PM2.5. The adhesion property, miRNAs level and expressions of IκBα, phosphorylated IκBα, NF-κB p65, phosphorylated NF-κB p65, and VCAM1 in ECs were determined. It was found that P-EVs activated IκBα-NF-κB-VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF-α inhibitor) or miR-326-3p inhibitor. Further study suggested that P-EVs induced upregulation of TNF-α and miR-326-3p in recipient ECs and contributed to the phosphorylation of NF-κB p65. Collectively, EVs derived from PM2.5-exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating IκBα-NF-κB-VCAM1 signaling.

ACE-2/ANG1-7 ameliorates ER stress-induced apoptosis in seawater aspiration-induced acute lung injury.

Previous studies have shown that apoptosis of alveolar cells can be regulated by autocrine of angiotensin (ANG)II and its counter regulatory ACE-2/ANG1-7 axis. Our earlier study has shown that endoplasmic reticulum (ER) stress in response to seawater aspiration eventually led to apoptosis in lung tissue. In this study, we examined the hypothesis that ER stress-induced apoptosis in seawater aspiration-induced acute lung injury (ALI) might also be regulated by the ANGII/ANG1-7 system. ER stress was induced by seawater stimulation and proteasome inhibitor MG132 (an ER stress inductor). Moreover, ER stress in seawater-stimulated lung tissues and rat pulmonary microvascular endothelial cells (RPMVECs) promoted ANGII expression and decreased ACE-2/ANG1-7 expression. ER stress induced by seawater stimulation also led to apoptosis. Apoptosis induced by seawater stimulation and MG132 were inhibited by ANGII receptor blocker and abrogated by the addition of ANG1-7. These results suggest that apoptosis induced by ER stress in seawater aspiration-induced ALI is regulated by ANG II/ANG1-7 in lung tissues and RPMVECs. In addition, the active form of X-box binding protein 1 (XBP1), spliced XBP1 (XBP1s), a transcription factor that regulates ER-associated degradation genes during ER stress was significantly activated in seawater stimulated cells. Based on this phenomenon we designed a tandem gene, Wfs1 promoter (a target gene promoter of XBP1s)- ACE2 and ANG1-7 and transfected this tandem gene into seawater-stimulated cells. ACE-2/ANG1-7 expression were significantly promoted and apoptosis was inhibited in cells transfected with the tandem gene. These results suggest that stimulation of ACE-2/ANG1-7 may be a therapeutic target of ER stress-induced apoptosis in seawater aspiration-induced ALI.

Endothelial semaphorin 7A promotes seawater aspiration-induced acute lung injury through plexin C1 and ß1 integrin.

Inflammation and edema are two main characteristics in seawater aspiration­induced acute lung injury (ALI). In a previous study of the authors, it was demonstrated that endothelial semaphorin 7A (SEMA7A) serves an important role in the development of seawater­induced inflammation and edema. However, the mechanism of endothelial SEMA7A­mediated ALI remains unclear. Therefore, the authors explored the effect of SEMA7A in rat pulmonary microvascular endothelial cells (RPMVECs) and the interaction between endothelial SEMA7A and alveolar macrophages during seawater aspiration­induced ALI. The role of SEMA7A in endothelial permeability was detected using plexin C1 blocking antibody or SEMA7A small interfering (si)RNA. In addition, RPMVECs were co­cultured with rat alveolar macrophage cell line­NR8383 cells and pro­inflammatory cytokine production was detected. Interaction between the ß1 integrin and SEMA7A was detected using the ß1 integrin blocking antibody or SEMA7A siRNA. Seawater stimulation induced endothelial cytoskeleton remodeling, endothelial permeability, phosphorylation of cofilin, and increased the vascular endothelial growth factor (VEGF) expression in RPMVECs. Moreover, seawater stimulation led to expression of proinflammatory cytokines and activated the nuclear factor­κB pathway in co­cultured cells. However, blockage with the plexin C1 antibody inhibited endothelial cytoskeleton remodeling, endothelial permeability, phosphorylation of cofilin, and treatment with SEMA7A siRNA inhibited expression of VEGF in RPMVECs. In addition, blockage with ß1 integrin antibody reduced expression of proinflammatory cytokines and inhibited activation of NF­κB in co­culture cells. These results suggest that SEMA7A promotes seawater induced lung edema via plexin C1 and stimulates seawater induced lung inflammation via ß1 integrin.

