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1.
Nature ; 626(7999): 529-534, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356067

RESUMO

The wealth of complex polar topologies1-10 recently found in nanoscale ferroelectrics results from a delicate balance between the intrinsic tendency of the materials to develop a homogeneous polarization and the electric and mechanical boundary conditions imposed on them. Ferroelectric-dielectric interfaces are model systems in which polarization curling originates from open circuit-like electric boundary conditions, to avoid the build-up of polarization charges through the formation of flux-closure11-14 domains that evolve into vortex-like structures at the nanoscale15-17 level. Although ferroelectricity is known to couple strongly with strain (both homogeneous18 and inhomogeneous19,20), the effect of mechanical constraints21 on thin-film nanoscale ferroelectrics has been comparatively less explored because of the relative paucity of strain patterns that can be implemented experimentally. Here we show that the stacking of freestanding ferroelectric perovskite layers with controlled twist angles provides an opportunity to tailor these topological nanostructures in a way determined by the lateral strain modulation associated with the twisting. Furthermore, we find that a peculiar pattern of polarization vortices and antivortices emerges from the flexoelectric coupling of polarization to strain gradients. This finding provides opportunities to create two-dimensional high-density vortex crystals that would enable us to explore previously unknown physical effects and functionalities.

2.
Biol Trace Elem Res ; 201(4): 1559-1566, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35486317

RESUMO

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-ß in the presence or absence of selenium, in the form of sodium selenite (2.0×10-6M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-ß. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.


Assuntos
Interleucina-10 , Selênio , Linfócitos T Reguladores/metabolismo , Selenito de Sódio/farmacologia , Selenito de Sódio/metabolismo , Antígeno CTLA-4/metabolismo , Selênio/farmacologia , Selênio/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Diferenciação Celular , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo
3.
Mol Ther Nucleic Acids ; 30: 553-568, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36457699

RESUMO

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

4.
Autoimmunity ; 55(7): 443-454, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35880661

RESUMO

The inflammasome AIM2 regulates multiple aspects of innate immune functions and serves as a critical mediator of inflammatory responses. AIM2 inflammasome activation leads to the production of pro-inflammatory cytokines, IL-1ß and IL-18 and participates triggering a pyroptosis response needed to counteract excessive cell proliferation. In addition, AIM2 expression and activation is wide regulated since alteration in its activity may derived in pathological consequences. Consequently, deregulated AIM2 activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of AIM2 inflammasome, as well as its contribution in rheumatoid arthritis and systemic lupus erythematous pathology. Finally, we highlight the participation of the AIM2-inflammasome at the level of joint in rheumatoid arthritis and at kidney in systemic lupus erythematous. The development of therapeutic strategies based on modulation of AIM2-inflammasome activity should have a tissue-specific focus.


Assuntos
Artrite Reumatoide , Proteínas de Ligação a DNA , Inflamassomos , Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-18
5.
Nat Mater ; 21(2): 188-194, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34857910

RESUMO

The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La0.7Sr0.3MnO3 combined with the superconducting cuprate YBa2Cu3O7. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.

