Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the ...modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP PAI < 1 and normal PP PAI ≥ 1) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Liver fibrosis is caused by chemicals or viral infection. The progression of liver fibrosis results in hepatocellular carcinogenesis in later stages. Recent studies have revealed the importance of ...DNA hypermethylation in the progression of liver fibrosis to hepatocellular carcinoma (HCC). However, the importance of DNA methylation in the early-stage liver fibrosis remains unclear.
To address this issue, we used a pathological mouse model of early-stage liver fibrosis that was induced by treatment with carbon tetrachloride (CCl4) for 2 weeks and performed a genome-wide analysis of DNA methylation status. This global analysis of DNA methylation was performed using a combination of methyl-binding protein (MBP)-based high throughput sequencing (MBP-seq) and bioinformatic tools, IPA and Oncomine. To confirm functional aspect of MBP-seq data, we complementary used biochemical methods, such as bisulfite modification and in-vitro-methylation assays.
The genome-wide analysis revealed that DNA methylation status was reduced throughout the genome because of CCl4 treatment in the early-stage liver fibrosis. Bioinformatic and biochemical analyses revealed that a gene associated with fibrosis, secreted phosphoprotein 1 (Spp1), which induces inflammation, was hypomethylated and its expression was up-regulated. These results suggest that DNA hypomethylation of the genes responsible for fibrosis may precede the onset of liver fibrosis. Moreover, Spp1 is also known to enhance tumor development. Using the web-based database, we revealed that Spp1 expression is increased in HCC.
Our study suggests that hypomethylation is crucial for the onset of and in the progression of liver fibrosis to HCC. The elucidation of this change in methylation status from the onset of fibrosis and subsequent progression to HCC may lead to a new clinical diagnosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Vascular injury associated with cannulation during extracorporeal membrane oxygenation (ECMO) induction is a rare but life-threatening complication. The presence of abnormal vascular anatomy ...increases the risk of vascular injury and should be recognized before cannulation. We report the case of a patient with coronavirus disease (COVID-19) who was expected to undergo ECMO. By performing computed tomography (CT), we identified the absence of right superior vena cava (RSVC) with a persistent left superior vena cava (PLSVC) that could have caused serious complications associated with ECMO cannulation. PLSVC is observed in less than 0.5% of the general population; however, the combination of PLSVC and an absent RSVC in visceroatrial situs solitus is extremely rare. Attempting cannulation for Veno-venous (VV)-ECMO from the right (or left) internal jugular vein to the right atrium may cause serious complications. Cannulation may fail or lead to complications even in patients with inferior vena cava malformations. Although these vascular abnormalities are rare, it is possible to avoid iatrogenic vascular injury by identifying their presence in advance. Since anatomical variations in the vessels from the deep chest and abdominal cavity cannot be visualized using chest radiography and ultrasonography, we recommend CT, if possible, for patients with severe respiratory failure, including those with COVID-19, who may be considered for VV-ECMO induction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ribosome biosynthesis is a major intracellular energy-consuming process. We previously identified a nucleolar factor, nucleomethylin (NML), which regulates intracellular energy consumption by ...limiting rRNA transcription. Here, we show that, in livers of obese mice, the recruitment of NML to rRNA gene loci is increased to repress rRNA transcription. To clarify the relationship between obesity and rRNA transcription, we generated NML-null (NML-KO) mice. NML-KO mice show elevated rRNA level, reduced ATP concentration, and reduced lipid accumulation in the liver. Furthermore, in high-fat-diet (HFD)-fed NML-KO mice, hepatic rRNA levels are not decreased. Both weight gain and fat accumulation in HFD-fed NML-KO mice are significantly lower than those in HFD-fed wild-type mice. These findings indicate that rRNA transcriptional activation promotes hepatic energy consumption, which alters hepatic lipid metabolism. Namely, hepatic rRNA transcriptional repression by HFD feeding is essential for energy storage.
