ABSTRACT
Objective To investigate the anti-injury and anti-inflammation protective effects of metformin in acute-liver-injury SD rat model induced by D-galactosamine and Pam3CSK4 .Methods Eighteen male Sprague-Dawley rats were treated with the mixture of D-galactosamine (350 mg/kg ) and Pam3CSK4 (50 μg/kg ) by intraperitoneal injection (i .p .) to construct acute liver injury model .The rats in intervention group were given PBS and metformin ,respectively .The liver and body weight were measured and the ratio of liver weight to body weight was calculated .HE staining was used to observe the pathological changes of the liver .Fasting serum was collected for detection of serological parameters .ELISA and RT-qPCR were used to determine the expression levels of IL-6 and TNF-α.Finally , activation of MAPK signal pathway in rat liver was detected by Western blot .Results Compared with those in control group , the ratio of body weight to liver weight , serum transaminase and proinflammatory cytokines IL-6 and TNF-a were all significantly increased in the two intervention groups .Meanwhile , hepatic degeneration and hepatic interstitial exudation indicated that D -galactosamine combined with Pam3CSK4 successfully constructed acute liver injury model in the SD rats.Compared with PBS group, the ratio of body weight to liver weight , hepatic damage , serum transaminase levels.and the expressions of proinflammatory cytokines IL-6 and TNF-a were significantly decreased in metformin-treated group.Meanwhile,the expressions of p-ERKl/2,p-SAPK/JNK and p-P38 MAPK decreased in liver tissues by metformin pretreatment,suggesting that metformin may play an anti-inflammatory effect by suppressing MAPK signaling pathway.Conclusion Metformin attenuated inflammatory reactions in SD rats with acute liver injury induced by D -galactosamine and Pam3CSK4.
ABSTRACT
This study was aimed to investigate the effect of dexamethasone (Dex) on immunosuppressive ability of mesenchymal stem cells (MSC) during expansion and differentiation of MSC. MSC were cultured in 96-well flat-bottom plates. Proliferation assays were performed by using the BrdU colorimetric ELISA Kit. To explore the effect of Dex on MSC immunosuppressive ability, MSC were firstly cultured in complete culture medium for 14 d with Dex (10 nmol/L), and then, peripheral blood mononuclear cells (PBMNC) were co-cultured with MSC in 96-well flat-bottom plates for 3 d. Phytohemagglutinin A (PHA, 10 µg/ml) was used to stimulate activation of PBMNC. The concentrations of IFN-γ in culture supernatants was detected by ELISA. The results indicated that there was no obvious difference in representative phenotypes of MSC between experimental and control groups after MSC were treated with low concentration of Dex (10 nmol/L) for 14 d, but the suppression of Dex-treated MSC on lymphocyte activation in same concentration of cells was significantly reduced as compared with control group. After the Dex-treated MSC were co-cultured with IFN-γ for 12 h, the immunoregulatory ability of MSC was recovered in a certain degree. It is concluded that the Dex impairs the immunosuppressive ability of MSC, the IFN-γ can protect and reverse the immunosuppressive ability of MSC impaired by Dex, so that, when the immunoregulatory activity of MSC is investigated, it is necessary to avoid adding Dex in the culture medium.
Subject(s)
Humans , Cells, Cultured , Dexamethasone , Immune Tolerance , Interferon-gamma , Allergy and Immunology , Leukocytes, Mononuclear , Lymphocyte Activation , Allergy and Immunology , Mesenchymal Stem Cells , Cell Biology , Allergy and ImmunologyABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>X-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors.</p><p><b>METHODS</b>Between July 1999 and December 2004, a total of 122 intracranial lesions in 78 patients with BM were treated using SRT in our Center. Forty-nine patients had a solitary lesion and 29 had multiple (2-6) lesions. The median SRT dose was 15 Gy (11-24 Gy) in single fraction for 38 lesions, and 24 Gy (11-40 Gy) in 2-6 fractions for 84 lesions. SRT was combined with whole brain radiotherapy (WBRT) of 30-40 Gy for 39 patients. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox model, respectively.</p><p><b>RESULTS</b>The median survival time was 12.9 months (1.7-77.4 months). The 1-year intracranial PFS rate was 87.4%. The 1-and 2-year OS rates were 53.9% and 25.8%, respectively. Univariate analysis showed that the 1-year OS rates were higher in the patients with pretreatment KPS of >/= 70, extracranial lesions controlled, or SRT combined with WBRT than in those with KPS of < 70 (60.7% vs. 29.4%, P = 0.002), extracranial lesions uncontrolled (69% vs. 44.9%, P = 0.005), or SRT alone (64.1% vs. 43.4%, P = 0.03). The benefit of treating with WBRT in combination was mainly achieved in the patients with extracranial lesions controlled or with more than one intracranial lesion. Multivariate analysis showed that KPS score and status of extracranial lesions were independent prognostic factors for OS.</p><p><b>CONCLUSIONS</b>SRT is an effective and safe modality for BM. SRT combined with WBRT may prolong the survival time of the patients with extracranial lesions controlled or multiple intracranial lesions. Independent prognostic factors for OS are KPS score and status of extracranial lesions.</p>