Background: Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples. Results: First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones. Conclusions: To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota potentially associated with cholesterol gallstones. Such a characterization of the biliary tract core microbiome has potentially important biological and medical implications regarding the role of bacteria in the formation cholesterol gallstones.

Exposure to chromium (Cr) causes a number of respiratory diseases, including lung cancer and pulmonary fibrosis. However, there is currently no safe treatment for Cr-induced lung damage. Here, we used in vivo and in vitro approaches to examine the protective effects of melatonin (MEL) on Cr-induced lung injury and to identify the underlying molecular mechanisms. We found that treatment of rats or a mouse lung epithelial cell MLE-12 with MEL attenuated K₂Cr₂O₇-induced lung injury by reducing the production of oxidative stress and inflammatory mediators and inhibiting cell apoptosis. MEL treatment upregulated the expression of silent information regulator 1 (Sirt1), which deacetylated the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α). In turn, this increased the expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and key anti-oxidant target genes. These results suggest that melatonin attenuates chromium-induced lung injury via activating the Sirt1/Pgc-1α/Nrf2 pathway. Dietary MEL supplement may be a potential new strategy for the treatment of Cr poisoning.

Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl₂). The results showed that luteolin ameliorated HgCl₂ induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl₂-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning.

Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.

Background: The aim of this study is to expand existing knowledge about the CRC-associated microbiome among Han Chinese, and to further discover the variation pattern of the human CRC microbiome across all population. Findings: Using pyrosequencing-based molecular monitoring of bacterial 16S rRNA gene from eight tumor/normal tissue pairs of eight Chinese CRC patients, we analyzed and characterized the basic features of the CRC-associated microbiome. Firstly, we discovered an increasing diversity among tumor-associated bacterial communities. Secondly, in 50% of Chinese CRC patients, we found a significant increase of Roseburia (P = 0.017), and a concurrent decrease of both Microbacterium (P = 0.009) and Anoxybacillus (P = 0.009) in tumor tissue. Conclusions: We discovered a novel CRC microbiome pattern in Chinese. Both the over-represented Roseburia bacteria at tumor sites and the over-represented Microbacterium and Anoxybacillus bacteria away from tumor sites were both closely related in Chinese CRC patients. Across several populations reported in this study and previously, we observed both common and distinctive patterns of human CRC microbiome’s association with a high-risk of CRC.