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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella luis Labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman luis Alejandro de Haro ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Concentric Centrifugal Figurate Erythema as an Unusual COVID-19 Evanescent Skin Manifestation in a Patient With CD3^(+)/CD45^(+)Lymphocyte Infiltration:A Case Report

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International Journal of Dermatology and Venereology 2024年第2期7卷 115-118页

作者： Lucía Achell Achell-Nava José luis Zaldivar-Fujigaki Rebeca Pérez-Cabeza de Vaca ana Maria Espinosa García luis Montiel López Dermatology Department National Medical Center 20 de NoviembreISSSTEMexico City 03229Mexico Biomedical Research Department National Medical Center 20 de NoviembreISSSTEMexico City 03100Mexico Clinical Pharmacology Division General Hospital of MexicoMexico City 06720Mexico Internal Medicine Department National Medical Center 20 de NoviembreISSSTEMexico City 03100Mexico

Introduction:Coronavirus disease 2019(COVID-19)may be associated with various skin *** them,figurate erythema(FE)is rare;only a few clinical reports have been ***,we reported an unusual concentric FE lesions and their immunohistochemical profile in a patient with *** presentation:A 52-year-old woman was diagnosed with *** month later,she developed asymptomatic annular erythematous concentric ring lesions on her inner right *** margin of every ring increased in coloration,and the lesions then completely resolved in 2 weeks.A biopsy revealed vasculitis of small vessels,an increase in the fluorescence intensity of CD3 and CD45,and negativity for COVID-19 ***:The results showed an unusual FE that has a clinical mixed type between erythema annulare centrifugum and erythema gyratum repens;the physiopathological mechanism in the FE due to COVID-19 is unknown;one theory involves rapid viral passage into the cutaneous vascular system that triggers an immune and inflammatory *** the results exhibited a negative COVID-19 RNA in the tissue,the CD3^(+)/CD45^(+)lymphocyte infiltration could explain the clinical pattern as a direct inflammatory response in the small vessel or as a delayed immune ***:Our findings suggest an immunohistochemical small vessel vasculitis pattern with an unusual clinical FE that differs from other types of COVID-19-associated FE or erythema reported previously.

关键词： erythema COVID-19 leukocytoclastic vasculitis skin manifestation CD3 complex CD45 antigen

Percutaneous decannulation of extracorporeal membrane oxygenation using MANTA device:A real-world single-center experience

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World Journal of Cardiology 2024年第10期16卷 574-579页

作者： Ioannis Milioglou Alice Qian Pedro Rafael Vieira de Oliveira Salerno Gabriel Tensol Rodrigues Pereira luis Augusto Palma Dallan Kelsey E Gray michael Morrison Yasir Abu-Omar Mohammad Eldiasty Cristian Baeza Department of Cardiology University Hospitals Cleveland Medical CenterClevelandOH 44106United States Department of Surgery University Hospitals Cleveland Medical Center and Case Western Reserve University School of MedicineClevelandOH 44106United States

BACKGROUND The MANTA vascular closure device(VCD)represents a novel approach to achieving hemostasis after large-bore femoral access *** clinical studies have evaluated the efficacy of the MANTA device across a range of patient populations undergoing different ***,there is still a paucity of data available concerning the use of MANTA devices in aiding the decannulation of venoarterial extracorporeal membrane oxygenation(VAECMO).AIM To present our single-center experience of utilizing the MANTA VCD in patients undergoing this *** This single-center study included all patients undergoing percutaneous decannulation of femoral VA-ECMO using the MANTA plug-based VCD between January 2021 and October 2023 at University Hospitals Cleveland Medical *** criteria were adult patients who required prolonged(>24 hours)hemodynamic support with *** included all-cause mortality,hemostasis,bleeding,limb ischemia,and site *** This is a retrospective cohort study of 19 patients with a mean age of 56.8 *** of them were males with a mean body mass index of *** most common extracorporeal membrane oxygenation indication was acute coronary syndrome complicated by cardiogenic shock at 36.8%.The mean length of intensive care unit stay for these patients was 18.8±8.42 *** out of 19 patients survived to *** MANTA device was successfully deployed in 19 patients,with 10 procedures conducted at the bedside and 9 in an operating room *** hemostasis was achieved within 5 minutes of MANTA deployment in 17 out of 19 *** 2 patients manual compression after Manta deployment was required to achieve adequate ***,acute lower extremity ischemia was noted in two patients,necessitating endovascular *** infections were reported at the site of MANTA *** Overall,based on our experience and that of other centers,the MANTA VCD

关键词： Extracorporeal membrane oxygenation MANTA Decannulation Hemostasis Ischemia

Predictors of survival in autoimmune liver disease overlap syndromes

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World Journal of Hepatology 2024年第9期16卷 1269-1277页

作者： Dujinthan Jayabalan Yi Huang luis Calzadilla-Bertot Malik Janjua Bastiaan de Boer John Joseph Wendy Cheng Simon Hazeldine Briohny W Smith Gerry C MacQuillan michael C Wallace George Garas Leon A Adams Gary P Jeffrey Medical School University of Western AustraliaNed-lands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of anatomical Pathology PathWest Laboratory MedicineNedlands 6009Western AustraliaAustralia Department of Gastroenterology and Hepatology Royal Perth HospitalPerth 6000Western AustraliaAustralia Department of Gastroenterology and Hepatology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Medical School University of Western AustraliaNedl-ands 6009Western AustraliaAustralia

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is *** To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related *** Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort ***-related death or transplantation(liver-related mortality)was determined using a population-based data linkage *** scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and *** was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any *** Survival in the rare,AILDOS is *** current study supports the LOS as a predictor of liver-related mortality in AIH-PBC *** trials investigating predictors of survival in AILDOS are required.

