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Shanghai, China

Lee E.-M.,Kyungpook National University | Kim A.-Y.,Kyungpook National University | Lee E.-J.,Kyungpook National University | Park J.-K.,Kyungpook National University | And 5 more authors.
Cell Transplantation | Year: 2015

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by mutations in the dystrophin gene. Adipose-derived stem cells (ASCs) are an attractive source of cells for stem cell therapy. Losartan has been reported to improve ASC transplantation in injured mouse muscles. In the present study, we investigated whether the combined treatment of losartan and ASCs in the injured muscles of mdx mice improves regeneration. The combined treatment of ASCs and losartan remarkably improved muscle regeneration and induced muscle hypertrophy. In addition, ASCs and losartan treatment downregulated transforming growth factor-b and inhibited muscle fibrosis. We observed cells coexpressing green fluorescent protein (GFP) and dystrophin in the muscle samples of mice transplanted with GFP-positive ASCs. In the coculture in vitro experiment, we also observed that the GFP ASCs differentiated into dystrophin-expressing myotubes. The present study shows that the combination of transplanted ASCs and treatment with losartan ameliorated muscle fibrosis and improved muscle regeneration in injured mdx mice. Thus, we suggest that combined treatment with losartan and ASCs could help to improve muscle regeneration in the muscles of injured patients, including DMD patients. © 2015 Cognizant Comm. Corp.

Duan X.-H.,Fudan University | Xu C.-Q.,Fudan University | Huang J.-H.,Fudan University | Zhou W.-J.,Animal Center | Sun B.,Fudan University
Pharmaceutical Biology | Year: 2013

Context: Homocysteine-induced endothelial cellular senescence may contribute to some cardiovascular disorders. Icariin (ICA), a flavonoid derived from Epimedium sagittatum Maxim. (Berberidaceae), has been reported to increase production of nitric oxide (NO) and reduce reactive oxygen species (ROS) levels in human umbilical vein endothelial cells (HUVECs). Objective: To observe the effects of ICA on homocysteine-induced senescence and the underlying mechanisms in HUVECs. Materials and methods: ICA at concentrations of 0.1, 1, and 5 μM was added into homocysteine pretreated HUVECs. Cellular senescence was assayed by senescence-associated β-galactosidase (SA-β-gal) staining and cumulative population doublings (CPDs). ICA (5 μM) was given orally to homocysteine-treated rats, luminal surface of aortic artery of rats was subjected to SA-β-gal staining. Protein expression was measured by western blot. Results: Homocysteine significantly increased cellular senescence both in vitro and in vivo. After treatment by ICA, the percentage of SA-β-gal-positive cells, and the ROS level significantly decreased. The CPDs were partially restored. ICA also significantly reduced the mean density of SA-β-gal staining in vivo. We found that NO production and phosphorylation of AKT, ERK, and endothelial NO synthase (eNOS) were elevated by ICA in HUVECs. Furthermore, the increased level of NO production was fully abolished by the phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin. The mitogen-activated protein kinase (MEK) inhibitor PD98059, which can inhibit phosphorylation of ERK, did not show this ability. Discussion and conclusion: Our results indicate that ICA delays homocyteine-induced endothelial senescence in vitro and in vivo. Activation of PI3K/Akt-eNOS-dependent signaling pathway may be responsible for this efficacy of ICA. © 2013 Informa Healthcare USA, Inc.

Sun Z.,Chinese Institute of Materia Medica | Sun Z.,Chengdu University of Traditional Chinese Medicine | Zhao Y.,Chinese Institute of Materia Medica | Liu T.,Chinese Institute of Materia Medica | And 6 more authors.
Thermochimica Acta | Year: 2013

The fingerprints of Aconitum L. plants, Radix Aconiti (RA), Radix Aconiti Singularis (RAS), Radix Aconiti Kusnezoffii (RAK), Radix Aconiti Lateralis Preparata (RALP) and Radix Aconiti Brachypodi (RAB), were established by ultra-high performance liquid chromatography (UPLC) and the metabolism of Aconitum L. plants on Escherichia coli (E. coli) were studied by microcalorimetry. The spectrum-effect relationships between UPLC fingerprints and bacterial metabolism were investigated using canonical correlation analysis (CCA). Because of their inherent differences of chemical compositions, the main actives of bacterial metabolism were different among five Aconitum L. plants. The potency bioactivity sequence of the tested five Aconitum L. products on E. coli was obtained that were RAB > RALP > RAK > RAS > RA. This work establishes a universal model of the combination of UPLC and microcalorimetry to study the spectrum-effect relationships of Aconitum L. plants, which offers some references for detecting principle components of traditional Chinese medicine on bioactivity. © 2013 Elsevier B.V.

Jia L.,Chinese Institute of Materia Medica | Jia L.,Chengdu University of Traditional Chinese Medicine | Zhao Y.,Chinese Institute of Materia Medica | Xing X.,Chinese Institute of Materia Medica | And 9 more authors.
Zhongguo Zhongyao Zazhi | Year: 2010

Objective: To investigate the objectivity and authenticity of the difference of the Cold and Hot nature between Mahuang decoction and Maxingshigan decoction based on the cold/hot plate differentiating assay. Method: The measuring time and dosage of Mahuang decoction and Maxingshigan decoction were investigated before the compliance experiment Meanwhile, the activities of adenosine triphosphatase were detected in order to probe into the mechanism of their action. Result: It was found that the drug dose should be 10 times amount to human dose(0.80 g·kg-1 of Mahuang decoction and 2.26 g·kg-1 of Maxing Shigan decoction) and the measuring time should be from 30 min to 60 min after administering. Compared with the control group, the remaining ratio of the mice treated with Mahuang decoction on the hot pad significantly decreased (P < 0.01). Compared with Mahuang decoction, the remaining ratio of the mice treated with Maxingshigan decoction on the hot pad significantly increased (P < 0.05). Compared with the control group, the Na+-K+-ATPase activity of liver tissue of the mice treated by Mahuang decoction significantly increased (P < 0.05), while the activity of Na+-K+-ATPase and Mg2+-Ca 2+-ATPase of liver tissue of the mice treated by Maxingshigan decoction reduced significantly (P < 0.05). Conclusion: This study showed that the differences of Cold and Hot nature of Mahuang decoction and Maxingshigan decoction were objectively existent from animal ethology, which was consistent with the traditional theroy of Chinese medicine. And the changes of ATPase activity of liver tissue might be the mechanism of drug action.

Yu K.,University of Sichuan | Yang J.,Hubei University of Medicine | Jiang Y.,Animal Center | Song R.,Chengdu BioSciTec Biotechnology Co. | Lu Q.,University of Sichuan
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: Previous studies have investigated the association between the vitamin D receptor (VDR) BsmI polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. Materials and Methods: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before November 2013. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) for VDR BsmI polymorphism and CRC were calculated in a fixed effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results: This meta-analysis included 14 case-control studies, which included 10,822 CRC cases and 11,779 controls. Overall, the variant genotype (BB) of the BsmI was associated with a lower CRC risk when compared with the wild-type bb homozygote (OR=0.66, 95%CI: 0.49-0.88). Similarly, a decreased CRC risk was also found in the dominant and recessive models. When stratifying for ethnicity, source of controls, and study sample size, associations were observed among Caucasians, population-based studies and studies with large study sample size (>1000 subjects). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. Conclusions: This updated meta-analysis suggests that the VDR BsmI polymorphism may be associated with a moderate protective effect against CRC.

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