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ABSTRACT: To analyse mutational points of FOXL2 gene in 5 Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and to predict structural changes of the mutational FOXL2 protein. So as to improve the diagnostic accuracy of this kind of disease.
Five milliliter samples of peripheral venous blood were collected from the patients.Genomic DNA was extracted from each sample. Three pairs of PCR primers which were used to amplify the exon of FOXL2 gene were designed. After PCR process, the products were analyzed by direct genomic sequencing.
The same c. 672_701dup30 (p. Ala224_Ala234dup) heterozygous mutation was detected from two different families. c.655C > T (p.Q219X), c.370 A > G (p. K124E) and c.858_874dup17 (p.P292fs) heterozygous mutations were detected from the other 3 sporadic cases.
Two novel heterozygous mutations in FOXL2 (c.370A > G, c.858_874dup17) which were detected from Chinese BPES patients expand the worldwide mutational spectrum of FOXL2 gene. Being detected from two different families we confirm c. 672_701dup30 heterozygous mutation as a mutation hotspot in China.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 11/2011; 47(11):1007-11.
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Li Li, Hui-Na Zhang,
Hou-Zao Chen,
Peng Gao,
Li-Hua Zhu,
Hong-Liang Li,
Xiang Lv,
Qing-Jun Zhang,
Ran Zhang,
Zhao Wang,
Zhi-Gang She,
Yu-Sheng Wei,
Guan-Hua Du,
De-Pei Liu,
Chih-Chuan Liang
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ABSTRACT: Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events involved in the pathophysiology of vascular diseases. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), has been reported to have the function of antiatherosclerosis, but its role in neointima formation remains unknown.
The present study was designed to investigate the role of SIRT1 in the regulation of neointima formation and to elucidate the underlying mechanisms.
A decrease in SIRT1 expression was observed following carotid artery ligation. smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) mice were generated. SIRT1 overexpression substantially inhibited neointima formation after carotid artery ligation or carotid artery wire injury. In the intima of injured carotid arteries, VSMC proliferation (proliferating cell nuclear antigen (PCNA)-positive cells) was significantly reduced. SIRT1 overexpression markedly inhibited VSMC proliferation and migration and induced cell cycle arrest at G1/S transition in vitro. Accordingly, SIRT1 overexpression decreased the induction of cyclin D1 and matrix metalloproteinase-9 (MMP-9) expression by treatment with serum and TNF-α, respectively, whereas RNAi knockdown of SIRT1 resulted in the opposite effect. Decreased cyclin D1 and MMP-9 expression/activity were also observed in injured carotid arteries from SMC-SIRT1 Tg mice. Furthermore, 2 targets of SIRT1, c-Fos and c-Jun, were involved in the downregulation of cyclin D1 and MMP-9 expression.
Our findings demonstrate the inhibitory effect of SIRT1 on the VSMC proliferation and migration that underlie neointima formation and implicate SIRT1 as a potential target for intervention in vascular diseases.
Circulation Research 05/2011; 108(10):1180-9. · 9.49 Impact Factor
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ABSTRACT: The proinflammatory cytokine TNF-alpha plays an important role in stimulating inflammatory responses of vascular smooth muscle cells (VSMCs). The anti-inflammatory function of Sirtuin 1 (SIRT1), a NAD-dependent class III histone/protein deacetylase, has been well documented, but how SIRT1 is regulated under inflammatory conditions is largely unknown. In the present research, we showed that levels of SIRT1 mRNA and protein expression increased in TNF-alpha-treated VSMCs. Overexpression of the p65/RelA subunit of NF-kappaB, a TNF-alpha-activated inflammatory transcription factor, in A7r5 cells, upregulated SIRT1 mRNA and protein expression as well as SIRT1 promoter activity, while knockdown of endogenous p65/RelA expression by RNAi not only led to a decrease in SIRT1's basal protein expression and promoter activity, but almost abolished the TNF-alpha-induced elevation of SIRT1 protein expression and SIRT1 promoter activity. Furthermore, using promoter deletion analysis and chromatin immunoprecipitation assays, we found that p65/RelA bound to the SIRT1 promoter at a consensus NF-kappaB binding site. Our study indicates that p65/RelA mediates the TNF-alpha-induced elevated expression of SIRT1 in VSMCs, shedding new light on the regulation of SIRT1 under inflammatory conditions.
