Abstract. Transcription factor Krüppel-like factors 5 (KLF5) is overexpressed in a wide range of tumor tissues and acts as a prognostic factor in cancer. However, the role of KLF5 in non-small cell lung cancer is not clear. Hypoxia plays a vital part in the development of cancer via hypoxia-inducible factor 1 (HIF-1). Our study showed that hypoxia (1% O 2 ) increased cell viability, clonality and proliferation and inhibited cell apoptosis in A549 cells. The expression of HIF-1α and KLF5 was increased time-dependently in hypoxia. Using small interfering RNA (siRNA) targeting KLF5 or HIF-1α, we demonstrated that KLF5 or HIF-1α knockdown inhibited hypoxia-induced cell survival and promoted cell apoptosis by actively downregulating cyclin B1, survivin and upregulating caspase-3. Given the similar effect of KLF5 and HIF-1α on cell survival, an attempt was made to investigate the putative interaction of them in hypoxia. KLF5 was revealed to co-immunoprecipitate with HIF-1α and hypoxia increased the amount of KLF5 and HIF-1α complex. Moreover, silencing of KLF5 decreased HIF-1α expression while KLF5 was not affected by HIF-1α inhibition in hypoxia, confirming the effect of KLF5 on upregulation of HIF-1α. In conclusion, this study identified hypoxia as a tumor promoter by triggering KLF5 → HIF-1α → cyclin B1/survivin/caspase-3 in lung cancer cells.

Aim: To study the effects of N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) on the phosphorylation of IκB kinase (IKK)β, IKKα, and IκBα in alveolar macrophages (AM), and to explore the pharmacological mechanisms of NAC and PDTC as inhibitors of NF-κB activation. Methods: AM were collected from bronchoalveolar lavage fluid from the patients with chronic obstructive pulmonary disease. The AM were incubated for 1.5 h with NAC and PDTC, and then stimulated for 90 min by either tumor necrosis factor (TNF)-α or interleukin (IL)-1. Western blotting was used to detect the protein phosphorylation levels of IKKβ, IKKα, and IκBα. NF-κB activity was analyzed by using an electrophoretic mobility shift assay. Results: NAC inhibited the phosphorylation of IKKβ, IKKα, and IκBα induced by TNF-α, but had no effect on the phosphorylation of IKKβ, IKKα and IκBα induced by IL-1. PDTC did not inhibit the phosphorylation of IκBα induced by TNF-α or IL-1. Similarly, NAC inhibited the activation of NF-κB induced by TNF-α, but had no effect on the activation of NF-κB induced by IL-1. PDTC significantly inhibited the activation of NF-κB induced by TNF-α and IL-1. The electrophoretic mobility shift assay also showed that PDTC and NAC do not directly inhibit NF-κB DNA binding activity in vitro. Conclusion: PDTC prevents the degradation of IκBα via the ubiquitylation-proteasome proteolytic pathway. NAC can inhibit the processes upstream of IKK activation induced by TNF-α, which results in the decline of NF-κB activity.

PurposeTo investigate the application value of “electronic alerts” (“e-alerts”) for acute kidney injury (AKI) among high-risk wards of hospitals.MethodsA prospective, randomized, controlled study was conducted. We developed an e-alert system for AKI and ran the system in intensive care units and divisions focusing on cardiovascular disease. The e-alert system diagnosed AKI automatically based on serum creatinine levels. Patients were assigned randomly to an e-alert group (467 patients) or non-e-alert group (408 patients). Only the e-alert group could receive pop-up messages.ResultsThe sensitivity, specificity, Youden Index and accuracy of the AKI e-alert system were 99.8, 97.7, 97.5 and 98.1%, respectively. The prevalence of the diagnosis for AKI and expanded-AKI (AKI or multiple-organ failure) in the e-alert group was higher than that in the non-e-alert group (AKI 7.9 and 2.7%, P = 0.001; expanded-AKI 16.3 and 6.1%, P < 0.001). The prevalence of nephrology consultation in the e-alert group was higher than that in the non-e-alert group (9.0 and 3.7%, P = 0.001). There was no significant difference in the prevalence dialysis, rehabilitation of renal function or death in the two groups.ConclusionThe e-alert system described here was a reliable tool to make an accurate diagnosis of AKI.