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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 | Fecal transplant policy and legislation显示文摘Fecal microbiota transplantation(FMT) has garnered significant attention in recent years in the face of a reemerging Clostridium difficile(C.difficile) epidemic.Positive results from the first randomized control trial evaluating FMT have encouraged the medical community to explore the process further and expand its application beyond C.difficile infections and even the gastrointestinal domain.However promising and numerous the prospects of FMT appear,the method remains limited in scope today due to several important barriers,most notably a poorly defined federal regulatory policy.The Food and Drug Administrationhas found it difficult to standardize and regulate the administration of inherently variable,metabolically active,and ubiquitously available fecal material.The current cumbersome policy,which classifies human feces as a drug,has prevented physicians from providing FMT and deserving patients from accessing FMT in a timely fashion,and subsequent modifications seem only to be temporary.The argument for reclassifying fecal material as human tissue is well supported.Essentially,this would allow for a regulatory framework that is sufficiently flexible to expand access to care and facilitate research,but also appropriately restrictive and centralized to ensure patient safety.Such an approach can facilitate the advancement of FMT to a more refined,controlled,and aesthetic process,perhaps in the form of a customized and wellcharacterized stool substitute therapy. | Dinesh Vyas Apoorva Aekka Arpita Vyas | 2015 | World Journal of Gastroenterology2015，21，1： | 4 |
| 4 | Lower extremity amputations and long-term outcomes in diabetic foot ulcers:A systematic review显示文摘BACKGROUNDDiabetes mellitus causes a large majority of non-traumatic major and minoramputations globally. Patients with diabetes are clinically complex with amultifactorial association between diabetic foot ulcers (DFU) and subsequentlower extremity amputations (LEA). Few studies show the long-term outcomeswithin the cohort of DFU-associated LEA.AIMTo highlight the long-term outcomes of LEA as a result of DFU.METHODSPubMed/MEDLINE and Google Scholar were searched for key terms, “diabetes”,“foot ulcers”, “amputations” and “outcomes”. Outcomes such as mortality, reamputation,re-ulceration and functional impact were recorded. Peer-reviewedstudies with adult patients who had DFU, subsequent amputation and follow upof at least 1 year were included. Non-English language articles or studiesinvolving children were excluded.RESULTSA total of 22 publications with a total of 2334 patients were selected against theinclusion criteria for review. The weighted mean of re-amputation was 20.14%,29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively withsignificantly higher rates associated with major amputation, re-amputation andischemic cardiomyopathy.CONCLUSIONPrevious LEA, level of the LEA and patient comorbidities were significant riskfactors contributing to re-ulceration, re-amputation, mortality and depreciatedfunctional status. | Ayeshmanthe Rathnayake Apoorva Saboo Usman H Malabu Henrik Falhammar | 2020 | World Journal of Diabetes2020，11，9： | 3 |
| 5 | Early diagnosis of bowel obstruction and strangulation by computed tomography in emergency department显示文摘BACKGROUND:Closed loop bowel obstruction is a specific type of mechanical obstruction with a high risk of strangulation and bowel infarction,especially in the small bowel.It is associated with a high mortality rate.Hence,it is important for emergency physicians to identify the presence of strangulation,while making the diagnosis of closed loop small bowel obstruction.METHODS:We reported three patients with strangulated closed loop small bowel obstruction associated with severe abdominal pain,who had been treated at the emergency department.Urgent computerized tomography was performed in the patients.RESULTS:Two patients were discharged with stable conditions,and one patient died after hemodialysis.CONCLUSION:Urgent computerized tomography of the abdomen serves as an important diagnostic tool in view of its ability to detect the site,level and cause of obstruction along with the distinctive CT appearance of closed loop small bowel obstruction and signs of ischemia.Early definitive diagnosis will guide subsequent management and improve outcomes. | Sohil Pothiawala Apoorva Gogna | 2012 | World Journal of Emergency Medicine2012，3，3： | 3 |
