Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Abstract

Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

Leveraging Long-Distance Singlet-Oxygen Transfer for Bienzyme-Locked Afterglow Imaging of Intratumoral Granule Enzymes

“…To further evaluate the tumor specificity of BAAP, a local inflammation model was established where lipopolysaccharide (LPS) was intratracheally injected to induce acute pneumonia (Figure a). − In LPS-treated mice, a 1.8-fold increase in NIRF signals was detected at 5 h p.i., yet minimal afterglow signals were detected from the lung area (Figure c,d), suggesting that BAAP could differentiate tumors from inflammatory lesions by activating the afterglow signal due to the presence of the tumor biomarker (CaB). Those results demonstrated that BAAP had the potential for the real-time imaging of the intratumoral granule enzyme as intended; more importantly, they proved the feasibility of SOT for the development of activatable afterglow probes within complex biological environments.…”

Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment

“…Lastly, an elevated level of inflammatory mediators enhances the permeability of the pulmonary vasculature, allowing plasma and inflammatory cells to leak into the interstitial and alveolar spaces, further worsening lung injury [19]. In summary, the pathogenesis of ALI in sepsis involves multiple interconnected pathways, as illustrated in Figure 2 [20]. Moreover, the inflammatory response promotes extensive infiltration of inflammatory cells, such as neutrophils and monocytes, into lung tissue.…”