Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.

Two previously uncharacterized potential broad-spectrum mercury (Hg) resistance operons (mer) are present on the chromosome of the soil Alphaproteobacteria Xanthobacter autotrophicus Py2. These operons, mer1 and mer2, contain two features which are commonly found in mer operons in the genomes of soil and marine Alphaproteobacteria, but are not present in previously characterized mer operons: a gene for the mercuric reductase (MerA) that encodes an alkylmercury lyase domain typical of those found on the MerB protein, and the presence of an additional gene, which we are calling merK, with homology to glutathione reductase. Here, we demonstrate that Py2 is resistant to 0.2 M inorganic mercury [Hg(II)] and 0.05 M methylmercury (MeHg). Py2 is capable of converting MeHg and Hg(II) to elemental mercury [Hg(0)], and reduction of Hg(II) is induced by incubation in sub toxic concentrations of Hg(II). Transcription of the merA genes increased with Hg(II) treatment, and in both operons merK resides on the same polycistronic mRNA as merA. We propose the use of Py2 as a model system for studying the contribution of mer to Hg mobility in soil and marine ecosystems. Bacterial mercury (Hg) resistance genes (mer) are important drivers in the biogeochemical cycle of Hg. These operons catalyze the conversion of inorganic mercury [Hg(II)] and sometimes methylmercury (MeHg) to elemental mercury [Hg(0)] (1). MeHg, which is more toxic than Hg(II) or Hg(0), is the form that biomagnifies in aquatic food webs (2, 3) and can cause toxicity to humans and animals that consume contaminated fish (4-6). Hg(II) is water soluble but sorbs strongly onto iron oxides and interacts with dissolved organic matter (7). Hg(0), the least toxic form, is both a liquid and a gas at room temperature and can evaporate from surface waters and soils (8, 9).All mer operons contain a gene encoding mercuric reductase, MerA, which converts Hg(II) to Hg(0), thereby conferring resistance (10). Some mer operons, called broad-spectrum mer operons, contain an additional gene encoding MerB, or alkylmercury lyase (AML), which degrades MeHg to Hg(II) and methane (11). Many mer operons contain genes for the transcriptional regulators MerR and MerD (12), as well the Hg transporters encoded by merT, merC, and merF, as well as additional Hg transfer proteins encoded by merP and merE (11, 13). Regulation of mer and the enzymatic activity of MerA is known in great detail for some operons and enzymes (10).It has been demonstrated that mer can influence the Hg cycle in lakes (14), but at present we know much less about the contribution of mer to the Hg cycle in soil and the terrestrial subsurface. It was long thought that Hg was relatively immobile in the subsurface due to sorption on sediment components such as iron oxides (1), but this assumption has come under scrutiny, since Hg has been unexpectedly found in groundwater at numerous sites, such as the Kirkwood-Cohansey aquifer in New Jersey (15, 16), the Waquoit Bay near Cape Cod, MA (17), and the coasts of California, northern ...

Compared to the extensive research on aquatic ecosystems, very little is known about the sources and trophic transfer of methylmercury (MeHg) in terrestrial ecosystems. In this study, we examine energy flow and trophic structure using stable carbon (δ13C) and nitrogen (δ15N) isotope ratios, respectively, and MeHg levels in basal resources and terrestrial invertebrates from four temperate forest ecosystems. We show that MeHg levels in biota increased significantly (p < 0.01) with δ13C and δ15N at all sites, implying the importance of both microbially processed diets (with increased δ13C) and trophic level (with increased δ15N) at which organisms feed, on MeHg levels in forest floor biota. The trophic magnification slopes of MeHg (defined as the slope of log10MeHg vs δ15N) for these forest floor food webs (0.20–0.28) were not significantly different (p > 0.05) from those observed for diverse temperate freshwater systems (0.24 ± 0.07; n = 78), demonstrating for the first time the nearly equivalent efficiencies with which MeHg moves up the food chain in these contrasting ecosystem types. Our results suggest that in situ production of MeHg within the forest floor and efficient biomagnification both elevate MeHg levels in carnivorous invertebrates in temperate forests, which can contribute to significant bioaccumulation of this neurotoxin in terrestrial apex predators.

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Cardiovascular disease (CVD) is the major cause of morbidity, mortality, and health care costs in the United States, and possibly around the world. Among the various risk factors of CVD, environmental and dietary exposures to mercury (Hg), a highly toxic metal traditionally regarded as a neurotoxin, has been recently suggested as a potential contributor towards human atherosclerotic development. In this study, we investigated the toxicity, type of cell death, dose-dependent uptake, and efflux of inorganic HgII (as HgCl2) and methylmercury or MeHg (as CH3HgCl) in EA.hy926 endothelial cells, as these two forms of Hg are often reported to be present in human blood among the general populations (~20–30% as HgII and ~70–80% as MeHg). Our results showed that HgII is more toxic than MeHg to the endothelial cells, owing to the higher uptake into the cytoplasm and perhaps importantly lower efflux of HgII by the cells, thus the “net” accumulation by the endothelial cells is higher for HgII than MeHg when exposed to the same Hg levels in the media. Furthermore, both HgII and MeHg were found to induce apoptotic and necrotic cell death. This study has important implications for the contributions of these two common Hg species to the development of atherosclerosis, an important process leading to CVD.