Palmitic acid hydroxystearic acids (PAHSAs) are endogenous lipids with anti-diabetic and anti-inflammatory effects. PAHSA levels are reduced in serum and adipose tissue of insulin-resistant people and high-fat diet (HFD)-fed mice. Here, we investigated whether chronic PAHSA treatment enhances insulin sensitivity and which receptors mediate PAHSA effects. Chronic PAHSA administration in chow- and HFD-fed mice raises serum and tissue PAHSA levels ∼1.4- to 3-fold. This improves insulin sensitivity and glucose tolerance without altering body weight. PAHSA administration in chow-fed, but not HFD-fed, mice augments insulin and glucagon-like peptide (GLP-1) secretion. PAHSAs are selective agonists for GPR40, increasing Ca flux, but not intracellular cyclic AMP. Blocking GPR40 reverses improvements in glucose tolerance and insulin sensitivity in PAHSA-treated chow- and HFD-fed mice and directly inhibits PAHSA augmentation of glucose-stimulated insulin secretion in human islets. In contrast, GLP-1 receptor blockade in PAHSA-treated chow-fed mice reduces PAHSA effects on glucose tolerance, but not on insulin sensitivity. Thus, PAHSAs activate GPR40, which is involved in their beneficial metabolic effects.

BackgroundMicroRNA-21 (miR-21) plays an important role in the pathogenesis and progression of liver fibrosis. Here, we determined the serum and hepatic content of miR-21 in patients with liver cirrhosis and rats with dimethylnitrosamine-induced hepatic cirrhosis and examined the effects of miR-21 on SPRY2 and HNF4α in modulating ERK1 signaling in hepatic stellate cells (HSCs) and epithelial-mesenchymal transition (EMT) of hepatocytes.MethodsQuantitative RT-PCR was used to determine miR-21 and the expression of SPRY2, HNF4α and other genes. Immunoblotting assay was carried out to examine the expression of relevant proteins. Luciferase reporter assay was performed to assess the effects of miR-21 on its predicted target genes SPRY2 and HNF4α. Primary HSCs and hepatocytes were treated with miR-21 mimics/inhibitors or appropriate adenoviral vectors to examine the relation between miR-21 and SPRY2 or HNF4α. ResultsThe serum and hepatic content of miR-21 was significantly higher in cirrhotic patients and rats. SPRY2 and HNF4α mRNA levels were markedly lower in the cirrhotic liver. MiR-21 overexpression was associated with enhanced ERK1 signaling and EMT in liver fibrosis. Luciferase assay revealed suppressed SPRY2 and HNF4α expression by miR-21. Ectopic miR-21 stimulated ERK1 signaling in HSCs and induced hepatocyte EMT by targeting SPRY2 or HNF4α. Downregulating miR-21 suppressed ERK1 signaling, inhibited HSC activation, and blocked EMT in TGFβ1-treated hepatocytes.ConclusionsMiR-21 modulates ERK1 signaling and EMT in liver fibrosis by regulating SPRY2 and HNF4α expression. MiR-21 may serve as a potentially biomarker as well as intervention target for hepatic cirrhosis.

BackgroundTo evaluate the diagnostic performance of MRI and 3D-TVS for assessment of deep myometrial invasion (MI), cervical involvement (CI), and Lymph node metastases (LNM) in endometrial cancer staging before surgery.Material/MethodsFrom January 2016 to December 2017, we reviewed data from 314 women with endometrial cancer who underwent preoperative MRI and 3D-TVS before surgery. The diagnostic sensitivity, specificity, PPV, NPV, and accuracy in detecting MI, CI, and LNM were estimated based on ultimate pathology results.ResultsThe sensitivity, specificity, PPV, NPV, and accuracy of MRI in the diagnosis of MI were 89.19%, 88.97%, 67.35%, 97.99%, and 89.01%, respectively, and the indexes of 3D-TVS for MI were 86.36%, 91.07%, 79.17%, 94.44%, and 89.74%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI for CI were 75% and 92.35%, 40.9%, 98.13%, and 91.2%, respectively. The indicators of 3D-TVS were 77.78%, 94.29%, 63.63%, 97.06%, and 92.4%, respectively. There were no significant differences in sensitivity, specificity, NPV, and accuracy between MRI and 3D-TVS in the diagnosis of MI and CI. For MI and CI, the sensitivity of combined MRI and 3D-TVS was higher than any other single method (P<0.05). For LNM, the sensitivity, specificity, PPV, NPV, and accuracy of MRI were 58.33%, 96.26%, 63.63%, 95.37%, and 92.43%, respectively.Conclusions3D-TVS is equivalent to MRI in predicting MI and CI. Combined MRI and 3D-TVS can improve the assessment sensitivity, and they are useful in optimizing individualized surgical procedures. The sensitivity of MRI for LNM prediction needs to be improved.