Single-cell RNA sequencing reveals heterogeneity of ALI model and epithelial cell alterations after exposure to electronic cigarette aerosol.

Electronic cigarettes (e-cigarettes) have been advertised as a healthier alternative to traditional cigarettes; however, their exact effects on the bronchial epithelium are poorly understood. Air-liquid interface culture human bronchial epithelium (ALI-HBE) contains various cell types, including basal cell, ciliated cell and secretory cell, providing an model that simulates the biological characteristics of normal bronchial epithelium. Multiplex single-cell RNA sequencing of ALI-HBE was used to reveal previously unrecognized transcriptional heterogeneity within the human bronchial epithelium and cell type-specific responses to acute exposure to e-cigarette aerosol (e-aerosol) containing distinct components (nicotine and/or flavoring).

Inhaled Macrophage Apoptotic Bodies-Engineered Microparticle Enabling Construction of Pro-Regenerative Microenvironment to Fight Hypoxic Lung Injury in Mice.

Oxygen therapy cannot rescue local lung hypoxia in patients with severe respiratory failure. Here, an inhalable platform is reported for overcoming the aberrant hypoxia-induced immune changes and alveolar damage using camouflaged poly(lactic--glycolic) acid (PLGA) microparticles with macrophage apoptotic body membrane (cMAB). cMABs are preloaded with mitochondria-targeting superoxide dismutase/catalase nanocomplexes (NCs) and modified with pathology-responsive macrophage growth factor colony-stimulating factor (CSF) chains, which form a core-shell platform called C-cMAB/NC with efficient deposition in deeper alveoli and high affinity to alveolar epithelial cells (AECs) after CSF chains are cleaved by matrix metalloproteinase 9.

An Inhalable Hybrid Biomimetic Nanoplatform for Sequential Drug Release and Remodeling Lung Immune Homeostasis in Acute Lung Injury Treatment.

Interactions of lung macrophages and recruited neutrophils with the lung microenvironment continuously aggravate the dysregulation of lung inflammation in the pathogenesis of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Either modulating macrophages or destroying neutrophil counts cannot guarantee a satisfactory outcome in ARDS treatment. Aimed at inhibiting the coordinated action of neutrophils and macrophages and modulating the hyper-inflammatory condition, an inhalable biomimetic sequential drug-releasing nanoplatform was developed for the combinatorial treatment of ALI.

Targeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata.

Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca signaling is a potential therapeutic strategy for asthma.

SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia.

Background: The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition.

Interactions of Inhaled Liposome with Macrophages and Neutrophils Determine Particle Biofate and Anti-Inflammatory Effect in Acute Lung Inflammation.

Since most current studies have focused on exploring how phagocyte internalization of drug-loaded nanovesicles by macrophages would affect the function and therapeutic effects of infiltrated neutrophils or monocytes, research has evaluated the specificity of the inhaled nanovesicles for targeting various phagocytes subpopulations. In this study, liposomes with various charges (including neutral (L1), anionic (L2), and cationic at inflammatory sites (L3)) were constructed to investigate how particle charge determined their interactions with key phagocytes (including macrophages and neutrophils) in acute lung injury (ALI) models and to establish correlations with their biofate and overall anti-inflammatory effect. Our results clearly indicated that neutrophils were capable of rapidly sequestering L3 with a 3.

The effects of intermittent hypoxia on hepatic expression of fatty acid translocase CD36 in lean and diet-induced obese mice.

Background: Both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are prevalent within obese individuals. We aimed to investigate the effects of intermittent hypoxia (IH), a clinical feature of OSA, on hepatic expression of fatty acid translocase (CD36) in relation to liver injury in lean and diet-induced obese mice.

Methods: Four-week-old male C57BL/6J mice were randomized to standard diet (SD) or high fat (HF) diet groups.

Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in nigrostriatal and cortical brain regions associated with pathogenic α-synuclein (αSyn) aggregate/oligomer accumulation. LRRK2 hyperactivity is a disease-modifying therapeutic target in PD. However, LRRK2 inhibition may be associated with peripheral effects, albeit with unclear clinical consequences.

Targeting mitochondrial permeability transition pore ameliorates PM-induced mitochondrial dysfunction in airway epithelial cells.

Particulate matter with aerodynamic diameter not larger than 2.5 μm (PM) escalated the risk of respiratory diseases. Mitochondrial dysfunction may play a pivotal role in PM-induced airway injury.

Therapeutic potential and mechanism of Dendrobium officinale polysaccharides on cigarette smoke-induced airway inflammation in rat.

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide, and is characterized by persistent respiratory symptoms and airflow limitation due to chronic airway inflammation. Cigarette smoking is a major risk factor for COPD. This study aims to determine the therapeutic effects of polysaccharides extracted from Dendrobium officinale (DOPs), a valuable traditional Chinese Medicinal herb, on cigarette smoke (CS)-induced airway inflammation in a rat passive smoking model.

Amelioration of Cigarette Smoke-Induced Mucus Hypersecretion and Viscosity by Polysaccharides and .

Chronic obstructive pulmonary disease (COPD), characterized by oxidative stress and inflammation, is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. polysaccharides (DOPs) are the main active ingredients extracted from , which have been reported to have antioxidant and anti-inflammatory activity as well as inhibition of mucin gene expression. This study is aimed at investigating the effect of DOPs on CS-induced mucus hypersecretion and viscosity and .