6.
Exp Mol Pathol ; 123: 104689, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34592200

RESUMO

The aim of this study was to analyze the expression of mBD4, mBD3 and CRAMP in joint of mice with type II collagen-induced arthritis/CIA and to explore its possible association with IL-10, IL-4, IFN-γ, IL-17, MMP3, RANK/RANKL/OPG and histological parameters. METHODS: CIA was induced in 44 DBA/1 J mice. The joints from mice were classified into the onset, peak and remission phase of CIA. Histological sections were stained with hematoxylin-eosin and safranin O. The expression of CRAMP, mBD-3, mBD-4, and MMP-3 was evaluated using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of IL-10, IL-4, IFN-γ, IL-17, RANK/RANKL/OPG was analyzed by RT-PCR. RESULTS: We observed that inflammation and immunostained cells for CRAMP increased in the peak and remission phases compared to the control group. In addition, increments in relative expressions of CRAMP were detected for the remission phase and in IL-4 and IL-17 in the peak phase compared to the control and onset phase. In addition, an increase in IL-10 in a peak phase compared to the control, as well as the relative expression of IFN-γ in remission phase was higher than in the onset phase. This was accompanied by an increase in cartilage damage in the peak phase compared to the control. Cells immunostained to MMP3 increased in the peak phase compared to the onset and control group, and relative expression of MMP3 was detected in the peak phase compared to the onset, remission, and control group. We observed that the relative expression of RANK and RANKL in the peak phase was higher than in control and onset phase. Finally, the relative expression of OPG in the peak phase compared to the onset, remission, and control group was detected. Regarding CRAMP behavior in the different phases studied, it was positively correlated with IL-4 and RANK, and showed a negative correlation with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio in the control group. Also was positively correlated with IFN-γ, IL-17, IL-4, IL-10, as well as with RANK, RANKL, and OPG in the onset and peak phases of the CIA. In the peak phase, CRAMP showed a positive association with MMP3, and we observed a direct correlation between CRAMP and IFN-γ and RANKL/OPG ratio in remission phase. mBD3 correlates positively with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio, and showed a negative correlation with CRAMP, MMP3, and RANK in the control group. Also, it was directly associated with IFN-γ, IL-17, IL-4, IL-10 and RANKL in the onset phase while it was inversely associated with CRAMP, MMP-3, RANK, RANKL, and OPG in the peak phase. Finally, mBD3 was inversely correlated with MMP3 in the remission phase and was directly associated with CRAMP, IFN-γ and RANKL/OPG ratio in this phase. mBD4 was directly associated with CRAMP, IFN-γ, IL-17, IL-4, IL-10, RANKL / OPG in the onset phase, and with CRAMP, IFN-γ, IL-17, IL-4, IL-10, MMP3, RANK, RANKL and OPG in the peak phase. Finally, mBD4 was positively associated with mBD3, IFN-γ, IL-17, IL-10, RANK, RANKL OPG and RANKL/OPG in the CIA remission phase. CONCLUSIONS: Our results demonstrate that CRAMP plays an important role in CIA progress and suggest that its abundance is associated with local pro- and anti-inflammatory status. This makes us propose CRAMP as a possible contributor of bone reconstruction in the last stage of CIA.


Assuntos
Artrite/genética , Remodelação Óssea/genética , Catelicidinas/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , beta-Defensinas/genética , Animais , Artrite/induzido quimicamente , Artrite/patologia , Colágeno Tipo II/toxicidade , Regulação da Expressão Gênica/genética , Humanos , Inflamação/genética , Inflamação/patologia , Camundongos
7.
Diabetes Res Clin Pract ; 173: 108692, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33571599

RESUMO

AIM: To determine the percentages of (CD19 + CD24 + CD38+, CD19 + CD24 + CD27+, CD19 + IL-10+)-Breg cells, IL-17 single and IL-17+/IFN-γ double producers T cells and IFN-γ+ T cells, in normal-glycemic individuals, prediabetes and T2DM patients, and to analyze the association of Breg cells with metabolic parameters of T2DM. METHODS: percentages of Breg cells, IL-17+ and IL-17 + IFN-γ+ T cells, IFN-γ+ T cells and IL-10 were determined by flow cytometry. IL-6 levels were evaluated by ELISA assay. RESULTS: increased IL-6 levels, IL-17+ and IL-17 + IFN-γ+ T cells and a diminution of IL-10 levels and CD19 + IL-10+ cells in T2DM patients were observed. We found that CD19 + CD24 + CD27+ cells and CD19 + CD24 + CD38+ cells were increased in T2DM patients. The percentages of CD19 + CD24 + CD38+ cells were associated with HOMA-B, TyG index, HDL and cholesterol values. In normal-glycemic individuals, CD19 + CD24 + CD27+ cells were inversely associated to triglycerides and TyG index. In prediabetes patients, CD19 + CD24 + CD38+ cells were inversely related with cholesterol and LDL. Finally, CD19 + CD24 + CD38+ cells were inversely related with HDL values in T2DM patients. CONCLUSION: Our results suggest that increased percentages of IL-17 single and IL-17/IFN-γ double producers T cells in T2DM patients may be a consequence of the initial CD19 + IL-10+ cells reduction. Furthermore, dyslipidemia could play an important role in percentages and activity of B regulatory cells.


