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| 1 | Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice显示文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon, potentially due to a reduction in intestinal inflammation and/or neoplasia. Taken together, these results suggest that reductions in endogenous UG, accompanied by dysregulation in GC-C signaling, may be an early event in inflammation-promoted colorectal neoplasia; an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice, demonstrating the utility for developing GC-C agonists as chemopreventive agents. | Wen-Chi L Chang Shet Masih Anusha Thadi Viren Patwa Apoorva Joshi Harry S Cooper Vaseem A Palejwala Margie L Clapper Kunwar Shailubhai | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，1： | 5 |
| 2 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 3 | Manipulation of the n-3 PUFA content of muscle and adipose tissue in lambs显示文摘 | Cooper S L Sinclair L A Wilkinson R G | 2004 | J Animal Sci2004，82，： | 1 |
| 4 | Building market structures from consumer preferences 显示文摘 | Cooper L G Inoue A | 1996 | Journal of Marketing Re- search1996，33，3： | 1 |
| 5 | Manipulation of the n-3 polyunsaturated fatty acid content of muscle and adipose tissue in lambs 显示文摘 | Cooper S L Sinclair L A Wilkinson R G | 2004 | Journal of Animal Science2004，82，： | 1 |
| 6 | Strain and medium-related variability in the yeast-mycelial transition of Aureobasidium pullulans显示文摘 | Gadd G M Cooper L A | 1984 | FEMS Microbiology Letters1984，23，1： | 1 |
| 7 | Documentation of cumulative impacts in environmental impact statements 显示文摘 | Cooper T A Canter L W | 1997 | Environmental Impact Assessment Review1997，7，： | 1 |
| 8 | Cardiorespiratory fitness,all-cause mortality,and risk of cardiovascular disease in Trinidadian men-the St James survey显示文摘 | MILLER G J COOPER J A BECHKES G L | 2005 | Int J Epidemiol2005，34，6： | 1 |
| 9 | Mod- eling QTL for complex traits: Detection and context for plant breeding显示文摘 | Cooper M van Eeuwijk F A Hammer G L | 2009 | Current Opinion in Plant Biology2009，12，： | 1 |
| 10 | Cone ratio data envelopment analysis and multi-objective programming显示文摘 | CHARNES A COOPER W W WEI Q L | 1989 | Int J Sys Sci1989，20，7： | 1 |
| 11 | Polyurethane elastomers: factors leading to reduced properties for polyurethane based on nonpolar soft segments 显示文摘 | SPECKHARD T A COOPER S L | 1986 | Rubber Chem Tech1986，59，： | 1 |
| 12 | Multiple roles of glutathione in the central nervous system显示文摘 | COOPER A J L KRISTAL B S | 1997 | Biochem J1997，378，8： | 1 |
| 13 | Superconductivity: The transition temperature peak below four electrons per atom显示文摘 | Cooper A S Corenzerst E Longinotti L D | 1970 | Proe Natl Aead Sci USA1970，67，： | 1 |
| 14 | Synthesis and properties of the α-keto acids显示文摘 | Cooper A J L Ginos J Z | 1983 | Chem Rev1983，83，： | 1 |
| 15 | Manipulation of the n-3 polyunsaturated fatty acid content of muscle and adipose tissue in lambs显示文摘 | Cooper S L Sinclair L A Wilkinson R G | 2004 | J Anim Sci2004，82，： | 1 |
| 16 | Critical path analyses via chance constrained and stochastic programming 显示文摘 | Charnes A Cooper W W Thompson G L | 1964 | Opera- tions Research1964，，： | 1 |
| 17 | Advancing dental implant surface technology- From micron- to nano-topography显示文摘 | MENDON~A G MENDON(~A D B S ARAG~ O F J L COOPER L F | 2008 | Biomaterials2008，29，28： | 1 |
| 18 | Hydrogen spillover in the context of hydrogen storage using solid-state materials显示文摘 | Cheng H Chen L Cooper A C | 2008 | Energy Environ Sci2008，1，3： | 1 |
| 19 | Grain refinement of aluminium alloys by inoculation 显示文摘 | GREER A L COOPER P S MEREDITH M W SCHNEIDER W SCHUMACHER P SPITTLE J A | 2003 | Advanced Engineering Materials2003，5，： | 1 |
| 20 | 'Pretty Prudent' or Rhetorically Responsive? The American Public’s Support for Military Action显示文摘 | Drury A Cooper Overby L Marvin Ang Adrian Li Yitan | 2010 | Political Research Quarterly2010，，1： | 1 |
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