Experimental biology and medicine
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Exp. Biol. Med. (Maywood) · Mar 2014
Transplantation of mesenchymal stem cells carrying the human receptor activity-modifying protein 1 gene improves cardiac function and inhibits neointimal proliferation in the carotid angioplasty and myocardial infarction rabbit model.
Although transplanting mesenchymal stem cells (MSCs) can improve cardiac function and contribute to endothelial recovery in a damaged artery, natural MSCs may induce neointimal hyperplasia by directly or indirectly acting on vascular smooth muscle cells (VSMCs). Receptor activity-modifying protein 1 (RAMP1) is the component and the determinant of ligand specificity of calcitonin gene-related peptide (CGRP). It is recently reported that CGRP and its receptor involve the proliferation and the apoptosis in vivo and in vitro, and the exogenous RAMP1 enhances the antiproliferation effect of CGRP in VSMCs. ⋯ Additionally, arterial hematoxylin-eosin staining revealed that the area of the neointima and the area ratio of intima/media were significantly decreased in the EGFP-hRAMP1-MSCs group. An immunohistological study showed that the expression of α-smooth muscle antigen and proliferating cell nuclear antigen in the neointima cells of the carotid artery of the EGFP-hRAMP1-MSCs group was approximately 50% lower than that of the EGFP-MSCs group, suggesting that hRAMP1 expression may inhibit VSMCs proliferation within the neointima. Therefore, compared with natural MSCs, EGFP-hRAMP1-engineered MSCs improved infarcted heart function and endothelial recovery from artery injury more efficiently, which will provide valuable information for the development of MSC-based therapy.
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Exp. Biol. Med. (Maywood) · Mar 2014
Sparstolonin B attenuates hypoxia-reoxygenation-induced cardiomyocyte inflammation.
Myocardial ischemia-reperfusion (MIR) injury is characterized by a rapid increase in cytokines and chemokines and an infiltration of inflammatory cells. Toll-like receptors (TLRs) 2 and 4 mediate these inflammatory responses. Herein we investigated the ability of Sparstolonin B (SsnB), a new selective TLR2/4 antagonist, to inhibit the TLR2/4-mediated inflammatory responses during cardiomyocyte hypoxia-reoxygenation injury as well as the responsible mechanisms. ⋯ Moreover, transwell migration assays revealed that the migration of mouse macrophages to hypoxia-reoxygenation injured cardiomyocytes was significantly reduced by SsnB (P < 0.05). In conclusion, our data indicate that the new selective TLR2 and TLR4 antagonist, SsnB, can substantially attenuate hypoxia-reoxygenation-induced inflammation of cardiomyocytes via inhibiting ERK1/2 and JNK signaling pathways. Accordingly, SsnB has the potential to serve as a therapeutic agent for the prevention of MIR injury.
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Exp. Biol. Med. (Maywood) · Mar 2014
Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-κB and signal transducer and activator of transcription 3 pathways.
Increasing evidence has demonstrated that mesenchymal stem cells (MSCs)-mediated regulation of macrophages is critical for inflammation response and tissue injury repair. However, the underlying mechanism is not well understood. In this study, we investigated the effect of mouse bone marrow-derived MSCs on macrophages under normal and inflammatory conditions. ⋯ MSC-CM treatment activated signal transducer and activator of transcription 3 (STAT3) but inhibited nuclear factor-κB (NF-κB) pathways in LPS-stimulated RAW264.7 cells. Moreover, STAT3 inhibitor S3I-201 antagonized the induction of IL-10, arginase 1, and CD206 by MSC-CM in RAW264.7 cells. Conclusively, our findings suggest that mouse MSCs induce macrophage M2 activation through the NF-κB and STAT3 pathways.
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Exp. Biol. Med. (Maywood) · Oct 2013
Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.
The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. ⋯ HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity.
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Exp. Biol. Med. (Maywood) · Oct 2013
Editorial Biography Historical ArticleBurt Sobel: a farewell to a friend, mentor, and dedicative leader of SEBM and EBM.