ATP-induced fibrogenic pathway in circulating cells obtained by idiopathic pulmonary fibrotic (IPF) patients is not blocked by nintedanib and pirfenidone.

Idiopathic pulmonary fibrosis (IPF) is a severe disability due to progressive lung dysfunction. IPF has long been viewed as a non-immune form of pulmonary fibrosis, but nowadays it is accepted that a chronic inflammatory response can exacerbate fibrotic patterns. IL-1-like cytokines and ATP are highly detected in the lung and broncho-alveolar lavage fluid of IPF patients.

Sphingosine-1-Phosphate Shapes Healthy Monocytes into An Immunosuppressive Phenotype.

Background/aims: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells.

Methods: To pursue this goal, we performed bioinformatic analyses of public datasets.

The activation of the AIM2 inflammasome after cigarette smoke exposure leads to an immunosuppressive lung microenvironment.

Cigarette smoke is widely known as contributing to chronic inflammation underlying several airway diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. In our previous studies we found that the lung of both COPD and cancer patients were characterized by the presence and activation of the AIM2 inflammasome. Here, we wanted to investigate the upstream step during the establishment of chronic lung inflammation after cigarette smoke exposure.

Absent in melanoma 2 (AIM2) positive profile identifies a poor prognosis of lung adenocarcinoma patients.

The absent in melanoma 2 (AIM2) inflammasome has been demonstrated as involved in tumor growth. In this study we used human samples of lung adenocarcinoma (LUAD) patients, taking advantage of a mouse model of smoking cessation. Human samples were stratified according to the smoking status, high-risk factor for this type of tumor.

Sex Differences in Sphingosine-1-Phosphate Levels Are Dependent on Ceramide Synthase 1 and Ceramidase in Lung Physiology and Tumor Conditions.

Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex 'instructions' in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes.

Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung.

The stimulator of interferon genes (STING) is a master regulator of innate immunity, involved in several inflammatory diseases. Our previous data showed that sphingosine-1-phosphate (S1P) is released during inflammatory conditions in the lung. The aim of this study was to understand the interplay between S1P and STING during both physiological and pathological conditions.

S1P-Induced TNF-α and IL-6 Release from PBMCs Exacerbates Lung Cancer-Associated Inflammation.

Sphingosine-1-phosphate (S1P) is involved in inflammatory signaling/s associated with the development of respiratory disorders, including cancer. However, the underlying mechanism/s are still elusive. The aim of this study was to investigate the role of S1P on circulating blood cells obtained from healthy volunteers and non-small cell lung cancer (NSCLC) patients.

Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined.

Post-COVID-19 Patients Who Develop Lung Fibrotic-like Changes Have Lower Circulating Levels of IFN-β but Higher Levels of IL-1α and TGF-β.

Purpose: SARS-CoV-2 infection induces in some patients a condition called long-COVID-19, herein post-COVID-19 (PC), which persists for longer than the negative oral-pharyngeal swab. One of the complications of PC is pulmonary fibrosis. The purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis.

Intracellular Sphingosine-1-Phosphate Receptor 3 Contributes to Lung Tumor Cell Proliferation.

Background/aims: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) exerts a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Epidemiological studies proved high levels of circulating S1P in non-small cell lung cancer (NSCLC) patients. Studies in literature suggest that high levels of S1P support carcinogenesis but the exact mechanism is still elusive.

Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma.

Cigarette smoking is the leading risk factor for COPD and lung cancer establishment. Epidemiologically, COPD patients are 6.35 times more likely to develop lung cancer.

Sphingosine-1-Phosphate Contributes to TLR9-Induced TNF-α Release in Lung Tumor Cells.

Background/aims: Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid involved in many lung physiological and pathological processes. Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer. The aim of our study was to understand the role of S1P in healthy versus tumor cells after Toll-Like Receptors (TLRs) activation, well-known modulators of sphingolipid metabolism.

Identification of a novel subpopulation of Caspase-4 positive non-small cell lung Cancer patients.

Background: Therapy/prognosis of Non-Small Cell Lung Cancer (NSCLC) patients are strongly related to gene alteration/s or protein expression. However, more than 50% of NSCLC patients are negative to key drugable biomarkers.

Methods: We used human samples of NSCLC and mouse models of lung adenocarcinoma.

Antioxidant and antimicrobial properties of Pelargonium sidoides DC and lactoferrin combination.

Lactoferrin (LAT), a multifunctional protein involved in numerous physiological functions, and the medicinal plant Pelargonium sidoides DC (PEL) have been described for their anti-inflammatory properties. Because the main advantage of natural products consists in administering them in combination rather than as single compound, we aimed to understand whether the combination of PEL and LAT, herein PELIRGOSTIM, could still prove beneficial or additive/synergistic activities during inflammatory conditions. To pursue this goal, we used macrophagic cells (J774.

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.

Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC).

A lesson from a saboteur: High-MW kininogen impact in coronavirus-induced disease 2019.

The newly identified coronavirus SARS-CoV-2 that spread from China is causing the pandemic COVID-19 with a fatality rate from 5-15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS-CoV-2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS-CoV-2 main protease (M ).

The combination of N-Acetyl-L-Cysteine, and (NAXX) exerts bacteriostatic activity against and .

Many herbal agents and medicinal plants have provided clinical interest due to their therapeutic properties, availability and lower side effects. The aim of this study was to understand the anti-bacterial activity of the combination of (PEL), (ADH) and N-Acetyl-L-Cysteine (NAC) (NAXX). We found that NAXX had strong and long-term bacteriostatic activity, which was related to its anti-oxidant activity.

AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway.

Chronic obstructive pulmonary disease (COPD) is a lung disorder characterized by persistent respiratory symptoms and progressive airflow limitation as a consequence of a chronic inflammatory response. Corticosteroids are the main treatment for COPD patients with a history of exacerbation, in that they attenuate exacerbation and dyspnea, and improve the response to bronchodilators. Nevertheless, despite corticosteroid administration, COPD patients still undergo exacerbation phases.

The Inhibition of Caspase-1- Does Not Revert Particulate Matter (PM)-Induced Lung Immunesuppression in Mice.

Air pollution is becoming a threatening issue for human health. Many epidemiological studies relate air pollution index to adverse effects in terms of disease incidence and/or disease exacerbation. In our previous studies, we found air pollutants can induce the release of pro-inflammatory cytokines from human peripheral blood cells.

Drug resistance in non-small cell lung Cancer (NSCLC): Impact of genetic and non-genetic alterations on therapeutic regimen and responsiveness.

The discovery of genetic alterations, that can be targeted therapeutically, has launched a new era for lung cancer research and personalized therapy. However, not all the identified new genetic driver mutations are therapeutically targetable due to high toxicity profile. On the other hand, those genetic alterations that could be pharmacologically targeted, are often subject of alternative mutations that lead to drug resistance, which represents one of the major clinical limitation.

AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells.

Chronic obstructive pulmonary disease (COPD) is now the fourth-leading cause of death worldwide and its prevalence is increasing. The progressive decline of lung function and airway remodelling are a consequence of chronic inflammatory responses. It was recently postulated the involvement of the inflammasome in COPD, although the underlying mechanism/s still need to be elucidated.

Correction: Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer.

[This corrects the article DOI: 10.18632/oncotarget.25049.

Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer.

Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need. A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4.

Activation of the Absent in Melanoma 2 Inflammasome in Peripheral Blood Mononuclear Cells From Idiopathic Pulmonary Fibrosis Patients Leads to the Release of Pro-Fibrotic Mediators.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2-3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood.