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Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

World Journal of Diabetes 2015年第6期6卷 807-827页

作者： Emanuel Monteiro Candeias inês carolina sebastio susana Maria Cardoso sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria sancha santos Catarina Resende oliveira Paula Isabel Moreira Ana Isabel Duarte CNC-Center for Neuroscience and Cell Biology Rua Larga Faculty of Medicine (1st Floor) University of Coimbra Institute for Interdisciplinary Research (IIIUC) University of Coimbra Casa Costa Alem?o-Pólo II Rua D Francisco de Lemos 3030-789 Coimbra Portugal Faculty of Medicine University of Coimbra Life sciences Department University of Coimbra Largo Marquês de Pombal 3004-517 Coimbra Portugal Institute of Biochemistry Faculty of Medicine University of Coimbra Institute of Physiology Faculty of Medicine University of Coimbra

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia in

关键词： Type 2 diabetes Glucagon-like peptide-1 Gut Brain Insulin Liraglutide Alzheimer disease Neuroprotection

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-segura Aleksandra Polishchuk Laura Nadal Marta Tomàs carolina silvera-simón Manel M.santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Effect of Magnesia Blending on the Magnetic Properties of Grain oriented silicon steel

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Journal of Chemistry and Chemical Engineering 2014年第2期8卷 191-194页

作者： carolina Cesconetto silveira sebastiāo da Costa Paolinelli Research Center Aperam South America Minas Gerais 35180-018 Brazil

Decarburized samples of grain oriented silicon steel were coated with alone and blended magnesias and submitted to the high temperature annealing. The magnesias and their blendings were characterized using granulometry measurements, ignition loss and reactivity tests. After high temperature annealing, forsterite film morphology, magnetic properties and Goss deviation were also analyzed. Better magnetic properties and sharper Goss orientation were found in samples which had used blended magnesias. These results are explained by the magnesias particle size distributions, forsterite film formation and rate of inhibitors release.

关键词： Forsterite glass film grain oriented magnesia silicon steel.

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optimizing oncolytic virus design:a“swiss army knife”approach to create a systemically delivered therapeutic

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signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： carolina s.Ilkow John Cameron Bell ottawa Hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

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Evaluation of a Pointwise Local Visual Pattern Exploration Method

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Tsinghua science and Technology 2012年第4期17卷 429-439页

作者： Matthew o.Ward Elke A.Rundensteiner carolina Ruiz Department of Computer science Worcester Polytechnic InstituteWorcesterMA 01609USA

sensitivity analysis is a powerful method for discovering the significant factors that contribute to understanding the interaction between variables in multivariate datasets. A number of sensitivity analysis methods fall into the class of local analysis, in which the sensitivity is defined as the partial derivatives of a target variable with respect to a group of independent variables. In a recent paper, we presented a novel pointwise local pattern exploration system for visual sensitivity analysis. Using this system, analysts are able to explore local patterns and the sensitivity at individual data points, which reveals the relationships between a focal point and its neighbors this paper we present several evaluations of the system, including case studies with real datasets, user studies the effectiveness of the visualizations and interactions, and a detailed description of the experience of a user In on

关键词： knowledge discovery sensitivity analysis local pattern visualization evaluation

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song divergence indicates an unclear relationship between the Neotropical and Nearctic Horned Larks

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Avian Research 2021年第2期12卷 161-172页

作者： Jimmy Alexander Vargas-Puentes Luis Alejandro Arias-sosa carolina Ramos-Montaño Grupo Ecología de organismos(GEo-UPTC) Escuela de Ciencias BiológicasUniversidad Pedagógica Y Tecnológica de ColombiaTunjaColombia

Background:some studies have indicated that the Horned Larks(Eremophila alpestris)should be considered as a species *** it split into four species or clades and seven subclades based on genetic,morphological,and biogeographic ***,other aspects like song divergence have not been studied and several subspe-cies have not been evaluated,leading to important information gaps in this group of *** this work,we aimed to assess the differences in song traits and playback response between the Nearctic subclade and the Neotropical or Colombian subspecies ***:We compared six song traits between these groups and performed field playback experiments,to test the response of the Neotropical larks to both *** tested the difference in the variables for separate as well as by principal component analysis(PCA).Results:We found significant differences(psong traits and the PCA analysis between the two ***,the PCA analysis showed a clearer divergence of the Neotropical songs in comparison to the Nearctic songs of different locations within North ***,the playback analysis showed a significantly lower response of *** to the songs of the Nearctic ***:Besides this song divergence,there are important ecological and biogeographic differences between the Neotropical and Nearctic Horned Larks,that indicate an unclear relationship between these two ***,further morphological and genetic studies are required to clarify the taxonomy of the Neotropical Horned Lark and define if they share the same evolutionary history as the other subspecies of the Nearctic subclade.

