Algorithm guided outlining of 105 pancreatic cancer liver metastases in Ultrasound

Algorithm guided outlining of 105 pancreatic cancer liver metastases in Ultrasound

The examiners first performed a manual segmentation and, after five weeks, a semiautomatic segmentation using the algorithm.
Semiautomatic segmentation algorithms promise a faster and more accurate way to segment lesions but are often performed on a small set of lesions by examiners that often worked with the algorithm before.
The median differences of manual and semiautomatic segmentations were significant (p < 0.01) in both cases. Two examiners with over 10 years-experience in performing and interpreting over 20,000 ultrasound examinations performed the measurements. Additionally, the examiners had never used the algorithm before. Regarding the manual segmentation, examiner 2 was faster, but both examiners needed less time, when they were using the semiautomatic algorithm. Interestingly, analyzing the dataset including the segmentations marked as “not satisfied” revealed that examiner 1 had images where he spent more time on the semiautomatic segmentation than on the manual outlining. Supplementary Figure 5 presents an example of a segmentation regarded by examiner 1 as inadequate compared to the segmentation of the same image by examiner 2, who was satisfied with the result. In this contribution, we presented the results of a fast, interactive segmentation algorithm for pancreatic liver metastases in ultrasound images.

Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells

Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells

We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) following ethanol treatment. In addition, increased ubiquitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol.
Hepatic triglycerides (TG) level in alcoholic fatty liver disease models was reduced by activating autophagy, and was elevated when autophagy was inhibited5,6.
The lipid content in AML12 cells as measured by the levels of TG and cholesterol was elevated in 24 hours after ethanol treatment (Fig.
SQSTM1 is important for LC3 to be associated with LDs and ethanol-induced lipophagy.
In addition, the SQSTM1 level was elevated significantly following PLIN knockdown, although the level of LC3 was only mildly affected (Supplementary Fig. Furthermore, the colocalization of SQSTM1 to the LDs was significantly reduced by the inhibition of PLIN expression in either ethanol alone (Fig. 7A and B) or ethanol plus CQ (Fig.
Using this model, we had the following findings: (1) Autophagy is activated by ethanol in AML12 cells, which requires ethanol to be oxidized; (2) Autophagy regulates the level of lipid content in ethanol-treated cells, consistent with previous in vivo studies that autophagy modulators affect hepatic lipid levels; (3) Autophagic degradation of lipid droplets is indicated by the colocalization of autophagosomes with the lipid droplets and the blockage of the degradation by lysosome inhibitors; (4) Recognition of lipid droplets by autophagosomes is mediated by SQSTM1, and involves ubiquitination signaling; and (5) PLIN could be a target recognized by SQSTM1 and serve as an anchor for autophagosomes on lipid droplets.

Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis

Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate.
Since Th17 and Treg have opposite functions, their balance could affect disease progression.
The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients.
Peripheral blood lymphocyte frequency was not associated with liver damage.
Hepatitis related to Hepatitis C virus (HCV) is a progressive disease, so liver failure as a consequence of HCV infection is one of the most common reasons for liver transplantation.
Blood CD4+ and CD8+ T cells response have limited impact on disease course whereas intrahepatic T cells seem to control disease pathogenesis7,8.
Normally, cytotoxic T lymphocytes (CTL, CD8+ T cells) are essential for infection control, as they migrate to infected tissues and mediate viral clearance.
Th17 lymphocytes represent a pro-inflammatory subset, which contribute to autoimmunity and tissue damage, while Tregs control the balance between immune activation and tolerance, by cell to cell contact or secreting IL-10 and TGF-β10.
Moreover, HCV immune response has been mainly studied in peripheral blood mononuclear cells (PBMC) samples because of the difficulty in obtaining HCV-infected liver tissue.
Liver injury in pediatric CHC would be largely associated with viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

Bile acid TUDCA improves insulin clearance by increasing the expression of insulin-degrading enzyme in the liver of obese mice

Bile acid TUDCA improves insulin clearance by increasing the expression of insulin-degrading enzyme in the liver of obese mice

Here, we demonstrated that 15 days treatment with TUDCA reestablished plasma insulin to physiological concentrations in high fat diet (HFD) mice, a phenomenon associated with increased insulin clearance and liver IDE expression.
This effect is probably due to increased IDE expression in the liver.
TUDCA treatment reduced body and fat pad weight in the HFD + TUDCA mice (Table 1) and also returned fed/fasted blood glucose concentrations to levels similar to the CON mice (Table 1).
During the ipITT, HFD mice displayed higher blood glucose, compared with CON mice (Fig.
The treatment with TUDCA restored insulin sensitivity in HFD + TUDCA mice (Fig.
Also, plasma insulin concentration was increased in the HFD mice (Fig.
Thus, reduction in the C-peptide:insulin ratio indicates a reduced insulin clearance, as we observed in the HFD mice (Fig.
3B and C), it restored the IDE protein expression in the HFD + TUDCA to levels similar to that of CON mice (Fig.
TUDCA treatment increases insulin clearance in HFD mice.
Full size image TUDCA treatment increases IDE expression, but not activity in HFD mice.

HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRα and PPARα dysregulation: implications for HIV-specific pathogenesis of NAFLD

HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRα and PPARα dysregulation: implications for HIV-specific pathogenesis of NAFLD

HIV patients develop hepatic steatosis.
Vpr enhanced association of LXRα with Lxrα and Srebp1c promoters, increased LXRE-LXRα binding, and broadly altered hepatic expression of LXRα-regulated lipid metabolic genes.
(A) Immunoblots show expression of transcription factors and their target proteins in Vpr-Tg vs. WT mice (N = 4 per group).
(F) Immunoblots show expression of transcription factor and their target proteins in sVpr-treated vs. vehicle-treated mice (N = 4 per group; N = 3 per group for ACC/pACC).
Full size image Vpr binds to LXRα and enhances LXRE-dependent promoter activity.
Data are presented as means ± SE of two replicates, and are representative of two experiments.
(A) Fatty acid oxidation was decreased in liver of Vpr-Tg compared to WT mice (P = 0.006; N = 6 per group).
(C) Pparα mRNA level was decreased in liver of Vpr-Tg compared to WT mice (N = 5–6 per group).
(B) Decreased protein level of MTP was present in liver of Vpr-Tg compared to WT mice (N = 4 per group).
(A) Scatterplot of gene expression from RNA-Seq in Vpr-Tg compared with WT mouse liver.