Biochemical and Biophysical Research Communications 07/2010; 397(3):569-75. · 2.48 Impact Factor
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ABSTRACT: Taking wheat cultivars drought-resistant Luohan-6 and drought-sensitive Zhoumai-18 as test objects, their seedlings ammonium assimilation enzyme activities and related parameters were determined under osmotic stress. The plant biomass had an obvious decrease under osmotic stress, with a larger decrement for Zhoumai-18 than Luohan-6. Osmotic stress increased the plant ammonium content, especially for Zhoumai-18. The glutamine synthetase (GS) activity varied with wheat cultivars. For Luohan-6, the GS activity increased significantly under low osmotic stress but decreased under high osmotic stress; while for Zhoumai-18, the GS activity decreased with increasing osmotic stress. The NADH-dependent glutamate dehydrogenase (NADH-GDH) increased with increasing osmotic stress, with a marked increment under low osmotic stress for Zhoumai-18, and under high osmotic stress for Luohan-6. The NAD(+)-dependent glutamate dehydrogenase (NAD(+)-GDH) and NADP-dependent isocitrate dehydrogenase (NADP-ICDH) activities also increased with increasing osmotic stress, with a greater increment of NAD(+)-GDH activity for Zhoumai-18, and of NADP-ICDH activity for Luohan-6. It was suggested that the increased drought resistance of wheat plants could be related to the increased ammonium assimilation resulted from the enhanced GS and NADH-GDH activities under low and high osmotic stress, respectively.
Ying yong sheng tai xue bao = The journal of applied ecology / Zhongguo sheng tai xue xue hui, Zhongguo ke xue yuan Shenyang ying yong sheng tai yan jiu suo zhu ban 10/2009; 20(10):2406-10.
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ABSTRACT: To elucidate the effect and the mechanisms of curcumin on the expression of the human homeobox gene NKX3.1 in the prostate cancer cell LNCaP.
The expression change of NKX3.1 in cells incubated with varying concentrations of curcumin was observed by Western blotting and RT-PCR. A dual luciferase reporter assay was used to test the effect of curcumin on the activity of the NKX3.1 1040 bp promoter. Curcumin-treated cells disposed to a designated amount of androgen analog R1881 and the androgen receptor (AR) antagonist flutamide, then the expression of NKX3.1 or the activity of the NKX3.1 promoter were investigated by Western blotting or reporter gene assay, respectively. Finally, Western blotting and electrophoretic mobility shift assay were performed to demonstrate the effect of curcumin on the expression of AR and its binding activity to the androgen response element (ARE).
Curcumin downregulated the expression of NKX3.1 and the activity of the NKX3.1 1040 bp promoter in LNCaP cells. R1881 increased the expression of NKX3.1, and the AR antagonist flutamide decreased the expression of NKX3.1 in LNCaP cells, while curcumin could inhibit androgen-AR mediated induction of NKX3.1 expression. Curcumin decreased the expression of AR and the binding activity to ARE directly.
Curcumin could downregulate NKX3.1 expression in LNCaP cells. It could also inhibit the androgen-AR mediated induction of NKX3.1 expression by downregulating AR expression and blocking its DNA binding activity.
