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| 1 | Platelet-rich plasma,an adjuvant biological therapy to assist peripheral nerve repair显示文摘Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft,are nowadays used to treat traumatic peripheral nerve injuries(PNI),focused on the enhancement of the intrinsic regenerative potential of injured axons.However,these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases,the functional recovery of nerve injuries is incomplete.Thus,new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field.In this sense,evidence is accumulating in both,preclinical and clinical settings,indicating that platelet-rich plasma products,and fibrin scaffold obtained from this technology,hold an important therapeutic potential as a neuroprotective,neurogenic and neuroinflammatory therapeutic modulator system,as well as enhancing the sensory and motor functional nerve muscle unit recovery. | Mikel Sánchez Ane Garate Diego Delgado Sabino Padilla | 2017 | Neural Regeneration Research2017，12，1： | 12 |
| 2 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 3 | Beta-blocker therapy in elderly patients with renal dysfunction and heart failure显示文摘OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^2.We analyzed the relationship between treatment with BB and mortality or cardiovascular events.The mean age of our population was 82.6±4.1 years.Mean ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,and<30 m L/min per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving BB.The median follow-up was28.04(IR:19.41-36.67)months.During the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;P<0.001).Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,P<0.0001),stage IIIb(GFR 30-45 m L/min per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFR<30 m L/min per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).CONCLUSIONS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better prognosis.Use of BB should be encouraged when possible. | Juan Martínez-Milla Marcelino Cortés García Julia Anna Palfy Mikel Taibo Urquía Marta López Castillo Ana Devesa Arbiol Ana Lucía Rivero Monteagudo María Luisa Martín Mariscal Inés Jiménez-Varas Sem Briongos Figuero Juan Antonio Franco-Pelaéz JoséTuñón | 2021 | Journal of Geriatric Cardiology2021，18，1： | 3 |
| 4 | Synthesis and biological evaluation of new symmetrical derivatives as cytotoxic agents and apoptosis inducers显示文摘 | CMRMEN S MIKEL E BEATRIZ M | 2005 | Bioorganic and Medicinal Chemistry2005，13，20： | 1 |
| 5 | Staphylococus aureus survival, staphylococcal enterotoxin production and shelf stabil- ity of country-cured hams manufactmed under different processing procedure 显示文摘 | PORTOCARRERO S M NEWMAN M MIKEL B | 2002 | Meat Science2002，62，2： | 1 |
| 6 | The hippocampus and nucleus accumbens as potential therapeutic targets for neurosur- gical intervention in schizophrenia显示文摘 | Mikell CB McKhann GM Segal S | 2009 | Stereotact Funet Neuro- surg2009，87，4： | 1 |
| 7 | Vitamin D3 supplementation of cull cows:effects on longissi- mus and semitendinosus muscle tenderness 显示文摘 | RIDER S N MIKEL W B XIONG Y L | 2004 | Journal of Animal Science2004，82，1： | 1 |
| 8 | Lexical Access in Bilingual Speech Production: Evidence from Language Switching in Highly Proficient Bilinguals and I2 Learners显示文摘 | COSTA MIKEL S | 2004 | Journal of Memory and Language2004，50，： | 1 |
| 9 | Power generation efficiency analysis of offshore wind farms connected to a SLPC single large power converter operated with variable frequencies considering wake effects显示文摘 | de Prada Gil Mikel Oriol G B Andreas S | 2012 | Energy2012，37，1： | 1 |
| 10 | Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon ceils in cuhure显示文摘 | Eduardo A Isabel A Mikel S | 2005 | J Orth Res2005，23，2： | 1 |
| 11 | Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture显示文摘 | EDUARDO A ISABEL A MIKEL S | 2005 | J Orth Res2005，23，2： | 1 |
| 12 | Lexical access in bilingual speech production Evidence from language switching in highly proficient bilinguals and L2 learners显示文摘 | COSTA A MIKEL S | 2004 | Joumal of Memo- ry and Language2004，50，： | 1 |
| 13 | Staphylococcus aureus survival,Staphylococcal enterotoxin production and shelf stability of country-cured hams manufactured under different processing procedures显示文摘 | Portocarrero S M Newman M Mikel B | 2002 | Meat Science2002，62，： | 1 |
| 14 | Two antioxidative lactobacilli strains as promising probiotics 显示文摘 | Kullisaar T Zilmer M Mikel S M | 2002 | Int J Food Microbiol2002，72，3： | 1 |
| 15 | Antioxidative probiotic fermented goats' milk decreases oxidative stressmediated atherogenicity in human subjects 显示文摘 | Kullisaar T Songisepp E Mikel S M | 2003 | Br J Nutr2003，90，8： | 1 |
| 16 | Exo , exo -2,3-Diaminoborneol-derived imidazolidinone as chiral auxiliary for asymmetric alkylations显示文摘 | Claudio Palomo Mikel Oiarbide Alberto Gonaz’alez Jesús M. García Fabienne Berrée | 1996 | Tetrahedron Letters1996，，26： | 1 |
| 17 | Lexical access in bilingual speech production:Evidence from language switching in highly proficient bilinguals and L2 learners显示文摘 | Costa A Mikel S | | 0，，： | 1 |
| 18 | Vitamin D3 supplementation of cull cows: Effects on longissimus andsemitendinosus muscle tendenaess显示文摘 | Rider S N Mikel W B Xiong Y L | 2004 | J Anim Sci2004，82，： | 1 |
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