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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 | Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models显示文摘AIM To investigate the effects of plecanatide and dolcanatide on maintenance of paracellular permeability, integrity of tight junctions and on suppression of visceral hypersensitivity. METHODS Transport of fluorescein isothiocyanate(FITC)-dextran was measured to assess permeability across cell monolayers and rat colon tissues. Effects of plecanatide and dolcanatide on the integrity of tight junctions in Caco-2 and T84 monolayers and on the expression and localization of occludin and zonula occludens-1(ZO-1) were examined by immunofluorescence microscopy. Anti-nociceptive activity of these agonists was evaluated in trinitrobenzene sulfonic acid(TNBS)-induced inflammatory as well as in non-inflammatory partial restraint stress(PRS) rat models. Statistical significance between the treatment groups in the permeability studies were evaluated using unpaired t-tests.RESULTS Treatment of T84 and Caco-2 monolayers with lipopolysaccharide(LPS) rapidly increased permeability, which was effectively suppressed when monolayers were also treated with plecanatide or dolcanatide. Similarly, when T84 and Caco-2 monolayers were treated with LPS, cell surface localization of tight junction proteins occludin and ZO-1 was severely disrupted. When cell monolayers were treated with LPS in the presence of plecanatide or dolcanatide, occludin and ZO-1 were localized at the cell surface of adjoining cells, similar to that observed for vehicle treated cells. Treatment of cell monolayers with plecanatide or dolcanatide without LPS did not alter permeability, integrity of tight junctions and cell surface localization of either of the tight junction proteins. In rat visceral hypersensitivity models, both agonists suppressed the TNBS-induced increase in abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity, and both agonists also reduced colonic hypersensitivity in the PRS model. CONCLUSION Our results suggest that activation of GC-C signaling might be involved in maintenance of barrier function, possibly through regulating normal localization of tight junction proteins. Consistent with these findings, plecanatide and dolcanatide showed potent antinociceptive activity in rat visceral hypersensitivity models. These results imply that activation of GC-C signaling may be an attractive therapeutic approach to treat functional constipation disorders and inflammatory gastrointestinal conditions. | Illona-Marie Boulete Anusha Thadi Catherine Beaufrand Viren Patwa Apoorva Joshi John A Foss E Priya Eddy Helene Eutamene Vaseem A Palejwala Vassilia Theodorou Kunwar Shailubhai | 2018 | World Journal of Gastroenterology2018,24,17: | 5 |
| 3 | Processed beetroot(Beta vulgaris L.)as a natural antioxidant in mayonnaise:Effects on physical stability,texture and sensory attributes显示文摘The oxidative and physical stability of the reformulated mayonnaise with processed beetroot was investigated and compared with a control(mayonnaise without beetroot)and a commercially available product.Processing of beetroot had an impact on the structural integrity of the antioxidants present.Microwaving(960 W for 7 min)was advantageous for preserving the betalain and polyphenol content of beetroot compared to roasting(180◦C for 90 min)and boiling(100◦C for 30 min).The oxidative stability of mayonnaise samples was determined by Rancimat and the thiobarbituric(TBA)assay.The addition of microwaved beetroot significantly enhanced the oxidative stability of mayonnaise at the end of a storage period of 4 weeks(4◦C).Although no significant differences(P>0.05)were detected between the mayonnaise samples containing beetroot and the commercial control,the latter was less susceptible to oxidation during storage.The turbiscan stability index(TSI)revealed that the commercial mayonnaise was less prone to destabilization phenomena.All the textural parameters increased with the incorporation of beetroot.The sensory evaluation revealed that,with the exception of graininess and uniformity,most of the sensory attributes are preserved if not improved with the addition of beetroot. | Vassilios Raikos Angela McDonagh Viren Ranawana Garry Duthie | 2016 | Food Science and Human Wellness2016,5,4: | 4 |
