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Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

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Neural Regeneration Research 2018年第10期13卷 1719-1730页

作者： Paul Denver paula l.McClean Greater los Angeles Veterans Affairs Healthcare System West Los Angeles Medical Center and Department of NeurologyUniversity of CaliforniaLos AngelesCAUSA Centre for Molecular Biosciences University of UlsterColeraine Northern Ireland UK Northern Ireland Centre for Stratified Medicine ClinicalTranslational and Research Innovation Centre (C-TRIC)University of UlsterDerry/Londonderry Northern Ireland UK

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

关键词： Alzheimer's disease aging inflammation cognitive function spatial learning insulin signaling synapses cytokines

Programmed cell death in seeds of angiosperms

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Journal of Integrative Plant Biology 2015年第12期57卷 996-1002页

作者： María paula lópez-Fernández Sara Maldonado laboratory of Plant Development Department of Biodiversity and Experimental Biology Faculty of Exact and Natural Sciences University of Buenos Aires National Research Council of Argentine (CONICET)

During the diversification of angiosperms, seeds have evolved structuralp chemical, molecular and physiolog- ically developing changes that specially affect the nucellus and endosperm. All through seed evolution, programmed celldeath （PCD） has played a fundamental role. However, examples of PCD during seed development are limited. The present review examines PCD in integuments, nucellus, suspensor and endosperm in those representative examples of seeds studied to date.

关键词： Caspases endosperm KDEl-CysEP metacaspases nucellus nucleases programmed cell death perisperm ricinosomes

The preventive and therapeutic potential of native Brazilian fruits on colorectal cancer

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Food Bioscience 2022年第2期46卷 55-72页

作者： Roberto de paula do Nascimento lívia Mateus Reguengo Ana paula da Fonseca Machado Mario Roberto Marostica Junior University of Campinas School of Food EngineeringMonteiro Lobato Street 8013083-862CampinasS˜ao Paulo stateBrazil

In the last years,colorectal cancer(CRC)has been increasing substantially in developing *** the consumption of fat and meat have been linked with increased CRC risk,fruits intake can be *** addition,since CRC’s chemotherapy may be accompanied with adverse effects,natural plant products have been postulated as alternative or complementary therapeutic *** fruits are rich sources of bioactive compounds,mainly phenolic compounds,with antioxidant,anti-inflammatory,and anticancer benefits,thus,future candidates for CRC ***,this narrative review aims to present and discuss the potential of native Brazilian fruits(e.g.,açaí,cocoa,jaboticaba,passionfruit)on *** studies performed from 2001 to present were ***-rich powders and extracts from Brazilian fruits are the most promising products for CRC *** with açaí(Euterpe oleracea)and cocoa(Theobroma cacao)are more numerous and their effects on CRC models in vitro and in vivo are demonstrated with more complexity in terms of molecular *** main signaling pathways modulated by the effects of native Brazilian fruits,so far studied on CRC,are associated with:***(B-cell lymphoma 2-and caspase 3-related proteins),***(pro-inflammatory interleukins and enzymes),and *** stress(antioxidant enzymes).In addition,adhesion molecules and nuclear factor kappa B have been shown to be downregulated,which can interfere positively in several cellular processes,including proliferation,angiogenesis,and *** investigation of signaling pathways of great relevance for CRC initiation and progression is still necessary.

关键词： Anthocyanin Bioactive compound Carcinogenesis Euterpe oleracea Phenolic compound Theobroma cacao

A photoswitchable organocatalyst controls trimethylene carbonate and δ-valerolactone copolymerization

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Science Bulletin 2018年第22期63卷 1460-1461页

作者： Madeline N.Riffel Zachary C.Hern paula l.Diaconescu Department of Chemistry and Biochemistry University of California

Switchable catalysts can be reversibly altered to produce two (or more)states displaying orthogonal *** use of compounds containing a "switchable"unit in ring opening polymerization (ROP)of cyclic esters and ethers has been an attractive area of research due to the biosourced and biodegradable nature of the polymers produced and enhanced control of the polymer structure. Such systems for ROP have been reported using various stimuli such as temperature [1],redox [2-6] or chemical reagents [7,8], electrodes [9],and,recently,light [10].

