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Engineering nanoparticles for targeting rheumatoid arthritis： Past, present, and future trends

Nano Research 2018年第9期11卷 4489-4506页

作者： isabel Matos Oliveira Cristiana Goncalves Rui Lufs Reis Joaquim Miguel Oliveira B's Research Group - Biomatefials Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine AvePark 4805-017 Barco Guimaraes Portugal ICVS/3B's-PTGovernment Associate Laboratory University of Minho Campus de Gualtar 4710-057 Braga Portugal The Discoveries Centre for Regenerative and Precision Medicine Headquarters at University of Minho Avepark 4805-017 Barco Guimaraes Portugal

Rheumatoid arthritis （RA） is a chronic inflammatory disease characterized by synovial joint inflammation and cartilage and bone tissue destruction. Although there exist some treatment strategies for RA, they are not completely safe and effective. Therefore, it is important to develop and test new drugs for RA that specifically target inflamed/swollen joints and simultaneously attenuate other possible damages to healthy tissues. Nanotechnology can be a good alternative to consider when envisioning predse medication for treating RA. Through the use of nanopartides, it is possible to increase bioavailability and bioactivity of therapeutics and enable selective targeting to damaged joints. Herein, recent studies using nanoparticles for the treatment of RA, namely with liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been reviewed. These therapeutic strategies have shown great promise in improving the treatment over that by traditional drugs. The results of these studies confirm that feasibility of the use of nanopartides is mainly due to their biocompatibility, low toxicity, controlled release, and selective drug delivery to inflamed tissues in animal RA models. Therefore, it is possible to claim that nanotechnology will, in the near future, play a crucial role in advanced treatments and patient-specific therapies for human diseases such as RA.

关键词： nanoparticles liposomes dendrimers rheumatoid arthritis

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An update on iron physiology

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World Journal of Gastroenterology 2009年第37期15卷 4617-4626页

作者： Manuel Muoz isabel Villar José Antonio García-Erce Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain Department of Hospital Pharmacy University Hospital Miguel Servet Zaragoza 50009 Spain Hematology and Hemotherapy University Hospital Miguel Servet Zaragoza 50009 Spain

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.

关键词： Iron metabolism Iron deficiency Functionaliron deficiency, Hepcidin Anemia of chronic disease

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Cell-type-specific memory consolidation driven by translational control

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Signal Transduction and Targeted Therapy 2021年第2期6卷 206-208页

作者： Qing Zhang isabel Bestard-Lorigados Weihong Song Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBCCanada Institute of Aging School of Mental Health and Kangning HospitalThe Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouChina

***’s group has significantly contributed to the understanding of translational control in learning and *** a recent Nature article,they further reported the cell-typespecific translational control underlying memory consolidation.1 Long-term potentiation(LTP)has been widely acknowledged as one of the main cellular models of learning and ***,there are two components of LTP driven by different stimulations and *** early phase of LTP(E-LTP)and short-term memory(STM)are evoked for short periods and are temporary,relying primarily on modifications of pre-existing *** late phase of LTP(L-LTP)and consequent longterm memory(LTM)are elicited by strong and repetitive stimulation and are long-lasting,requiring new protein synthesis.

关键词： synthesis. translational stimulation

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Two-tiered reconstruction of Late Pleistocene to Holocene changes in the freezing level height in the largest glacierized areas of the Colombian Andes

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Journal of Mountain Science 2022年第3期19卷 615-636页

作者： Daniel RUIZ-CARRASCAL Daniel GONZALEZ-DUQUE isabel RESTREPO-CORREA Department of Ecology Evolution and Environmental BiologyColumbia University in the City of New YorkNew YorkNY 10027USA Department of Civil and Environmental Engineering Vanderbilt University40024th Avenue South269 Jacobs HallNashville TN 3720USA Department of Earth Sciences Universidad EAFITCarrera 49 No.7Sur-50MedellínColombia

