11 research outputs found
NMJ morphology of <i>m. soleus</i> of NT-1654 and vehicle treated SARCO mice.
<p><b>A:</b> Confocal images of the NMJs in <i>soleus</i> muscle of P30 Control or SARCO mice, treated or not treated with NT-1654 as indicated. The postsynaptic AChRs were stained with Alexa-555 conjugate α-bungarotoxin (red) and the presynapse was stained with anti-neurofilament and synaptophysin antibodies (NF-Syn; green). The postsynapses were highly fragmented, partially or completely lost in <i>soleus</i> muscle of SARCO mice. The postsynapses of NT-1654 treated SARCO mice resembled those in Control mice, showing pretzel like structures and much less fragmentation. Scale bar: 50 µm. <b>B:</b> The postsynapses in Control mice showed fragmentation class 0 (no fragmentation, for illustration see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088739#pone.0088739.s003" target="_blank">figure S3</a>). The postsynapses of NT-1654 treated SARCO mice were mostly classified into class 1, whereas the postsynapse of SARCO mice showed class 1-4 with a peak at class 3. <b>C:</b> Many NMJs of SARCO mice have terminal nerve sprouting, which was dramatically reduced in the NT1654 treated SARCO mice. Data present mean ± standard deviation, n  =  2 mice, 100 NMJs were counted in each mouse.</p
Fiber type distribution of <i>m. soleus</i> of NT-1654 and vehicle treated SARCO mice.
<p><b>A:</b> Consecutive muscle cross sections of <i>soleus</i> stained with myosine heavy chain (MHC) specific antibodies or cytochrome C oxidase (COX) staining as indicated. Control and treated SARCO mice show clearly separated type I and II fibers. SARCO mice have a significantly increased amount of hybrid fibers (indicated with asterisks). Cytochrome C staining of <i>soleus</i> sections shows a massive reduction of reactivity in SARCO mice which is reverted back to WT levels in treated SARCO mice. <b>B:</b> Quantitative analysis of muscle fibers of <i>soleus.</i> Bars represent mean values ± standard deviation. Control and treated SARCO mice have almost no hybrid fibers and are indistinguishable from each other. Compared to treated ones, SARCO mice have significantly increased hybrid fibers. Type I fibers are significantly decreased. The total fiber number in SARCO mice is also significantly decreased compared to treated animals. Number of animals: wt  =  3; SARCO treated  =  5, SARCO  =  3. * p<0.05; ** p<0.01. Scale bar: 100 µm.</p
NMJ recovery after sciatic nerve crush.
<p><b>A:</b> Confocal images of the neuromuscular junctions (NMJs) in <i>soleus</i> muscle of Thy1-YFP mice after 14 days sciatic nerve crushing, treated with NT-1654 or PBS (Control) as indicated. The postsynaptic AChR was stained with Alexa-555 conjugate α-bungarotoxin (red) and the presynapse was visualized by the transgenic expression of YFP in motor neurons (green). The NMJs in <i>soleus</i> muscle are fully re-innervated after 14 days sciatic nerve crushing. The NMJs of NT-1654 treated mice showed significantly less nerve sprouting than those treated with PBS (Control). The number of nerve sprouting in each NMJ was counted and shown in <b>B.</b> NMJs in the NT-1654 treated mice have significantly fewer events of nerve sprouting and significantly fewer number of nerve sprouts than those of Control mice. Data present mean ± standard error, *: p<0.05 (two ways t-test), 100 NMJs were counted in each mouse, n  =  3 mice, scale bar: 50 µm.</p
Baseline and treatment features of study (A) and validation (B) cohorts.
<p>n.d.  =  not detectable, SVR = Sustained virologic response, SC = HBeAg to anti-HBe seroconversion, Rel = relapse, NR = no response, OTR = on treatment response.</p><p>Baseline and treatment features of study (A) and validation (B) cohorts.</p
Differentially expressed miRNAs comparing Baseline (BL) and Week 12 (Wk 12) sera in 14 Peg-IFN HBeAg negative CHB patients.
