ObjectivePublished studies have evaluated the impact of stromal myofibroblasts on prognosis in solid cancers. However, the results of these studies remain controversial. We therefore performed a meta-analysis to address this issue.MethodsThe PubMed, ISI Web of Science and Embase databases were searched through November 30th, 2015 by two investigators, and a total of 17 studies that contained 2606 patients were included. Stromal myofibroblasts were quantified in solid cancers using α-smooth muscle actin staining. Pooled Odds Ratio with 95% Confidence Intervals were calculated, and publication bias was analyzed.ResultsThe results of this study suggest that in solid cancers, a high density of stromal myofibroblasts is significantly associated with poor 3- and 5-year overall survival (pooled odds ratio (95% confidence interval): 1.33 (1.10–1.60) for 3-year overall survival and 1.68 (1.22–2.32) for 5-year overall survival). In addition, a high density of stromal myofibroblasts also predicted poor 3- and 5-year disease-free survival (1.30 (1.05–1.60) for 3-year disease-free survival and 1.36 (1.01–1.83) for 5-year disease-free survival). However, stromal myofibroblasts were not associated with 3- and 5-year cancer-specific survival. No publication bias was found for all analyses.ConclusionsThe results of this study suggest that a high density of stromal myofibroblasts is associated with poor survival in solid cancers. More studies were required to investigate the prognostic value of stromal myofibroblasts in different types of solid cancers.

Many of the neurodegenerative disorders such as Huntington's disease (HD) are caused by the accumulation of intracytoplasmic aggregate-prone proteins. These toxic protein aggregates are mainly degraded by autophagy, thus elevating the autophagy level to enhance the degradation of these proteins representing an emerging viable approach for the treatment of neurodegenerative diseases. In this report we showed that graphene oxide (GO), an engineered nanomaterial with enormous potential in biomedical applications, effectively enhanced the clearance of mutant huntingtin (Htt), the aggregate-prone protein underlying the pathogenesis of HD. This enhancing effect of GO was autophagy-mediated, as blocking autophagy by chemical inhibitors at either the autophagosome formation stage or the autophagosome-lysosome fusion stage, or more specifically by knocking-down an essential autophagy gene, led to a significant reduction in the ability of GO to elicit Htt degradation. Interestingly, the autophagy induced by GO had the normal capacity to degrade its cargo including LC3-II and Htt, but not p62/SQSTM1 (p62), and was dependent on the activation of class III phosphatidylinositol 3-kinase (PtdIns3K) and MEK/ERK1/2 signaling pathways, without mTOR involvement. GO also increased ubiquitination of Htt, an event necessary for Htt's clearance. Furthermore, ubiquitinated huntingtin protein preferentially binds to GO, and abundant GO was found in autophagosomes and autolysosomes, thus raising the possibility that GO may directly deliver the bound protein to autophagosomes for degradation. Our results revealed a novel biological function of GO and may have implications for developing nanomaterial-based therapeutics for neurodegenerative diseases.

Our results suggest that missed injuries that result in sepsis or bile leak as well as high injuries that require hepaticojejunostomy will result in a higher stricture rate after repair.

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.