CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function. Here, we observed reduced expression of carnitine palmitoyltransferase 1A (CPT1A), a key rate-limiting enzyme of fatty acid oxidation (FAO), in macrophages of lipopolysaccharide (LPS)-induced ALI mouse model. We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by interleukin-10 (IL-10). METHODS: After nasal inhalation rIL-10 and/or LPS, wild type (WT), IL-10-/-, Cre-CPT1Afl/fl and Cre+CPT1Afl/fl mice were sacrificed to harvest bronchoalveolar lavage fluid, blood serum and lungs to examine cell infiltration, cytokine production, lung injury severity and IHC. Bone marrow-derived macrophages (BMDMs) were extracted from mice and stimulated by exogenous rIL-10 and/or LPS. The qRT-PCR, Seahorse XFe96 and FAO metabolite related kits were used to test the glycolysis and FAO level in BMDMs. Immunoblotting assay, confocal microscopy and fluorescence microplate were used to test macrophage polarization as well as mitochondrial structure and function damage. RESULTS: In in vivo experiments, we found that mice lacking CPT1A or IL-10 produced an aggravate inflammatory response to LPS stimulation. However, the addition of rIL-10 could alleviate the pulmonary inflammation in mice effectively. IHC results showed that IL-10 expression in lung macrophage decreased dramatically in Cre+CPT1Afl/fl mice. The in vitro experiments showed Cre+CPT1Afl/fl and IL-10-/- BMDMs became more "glycolytic", but less "FAO" when subjected to external attacks. However, the supplementation of rIL-10 into macrophages showed reverse effect. CPT1A and IL-10 can drive the polarization of BMDM from M1 phenotype to M2 phenotype, and CPT1A-IL-10 axis is also involved in the process of maintaining mitochondrial homeostasis. CONCLUSIONS: CPT1A modulated metabolic reprogramming and polarisation of macrophage under LPS stimulation. The protective effects of CPT1A may be partly attributed to the induction of IL-10/IL-10 receptor expression.

Bronchial Cryo-Denervation for Severe Asthma: A Pilot Study.

INTRODUCTION: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at a 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse events, technical feasibility, and changes in pulmonary function; asthma control questionnaire-7 (ACQ-7); and asthma control test (ACT). RESULTS: BCD was performed on all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged, and significant improvements from baseline ACQ-7 (mean, -1.19, p = 0.0032) and ACT (mean, 3.18, p = 0.0011) scores were observed since the first month's follow-up after a single lung airway treatment, with similar trends till the end of the 12-month follow-up. CONCLUSION: This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

An underlying mechanism behind interventional pulmonology techniques for refractory asthma treatment: Neuro-immunity crosstalk.

Asthma is a common disease that seriously threatens public health. With significant developments in bronchoscopy, different interventional pulmonology techniques for refractory asthma treatment have been developed. These technologies achieve therapeutic purposes by targeting diverse aspects of asthma pathophysiology. However, even though these newer techniques have shown appreciable clinical effects, their differences in mechanisms and mutual commonalities still deserve to be carefully explored. Therefore, in this review, we summarized the potential mechanisms of bronchial thermoplasty, targeted lung denervation, and cryoablation, and analyzed the relationship between these different methods. Based on available evidence, we speculated that the main pathway of chronic airway inflammation and other pathophysiologic processes in asthma is sensory nerve-related neurotransmitter release that forms a "neuro-immunity crosstalk" and amplifies airway neurogenic inflammation. The mechanism of completely blocking neuro-immunity crosstalk through dual-ablation of both efferent and afferent fibers may have a leading role in the clinical efficacy of interventional pulmonology in the treatment of asthma and deserves further investigation.

Locally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner.

Acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome with no effective therapeutic intervention. Neutrophils function in the overwhelming inflammatory process of acute lung injury (ALI) caused by ARDS; however, the phenotypic heterogeneity of pulmonary neutrophils in ALI/ARDS remains largely unknown. Here, using single-cell RNA sequencing, we identify two transcriptionally and functionally heterogeneous neutrophil populations (Fth1hi Neu and Prok2hi Neu) with distinct locations in LPS-induced ALI mouse lungs. Exposure to LPS promotes the Fth1hi Neu subtype, with more inflammatory factors, stronger antioxidant, and decreased apoptosis under the regulation of interleukin-10. Furthermore, prolonged retention of Fth1hi Neu within lung tissue aggravates inflammatory injury throughout the development of ALI/ARDS. Notably, ARDS patients have high ratios of Fth1 to Prok2 expression in pulmonary neutrophils, suggesting that the Fth1hi Neu population may promote the pathological development and provide a marker of poor outcome.

