期刊：
Journal of Hazardous Materials,2010年179(1-3):742-747 ISSN：0304-3894
通讯作者：
Xiao, Xiaohe
作者机构：
[Kong, Weijun; Liu, Wei; Xiao, Xiaohe; Li, Xing-Feng; Zhao, Yanling; Jin, Cheng; Zhang, Ping] 302 Mil Hosp China, China Mil Inst Chinese Mat Med, Beijing 100039, Peoples R China.;[Kong, Weijun; Li, Zulun] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu 611137, Peoples R China.;[Liu, Wei] Jiangxi Univ Tradit Chinese Med, Coll Pharm, Nanchang 330004, Peoples R China.;[Li, Xing-Feng] Hunan Univ Tradit Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Xiao, Xiaohe] 3;302 Mil Hosp China, China Mil Inst Chinese Mat Med, Beijing 100039, Peoples R China.
关键词：
Bile acid derivative;MANOVA;Microcalorimetry;PCA;S. aureus
摘要：
The effects of two bile acid derivatives, cholic acid (CA) and deoxycholic acid (DCA) on Staphylococcus aureus (S. aureus) growth were investigated and compared by microcalorimetry coupled with multiple analytical methods. The heat power (HP)-time curves of S. aureus growth affected by CA and DCA were studied by similarity analysis (SA), respectively. Then the quantitative thermo-kinetic parameters obtained from these curves were investigated by the multivariate analysis of variance (MANOVA) and principal component analysis (PCA). By analyzing the two main parameters, growth rate constant k(2) of the second exponential phase and the heat power P-2 of the second highest peak, together with the minimum inhibitory concentration (MIC) values of 10 mu g/mL for CA and 20 mu g/mL for DCA, it could be concluded that the antibacterial effect of CA was stronger than that of DCA. The existence of alpha-OH at C-7 position of steroid nucleus of bile acid derivatives enhanced the hydrophilicity of compound CA and its inhibitory effect on S. aureus. This study provides a useful method and idea to accurately evaluate the antibacterial effects of bile acid derivatives, which provides some references for screening out new antibacterial agents with high efficacy and low toxicity. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.
摘要：
The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)–dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and β-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants.
摘要：
Three new isopimarane diterpenoids, trogopteroids A-C (1-3), four new aromatic diterpenoids, trogopteroids D-G (4-7), and 12 known diterpenoids were isolated from the feces of Trogopterus xanthipes. Their structures were identified using spectroscopic methods. The relative configuration of 1 was confirmed by quantum calculations. Compound 1 represents the first example of a norisopimarane diterpenoid with an 8alpha,15alpha-olide ring. With the exception of compound 14, all diterpenoids were evaluated for cytotoxicity against seven human tumor cell lines.
摘要：
Angiogenesis in the infarct periphery can improve blood flow. Vascular endothelial growth factor (VEGF) has been considered a potential therapeutic target for stroke. Buyang Huanwu decoction (BYHWD) is a classic traditional formula in traditional Chinese medicine and is used to treat stroke; in addition, the promotion effects on VEGF protein expression have been confirmed. However, little is known about how BYHWD regulates angiogenesis, or about the effects of BYHWD on VEGF mRNA expression. For this reason, the present study measured microvessel density in rats with cerebral ischemia using immunohistochemistry. In addition, VEGF expression was measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay to determine the effects of BYHWD on angiogenesis and VEGF expression in rats with cerebral ischemia. Results demonstrated that microvessel density, as well as VEGF mRNA and protein expression, increased after 7 and 14 days of BYHWD treatment, which suggests that BYHWD promoted angiogenesis following cerebral ischemia and upregulated VEGF mRNA and protein expression in ischemic cerebral regions
通讯机构：
[Peng, Qing-Hua] H;Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha 410007, Hunan, Peoples R China.
关键词：
dry;eye;LACRIMAL;GLAND;extract;of;buddleja;OFFICINALIS;ANDROGEN;lacrimal gland;extract of buddleja officinalis;androgen
摘要：
AIM: To assess the effects of extract of Buddleja officinalis on tear secretion volume, tear film stability, expressions of TGF-beta 1, IL-1 beta, TNF-alpha in lacrimal gland of castrated rabbits with dry eye. METHODS: A total of 30 victory rabbits were divided averagely into normal group (A), model group (B), therapy group with low dose extract of Buddleja officinalis (C), therapy group with high dose extract of Buddleja officinalis (D) and therapy group with genistein (E). The dry eye model was established with orchiectomy on Group B, C, D, E. Group C, D, E were administered intragastrically with corresponding dose extract of Buddleja officinalis or genistein for 30 days. All rabbits were detected with SIT. TGF-beta 1, IL-1 beta, TNF-alpha were detected with immunohistochemistry and the ultrastructure of lacrimal gland was observed under transmission electron microscope. RESULTS: The SIT value of group C, D, E were respectively 13.167 +/- 4.957, 14.667 +/- 5.279, 8.667 +/- 0.516, obviously higher than that of group B 5.667 +/- 2.338 (P<0.01). The positive expression of IL-1 beta in acinar cell and glandular tube cell of group C, D were 0.470 +/- 0.048, 0.510 +/- 0.088, obviously lower than that of group B 0.770 +/- 0.118 (P <0.01). The positive expression of TNF-alpha of group C, D were 0.498 +/- 0.156, 0.435 +/- 0.069, obviously lower than that of group B 0.769 +/- 0.095 too (P <0.01). The positive expression of TGF-beta 1 of group C, D were 0.406 +/- 0.171, 0.497 +/- 0.147, obviously higher than that of group B 0.222 +/- 0.113(P<0.01). Any result of group C, D was positive compared with that of group E (P <0.05). Ultrastructure of the lacrimal gland of group C, D, E was well preserved, especially in D group it was remarkable. CONCLUSION: The extract of Buddleja officinalis can adjust lacrimal gland partial inflammation of dry eye.
关键词：
Traditional Chinese Medicine;Qiwei Baizhu Powder;Human Rotavirus;Intestinal mucosa epithelial cells;Th1/Th2
摘要：
Aim of this study: Qiwei Baizhu Powder (QWBZP) is a traditional herbal prescription that has been used traditionally for the treatment of infantile diarrhea, including the infantile diarrhea caused by Human Rotavirus (HRV). In this study, we investigated the pharmacological activity of QWBZP extract. Materials and methods: NIH suckling mice with HRV induced diarrhea were used. Density of CD3(+), CD4(+) and CD8(+) T cells, mRNA expression of IL-2, IFN-gamma, IL-4 and IL-10 in intestinal mucosa epithelial cells were assayed. Results: QWBZP extract promoted the expressions of mRNA of IL-2, IL-4, IL-10 and IFN-gamma in intestinal mucosa epithelial cells. Also, we found that the density of CD8(+) cells in intestinal mucosa epithelial cells was significantly lower in QWBZP group than in Model group, while the density of CD8(+) cells was significantly higher in QWBZP group than in Model group. Conclusion: These data suggest that QWBZP extract may exhibit antiviral effects through modulating the densities of T-cell subsets and the expressions of their cytokines in small intestinal mucosa epithelial cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
期刊：
LETTERS IN DRUG DESIGN & DISCOVERY,2010年7(6):415-420 ISSN：1570-1808
通讯作者：
Zhang, Huibin
作者机构：
[Zhou, Jinpei] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China.;[Gao, Hui; Qian, Hai; Zhu, Xiaoyun; Ni, Shuaijian; Zhang, Huibin; Huang, Wenlong] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Peoples R China.;[Zhang, Chuntao] Hunan Univ Tradit Chinese Med, Organ & Med Chem Teaching & Res Sect, Changsha 410208A, Peoples R China.;[Zhang, Huibin] China Pharmaceut Univ, Ctr Drug Discovery, 24 Tongjiaxiang, Nanjing 210009, Peoples R China.
通讯机构：
[Zhang, Huibin] C;China Pharmaceut Univ, Ctr Drug Discovery, 24 Tongjiaxiang, Nanjing 210009, Peoples R China.
摘要：
In order to complete the SAR and discover new potent and selective PCOs, some changes were made to the C-4 and C-2 substitutions of cromakalim. A series of 4 -amino acid substituted -2, 2-dialkylchromans structurally related to cromakalim were synthesized and evaluated, as ATP-sensitive potassium channel openers (8a-l). Preliminary biological tests suggested that these compounds exhibited potent to mild relaxation activity of the KCl-contracted rat aortic strips. Compounds 8b (IC50 =0.25μM), 8f (IC50 =6.44μM) and 8j (IC50 =8.65μM) exhibited commendable opening activity of potassium channels. In addition to anti-hypertension, these compounds can also be considered as lead candidates for the further development of myocardial antiischemic drugs.
摘要：
Atherosclerosis is characterized by a chronic inflammatory condition that involves numerous cellular and molecular inflammatory components. A wide array of inflammatory mediators, such as cytokines and proteins produced by macrophages and other cells, play a critical role in the development and progression of the disease. ATP-binding membrane cassette transporter A1 (ABCA1) is crucial for cellular cholesterol efflux and reverse cholesterol transport (RCT) and is also identified as an important target in antiatherosclerosis treatment. Evidence from several recent studies indicates that inflammation, along with other atherogenic-related mediators, plays distinct regulating roles in ABCA1 expression. Proatherogenic cytokines such as interferon (IFN)-γ and interleukin (IL)-1β have been shown to inhibit the expression of ABCA1, while antiatherogenic cytokines, including IL-10 and transforming growth factor (TGF)-β1, have been shown to promote the expression of ABCA1. Moreover, some cytokines such as tumor necrosis factor (TNF)-α seem to regulate ABCA1 expression in species-specific and dose-dependent manners. Inflammatory proteins such as C-reactive protein (CRP) and cyclooxygenase (COX)-2 are likely to inhibit ABCA1 expression during inflammation, and inflammation induced by lipopolysaccharide (LPS) was also found to block the expression of ABCA1. Interestingly, recent experiments revealed ABCA1 can function as an antiinflammatory receptor to suppress the expression of inflammatory factors, suggesting that ABCA1 may be the molecular basis for the interaction between inflammation and RCT. This review aims to summarize recent findings on the role of inflammatory cytokines, inflammatory proteins, inflammatory lipids, and the endotoxin-mediated inflammatory process in expression of ABCA1. Also covered is the current understanding of the function of ABCA1 in modulating the immune response and inflammation through its direct and indirect antiinflammatory mechanisms including lipid transport, high-density lipoprotein (HDL) formation and apoptosis.
