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| 1 | Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease显示文摘Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible. | Madhuri Venigalla Erika Gyengesi Gerald Münch | 2015 | Neural Regeneration Research2015，10，8： | 11 |
| 2 | Role of polyethylene particles in peri-prosthetic osteolysis:A review显示文摘There is convincing evidence that particles produced by the wear of joint prostheses are causal in the periprosthetic loss of bone,or osteolysis,which,if it progresses,leads to the phenomenon of aseptic loosening.It is important to fully understand the biology of this bone loss because it threatens prosthesis survival,and loosened implants can result in peri-prosthetic fracture,which is disastrous for the patient and presents a difficult surgical scenario.The focus of this review is the bioactivity of polyethylene(PE)particles,since there is evidence that these are major players in the development and progression of osteolysis around prostheses which use PE as the bearing surface.The review describes the biological consequences of interaction of PE particles with macrophages,osteoclasts and cells of the osteoblast lineage,including osteocytes.It explores the possible cellular mechanisms of action of PE and seeks to use the findings to date to propose potential nonsurgical treatments for osteolysis.In particular,a nonsurgical approach is likely to be applicable to implants containing newer,highly cross-linked PEs(HXLPEs),for which osteolysis seems to occur with much reduced PE wear compared with conventional PEs.The caveat here is that we know little as yet about the bioactivity of HXLPE particles and addressing this constitutes our next challenge. | Gerald J Atkins David R Haynes Donald W Howie David M Findlay | 2011 | World Journal of Orthopedics2011，2，10： | 11 |
| 3 | Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients显示文摘AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation. | Taher Abu Hejleh Barry R DeYoung Eric Engelman Jeremy M Deutsch Bridget Zimmerman Thorvardur R Halfdanarson Daniel J Berg Kalpaj R Parekh William R Lynch Mark D Iannettoni Sudershan Bhatia Gerald Clamon | 2012 | World Journal of Gastrointestinal Oncology2012，4，5： | 5 |
| 4 | 高血压病并胰岛素抵抗患者单核细胞粘附功能的变化显示文摘观察高血压、胰岛素抵抗对单核细胞—血管内皮粘附功能的影响 ,采用改良的胰岛素抑制试验和单核细胞—血管内皮细胞粘附试验检测 33例高血压病患者和 32例正常对照者的胰岛素敏感性和单核细胞—血管内皮粘附功能。结果发现 ,高血压病患者单核细胞对内皮的粘附性显著高于正常对照者 (P <0 .0 1) ,且高血压患者稳态血糖浓度与单核细胞粘附数显著正相关 (r=0 .6 1,P <0 .0 0 1) ,正常对照者稳态血糖浓度与单核细胞粘附数也显著正相关 (r=0 .71,P <0 .0 0 1) ,而平均动脉压只有在两组合并分析时与单核细胞粘附数存在显著正相关关系 (r=0 .4 3,P <0 .0 0 1)。经多元回归分析发现 ,稳态血糖浓度及胰岛素浓度与单核细胞粘附数有独立的相关关系。结果提示 ,高血压、胰岛素抵抗使单核细胞对血管内皮的粘附性增强 ,这可能是高血压、胰岛素抵抗等代谢异常易发生动脉粥样硬化的机制之一。 | 李伟 吴智勇 Gerald M Reaven Philip S Tsao | 2002 | 中国动脉硬化杂志2002，10，2： | 4 |
| 5 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 6 | RANKL/RANK control Brca1 mutation-driven mammary tumors显示文摘 | Verena Sig Kwadwo Owusu-Boaitey Puma A Joshi Anoop Kavirayani Gerald Wimsberger Maria Novatchkova Ivona Kozieradzki Daniel Schramek Nnamdi Edokobi Jerome Hersl Aishia Sampson Ashley Odai-Afotey Conxi Lazaro Eva Gonzalez-Suarez Miguel A Pujaaa for CIMBA Holger Heyn Enrique Vidal Jennifer Cru. ickshank Hal Berman Renu Sarao Melita Tieevic Iris Uribesalgo Luigi Tortola Shuan Rao Yen Tan Georg Pfeiler Eva YHP Lee Zsuzsanna Bago-Horvath Lukas Kenner Helmuth Popper Christian Singer Rama Khokha LaundeRe P Jones Josef M Penninger | 2016 | Cell Research2016，26，7： | 3 |