Acta Pharmacologica Sinica 04/2007; 28(3):423-30. · 1.95 Impact Factor
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ABSTRACT: Aim: To elucidate the effect and the mechanisms of curcumin on the expression of the human homeobox gene NKX3.1 in the prostate cancer cell LNCaP. Methods: The expression change of NKX3.1 in cells incubated with varying concentrations of curcumin was observed by Western blotting and RT-PCR. A dual luciferase reporter assay was used to test the effect of curcumin on the activity of the NKX3.1 1040 bp promoter. Curcumin-treated cells disposed to a designated amount of androgen analog R1881 and the androgen receptor (AR) antagonist flutamide, then the expression of NKX3.1 or the activity of the NKX3.1 promoter were investigated by Western blotting or reporter gene assay, respectively. Finally, Western blotting and electrophoretic mobility shift assay were performed to demonstrate the effect of curcumin on the expression of AR and its binding activity to the androgen response element (ARE). Results: Curcumin downregulated the expression of NKX3.1 and the activity of the NKX3.1 1040 bp promoter in LNCaP cells. R1 881 increased the expression of NKX3.1, and the AR antagonist flutamide decreased the expression of NKX3.1 in LNCaP cells, while curcumin could inhibit androgen-AR mediated induction of NKX3.1 expression. Curcumin decreased the expression of AR and the binding activity to ARE directly. Conclusion: Curcumin could downregulate NKX3.1 expression in LNCaP cells. It could also inhibit the androgen-AR mediated induction of NKX3.1 expression by downregulating AR expression and blocking its DNA binding activity.
Acta Pharmacologica Sinica 02/2007; 28(3):423 - 430. · 1.95 Impact Factor
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ABSTRACT: To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-(2-(4-octylphenyl) ethyl) propane-1,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage.
Liver tissue or hepatocyte injury was monitored biochemically by measuring alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) activity. Hematoxylin and eosin (HE) staining was used for histopathological examination. To evaluate the role of IFN-gamma and IL-4 in the liver injury, serum levels of IFN-gamma and IL-4 were determined using commercially available ELISA kit at 12 h after Con A challenge. We also determined FTY 720-induced spleen cell apoptosis by flow cytometry analysis or spleen cell proliferation test.
Different doses of FTY 720 treatment dramatically reduced circulating markers of hepatocyte injury in two kinds of immunological liver injury models. FTY 720 dramatically reduced the elevated serum IFN-gamma and IL-4 levels after Con A injection. Effect of spleen cell supernatants treated with Con A or FTY 720 on hepatocytes showed that ALT activities in cultured hepatocyte supernatants in Con A treatment group increased markedly and FTY 720 could reduce this elevated ALT activities in FTY 720 treatment group. FTY 720 dose-dependently increased the percentage of apoptotic cells in T cells and inhibited splenocyte proliferation induced by Con A.
Pretreatment with FTY 720 was shown to produce protective effect on the immune liver injury in mice. The possible mechanism of FTY 720 on Con A-induced liver damage is that it could inhibit lymphocyte proliferation and induce lymphocyte apoptosis, resulting in the reduction of IL-4 or IFN-gamma release, and subsequently protecting liver from being damaged by Con A.
World Journal of Gastroenterology 02/2005; 11(4):573-6. · 2.47 Impact Factor
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ABSTRACT: Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed anti-tumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.
Acta Pharmacologica Sinica 12/2004; 25(11):1387-95. · 1.95 Impact Factor
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ABSTRACT: To investigate the hypoglycemic effect of Ganoderma lucidum polysaccharides (Gl-PS) in the normal fasted mice and its possible mechanism.
Normal fasted mice were given a single dose of Gl-PS 25, 50, and 100 mg/kg by i.p. and the serum glucose was measured at 0, 3, and 6 h after administration. Gl-PS 100 mg/kg were also given by i.p. and the serum glucose and insulin levels were measured at 0 min, 30 min, 1 h, 3 h, 6 h, and 12 h. Pancreatic islets were isolated and incubated with glucose 5.6 mmol/L and different concentration of Gl-PS, the insulin content of islets and insulin release were examined. The islets fluorescent intensity of [Ca2+]i was also studied with a confocal microscope. Verapamil and egtazic acid were used to testify whether the insulin-releasing effect of Gl-PS was mediated by its ability to raise the Ca2+ influx.
