Identification of KIFC1 as a putative vulnerability in lung cancers with centrosome amplification.

Centrosome amplification (CA), an abnormal increase in the number of centrosomes in the cell, is a recurrent phenomenon in lung and other malignancies. Although CA promotes tumor development and progression by inducing genomic instability (GIN), it also induces mitotic stress that jeopardizes cellular integrity. CA leads to the formation of multipolar mitotic spindles that can cause lethal chromosome segregation errors.

Lysophosphatidic Acid Receptor 1 (LPA) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.

Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive.

Rapamycin Exacerbates Pneumonia by Inhibiting mTOR-RPS6 in Macrophages.

Purpose: This study aimed to explore the effect of Rapamycin (Rapa) in () pneumonia and clarify its possible mechanism.

Methods: We investigated the effects of Rapa on pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis.

A Spontaneous H2-Aa Point Mutation Impairs MHC II Synthesis and CD4 T-Cell Development in Mice.

Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa.

Lipid metabolism in asthma: Immune regulation and potential therapeutic target.

Asthma is a chronic inflammatory disease of the lungs that poses a considerable health and socioeconomic burden. Several risk factors work synergistically to affect the progression of asthma. Lipid metabolism, especially in distinct cells such as T cells, macrophages, granulocytes, and non-immune cells, plays an essential role in the pathogenesis of asthma, as lipids are potent signaling molecules that regulate a multitude of cellular response.

Homeostatic and early-recruited CD101 eosinophils suppress endotoxin-induced acute lung injury.

Introduction: Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI.

Methods: Pulmonary eosinophils were identified by flow cytometry.

Cigarette smoke-initiated autoimmunity facilitates sensitisation to elastin-induced COPD-like pathologies in mice.

It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease (COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2 weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3 days or 1 month.

Inactivation of MTOR promotes autophagy-mediated epithelial injury in particulate matter-induced airway inflammation.

Particulate matter (PM) is able to induce airway epithelial injury, while the detailed mechanisms remain unclear. Here we demonstrated that PM exposure inactivated MTOR (mechanistic target of rapamycin kinase), enhanced macroautophagy/autophagy, and impaired lysosomal activity in HBE (human bronchial epithelial) cells and in mouse airway epithelium. Genetic or pharmaceutical inhibition of MTOR significantly enhanced, while inhibition of autophagy attenuated, PM-induced IL6 expression in HBE cells.

Author Correction: Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.

Since the publication of the article, the authors became aware that Figs. 1c, 5k and 6m contained errors in representative image and PAS score in control groups. The corrected Figs.

Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury.

Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31 cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury.

Autophagy as a double-edged sword in pulmonary epithelial injury: a review and perspective.

Pulmonary epithelial cells form the first line of defense of human airways against foreign irritants and also represent as the primary injury target of these pathogenic assaults. Autophagy is a revolutionary conserved ubiquitous process by which cytoplasmic materials are delivered to lysosomes for degradation when facing environmental and/or developmental changes, and emerging evidence suggests that autophagy plays pivotal but controversial roles in pulmonary epithelial injury. Here we review recent studies focusing on the roles of autophagy in regulating airway epithelial injury induced by various stimuli.

Activating transcription factor 3 represses cigarette smoke-induced IL6 and IL8 expression via suppressing NF-κB activation.

Airway and lung inflammation is a fundamental hallmark of chronic obstructive pulmonary disease (COPD). Activating transcription factor 3 (ATF3) has been reported to negatively regulate many pro-inflammatory cytokines and chemokines. However, little is known about the impact of ATF3 on the inflammatory response of COPD.

Activating Transcription Factor 3 Is Essential for Cigarette Smoke-Induced Mucin Expression via Interaction with Activator Protein-1.

Mucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction.

Autophagy plays an essential role in cigarette smoke-induced expression of MUC5AC in airway epithelium.

Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells.

Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation, and remodeling in a murine model of chronic asthma.

Suhuang antitussive capsule (Suhuang), a traditional Chinese medication, is found effective in treating chronic cough and cough variant asthma (CVA). This study aimed to determine the possible effects and underlying mechanisms of Suhuang on chronic ovalbumin (OVA)-induced airway hyperresponsiveness (AHR), inflammation, and remodeling in mice. Mice were randomly assigned to six experimental groups: control, OVA model with or without Suhuang (low dose: 3.

Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium.

Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes.

Nuclear erythroid 2 p45-related factor-2 Nrf2 ameliorates cigarette smoking-induced mucus overproduction in airway epithelium and mouse lungs.

Background And Objective: Nuclear erythroid 2 p45-related factor-2 (Nrf2) is known to play important roles in airway disorders, whereas little has been investigated about its direct role in airway mucus hypersecretion. The aim of this study is to determine whether this factor could protect pulmonary epithelium and mouse airway from cigarette-induced mucus overproduction.

Methods: Using genetic approaches, the role of Nrf2 on cigarette smoking extracts (CSE) induced MUC5AC expression was investigated in lung A549 cells.

mTOR and autophagy in regulation of acute lung injury: a review and perspective.

The mammalian target of rapamycin (mTOR) is a central regulator of many major cellular processes including protein and lipid synthesis and autophagy, and is also implicated in an increasing number of pathological conditions. Emerging evidence suggests that both mTOR and autophagy are critically involved in the pathogenesis of pulmonary diseases including acute lung injury (ALI). However, the detailed mechanisms of these pathways in disease pathogenesis require further investigations.