The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells.

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.

An analysis of the dynamic changes in the self-efficacy and quality of life of elderly patients with chronic obstructive pulmonary disease following community-based rehabilitation.

OBJECTIVE: This study aimed to investigate the effects of community-based rehabilitation (CBR) on the self-efficacy and quality of life in elderly patients with chronic obstructive pulmonary disease (COPD). METHOD: Eighty-one elderly patients with COPD admitted to our hospital were recruited as the study cohort and were randomly divided into a control group (n=41) and a study group (n=40). The control group underwent outpatient rehabilitative treatment, and the study group additionally underwent CBR. The treatment effects of the two groups at 1 month, 3 months, and 6 months of intervention were assessed using their pulmonary function and quality of life scores. RESULTS: After completion of the CBR, the patients in the study group and the control group were scored using the CSES scale, which did not differ at 1 month of intervention, but the scores were higher in the study group than they were in the control group at 3 and 6 months of intervention (P < 0.05). The patients in the study group also scored higher on the WHOQOL-BREF scale than the control group (P < 0.05). CONCLUSION: CBR improves the self-efficacy and quality of life in elderly patients with COPD.

Inhibitor discovery for the E. coli meningitis virulence factor IbeA from homology modeling and virtual screening.

Escherichia coli (E. coli) K1 is the most common Gram-negative bacteria cause of neonatal meningitis. The penetration of E. coli through the blood-brain barrier is a key step of the meningitis pathogenesis. A host receptor protein, Caspr1, interacts with the E. coli virulence factor IbeA and thus facilitates bacterial penetration through the blood-brain barrier. Based on this result, we have now predicted the binding pattern between Caspr1 and IbeA by an integrated computational protocol. Based on the predicted model, we have identified a putative molecular binding pocket in IbeA, that directly bind with Caspr1. This evidence indicates that the IbeA (229-343aa) region might play a key role in mediating the bacteria invasion. Virtual screening with the molecular model was conducted to search for potential inhibitors from 213,279 commercially available chemical compounds. From the top 50 identified compounds, 9 demonstrated a direct binding ability to the residues within the Caspr1 binding site on IbeA. By using human brain microvascular endothelial cells (hBMEC) with E. coli strain RS218, four molecules were characterized that significantly attenuated the bacteria invasions at concentrations devoid of cell toxicity. Our study provides useful structural information for understanding the pathogenesis of neonatal meningitis, and have identified drug-like compounds that could be used to develop effective anti-meningitis agents.