关键词： Autoimmune liver disease overlap syndromes Liver outcome score Liver-related death Hepascore Autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis

Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies

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World Journal of Gastroenterology 2013年第38期19卷 6383-6397页

作者： michael luis.ana tavares Liliana S Carvalho Lúcio Lara-Santos António Araújo Ramon Andrade de Mello Gastrointestinal Unit Service of Medical OncologyPortuguese Oncology Institute4200-072 PortoPortugal Gastrointestinal Unit Experimental Pathology and Therapeutics GroupResearch Center-Portuguese Oncology Institute4200-072 PortoPortugal Department of Pharmacology and Therapeutics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal Institute of Cellular and Molecular Biology 4150-180 PortoPortugal Gastrointestinal Unit Section of Surgical OncologyPortuguese Oncology Institute4200-072 PortoPortugal Department of Medicine Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in *** the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong ***,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)***,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based ***,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this ***,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.

关键词： Gastric cancer Human epidermal growth factor receptor 2 Biomarkers Target therapies Trastuzumab Lapatinib Pertuzumab Trastuzumab-DM1 Afatinib

From strength to precision: A systematic review exploring the clinical utility of 7-Tesla magnetic resonance imaging in abdominal imaging

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World Journal of Radiology 2024年第1期16卷 20-31页

作者： Arosh S Perera Molligoda Arachchige ana Claudia Teixeira de Castro Gonçalves Ortega Federica Catapano Letterio S Politi michael N Hoff Faculty of Medicine Humanitas UniversityPieve Emanuele 20072MilanItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20072MilanItaly IRCCS Humanitas Research Hospital Rozzano 20089MilanItaly Department of Neuroradiology IRCCS Humanitas Research HospitalRozzano 20089MilanItaly Department of Radiology and Biomedical Imaging University of CaliforniaSan FranciscoCA 94143United States

BACKGROUND After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging(MRI)have demonstrated the feasibility as well as diagnostic capabilities of liver,kidney,and prostate MRI at ***,the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks,primarily stemming from heightened artifacts and limitations in Specific Absorption Rate,***,evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant *** To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends,details relevant challenges,and provides a concise set of potential *** This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.A PubMed search,utilizing Medical Subject Headings terms such as"7-Tesla"and organ-specific terms,was conducted for articles published between January 1,1985,and July 25,*** criteria included studies exploring 7T MRI for imaging human abdominal organs,encompassing various study types(in-vivo/ex-vivo,method development,reviews/meta-analyses).Exclusion criteria involved animal studies and those lacking extractable *** selection involved initial identification via title/abstract,followed by a full-text review by two researchers,with discrepancies resolved through *** extraction covered publication details,study design,population,sample size,7T MRI protocol,image characteristics,endpoints,and *** The systematic review included a total of 21 *** distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate(n=8),followed by the kidney(n=6)and the hepato

关键词： 7-Tesla magnetic resonance imaging Abdominal Prostate Kidney Renal Pancreas Hepatobiliary Liver Small bowel

Dealing with Multisource Information for Estuarine Flood Risk Appraisal in Two Western European Coastal Areas

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International Journal of Disaster Risk Science 2022年第2期13卷 199-213页

作者： ana Rodrigues Rilo Alexandre Manuel de Oliveira Soares tavares Paula Maria dos Santos Freire José luis Zêzere Estuarine and Coastal Zones Unit LNEC-National Civil Engineering Laboratory.1700-075 LisbonPortugal Centre of Geographical Studies Institute of Geography and Spatial PlanningUniversidade de Lisboa1700-066 LisbonPortugal Centre for Social Studies and Earth Sciences Department Coimbra University3030-790 CoimbraPortugal

Estuaries are usually affected by compound flooding triggers that cause diverse territorial *** fluvial flood risk assessment frameworks are well established in the literature,integrated management instruments that deal with estuarine flood risk remain incomplete and often *** research presents a methodology to extract relevant information from multiple sources post-event and a database building process that is applied to two contrasting estuaries(the Tagus River estuary in Portugal,and the Shannon River estuary in Ireland)in the Western European coastal ***,a total of 274 documents were analyzed and the information was stored in two *** correspondence analysis was applied to extract the most informative and relevant estuarine flood *** integrated estuarine flood risk assessment framework is presented and discussed based on the extracted *** framework is driven by two distinct dimensions(oceanic and hydrographic)and revealed the transversal position of triggers of estuarine floods,reflecting the compounding effects usually present in these *** results also highlight two levels of flood risk mostly based on damage typology.

关键词： Estuarine floods Estuarine flood indicators Multiple correspondence analysis Post-hazard multisource information Western Europe