|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis显示文摘Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA. | Wenhao Jiang Yunyun Jin Shiwei Zhang Yi Ding Konglin Huo Junjie Yang Lei Zhao Baoning Nian Tao PZhong Weiqiang Lu Hankun Zhang Xu Cao Karan Mehul Shah Ning Wang Mingyao Liu Jian Luo | 2022 | Bone Research2022，10，2： | 7 |
| 2 | Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia显示文摘Prior studies have investigated sperm retrieval rates in men with non obstructive azoospermia(NOA)secondary to specific etiologies,yet most cases of NOA are idiopathic.We compared sperm retrieval rates and testicular histopathology in idiopathic NOA(iNOA)and nonidiopathic NOA(niNOA).We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction(microTESE)between 2000 and 2016.Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic.Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology.Among 224 men,86(38.4%)were idiopathic,75(33.5%)were nonidiopathic,and 63(28.1%)did not undergo genetic testing.Median age and serum testosterone were higher among iNOA or no testing versus niNOA.Median follicle-stimulating hormone(FSH)was lower among iNOA or no testing versus niNOA.A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele.Sperm retrieval rates were similar between iNOA,niNOA,and no testing(41.8%vs 48.0%vs 55.6%,respectively;P=0.255).Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA(31.4%and 27.0%vs 16.0%,P=0.073).On multivariable analysis,iNOA was not associated with sperm retrieval or spermatogenesis(P=0.430 and P=0.078,respectively).Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA.These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation. | Arighno Das Joshua A Halpern Annie L Darves-Bornoz Mehul Patel James Wren Mary Kate Keeter Robert E Brannigan | 2020 | Asian Journal of Andrology2020，22，6： | 3 |
| 3 | Development of a Direct Competitive Enzyme-Linked Immunosorbent Assay for the Detection of Fluoroquinolone Residues in Shrimp显示文摘 | Sheryl A. Tittlemier Jean-Marc Gélinas Guy Dufresne Mehul Haria Jessica Querry Chantal Cleroux Cathie Ménard Philippe Delahaut Gurmit Singh Nathalie Fischer-Durand Samuel Benrejeb Godefroy | 2008 | Food Analytical Methods2008，，1： | 2 |
| 4 | Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome:A prospective multi-centre cohort study显示文摘BACKGROUND Autoimmune markers including plasma cells(PC),anti-smooth-muscle antibody(ASMA),anti-nuclear antibody(ANA),and raised immunoglobulin G(IgG)are commonly observed in non-alcoholic steatohepatitis(NASH),however their clinical significance is unknown.AIM To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes.METHODS Consecutive patients with biopsy proven NASH from Christchurch Hospital,New Zealand and Singapore General Hospital(SGH)were included between 2005 to 2016 in a prospective multi-centre cohort study.Patients with other causes of chronic liver disease were excluded.IgG>14 g/L or globulin fraction>50%,ANA≥1:40,SMA≥1:40 were considered positive.Multivariate analysis was performed to assess which markers were independently associated with mortality and hepatic decompensation.RESULTS Total 261 patients were included of which 201 were from SGH.The median age was 53 and 51.9%were male.Advanced fibrosis was present in 31.4%at diagnosis.PC,ASMA,ANA and raised IgG were observed in 13.1%,4.9%,27.8%and 30.1%of patients respectively.After multivariate analysis,elevated IgG[Hazard Ratio(HR)6.79,95%CI:2.93-17.15]and fibrosis stage(HR 1.37,95%CI:1.03-1.87)were found to be independently associated with increased risk of liver decompensation.Age(HR 1.06,95%CI:1.02-1.10)and elevated IgG(HR 3.79,95%CI:1.90-7.68)were independent factors associated with higher mortality risk.CONCLUSION Elevated IgG,rather than ANA,ASMA or plasma cells,is independently associated with increased risk of hepatic decompensation and mortality in NASH.It could hence be important for prognostication. | Marianne Anastasia De Roza Mehul Lamba George Boon-Bee Goh Johnathan Huey-Ming Lum Mark Chang-Chuen Cheah Jing Hieng Jeffrey Ngu | 2021 | World Journal of Gastroenterology2021，27，43： | 2 |
