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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr angela Schulz Martina Strnadová Akhil velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.v.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Bioactive properties of glycosaminoglycans extracted from Turkey (Meleagris gallopavo) by-products

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Food Bioscience 2022年第2期46卷 321-329页

作者： Evellin Balbinot-Alfaro Claudio R.Novello Elisˆangela Düsman Alexandre T.Alfaro Helyn P.O.Barddal Igor v.Almeida veronica E.P.vicentini vil´asia G.Martins School of Chemistry and Food Federal University of Rio GrandeRio GrandeRSBrazil Department of Food Technology Federal University of TechnologyParan´aFrancisco Beltr˜aoPRBrazil Department of Biochemistry and Molecular Biology Federal University of Paran´aCuritibaPRBrazil Federal Rural University of Amazonia Capit˜ao PoçoPABrazil Department of Biotechnology State University of Maring´aMaring´aPRBrazil

Turkey wattle is a by-product generated during slaughter,which has a large amount of connective tissue and is a potential source of glycosaminoglycans(GAGs).This study aimed to extract GAGs from the turkey wattle(Meleagris gallopavos)and investigate its anticoagulant activity,and its cytotoxic and antiproliferative activity in tumor *** sulfate(CS-4 and CS-6)and dermatan sulfate(DS)present in the F-vII fraction and hyaluronic acid(HA)in the F-v fraction were *** HA showed a high molecular weight(1.0×10^(6) Da)and an apparent cytotoxic/antiproliferative effect against human hepatoma cells.F-vII fraction has an apparent cytotoxic/antiproliferative effect against renal adenoma cells and anticoagulant potential in *** results achieved in this study demonstrated that wattle,a by-product of turkey industrialization,has the potential to be valued as a raw material for the extraction of GAGs with bioactive properties.

关键词： Poultry By-products Hyaluronic acid Dermatan sulfate Chondroitin sulfate

Nanostructured biohybrid material with wide-ranging antiviral action

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Nano Research 2023年第8期16卷 11455-11463页

作者： Noelia Losada-Garcia angela vazquez-Calvo David Ortega-Alarcon Olga Abian Adrian velazquez-Campoy Pilar Domingo-Calap Antonio Alcami Jose M.Palomo Instituto de Catálisis y Petroleoquímica(ICP) CSICC/Marie Curie 2.Madrid 28049Spain Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas(CSIC)-Universidad Autónoma de Madrid(UAM)Madrid 28049Spain Institute of Biocomputation and Physics of Complex Systems(BIFI) Joint Unit GBsC-CSIC-BIFIUniversity of ZaragozaZaragoza 50018Spain Fundación Instituto de Investigación Sanitaria de Aragón(IIS Aragón) Zaragoza 50009Spain CIBERehd Madrid 28029Spain Instituto de Biología Integrativa de Sistemas I2SyBioUniversitat de València-CSICValència E-46071Spain

Respiratory pathogens kill more people than any other infectious agent each year *** of novel,economically friendly,sustainable,and highly efficient materials against viruses is a major ***,we describe a nanostructured material composed of very small crystalline phosphate copper nanoparticles synthesized using a new biohybrid technology that employs a biological agent for its formation at room temperature in aqueous *** evaluation of different enzymes in the final preparation of the nanomaterial or even in synthetic methods was *** characterization revealed the formation of Cu species in the protein *** best biomaterial synthesized using a lipase called BioCuNPs showed excellent inhibition capacity against functional proteins of severe acute respiratory syndrome coronavirus 2(SARS-Cov-2);for example,assent 3-chymotrypsin like protease(3CLpro)complete inhibition was achieved by using 5µg/mL,or acetone(ACE)–spike protein interaction was inhibited by more than 80%in the presence of 400µg/mL of *** these in vitro results into account,an efficacy analysis against human coronavirus 229E(HCov-E229)coronavirus was performed.A virus reduction of 99%was obtained in 5 ***,SARS-Cov-2 virus was tested to demonstrate high efficiency,with>99%inhibition in 15 min using 500 microgram of *** determine the wide applicability of this nanohybrid against viruses,an evaluation was carried out against a non-enveloped virus such as Human Rhinovirus(HRv-14),obtaining a virus reduction of 99.9%in 5 ***,the virucidal capacity against different bacteriophages was also evaluated,obtaining an excellent inhibition effect against PhageΦX174(99.999%reduction in 5 min).