| 7 | Hydrogen peroxide mediates pro-inflammatory cell-to-cell signaling: a new therapeutic target for inflammation?显示文摘Nitric oxide is now universally recognized as an extracellular signaling molecule. Nitric oxide, produced in one cell, diffuses across the extracellular space and acts with targets in an adjoining cell. In this study, we present proof that hydrogen peroxide - like nitric oxide - acts as a true first (intercellular) messenger for a multitude of pro-inflammatory ligands. RAW 264.7 macrophages were activated with three different ligands, lipopolysaccharide, interferon-gamma or advanced glycation end products in the presence of increasing concentrations of (hydrogen peroxide scavenging) catalase. As inflammatory readouts, nitric oxide and tumor necrosis factor were determined. We hypothesize that hydrogen peroxide travels between cells propagating the signal, then a certain percentage of the readout should be inhibited by catalase in a concentration- dependent manner. The experiment showed concentration-dependent inhib让ion of nitric oxide and tumor necrosis factor-a production in response to all three ligands/ligand combinations (interferon-gamma, lipopolysaccharide, and chicken egg albumin-derived advanced glycation end product) in the presence of increasing concentration of catalase. For example, catalase inhibited 100% of nitric oxide and 40% of tumor necrosis factor-a production at its highest concentration. Our results suggest that hydrogen peroxide travels through cell membranes into the extracellular space and enters and activates ad;acent cells. Like rdtric oxide, we suggest that it is a ubiquitous first messenger, able to transmit cell-to-cell pro-inflammatory signals such as nitric oxide and tumor necrosis factor-a. In a therapeutic setting, our data suggest that compounds acting as hydrogen peroxide scavengers might not even need to enter the cell to act as anti-inflammatory drugs. | Dhanushka Gunawardena Ritesh Raju Gerald Münch | 2019 | Neural Regeneration Research2019，14，8： | 3 |
| 8 | Radioembolization with yttrium‐90 glass microspheres in hepatocellular carcinoma: European experience on safety and long‐term survival显示文摘 | Philip Hilgard Monia Hamami Amr El Fouly André Scherag Stefan Müller Judith Ertle Till Heusner Vito R. Cicinnati Andreas Paul Andreas Bockisch Guido Gerken Gerald Antoch | 2010 | Hepatology2010，，： | 3 |
| 9 | Bovine immunoglobulin protein isolates for the nutritional management of enteropathy显示文摘The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus(HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome(IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function(e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management ofenteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasmaor serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy. | Bryon W Petschow Anthony T Blikslager Eric M Weaver Joy M Campbell Javier Polo Audrey L Shaw Bruce P Burnett Gerald L Klein J Marc Rhoads | 2014 | World Journal of Gastroenterology2014，20，33： | 2 |
| 10 | Neural invasion in pancreatic cancer: A mutual tropism between neurons and cancer cells显示文摘 | Güralp O. Ceyhan Ihsan Ekin Demir Burak Altintas Ulrich Rauch Gerald Thiel Michael W. Müller Nathalia A. Giese Helmut Friess Karl-Herbert Sch?fer | 2008 | Biochemical and Biophysical Research Communications2008，，3： | 2 |
| 11 | Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy显示文摘AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI).METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation.RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological defi cits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001].CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE. | Falk R Miese Hans-Jrg Wittsack Gerald Kircheis Arne Holstein Christian Mathys Ulrich Mdder Mathias Cohnen | 2009 | World Journal of Gastroenterology2009，15，41： | 2 |
| 12 | Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life. | Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant | 2022 | World Journal of Diabetes2022，13，3： | 2 |
| 13 | Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease显示文摘 | Velandai Srikanth Annette Maczurek Thanh Phan Megan Steele Bernadette Westcott Damian Juskiw Gerald Münch | 2009 | Neurobiology of Aging2009，，5： | 2 |