Nogo-B promotes epithelial-mesenchymal transition in lung fibrosis via PERK branch of the endoplasmic reticulum stress pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal chronic pulmonary fibrosis disease and pathological mechanisms of fibrogenesis in IPF are still to be elucidated. Here, we investigated the potential role of Nogo-B in pulmonary fibrogenesis. METHODS: A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). Lung epithelial cells MLE-12 and TC-1 JHU-1 were cultured for TGF-ß treatment. The extent of lung fibrosis was evaluated using hematoxylin and eosin (HE) staining and Masson staining in model mice and Nogo-B knockout mice. The protein levels of Nogo-B, endoplasmic reticulum stress (ERS) sensors including PERK, IRE1α, ATF6 and epithelial-mesenchymal transition (EMT) markers including E-cadherin and N-cadherin, vimentin were assayed by Western blotting respectively after Nogo-B knockdown or overexpression with lentivirus. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate cytokine levels of TGF-ß, TNF-α, IL-1ß, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF). RESULTS: Nogo-B expression was up-regulated in lung tissues of fibrosis model mice and alveolar epithelial cells. Nogo-B knockdown significantly attenuated lung fibrogenesis, downregulated the levels of inflammatory cytokines, inhibited EMT as well as decreased the level of phosphor-PERK/PERK but not the levels of phosphor-IRE1α/IRE1α and c-ATF6. Additionally, a potential efficacy of PERK blockade was demonstrated in improving the extent of lung fibrosis in model mice. CONCLUSIONS: This study discovered that involvement of Nogo-B in pulmonary fibrogenesis was associated with the PERK branch of ERS pathway and EMT. Nogo-B could be considered as a potential therapeutic target for the treatment of IPF.

Geranylgeranyl diphosphate synthase deficiency hyperactivates macrophages and aggravates lipopolysaccharide-induced acute lung injury.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in patients with ARDS compared with healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control (GGPPSfl/fl) and myeloid-selective knockout (GGPPSfl/flLysMcre) mice were then generated. Interestingly, using an LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency upregulated the production of LPS-induced IL-6, IL-1ß, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

Geranylgeranyl diphosphate synthase 1 knockout ameliorates ventilator-induced lung injury via regulation of TLR2/4-AP-1 signaling.

OBJECTIVE: To investigate the role of geranylgeranyl diphosphate synthase 1 (GGPPS1) in ventilator-induced lung injury along with the underlying mechanism. METHODS: A murine VILI model was induced by high-tidal volume ventilation in both wild-type and GGPPS1 knockout mice. GGPPS1 expression was detected in the bronchoalveolar lavage fluid (BALF) supernatants of acute respiratory distress syndrome (ARDS) patients and healthy volunteers, as well as in lung tissues and BALF supernatants of the VILI mice using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western bolt and immunohistochemical (IHC). The wet/dry ratio, total BALF proteins, and lung injury score were analyzed. The percentage of neutrophils was detected by flow cytometry and IHC. Inflammatory cytokine levels were measured by ELISA and qRT-PCR. The related expression of Toll-like receptor (TLR)2/4 and its downstream proteins was evaluated by western blot. RESULTS: GGPPS1 in BALF supernatants was upregulated in ARDS patients and the VILI mice. Depletion of GGPPS1 significantly alleviated the severity of ventilator induced lung injury in mice. Total cell count, neutrophils and inflammatory cytokines (interleukin [IL]-6, IL-1ß, IL-18 and tumor necrosis factor-α) levels in BALF were reduced after GGPPS1 depletion. Moreover, addition of exogenous GGPP in GGPPS-deficient mice significantly exacerbated the severity of ventilator induced lung injury as compared to the PBS treated controls. Mechanistically, the expression of TLR2/4, as well as downstream proteins including activator protein-1 (AP-1) was suppressed in lung tissues of GGPPS1-deficient mice. CONCLUSION: GGPPS1 promoted the pathogenesis of VILI by modulating the TLR2/4-AP-1 signaling pathway, and GGPPS1 knockout significantly alleviated the lung injury and inflammation in the VILI mice.

GSDMD is required for effector CD8+ T cell responses to lung cancer cells.