摘要：
A series of bis(fluoroalkanesulfon)amides were synthesized in good yield from the reaction of fluoroalkanesulfonamides and fluoroalkylsulfonyl fluorides. Ionic liquids based on these amide anions and an imidazolium cation demonstrated high densities and a wide temperature range for the liquid state.
期刊：
Journal of Cardiovascular Pharmacology,2010年56(3):309-319 ISSN：0160-2446
通讯作者：
Tang, Chao-Ke
作者机构：
[Tan, Chun-Zhi; Tang, Chao-Ke; Liu, Xie-Hong; Yin, Kai; Tang, Ya-Ling; Mo, Zhong-Cheng; Jiang, Jin; Xiao, Ji; Cui, Li-Bao] Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Changsha, Hunan, Peoples R China.;[Liu, Xie-Hong] Changsha Med Univ, Changsha, Hunan, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Tang, Chao-Ke] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
ABCA1, D4-F, Cdc42/cAMP/PKA, atherosclerosis, reverse cholesterol transport
摘要：
Adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays a crucial role in apolipoprotein A-I (apoA-I) binding activity and promotes cellular cholesterol efflux. ApoA-I mimetic peptide D4-F has reported to have the similar ability as apoA-I. However, the detailed mechanisms of ABCA1 regulation by D4-F are not understood. In the present study, we investigated the effects of D4-F on ABCA1 expression and ABCA1-dependent cholesterol efflux and examined the role of Cdc42/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway on the regulation of ABCA1 by D4-F in THP-1 macrophage-derived foam cells. Results showed that D4-F stabilized ABCA1 protein and enhanced ABCA1-dependent cholesterol efflux but had no effect on ABCA1 messenger RNA expression. We also revealed that D4-F enhanced cAMP level and PKA activity and ABCA1 serine phosphorylation. Short interfering RNA of PKA led to reduction of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux compensated by D4-F. PKA-specific activation by PKA agonist enhanced the upregulation of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux by D4-F. However, ABCA1 expression did not change by treatment with PKA agonist or PKA-short interfering RNA. We found that secramine B of Cdc42 inhibitor reduced the cAMP level compensated by D4-F. These results provide evidence that D4-F enhances ABCA1 serine phosphorylation and ABCA1-dependent cholesterol efflux through Cdc42/cAMP/PKA pathway in THP-1 macrophage-derived foam cells.
作者：
He Qing-Zhi;Tuo Qin-Hui;Zeng Huai-Cai;Zhu Bing-Yang;Rang Wei-Qing;...
期刊：
生物化学与生物物理进展,2010年37(8):881-890 ISSN：1000-3282
通讯作者：
Tang Xiao-Qing
作者机构：
[Zhu Bing-Yang; Tuo Qin-Hui; Liao Duan-Fang; He Qing-Zhi] Univ S China, Prov Key Lab Pharmacoprotom, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Tang Xiao-Qing] Univ S China, Dept Physiol, Sch Med, Hengyang 421001, Peoples R China.;[Liao Duan-Fang] Hunan Univ Chinese Med, Dept Tradit Chinese Diagnot, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Rang Wei-Qing; Zeng Huai-Cai] Univ S China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
通讯机构：
[Tang Xiao-Qing] U;Univ S China, Dept Physiol, Sch Med, Hengyang 421001, Peoples R China.
关键词：
Daxx;Ox-LDL;macrophage;apoptosis;caveolin-1
摘要：
To explore whether Daxx mediates oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and apopotosis in macrophage and the underlying molecular mechanisms, intracellular lipid droplets and lipid levels were assayed by oil red O staining and high performance liquid chromatography (HPLC), respectively, the apoptotic effect of RAW264.7 cells induced by Ox-LDL was analyzed by flow cytometric analysis and acridine orange/ethidium bromide (AO/EB) staining, the mRNA expressions of Daxx was quantified by Real time RT- PCR, the protein expression of caveolin-1 was detected by Western-blotting, Daxx-specific small interfering RNA(Daxx siRNA) was transfected to RAW264.7 cell by lipofectamin. Ox-LDL up-regulated the expression of Daxx mRNA, increased the accumulation of intercellular cholesterol in RAW264.7 macrophages, and induced the apoptosis of RAW264.7 macrophages. However, Ox-LDL-induced intercellular cholesterol accumulation and apoptosis in RAW264.7 cells was prevented by Daxx siRNA. Ox-LDL also induced caveolin-1 expression and this effect is significantly suppressed by Daxx siRNA. It can be concluded that Daxx mediates Ox-LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating caveolin-1 expression. These findings provide an important demonstration that Daxx might be associated with the development of atherosclerosis.
摘要：
Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.