<p>Of the 8 miRNAs presenting p<0.05 only miR-30e-3p passes the Bonferroni correction (cut-off <0.000758) for multiple testing (<b>ΔΔ</b>Cq 1.7 up-regulation, p = 0.000354).</p><p>Differentially expressed miRNAs comparing Baseline (BL) and Week 12 (Wk 12) sera in 14 Peg-IFN HBeAg negative CHB patients.</p
Dynamic variation of miRNA profiles at Baseline (BL), during (week 12, 24 and End of Treatment, EOT) and after therapy (week 24 post-treatment follow-up, PT-FU) according to treatment response (NR, REL, SVR) in 14 Peg-IFN treated patients.
<p>Statistical analysis by one way ANOVA.</p><p>Dynamic variation of miRNA profiles at Baseline (BL), during (week 12, 24 and End of Treatment, EOT) and after therapy (week 24 post-treatment follow-up, PT-FU) according to treatment response (NR, REL, SVR) in 14 Peg-IFN treated patients.</p
MiR-B-Index in HBV carriers: diagnostic performance to identify inactive carriers (AUROCs), index kinetics in Peg-IFN treated patients by outcome and distribution of the index values by treatment outcome and phase of HBV infection.
<p><b>A)</b> Receiver operating characteristic curve for MiR-B-Index in IC vs patients with chronic hepatitis (HBeAg positive or negative CHB, HBV/HDV chronic hepatitis, ALD1): 0.9520 (95% CI 0.903 to 1.000, p<0.001); <b>B)</b> ROC for MiR-B-Index in IC vs HBeAg negative CHB (ALD2): 0.954 (95% CI 0.902 to 1.000, p<0.001; <b>C)</b> Kinetics of MiR-B-Index in 14 patients treated with Peg-IFN: MiR-B-Index values progressively increased in SVR, whereas they showed minor fluctuations in REL/NR (p<0.001); <b>D)</b> Whisker plot of the MiR-B-Index (y-axis) values in BL CHB patients treated with Peg-IFN (NR, REL and SVR), 24 week post-T-FU of REL/NR and SVR and IC, separately (CHB-BL vs IC p<0.001; SVR-BL vs SVR PT-FU p<0.001; REL/NR BL vs REL/NR PT-FU p = 0.462; SVR PT-FU vs IC p = 0.792).</p
Comparison of miRNA profile of SVR vs NR and REL at different time points by Student’s t test analysis: a total of 21 miRNA (out of 66 tested) showed significant differential expression after Bonferroni correction (cut-off<0.000758).
<p>Comparison of miRNA profile of SVR vs NR and REL at different time points by Student’s t test analysis: a total of 21 miRNA (out of 66 tested) showed significant differential expression after Bonferroni correction (cut-off<0.000758).</p
One-way ANOVA and Wilcoxon Mann Whitney U test in 61 untreated HBV carriers: 31 miRNAs (out of 66 tested) showed significant differential expression after either ANOVA or the U test on the four group comparison (Bonferroni multiple testing cut-off = 0.000758).
<p>One-way ANOVA and Wilcoxon Mann Whitney U test in 61 untreated HBV carriers: 31 miRNAs (out of 66 tested) showed significant differential expression after either ANOVA or the U test on the four group comparison (Bonferroni multiple testing cut-off = 0.000758).</p
Hierarchical clustering of miRNAs from HBsAg particles and samples.
<p>The heatmap shows the result of the two-way hierarchical clustering of miRNAs from HBsAg particles and samples (zero centered). The colour scale shown at the top illustrates the relative expression level of a miRNA across all samples: red colour represents an expression level above mean, blue colour represents expression lower than the mean. The SVR post-T FU (Peg-IFN treated patients) group clusters with the IC group.</p