Sodium-dependent uptake of bile acids across the hepatic basolateral membrane is rapidly and profoundly diminished during sepsis, thus contributing to the pathogenesis of sepsisassociated cholestasis. This effect is mediated by endotoxin or effector cytokines, which reduce expression of several hepatobiliary transporters, including the sodium-dependent bile acid transporter gene, ntcp . We test here the hypothesis that endotoxin treatment leads to impaired binding activity of ntcp promoter trans -acting factors, resulting in reduction of ntcp mRNA expression. After endotoxin administration, ntcp mRNA levels reached their nadir by 16 h, and nuclear run-on assays demonstrated a marked reduction in ntcp gene transcription. At 16 h after treatment, nuclear binding activities of two key factors that transactivate the ntcp promoter, hepatocyte nuclear factor (HNF) 1 and Footprint B binding protein (FpB BP), decreased to 44 and 47% of pretreatment levels, respectively, while levels of the other known ntcp promoter transactivator, signal transducer and activator of transcription 5, were unaffected. In contrast, the universal inflammatory response factors nuclear factor B and activating protein 1 were both upregulated significantly. Examination of nuclear extracts obtained at sequential time points revealed that the maximal decrease in nuclear activities of both HNF1 and FpB BP preceded the nadir of ntcp mRNA expression by 6-10 h. Furthermore, these two nuclear factors returned towards normal levels before the recovery of ntcp mRNA levels observed by 48 h. Since HNF1 ␣ mRNA levels were unchanged at all time points, HNF1 is likely to be regulated posttranscriptionally by endotoxin. We conclude that the downregulation of ntcp gene expression by endotoxin is mediated at the level of transcription through tandem reductions in the nuclear binding activity of two critical transcription factors. These findings provide new insight into the coordinated downreg-
Our previous research on coprolite specimens from the mummies of Joseon Dynasty (1392-1910 CE) has revealed various species of parasite eggs. Herein, we added 2 new helminthic cases of human remains from Joseon-period graves in the Republic of Korea (Korea). The organic materials precipitated on the hip bones of 2 half-mummied cases (Goryeong and Gwangmyeong cases) were collected, rehydrated, and examined by a microscope. In the sample from Goryeong-gun (gun=County), ova of <i>Trichuris trichiura, Clonorchis sinensis</i>, and <i>Metagonimus</i> spp. were detected, and eggs of <i>T. trichiura</i> and <i>A. lumbricoides</i> were found from the sample of Gwangmyeong-si (si=City). By adding this outcome to the existing data pool, we confirm our previous estimates of Joseon-period parasite infection rates. The overall rates of <i>A. lumbricoides, T. trichiura</i>, and <i>C. sinensis</i> decreased dramatically from Joseon to the modern period. In Goryeong mummy specimen, we also found <i>Metagonimus</i> spp. eggs that has rarely been detected in archaeological samples so far.
is a bacterium that grows in the stomach mucosal epithelium, and can induce gastric diseases. Although many studies on modern genomes have been reported from all over the world, a comprehensive picture of is still lacking. Therefore, there is a pressing need to obtain archaeological specimens and to subject the ancient DNA (aDNA) extracted therefrom to analysis. Considering the typically excellent state of preservation of Joseon mummies discovered in Korea, we thus tried to isolate ancient DNA from their mummified stomach specimens. After screening Korean mummy stomachs containing remnant DNA, (s- and m-region) alleles were successfully identified in the stomach isolates of two samples. The strains identified had s1/m2 (Cheongdo mummy) and s1 (Dangjin mummy) alleles. This paper is significant in that it is the first report of presumptive ancient DNA obtained from East Asian archaeological specimens. However, full characterization and exploitation of ancient DNA remnant in Joseon mummy specimens will require subsequent investigations utilizing the most cutting-edge techniques established for the analysis of ancient intestinal-content samples, such as next-generation sequencing (NGS).
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