关键词： antiviral compound coronaviruses copper nanoparticles nanobiotechnology viruses

Impact of chronic exposure to bevacizumab on EpCAM-based detection of circulating tumor cells

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Chinese Journal of Cancer Research 2015年第5期27卷 491-496页

作者： Chiara Nicolazzo Isabella Massimi Lavinia v.Lotti Simone vespa Cristina Raimondi Fabio Maria Pulcinelli angela Gradilone Paola Gazzaniga Dipartimento di Medicina Molecolare Sapienza Università di Roma Dipartimento di Medicina Sperimentale Sapienza Università di Roma

Background： Circulating tumor cells （CTCs） are often undetected through the immunomagnetic epithelial cell adhesion molecule （EpCAM）-based CellSearch~ System in breast and colorectal cancer （CRC） patients treated with bevacizumab （BEv）, where low CTC numbers have been reported even in patients with evidence of progression of disease. To date, the reasons for this discrepancy have not been clarified. This study was carried out to investigate the molecular and phenotypic changes in CRC cells after chronic exposure to BEv in vitro. Methods： The human CRC cell line WiDr was exposed to a clinically relevant dose of BEv for 3 months in vitro. The expression of epithelial and mesenchymal markers and EpCAM isoforms was determined by western blotting and immunofluorescence. To evaluate the impact of EpCAM variant isoforms expression on CTC enumeration by CellSearch, untreated and treated colon cancer cells were spiked into 7.5 mL of blood from a healthy donor and enumerated by CellSearch. Results： Chronic exposure of CRC cell line to BEv induced decreased expression of EpCAM 40 kDa isoform and increased expression EpCAM 42 kDa isoform, together with a decreased expression of cytokeratins （CK）, while no evidence of epithelial to mesenchymal transition （EMT） in treated cells was observed. The recovery rate of cells through CellSearch was gradually reduced in course of treatment with BEv, being 84% , 70% and 40% at l, 2 and 3 months, respectively. Conclusions： We hypothesize that BEv may prevent CellSearch from capturing CTCs through altering EpCAM isoforms.

关键词： Circulating tumor cells (CTCs) epithelial cell adhesion molecule (EpCAM) isoform bevacizumab(BEv) colorectal cancer (CRC)

Effectiveness of oral probiotics supplementation in the treatment of adult small chalazion

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International Journal of Ophthalmology(English edition) 2022年第1期15卷 40-44页

作者： Mariaelena Filippelli Roberto dell'Omo angela Amoruso Ilaria Paiano Marco Pane Pasquale Napolitano Giuseppe Campagna Silvia Bartollino Ciro Costagliola Department of Medicine and Health Sciences “V.Tiberio”University of MoliseCampobassoMolise 86100Italy Probiotical Research Srl R&D DepartmentNovaraPiemonte 28100Italy Department of Medical-Surgical Sciences and Translational Medicine University of Rome“Sapienza”Rome 00185Italy

AIM:To define the possible beneficial impact of probiotics oral supplementation on patients affected by ***:Prospective comparative pilot study on 20 adults suffering from chalazion randomly divided into two *** first group(n=10)received conservative treatment with lid hygiene,warm compression,and dexamethasone/tobramycin ointment for at least 20 *** second group(n=10),in addition to the conservative treatment,received a mixture of probiotic microorganisms of Streptococcus thermophilus ST10(DSM 25246),Lactococcus lactis LLC02(DSM 29536)and Lactobacillus delbrueckii(DSM 16606)once a day up to 3 *** were classified according to their size into three groups:small(vative treatment with and without probiotics supplementation failed to resolve the lesion,invasive methods were used,intralesional steroid injection in medium size chalazion and surgical incision and curettage for the largest ***:Medical treatment with or without probiotics supplementation was effective only on the small size *** was a significant difference in the time taken for complete resolution of small size chalazia between the two groups in favor of the patients receiving probiotics(38.50±9.04 d vs 21.00±7.00 d,P=0.039).Medium and large size chalazia did not respond to medical treatment with or without probiotics supplementation over the follow-up period(3 mo).The treatment did not induce any complications in both groups and no recurrence of chalaziosis was recorded in both ***:The considerable difference in time taken for complete resolution of small chalazia between the two groups in favor of the experimental one confirms the presence of a gut-eye axis.

