Targeting reprogrammed metabolism as a therapeutic approach for respiratory diseases.

Metabolic reprogramming underlies the etiology and pathophysiology of respiratory diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). The dysregulated cellular activities driving airway inflammation and remodelling in these diseases have reportedly been linked to aberrant shifts in energy-producing metabolic pathways: glycolysis and oxidative phosphorylation (OXPHOS). The rewiring of glycolysis and OXPHOS accompanying the therapeutic effects of many clinical compounds and natural products in asthma, IPF, and COPD, supports targeting metabolism as a therapeutic approach for respiratory diseases.

Dexamethasone protects against Aspergillus fumigatus-induced severe asthma via modulating pulmonary immunometabolism.

Severe asthma is a difficult-to-treat chronic airway inflammatory disease requiring systemic corticosteroids to achieve asthma control. It has recently been shown that drugs targeting immunometabolism have elicited anti-inflammatory effects. The purpose of this study was to investigate potential immunometabolic modulatory actions of systemic dexamethasone (Dex) in an Aspergillus fumigatus (Af)-induced severe asthma model.

Targeting the renin angiotensin system for respiratory diseases.

Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative evidence from experimental to clinical studies supports the notion that dysregulation of RAS contributes to the pro-inflammatory, pro-oxidative, and pro-fibrotic processes that occur in pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI). Pharmacological intervention of the various RAS components can be a novel therapeutic strategy for the treatment of these respiratory diseases.

Degradation of MK2 with natural compound andrographolide: A new modality for anti-inflammatory therapy.

The p38-MK2 signaling axis functions as an initiator of inflammation. Targeting the p38-MK2 signaling axis represents a direct therapeutic intervention of inflammatory diseases. We described here a novel role of andrographolide (AG), a small-molecule ent-labdane natural compound, as an inhibitor of p38-MK2 axis via MK2 degradation.

Angiotensin II type-2 receptor activation in alveolar macrophages mediates protection against cigarette smoke-induced chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. Alveolar macrophages (AMs) are the first line immune defense in the respiratory system and play a critical role in the lung homeostasis.

Eosinophilic endotype of chronic obstructive pulmonary disease: similarities and differences from asthma.

Approximately 25% to 40% of patients with chronic obstructive pulmonary disease (COPD) have the eosinophilic endotype. It is important to identify this group accurately because they are more symptomatic and are at increased risk for exacerbations and accelerated decline in forced expiratory volume in the 1st second. Importantly, this endotype is a marker of treat ment responsiveness to inhaled corticosteroid (ICS), resulting in decreased mortality risk.