| 6 | Isolation and in silico evaluation of antidiabetic molecules of Cynodon dactylon (L.)显示文摘 | Hasthi V. Annapurna Babu Apoorva Natesan Ravichandran Kallur Purushothaman Arun Pemaiah Brindha Sethuraman Swaminathan Mahadevan Vijayalakshmi Arumugam Nagarajan | 2013 | Journal of Molecular Graphics and Modelling2013，，： | 2 |
| 7 | Oxidative stress in coronary artery disease: epigenetic perspective显示文摘 | Sana Venkata Vijaya Lakshmi Shaik Mohammad Naushad Cheruku Apoorva Reddy Kankanala Saumya Damera Seshagiri Rao Srigiridhar Kotamraju Vijay Kumar Kutala | 2013 | Molecular and Cellular Biochemistry2013，，1： | 2 |
| 8 | Randomized Clinical Trial of Cutting Balloon Angioplasty versus High-Pressure Balloon Angioplasty in Hemodialysis Arteriovenous Fistula Stenoses Resistant to Conventional Balloon Angioplasty显示文摘 | Syed Arafat Aftab Kiang Hiong Tay Farah G. Irani Richard Hoau Gong Lo Apoorva Gogna Benjamin Haaland Seck Guan Tan Siew Png Chng Shanker Pasupathy Hui Lin Choong Bien Soo Tan | 2013 | Journal of Vascular and Interventional Radiology2013，，： | 2 |
| 9 | GroEL1: A Dedicated Chaperone Involved in Mycolic Acid Biosynthesis during Biofilm Formation in Mycobacteria显示文摘 | Anil Ojha Mridula Anand Apoorva Bhatt Laurent Kremer William R. Jacobs Graham F. Hatfull | 2005 | Cell2005，，5： | 1 |
| 10 | Effect of hemodialysis on plasma myeloperoxidase activity in end stage renal disease patients显示文摘 | Rao AM Apoorva R Anand U | 2012 | Indian J Clin Biochemistry2012，27，3： | 1 |
| 11 | A New Approach to Extensible Continuum Robot Control Using the Sliding-Mode显示文摘 | Apoorva Deepak Kapadia Ian David Walker Darren Merritt Dawson Enver Tatlicioglu | 2011 | Computer Technology and Application2011，2，4： | 1 |
| 12 | New drugs and vaccines for drug-resistant Mycobacterium tuberculosis infections显示文摘 | Lynn GD Apoorva B Veemal B | | 0，，： | 1 |
| 13 | New drugs and vaccines for drug-resistant Mycobacterium tuberculosis infections显示文摘 | Lynn GD Apoorva B Veemal B | 2008 | Expert Rev Vaccines2008，4，7： | 1 |
| 14 | An analytical study of fundamental mobility properties for encounter-based protocols显示文摘 | SPYROPOULOS Thrasyvoulos JINDAL Apoorva PSOUNIS Konstantinos | 2008 | International Journal of Autonomous and Adaptive Communications Systems2008，1，1： | 1 |
| 15 | Deletion of kasB in Mycobacterium tuberculosis caused loss of acidfastness and subclinical latent tuberculosis in immunocompetent mice 显示文摘 | APOORVA B NAGATOSHI F KIRAMNAI B | 2007 | Microbilolgy2007，104，12： | 1 |
| 16 | Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-analysis显示文摘 | Rita Del Pinto Davide Pietropaoli Apoorva K. Chandar Claudio Ferri Fabio Cominelli | 2015 | Inflammatory Bowel Diseases2015，，11： | 1 |
| 17 | Modeling spatially correla- ted data in sensor networks 显示文摘 | Apoorva Jindal Konstantinos Psounis | 2006 | ACM Transactions on Sensor Net- works (TOSN)2006，2，4： | 1 |
| 18 | Modeling of HCCI combustion and emissions using detailed chemistry显示文摘 | William L Easley Apoorva Agarwal George A Lavoie | 2001 | SAE Paper2001，，： | 1 |
| 19 | Best practices for communication between client and vendor in IT outsourcing proj ects显示文摘 | Sharma R Apoorva S R Madireddy V Jain V | 2008 | Journal of Information Information Technology and Organizations2008，3，： | 1 |
| 20 | Prevalence and severity of periodontal disease in type 2 diabetes mellitus ( non-insulin-dependent dia- betes mellitus ) patients in Bangalore city: An epidemiologieal study显示文摘 | Apoorva SM Sridhar N | 2013 | J Indian Soe Periodontol2013，17，1： | 1 |
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