关键词：催化剂状态

In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： Ana lMartínez-lópez Carlos JGonzález-Navarro paula Aranaz JosélVizmanos Juan MIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of *** nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/*** intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium *** therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose *** this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in *** finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in *** effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

Agmatine as a novel candidate for rapid-onset antidepressant response

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World Journal of Psychiatry 2021年第11期11卷 981-996页

作者： Ana paula Valverde Anderson Camargo Ana lúcia S Rodrigues Department of Biochemistry Campus UniversitárioCenter for Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisSC 88040900Brazil

Major depressive disorder(MDD)is a disabling and highly prevalent mood disorder as well as a common cause of *** stress,inflammation,and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of *** conventional antidepressants are widely used in the clinic,they can take weeks to months to produce therapeutic *** discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of ***,the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic ***,agmatine,an endogenous glutamatergic modulator,has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway,similar to ***,recent evidence has demonstrated that the modulation of the NlR family pyrin domain containing 3 inflammasome and gut microbiota,which have been shown to play a crucial role in the pathophysiology of MDD,may also participate in the antidepressant-like effects of both ketamine and *** review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical *** the anti-inflammatory properties of agmatine,it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory ***,the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.

关键词： Agmatine Fast-acting antidepressants Ketamine Major depressive disorder Microbiota-gut-brain axis Neuroinflammation

Native and exotic seed dispersal by the stone marten(Martes foina):implications for the regeneration of a relict climactic forest in central Portugal

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Integrative Zoology 2019年第3期14卷 280-292页

作者： lúcia PEREIRA Ana VASQUES paula MAIA Maria João RAMOS PEREIRA Carlos FONSECA Milena MATOS CESAM-Centre for Environmental and Marine Studies-Wildlife Research Unit Department of BiologyUniversity of AveiroAveiroPortugal CESAM-Centre for Environmental and Marine Studies-Department of Environment and Planning University of AveiroAveiroPortugal Erasmus University College Life Sciences DepartmentRotterdamthe Netherlands Institute of Biosciences PPGBANDepartment of ZoologyUniversidade Federal do Rio Grande do SulBrazil Bioliving Association FrossosAlbergaria-a-VelhaPortugal

The stone marten(Martes foina)is a carnivorous mammal that often consumes fleshy fruits,thus potentially promoting seed *** present study was developed in Bussaco National Forest,central Portugal,and aimed to assess the potential role of the stone marten in dispersing native and exotic plants in different forest landscape *** from stone marten scats and fleshy fruits were collected monthly and were thereafter identified and sowed in a nursery,following a randomized experimental *** emergence was monitored *** linear models were used to test for differences in time and success of emergence between seeds from scats and fruits of 3 native species(Rubus ulmifolius,Arbutus unedo and Celtis australis)and 1 exotic plant species with invasive behavior(Prunus laurocerasus).Fruit consumption by the stone martens significantly increased and accelerated the germination of the native *** but had no effect on the other 2 native species or on the invasive *** suggested that stone martens contribute to gene flow and forest regeneration by dispersing native plant ***,although the germination was not enhanced in the invasive species,the preference of stone martens for these fruits may potentially contribute to the proliferation of *** study represents a contribution to better understanding the fauna and flora interactions,enabling for a more conscious and effective decision-making in forest management.