Gl-PS dose-dependently lowered the serum glucose levels at 3 h and 6 h after administration. Gl-PS 100 mg/kg raised the circulating insulin levels at 1 h after administration. In vitro, Gl-PS had no effect on islets insulin content, but it stimulated the insulin release after incubation with glucose 5.6 mmol/L. Confocal microscope showed that Gl-PS 100 mg/L had the capacity to raise the [Ca2+]i. The insulin-releasing effect of Gl-PS was inhibited by verapamil/egtazic acid.
Gl-PS possesses the hypoglycemic effect on normal mice; one mechanism is through its insulin-releasing activity due to a facilitation of Ca2+ inflow to the pancreatic beta cells.
Acta Pharmacologica Sinica 03/2004; 25(2):191-5. · 1.95 Impact Factor
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ABSTRACT: This study was undertaken to investigate the protective effect against alloxan-induced pancreatic islets damage by Ganoderma lucidum Polysaccharides (Gl-PS) isolated from the fruiting body of Ganoderma lucidum (Leyss. ex Fr.) Karst. In vitro, alloxan caused dose-dependent toxicity on the isolated pancreatic islets. Pre-treatment of islets with Gl-PS for 12 h and 24 h significantly reversed alloxan-induced islets viability loss. Gl-PS was also found to inhibit the free radicals production induced by alloxan in the isolated pancreatic islets using confocal microscopy. Gl-PS dose-dependently increased serum insulin and reduced serum glucose levels when pretreated intragastrically for 10 days in alloxan-induced diabetic mice. It was found that the pancreas homogenates had higher lipid peroxidation products in alloxan-treated mice than in the Gl-PS-treated animals. Aldehyde fuchsin staining revealed that alloxan caused nearly all the beta cells disappearing from the pancreatic islets, while Gl-PS partly protected the beta cells from necrosis. Alloxan (60 mg/kg) induced NF-kappa B activation in the pancreas at 30 min after injection, pretreatment with Gl-PS inhibited alloxan-induced activation of NF-kappa B. These results suggest that Gl-PS was useful in protecting against alloxan-induced pancreatic islets damage in vitro and in vivo; one of the mechanisms is through its scavenging ability to protect the pancreatic islets from free radicals-damage induced by alloxan.
Life Sciences 10/2003; 73(18):2307-19. · 2.53 Impact Factor
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Jun Wu,
Ming-Liang Cheng,
Guo-Hao Zhang,
Rong-Wei Zhai,
Neng-Hui Huang,
Cheng-Xiu Li,
Tian-Yong Luo,
Shuang Lu,
Zhi-Qin Yu,
Yu-Mei Yao,
Ying-Ying Zhang,
Lan-Zhen Ren,
Lan Ye,
Ling Li, Hui-Na Zhang
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ABSTRACT: To explore the relevance of Maotai liquor and liver diseases.
Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor. Experimental histopathological study was conducted as follows: sixty male Wistar rats were divided into 3 groups randomly and fed with Maotai liquor, ordinary white wine, and physiological saline respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches, then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to measure the liver indexes, GSH, and MDA. Histopathological examinations were also performed. Another eighty mice were randomly divided into 4 groups and fed with Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and physiological saline. The animals were sacrificed after 4 weeks and serum ALT was determined. Then the livers were harvested and liver indexes and MDA were measured.
The incidence rate of hepatic symptoms, splenomegaly, liver function impairment, reversal of Albumin/Globulin and increased diameter of portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively. There was no significant difference between the Maotai group and the non-alcoholic control group P>0.05 . Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was no obvious hepatic fibrosis or cirrhosis. A comparison was made between the Maotai liquor group and the ordinary white wine group. It was found that hepatic MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had an obvious decrease in the Maotai liquor group (P<0.05); hepatic GSH were 0.12 mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/-0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai liquor group (P<0.05). After the 20 rats had been fed with ordinary white wine for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of hepatocytes, and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed; after 12 weeks, the fibrous tissue proliferation continued and early cirrhosis appeared. Compared with the ordinary white wine group, fatty infiltration was observed in the 8-week and 12-week groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor group (P<0.05).
Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.
World Journal of Gastroenterology 06/2002; 8(3):571-4. · 2.47 Impact Factor
