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| 1 | 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 |
| 2 | Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer显示文摘BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive factors.AIM To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC patients.METHODS This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese hospitals.Means were compared through non-parametric Mann-Whitney tests.Receiver operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent variable.RESULTS This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of death.CONCLUSION Higher NLR is correlated with longer survival time.High LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT and dying.Patients with TSR and a pathological response have better OS and lower risk of dying. | Tiago Cruz Tomás Ines Eiriz Marina Vitorino Rodrigo Vicente Joao Gramaca Alicia Guadalupe Oliveira Paulo Luz Mafalda Baleiras Ana Sofia Spencer Luísa Leal Costa Patrícia Liu Joana Mendonca Magno Dinis Teresa Padrao Marisol Correia Goncalo Atalaia Michelle Silva Teresa Fiúza | 2022 | World Journal of Gastrointestinal Oncology2022，14，7： | 2 |
| 3 | Reliable gastric closure after natural orifice translumenal endoscopic surgery (NOTES) using a novel automated flexible stapling device显示文摘 | O. R. Meireles S. V. Kantsevoy L. R. Assumpcao P. Magno X. Dray S. A. Giday A. N. Kalloo E. J. Hanly M. R. Marohn | 2008 | Surgical Endoscopy2008，，7： | 2 |
| 4 | Additive anticonvulsant effects of creatine supplementation and physical exercise against pen- tylenetetrazol-induced seizures 显示文摘 | Leonardo Magno Rambo Leandro Rodrigo Ribeiro Mauro Schneider Oliveira | 2009 | Neurochemistry Inter- national2009，55，： | 1 |
| 5 | Antimonide- based compound semiconductors for electronic devices : a review 显示文摘 | BENNETT B R MAGNO R BOOS J B | 2005 | SSE2005，49，12： | 1 |
| 6 | Promotermethylation regulation Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells显示文摘 | Akhtar M Cheng Y Magno RM | 2001 | Cancer Res2001，61，6： | 1 |
| 7 | An invariance in the isohetanes of petroleum显示文摘 | Magno F D | 1987 | Science1987，237，： | 1 |
| 8 | Variation of some fermentative sulfur compounds in Italian 'Millesimè' classic sparkling wines during aging and storage on lees显示文摘 | FEDRIZZI B MAGNO F FINATO F | | 0，，17： | 1 |
| 9 | Glutathione S-transferases: an overview in cancer research显示文摘 | Giuliano Di Pietro Luiz Alexandre V Magno Fabrício Rios-Santos | 2010 | Expert Opinion on Drug Metabolism & Toxicology2010，，2： | 1 |
| 10 | Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the national health and nutrition examination survey, 1999 to 2004显示文摘 | Nguyen NT Magno CP Lane KT | 2008 | J Am Coll Surg2008，207，6： | 1 |
| 11 | Promoter methlation regulates Helicohacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells 显示文摘 | Akhtar M Cheng Y Magno RM | 2001 | cancer Res2001，61，6： | 1 |
| 12 | Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure显示文摘 | Dr. Giampiero Rocca Antonino Stefano Ermanno Eleuteri Rita Anzalone Francesca Magno Simona Corrao Tiziana Loria Anna Martorana Claudio Gangi Marilena Colombo Fabrizio Sansone Francesco Patanè Felicia Farina Mauro Rinaldi Francesco Cappello Pantaleo Giannu | 2009 | Basic Research in Cardiology2009，，3： | 1 |
| 13 | Analysis of prognostic factors in patients with isolated chest wall recurrence of breast cancer 显示文摘 | MAGNO L BIGNARDI M MICHELETTI E | 1987 | Cancer1987，60，： | 1 |
| 14 | Antimonidebased com- pound semiconductors for electronic deviees显示文摘 | Bennett B R Magno R Boos J B | 2005 | Solid State Electron2005，49，12： | 1 |
| 15 | Contrast-enhanced second-harmonic sonography in the detection of pseudocapsule in renal cell carcinoma显示文摘 | Ascenti G Gaeta M Magno C | 2004 | AJR Am J Roentgenol2004，182，6： | 1 |
| 16 | The role of the calcium-sens- ing receptor in human disease 显示文摘 | Ward BK Magno AL Walsh JP | 2009 | Clinical Biochemistry2009，10，3： | 1 |
| 17 | Steroids of the marine sponge Cinachyra tarentina: isolation of cholest- 4-ene-3, 6-dione and (24R)-24-ethylcholest-4-ene-3, 6- dione 显示文摘 | Aiello A Fattorusso E Magno S | 1991 | JNatProd1991，54，1： | 1 |
| 18 | The role of metacognitive skills in developing critical thinking显示文摘 | Magno C | 2010 | Metacognition and Learning2010，5，2： | 1 |
| 19 | Glutathione S-transferases: an overview in cancer research显示文摘 | Di Pietro G Magno LA Rios-Santos F | 2010 | Expert Opin Drug Metah Toxicol2010，6，2： | 1 |
| 20 | Managing Product Recalls: The Effects of Time, Responsible vs. Opportunistic Recall Management and Blame on Consumers’ Attitudes显示文摘 | Francesca Magno | 2012 | Procedia - Social and Behavioral Sciences2012，，： | 1 |
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