摘要:
Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL.kg(-1)) at a dose of 200 mg.kg(-1) twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. A tier Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, alpha-SM A, transforming growth factor (TGF)-beta 1, p-Smad 2/3, Smad 2/3, Smad4, NF-kappa B-p65, p-NF-kappa B-p65, IL-1 beta, IL-6, AKT, and p-AKT were determined using Western blotting. Results: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and alpha-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-beta 1, Smad4, p-Smad 2/3, Smad 2/3,, p-NF-kappa B-p65/NF-KB-p65, IL-1 beta, IL-6, and p-AKT/AKT significantly decreased after the treatment. Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-beta 1/Smad, NF-kappa B, and AKT signaling pathways and the reduction of extracellular matrix deposition.
期刊:
Evidence-Based Complementary and Alternative Medicine,2018年2018:5290514 ISSN:1741-427X
通讯作者:
Yan, Miao;Fan, Xin-Rong
作者机构:
[Yan, Miao; Zhang, Ling] Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;[Zhang, Ling; Fan, Xin-Rong] China Acad Chinese Med Sci, Inst BasicTheory Chinese Med, Beijing 100700, Peoples R China.;[He, Qing-Hu; Nie, Yu-Song; Zhang, Ling; Fan, Xin-Rong; Xie, Hui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhang, Min] Shanxi Univ Chinese Med, Clin Med Coll 1, Xianyang 712000, Shanxi, Peoples R China.
通讯机构:
[Yan, Miao; Fan, Xin-Rong] C;[Fan, Xin-Rong] H;Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;China Acad Chinese Med Sci, Inst BasicTheory Chinese Med, Beijing 100700, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
摘要:
Isoprenoids and prenylated proteins regulate a variety of cellular functions, including neurite growth and synaptic plasticity. Importantly, they are implicated in the pathogenesis of several diseases, including Alzheimer's disease (AD). Recently, we have shown that two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), have differential effects in a mouse model of AD. Haplodeficiency of either FT or GGT attenuates amyloid-beta deposition and neuroinflammation but only reduction in FT rescues cognitive function. The current study aimed to elucidate the potential mechanisms that may account for the lack of cognitive benefit in GGT-haplodeficient mice, despite attenuated neuropathology. The results showed that the magnitude of long-term potentiation (LTP) was markedly suppressed in hippocampal slices from GGT-haplodeficient mice. Consistent with the synaptic dysfunction, there was a significant decrease in cortical spine density and cognitive function in GGT-haplodeficient mice. To further study the neuron-specific effects of GGT deficiency, we generated conditional forebrain neuron-specific GGT-knockout (GGT(f/f)Cre+) mice using a Cre/LoxP system under the CAMKII alpha promoter. We found that both the magnitude of hippocampal LTP and the dendritic spine density of cortical neurons were decreased in GGT(f/f)Cre+ mice compared with GGT(f/f)Cre- mice. Immunoblot analyses of cerebral lysate showed a significant reduction in cell membrane-associated (geranylgeranylated) Rac1 and RhoA but not (farnesylated) H-Ras, in GGT(f/f)Cre+ mice, suggesting that insufficient geranylgeranylation of the Rho family of small GTPases may underlie the detrimental effects of GGT deficiency. These findings reinforce the critical role of GGT in maintaining spine structure and synaptic/cognitive function in development and in the mature brain. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
作者机构:
[Peng, Tingting; Tang, Qianli; Liao, Xianjiu] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, 98 Chengxiang Rd, Baise 533000, Guangxi, Peoples R China.;[Li, Liqing; Ge, Bin; Tang, Qianli; Liao, Xianjiu] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Pan, Jianbin] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing, Jiangsu, Peoples R China.
通讯机构:
[Tang, Qianli] Y;Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, 98 Chengxiang Rd, Baise 533000, Guangxi, Peoples R China.
关键词:
carbon nitride nanosheet;catalytic hairpin assembly;intracellular signal amplification;microRNA;nanoprobe
摘要:
In this study, an ultrasensitive fluorescence turn-on assay for in situ sensing of intracellular microRNA (miRNA) was developed utilizing a carbon nitride nanosheet (CNNS) and a catalytic hairpin assembly (CHA). The CHA showed favourable signal amplification for low-level biomarkers, and CNNS was an excellent candidate as a fluorescence quencher and gene vector. Moreover, the hairpin DNA of CHA could be adsorbed onto the surface of CNNS. An enzyme-free fluorescence biosensor for ultrasensitive sensing of intracellular miRNA in cells based on CHA and CNNS was designed. When faced with target miRNA, the fluorescence was recovered due to the miRNA, which could trigger cycling of CHA circuits, leading to the production of a marked enhanced fluorescence signal. Compared with traditional methods, the proposed method is convenient, with low cytotoxicity, and high specificity and ultrasensitivity. It has promising potential for detection low-level biomarkers.
作者机构:
[向彪; 蒋司晨; 欧阳林旗; 魏凤; 邓桂明] The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[肖小芹] The College of Integrated Traditional Chinese and Western medicine of Hunan University of Chinese Medicine, Changsha, 410208, China;[朱青; 刘景诗] Department of Pharmacy, The Affiliate Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
通讯机构:
[Ouyang, L.-Q.] T;The First Hospital of Hunan University of Chinese Medicine, Changsha, China