Assuntos
Linfócitos B Reguladores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Estado Pré-Diabético/metabolismo , Adulto , Feminino , Humanos , Masculino
8.
Sci Rep ; 10(1): 20067, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208754

RESUMO

Exposure to 17α-ethynylestradiol (EE2, 5 µg/g food) impairs some reproductive events in the protandrous gilthead seabream and a short recovery period does not allow full recovery. In this study, spermiating seabream males in the second reproductive cycle (RC) were fed a diet containing 5 or 2.5 µg EE2/g food for 28 days and then a commercial diet without EE2 for the remaining RC. Individuals were sampled at the end of the EE2 treatment and then at the end of the RC and at the beginning of the third RC, 146 and 333 days after the cessation of treatment, respectively. Increased hepatic transcript levels of the gene coding for vitellogenin (vtg) and plasma levels of Vtg indicated both concentrations of EE2 caused endocrine disruption. Modifications in the histological organization of the testis, germ cell proliferation, plasma levels of the sex steroids and pituitary expression levels of the genes coding for the gonadotropin ß-subunits, fshß and lhß were detected. The plasma levels of Vtg and most of the reproductive parameters were restored 146 days after treatments. However, although 50% of the control fish underwent sex reversal as expected at the third RC, male-to female sex change was prevented by both EE2 concentrations.


Assuntos
Etinilestradiol/farmacologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Reprodução , Espermatogênese , Transexualidade/prevenção & controle , Vitelogeninas/metabolismo , Animais , Estrogênios/farmacologia , Feminino , Proteínas de Peixes/genética , Fígado/efeitos dos fármacos , Masculino , Dourada , Testículo/efeitos dos fármacos , Transexualidade/genética , Vitelogeninas/genética
9.
Appl Surf Sci ; 529: 147100, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33154607

RESUMO

We investigate the intercalation process of oxygen in-between a PVD-grown graphene layer and different copper substrates as a methodology for reducing the substrate-layer interaction. This growth method leads to an extended defect-free graphene layer that strongly couples with the substrate. We have found, by means of X-ray photoelectron spectroscopy, that after oxygen exposure at different temperatures, ranging from 280 °C to 550 °C, oxygen intercalates at the interface of graphene grown on Cu foil at an optimal temperature of 500 °C. The low energy electron diffraction technique confirms the adsorption of an atomic oxygen adlayer on top of the Cu surface and below graphene after oxygen exposure at elevated temperature, but no oxidation of the substrate is induced. The emergence of the 2D Raman peak, quenched by the large interaction with the substrate, reveals that the intercalation process induces a structural undoing. As suggested by atomic force microscopy, the oxygen intercalation does not change significantly the surface morphology. Moreover, theoretical simulations provide further insights into the electronic and structural undoing process. This protocol opens the door to an efficient methodology to weaken the graphene-substrate interaction for a more efficient transfer to arbitrary surfaces.

