Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.

Early enteral nutrition is beneficial for acute pancreatitis (AP), but the optimal timing and criteria remain unclear. The aim of this study was to explore the feasibility and safety of early oral refeeding (EORF) based on hunger in patients with moderate or severe AP. In a prospective, single-center, controlled, randomized clinical trial (ChiCTR-TRC-12002994), eligible patients with moderate or severe AP were randomized to either EORF or conventional oral refeeding (CORF). Patients in the EORF group restarted an oral diet when they felt hungry, regardless of laboratory parameters. Those in the CORF group restarted an oral diet only when clinical and laboratory symptoms had resolved. Clinical outcomes were compared between the two groups. In all, 146 eligible patients with moderate or severe AP were included and randomized to the EORF (n = 70) or CORF (n = 76) group. There were eight dropouts after randomization (three in EORF group; five in CORF group). The groups had similar baseline characteristics. The total length of hospitalization (13.7 ± 5.4 d versus 15.7 ± 6.2 d; P = 0.0398) and duration of fasting (8.3 ± 3.9 d versus 10.5 ± 5.1 d; P = 0.0047) were shorter in the EORF group than in the CORF group. There was no difference in the number of adverse events or complications between the two groups. The mean blood glucose level after oral refeeding was higher in the EORF group than in the CORF group (P = 0.0030). This controlled, randomized clinical trial confirmed the effectiveness and feasibility of EORF based on hunger in patients with moderate or severe AP. EORF could shorten the length of hospitalization in patients with moderate or severe AP.

To evaluate the safety and efficacy of early oral refeeding (EORF) in patients with mild acute pancreatitis (AP) and to investigate the optimal duration to commence EORF. A prospective, randomized, controlled trial was conducted in patients with mild AP. Patients with EORF (started oral feeding once they subjectively felt hungry) were compared with patients receiving routine oral refeeding (RORF) for time interval between disease onset and initiation of oral refeeding, total length of hospitalization (LOH), postrefeeding LOH, and adverse gastrointestinal events. There were 75 and 74 patients in the EORF group and the RORF group, respectively, with comparable baseline characteristics. Patients in the EORF group started refeeding significantly earlier than those in the RORF group (4.56 ± 1.53 vs 6.75 ± 2.29 days; P < 0.05). Moreover, patients in the EORF group had significantly shorter total (6.8 ± 2.1 vs 10.4 ± 4.1 days; P < 0.01) and post refeeding LOH (2.24 ± 0.52 vs 3.27 ± 0.61 days; P < 0.01). There was no significant difference in adverse gastrointestinal events between the 2 groups. In patients with mild AP, EORF, with the subjective feeling of hunger, is safe, feasible, and reduces LOH.

Severity of acute pancreatitis contributes to the modality of cell death. Pervious studies have demonstrated that the herb medicine formula “Dachengqi Decoction” (DCQD) could ameliorate the severity of acute pancreatitis. However, the biological mechanisms governing its action of most remain unclear. The role of apoptosis/necrosis switch within acute pancreatitis has attracted much interest, because the induction of apoptosis within injured cells might suppress inflammation and ameliorate the disease. In this study, we used cerulein (10⁻⁸ M)-stimulated AR42J cells as an in vitro model of acute pancreatitis and retrograde perfusion into the biliopancreatic duct of 3.5% sodium taurocholate as an in vivo rat model. After the treatment of DCQD, cell viability, levels of apoptosis and necrosis, reactive oxygen species positive cells, serum amylase, concentration of nitric oxide and inducible nitric oxide syntheses, pancreatic tissue pathological score and inflammatory cell infiltration were tested. Pretreatment with DCQD increased cell viability, induced apoptosis, decreased necrosis and reduced the severity of pancreatitis tissue. Moreover, treatment with DCQD reduced the generation of reactive oxygen species in AR42J cells but increased the concentration of nitric oxide of pancreatitis tissues. Therefore, the regulation of apoptosis/necrosis switch by DCQD might contribute to ameliorating the pancreatic inflammation and pathological damage. Further, the different effect on reactive oxygen species and nitric oxide may play an important role in DCQD-regulated apoptosis/necrosis switch in acute pancreatitis.