1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Lung Injury By Inhibiting The Translocation Of NF-κB and RhoA.

Our previous study have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses seawater aspiration-induced ALI in vitro and in vivo. We also have confirmed that treatment with calcitriol ameliorates seawater aspiration-induced inflammation and pulmonary edema via the inhibition of NF-κB and RhoA/Rho kinase pathway activation. In our further work, we investigated the effect of calcitriol on nuclear translocation of NF-κB and membrane translocation of RhoA in vitro. A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not for 48 h and then stimulated with 25% seawater for 40 min. After these treatments, cells were collected and performed with immunofluorescent staining to observe the translocation of NF-κB and RhoA and the cytoskeleton remodeling. In vitro, seawater stimulation activates nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. In addition, seawater administration also induced cytoskeleton remodeling in A549 cells and RPMVECs. However, pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways, as demonstrated by the reduced nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. Meanwhile, treatment of calcitriol also regulated the cytoskeleton remodeling in both A549 cells and RPMVECs. These results demonstrated that treatment with calcitriol ameliorates seawater aspiration-induced ALI via inhibition of nuclear translocation of NF-κB and membrane translocation of RhoA and protection of alveolar epithelial and pulmonary microvascular endothelial barrier.

Identification of distinct genes associated with seawater aspiration­induced acute lung injury by gene expression profile analysis.

Seawater aspiration­induced acute lung injury (ALI) is a syndrome associated with a high mortality rate, which is characterized by severe hypoxemia, pulmonary edema and inflammation. The present study is the first, to the best of our knowledge, to analyze gene expression profiles from a rat model of seawater aspiration­induced ALI. Adult male Sprague­Dawley rats were instilled with seawater (4 ml/kg) in the seawater aspiration­induced ALI group (S group) or with distilled water (4 ml/kg) in the distilled water negative control group (D group). In the blank control group (C group) the rats' tracheae were exposed without instillation. Subsequently, lung samples were examined by histopathology; total protein concentration was detected in bronchoalveolar lavage fluid (BALF); lung wet/dry weight ratios were determined; and transcript expression was detected by gene sequencing analysis. The results demonstrated that histopathological alterations, pulmonary edema and total protein concentrations in BALF were increased in the S group compared with in the D group. Analysis of differential gene expression identified up and downregulated genes in the S group compared with in the D and C groups. A gene ontology analysis of the differential gene expression revealed enrichment of genes in the functional pathways associated with neutrophil chemotaxis, immune and defense responses, and cytokine activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the cytokine­cytokine receptor interaction pathway was one of the most important pathways involved in seawater aspiration­induced ALI. In conclusion, activation of the cytokine­cytokine receptor interaction pathway may have an essential role in the progression of seawater aspiration­induced ALI, and the downregulation of tumor necrosis factor superfamily member 10 may enhance inflammation. Furthermore, IL­6 may be considered a biomarker in seawater aspiration­induced ALI.

Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.

Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.

1α,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-κB and RhoA/Rho kinase pathways.

INTRODUCTION: Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration-induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism. METHODS: Male SD rats receiving different doses of calcitriol or not, underwent seawater instillation. Then lung samples were collected at 4 h for analysis. In addition, A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not and then stimulated with 25% seawater for 40 min. After these treatments, cells samples were collected for analysis. RESULTS: Results from real-time PCR showed that seawater stimulation up-regulated the expression of vitamin D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also activates NF-κB and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved lung histopathologic changes, reduced inflammation, lung edema and vascular leakage. CONCLUSIONS: These results demonstrated that NF-κB and RhoA/Rho kinase pathways are critical in the development of lung inflammation and pulmonary edema and that treatment with calcitriol could ameliorate seawater aspiration-induced ALI, which was probably through the inhibition of NF-κB and RhoA/Rho kinase pathways.