10.
Phys Rev Lett ; 125(26): 266802, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33449729

RESUMO

The persistence of ferroelectricity in ultrathin layers relies critically on screening or compensation of polarization charges which otherwise destabilize the ferroelectric state. At surfaces, charged defects play a crucial role in the screening mechanism triggering novel mixed electrochemical-ferroelectric states. At interfaces, however, the coupling between ferroelectric and electrochemical states has remained unexplored. Here, we make use of the dynamic formation of the oxygen vacancy profile in the nanometer-thick barrier of a ferroelectric tunnel junction to demonstrate the interplay between electrochemical and ferroelectric degrees of freedom at an oxide interface. We fabricate ferroelectric tunnel junctions with a La_{0.7}Sr_{0.3}MnO_{3} bottom electrode and BaTiO_{3} ferroelectric barrier. We use poling strategies to promote the generation and transport of oxygen vacancies at the metallic top electrode. Generated oxygen vacancies control the stability of the ferroelectric polarization and modify its coercive fields. The ferroelectric polarization, in turn, controls the ionization of oxygen vacancies well above the limits of thermodynamic equilibrium, triggering the build up of a Schottky barrier at the interface which can be turned on and off with ferroelectric switching. This interplay between electronic and electrochemical degrees of freedom yields very large values of the electroresistance (more than 10^{6}% at low temperatures) and enables a controlled switching between clockwise and counterclockwise switching modes in the same junction (and consequently, a change of the sign of the electroresistance). The strong coupling found between electrochemical and electronic degrees of freedom sheds light on the growing debate between resistive and ferroelectric switching in ferroelectric tunnel junctions, and moreover, can be the source of novel concepts in memory devices and neuromorphic computing.

11.
Phys Med ; 66: 88-96, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31574423

RESUMO

PURPOSE: To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses. METHODS AND MATERIALS: Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking. RESULTS: Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques. CONCLUSIONS: According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed.


Assuntos
Fótons/uso terapêutico , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional , Humanos , Masculino , Probabilidade , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Tomografia Computadorizada por Raios X
12.
2d Mater ; 6(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30984408

RESUMO

We describe the reversible intercalation of Na under graphene on Ir(111) by photo-dissociation of a previously adsorbed NaCl overlayer. After room temperature evaporation, NaCl adsorbs on top of graphene forming a bilayer. With a combination of electron diffraction and photoemission techniques we demonstrate that the NaCl overlayer dissociates upon a short exposure to an X-ray beam. As a result, chlorine desorbs while sodium intercalates under the graphene, inducing an electronic decoupling from the underlying metal. Low energy electron diffraction shows the disappearance of the moiré pattern when Na intercalates between graphene and iridium. Analysis of the Na 2p core-level by X-ray photoelectron spectroscopy shows a chemical change from NaCl to metallic buried Na at the graphene/Ir interface. The intercalation-decoupling process leads to a n-doped graphene due to the charge transfer from the Na, as revealed by constant energy angle resolved X-ray photoemission maps. Moreover, the process is reversible by a mild annealing of the samples without damaging the graphene.

13.
Phys Rev Lett ; 122(3): 037601, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30735408

RESUMO

The electronic reconstruction occurring at oxide interfaces may be the source of interesting device concepts for future oxide electronics. Among oxide devices, multiferroic tunnel junctions are being actively investigated as they offer the possibility to modulate the junction current by independently controlling the switching of the magnetization of the electrodes and of the ferroelectric polarization of the barrier. In this Letter, we show that the spin reconstruction at the interfaces of a La_{0.7}Sr_{0.3}MnO_{3}/BaTiO_{3}/La_{0.7}Sr_{0.3}MnO_{3} multiferroic tunnel junction is the origin of a spin filtering functionality that can be turned on and off by reversing the ferroelectric polarization. The ferroelectrically controlled interface spin filter enables a giant electrical modulation of the tunneling magnetoresistance between values of 10% and 1000%, which could inspire device concepts in oxides-based low dissipation spintronics.

14.
Radiat Prot Dosimetry ; 185(2): 183-195, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-30649534

RESUMO

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.


Assuntos
Filtração/instrumentação , Segunda Neoplasia Primária/epidemiologia , Neoplasias/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Filtração/métodos , Humanos , Incidência , Neoplasias/classificação , Neoplasias/patologia , Segunda Neoplasia Primária/diagnóstico , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Espanha/epidemiologia
15.
Nanotechnology ; 30(6): 065606, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30523845

RESUMO

Gas-phase synthesis of nanoparticles with different structural and chemical distribution is reported using a circular magnetron sputtering in an ion cluster source by applying high-power impulses. The influence of the pulse characteristics on the final deposit was evaluated on Au nanoparticles. The results have been compared with the more common direct current approach. In addition, it is shown for the first time that high-power impulses in magnetron based gas aggregation sources allows the growth of binary nanoparticles, CoAu in this case, with a variety of crystalline and chemical arrangements which are analyzed at the atomic level.

