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| 1 | Increased hepcidin expression in colorectal carcinogenesis显示文摘AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae- mia and whether it might have a role in colorectal car- cinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using im- munohistochemistry. RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi- tively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres- sion. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism. | Douglas G Ward Keith Roberts Matthew J Brookes Howard Joy Ashley Martin Tariq Ismail Robert Spychal Tariq Iqbal Chris Tselepis | 2008 | World Journal of Gastroenterology2008，14，9： | 12 |
| 2 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 3 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 4 | Is iron overload in alcohol-related cirrhosis mediated by hepcidin?显示文摘In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation.We demonstrate a reciprocal relation-ship between serum or urinary hepcidin and serum ferritin,which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin.The ferritin level falls with increasing hepcidin production after transplantation.Neither inflammatory indices(IL6)nor erythropoietin appear to be related to hepcidin expression in this case.We suggest that inappropriately low hepcidin production by the cirrhotic liver may contribute substantially to elevated tissue iron stores in cirrhosis and speculate that hepcidin replacement in these patients may be of therapeutic benefi t in the future. | Tariq Iqbal Azzam Diab Douglas G Ward Matthew J Brookes Chris Tselepis Jim Murray Elwyn Elias | 2009 | World Journal of Gastroenterology2009，15，46： | 2 |
| 5 | Interstitial cells of Cajal and electrical activity in ganglionic and aganglionic colons of mice显示文摘 | Ward S M G ershon M D Keef K | 2002 | Am J Physiol2002，283，2： | 2 |
| 6 | Does physical activity affect quality of life, disease symptoms and immune measures in patients with inflammatory bowel disease? A systematic review显示文摘 | Packer N Hoffman-Goetz L Ward G | 2010 | Journal of Sports Medicine and Physical Fitness2010，，： | 2 |
| 7 | Plasmid DNA encoding replicating Foot-and-mouth disease virus genomes induces antiviral immune response in swine显示文摘 | Ward G Rieder E Mason P W | 1997 | J Virol1997，71，： | 1 |
| 8 | Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphoryla- ted histone H2AX 显示文摘 | Ward I M Minn K Jorda K G | 2003 | J Biol Chem2003，278，19： | 1 |
| 9 | Clinical Importance of Delays in the Initiation of Appropriate Antibiotic Treatment for Ventilator-associated Pneumonia显示文摘 | Iregui M Ward S Sherman G | 2002 | Chest2002，122，1： | 1 |
| 10 | Time-Resolved Electronic Phase Transitions in Manganites 显示文摘 | Ward T Z Zhang X G Yin L F | 2009 | Phys Rev Lett2009，102，： | 1 |
| 11 | Cytokine storm in a phase 1 trial 6f the anti-CD28 monoclonal antibody TGN1412 显示文摘 | Suntharalingam G Perry MR Ward S | 2006 | N Engl J Med2006，355，10： | 1 |
| 12 | The insulin receptor changes conformation in unforeseen ways on ligand binding:sharpening the picture of insulin receptor activation显示文摘 | Ward Colin W Menting John G Lawrence Michael C | 2013 | Bioessays2013，35，11： | 1 |
| 13 | Mineral discrimination and removal of inductive coupling with multrfrequency IP 显示文摘 | Pelton W H Ward S H Hallof P G | 1978 | Geophysics1978，43，3： | 1 |
| 14 | Changes in the sertun proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis显示文摘 | Ward D G Cheng Y N'Kontehou G | 2006 | Br J Cancer2006，94，2： | 1 |
| 15 | Seeing is believing: the importance of video laryngoscopy in teaching and in managing the difficult airway显示文摘 | Kaplan M B Ward D Hagberg C A Berci G Hagiike M | 2006 | Surg Endosc2006，202，： | 1 |
| 16 | Molecular characterization of the Fusarium graminearum species complex in Japan 显示文摘 | Suga H Karugia G W Ward T | 2008 | Phytopathology2008，98，15： | 1 |
| 17 | Differentiation of bifidobacteria by use of plused-field get eletrophoresis and ploymerase chain reaction 显示文摘 | ROY D WARD P CHAMPAGNE G | 1996 | Int J Food Microbiol1996，29，1： | 1 |
| 18 | The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes 显示文摘 | Sotsios Y Whittaker G C Westwick J Ward S G | 1999 | J Immunol1999，163，： | 1 |
| 19 | Design environment for low-amplitude ther- moacoustie engines显示文摘 | Ward W C Swift G W | 1994 | Journal of the Acoustical Society of America1994，95，6： | 1 |
| 20 | Influence of crown class and shade tolerance on individual tree development during deciduous forest succession in Connecticut显示文摘 | Ward J S Stephens G R | 1993 | Forest Ecology and Management1993，60，34： | 1 |
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