Correlation between level of autophagy and frequency of CD8+ T cells in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive. Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients. METHODS: Subjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function. Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis. RT-PCR and western blotting were used to measure levels of LC3 and p62. RESULTS: Frequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower. In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies. Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies. CONCLUSION: Autophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.

Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL.

Acetaminophen (APAP) is one of the most commonly used drugs worldwide, and APAP-induced liver injury is the most frequent cause of acute liver failure in developed countries. However, the mechanisms of APAP-induced hepatotoxicity are not well understood, and treatment options for the disorder are very limited. Here, we show that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a major mediator of APAP-induced liver injury in mice, and its blockade markedly ameliorates the liver failure. In APAP-treated mice, TRAIL was expressed in the liver, spleen, and peripheral blood primarily by CD11b+Gr1+ neutrophils. The concentration of soluble TRAIL in the blood, and the frequencies of TRAIL+ leukocytes in the spleen and liver positively correlated with the severity of liver injury. APAP sensitized hepatocytes to TRAIL-induced apoptosis by upregulating the expression of the TRAIL receptor DR5 (death receptor 5), presumably through its transcription factor CHOP (C/EBP homologous protein). Importantly, blocking TRAIL with a soluble DR5-Fc fusion protein (sDR5-Fc) significantly attenuated APAP-induced liver injury, the hepatic infiltration of leukocytes, the levels of inflammatory cytokines, and the mortality of mice. When administered alongside N-acetylcysteine, sDR5-Fc further protected against APAP-induced acute liver injury. Thus, the TRAIL-DR5 signaling pathway plays a key role in APAP-induced liver inflammation and failure, and its blockade represents an effective new strategy to treat the liver disease.

Self-assembled dual-modality contrast agents for non-invasive stem cell tracking via near-infrared fluorescence and magnetic resonance imaging.

Stem cells hold great promise for treating various diseases. However, one of the main drawbacks of stem cell therapy is the lack of non-invasive image-tracking technologies. Although magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging have been employed to analyse cellular and subcellular events via the assistance of contrast agents, the sensitivity and temporal resolution of MRI and the spatial resolution of NIRF are still shortcomings. In this study, superparamagnetic iron oxide nanocrystals and IR-780 dyes were co-encapsulated in stearic acid-modified polyethylenimine to form a dual-modality contrast agent with nano-size and positive charge. These resulting agents efficiently labelled stem cells and did not influence the cellular viability and differentiation. Moreover, the labelled cells showed the advantages of dual-modality imaging in vivo.

An association network analysis among microeukaryotes and bacterioplankton reveals algal bloom dynamics.

Algal blooms are a worldwide phenomenon and the biological interactions that underlie their regulation are only just beginning to be understood. It is established that algal microorganisms associate with many other ubiquitous, oceanic organisms, but the interactions that lead to the dynamics of bloom formation are currently unknown. To address this gap, we used network approaches to investigate the association patterns among microeukaryotes and bacterioplankton in response to a natural Scrippsiella trochoidea bloom. This is the first study to apply network approaches to bloom dynamics. To this end, terminal restriction fragment (T-RF) length polymorphism analysis showed dramatic changes in community compositions of microeukaryotes and bacterioplankton over the blooming period. A variance ratio test revealed significant positive overall associations both within and between microeukaryotic and bacterioplankton communities. An association network generated from significant correlations between T-RFs revealed that S. trochoidea had few connections to other microeukaryotes and bacterioplankton and was placed on the edge. This lack of connectivity allowed for the S. trochoidea sub-network to break off from the overall network. These results allowed us to propose a conceptual model for explaining how changes in microbial associations regulate the dynamics of an algal bloom. In addition, key T-RFs were screened by principal components analysis, correlation coefficients, and network analysis. Dominant T-RFs were then identified through 18S and 16S rRNA gene clone libraries. Results showed that microeukaryotes clustered predominantly with Dinophyceae and Perkinsea while the majority of bacterioplankton identified were Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The ecologi-cal roles of both were discussed in the context of these findings.