16.
Mol Biochem Parasitol ; 225: 73-83, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30179636

RESUMO

Helminths are complex pathogens that ensure their long-term survival by influencing the immune responses of their host. Excretory/secretory products (ESP) can exert immunoregulatory effects which foster parasite survival. Galectins represent a widespread group of ß-galactoside-binding proteins which are involved in a multitude of biological processes operative in parasite-host interaction. We had earlier identified seven galectins in Strongyloides ratti, four of them detected in the ESP of distinct developmental stages of the parasite. In the present report, we focused on the characterization of two of them, Sr-galectin-1 (Sr-Gal-1) and Sr-galectin-3 (Sr-Gal-3). While Sr-Gal-3 expression was strongest in parasitic females, Sr-Gal-1 was predominantly expressed in free-living females. Both proteins were cloned and recombinantly expressed in an E. coli expression system. Their glycan-binding activity was verified by haemagglutination and glycan array analysis. Furthermore, primary immunological activities of the Sr-galectins were initially investigated by the application of an in vitro mucosal 3D-culture model, comprising of mucosa-associated epithelial and dendritic cells. The Sr-galectins stimulated preferentially the release of the type 2 cytokines thymic stromal lymphopoietin and IL-22, a first indication for immunoregulatory activity. In addition, the Sr-galectins dose-dependently fostered cell migration. Our results confirm the importance of these carbohydrate-binding proteins in host-parasite-interaction by indicating possible interaction with the host mucosa-associated cells.


Assuntos
Galectinas/metabolismo , Intestinos/parasitologia , Polissacarídeos/metabolismo , Strongyloides ratti/metabolismo , Animais , Clonagem Molecular , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Galectinas/genética , Expressão Gênica , Perfilação da Expressão Gênica , Hemaglutinação , Masculino , Ligação Proteica , Ratos Wistar , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Strongyloides ratti/genética
17.
Obes Res Clin Pract ; 12(6): 513-519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30115554

RESUMO

STATEMENTS OF THE PROBLEM: Regulatory B (Breg) cells have a critical role in adipose tissue homeostasis, and although subtypes of Breg cells have been described, their contribution during obesity is unclear. Therefore, the levels of regulatory B cells in adipose tissue and peripheral blood samples drawn from individuals with overweight, obesity, and normal-weight were evaluated. METHODS: The percentages of Breg cells were analyzed by flow cytometry. The activity of Breg cells was assessed by measuring the release of IFN-γ in the supernatants of co-cultures of CD4+ T and regulatory B cells with an ELISA assay. The levels of IL-17 and IFN-γ produced by the CD4+ T cells were assessed using an ELISA assay. RESULTS: Diminished frequencies of Breg cells with phenotypes CD19+CD27+CD38High, CD19+CD24HighCD38High, and CD19+CD24HighCD38HighIL-10+ cells were observed in the blood samples from the individuals with overweight and obesity but not in the individuals with normal-weight. The production of IFN-γ in CD4+ T-cell cultures showed a decrease in the presence of Breg cells in individuals with obesity and normal-weight. We found fewer percentages of CD19+CD27+CD38High cells in the adipose tissue samples from individuals with overweight and obesity compared to individuals with normal-weight. In addition, elevated levels of IL-17 and IFN-γ in the supernatants of the cultures of CD4+ T cells from the individuals with obesity compared to the individuals with normal-weight were observed. CONCLUSIONS: The results suggest that individuals with obesity show increased levels of Th1/Th17 cytokines, which might be caused by the decreased frequency of regulatory B cells.