One way of deducing vertical shifts in the altitudinal distribution of Colombian high-altitude páramo environments is by inferring fluctuations in the height of the local freezing *** our research,we are implementing two complementary approaches to reconstruct Late Pleistocene to Holocene changes in the freezing level height(FLH)in two of the most extensively glacier-covered areas of the northern *** combined remote sensing and field-based geomorphological mapping with time-series reconstruction of changes in the altitude of the 0°C *** in the FLH were based on alreadypublished~30 kyr paleo-reconstructions of sea surface temperatures(SSTs)of the eastern tropical Pacific and the western tropical Atlantic,as well as on reconstructed long-term sea level changes and empirical orthogonal functions of present-day(historical)Indo-Pacific and tropical Atlantic SST *** also analyzed the probability distribution of air-sea temperature differences and the spatial distribution of grid points with SSTs above the minimum threshold necessary to initiate deep *** considered available historical nearsurface and free air temperature data of ERA-Interim reanalysis products,General Circulation Model(GCM)simulations,weather stations,and(deployed by our group)digital sensors,to assess the normal Environmental Lapse Rates(ELRs)at the regional to local *** combined maps of glacial landforms and our reconstructed FLHs provided us with a wellfounded inference of potential past glacier advances,narrowing down the coarse resolution of ice margins suggested by previous research *** extent of the areas with temperatures below the freezing point suggested here for the summits of our main study site exceeds in magnitude the corresponding glacier icecaps and front advances proposed by previous ***,our average lowest altitudes of the FLH for our comparative site are consistently above the main glacier-front advances previously su

关键词： Glacial events Colombian Andes Climate reconstruction Geomorphology Mountain glaciers Freezing level height

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Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

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Light(Science & Applications) 2020年第1期9卷 1086-1094页

作者： isabel Barth Donato Conteduca Christopher Reardon Steven Johnson Thomas F.Krauss Department of Physics University of YorkYO105DD YorkUK Department of Electronic Engineering University of YorkYO105DD YorkUK

Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity,low-cost,and reliable *** the most sensitive modalities,interferometry offers particularly high performance,but typically lacks the required operational simplicity and ***,we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent *** sensor exploits the simultaneous excitation of two orthogonally polarized modes,and detects the relative phase change caused by biomolecular binding on the sensor *** wide dynamic range of the sensor,which is essential for fabrication and angle tolerance,as well as versatility,is controlled by integrating multiple,tuned structures in the field of *** approach circumvents the trade-off between sensitivity and dynamic range,typical of other phase-sensitive modalities,without increasing *** sensor enables the challenging label-free detection of procalcitonin,a small protein(13 kDa)and biomarker for infection,at the clinically relevant concentration of 1 pg mL^(−1),with a signal-to-noise ratio of *** result indicates the utility for an exemplary application in antibiotic guidance,and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.

关键词： dielectric integrating simplicity

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Evolution and Continuity of Linguistic Systems

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Language and Semiotic Studies 2022年第1期8卷 24-36页

作者： isabel Victoria Galleguillos Jungk Pontifical Catholic University of Sao Paulo University of Sao Paulo Brazil

In the inspiring extract highlighted in this paper,Saussure observes how the relation between the elements of the sign change and evolve over *** his Cours,he also details the elements of the linguistic sign and the principles governing them,defining language as a system of *** the natural resistance to changes in language in order to enable it to continually fulfill its function,that is,despite the necessary immutability of linguistic signs,they change over time,by being in constant contact with the communities of speakers,to whom language actually *** may seem paradoxical because language is composed of arbitrary relations between signified and signifier that seek to represent *** refers to a principle of change in language linked to a principle of *** present study focuses on the semiotic and communicational aspects of the development of linguistic systems in time,understood from a systemic *** is sought to evince how signs perpetuate themselves and evolve through their constant interaction with real communities of language *** approach can offer new insights about the continuity of linguistic systems as systems of signs that present immutable and mutable characters,and whose evolution can be understood based on open systems parameters,such as permanence,autonomy and sensitivity to flows of information,as studied by current theories and authors,showing that,to preserve its semiological life (CGL,1959,p.76),a living language must continuously reflect the purposes of its users.

