ABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear. METHODS: MSCs were isolated from the bone marrow (BM) of 4-6-week-old male C57BL/6 N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. The mice were given intraperitoneal injections of MSCs with or without transfection or AG490, recombinant mouse tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rmTSG-6), or saline at day 10. Blood samples and hepatic tissues were collected at day 11. Various assays such as biochemistry, histology, and flow cytometry were performed. RESULTS: MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-É, but increasing glutathione, IL-10, and TSG-6, compared to control mice. Few MSCs engrafted into the inflamed liver. Knockdown of TSG-6 in MSCs significantly attenuated their effects, and injection of rmTSG-6 achieved similar effects to MSCs. The signal transducer and activator of transcription 3 (STAT3) was activated in mice with AH, and MSCs and rmTSG-6 inhibited the STAT3 activation. Injection of MSCs plus AG490 obtained more alleviation of liver injury than MSCs alone. CONCLUSIONS: BM-MSCs injected into mice with AH do not engraft the liver, but they secrete TSG-6 to reduce liver injury and to inhibit STAT3 activation.
Subject(s)
Cell Adhesion Molecules/metabolism , Chemical and Drug Induced Liver Injury/therapy , Ethanol/adverse effects , Mesenchymal Stem Cells/metabolism , STAT3 Transcription Factor/metabolism , Animals , Disease Models, Animal , Female , MiceABSTRACT
The objective of the study was to explore the effects of behavioral and cognitive development in rats after prenatal exposure to 1800 and 2400 MHz radiofrequency fields. Pregnant female rats were exposed to radiofrequency fields beginning on the 21st day of pregnancy. The indicators of physiological and behavioral development were observed and measured in the offspring rats: Y maze measured at 3-weeks postnatal, open field at 7-weeks postnatal, and the expression of N-methyl-D-aspartate receptors (NMDARs) measured by reverse transcription-PCR in the hippocampus at 9-weeks postnatal. The body weight of the 1800 MHz group and the 1800 MHz + WiFi group showed a downward trend. The eye opening time of newborn rats was much earlier in the WiFi group than in the control group. Compared to the control group, the overall path length of the 1800 MHz + WiFi group was shortened and the stationary time was delayed. The path length of the WiFi group was shortened and the average velocity was increased in the error arm. The 1800 MHz + WiFi group displayed an increased trend in path length, duration, entry times and stationary time in the central area. In both the 1800 MHz + WiFi and WiFi groups, NR2A and NR2B expression was down-regulated, while NR2D, NR3A and NR3B were up-regulated. Moreover, NR1 and NR2C in the WiFi group were also up-regulated. Prenatal exposure to 1800 MHz and WiFi radiofrequency may affect the behavioral and cognitive development of offspring rats, which may be associated with altered mRNA expression of NMDARs in the hippocampus.
Subject(s)
Behavior, Animal/radiation effects , Cognition/radiation effects , Prenatal Exposure Delayed Effects/physiopathology , Radio Waves , Animals , Female , Gene Expression Regulation/radiation effects , Hippocampus/metabolism , Maze Learning/radiation effects , Pregnancy , Prenatal Exposure Delayed Effects/genetics , Protein Subunits/genetics , Protein Subunits/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolismABSTRACT
OBJECTIVE: To identify the effects of NMDA receptor subunits NR2A and NR2B expression in rat's hippocampus after exposure to 1800 MHz radiofrequency radiation. METHODS: Four-week old female Wistar rats were randomly divided into four groups, with 12 animals for each. The subjects in two experimental groups had been continuously exposed to 1800 MHz microwave radiation (CW) with respective power density of 0.5 mW/cm(2) and 1.0 mW/cm(2) 12 hours each day for 21 days. Meanwhile, sham-controls were carried out. The brain tissue sections were performed by immunohistochemistry to demonstrate both expressions of NR2A, NR2B immune-activity in the hippocampal CA1, CA3 and DG by using computer-assisted image analysis system. RESULTS: In NR2A: the expression of 0.5 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA3 [(8.5 +/- 1.5) vs (11.1 +/- 1.8), P < 0.01] and had not been significantly changed in CA1 and DG. The expression of 1.0 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1 and CA3 [(7.9 +/- 1.6) vs (9.7 +/- 1.5); (8.4 +/- 1.7) vs (11.1 +/- 1.8), respective P < 0.05, P < 0.01] and had not been significantly changed in DG. In NR2B: the expression of 0.5 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1 and CA3 [(16.4 +/- 1.0) vs (17.8 +/- 1.6); (9.6 +/- 1.9) vs (11.2 +/- 2.1), respective P < 0.05]. The expression of 1.0 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1, CA3 and DG [(13.1 +/- 2.4) vs (17.8 +/- 1.6); (9.3 +/- 1.4) vs (11.2 +/- 2.1); (7.3 +/- 0.1) vs (8.5 +/- 1.0), respective P < 0.01, P < 0.05, P < 0.05]. CONCLUSION: There were findings of the effects on NMDA receptor subunits in different hippocampus sections after exposure to 1800 MHz radiofrequency radiation.