关键词： microbiome probiotics chalaziosis adults

Combination therapy of dabrafenib plus trametinib in patients with BRAF^(v600E)-mutated biliary tract cancer

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Hepatobiliary & Pancreatic Diseases International 2021年第5期20卷 506-507页

作者： Alessandro Rizzo angela Dalia Ricci Giovanni Brandi Division of Oncology Azienda Ospedaliero-Universitaria di Bolognavia Albertoni 15BolognaItaly

To the Editor: In the last decade, next-generation sequencing(NGS)-based molecular profiling has shed light on the molecular landscape of biliary tract cancer(BTC), revealing the presence of several potentially actionable mutations [1]. According to Clinical ***, there are at least 40 phase I to Iv ongoing trials aimed at evaluating the role of targeted treatments in BTC, as monotherapy or in combination with other anticancer agents [2]. Early encouraging results have been observed with therapies targeting IDH mutations, FGFR fusions, HER family and, more recently, BRAF mutations [3].

关键词： BRAF cancer Clinical

Comparison of PM_(10) concentrations and metal content in three different sites of the venice Lagoon: An analysis of possible aerosol sources

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Journal of Environmental Sciences 2012年第11期24卷 1954-1965页

作者： Daniele Contini Franco Belosi Andrea Gambaro Daniela Cesari angela Maria Stortini Maria Chiara Bove Institute of Atmospheric Sciences and Climate ISAC-CNRLecceItaly Institute of Atmospheric Sciences and Climate ISAC-CNRBolognaItaly Department of Environmental Sciences Informatics and StatisticsUniversity Ca'Foscari of VeniceVeneziaItaly Institute of Atmospheric Sciences and Climate ISAC-CNRLecceItaly. Institute for the Dynamics of Environmental Processes IDPA-CNRVeneziaItaly

The venice Lagoon is exposed to atmospheric pollutants from industrial activities, thermoelectric power plants, petrochemical plants, incinerator, domestic heating, ship traffic, glass factories and vehicular emissions on the mainland. In 2005, construction began on the mobile dams （MOSE）, one dam for each channel connecting the lagoon to the Adriatic Sea as a barrier against high tide. These construction works could represent an additional source of pollutants. PM10 samples were taken on random days between 2007 and 2010 at three different sites： Punta Sabbioni, Chioggia and Malamocco, located near the respective dam construction worksites. Chemical analyses of v, Cr, Fe, Co, Ni, Cu, Zn, As, Mo, Cd, Sb, T1 and Pb in PM10 samples were performed by Inductively coupled plasma- quadrupole mass spectrometry （ICP-QMS） and results were used to identify the main aerosol sources. The correlation of measured data with meteorology, and source apportionment, failed to highlight a contribution specifically associated to the emissions of the MOSE construction works. The comparison of the measurements at the three sites showed a substantial homogeneity of metal concentrations in the area. Source apportionment with principal component analysis （PCA） and positive matrix factorization （PMF） showed that a four principal factors model could describe the sources of metals in PM10. Three of them were assigned to specific sources in the area and one was characterised as a source of mixed origin （anthropogenic and crustal）. A specific anthropogenic source of PM10 rich in Ni and Cr, active at the Chioggia site, was also identified.