| 14 | DBP formation during chloramination 显示文摘 | Diehl Alicia C Speitel Jr Gerald E Symons James M | 2000 | American Water Works Association2000，92，6： | 2 |
| 15 | Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials显示文摘 | Peter M Rothwell F Gerald R Fowkes Jill FF Belch Hisao Ogawa Charles P Warlow Tom W Meade | 2011 | The Lancet2011，，9759： | 2 |
| 16 | Tm(DOTP)5- :a 23 Na+ shift agent for perfused rat hearts显示文摘 | Buster D C Castro M M Geraldes C F | 1990 | Magn Reson Med1990，15，： | 2 |
| 17 | Cardiovascular magnetic resonance: Diagnostic utility and specific considerations in the pediatric population显示文摘Cardiovascular magnetic resonance is a non-invasive imaging modality which is emerging as important tool for the investigation and management of pediatric cardiovascular disease. In this review we describe the key technical and practical differences between scanning children and adults, and highlight some important considerations that must be taken into account for this patient population. Using case examples commonly seen in clinical practice, we discuss the important clinical applications of cardiovascular magnetic resonance, and briefly highlight key future developments in this field. | Frances M Mitchell Sanjay K Prasad Gerald F Greil Peter Drivas Vassilios S Vassiliou Claire E Raphael | 2016 | World Journal of Clinical Pediatrics2016，5，1： | 2 |
| 18 | Gastroesophageal reflux disease after diagnostic endoscopy in the clinical setting显示文摘AIM: To investigate the outcome of patients with symptoms of gastroesophageal reflux disease (GERD) referred for endoscopy at 2 and 6 mo post endoscopy. METHODS: Consecutive patients referred for upper endoscopy for assessment of GERD symptoms at two large metropolitan hospitals were invited to participate in a 6-mo non-interventional (observational) study.The two institutions are situated in geographically and socially disparate areas. Data collection was by selfcompletion of questionnaires including the patient assessment of upper gastrointestinal disorders symptoms severity and from hospital records. Endoscopic finding using the Los-Angeles classification, symptom severity and it's clinically relevant improvement as change of at least 25%, therapy and socio-demographic factors were assessed. RESULTS: Baseline data were available for 266 patients and 2-mo and 6-mo follow-up data for 128 and 108 patients respectively. At baseline, 128 patients had erosive and 138 non-erosive reflux disease. Allmost all patient had proton pump inhibitor (PPI) therapy in the past. Overall, patients with non-erosive GERD at the index endoscopy had significantly more severe symptoms as compared to patients with erosive or even complicated GERD while there was no difference with regard to medication. After 2 and 6 mo there was a small, but statistically significant improvement in symptom severity (7.02 ± 5.5 vs 5.9 ± 5.4 and 5.5 ± 5.4 respectively); however, the majority of patients continued to have symptoms (i.e. , after 6 mo 81% with GERD symptoms). Advantaged socioeconomic status as well as being unemployed was associated with greater improvement. CONCLUSION: The majority of GORD patients receive PPI therapy before being referred for endoscopy even though many have symptoms that do not sufficiently respond to PPI therapy. | Nora B Zschau Jane M Andrews Richard H Holloway Mark N Schoeman Kylie Lange William CE Tam Gerald J Holtmann | 2013 | World Journal of Gastroenterology2013，19，16： | 2 |
| 19 | Clinical, pathologic ,and molecular spectrum of tumors associated with t(11;22) (p13;q12): desmop lastic small round cell tumor and its variants显示文摘 | Gerald W L Ladanyi M de Alava E | 1998 | J Clin Oncol1998，16，9： | 1 |
| 20 | Activation of PKC-delta and SHP-1 by hyperglycemia causes vaseular cell apop- tosis and diabetic retinopathy 显示文摘 | Geraldes P Hiraoka-Yamamoto J Matsumoto M | 2009 | Nat Med2009，15，11： | 1 |
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