关键词： Birdsong Eremophila alpestris peregrina song features speciation Reproductive barrier

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A conserved arbuscular mycorrhizal fungal core-species community colonizes potato roots in the Andes

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Fungal Diversity 2016年第2期77卷 317-333页

作者： carolina senés-Guerrero Arthur schüßler Department of Biology GeneticsLudwig-Maximilians UniversityGrosshaderner Str.482152 PlaneggMartinsriedGermany

Plant-symbiotic arbuscular mycorrhizal fungi(AMF)are of high global ecological and economic importance,but describing environmental communities of AMF at the species level remains a challenge,despite the need to understand AMF-plant preferences and to apply AMF in sustainable ***,the potato-associated AMF species community composition was assessed for three Andean countries along an altitudinal gradient and at different plant stages,by using 454 Gs-FLX+sequencing of a 760 bp LsU rRNA gene PCR *** methods were compared:defining oTUs based on a simple sequence similarity threshold,or affiliating reference sequences to species based on a high throughput phylogenetic annotation approach using an evolutionary placement algorithm(EPA).The EPA-based approach was not only more precise,but also fundamental to robustly unveil the AMF species community *** principal advantage of this approach was also demonstrated by using artificially constructed datasets based on validated public database *** affiliation of sequence reads to species using phylogenetic annotation revealed a surprisingly conserved AMF core-species community structure in Andean potatoes,regardless of different plant stages and environmental *** total,41 species were detected and in some cases more than 25 species were found colonizing an individual root *** species were identified as dominant colonizers,co-occurring with Cetraspora nodosa and certain Claroideoglomus and Rhizophagus species in most potato root samples.

关键词： 454 pyrosequencing Andean ecosystems Arbuscular mycorrhizal fungi species communities DNA based species identification Evolutionary placement algorithm solanum tuberosum(potato)

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Diagnostic tests for hepatitis C: Recent trends in electrochemical immunosensor and genosensor analysis

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World Journal of Gastroenterology 2014年第42期20卷 15476-15491页

作者： carolina V Uliana Carla s Riccardi Hideko Yamanaka Department of Chemistry Federal University of Sao Carlos Department of Physical Chemistry Institute of Chemistry Sao Paulo State University Department of Analytical Chemistry Institute of Chemistry of Araraquara Sao Paulo State University (UNESP)

Hepatitis C is a liver disease that is transmitted through contact with the blood of an infected person. An estimated 150 million individuals worldwide have been chronically infected with the hepatitis C virus(HCV). Hepatitis C shows significant genetic variation in the global population, due to the high rate of viral RNA mutation. There are six variants of the virus(HCV genotypes 1, 2, 3, 4, 5, and 6), with 15 recorded subtypes that vary in prevalence across different regions of the world. A variety of devices are used to diagnose hepatitis C, including HCV antibody test, HCV viral load test, HCV genotype test and liver biopsy. Rapid, inexpensive, sensitive, and robust analytical devices are therefore essential for effective diagnosis and monitoring of disease treatment. This review provides an overview of current electrochemical immunosensor and genosensortechnologies employed in HCV *** are a limited number of publications showing electrochemical biosensors being used for the detection of *** to their simplicity,specificity,and reliability,electrochemical biosensor devices have potential clinical applications in several viral infections.

关键词： Hepatitis C virus Immunosensors Genosensors Electrochemical detection Diagnostic tests

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Radiomics in pancreatic cancer for oncologist:Present and future

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 356-361页

作者： carolina de la Pinta Radiation oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Radiomics is changing the world of medicine and more specifically the world of *** diagnosis and treatment improve the prognosis of patients with *** treatment,the evaluation of the response will determine future *** oncology,every change in treatment means a loss of therapeutic options and this is key in pancreatic *** has been developed in oncology in the early diagnosis and differential diagnosis of benign and malignant lesions,in the evaluation of response,in the prediction of possible side effects,marking the risk of recurrence,survival and prognosis of the *** studies have validated its use to differentiate normal tissues from tumor tissues with high sensitivity and specificity,and to differentiate cystic lesions and pancreatic neuroendocrine tumor grades with texture *** addition,these parameters have been related to survival in patients with pancreatic cancer and to response to radiotherapy and *** review aimed to establish the current status of the use of radiomics in pancreatic cancer and future perspectives.

关键词： Pancreatic cancer Radiomics Radiogenomics

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