关键词： linguistic systems linguistic mutability evolution continuity systems parameters

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World Journal of Gastroenterology 2022年第30期28卷 4231-4234页

作者： Manuel Muro Aurelia Collados-Ros isabel Legaz Immunology Service Instituto Murciano de investigación biosanitaria(IMIB)Hospital Clínico Universitario Virgen de la Arrixaca(HCUVA)Murcia 30120Spain Department of Legal and Forensic Medicine Biomedical Research Institute(IMIB)Regional Campus of International Excellence“Campus Mare Nostrum”Faculty of MedicineUniversity of MurciaMurcia 30100Spain

Alcohol intake is a risk factor for cancer development and metastatic disease *** vesicle(EV)-mediated interorgan communication is assumed to be significant in boosting tumorigenic pathways and disease *** research indicates that exosomes have a variety of roles in the development of cancer during pathophysiological *** involvement of EV signaling during cancer progression in the alcohol environment is ***,understanding communication networks and the role of EVs as biomarkers can contribute significantly to developing strategies to address the serious public health problems associated with alcohol consumption and cancer.

关键词： Exosomes Liver metastasis Alcohol-associated liver disease Cancer

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The drama of memory in Shakespeare's history plays

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作者： Karremann isabel

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Hepatitis B viral infection and role of alcohol

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World Journal of Gastroenterology 2022年第35期28卷 5233-5236页

作者： Manuel Muro Aurelia Collados-Ros isabel Legaz Department of Immunology Clinical University HospitaĺVirgen de la Arrixaca-IMIB(Murcian Institute of Biomedical Investigation)Murcia 30120Spain Department of Legal and Forensic Medicine Biomedical Research Institute(IMIB)Regional Campus of International Excellence"Campus Mare Nostrum"Faculty of MedicineUniversity of Murcia(Spain)Universidad de MurciaEspinardo 30100MurciaSpain

End-stage liver disease is frequently caused by hepatitis B virus (HBV) andalcohol consumption. Notably, the mechanism by which alcohol affects the courseof HBV-associated liver disease is unknown, and additional research is needed inthis area. A reduced immunological response, oxidative stress, endoplasmicreticulum stress, Golgi apparatus stress, and enhanced HBV replication are a fewpotential causes.

关键词： Hepatitis B virus Alcohol Hepatocarcinoma Immunity Liver disease

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Changes in demand and supply of ecosystem services under scenarios of future land use in Vorarlberg, Austria

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Journal of Mountain Science 2019年第12期16卷 2793-2809页

作者： SAUTER isabel KIENAST Felix BOLLIGER Janine WINTER Benjamin PAZuR Robert Swiss Federal Research Institute WSL Zurcherstrasse 1118903 BirmensdorfSwitzerland ALPS-Centre for Climate Change Adaptation Grabenweg 686020 InnsbruckAustria Institute of Geography University of InnsbruckInnrain 526020 InnsbruckAustria Institute of Geography Slovak Academy of SciencesStefanikova 4981473 BratislavaSlovakia

Ecosystem services(ES)are highly impacted by human-induced land-use *** urbanization and agricultural land abandonment in Western Europe necessitate assessments of future land-change impacts on ES to ensure sustainable service *** present study aims at evaluating future demand and supply of three key services(flood protection,nearby recreation and biodiversity)in the mountainous region of Vorarlberg,*** mapped the ES for the referenced time step 2016 and two scenarios for 2050,assuming the continuation of current land-change trends and pressure on landscape *** for the referenced landscape in 2016 show the highest ES supply for intermediate levels,while ES supply was low in the lowlands and valley bottoms and in high-elevation *** found a high positive correlation of ES with the distribution of forested *** contrast,service demand was highest in lowelevation areas and decreased with increasing *** indicates that densely settled and intensively used agricultural areas currently suffer from ES *** projected future development of land use showed an increase in both supply and demand of the selected *** overall service supply increased more than the respective demand due to some reforestation of open *** forests were found to be important synergistic areas for overall service provision,we expect decreasing demand on related ***,demand was found to exceed the supply of ES,especially in the densely populated Rhine valley-requiring further policy *** ES-related information may contribute to regional policy making and ensure the long-term provision of ESs for future generations.

关键词： Land-use change Future land-use scenarios Regional assessment Ecosystem services Synergies Conflicts

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