Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups. Subsequently, the expression levels of proteins involved in the mitochondria-associated apoptotic pathway were studied by western blot analysis. Hesperidin was identified to induce A549 cell apoptosis by downregulating the levels of B-cell lymphoma-2 (Bcl-2) and Bcl extra large protein and simultaneously upregulating the levels of Bcl-2-associated X protein, BH3 interacting-domain death agonist (Bid), tBid, cleaved caspase-9, cleaved caspase-3 and cleaved poly(adenosine diphosphate ribose)polymerase. The effect of hesperidin on the cell cycle was assessed by flow cytometry. Hesperidin was observed to cause G0/G1 arrest of A549 cells by decreasing the expression of cyclin D1 and increasing the expression of p21 and p53. In summary, it was demonstrated that hesperidin induced apoptosis through the mitochondrial apoptotic pathway and induced G0/G1 arrest in human NSCLC A549 cells. Therefore, hesperidin may be developed as a potential therapeutic drug for the treatment of NSCLC.

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Podocytes play a key role in the formation of cellular crescents in experimental and human diseases. However, the underlying mechanisms for podocytes in promoting crescent formation need further investigation. Here, we demonstrated that mammalian target of rapamycin complex 1 (mTORC1) signaling was remarkably activated and hypoxia-inducible factor (HIF) 1α expression was largely induced in cellular crescents from patients with crescentic glomerular diseases. Specific deletion of Tsc1 in podocytes led to mTORC1 activation in podocytes and kidney dysfunction in mice. Interestingly, 33 of 36 knockouts developed cellular or mixed cellular and fibrous crescents at 7 wk of age (14.19 ± 3.86% of total glomeruli in knockouts vs. 0% in control littermates, n = 12–36, P = 0.04). All of the seven knockouts developed crescents at 12 wk of age (30.92 ± 11.961% of total glomeruli in knockouts vs. 0% in control littermates, n = 4–7, P = 0.002). Most notably, bridging cells between the glomerular tuft and the parietal basement membrane as well as the cellular crescents were immunostaining positive for WT1, p-S6, HIF1α, and Cxcr4. Furthermore, continuously administrating rapamycin starting at 7 wk of age for 5 wk abolished crescents as well as the induction of p-S6, HIF1α, and Cxcr4 in the glomeruli from the knockouts. Together, it is concluded that mTORC1 activation in podocytes promotes cellular crescent formation, and targeting this signaling may shed new light on the treatment of patients with crescentic glomerular diseases.

Akirin is an essential nuclear protein involved in the regulation of NF-κB signaling pathway. In most invertebrates, Akirin regulates NF-κB-related Imd and Toll pathways, however, in Drosophila, it only controls the Imd pathway, whereas its role in NF-κB signaling pathway in other insect species is unclear. In the present study, we used white-backed planthopper Sogatella furcifera as a model to investigate the functional activity of Akirin in insects. The sequence of Akirin cDNA was extracted from transcriptome database of S. furcifera; it contained a 585 bp open reading frame (ORF) encoding a putative protein of 194 amino acids. S. furcifera Akirin (SfAkirin) had a molecular weight of about 21.69 kDa and a theoretical pI of 8.66 and included a nuclear localization signal (NLS) of five amino acid residues at the N-terminal region. Evolutionary analysis showed that SfAkirin was evolutionary closer to Akirins of such relatively distant species as crustaceans than to those of some insect orders like Diptera and Hymenoptera. Tissue-specific expression analysis showed that the SfAkirin gene was expressed in all examined tissues, with the highest expression levels detected in the testis, followed by the ovary, whereas the lowest expression was found in the head. Real-time quantitative PCR analysis showed that SfAkirin mRNA was strongly induced in response to injection of heat-inactivated Escherichia coli and Bacillus subtilis, whereas SfAkirin silencing by RNA interference significantly reduced the expression of NF-κB dependent transcription factors Dorsal and Relish after B. subtilis and E. coli challenge, respectively. Our results suggest that SfAkirin may control the immune response of S. furcifera against bacterial infection via both Imd and Toll signaling pathways.

Optically pure sulfoxides are noteworthy compounds that find wide applications in various industrial fields. Here we report a methionine sulfoxide reductase B (MsrB) homologue that exhibits high enantioselectivity and broad...