GSDMD is a recently discovered pyroptosis executioner in monocytes whose N-terminal domain can insert into the inner leaflet of cell membranes and form extensive pores. However, the function of GSDMD in other biological systems remains unclear. In this study, we showed that the expression of GSDMD was consistently correlated with CD8+ T cell markers in The Cancer Genome Atlas (TCGA) cohorts. GSDMD cleavage increased in OT-1 cytotoxic T lymphocytes (CTLs) and human activated CD8+ T cells. Colocalization of GSDMD with granzyme B was observed in the proximity of immune synapses, and GSDMD deficiency reduced the cytolytic capacity of CD8+ T cells. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in CTLs and demonstrated that GSDMD is required for an optimal CTL response to cancer cells.

Inhibition of GGPPS1 attenuated LPS-induced acute lung injury and was associated with NLRP3 inflammasome suppression.

Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intratracheally instilled to induce ALI in lung-specific GGPPS1-knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells was examined. The severity of lung injury and inflammation was determined in lung-specific GGPPS1 knockout and wild-type mice by measuring alveolar exudate, neutrophil infiltration, lung injury, and cell death. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro. We found that GGPPS1 levels increased significantly in lung tissues and alveolar epithelial cells in LPS-induced ALI mice. Compared with wild-type and simvastatin treated mice, the specific deletion of pulmonary GGPPS1 attenuated the severity of lung injury by inhibiting apoptosis of AECs. Furthermore, deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1ß release and pyroptosis, by downregulating NLRP3 expression. Finally, downregulation of GGPPS1 reduced the membrane expression of Ras-related protein Rab10 and Toll-like receptor 4 (TLR4) and inhibited the phosphonation of IκB. This effect might be attributed to the downregulation of GGPP levels. Our results suggested that inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI predominantly by suppressing the NLRP3 inflammasome through Rab10-mediated TLR4 replenishment.

Topotecan Alleviates Lipopolysaccharide-Mediated Acute Lung Injury Via the NF-κB Signaling Pathway.

BACKGROUND: The topoisomerase 1 (Top1) inhibitor has been reported to inhibit inflammatory genes induced by virus and protect mice from sepsis. Its role in acute lung injury (ALI) remains unknown. This study aimed to explore the effects of topotecan (TPT), a Top 1 inhibitor, in lipopolysaccharide (LPS)-ALI. MATERIALS AND METHODS: THP-1 cells were stimulated with LPS and then treated with or without TPT. Inflammatory cytokines expression was measured by ELISA. In vivo, we also detected the effect of TPT in LPS-induced ALI mouse model through hematoxylin-eosin staining of lung tissue and the quantification of total protein, total cell count, and cytokines in bronchoalveolar lavage fluid. To investigate the effect of TPT on transcriptome levels, microarray analyses were performed. KEGG analysis was applied to determine potential pathways modified by TPT. Microarray results were confirmed by real-time PCR and Western blot. RESULTS: TPT significantly decreased the expression of TNF-α and IL-1ß induced by LPS in THP-1 cells. In an LPS-induced ALI mouse model, TPT significantly attenuated lung injury and decreased the levels of total protein, total cell count, and inflammatory cytokine expression in bronchoalveolar lavage fluid. Microarray results showed that TPT significantly increased expression of 958 genes and decreased expression of 1400 genes in THP-1 cells upon LPS stimulation. KEGG analysis demonstrated that differentially expressed genes function in multiple signaling pathways, including the nuclear factor (NF)-κB signaling pathway. The downstream gene of NF-κB, including c-IAP1/2, c-FLIP, Bcl-2, IL-8, and VCAM-1, and the phosphorylation of NF-κB p105, p65, and IκB-α were significantly decreased after TPT administration in THP-1 cells. CONCLUSIONS: In conclusion, TPT attenuates LPS-induced ALI through inhibiting the NF-κB signaling pathway, suggesting that TPT might serve as a useful therapeutic for ALI. Thus, our study has provided new insight for current ALI treatment.

Extracellular mitochondrial DNA promote NLRP3 inflammasome activation and induce acute lung injury through TLR9 and NF-κB.

