Yu-Mei Xie

Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo

Activation of hepatic stellate cells (HSC) represents a critical event in fibrosis, and connective tissue growth factor (CTGF) plays a profibrotic activity and a key factor in the pathogenesis of tissue fibrosis. The current study aimed to determine whether lentivirus-mediated short hairpin RNA (shRNA)–targeted CTGF downregulates the CTGF expression and furthermore whether it suppresses the activation and proliferation of HSC in vitro and prevents liver fibrosis in vivo. HSC-T6 cells were treated with recombinant lentivirus carrying CTGF siRNA. Real-time PCR, Western blotting, MTT, and flow cytometry were performed to investigate the activation and proliferation of HSC-T6 cells in response to CTGF silence. CCl4-induced rats were received lentivirus containing CTGF siRNA by intraportal vein injection. Levels of liver fibrosis were assessed by biochemical and histopathologic examinations. Recombinant lentivirus containing CTGF siRNA could effectively and specifically downregulate the expression of CTGF in both HSC-T6 cells and CCl4-induced rats with liver fibrosis. Blockade of CTGF resulted in significant inhibition of HSC activation and proliferation with decrease in TIMPs, MMP2, MMP9, and collagen I, as well as increase in cells in S phase. Silencing CTGF expression with siRNA prevented liver fibrosis in CCl4-induced rat model. These findings indicated that CTGF plays a key role in the pathogenesis of liver fibrosis and lentiviral-mediated CTGF siRNA has the potential to be an effective treatment for liver fibrosis.

In Vitro Hepatic Differentiation of Mesenchymal Stem Cells from Human Fetal Bone Marrow

We examined whether human fetal mesenchymal stem cells (FMSCs) derived from fetal bone marrow were able to differentiate into functional hepatocyte-like cells in vitro The surface phenotype of FMSCs was characterized by flow cytometry. To induce hepatic differentiation of FMSCs, we added hepatocyte growth factor, basic fibroblast growth factor and oncostatin M into the cell culture medium. After 21 days of hepatocyte induction, FMSCs expressed the hepatocyte-specific markers, α-fetoprotein and cytokeratin 18, as demonstrated by immunofluorescence staining. Differentiated FMSCs also demonstrated in vitro functions characteristic of liver cells, including albumin production, urea secretion and glycogen storage. In conclusion, fetal bone marrow-derived FMSCs are able to differentiate into functional hepatocyte-like cells and may serve as a source of cells for liver disease therapy.

Effects of metformin and rosiglitazone on peripheral insulin resistance and β-cell function in obesity: a double-blind, randomized, controlled study.

Metformin and rosiglitazone combination therapy is known to improve insulin resistance and postpone diabetes mellitus development in subjects with impaired glucose tolerance. This double-blind, randomized, controlled study assessed this combination therapy for preventing type 2 diabetes in obese subjects with hyperinsulinaemia. Subjects received metformin (500 mg three times daily, orally) plus either rosiglitazone (4 mg once daily, orally; n = 94) or placebo (n = 95) and were followed for 6 months. Blood pressure, body fat, body mass index (BMI), lipid and insulin levels were recorded pre-and post-treatment. Metformin plus rosiglitazone significantly decreased blood pressure, lipids, BMI, and fasting and postmeal insulin levels. Metformin plus placebo led to a significant decrease in blood pressure, BMI and lipid levels, but fasting and postmeal insulin levels were unchanged. Adverse events were similar between the two groups. The metformin and rosiglitazone combination increased insulin sensitivity and β-cell function recovered. This approach may represent a therapeutic option for preventing development of type 2 diabetes in obese subjects with hyperinsulinaemia.

Kinetics of Th17 Cytokines During Telbivudine Therapy in Patients With Chronic Hepatitis B

Th17 cells and the secreting cytokines play an important role in the immune response and inflammation that is induced by hepatitis B virus (HBV). However, it remains not fully elucidated how the antiviral agents affect Th17 cytokines and signal pathway. Telbivudine therapy has been proved to inhibit HBV replication effectively and to improve clinical outcome of chronic hepatitis B (CHB). Thus, in this study, the effect of decrease in viral load and liver dysfunction resulting from telbivudine treatment on Th17 cells and the related cytokines IL-17, IL-22, and IL-23 were analyzed. Peripheral blood mononuclear cells and serum from twenty-four CHB patients were harvested at 0, 12, 24, 36, and 48 weeks after initiation of telbivudine treatment. In parallel to the reduction of HBV DNA and normalization of serum ALT, significant declines in circulating HBV-specific Th17 cells and IL-22 production were found during antiviral therapy. The expression of serum IL-22 and IL-23, but not IL-17 also decreased during therapy. Our findings suggest that antiviral effect of telbivudine may attribute to both direct virus inhibition and regulation of inflammation, which further improve the understanding of pathogenesis of HBV infection and develop antiviral strategy for controlling viral hepatitis.

Short-term effects of combined treatment with potassium bromide and methimazole in patients with Graves’ disease

Background: Potassium bromide is used as a sedative and an anti-epileptic drug for children and adolescents. Rodent animal studies have shown that bromide ions inhibit thyroid hormone synthesis by decreasing the iodine concentration in thyroid tissue. Aim: To observe the short-term clinical effects of combined treatment with potassium bromide and methimazole in patients with Graves’ disease. Materials and methods: Sixty patients with Graves’ diseases were randomized in groups. Thirty patients in the combined treatment group were treated with methimazole (10 mg, tid) and potassium bromide (1 g, tid); 30 patients in the methimazole only group were treated with methimazole (10 mg, tid) and starch placebo (1 g, tid). All the patients were treated with metoprolol tartrate (25 mg, bid) to control the symptoms and signs of hyperthyroidism. Patients were treated for one month. Clinical symptoms and potential side effects were monitored. Serum thyroid hormone levels were measured before and after the treatments. Results: Clinical hyperthyroidism symptoms were improved in both groups, with or without potassium bromide. Patients in the combined treatment group displayed improved clinical hyperthyroidism symptoms 10 days earlier on average (p<0.05). Furthermore, blood thyroid hormone levels decreased to normal levels in 93% (28/30) of patients in the combined treatment group, compared with only 37% (5/30) of patients in the methimazole only group (p<0.05). Conclusions: Treatment of patients with Graves’ disease with a novel combination therapy consisting of potassium bromide and methimazole resulted in a rapid improvement in clinical symptoms and decreased blood thyroid hormone levels to homeostatic levels faster than methimazole treatment alone.