The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.
Helicobacter pylori infection has been reported to be very common in patients with chronic liver diseases, including cirrhosis. To elucidate the pathological effect of H. pylori infection on the progression of hepatic fibrosis, C57BL/6 mice and Sprague-Dawley rats were orally inoculated with H. pylori, and hepatic fibrosis was induced with carbon tetrachloride (CCl 4 ) administration. We observed the histopathological changes and the presence of H. pylori genes by PCR in the liver. Significant increase in the fibrotic score as well as in serum alanine aminotransferase and aspartate aminotransferase levels was shown in the CCl 4 þ H. pylori group compared with that in the CCl 4 -treated group. Compared with the CCl 4 -treated group, a-smooth muscle actin and transforming growth factor-b1 were enhanced; however, senescence marker protein-30, a multifunctional protein protecting hepatocytes against oxidative stress and apoptosis, was suppressed in the CCl 4 þ H. pylori group. The 16S rRNA (400 bp) was demonstrated by PCR for H. pylori genes from genomic DNA extracted from the liver, and H. pylori-infected mice showed 93.8% (15 of 16) seropositivity by contrast with seronegativity in all H. pylori-noninfected mice. In addition, immunohistochemical study against H. pylori showed positive antigen fragments in the liver of the infected groups. Consequently, our data suggest that H. pylori infection could be an important contributing infectious factor to the development of liver cirrhosis.
Background Airway management is a part of routine anesthetic procedures; however, serious complications, including hypoxia and death, are known to occur in cases of difficult airways. Therefore, alternative techniques such as fiberoptic bronchoscope-assisted intubation (FOB intubation) should be considered, although this method requires more time and offers a limited visual field than does intubation with a direct laryngoscope. Oxygen insufflation through the working channel during FOB intubation could minimize the risk of desaturation and improve the visual field. Therefore, the aim of this prospective randomized controlled study was to evaluate the utility and safety of oxygen insufflation through the working channel during FOB intubation in apneic patients. Methods Thirty-six patients were randomly allocated to an N group (no oxygen insufflation) or an O group (oxygen insufflation). After preoxygenation, FOB intubation was performed with (O group) or without (N group) oxygen insufflation in apneic patients. The primary outcome was the velocity of decrease in the partial pressure of oxygen (PaO2) during FOB intubation (VPaO2, mmHg/sec) defined as the difference of PaO2 before and after intubation divided by the time to intubation. The secondary outcomes included the success rate for FOB intubation, time to intubation, visual field during FOB intubation, findings of arterial blood gas analysis, and occurrence of FOB intubation-related complications. Results We found that VPaO2 was significantly greater in the N group than in the O group (1.0 ± 0.4 vs. 0.4 ± 0.4; p < 0.001), while the visual field was similar between groups. There were no significant intergroup differences in the secondary outcomes. Conclusions These findings suggest that oxygen insufflation through the working channel during FOB intubation aids in extending the apneic window during the procedure. Trial registration ClinicalTrials.gov, NCT02625194, registered at December 9, 2015.
Multimodal prophylaxis for postoperative nausea and vomiting (PONV) has been recommended, even in low-risk patients. Midazolam is known to have antiemetic properties. We researched the effects of adding midazolam to the dual prophylaxis of ondansetron and dexamethasone on PONV after gynecologic laparoscopy. In this prospective, randomized, double-blinded trial, 144 patients undergoing gynecological laparoscopic surgery under sevoflurane anesthesia were randomized to receive either normal saline (control group, n = 72) or midazolam 0.05 mg/kg (midazolam group, n = 72) intravenously at pre-induction. All patients were administered dexamethasone 4 mg at induction and ondansetron 4 mg at the completion of the laparoscopy, intravenously. The primary outcome was the incidence of complete response, which implied the absence of PONV without rescue antiemetic requirement until 24 h post-surgery. The complete response during the 24 h following laparoscopy was similar between the two groups: 41 patients (59%) in the control group and 48 patients (72%) in the midazolam group (p = 0.11). The incidence of nausea, severe nausea, retching/vomiting, and administration of rescue antiemetic was comparable between the two groups. The addition of 0.05 mg/kg midazolam at pre-induction to the dual prophylaxis had no additive preventive effect on PONV after gynecologic laparoscopy.
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