Pretreating mesenchymal stem cells with IL-6 regulates the inflammatory response of DSS-induced ulcerative colitis in rats.

The immunomodulatory properties of mesenchymal stem cells (MSCs) have been broadly investigated in research on inflammatory diseases including ulcerative colitis. Treating MSCs with an inflammatory stimulus before transplantation is an adaptive strategy that helps MSCs survive in areas of inflammation and promotes the regulation of local immune responses. This study aimed to examine the effects of pretreating bone marrow MSCs (BMSCs) with Interleukin-6 (IL-6) on attenuation of dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. Experimental ulcerative colitis was induced in Wistar rats by administering 2% DSS in their water for 7 days and normal water for the next 3 days. The experimental group received 1 × 106/0.4 ml of BMSCs that were treated with IL-6 for 24 h. Histological changes, colon length, and disease activity index were compared among groups, and the levels of TNF-α, IL-6, and IL-1ß in homogenate supernatants were evaluated using ELISA. IL-6-pretreated BMSCs significantly reduced the colonic damage score. The colon length shortened by 6.1 ± 0.14 cm for the rats that received IL-6-pretreated BMSCs, whereas the control group rats' value was 3.8 ± 0.14 cm on the 14th day. The levels of pro-inflammatory cytokines were significantly decreased in the colons of the IL-6-pretreated BMSCs group compared with those of the control group (p < 0.05). This study revealed that IL-6-pretreated BMSCs ameliorated DSS-induced colitis via local anti-inflammatory action and suggested that IL-6-pretreated BMSCs are a promising therapeutic agent for ulcerative colitis treatment.

Effects of alendronate combined with local radiotherapy on serum Akt/GSK3ß and bone metabolism levels in patients with bone metastases from primary liver cancer.

OBJECTIVE: To investigate the effects of alendronate combined with local radiotherapy on the level of serum Akt/GSK3ß and bone metabolism in patients of primary liver cancer with bone metastases. METHODS: Clinical data of 68 patients of primary liver cancer with bone metastases and treated in Shanghai General Hospital, a hospital affiliated to Shanghai Jiao Tong University School of Medicine, were retrospectively analyzed. According to the different surgical methods, the patients were divided into a control group, with 33 cases treated with local radiotherapy plus Oxycodone hydrochloride extended-release tablets, and a study group, with 35 cases treated with alendronate combined with local radiotherapy. The remission rate and adverse reaction rate were compared between the two groups. In addition, we observed and compared the liver function indexes (total bilirubin (TBIL), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), serum Akt/GSK3ß level, bone metabolism levels (bone alkaline phosphatase (BAP) and levels of osteocalcin (OST)), α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), osteopontin (OPN), matrix metallopeptidase 9 (MMP-9), and quality of life of the patients in two groups before and after treatment. RESULTS: A higher remission rate was observed in the study group (94.29%) than that in the control group (75.76%) (P<0.05). There was no significant difference in the adverse reaction rate between the study group (20.00%) and the control group (12.12%) (P>0.05). In both groups, the post-treatment serum levels of TBIL, ALT, ALP, Akt, GSK3ß, AFP, VEGF, OPN, MMP-9, hardship and nausea due to cancer were all decreased, while serum levels of BAP and OST, and psychological, physical and social functions were all increased (all P<0.05). The improvement of the above indicators in the study group were better than those in the control group (all P<0.05). CONCLUSION: The use of alendronate combined with local radiotherapy received good response in patients of primary liver cancer with bone metastasis. In addition, their liver function, bone metabolism levels and quality of life all improved without increasing adverse reactions. The underlying mechanism may be related to the regulation of Akt and GSK3ß levels.

Sanguinarine promotes apoptosis of hepatocellular carcinoma cells via regulating the miR-497-5p/CDK4 axis.

OBJECTIVE: To determine the effect of sanguinarine on the biological behavior of hepatocellular carcinoma (HCC) cells via regulating the miR-497-5p/cyclin-dependent kinase 4 (CDK4) axis. METHODS: Swiss Target Prediction was used for target prediction of sanguinarine. The targets were analyzed with KEGG enrichment analysis, and CDK4 was included in this study. Target prediction website, Diana tools enrichment analysis, and dual-luciferase reporter assay were adopted to identify the target miRNAs for CDK4. We measured expression levels of CDK4 and miR-497-5p in cancerous tissues, normal liver L02 cells, HepG2 HCC cells and sanguinarine-treated HepG2 cells. The expression of CDK4/miR-497-5p in HCC cells was intervened by treating HCC cells with sanguinarine. Cell proliferation, invasion and apoptosis were measured with CCK8, Transwell and flow cytometry, respectively. RESULTS: CDK4 was shown to be a target for sanguinarine. Compared with L02 cells, CDK4 expression in HCC cells was significantly increased, but sanguinarine inhibited the CDK4 expression in HCC cells. The proliferation and invasion of HCC cells were inhibited, and the apoptosis was promoted by sanguinarine, but these effects were reversed by CDK4 overexpression (both P<0.05). miR-497-5p was confirmed to be a target miRNA for CDK4, and its expression was decreased in HCC cells but could be promoted by sanguinarine. The effect of miR-497-5p knockdown on HCC cells was partially reversed by si-CDK4. CONCLUSION: Sanguinarine inhibits the proliferation and invasion of HCC cells, and induces the apoptosis of HCC cells by regulating the expression of miR-497-5p/CDK4.

Drug-eluting beads transarterial chemoembolization sequentially combined with radiofrequency ablation in the treatment of untreated and recurrent hepatocellular carcinoma.

BACKGROUND: Drug-eluting beads transarterial chemoem-bolization (DEB-TACE) has the advantages of slow and steady release, high local concentration, and low incidence of adverse drug reactions compared to the traditional TACE. DEB-TACE combined with sequentially ultrasound-guided radiofrequency ablation (RFA) therapy has strong anti-cancer effects and little side effects, but there are fewer related long-term studies until now. AIM: To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma (HCC). METHODS: Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited. Forty patients with untreated HCC were included in Group A, and 36 patients with recurrent HCC were included in Group B. In addition, 40 patients with untreated HCC who were treated with hepatectomy were included in Group C. The serological examination, preoperative magnetic resonance imaging examination, and post-treatment computed tomography enhanced examination were performed for all patients. The efficacy was graded as complete remission (CR), partial remission (PR), stable disease and progressive disease at the 3rd, 6th, and 9th. All patients were followed up for 3 years and their overall survival (OS), disease-free survival (DFS) were assessed. RESULTS: The efficacy of Group A and Group C was similar (P > 0.05), but the alanine aminotransferase, aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C (all P < 0.05). The proportions of CR (32.5%), PR (37.5%) were slightly higher than Group A (CR: 27.5%, PR: 35%), but the difference was not statistically significant (χ 2 = 0.701, P = 0.873). No operational-related deaths occurred in Group A and Group C. The OS (97.5%, 84.7%, and 66.1%) and the DFS (75.0%, 51.7%, and 35.4%) of Group A at the 1st, 2nd, and 3rd year after treatment were similar with those of Group C (OS: 90.0%, 79.7%, and 63.8%; DFS: 80.0%, 59.7%, and 48.6%; P > 0.05). The OS rates in Group A and Group B (90%, 82.3%, and 66.4%) were similar (P > 0.05). The DFS rates in Group B (50%, 31.6%, and 17.2%) were lower than that of Group A (P = 0.013). CONCLUSION: The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy. Patients with recurrent HCC could get a longer survival time through the combined treatment.