排序方式: 共有38条查询结果,搜索用时 15 毫秒
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Deepak Poudyal Xiangli Cui Phuong Mai Le Anne B. Hofseth Anthony Windust Mitzi Nagarkatti Prakash S. Nagarkatti Aaron J. Schetter Curtis C. Harris Lorne J. Hofseth 《PloS one》2013,8(10)
Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG) has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR) expression has been observed in several disease conditions including colon cancer. Using global miR expression profiling, we observed increased miR-29b in colon cancer cells following exposure to HAG. Since miR-29b plays a role in regulating the migration of cancer cells, we hypothesized that HAG induces miR-29b expression to target matrix metalloproteinase-2 (MMP-2) thereby suppressing the migration of colon cancer cells. Results are consistent with this hypothesis. Our study supports the understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG suppresses the migration of colon cancer cells. 相似文献
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Xiangli Cui Erin E. Witalison Alena P. Chumanevich Alexander A. Chumanevich Deepak Poudyal Venkataraman Subramanian Aaron J. Schetter Curtis C. Harris Paul R. Thompson Lorne J. Hofseth 《PloS one》2013,8(1)
Protein Arginine Deiminases (PADs) catalyze the post-translational conversion of peptidyl-Arginine to peptidyl-Citrulline in a calcium-dependent, irreversible reaction. Evidence is emerging that PADs play a role in carcinogenesis. To determine the cancer-associated functional implications of PADs, we designed a small molecule PAD inhibitor (called Chor-amidine or Cl-amidine), and tested the impact of this drug on the cell cycle. Data derived from experiments in colon cancer cells indicate that Cl-amidine causes a G1 arrest, and that this was p53-dependent. In a separate set of experiments, we found that Cl-amidine caused a significant increase in microRNA-16 (miRNA-16), and that this increase was also p53-dependent. Because miRNA-16 is a putative tumor suppressor miRNA, and others have found that miRNA-16 suppresses proliferation, we hypothesized that the p53-dependent G1 arrest associated with PAD inhibition was, in turn, dependent on miRNA-16 expression. Results are consistent with this hypothesis. As well, we found the G1 arrest is at least in part due to the ability of Cl-amidine-mediated expression of miRNA-16 to suppress its'' G1-associated targets: cyclins D1, D2, D3, E1, and cdk6. Our study sheds light into the mechanisms by which PAD inhibition can protect against or treat colon cancer. 相似文献
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Poudyal H Panchal SK Waanders J Ward L Brown L 《The Journal of nutritional biochemistry》2012,23(2):153-162
Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection. 相似文献
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Melissa Carrillo Suraj Pandey Juan Sanchez Moraima Noda Ishwor Poudyal Luis Aldama Tek Narsingh Malla Elin Claesson Weixiao Yuan Wahlgren Denisse Feliz Vukica Šrajer Michał Maj Leticia Castillon So Iwata Eriko Nango Rie Tanaka Tomoyuki Tanaka Luo Fangjia Marius Schmidt 《Structure (London, England : 1993)》2021,29(7):743-754.e4
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Chumanevich AA Causey CP Knuckley BA Jones JE Poudyal D Chumanevich AP Davis T Matesic LE Thompson PR Hofseth LJ 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(6):G929-G938
Inflammatory bowel diseases (IBDs), mainly Crohn's disease and ulcerative colitis, are dynamic, chronic inflammatory conditions that are associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism for regulating IBD. Peptidylarginine deiminases (PADs) catalyze the posttranslational conversion of peptidylarginine to peptidylcitrulline in a calcium-dependent, irreversible reaction and mediate the effects of proinflammatory cytokines. Because PAD levels are elevated in mouse and human colitis, we hypothesized that a novel small-molecule inhibitor of the PADs, i.e., chloramidine (Cl-amidine), could suppress colitis in a dextran sulfate sodium mouse model. Results are consistent with this hypothesis, as demonstrated by the finding that Cl-amidine treatment, both prophylactic and after the onset of disease, reduced the clinical signs and symptoms of colitis, without any indication of toxic side effects. Interestingly, Cl-amidine drives apoptosis of inflammatory cells in vitro and in vivo, providing a mechanism by which Cl-amidine suppresses colitis. In total, these data help validate the PADs as therapeutic targets for the treatment of IBD and further suggest Cl-amidine as a candidate therapy for this disease. 相似文献
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Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques 总被引:12,自引:0,他引:12
Hel Z Venzon D Poudyal M Tsai WP Giuliani L Woodward R Chougnet C Shearer G Altman JD Watkins D Bischofberger N Abimiku A Markham P Tartaglia J Franchini G 《Nature medicine》2000,6(10):1140-1146
Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4 + and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization. 相似文献
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Black pepper is used worldwide to enhance food flavor. We investigated dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol. After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function. These changes clearly suggest that piperine reduces symptoms of human metabolic syndrome in HCHF-fed rats by reducing inflammation and oxidative stress. 相似文献
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Hemant Poudyal Senthil A. Kumar Aarjit Iyer Jennifer Waanders Leigh C. Ward Lindsay Brown 《The Journal of nutritional biochemistry》2013,24(7):1381-1392
We investigated the changes in adiposity, cardiovascular and liver structure and function, and tissue fatty acid compositions in response to oleic acid-rich macadamia oil, linoleic acid-rich safflower oil and α-linolenic acid-rich flaxseed oil (C18 unsaturated fatty acids) in rats fed either a diet high in simple sugars and mainly saturated fats or a diet high in polysaccharides (cornstarch) and low in fat. The fatty acids induced lipid redistribution away from the abdomen, more pronounced with increasing unsaturation; only oleic acid increased whole-body adiposity. Oleic acid decreased plasma total cholesterol without changing triglycerides and nonesterified fatty acids, whereas linoleic and α-linolenic acids decreased plasma triglycerides and nonesterified fatty acids but not cholesterol. α-Linolenic acid improved left ventricular structure and function, diastolic stiffness and systolic blood pressure. Neither oleic nor linoleic acid changed the left ventricular remodeling induced by high-carbohydrate, high-fat diet, but both induced dilation of the left ventricle and functional deterioration in low fat-diet-fed rats. α-Linolenic acid improved glucose tolerance, while oleic and linoleic acids increased basal plasma glucose concentrations. Oleic and α-linolenic acids, but not linoleic acid, normalized systolic blood pressure. Only oleic acid reduced plasma markers of liver damage. The C18 unsaturated fatty acids reduced trans fatty acids in the heart, liver and skeletal muscle with lowered stearoyl-CoA desaturase-1 activity index; linoleic and α-linolenic acids increased accumulation of their C22 elongated products. These results demonstrate different physiological and biochemical responses to primary C18 unsaturated fatty acids in a rat model of human metabolic syndrome. 相似文献