Size effect of curcumin nanocrystals on dissolution, airway mucosa penetration, lung tissue distribution and absorption by pulmonary delivery.

Nanocrystals (NCs) have been introduced for use in pulmonary delivery in recent decades. Although the deposition and bioavailability have been extensively studied, little is known about the biofate, which influences the drug release and absorption process of NCs. In this study, we fabricated three different sized curcumin NCs by adjusting the parameters of mill machine using a wet milling method and studied the size effect on pulmonary absorption.

Rational particle design to overcome pulmonary barriers for obstructive lung diseases therapy.

Pulmonary delivery of active drugs has been applied for the treatment of obstructive lung diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis, for several decades and has achieved progress in symptom management by bronchodilator inhalation. However, substantial progress in anti-inflammation, prevention of airway remodeling and disease progression is limited, since the majority of the formulation strategies focus only on particle deposition, which is insufficient for pulmonary delivery of the drugs. The lack of knowledge on lung absorption barriers in obstructive lung diseases and on pathogenesis impedes the development of functional formulations by rational design.

Differential metabolic and inflammatory responses to intermittent hypoxia in substrains of lean and obese C57BL/6 mice.

Aims: This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J).

Materials And Methods: Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week.

Low-Frequency Intermittent Hypoxia Suppresses Subcutaneous Adipogenesis and Induces Macrophage Polarization in Lean Mice.

Background: The relationship between obstructive sleep apnoea (OSA) and metabolic disorders is complex and highly associated. The impairment of adipogenic capacity in pre-adipocytes may promote adipocyte hypertrophy and increase the risk of further metabolic dysfunction. We hypothesize that intermittent hypoxia (IH), as a pathophysiologic feature of OSA, may regulate adipogenesis by promoting macrophage polarization.

(-)-Epigallocatechin-3-gallate suppresses cigarette smoke-induced inflammation in human cardiomyocytes via ROS-mediated MAPK and NF-κB pathways.

Background: Cigarette smoking is the leading cause for the initiation and development of cardiovascular disease (CVD). Oxidative stress and inflammatory responses play important roles in the pathophysiological processes of smoking-induced cardiac injury. (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, which is made from Camellia sinensis leaves, has been reported to possess potent anti-oxidant property.

Haemin attenuates intermittent hypoxia-induced cardiac injury via inhibiting mitochondrial fission.

Obstructive sleep apnoea (OSA) characterized by intermittent hypoxia (IH) is closely associated with cardiovascular diseases. IH confers cardiac injury via accelerating cardiomyocyte apoptosis, whereas the underlying mechanism has remained largely enigmatic. This study aimed to explore the potential mechanisms involved in the IH-induced cardiac damage performed with the IH-exposed cell and animal models and to investigate the protective effects of haemin, a potent haeme oxygenase-1 (HO-1) activator, on the cardiac injury induced by IH.

Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach.

The presence of serotonin in cigarette smoke - a possible mechanistic link to 5-HT-induced airway inflammation.

We previously reported the involvement of serotonin (5-HT) metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo. Here, we report cigarette smoke as a source of serotonin (5-HT) to the airways and aim at investigating the effects of 5-HT on oxidative stress and inflammation in human bronchial epithelial cells (BEAS-2B). A 5-HT analog was identified to be present in aqueous phase cigarette smoke using the LC-MS/MS approach, which was later confirmed by a 5-HT enzyme-linked immune assay (EIA).

[The role of heme oxygenase-1 in the protection of chronic intermittent hypoxia-induced lung injury in vivo].

Objective: To investigate the effect of chronic intermittent hypoxia (CIH) on inflammatory and pathological changes of the lung in an animal model as well as the protective effect of heme oxygenase-1 in this process.

Methods: Twenty-four Male Sprague-Dawley rats were randomly divided into 4 groups: intermittent normoxia (IN) group, CIH group, IN+hemin injection (hemin) group and CIH+hemin injection (CIH+hemin) group. The CIH profiling was repetitive 4 min 10% O₂and 2 min 21% O₂for 8 hours per day for 6 weeks.

Downregulation of thymidylate synthase with arsenic trioxide in lung adenocarcinoma.

Thymidylate synthase (TYMS) is an important chemotherapeutic target in non-small cell lung cancer (NSCLC). Arsenic trioxide (ATO) has been shown to suppress TYMS in a colonic cancer model. We examined the effects of TYMS suppression by ATO in lung adenocarcinoma.

Combination of arsenic trioxide and chemotherapy in small cell lung cancer.

Introduction: Small cell lung cancer (SCLC) carries high mortality despite standard chemotherapy. Arsenic trioxide (ATO) has demonstrated clinical efficacy in leukemia and in vitro activity in various solid tumors. This study was conducted to determine the in vitro and in vivo combination effects of ATO and chemotherapy in SCLC.

Erlotinib-induced autophagy in epidermal growth factor receptor mutated non-small cell lung cancer.

Purpose: Erlotinib is a commonly used tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC). Autophagy is a catabolic process in response to stress and deprivation of nutrients. This study aims to investigate whether autophagy confers acquired resistance to erlotinib treatment in NSCLC.

Intermittent hypoxia-induced NF-κB and HO-1 regulation in human endothelial EA.hy926 cells.

Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA) which is increasingly recognized as an independent risk factor for atherosclerosis. Oxidative stress, inflammation, and cell apoptosis are major pathological events initiating or accelerating atherogenesis. This study addressed whether IH would affect these proatherogenic factors in endothelial cells and the mechanistic pathways involved.