关键词： MOdulo Sperimentale Elettromeccanico metals venice Lagoon PM10 principal component analysis positive matrixfactorization

High efficient processing area of difficult-to-machine materials by using temperature-horsepower criterion

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黑龙江科技大学学报 2015年第4期25卷 386-393页

作者： angela S G ZHANG Dan SERGEY B v MARINA K A Komsomolsk-on-Amur State Technical University Komsomolsk-on-Amur 681013 Russia

Дляпроблемывысокойстоимостирежущийтруднообрабатываемыхматериалов,производилиоптимизациипараметровпроцессареж... 详细信息

Дляпроблемывысокойстоимостирежущийтруднообрабатываемыхматериалов,производилиоптимизациипараметровпроцессарежущийинструмента,получилитехнологическийпроцессрезкитруднообрабатываемыхматериалов, улучшениепроизводительностиинструме-нттруднообрабатываемыхматериалов, создалимоделипараметровпроцессарезки, наконецполучитьтехнологическийпроцесструднообрабатываемыхматериалов.

关键词：俄语学习外语学习学习方法俄语翻译

Molecular diagnosis of Chagas disease:a systematic review and meta-analysis

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Infectious Diseases of Poverty 2023年第5期12卷 93-93页

作者： Guillermo Pascual-vázquez Montserrat Alonso-Sardón Beatriz Rodríguez-Alonso Javier Pardo-Lledías angela Romero Alegría Pedro Fernández-Soto Juan Luis Muñoz Bellido Antonio Muro Moncef Belhassen-García Infectious and Tropical Diseases Group (E-INTRO) Biomedical Research Institute of Salamanca (IBSAL) Tropical Diseases Research Center of the University of Salamanca (CIETUS) Faculty of Pharmacy University of Salamanca Salamanca Spain Area of Preventive Medicine Epidemiology and Public Health Department of Biomedical and Diagnostic Sciences Faculty of Medicine E-INTRO IBSAL CIETUS University of Salamanca Salamanca Spain Internal Medicine Service University Health Care Complex of Salamanca (CAUSA) E-INTRO IBSAL CIETUS Salamanca Spain Internal Medicine Department Hospital Marqués de Valdecilla University of Cantabria IDIVAL (Valdecilla Research Institute) Santander Spain Internal Medicine Service CAUSA. E-INTRO IBSAL CIETUS Salamanca Spain Infectious and Tropical Diseases Group (E-INTRO) IBSAL. CIETUS. Faculty of Pharmacy University of Salamanca Salamanca Spain Microbiology and Parasitology Service CAUSA IBSAL CIETUS CSIC Department of Biomedical and Diagnostic Sciences University of Salamanca Salamanca Spain Internal Medicine Service. Infectious Diseases Section CAUSA IBSAL CIETUS University of Salamanca Salamanca Spain

Background The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological ***,serology is the reference standard technique;occasionally,results are inconclusive,and a different diagnostic technique is *** guidelines recommend molecular testing.A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood *** A systematic review was conducted up to July 27,2022,including studies published in international *** and exclusion criteria were defined to select eligible *** were extracted and presented according to PRISMA 2020 *** quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2).A random-effects model was used to calculate pooled sensitivity,specificity,and diagnostic odds ratio(DOR).Forest plots and a summary of the receiving operating characteristics(SROC)curves displayed the *** was determined by I^(2)and Tau^(2)statistics and P *** plots and Deek's test were used to assess publication bias.A quantitative meta-analysis of the different outcomes in the two different clinical phases was *** We identified 858 records and selected 32 *** pertained to endemic countries and nonendemic areas with adult and paediatric *** sample sizes ranged from 17 to 708 *** were no concerns regarding the risk of bias and applicability of all included studies.A positive and nonsignificant correlation coefficient(S=0.020;P=0.992)was obtained in the set of studies that evaluated diagnostic tests in the acute phase population(ACD).A positive and significant correlation coefficient(S=0.597;P<0.000)was obtained in the case of studies performed in the chronic phase population(

关键词： Chagas disease Trypanosoma cruzi Molecular diagnosis Polymerase chain reaction Loop-mediated isothermal amplification