Dried Cannabis Use, Tobacco Smoking, and COVID-19 Infection: Findings from a Longitudinal Observational Cohort Study.

Objective: The potential impact of cigarette and cannabis smoking on COVID-19 infection outcomes is not well understood. We investigated the association between combustible tobacco use and dried cannabis use with COVID-19 infection in a longitudinal cohort of community adults.

Method: The sample comprised 1,343 participants, originally enrolled in 2018, who reported their cigarette and cannabis use in 11 assessments over 44 months, until 2022.

Cannabis smoke suppresses antiviral immune responses to influenza A in mice.

Rationale: Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking; however, since cannabinoids exhibit anti-inflammatory effects, cannabis smoke exposure may impact viral infection in distinct ways.

Methods: Male and female BALB/c mice were exposed daily to cannabis smoke and concurrently intranasally instilled with IAV.

Humanization of the mdx Mouse Phenotype for Duchenne Muscular Dystrophy Modeling: A Metabolic Perspective.

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy (MD) that is characterized by early muscle wasting and lethal cardiorespiratory failure. While the mdx mouse is the most common model of DMD, it fails to replicate the severe loss of muscle mass and other complications observed in patients, in part due to the multiple rescue pathways found in mice. This led to several attempts at improving DMD animal models by interfering with these rescue pathways through double transgenic approaches, resulting in more severe phenotypes with mixed relevance to the human pathology.

Smoking status impacts treatment efficacy in smoke-induced lung inflammation: A pre-clinical study.

Smoking status and smoking history remain poorly accounted for as variables that could affect the efficacy of new drugs being tested in chronic obstructive pulmonary disease (COPD) patients. As a proof of concept, we used a pre-clinical model of cigarette smoke (CS) exposure to compare the impact of treatment during active CS exposure or during the cessation period on the anti-inflammatory effects IL-1α signaling blockade. Mice were exposed to CS for 2 weeks, followed by a 1-week cessation, then acutely re-exposed for 2 days.

Role of progression of training volume on intramuscular adaptations in patients with chronic obstructive pulmonary disease.

Quadriceps dysfunction is a common systemic manifestation of chronic obstructive pulmonary disease (COPD), for which treatment using resistance training is highly recommended. Even though training volume is suggested to be a key explanatory factor for intramuscular adaptation to resistance training in healthy older adults, knowledge is scarce on the role of progression of training volume for intramuscular adaptations in COPD. This study was a sub-analysis of a parallel-group randomized controlled trial.

Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects.

There are no therapeutics that directly enhance chronic endothelial nitric oxide (NO) release, which is typically associated with vascular homeostasis. In contrast, angiotensin II (AngII) receptor type 1 (AT1R) blockers (ARBs) can attenuate AngII-mediated oxidative stress, which often leads to increased endothelial NO bioavailability. Herein, we investigate the potential presence of direct, AngII/AT1R-independent ARB class effects on endothelial NO release and how this may result in enhanced aortic wall homeostasis and endothelial NO-specific transcriptome changes.

Recombinant human β-defensin 2 delivery improves smoking-induced lung neutrophilia and bacterial exacerbation.

Treatment of the cigarette smoke-associated lung diseases, such as chronic obstructive pulmonary disease (COPD), has largely focused on broad-spectrum anti-inflammatory therapies. However, these therapies, such as high-dose inhaled corticosteroids, enhance patient susceptibility to lung infection and exacerbation. Our objective was to assess whether the cationic host defense peptide, human β-defensin 2 (hBD-2), can simultaneously reduce pulmonary inflammation in cigarette smoke-exposed mice while maintaining immune competence during bacterial exacerbation.

Glycerol contained in vaping liquids affects the liver and aspects of energy homeostasis in a sex-dependent manner.

Vaping is increasingly popular among the young and adult population. Vaping liquids contained in electronic cigarettes (e-cigarettes) are mainly composed of propylene glycol and glycerol, to which nicotine and flavors are added. Among several biological processes, glycerol is a metabolic substrate used for lipid synthesis in fed state as well as glucose synthesis in fasting state.

Cholesterol absorption blocker ezetimibe prevents muscle wasting in severe dysferlin-deficient and mdx mice.

Background: Muscular dystrophy (MD) causes muscle wasting and is often lethal in patients due to a lack of proven therapies. In contrast, mouse models of MD are notoriously mild. We have previously shown severe human-like muscle pathology in mdx [Duchenne MD (DMD)] and dysferlin-deficient limb-girdle MD type 2B (LGMD2B) mice by inactivating the gene encoding for apolipoprotein E (ApoE), a lipid transporter synthesized by the liver, brain and adipocytes to regulate lipid and fat metabolism.

Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure.

Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions in surfactant homeostasis are typically thought of in the context of respiratory distress and premature infants, many lung diseases have been noted to have significant surfactant abnormalities. Nevertheless, preclinical and clinical studies of pulmonary disease too often overlook the potential contribution of surfactant alterations - whether in quantity, quality or composition - to disease pathogenesis and symptoms.

Effect of Dysferlin Deficiency on Atherosclerosis and Plasma Lipoprotein Composition Under Normal and Hyperlipidemic Conditions.

Dysferlinopathies are a group of muscle disorders caused by mutations to dysferlin, a transmembrane protein involved in membrane patching events following physical damage to skeletal myofibers. We documented dysferlin expression in vascular tissues including non-muscle endothelial cells, suggesting that blood vessels may have an endogenous repair system that helps promote vascular homeostasis. To test this hypothesis, we generated dysferlin-null mice lacking apolipoprotein E (ApoE), a common model of atherosclerosis, dyslipidemia and endothelial injury when stressed with a high fat, and cholesterol-rich diet.

Blood pressure-independent inhibition of Marfan aortic root widening by the angiotensin II receptor blocker valsartan.

Marfan syndrome (MFS) is a genetic disorder that results in accelerated aortic root widening and aneurysm. However, management of MFS patients with blood pressure (BP)-lowering medications, such as angiotensin II (AngII) receptor blocker (ARB) losartan, continues to pose challenges due to their questionable efficacy at attenuating the rate of aortic root widening in patients. Herein we investigate the anti-aortic root widening effects of a sub-BP-lowering dose valsartan, an ARB previously linked to non-BP lowering anti-remodeling effects.

Neutrophils and IL-1α Regulate Surfactant Homeostasis during Cigarette Smoking.

Cigarette smoke exposure induces inflammation marked by rapid and sustained neutrophil infiltration, IL-1α, release and altered surfactant homeostasis. However, the extent to which neutrophils and IL-1α contribute to the maintenance of pulmonary surfactant homeostasis is not well understood. We sought to investigate whether neutrophils play a role in surfactant clearance as well as the effect of neutrophil depletion and IL-1α blockade on the response to cigarette smoke exposure.

Critical importance of dietary methionine and choline in the maintenance of lung homeostasis during normal and cigarette smoke exposure conditions.

Genetic predispositions and environmental exposures are regarded as the main predictors of respiratory disease development. Although the impact of dietary essential nutrient deficiencies on cardiovascular disease, obesity, and type II diabetes has been widely studied, it remains poorly explored in chronic respiratory diseases. Dietary choline and methionine deficiencies are common in the population, and their impact on pulmonary homeostasis is currently unknown.

Angiotensin II receptor blocker losartan exacerbates muscle damage and exhibits weak blood pressure-lowering activity in a dysferlin-null model of Limb-Girdle muscular dystrophy type 2B.

There is no cure or beneficial management option for Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). Losartan, a blood pressure (BP) lowering angiotensin II (AngII) receptor type 1 (ATR1) blocker (ARB) with unique anti-transforming growth factor-β (TGF-β) properties, can protect muscles in various types of MD such as Duchenne MD, suggesting a potential benefit for LGMD2B patients. Herein, we show in a mild, dysferlin-null mouse model of LGMD2B that losartan increased quadriceps muscle fibrosis (142%; P<0.

Sildenafil Prevents Marfan-Associated Emphysema and Early Pulmonary Artery Dilation in Mice.

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in fibrillin-1 (Fbn1). Although aortic rupture is the major cause of mortality in MFS, patients also experience pulmonary complications, which are poorly understood. Loss of basal nitric oxide (NO) production and vascular integrity has been implicated in MFS aortic root disease, yet their contribution to lung complications remains unknown.

Pharmacological activation of liver X receptor during cigarette smoke exposure adversely affects alveolar macrophages and pulmonary surfactant homeostasis.

Smoking alters pulmonary reverse lipid transport and leads to intracellular lipid accumulation in alveolar macrophages. We investigated whether stimulating reverse lipid transport with an agonist of the liver X receptor (LXR) would help alveolar macrophages limit lipid accumulation and dampen lung inflammation in response to cigarette smoke. Mice were exposed to cigarette smoke and treated intraperitoneally with the LXR agonist T0901317.

Inhibition of Marfan Syndrome Aortic Root Dilation by Losartan: Role of Angiotensin II Receptor Type 1-Independent Activation of Endothelial Function.

Marfan syndrome (MFS) is a genetic disorder that frequently leads to aortic root dissection and aneurysm. Despite promising preclinical and pilot clinical data, a recent large-scale study using antihypertensive angiotensin II (AngII) receptor type 1 (ATR1) blocker losartan has failed to meet expectations at preventing MFS-associated aortic root dilation, casting doubts about optimal therapy. To study the deleterious role of normal ATR1 signaling in aortic root widening, we generated MFS mice lacking ATR1a expression in an attempt to preserve protective ATR2 signaling.