关键词： germination invasive species Martes foina Prunus laurocerasus relict climactic forest

Bull spermatozoa selected by thermotaxis exhibit high DNA integrity,specific head morphometry,and improve ICSI outcome

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Journal of Animal Science and Biotechnology 2023年第3期14卷 1001-1011页

作者： Sara Ruiz-Diaz Rosane Mazzarella paula Navarrete-lopez Raul Fernandez-Gonzalez Celia de Frutos Maria Maroto Claudia Cucala paula Beltran-Brena Marta lombo Dimitrios Rizos Alfonso Gutierrez-Adan Department of Animal Reproduction INIA-CSIC28040 MadridSpain Mistral Fertility Clinics S.l Clinica TambreCalle Tambre828002 MadridSpain

Background Sperm migration by thermotaxis is a guidance mechanism that operates along the oviduct and it has proved to be a valid method for selecting spermatozoa with low DNA fragmentation(SDF)in mice,humans,and *** study aimed to analyse if bull spermatozoa could be selected by thermotaxis and to assess their quality in terms of SDF as well as determine the presence of a specific sperm subpopulation based on sperm morphometry and assess their fertilizing capacity by *** We used frozen-thawed sperm from 6 bulls and sperm selection by thermotaxis was performed with TAlP medium supplemented with 25 mmol/l of HEPES and 5 mmol/l of *** these conditions,sperm selection was achieved,obtaining a net thermotaxis of 3.6%.Subsequently,we analysed the SDF of the migrated and not-migrated spermatozoa using the neutral COMET assay,and we evaluated the size of the sperm head using Hemacolor■ staining with Motic Images Plus 3 ***,migrated and not-migrated spermatozoa by thermotaxis were used to fertilize bovine in vitro matured(IVM)oocytes by ICSI,a very inefficient procedure in cattle that is only successful when the oocyte is artificially *** The results showed lower SDF(χ^(2),Plower head size parameters(length and width,Plations structure varied between groups,highlighting cluster 2,characterized by spermatozoa with small head size,and high ellipticity and elongated heads,as the most abundant in the thermotaxis migrated *** performed ICSI(without oocyte artificial activation)with the thermotactic sperm,the blastocyst rate was 32.2%±9.3%in the group microinjected with the thermotactic spermatozoa vs.8.3%±7.8%in the group of not-migrated sperm(χ^(2),Plusion Our results showed that bull sperm selection by thermotaxis has a much higher D

关键词： ART Bovine Sperm morphometry Sperm selection Thermotaxis

Growth trends and environmental drivers of major tree species of the northern hardwood forest of eastern North America

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Journal of Forestry Research 2023年第1期34卷 37-50页

作者： Rebecca l.Stern Paul G.Schaberg Shelly A.Rayback Christopher F.Hansen paula F.Murakami Gary J.Hawley Rubenstein School of Environment and Natural Resources The University of VermontBurlingtonVT 05405USA ERM MalvernPA 19355USA Forest Service United States Department of AgricultureNorthern Research StationBurlingtonVT 05405USA Department of Geography The University of VermontBurlingtonVT 05405USA

The future health and productivity of tree species in the northern hardwood forest of eastern North America are uncertain considering changes in climate and pollution loading *** better understand the trajectory of the northern hardwood forest,we studied the growth of three tree species emblematic of it:sugar maple(Acer saccharum Marsh),American beech(Fagus grandifolia Ehrh.),and yellow birch(Betula alleghaniensis Britton),plus a fourth species,red maple(Acer rubrum l.),whose abundance has increased in the *** also analyzed the link between growth and several factors for690 trees in 45 plots throughout Vermont,USA:tree age and size,site elevation,and climate and acid deposition *** their chronologies(1945-2014),all four species exhibited increasing growth followed by plateaued growth indicative of a maturing *** all species,summer moisture was positively correlated with growth,summer temperature was negatively associated with growth,and winter moisture or snow were positively correlated with *** last association was expected for sugar ***,our data suggest that winter snowpack may be more broadly relevant in sustaining tree growth in a region where snow has historically insulated the soil from freezing that can damage roots and lead to reduced aboveground *** of pollution deposition were also correlated with growth for all species except American beech—a species with documented tolerance to pollutant *** the four species studied,red maple had the fewest associations with environmental variables,which suggests that it may be less susceptible to growth reductions as the climate changes.

关键词： Climate change Sugar maple Yellow birch American beech Red maple