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Although rapid progression and a poor prognosis in influenza A virus (IAV) infection–induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV‐induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV‐infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV‐inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1‐dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV‐infected pDHBE cells; however, these changes were rescued by OMA1‐siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV–induced cellular energy exhaustion via OMA1‐OPA1‐S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV. [ABSTRACT FROM AUTHOR]

Purpose Gemcitabine has been used as a therapeutic drug combined with cisplatin for the treatment of lung cancer patients. However, the prognosis is poor due to acquired resistance. Accumulating studies have revealed that autophagy may contribute to the drug resistance. Therefore, the present study is aimed to clarify the mechanisms underlying gemcitabine-acquired resistance. Methods SPC-A1 and A549 cells were incubated with gemcitabine followed by assessment of cell viability with MTT assays. GFP-LC3 transient transfection, MDC staining, and transmission electron microscopy were used to detect the change of autophagy at morphological level. Flow cytometry was used to monitor the effect of 3-MA on gemcitabine-induced apoptosis. Western blot analysis was used to detect the expression of p62, LC3, Beclin-1, ATG5, activated caspase 3, Bax, BNIP3, BNIP3L, and Bcl-2. Results Our study showed that gemcitabine significantly induced both autophagy and apoptosis in human lung cancer cells SPC-A1 and A549. Of interest was that when autophagy was inhibited by 3-MA, the gemcitabine-induced apoptosis was effectively enhanced, suggesting that gemcitabine can activate autophagy to impair the chemosensitivity of lung cancer cells. Furthermore, the inhibition of autophagy by 3-MA further increased the expression of activated caspase 3, Bax, BNIP3, and BNIP3L, all are critical apoptotic mediators. Contrarily, 3-MA treatment further decreased the expression of Bcl-2, which is an important anti-apoptotic protein. Conclusion Our study indicated that autophagy protected human lung cancer cells from gemcitabine-induced apoptosis, and the combined use of gemcitabine and an autophagic inhibitor in lung cancer patients may be an effective therapeutic strategy., Author(s): Hui-Mei Wu[sup.1] , Li-Jie Shao[sup.1] , Zi-Feng Jiang[sup.1] , Rong-Yu Liu[sup.1] Author Affiliations: (1) Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Jixi Road 218, 230022, [...]

Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice. [ABSTRACT FROM AUTHOR]