Involvement of protoporphyrin IX accumulation in the pathogenesis of isoniazid/rifampicin-induced liver injury: the prevention of curcumin

<p>Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR–humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively. Herein, this study focused on the role of INH/RFP in these processes. We observed PPIX accumulation in human hepatocytes (L-02) and mouse livers. FECH expression was initially found downregulated both in L-02 cells and mouse livers and expression levels of ALAS1 and BCRP were elevated in L-02 cells after INH/RFP treatment, indicating FECH inhibition and ALAS1 induction might confer a synergistic effect on PPIX accumulation. Additionally, our results revealed that curcumin alleviated INH/RFP-induced liver injury, declined PPIX levels and induced FECH expression in both L-02 cells and mice. In conclusion, our data provide a novel insight in the mechanism of INH/RFP-induced PPIX accumulation and evidence for understanding pathogenesis of INH/RFP-induced liver injury, and suggest that amelioration of PPIX accumulation might be involved in the protective effect of curcumin on INH/RFP-induced liver injury.</p

Pyrrole Alkaloids with Potential Cancer Chemopreventive Activity Isolated from a Goji Berry-Contaminated Commercial Sample of African Mango

Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1<i>H</i>-pyrrol-1-yl]­propanoate, <b>1</b>, along with seven known compounds, <b>2</b>–<b>8</b>. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound <b>1</b>g showed hydroxyl radical-scavenging activity with an ED₅₀ value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1<i>H</i>-pyrrol-1-yl]­butanoic acid (<b>2</b>) was active in both the hydroxyl radical-scavenging (ED₅₀ 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and ¹H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with <i>N</i>-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample

Additional file 1: Table S1. of Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest

The general characters of three sampling sites in the tropical rainforest. Table S2. The environmental factors of three sampling sites in the tropical rainforest. (DOC 40 kb

Antioxidant and Quinone Reductase-Inducing Constituents of Black Chokeberry (Aronia melanocarpa) Fruits

Using in vitro hydroxyl radical-scavenging and quinone reductase-inducing assays, bioactivity-guided fractionation of an ethyl acetate-soluble extract of the fruits of the botanical dietary supplement, black chokeberry (Aronia melanocarpa), led to the isolation of 27 compounds, including a new depside, ethyl 2-[(3,4-dihydroxybenzoyloxy)-4,6-dihydroxyphenyl] acetate (<b>1</b>), along with 26 known compounds (<b>2</b>–<b>27</b>). The structures of the isolated compounds were identified by analysis of their physical and spectroscopic data ([α]_D, NMR, IR, UV, and MS). Altogether, 17 compounds (<b>1</b>–<b>4</b>, <b>9</b>, <b>15</b>–<b>17</b>, and <b>19</b>–<b>27</b>) showed significant antioxidant activity in the hydroxyl radical-scavenging assay, with hyperin (<b>24</b>, ED₅₀ = 0.17 μM) being the most potent. The new compound (<b>1</b>, ED₅₀ = 0.44 μM) also exhibited potent antioxidant activity in this assay. Three constituents of black chokeberry fruits doubled quinone reductase activity at concentrations <20 μM, namely, protocatechuic acid [<b>9</b>, concentration required to double quinone reductase activity (CD) = 4.3 μM], neochlorogenic acid methyl ester (<b>22</b>, CD = 6.7 μM), and quercetin (<b>23</b>, CD = 3.1 μM)

Additional file 1 of Niche differentiation and biogeography of Bathyarchaeia in paddy soil ecosystems: a case study in eastern China

Additional file 1: It’s.xlsx file and include two tables. The title of the tables are Physicochemical parameter details of the samples (Table S1) and Nice overlap of Bathyarchaeia and other archaea (Table S2), respectively

Additional file 2: Figure S1. of Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest

The principal component analysis of plant community structure in three sampling sites. Figure S2. The normalized signal intensity of detected genes from different gene categories. Figure S3. The normalized signal intensity of detected key genes involved in carbon fixation. Figure S4. The normalized signal intensity of detected key genes involved in methane cycle. Figure S5. The normalized signal intensity of the detected key genes involved in phosphorus cycle. Figure S6. Study sites in Jianfengling Forest Area. (DOCX 1154 kb

Synthesis and characterization of a pair of temperature and cosolvent-dependent Zn(II)-organic frameworks containing a novel discrete single-walled Zn(II)-organic coordination polymer nanotube

