Screening of significant biomarkers related with prognosis of liver cancer by lncRNA-associated ceRNAs analysis

This study aimed to identify significant biomarkers related to the prognosis of liver cancer using long noncoding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) analysis. Differentially expressed mRNA and lncRNAs between liver cancer and paracancerous tissues were screened, and the functions of these mRNAs were predicted by gene ontology and pathway enrichment analyses. A ceRNA network consisting of differentially expressed mRNAs and lncRNAs was constructed. LncRNA FENDRR and lncRNA HAND2-AS1 were hub nodes in the ceRNA network. A risk score assessment model consisting of eight genes (PDE2A, ESR1, FBLN5, ALDH8A1, AKR1D1, EHHADH, ADRA1A, and GNE) associated with prognosis were developed. Multivariate Cox regression suggested that both pathologic_T and risk group could be regarded as independent prognostic factors. Furthermore, a nomogram model consisting of pathologic_T and risk group showed a good prediction ability for predicting the survival rate of liver cancer patients. The nomogram model consisting of pathologic_T and a risk score assessment model could be regarded as an independent factor for predicting prognosis of liver cancer.     

Longitudinal Metabolomics Profiling of Parkinson’s Disease-Related α-Synuclein A53T Transgenic Mice

Metabolic homeostasis is critical for all biological processes in the brain. The metabolites are considered the best indicators of cell states and their rapid fluxes are extremely sensitive to cellular changes. While there are a few studies on the metabolomics of Parkinson’s disease, it lacks longitudinal studies of the brain metabolic pathways affected by aging and the disease. Using ultra-high performance liquid chromatography and tandem mass spectroscopy (UPLC/MS), we generated the metabolomics profiling data from the brains of young and aged male PD-related α-synuclein A53T transgenic mice as well as the age- and gender-matched non-transgenic (nTg) controls. Principal component and unsupervised hierarchical clustering analyses identified distinctive metabolites influenced by aging and the A53T mutation. The following metabolite set enrichment classification revealed the alanine metabolism, redox and acetyl-CoA biosynthesis pathways were substantially disturbed in the aged mouse brains regardless of the genotypes, suggesting that aging plays a more prominent role in the alterations of brain metabolism. Further examination showed that the interaction effect of aging and genotype only disturbed the guanosine levels. The young A53T mice exhibited lower levels of guanosine compared to the age-matched nTg controls. The guanosine levels remained constant between the young and aged nTg mice, whereas the aged A53T mice showed substantially increased guanosine levels compared to the young mutant ones. In light of the neuroprotective function of guanosine, our findings suggest that the increase of guanosine metabolism in aged A53T mice likely represents a protective mechanism against neurodegeneration, while monitoring guanosine levels could be applicable to the early diagnosis of the disease.     

Nitrogenase diversity and activity in the gastrointestinal tract of the wood-eating catfish Panaque nigrolineatus

The Amazonian catfish, Panaque nigrolineatus, consume large amounts of wood in their diets. The nitrogen-fixing community within the gastrointestinal (GI) tract of these catfish was found to include nifH phylotypes that are closely related to Clostridium sp., Alpha and Gammaproteobacteria, and sequences associated with GI tracts of lower termites. Fish fed a diet of sterilized palm wood were found to contain nifH messenger RNA within their GI tracts, displaying high sequence similarity to the nitrogen-fixing Bradyrhizobium group. Nitrogenase activity, measured by acetylene reduction assays, could be detected in freshly dissected GI tract material and also from anaerobic enrichment cultures propagated in nitrogen-free enrichment media; nifH sequences retrieved from these cultures were dominated by Klebsiella- and Clostridium-like sequences. Microscopic examination using catalyzed reporter deposition-enhanced immunofluorescence revealed high densities of nitrogenase-containing cells colonizing the woody digesta within the GI tract, as well as cells residing within the intestinal mucous layer. Our findings suggest that the P. nigrolineatus GI tract provides a suitable environment for nitrogen fixation that may facilitate production of reduced nitrogen by the resident microbial population under nitrogen limiting conditions. Whether this community is providing reduced nitrogen to the host in an active or passive manner and whether it is present in a permanent or transient relationship remains to be determined. The intake of a cellulose rich diet and the presence of a suitable environment for nitrogen fixation suggest that the GI tract microbial community may allow a unique trophic niche for P. nigrolineatus among fish.     

Functional role of hedgehog pathway in osteoarthritis

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.     

Analysis and assessment of heavy metals pollution in soils around a Pb and Zn smelter in Baoji City,Northwest China

Soil heavy metal pollution from mining activities is potentially harmful to human health through the food chain. In this study, a total of 43 soil samples were collected from a depth of 0–20 cm from fields close to a Pb and Zn smelter. The samples were used to: 1) analyze the pollution level of heavy metals (Pb, Zn, Cr, and Cu) and spatial distribution pattern; 2) evaluate the degree of accumulation and enrichment, potential ecological risk, and human health risk; and 3) perform source apportionment in Fengxiang County, Shaanxi Province of China. The results showed that the concentration ranged from 43.67 to 189.55, 131.43 to 239.53, 74.77 to 112.25, and 24.69 to 37.71 mg·kg^?1 for Pb, Zn, Cr, and Cu, respectively, and the mean concentration for Pb, Zn, Cr, and Cu was 129.46, 192.85, 91.98 and 31.67 mg·kg^?1, respectively. The concentrations were greater than the Shaanxi Province background values, while they were lower than the second-level limits of Environmental Quality Standard for Soils of China (EQSS). The spatial distribution of heavy metal contents showed a banded in soil except Cu. The spatial distribution pattern and pollution assessment indexes (I_geo, EF) indicated that the investigated metals had been accumulated in the study areas, and implied significant influences from anthropogenic activities, local meteorological situation, and soil properties. The ecological risk assessment showed that the risks were relatively low (RI<150). Compared with the exposure risk for adults, that for children was significantly greater. The ingestion of heavy metals in the soils by humans was the main exposure pathway compared with the dermal exposure. There may be a risk of noncarcinogenic adverse health effects (HQ < 1, 0.377 ≤ HI≤1.553) on children, but the adults were unlikely to experience obvious adverse health effects (HQ < 1, HI < 1). The carcinogenic risk of Cr for adults and children was at an unacceptable level. The carcinogenic and noncarcinogenic risks were in the order of children > adults. The correlation analysis showed that Pb, Cr, and Cu have identical anthropogenic and natural sources, while Zn has another identical source. This study could provide a basis for the sustainable management of this region by reducing metal inputs and to protect soils from long-term heavy metal accumulation.