AIMTo investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.METHODSA CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.RESULTSWe demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1.CONCLUSIONTransplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

To evaluate the change in phosphatase and tensin homology deleted on chromosome ten (PTEN) expression in liver fibrogenesis, particularly the reversal of fibrogenic liver tissues, and to investigate the relation with the proliferation and apoptosis of hepatic stellate cells (HSCs) in vivo, a rat model of hepatic fibrosis was established by hypodermic injection of carbon tetrachloride (CCl4) mixed with olive oil at the concentration of 40% for 5 weeks (2 ml/kg, twice a week). Reversal of fibrosis was achieved with normal feedings for 4 weeks after CCl4 injection for 5 weeks. The expression of PTEN was measured by immunofluorescence, western blot analysis and real-time PCR. Co-expression of α-smooth muscle actin (α-SMA) with PTEN and α-SMA with terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) were assessed by confocal laser scanning microscopy. The results displayed that the expression of PTEN was reduced with fibrosis in both rat liver tissues and activated HSCs. By contrast, PTEN expression was increased with the reversal of liver fibrosis. Compared to the fibrogenic state, there were increased numbers of apoptotic activated HSCs during reversal of fibrosis. These data suggest that the dynamic expression of PTEN in rat liver tissues is negatively correlated with liver fibrosis and activated HSCs and is positively correlated with reversal of fibrosis and apoptotic activated HSCs. Modulation of PTEN expression may be an effective and novel method for the treatment of liver fibrosis.

BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3 (Tim-3), transforming growth factor β (TGF-β), and chemokine-12 (CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) have not been elucidated. AIM To examine the correlation between Tim-3, TGF-β and CXCL12 expression and DLBCL prognosis. METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups, respectively. The expression of Tim-3, TGF-β, and CXCL12 was detected immunohistochemically. Patients were followed up for 3 years, and progression-free survival was recorded. Cox multifactorial analysis was performed to analyze the risk factors for poor prognosis. RESULTS The positive expression rates of Tim-3, TGF-β, and CXCL12 were higher in DLBCL tissues than in non-cancerous (control) tissues ( P < 0.05). One-year post-surgery, the positive expression rates of Tim-3, TGF-β, and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment ( P < 0.05). The 3-year progression-free survival of 97 patients with DLBCL was 67.01% (65/97). Univariate analysis revealed that clinical stage, bone marrow infiltration, International Prognostic Index (IPI) score, Tim-3 positivity, TGF-β positivity, and CXCL12 positivity were associated with poor prognosis ( P < 0.05). Multivariate Cox regression analysis demonstrated that clinical stage III–IV, bone marrow infiltration, mediate-to-high-risk IPI scores, Tim-3 positivity, TGF-β positivity, and CXCL12 positivity were independent risk factors affecting prognosis ( P < 0.05). CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3, TGF-β, and CXCL12, and a high expression of all three indicates a poor prognosis.

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