The roles of the glucagon-like peptide-2 and the serum TGF-ß1 levels in the intestinal barrier and immune functions in rats with obstructive jaundice.

OBJECTIVE: To determine the mechanisms by which glucagon-like peptide-2 (GLP-2) impacts the intestinal barrier function, the immune function, and the serum transforming growth factor-ß1 (TGF-ß1) levels in rats with obstructive jaundice. METHODS: Overall, 72 SPF-grade healthy Wistar rats were randomly divided into 4 groups containing 18 rats each: the observation group (ligation of common bile duct, intraperitoneal GLP-2 injection), the control group (ligation of common bile duct, normal saline), the sham-operated group (common bile duct exposed without ligation, normal saline), and the blank group. The serum immune function and the TGF-ß1 levels were measured on days 3, 7, and 14 after the intervention. RESULTS: The body mass was determined to be significantly less in the control group than in the other three groups on day 14 after the intervention (P < 0.05). The TGF-ß1, endotoxin, alanine aminotransferase (ALT), and bilirubin were expressed at significantly higher levels in the control group compared with the blank and sham-operated groups and were the highest at each time point, but the levels in the observation group were significantly decreased after the intervention (P < 0.05). CONCLUSIONS: We found that GLP-2 can decrease the serum TGF-ß1 levels, regulate the immune function, reduce the endotoxin and bilirubin, and protect the intestinal barrier function in rats with obstructive jaundice.

SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma.

A previous study reported that histone methyltransferase SETD3 is up-regulated in tumor tissues of hepatocellular carcinoma (HCC) and is associated with the growth of HCC. However, the clinical significance and the effect of SETD3 on HCC metastasis remain unclear. In the present study, both the protein and mRNA expression levels of SETD3 were measured in a larger cohort of HCC patients. The results showed that the protein level of SETD3 in HCC tissues was significantly higher than that in non-tumorous tissues, which was inconsistent with the mRNA expression level of SETD3. The high protein level of SETD3 in HCC tissues was significantly associated with male gender, poor pathological differentiation, liver cirrhosis and unfavorable prognosis of HCC patients. Subsequently, we demonstrated that SETD3 could be regulated at post-transcriptional step by a couple of miRNAs (miR-16, miR-195 and miR-497). Additionally, in vitro and in vivo experiments revealed that SETD3 played opposing roles in proliferation and metastasis of HCC: promoting proliferation but inhibiting metastasis. Mechanistic experiments revealed that doublecortin-like kinase 1 (DCLK1) was a downstream target of SETD3. SETD3 could increase the DNA methylation level of DCLK1 promoter to inhibit the transcription of DCLK1. Further study revealed that DCLK1/PI3K/matrix metalloproteinase (MMP) 2 (MMP-2) was an important pathway that mediated the effect of SETD3 on HCC metastasis. In conclusion, the present study revealed that SETD3 is associated with tumorigenesis and is a promising biomarker for predicting the prognosis of HCC patients after surgical resection. In addition, SETD3 plays inhibitory role in HCC metastasis partly through DCLK1/PI3K/MMP-2 pathway.

CircSETD3 (Hsa_circ_0000567) acts as a sponge for microRNA-421 inhibiting hepatocellular carcinoma growth.

BACKGROUND: Circular RNAs (circRNAs) play important roles in tumourigenesis and tumour progression. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) are largely unclear. METHODS: The expression profiles of circRNAs in HCC were identified through microarray analysis and were validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of HCC cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: CircSETD3 (hsa_circRNA_0000567/hsa_circRNA_101436) was significantly downregulated in HCC tissues and cell lines. Low expression of circSETD3 in HCC tissues significantly predicted an unfavourable prognosis and was correlated with larger tumour size and poor differentiation of HCC in patients. In vitro experiments showed that circSETD3 inhibited the proliferation of HCC cells and induced G1/S arrest in HCC cells. In vivo studies revealed that circSETD3 was stably overexpressed in a xenograft mouse model and inhibited the growth of HCC. Furthermore, we demonstrated that circSETD3 acts as a sponge for miR-421 and verified that mitogen-activated protein kinase (MAPK)14 is a novel target of miR-421. CONCLUSION: CircSETD3 is a novel tumour suppressor of HCC and is a valuable prognostic biomarker. Moreover, circSETD3 inhibits the growth of HCC partly through the circSETD3/miR-421/MAPK14 pathway.

miR-517a promotes Warburg effect in HCC by directly targeting FBP1.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide. Our aim is to explore the expression and biological function of miR-517a in HCC. MATERIALS AND METHODS: We performed qRT-PCR to detect the expression of miR-517a in clinical samples and cell lines. CKK-8 assay and colony formation assay were employed to detect the miR-517a regulated cell proliferation. Glucose uptake and lactate production were examined to determine the Warburg effect. We also performed ECAR assay using Seahorse system. Luciferase acitivy assay was used to examine the binding of FBP1 3'UTR by miR-517a. RESULTS: miR-517a was upregulated in HCC samples in both genomic and mRNA levels. Moreover, overexpression of miR-517a promoted cell proliferation and Warburg effect. Mechanically, miR-517a could directly target the 3'-UTR of FBP1. In addition, restoring the expression of FBP1 inhibited cell growth. CONCLUSION: We demonstrated that miR-517a acts as an oncogene to promote Warburg effect in HCC, favoring tumor growth, and miR-517a/FBP1 could be a novel target for HCC treatment.

Glycosylation change of alpha-1-acid glycoprotein as a serum biomarker for hepatocellular carcinoma and cirrhosis.

AIM: This research is to explore the glycosylation change of alpha-1-acid glycoprotein (AGP) in hepatocellular carcinoma (HCC), cirrhosis and controls. METHODS: The affinity chromatography and lectin affinity techniques were used to separate and enrich glycosylated AGP, and combined with mass spectrometry to identify and relatively quantify the glycopeptides from AGP. RESULTS: The sialylation and fucosylation of AGP were different among HCC, cirrhosis and controls. The highly sialylated and fucosylated peptides from AGP were found in HCC and cirrhosis compared with controls. These glycopeptides showed excellent diagnostic ability to differentiate HCC from cirrhosis (area under the curve >0.9). In addition, these glycopeptides showed significantly different among four HCC stages. CONCLUSION: The sialylation and fucosylation change of AGP may serve as serum biomarker for HCC and cirrhosis.

Simplified pancreatoduodenectomy for complex blunt pancreaticoduodenal injury.

A 34-year-old man admitted to our department with complex blunt pancreaticoduodenal injury after a car accident. The wall of the first, second, and third portions of the duodenum was extensively lacerated, and the pancreas was longitudinally transected along the superior mesenteric vein-portal vein trunk. The pancreatic head and the uncinate process were devitalized and the distal common bile duct and the proximal main pancreatic duct were completely detached from the Vater ampulla. The length of the stump of distal common bile located at the cut surface of remnant pancreas was approximately 0.6 cm. A simplified Kausch-Whipple's procedure was performed after debridement of the devitalized pancreatic head and resection of the damaged duodenum in which the stump of distal common bile duct and the pancreatic remnant were embedded into the jejunal loop. Postoperative wound abscess appeared that eventually recovered by conservative treatment. During 16 months follow-up the patient has been stable and healthy. A simplified pancreaticoduodenectomy is a safe alternative for the Whipple procedure in managing complex pancreaticoduodenal injury in a hemodynamically stable patient.