Telomere length distribution between peripheral blood leukocyte and liver tissue in BA patients: (A) Mean levels of relative telomere length for peripheral blood leukocytes and liver tissue in BA patients; (B) Correlation between relative telomere length in peripheral blood leukocytes and liver tissue in BA patients.

<p>Telomere length distribution between peripheral blood leukocyte and liver tissue in BA patients: (A) Mean levels of relative telomere length for peripheral blood leukocytes and liver tissue in BA patients; (B) Correlation between relative telomere length in peripheral blood leukocytes and liver tissue in BA patients.</p

Telomere Length in Peripheral Blood Leukocytes Is Associated with Severity of Biliary Atresia

<div><p>Objective</p><p>The purpose of this study was to investigate the association of telomere length in peripheral blood leukocytes with the severity of biliary atresia (BA).</p><p>Methods</p><p>One hundred and fourteen BA patients and 114 age-matched healthy controls were enrolled. Relative telomere length (RTL) was assessed using a quantitative real-time polymerase chain reaction. Multivariate regression analysis was used to estimate RTL as an independent risk factor of BA. Receiver operating characteristic curve analysis was used to calculate the accuracy of biomarkers in the prediction of liver cirrhosis.</p><p>Results</p><p>BA patients had significantly shorter telomeres than healthy controls (<i>p</i> < 0.0001). The RTL in BA patients with jaundice was considerably lower than that of patients without jaundice (<i>p</i> = 0.005). Moreover, RTL was markedly shorter in patients with cirrhosis (F4), as compared to patients with mild fibrosis (F2) and non-fibrosis (F0-F1, <i>p</i> < 0.0001). Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA. Tertile analysis showed a dose-response effect for this association (<i>p</i> trend < 0.0001). Additionally, RTL in BA children revealed a negative correlation with age (<i>r</i> = -0.50, <i>p</i> < 0.001). We noted an association between reduction of RTL and liver stiffness scores, adjusted for age and gender (<i>b</i> = -0.01, <i>p</i> < 0.0001). Short RTL can be employed to distinguish cirrhosis patients from non-cirrhosis patients (AUC = 0.78). Further analysis showed a linear correlation between leukocyte RTL and liver RTL in BA patients (<i>r</i> = 0.83, <i>p</i> < 0.001).</p><p>Conclusion</p><p>The findings of this study provide evidence that telomere shortening is associated with an elevated risk of liver cirrhosis in BA.</p></div

Scatter plot demonstrating correlation between relative telomere length of peripheral blood leukocytes and age in controls and BA patients: (A) Relative telomere length decrease with age in the controls; (B) Significant relative telomere length decrease with age in BA patients.

<p>Scatter plot demonstrating correlation between relative telomere length of peripheral blood leukocytes and age in controls and BA patients: (A) Relative telomere length decrease with age in the controls; (B) Significant relative telomere length decrease with age in BA patients.</p

Box-plot illustrating telomere length distribution in subjects among different groups: The line through the middle of the boxes represents the median of T/S value and the top and bottom of each box represents the first and third quartiles.

<p>The lower and upper error bars are computed as the lower and upper quartiles, respectively. (A) Relative telomere length in BA patients and healthy controls; (B) Relative telomere length in BA patients and controls, according to age group; (C) Relative telomere length in patients with and without jaundice; (D) Relative telomere length in BA subgroups, including non-fibrosis (F0-F1), mild fibrosis (F2), severe fibrosis (F3), and liver cirrhosis (F4).</p

Telomere length assessment finding in two sets of twins by BA discordance: (A) Amplification plot and relative telomere length analysis in nine-year-old twin girls who were discordant for BA (set 1); (B) Amplification plot and relative telomere length analysis in nineteen-year-old twin women affected by BA discordance (set 2).