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•HFD feeding represses rRNA transcription in mouse livers by recruiting NML•NML-KO mice show elevated rRNA level and reduced ATP concentration•Hepatic NML deficiency results in altered hepatic lipid metabolism•Hepatic rRNA transcriptional repression by HFD feeding is essential for energy storage
Ribosome biosynthesis is a major intracellular energy-consuming process. The nucleolar factor NML regulates intracellular energy consumption by limiting rRNA transcription. In this study, Oie et al. show that, in livers of obese mice, the recruitment of NML to rRNA gene loci is increased to repress rRNA transcription. rRNA transcriptional activation modulates energy consumption, altering hepatic lipid metabolism. Thus, hepatic rRNA transcriptional repression by high-fat-diet feeding is essential for energy storage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Protein ubiquitination is a post-translational protein modification that regulates many biological conditions. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1. However, ...the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12(mt/mt)) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12(mt/mt) embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16. In contrast, Trip12(mt/mt) ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12(mt/mt) ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► In mitosis, MYBBP1A translocates from the nucleolus to the cytoplasm. ► MYBBP1A interacts with p53 under nocodazol treatment. ► MYBBP1A enhances acetylation of p53. ► MYBBP1A prevents ...polyploidization via p53 activation.
Cells eventually exit from mitosis during sustained arrest at the spindle checkpoint, without sister chromatid separation and cytokinesis. The resulting tetraploid cells are arrested in the subsequent G1 phase in a p53-dependent manner by the regulatory function of the postmitotic G1 checkpoint. Here we report how the nucleolus plays a critical role in activation of the postmitotic G1 checkpoint. During mitosis, the nucleolus is disrupted and many nucleolar proteins are translocated from the nucleolus into the cytoplasm. Among the nucleolar factors, Myb-binding protein 1a (MYBBP1A) induces the acetylation and accumulation of p53 by enhancing the interaction between p300 and p53 during prolonged mitosis. MYBBP1A-dependent p53 activation is essential for the postmitotic G1 checkpoint. Thus, our results demonstrate a novel nucleolar function that monitors the prolongation of mitosis and converts its signal into activation of the checkpoint machinery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To elucidate the sensory effects of GPR120 agonists on fat-containing foods, changes in the sensory characteristics of normal-fat whipped cream following the addition of the potent GPR120 agonist, ...TUG-891, were examined using descriptive analysis. Trained panellists selected 12 attributes from sensory words collected in evaluations of whipped cream with fat contents of 35 and 47%. Addition of 26 μm TUG-891 to normal-fat whipped cream significantly enhanced the intensity of the mouthcoating (initial, middle & last, and long-lasting), thickness of taste, and denseness, and also significantly decreased the score for melting speed in the mouth. Sensory scores for these attributes in normal-fat whipped cream were equivalent (mouthcoating) or close (thickness of taste, denseness, and melting speed in the mouth) to those of full-fat whipped cream. Therefore, GPR120 agonists appear to possess some of the functions of fat in dairy cream.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Role of GPR120 agonists in fat perception in humans was investigated.•GPR120 agonists enhanced the fatty orosensation when added to fat-containing system.•GPR120 agonists did not evoke the fatty ...orosensation by themselves.•Sensory activity of GPR120 agonists positively correlated with GPR120 activity.•GPR120 could be involved in the enhancement of fatty orosensation in humans.
Dietary fat, an important macronutrient, has been considered to be perceived by texture and olfaction. Recently, fatty acid transporter, CD36, and fatty acid receptor, GPR120 are considered to be involved in human gustatory fatty acids perception in humans. However, limited information is currently available to show that agonists of CD36 and GPR120 evoke fatty oral sensations regarding to dietary fat in humans. Therefore, the role of GPR120 agonists in dietary fat perception in humans was investigated herein. An emulsion prepared from vegetable oil had a stronger fatty orosensation, an orosensation similar to an oily mouth-coating sensed 5 – 10 s after tasting, than that prepared from mineral oil; however, the physical properties of both emulsions, such as viscosity, particle distribution, interfacial tension, contact angle, frictional load, and ζ-electric potential were similar. The potent GPR120 agonist, TUG-891 enhanced the fatty orosensation when added to the emulsion prepared from vegetable oil, but not to that from mineral oil. All GPR120 agonists tested enhanced the fatty orosensation when added to a low-fat food system whereas they did not evoke any fatty sensation in aqueous solution at the concentrations tested in food system, and sensory activity positively correlated with GPR120 activity. These results suggest that GPR120 agonists enhance the fatty orosensation in humans when added to vegetable oil or a low-fat food system, but do not evoke it by themselves.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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