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| 1 | SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation显示文摘Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases. | Xavier Palomer MSilvia Román-Azcona Javier Pizarro-Delgado Ana Planavila Francesc Villarroya Brenda Valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 2 | Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology显示文摘AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical limitations.RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may helpto explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients.CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose. | Nahum Calvo Raúl Beltrán-Debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven | 2015 | World Journal of Gastroenterology2015，21，24： | 2 |
| 3 | Pre-oxidation of an extremely polluted industrial wastewater by the Fenton’s reagent显示文摘 | Nora San Sebastián Mart??nez Josep F??guls Fernández Xavier Font Segura Antoni Sánchez Ferrer | 2003 | Journal of Hazardous Materials2003，，3： | 2 |
| 4 | Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective显示文摘Until very recently, treatment for chronic hepatitis C virus(HCV) infection has been based on the combination of two non-viral specific drugs: pegylated interferon-α and ribavirin, which is effective in, overall, about 40%-50% of cases. To improve the response to treatment, novel drugs have been designed to specifically block viral proteins. Multiple compounds are under development, and the approval for clinical use of the first of such direct-acting antivirals in 2011(Telaprevir and Boceprevir), represents a milestone in HCV treatment. HCV therapeutics is entering a new expanding era, and a highly-effective cure is envisioned for the first timesince the discovery of the virus in 1989. However, any antiviral treatment may be limited by the capacity of the virus to overcome the selective pressure of new drugs, generating antiviral resistance. Here, we try to provide a basic overview of new treatments, HCV resistance to new antivirals and some considerations derived from a Public Health perspective, using HCV resistance to protease and polymerase inhibitors as examples. | Karina Salvatierra Sabrina Fareleski Alicia Forcada F Xavier López-Labrador | 2013 | World Journal of Virology2013，2，1： | 2 |
| 5 | 25 Gbps low-voltage hetero-structured silicongermanium waveguide pin photodetectors for monolithic on-chip nanophotonic architectures显示文摘Near-infrared germanium(Ge) photodetectors monolithically integrated on top of silicon-on-insulator substrates are universally regarded as key enablers towards chip-scale nanophotonics, with applications ranging from sensing and health monitoring to object recognition and optical communications. In this work, we report on the highdata-rate performance pin waveguide photodetectors made of a lateral hetero-structured silicon-Ge-silicon(Si-Ge-Si) junction operating under low reverse bias at 1.55 μm. The pin photodetector integration scheme considerably eases device manufacturing and is fully compatible with complementary metal-oxide-semiconductor technology. In particular, the hetero-structured Si-Ge-Si photodetectors show efficiency-bandwidth products of^9 GHz at-1 V and ~30 GHz at-3 V, with a leakage dark current as low as ~150 nA, allowing superior signal detection of high-speed data traffic. A bit-error rate of 10-9 is achieved for conventional 10 Gbps, 20 Gbps, and25 Gbps data rates, yielding optical power sensitivities of-13.85 dBm,-12.70 dBm, and-11.25 dBm, respectively. This demonstration opens up new horizons towards cost-effective Ge pin waveguide photodetectors that combine fast device operation at low voltages with standard semiconductor fabrication processes, as desired for reliable on-chip architectures in next-generation nanophotonics integrated circuits. | DANIEL BENEDIKOVIC LéOPOLD VIROT GUY AUBIN FARAH AMAR BERTRAND SZELAG BAYRAM KARAKUS JEAN-MICHEL HARTMANN CARLOS ALONSO-RAMOS XAVIER LE ROUX PAUL CROZAT ERIC CASSAN DELPHINE MARRIS-MORINI CHARLES BAUDOT FRéDéRIC BOEUF JEAN-MARC FéDéLI CHRISTOPHE KOPP LAURENT VIVIEN | 2019 | Photonics Research2019，7，4： | 2 |
| 6 | ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is stimulated by glucose in pancreatic β-cells显示文摘 | Xavier G S Rutter G A Diraison F | 2006 | J Lip Res2006，11，47： | 1 |
| 7 | Use of Fenton for the treatment of leachate from composting of different wastes显示文摘 | Daniel T Xavier F Antoni S | 2006 | Journal of Hazardous Materials2006，136，12： | 1 |
| 8 | Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal impairment and mortality 显示文摘 | Miguei N Antonio F Xavier F | 1998 | Hepatology1998，27，5： | 1 |
| 9 | TGA study examining the effect of pressure and peak temperature on biochar yield during pyrolysis of two-phase olive mill waste显示文摘 | Joan J Manyà F Xavier Roca J Francisco Perales | 2012 | Journal of Analytical and Applied Pyrolysis2012，103，： | 1 |
| 10 | Amylin,food intake,and obesity显示文摘 | Tarek K Reda Allan Geliebter F Xavier Pi-Sunyer | 2002 | Obes Res2002，10，10： | 1 |
| 11 | Fluid flow and pumping efficiency in an ejector-venturi scrubber 显示文摘 | XAVIER G SARRA M JAVIER LAFUENTE F | 2004 | Chemical and Engineering Processing2004，43，2： | 1 |
| 12 | Affinity for inor- ganic carbon of Gracilaria tenuistipitata cultured at low and high irradiance 显示文摘 | Mercado J M Carmona R Xavier Niell F | 2000 | Planta2000，210，： | 1 |
| 13 | The class constrained bin packing problem with applications to video on demand显示文摘 | Xavier E C Miyazawa F K | 2008 | Theoretical Computer Science2008，393，： | 1 |
| 14 | Efficacy and tolerability of fluvastatin extended-release delivery system:A pooled analysis显示文摘 | Ballantyne CM Pazzucconi F Xavier P | | 0，，02： | 1 |
| 15 | Toxicological and metabolic investigations of the safety of LAE显示文摘 | Stephen A R Xavier R Joseph F | 2004 | Food and Chemical Toxicology2004，42，： | 1 |
| 16 | Population structure and systematics of Opsariichthys bidens in south-east China using a new nuclear marker:the introns (EPIC-PCR)显示文摘 | Berrebi P Xavier X Fang F | 2006 | Biological Journal of the Linnean Society2006，87，1： | 1 |
| 17 | Lipase catalyzed modification of milk fat 显示文摘 | Balcao Victor M Xavier Malcata F | 1998 | Biotechnology Advances1998，16，2： | 1 |
| 18 | Influence of glass fiber content on the morphology and meehnical properties in injection mould- ed polypropylene composites显示文摘 | XAVIER S F | 1985 | Polymer Composition1985，6，2： | 1 |
| 19 | Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial显示文摘 | Christina Davies Hongchao Pan Jon Godwin Richard Gray Rodrigo Arriagada Vinod Raina Mirta Abraham Victor Hugo Medeiros Alencar Atef Badran Xavier Bonfill Joan Bradbury Michael Clarke Rory Collins Susan R Davis Antonella Delmestri John F Forbes Peiman Hadd | 2012 | The Lancet2012，，： | 1 |
| 20 | Adances and perspectives in using microalgae to produce biodiesel显示文摘 | AMANO M HELENA GUEDES CATAEINA MALCATA XAVIER F | 2011 | Applied Energy2011，88，： | 1 |
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