<p>Telomere length assessment finding in two sets of twins by BA discordance: (A) Amplification plot and relative telomere length analysis in nine-year-old twin girls who were discordant for BA (set 1); (B) Amplification plot and relative telomere length analysis in nineteen-year-old twin women affected by BA discordance (set 2).</p

Receiver operating characteristic (ROC) curve representing diagnostic value of relative telomere length in biliary atresia patients with cirrhosis: The optimal cut-off value of relative telomere length at 0.58 as a marker discriminating between BA patients with and without cirrhosis.

<p>Receiver operating characteristic (ROC) curve representing diagnostic value of relative telomere length in biliary atresia patients with cirrhosis: The optimal cut-off value of relative telomere length at 0.58 as a marker discriminating between BA patients with and without cirrhosis.</p

Clinicopathologic characteristics of biliary atresia patients and age-matched healthy controls.

<p>Abbreviations: BA = biliary atresia; AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; NS = not significant; NA = not available</p><p>Clinicopathologic characteristics of biliary atresia patients and age-matched healthy controls.</p

sj-pdf-1-imr-10.1177_03000605221121940 - Supplemental material for Type 1 diabetes mellitus induced by PD-1 inhibitors in China: a report of two cases

Supplemental material, sj-pdf-1-imr-10.1177_03000605221121940 for Type 1 diabetes mellitus induced by PD-1 inhibitors in China: a report of two cases by Jingmei Luo, Jiagang Feng, Chunyan Liu, Zhongce Yang, Dong Zhan, Yanan Wu, Li Pan and Lihua Zhang in Journal of International Medical Research</p

Resveratrol activates the PI3-K/Akt signaling pathway in RAW 264.7 macrophage cells.

<p>Panel A shows that RAW 264.7 cells were treated with resveratrol (5 µM) for the indicated times, Panel B shows that RAW 264.7 cells were pre-treated with resveratrol (5 µM) for 1 h in the absence or presence of wortmannin (1 µM), then exposed to LPS (5 µg/ml) for 40 min and Panel C shows that the cells were incubated with LPS (5 µg/ml) without or with 5 µM resveratrol for the indicated times. Various treated RAW 264.7 cell lysates (50 µg protein) were prepared and subjected to Western blot analysis by using antibodies specific for total Akt and phosphorylated forms of Akt (shown as phospho-Akt) as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044107#s4" target="_blank">methods</a>. The relative protein levels were quantified by scanning densitometry and normalized to total Akt. The values shown are mean ± SEM of data from three independent experiments. ^#Significant compared with control alone, <i>p</i><0.05. ^*Significant compared with LPS alone, <i>p</i><0.05. ^ΔSignificant compared with resveratrol + LPS, <i>p</i><0.05.</p

Inhibition of the phosphorylation of CREB, and MAPKs signaling by resveratrol is PI3-K-dependent during RAW 264.7 macrophage cells activation by LPS.

<p>Approximately 1×10⁶ cells/ml were seeded in six-well plates and incubated until 80% confluency. Cells were pre-treated with resveratrol (1, 5, and 10 µM) for 1 h in the absence or presence of wortmannin (1 µM), then exposed to LPS (5 µg/ml) for 30 min. Cell lysates (50 µg protein) were prepared and subjected to Western blot analysis by using antibodies specific for phosphorylated forms of CREB, ERK1/2, JNK and p38 MAPK (shown as phospho-IκB-α, etc.) as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044107#s4" target="_blank">methods</a>. Equivalent loading of cell lysates was determined by reprobing the blots with anti-β-actin, total ERK1/2, JNK or p38 MAPK antibodies. The relative protein levels were quantified by scanning densitometry and normalized to β-actin, total ERK1/2, JNK or p38 MAPK. The values shown are mean ± SEM of data from three independent experiments. ^#Significant compared with control alone, <i>p</i><0.05. ^*Significant compared with LPS alone, <i>p</i><0.05. ^ΔSignificant compared with resveratrol + LPS, <i>p</i><0.05.</p