| 5 | Intermittent gastric outlet obstruction caused by a prolapsing antral gastric polyp显示文摘Most gastric polyps have an asymptomatic presentation and are an incidental finding on upper endoscopy. Symptomatic presentations can range from an ulcerated polyp leading to anemia and occult bleed to complete gastric outlet obstruction. We report a case of an 89-year-old woman who presented with postprandial nausea and early satiety. Her upper endoscopy revealed a 2 cm pedunculated hyperplastic polyp arising from the antrum of the stomach which was seen prolapsing into the pylorus causing intermittent gastric outlet obstruction. In the present report, we statistically analyzed 39 prolapsing gastric polyps previously reported in the English literature and demonstrate the current utility of monopolar snare polypectomy in establishing a histological diagnosis while offering simultaneous treatment. Additionally, we review the literature for the management of all hyperplastic gastric polyps in relation to advancements in digestive endoscopy. | Mehul Parikh Brian Kelley Gabriel Rendon Bincy Abraham | 2010 | World Journal of Gastrointestinal Oncology2010，2，5： | 2 |
| 6 | Abdominal apoplexy: A case study of the spontaneous rupture of the gastroepiploic artery显示文摘 | Mehul Jadav Yvan Ducheine Donald Brief Larry Carter Theresa McWhite James Hardy | 2004 | Current Surgery2004，，4： | 1 |
| 7 | RBBB, ECG Rv strain, and abnormal car- diac biomarkers in diagnosis of right ventricular dysfunction and outcomes in critically ill patients显示文摘 | Rajan S Mohan L Mehul P | 2011 | Am J Respir Crit Care Med2011，183，： | 1 |
| 8 | Synthesis of N-arylquinolone derivatives bearing 2-thiophenoxyquinolines and their antimicrobial evaluation显示文摘A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives8a–f and 9a–f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 8c, 9c and 9e exhibited comparable antimicrobial activity to first line drugs. | Mehul B.Kanani Manish P.Patel | 2014 | Chinese Chemical Letters2014，25，7： | 1 |
| 9 | Kimura disease with advanced renal damage with anti-tubular basement membrane antibody显示文摘 | Mehul P. Dixit Katherine M. Scott Erika Bracamonte Naznin M. Dixit Michael J. Schumacher John Hutter Raymond Nagle | 2004 | Pediatric Nephrology2004，，12： | 1 |
| 10 | Outcome After Hip Fracture in Individuals Ninety Years of Age and Older显示文摘 | Mehul R. Shah Gina B. Aharonoff Philip Wolinsky Joseph D. Zuckerman Kenneth J. Koval | 2003 | 2003 (8 SU)2003，，8： | 1 |
| 11 | Adhesive Small Bowel Ob-struction in Children and Adolescents : Operative Utilization and Fac-tors Associated with Bowel Loss 显示文摘 | Timothy BL Mehul VR Marleta R | 2011 | Journal of the American Collegeof Surgeons2011，212，5： | 1 |
| 12 | 5'-nucleotidase is involved in chick embryo myoblast spreading on laminin显示文摘 | Mehul B Doyannette-Moyne MA Aubery M | 1990 | Cell Biol Int Rep1990，14，2： | 1 |
| 13 | Referral Web:Combining social networks and collaborative filtering显示文摘 | Henry Kautz Bart Selman Mehul Shah | 1997 | Communications of the ACM1997，40，3： | 1 |
| 14 | A physician team 's experiences in community-based participatory research:insights into effective group collaborations 显示文摘 | Mehul Dalai Rachel Skeete Heather L Yeo | 2009 | American journal of preventive medicine2009，37，6： | 1 |
| 15 | Urinary conjugated α-tocopheronolactone—a biomarker of oxidative stress in children with type 1 diabetes显示文摘 | Gayatri Sharma David P. Muller Stephen M. O’Riordan Sinead Bryan Mehul T. Dattani Peter C. Hindmarsh Kevin Mills | 2013 | Free Radical Biology and Medicine2013，，： | 1 |
| 16 | Plasma Flaps and slats:an application of weakly ionized plasma actuators显示文摘 | Chuan H Thomas C C Mehul P P | | 0，，3： | 1 |
| 17 | Dattani hypopituitarism oddities:con-genital causes显示文摘 | Daniel K Mehul T | 2007 | HormRes2007，68，5： | 1 |
| 18 | Notch-1 immunoexpression is increased in Alzheimer’s and Pick’s disease显示文摘 | Mehul H. Nagarsheth Alex Viehman Sara M. Lippa Carol F. Lippa | 2006 | Journal of the Neurological Sciences2006，，1： | 1 |
| 19 | Outcome After Hip Fracture in Individuals Ninety Years of Age and Older显示文摘 | Mehul R Shah Gina B Aharonoff Philip Wolinsky Joseph D Zuckerman Kenneth J Koval | 2001 | Journal of Orthopaedic Trauma2001，，1： | 1 |
| 20 | Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study显示文摘 | Christoph Troppmann Jonathan L. Pierce Mehul M. Gandhi Brian J. Gallay John P. McVicar Richard V. Perez | 2003 | Transplantation2003，，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员