<div><p>A pair of temperature and cosolvent-controlled assemblies of one dimensional (1-D) and two dimensional (2-D) Zn(II)-organic frameworks (ZOFs] based on 5-iodoisophthalic acid (H₂IIP) and an auxiliary flexible ligand, 1,4-bis(triazol-1-ylmethyl)benzene (bbtz) with different structures, has been rationally designed and successfully synthesized. Results show that when the reaction was carried out under ambient condition, the novel discrete single-walled Zn(II)-organic coordination polymer nanotube {[Zn(IIP)(bbtz)(H₂O)]·H₂O}_n (SWCPNT<b>-1</b>), which shows a fascinating 3-D supramolecular interdigitated columnar microporous architecture supported by face to face <i>π</i>⋯<i>π</i> stacking interactions and hydrogen bonds, was generated, whereas under solvothermal condition at 120 °C, an interesting 3-D-polycatenated array of layers, [Zn(IIP)(bbtz)] (<b>2</b>), which further extends into a threefold-interpenetrated 3-D supramolecular mesoporous framework with 1-D channels (<i>ca.</i> 3.46 × 1.54 nm²) through C–I⋯O halogen bonds would be obtained. Interestingly, the reversible <i>in situ</i> rapid rehydration from static air is significantly observed in the discrete SWCPNT<b>-1</b>, revealing its potential application as water absorbent and sensing material. The dehydrated SWCPNT<b>-1</b> shows selective gas adsorption of CO₂ over N₂. Luminescent studies show that SWCPNT<b>-1</b>, dehydrated SWCPNT<b>-1,</b> and <b>2</b> exhibit blue fluorescence in the solid state. The water molecules in SWCPNT<b>-1</b> affect its fluorescent property.</p></div

Widespread Distribution of Soluble Di-Iron Monooxygenase (SDIMO) Genes in Arctic Groundwater Impacted by 1,4-Dioxane

Soluble di-iron monooxygenases (SDIMOs), especially group-5 SDIMOs (i.e., tetrahydrofuran and propane monooxygenases), are of significant interest due to their potential role in the initiation of 1,4-dioxane (dioxane) degradation. Functional gene array (i.e., GeoChip) analysis of Arctic groundwater exposed to dioxane since 1980s revealed that various dioxane-degrading SDIMO genes were widespread, and PCR-DGGE analysis showed that group-5 SDIMOs were present in every tested sample, including background groundwater with no known dioxane exposure history. A group-5 <i>thmA</i>-like gene was enriched (2.4-fold over background, <i>p</i> < 0.05) in source-zone samples with higher dioxane concentrations, suggesting selective pressure by dioxane. Microcosm assays with ¹⁴C-labeled dioxane showed that the highest mineralization capacity (6.4 ± 0.1% ¹⁴CO₂ recovery during 15 days, representing over 60% of the amount degraded) corresponded to the source area, which was presumably more acclimated and contained a higher abundance of SDIMO genes. Dioxane mineralization ceased after 7 days and was resumed by adding acetate (0.24 mM) as an auxiliary substrate to replenish NADH, a key coenzyme for the functioning of monoxygenases. Acetylene inactivation tests further corroborated the vital role of monooxygenases in dioxane degradation. This is the first report of the prevalence of oxygenase genes that are likely involved in dioxane degradation and suggests their usefulness as biomarkers of dioxane natural attenuation

Indigo production from indole by microbial communities.

<p><b>A.</b> Indigo production by three activated sludge systems. <b>B.</b> Indole consumption by three activated sludge systems. G1, non-augmented AS; G2, AS plus <i>Comamonas</i> sp. MQ; G3, AS plus <i>E</i>. <i>coli</i>_<i>nagAc</i>. The concentrations of indole and indigo were measured by HPLC at the end of SBR operation cycle.</p

Community compositions of three treatments in T1, T2 and T3 stages.

<p><b>A.</b> Phylogenetic tree of the shared 16S rRNA gene sequences constructed by the neighbor-joining method with 1,000 bootstrap replicates. The number in parentheses represented the relative abundances of each OTU, and only OTUs accounting for more than 0.05% of the shared sequences were shown. Sequences of typical indigo-producing strains reported previously were indicated with symbol (●) and the accession number. <b>B.</b> Relative abundance of the dominant families from the shared OTUs. <b>C.</b> Heat map of the 10 most abundant genera in each treatment. The color intensity in each cell showed the relative abundance of a genus in a treatment.</p