| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T118 |
0-371 |
Sentence |
denotes |
Extensive studies utilizing both in vitro and in vivo models of acute lung injury have demonstrated the protective role of autophagy via regulating inflammatory-oxidative stress, apoptosis, and pathogen clearance mechanisms, even though there were some initial opposing studies [117,118,119], the subsequent detailed evaluation validates the protective role as discussed. |
| T119 |
372-519 |
Sentence |
denotes |
In general, autophagy is induced upon exposure to common triggers of ALI, such as LPS, bacterial infections, hyperoxia, sepsis, etc. [120,121,122]. |
| T120 |
520-658 |
Sentence |
denotes |
There seems to be a consensus that autophagy indeed plays a protective role in LPS-induced acute lung injury and inflammation [82,83,123]. |
| T121 |
659-987 |
Sentence |
denotes |
In support of this, LPS-mediated severe lung injury in mice, as quantified by lung edema, elevated leukocyte infiltrations, hemorrhages, and increased inflammatory cytokines (IL-1β and TNFα) in the bronchoalveolar lavage fluid (BALF), was further exacerbated by autophagy inhibition, thereby suggesting its protective role [82]. |
| T122 |
988-1222 |
Sentence |
denotes |
Mechanistically, the activation of the mammalian target of rapamycin (mTOR) and the resulting autophagy dysfunction has been implicated in promoting LPS-induced lung injury, possibly through the activation of NFκB signaling [124,125]. |
| T123 |
1223-1465 |
Sentence |
denotes |
Further evidence comes from studies demonstrating the utility of autophagy inducers and/or antioxidant drugs in ameliorating LPS-induced acute lung injuries, while treatment with autophagy inhibitors reversed the beneficial effects [125,126]. |
| T124 |
1466-1756 |
Sentence |
denotes |
Autophagy is also protective in sepsis-induced lung injury, as a deficiency of proteins interacting with C-kinase 1 (PICK1) in mice leads to defective autophagy, and more severe acute lung injury in the cecal ligation and puncture (CLP) model of sepsis, as compared to WT animals [120,127]. |
| T125 |
1757-2028 |
Sentence |
denotes |
Additionally, in murine models of hyperoxia-induced ALI, which resembles features of bronchopulmonary dysplasia (BPD), autophagy is proposed as a protective mechanism, and markers of defective autophagy are found in the lungs of human neonates with established BPD [128]. |
| T126 |
2029-2437 |
Sentence |
denotes |
Another recent study describes the suppression of autophagy as a critical mechanism of chronic parenteral nutrition-mediated lung injury, and treatment with the autophagy inducer, rapamycin (an mTOR inhibitor that initiates nucleation, autophagosome elongation, autophagosome maturation, and autophagosome termination), reversed the lung injury features in the animal model of parenteral nutrition [129,130]. |
| T127 |
2438-2632 |
Sentence |
denotes |
Finally, mice deficient in crucial autophagy proteins such as Atg7, Atg5 and Atg4a demonstrate more severe ALI features [83,121,130,131], thus confirming the protective role of autophagy in ALI. |