Assuntos
Tecido Adiposo/patologia , Linfócitos B Reguladores/patologia , Obesidade/patologia , Sobrepeso/patologia , Tecido Adiposo/metabolismo , Adulto , Linfócitos B Reguladores/metabolismo , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Contagem de Linfócitos , Masculino , Obesidade/sangue , Sobrepeso/sangue , Adulto Jovem
18.
Int J Biochem Cell Biol ; 100: 42-48, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29729889

RESUMO

Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMI < 25 kg/m2 (BMI < 25) and BMI ≥ 25 kg/m2 (BMI ≥ 25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMI ≥ 25 compared to BMI < 25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue.


Assuntos
Tecido Adiposo/metabolismo , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Receptor A2A de Adenosina/metabolismo , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino
19.
J Steroid Biochem Mol Biol ; 174: 48-55, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28739284

RESUMO

In teleosts, spermatogenesis is regulated by pituitary gonadotropins and sex steroids. 5α-dihydrotestosterone (DHT), derived from testosterone (T) through the action of 5α-reductase, has recently been suggested to play a physiologically important role in some fish species. In this study, gilthead seabream, Sparus aurata L., males received an implant of 1µgT/g body mass (bm) or vehicle alone and, 7days later, 1mg finasteride (FIN, an inhibitor of 5α-reductase)/kg bm or vehicle. Serum levels of T, 11-ketotestosterone (11KT), DHT and 17ß-estradiol (E2), and the mRNA levels of the main enzymes involved in their synthesis, were analysed. T promoted a transient increase in the serum levels of T, 11KT and E2 but a decrease in those of DHT at day 15 following T injection, in accordance with the up-regulation of mRNA levels of the enzymes involved in T transformation to 11KT (coding genes: cyp11b1 and hsd11b) and the down-regulation of mRNA levels of the enzyme responsible for T transformation to DHT (coding gene: srd5a). Interestingly, a similar effect was observed when FIN was injected. However, when fish were injected with T and FIN successively (T+FIN), control levels were not recovered at the end of the experimental period (28days). DHT seems to regulate E2 serum levels via the down-regulation of mRNA levels of aromatase (coding gene: cyp19a1a), which is needed for the transformation of T into E2. The testis histology, together with the proliferative rates recorded upon T, FIN or T+FIN treatment, suggests that DHT is involved in the onset of the meiotic phase of spermatogenesis.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Inibidores de 5-alfa Redutase/farmacologia , Androgênios/farmacologia , Di-Hidrotestosterona/sangue , Finasterida/farmacologia , Testosterona/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Androgênios/sangue , Animais , Aromatase/genética , Estradiol/sangue , Proteínas de Peixes/genética , Masculino , Dourada , Esteroide 11-beta-Hidroxilase/genética , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testosterona/análogos & derivados , Testosterona/sangue
20.
J Hazard Mater ; 340: 281-290, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28715751

RESUMO

Novel ternary ZnO/Fe3O4-sepiolite nanostructured materials were developed in a two-step procedure based on the incorporation of ZnO nanoparticles on a substrate composed by magnetite nanoparticles previously assembled to the sepiolite fibrous silicate (Fe3O4-sepiolite). The structural and morphological characterization shows that both, ZnO and Fe3O4 nanoparticles, were homogeneously dispersed on the surface of sepiolite. Therefore, the resulting material is characterized as a multifunctional nanoplatform simultaneously providing magnetic and photoactive properties. ZnO/Fe3O4-sepiolite materials exhibit superparamagnetic properties at room temperature, which is one of the sought properties in view to facilitate their recovery from the reaction medium after application as heterogeneous catalysts. ZnO/Fe3O4-sepiolite materials were tested as photocatalysts using methylene blue dye in water as model of a pollutant molecule, showing full decolorization after 2h of UV irradiation. Moreover, the photocatalytic activity of this nanoplataform may be maintained after reuse in several consecutive cycles of treatment. Remarkably, the ZnO/magnetite-sepiolite nanostructured material displays a similar activity as ZnO/sepiolite materials, but shows the additional advantage of easier recovery by means of a magnet which facilitates its reuse.

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