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Aim: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs)., Methods: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition., Results: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN., Conclusion: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women.

Aim: To assess the impact of Arpin protein and tight junction (TJ) proteins in the intestinal mucosa on bacterial translocation in patients with severe acute pancreatitis (SAP)., Methods: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation (BT) in the blood [i.e., BT(+) and BT(-)]. Twenty healthy individuals were included in the control group. BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting., Results: Bacterial DNA was detected in the peripheral blood of 62.0% of patients (31/50) with SAP. The expression of TJ proteins in SAP patients was lower than that in healthy controls. In contrast, Arpin protein expression in SAP patients was higher than in healthy controls (0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05). Among SAP patients, those positive for BT showed a higher level of claudin-2 expression (0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin (OC) (0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1 (0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT (-) patients. Moreover, the level of Arpin expression in BT (+) patients was higher than in BT (-) patients (0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05)., Conclusion: Arpin protein affects the expression of tight junction proteins and may have an impact on BT. These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.

Aim: To investigate the effect of T helper (Th) 17/T regulatory (Treg) cells on hepatic fibrosis in mice and its possible mechanism., Methods: Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. Hepatic pathological changes were observed by hematoxylin and eosin staining; the protein levels of interleukin (IL)-6, transforming growth factor (TGF)-β and α-smooth muscle actin (SMA) in liver tissue were determined by Western blotting; and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry. In addition, hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells. Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation., Results: In the model group, there were different degrees of fibroplasia, degeneration and necrosis. The protein levels of IL-6, TGF-β and α-SMA in liver tissue were significantly higher than those in the control group at 12 wk (P < 0.05). Compared with the control group, the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually. Furthermore, at 4, 8 and 12 wk, there were significant differences in the number of Th17 cells (0.52% ± 0.16%, 1.46% ± 0.24%, and 2.60% ± 0.41%, respectively, P < 0.05) and Treg cells (2.99% ± 0.40%, 2.16% ± 0.50%, and 1.49% ± 0.34%, respectively, P < 0.05). In vitro, Th17 cells promoted, whereas Treg cells inhibited the expression of α-SMA, both in a dose-dependent manner, compared with the control group., Conclusion: Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.