| 4 | Minimally invasive ultra- sound method for intra-articular diagnostics of cartilage degener- ation显示文摘 | Viren T Saarakkala S Kaleva E | 2009 | Ultrasound Med Biol2009,35,9: | 1 |
| 5 | Ultrasound evaluation of mechanical injury of bovine knee articular cartilage under arthro scopic control显示文摘 | Viren T Saarakkala S Tiitu V | 2011 | IEEE Trans Ultrason Ferroelectr Freq Con- trol2011,58,1: | 1 |
| 6 | In vitro development of angiosperm floral buds and organs显示文摘 | Rajeev Rastogi Viren K. Sawhney | 1989 | Plant Cell Tissue and Organ Culture1989,,3: | 1 |
| 7 | Personality, individual differences, and demographic antecedents of self - reported household waste management behaviours 显示文摘 | VIREN S CHAMORRO -PREMUZIC T SNELGAR R | 2011 | Journal of Environmental Psychology2011,31,1: | 1 |
| 8 | Exploratory analysis and visualization of speech and music by locally linear embedding显示文摘 | Viren J Lawrence K S | | 0,,: | 1 |
| 9 | , Does the Value-added Tax Shift to Consumption Prices? 显示文摘 | Viren M | 2009 | AUCO Czech Economic Review2009,3,2: | 1 |
| 10 | Social security and household saving in an international cross section显示文摘 | KOSKELA E VIREN M | 1983 | American Economic Review1983,73,1: | 1 |
| 11 | Multicenter validation study of pathologic response and tumor thickness at the tumor‐normal liver interface as independent predictors of disease‐free survival after preoperative chemotherapy and surgery for colorectal liver metastases显示文摘 | Antoine Brouquet Giuseppe Zimmitti Scott Kopetz Judith Stift Catherine Julié Anne‐Isabelle Lemaistre Atin Agarwal Viren Patel Stephane Benoist Bernard Nordlinger Alessandro Gandini Michel Rivoire Stefan Stremitzer Thomas Gruenberger Jean‐Nicolas Vauthey D | 2013 | Cancer2013,,15: | 1 |
| 12 | Evaluation of Patient Simulator Performance as an Adjunct to the Oral Examination for Senior Anesthesia Residents显示文摘 | Georges L. Savoldelli Viren N. Naik Hwan S. Joo Patricia L. Houston Marianne Graham Bevan Yee Stanley J. Hamstra | 2006 | Anesthesiology2006,,3: | 1 |
| 13 | Delivery of orally supplemented α-tocotrienol to vital organs of rats and tocopherol-transport protein deficient mice显示文摘 | Savita Khanna Viren Patel Cameron Rink Sashwati Roy Chandan K. Sen | 2005 | Free Radical Biology and Medicine2005,,: | 1 |
| 14 | Context Matters: Investigating the Impact of Contextual Information on Aesthetic Appreciation of Paintings by Max Ernst and Pablo Picasso 显示文摘 | Viren Swami | 2013 | Psychology of Aesthetics Creativity and the Arts2013,7,3: | 1 |
| 15 | Why Do Growth Rates Differ? Evidence from Cross-country Data on Private Sector Production 显示文摘 | KILPONEN J VIREN M | 2010 | Empirica2010,37,3: | 1 |
| 16 | The 1911 Revolution and the Politics of Failure: Takeuchi Yoshimi and Global Capitalist Modernity显示文摘中国历史学家认为 1911 革命是一条不完全的资产阶级革命,特别与更多相比成功 1949 革命。在他们在 1990 年代初的著名的道,在另一方面,李泽厚和刘在富宣称一 1911 革命再想应该导致我们完全拒绝革命的概念。在这两明确的表达,作为向任何革命是无益的社会主义或示范的垫脚石, 1911 革命在某些方面被连接到资本主义的合法性。在战后的日本,当日本知识分子在第二次世界大战正在辩论美国职业和日本角色的后果时,然而, 1911 革命有不同意义。战后的日本汉学家经常作为希望的一个符号转到 1911 革命,尽管有它的失败。Takeuchi Yoshimi 是这个智力的趋势的先驱,他主张 1911 革命不同于 Meiji Ishin,它是西方的新式的苍白的模仿,代表了革命主观的唯一的肯定,精确因为它在现代化的起始的尝试失败了。Takeuchi 和他 1911 革命怎么从失败生产了主观的门徙讨论说明采用的战后的日本汉学家在关于主观和反对殖民主义的争论的 1911 革命。他们的作品的分析将打开方法到在它在第 20 世纪联系到资本主义和它的不满的轨道的日本认为 1911 革命和它的感觉。 | Viren Murthy | 2012 | Frontiers of Literary Studies in China-Selected Publications from Chinese Universities2012,6,1: | 1 |
| 17 | An assessment of adult risks of paresthesia due to mercury from coal combustion显示文摘 | F. W. Lipfert P. D. Moskowitz V. Fthenakis M. Dephillips J. Viren L. Saroff | 1995 | Water Air & Soil Pollution (-)1995,,1: | 1 |
| 18 | Shock tunnel study of spiked aerodynamic bodies flying at hypersonic Math number 显示文摘 | Viren M Saravanan S Reddy K P J | 2007 | Shock Waves2007,12,3: | 1 |
| 19 | Minimally invasive ultrasound method for intra-articular diagnostics of cartilage degeneration显示文摘 | Viren T Saarakkala S Kaleva E | 2009 | Ultr~sound Med Biol2009,35,9: | 1 |
| 20 | Quantitative evaluation of spontaneously and surgically repaired rabbit articular cartilage using intra-articular ultrasound method in situ显示文摘 | Viren T Saarakkala S Jurvelin JS | 2010 | Ultrasound Med Biol2010,36,5: | 1 |