BACKGROUND: Extracellular mitochondrial DNA (mtDNA) was demonstrated to be capable of inducing pulmonary inflammation through TLR9 while its role in NLRP3 inflammation activation remains unknown. METHODS: C57BL/6 mice were challenged intratracheally with mtDNA. Pulmonary pathology, the NLRP3 and caspase-1 p20 in lung tissues were assayed. PMA-primed THP-1 macrophages were incubated with mtDNA in vitro and cell-free medium were concentrated to detect caspase-1 p20 subunit and NLRP3 by Western blotting. Additionally, IL-1ß, L-18, TNF-α and caspase-1 activity in culture were also analyzed by ELISA kits and activity assay kit. RESULTS: Intratracheal administration of mtDNA increased NLRP3 and caspase-1 p20 subunit in lung together with excessive inflammation and damage. Inhibition of caspase-1 substantially diminished mtDNA-induced lung injury and inflammation. Exposed to mtDNA in THP-1 macrophages resulted in significant up-regulation of NLRP3 and increased caspase-1 p20 subunit release in culture. It also led to significant increased transcripts of NLRP3, ASC, caspase-1 and release of IL-1ß, IL-18 and TNF-α in culture media. Futhermore, mtDNA exposure resulted in significant up-regulation of phosho -p38 MAPK and nucleus translocation of NF-κB. mtDNA-induced Transcripts of NLRP3 and ASC were inhibited by p38 siRNA inhibitor or NF-κB inhibitor. CONCLUSIONS: Extracellular mtDNA promote NLRP3 inflammasome activation, acute pulmonary inflammation and injury through TLR9, p38 MAPK and NF-κB pathways.

Polarization patterns under different sky conditions and a navigation method based on the symmetry of the AOP map of skylight.

The polarization states of a skylight can be used for navigation by a lot of insects as well as by human beings. However, the polarization patterns of skylight are greatly influenced by the atmospheric conditions. This paper studied the polarization patterns of skylight under different sky conditions by polarized imaging measurements, in which the AOT (Aerosol Optical Thickness) and clouds were taken into account. The results showed that both the aerosol and cloud disturbed the polarization patterns of the skylight, but the patterns of AOP (Angle of Polarization) showed great robustness. The symmetry of the AOP images was found to be quite steady under most of the sky conditions. We proposed a navigation method by finding out the solar meridian according to the symmetry of an AOP map. The results showed that the solar meridian can be identified accurately under different situations. The calculation errors slightly fluctuated along with the aerosol and cloud.

Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute Pancreatitis Patients: A Pilot Study.

BACKGROUND: Specific plasma biomarkers in predicting pancreatic necrosis (PNec) are needed in treating acute pancreatitis (AP). AIMS: To investigate the prognostic value of plasma mitochondrial DNA fragments (mtDNA) in patient with AP for PNec. METHODS: AP patients with symptoms onset within 72 h were prospectively enrolled from June 2015 through June 2017 and were assessed for PNec using contrast-enhanced CT scan. Plasma mtDNA concentration (specific mitochondrial gene ND1) was measured using qRT-PCR. RESULTS: Of the 74 AP patients included, significant higher median level of plasma mtDNA was found in severe AP patients than in mild AP patients and healthy controls, but not in moderately severe AP patients. Patients with PNec had higher level of plasma mtDNA than those without PNec (774.2 [IQR 397.6-2205.0] vs. 169.5 [IQR 73.6-683.4] pg/ml, P < 0.05). The area under the receiver operator characteristic curve (ROC-AUC) of mtDNA for predicting PNec was higher than that of CRP (0.813 [95% CI 0.705-0.895] vs. 0.678 [95% CI 0.558-0.783]). Using a cutoff value of 302.5 pg/ml, the sensitivity and specificity for diagnosing PNec were 90.9 and 68.3%, respectively. Finally, plasma mtDNA levels decreased significantly after continuous renal replacement therapy (717.7 [IQR 307.00-1370.00] vs. 237.5 [IQR 117.20-464.80] pg/ml, P < 0.01). CONCLUSIONS: Elevated plasma mtDNA content in AP patients may be used as a more accurate early predictor of PNec in contrast to traditional CRP.

Topotecan alleviates ventilator-induced lung injury via NF-κB pathway inhibition.

OBJECTIVE: We investigated the effect of topotecan on injury and inflammation in a model of ventilator-inducedlunginjury (VILI). METHODS: Acute lung injury (ALI) was induced in mice by high-tidal volume ventilation, and the mice were then treated with topotecan or PBS. Lung tissue and bronchoalveolar lavage fluid were collected to assess pulmonary vascular leaks, inflammation, and cell apoptosis. RESULTS: Compared to PBS treatment, topotecan significantly decreased the ALI score, myeloperoxidase (MPO) content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type Ⅱ alveolar epithelial cell apoptosis. Moreover, topotecan inhibited NF-κB expression and activation in the VILI model. CONCLUSION: Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway.

Improved atmospheric effect elimination method for the roughness estimation of painted surfaces.

We propose a method for eliminating the atmospheric effect in polarimetric imaging remote sensing by using polarimetric imagers to simultaneously detect ground targets and skylight, which does not need calibrated targets. In addition, calculation efficiencies are improved by the skylight division method without losing estimation accuracy. Outdoor experiments are performed to obtain the polarimetric bidirectional reflectance distribution functions of painted surfaces and skylight under different weather conditions. Finally, the roughness of the painted surfaces is estimated. We find that the estimation accuracy with the proposed method is 6% on cloudy weather, while it is 30.72% without atmospheric effect elimination.

Overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma.

This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down-regulated in SPCA-1, PC9 and A549 cells using siRNA and up-regulated in A549 cells using an adenoviral vector. The biological roles of GGPPS in cell proliferation, apoptosis, migration and invasion were determined by MTT and colony formation assays, flow cytometry, and transwell and wound-healing assays, respectively. In addition, the regulatory roles of GGPPS on the expression of several epithelial-mesenchymal transition (EMT) markers were determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown of GGPPS in SPCA-1 and PC9 cells. GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E-cadherin and reduced the expression of N-cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating EMT.

Plasma long noncoding RNA IL-7R as a prognostic biomarker for clinical outcomes in patients with acute respiratory distress syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate a variety of genes and biological processes. Lnc-IL7R plays a considerable role in the regulation of inflammation, but its prognostic potential in acute respiratory distress syndrome (ARDS) has not been fully explained. In this study, the role of lnc-IL7R as a potential biomarker in ARDS was examined. OBJECTIVE: Role of lnc-IL7R as potential biomarker in ARDS. METHODS: LncRNA-IL7R was isolated from the plasma of patients with ARDS and healthy controls and clinical indexes were obtained within 24 h after admission. The relative expression of lnc-IL7R was obtained by quantitative real-time PCR. The correlations between lnc-IL7R and continuous variables in ARDS were tested using Spearman's coefficients. RESULTS: A total of 85 ARDS patients and 49 healthy controls were included. Plasma lnc-IL7R was significantly down-regulated in ARDS compared with the levels in healthy control individuals, especially in severe ARDS (P < .01). The area under the curve (AUC) of lnc-IL7R for ARDS diagnosis was 0.87 (sensitivity 75.3%, specificity 93.9%). The lnc-IL7R levels were correlated with the severity of ARDS (ρ = -0.31, P = .0215), oxygenation index (ρ = 0.61, P < .001), APACHE II score (ρ = -0.04, P = .0230), CRP (ρ = -0.26, P = .0148) and WBC (ρ = -0.29, P = .0064). Lnc-IL7R relative value ≥ 0.33 showed the lower 28-day mortality in the patients with ARDS(P < .05).The survivors showed higher lnc-IL7R level and lower APACHE II score, SOFA score and length of mechanical ventilation than in the non-survivors (P = .0109, P < .001, P < .001 and P = .017, respectively). CONCLUSIONS: Lnc-IL7R is a novel biomarker for the diagnosis of ARDS and predicts the severity of ARDS and 28-day mortality in this patients cohort. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-DOD-16008657).

Biomarkers for patients with trauma associated acute respiratory distress syndrome.

Trauma is a major factor that contributes to the risk for acute respiratory distress syndrome (ARDS). Biomarkers that predict the risk, diagnosis, treatment response and prognosis of ARDS after trauma have been widely investigated. In addition to their applications in clinical diagnosis and treatment, these biomarkers provide important insights into our understanding of the pathogenesis of ARDS. This review begins with a brief introduction regarding the incidence and pathogenesis of trauma-associated ARDS. Then, we focus on reviewing the clinical trials that have been designed to investigate the value of biomarkers in ARDS after trauma. Biomarkers with a confirmed value in ARDS have been organized on the basis of key pathogenic processes that are central to ARDS and are described in detail. Among these, angiopoietin 2 (Ang-2), L-selectin, Clara cell protein 16 (CC16), soluable receptor for advanced glycation end products (sRAGE), Surfactant protein D (SP-D), histones, mtDNAs and some biomarker panels had a certain association with the diagnosis and prognosis of trauma-related ARDS. Further investigations are needed regarding the design of trials, the best sampling approaches and the optimal combinations of the biomarker panels.

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients.

BACKGROUND: Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. METHODS: PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. RESULTS: In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. CONCLUSIONS: Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC.