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1.
ACS Appl Mater Interfaces ; 15(51): 59731-59745, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38091526

RESUMO

A novel biobased pickering emulsion (PE) material was prepared by the encapsulation of Cyanex 923 (Cy923) into chitosan (CS) to selectively recover rare earth elements (REEs) from the aqueous phase. The preparation of PE was optimized through sequentially applying a 23 full factorial design, followed by a 33 Box-Behnken design varying the Cy923 content, CS concentration, and pH of CS. The material was characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), optical microscopy, rheological, compositional, and stability measurements. The resultant material was evaluated in the removal of yttrium by pH influence, nitrate concentration, kinetics, equilibrium isotherms, reusability, and a comparison with liquid-liquid (L-L) extraction and tested in a real scenario to extract Y from a fluorescent lamp powder waste. In addition, the selectivity of PE for REE was investigated with Y/Ca, Gd/Ca, and La/Ni systems. PE extracts REE at 1 ≤ pH ≤ 5 at nitrate concentrations up to 2 mol/L. The kinetics and equilibrium studies showed reaction times <5 min and a maximum sorption capacity of 89.98 mg/g. Compared with L-L extraction, PE consumed 48% less Cy923 without using organic diluents. PE showed a remarkable selectivity for REE in the systems evaluated, showing separation factors of 22.62, 9.35, and 504.64 for the blends Y/Ca, Gd/Ca/Mg, and La/Ni, respectively. PE showed excellent selectivity extracting Y from a real aqueous liquor from the fluorescent lamp powder. PE demonstrates to be an effective and sustainable alternative for REE recovering due to its excellent efficiency in harsh conditions, favorable green chemistry metrics, and use of a biopolymer material in its composition avoiding the use of organic solvents used in L-L extraction.

2.
ACS Sustain Chem Eng ; 11(44): 15975-15983, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37969885

RESUMO

This article investigates the economic and environmental implications of implementing green ammonia production plants in Spain. To this end, one business-as-usual scenario for gray ammonia production was compared with three green ammonia scenarios powered with different renewable energy sources (i.e., solar photovoltaic (PV), wind, and a combination of solar PV and wind). The results illustrated that green ammonia scenarios reduced the environmental impacts in global warming, stratospheric ozone depletion, and fossil resource scarcity when compared with conventional gray ammonia scenario. Conversely, green ammonia implementation increased the environmental impacts in the categories of land use, mineral resource scarcity, freshwater eutrophication, and terrestrial acidification. The techno-economic analysis revealed that the conventional gray ammonia scenario featured lower costs than green ammonia scenarios when considering a moderate natural gas cost. However, green ammonia implementation became the most economically favorable option when the natural gas cost and carbon prices increased. Finally, the results showed that developing efficient ammonia-fueled systems is important to make green ammonia a relevant energy vector when considering the entire supply chain (production/transportation). Overall, the results of this research demonstrate that green ammonia could play an important role in future decarbonization scenarios.

3.
J Pediatr Surg ; 58(11): 2149-2155, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37286413

RESUMO

AIM: Sarcopenia is associated with poor prognosis in adult oncologic patients, with little evidence of this association in pediatric population, including hepatoblastoma. METHODS: Retrospective study in patients with hepatoblastoma, divided into those with or without sarcopenia. Sarcopenia was assessed by measuring psoas muscle area (PMA) at L4-L5 level on the CT/MR and defined as z-score values ≤ 2. Relapse and mortality were analyzed. RESULTS: Twenty-one patients (57.1% male) were included, with median age 35.7 months (IQR: 23.5-58.5). Seven (33.3%) had sarcopenia on initial studies compared to 14 (66.7%) who did not. No differences were found between groups in age, weight, PRETEXT, surgical treatment or. α-fetoprotein levels. Sarcopenia was associated with a higher rate of metastases at diagnosis (49.2% vs 0.0%; p = 0.026) and surgical complications (57.1% vs 21.4%, p = 0.047). After a median follow-up of 65.1 months (1.7-144.8), 2 patients (28.6%) had tumor relapse in sarcopenic group compared to 1 (7.1%) in non-sarcopenic group. Two patients died in sarcopenic group and 1 in non-sarcopenic group. Median event-free survival (EFS) was lower in sarcopenic group (100.38 ± 25.63 vs 118.91 ± 11.52 months) as well as overall survival (OS) (101.72 ± 24.86 vs 121.78 ± 8.75 months) with no statistical significance. Five-year EFS was also lower in sarcopenic group (71% vs 93%) as well as 5-year OS (71% vs 87%). CONCLUSIONS: Sarcopenia at diagnosis was associated with a higher rate of metastases and surgical complications in hepatoblastoma. Our data shows the first evidence of its role as a possible poor prognostic factor, influencing survival and risk of relapse. LEVEL OF EVIDENCE: II. TYPE OF STUDY: Original article. Retrospective study.

4.
Polymers (Basel) ; 15(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37050279

RESUMO

Neodymium (Nd) is a key rare earth element (REE) needed for the future of incoming technologies including road transport and power generation. Hereby, a sustainable adsorbent material for recovering Nd from the aqueous phase using a residue from the saccharification process is presented. Banana rachis (BR) was treated with cellulases and polyethylene glycol (PEG) to produce fermentable sugars prior to applying the final residue (BR-PEG) as an adsorbent material. BR-PEG was characterized by scanning electron microscopy (SEM), compositional analysis, pH of zero charge (pHpzc), Fourier transform infrared analysis (FTIR) and thermogravimetric analysis (TGA). A surface response experimental design was used for obtaining the optimized adsorption conditions in terms of the pH of the aqueous phase and the particle size. With the optimal conditions, equilibrium isotherms, kinetics and adsorption-desorption cycles were performed. The optimal pH and particle size were 4.5 and 209.19 µm, respectively. BR-PEG presented equilibrium kinetics after 20 min and maximum adsorption capacities of 44.11 mg/g. In terms of reusage, BR-PEG can be efficiently reused for five adsorption-desorption cycles. BR-PEG was demonstrated to be a low-cost bioresourced alternative for recovering Nd by adsorption.

5.
Lancet ; 400(10362): 1513-1521, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36522207

RESUMO

BACKGROUND: Internationally, a single standard chemotherapy treatment for Ewing sarcoma is not defined. Because different chemotherapy regimens were standard in Europe and the USA for newly diagnosed Ewing sarcoma, and in the absence of novel agents to investigate, we aimed to compare these two strategies. METHODS: EURO EWING 2012 was a European investigator-initiated, open-label, randomised, controlled phase 3 trial done in 10 countries. We included patients aged 2-49 years, with any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or Ewing-like sarcomas. The eligibility criteria originally excluded patients with extrapulmonary metastatic disease, but this was amended in the protocol (version 3.0) in September, 2016. Patients were randomly assigned (1:1) to either the European regimen of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, with ifosfamide or cyclophosphamide, or busulfan and melphalan (group 1); or the US regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and cyclophosphamide, or vincristine, actinomycin D, and ifosfamide, with busulfan and melphalan (group 2). All drugs were administered intravenously. The primary outcome measure was event-free survival. We used a Bayesian approach for the design, analysis, and interpretation of the results. Patients who received at least one dose of study treatment were considered in the safety analysis. The trial was registered with EudraCT, 2012-002107-17, and ISRCTN, 54540667. FINDINGS: Between March 21, 2014, and May 1, 2019, 640 patients were entered into EE2012, 320 (50%) randomly allocated to each group. Median follow-up of surviving patients was 47 months (range 0-84). Event-free survival at 3 years was 61% with group 1 and 67% with group 2 (adjusted hazard ratio [HR] 0·71 [95% credible interval 0·55-0·92 in favour of group 1). The probability that the true HR was less than 1·0 was greater than 0·99. Febrile neutropenia as a grade 3-5 treatment toxicity occurred in 234 (74%) patients in group 1 and in 183 (58%) patients in group 2. More patients in group 1 (n=205 [64%]) required at least one platelet transfusion compared with those in group 2 (n=138 [43%]). Conversely, more patients required blood transfusions in group 2 (n=286 [89%]) than in group 1 (n=277 [87%]). INTERPRETATION: Dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma. FUNDING: The European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration; The National Coordinating Centre in France, Centre Léon Bérard; SFCE; Ligue contre le cancer; Cancer Research UK.


Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/etiologia , Sarcoma de Ewing/patologia , Ifosfamida/efeitos adversos , Etoposídeo , Vincristina , Dactinomicina/efeitos adversos , Bussulfano/uso terapêutico , Melfalan/efeitos adversos , Teorema de Bayes , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Doxorrubicina , Intervalo Livre de Doença
6.
Cell Rep ; 41(10): 111761, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36476851

RESUMO

Ewing sarcoma (EwS) is characterized by EWSR1-ETS fusion transcription factors converting polymorphic GGAA microsatellites (mSats) into potent neo-enhancers. Although the paucity of additional mutations makes EwS a genuine model to study principles of cooperation between dominant fusion oncogenes and neo-enhancers, this is impeded by the limited number of well-characterized models. Here we present the Ewing Sarcoma Cell Line Atlas (ESCLA), comprising whole-genome, DNA methylation, transcriptome, proteome, and chromatin immunoprecipitation sequencing (ChIP-seq) data of 18 cell lines with inducible EWSR1-ETS knockdown. The ESCLA shows hundreds of EWSR1-ETS-targets, the nature of EWSR1-ETS-preferred GGAA mSats, and putative indirect modes of EWSR1-ETS-mediated gene regulation, converging in the duality of a specific but plastic EwS signature. We identify heterogeneously regulated EWSR1-ETS-targets as potential prognostic EwS biomarkers. Our freely available ESCLA (http://r2platform.com/escla/) is a rich resource for EwS research and highlights the power of comprehensive datasets to unravel principles of heterogeneous gene regulation by chimeric transcription factors.


Assuntos
Sarcoma de Ewing , Humanos , Sarcoma de Ewing/genética , Multiômica , Oncogenes , Linhagem Celular , Fatores de Transcrição
7.
Int J Mol Sci ; 23(15)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35955799

RESUMO

Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.


Assuntos
Neoplasias Ósseas , Endoglina/metabolismo , Sarcoma de Ewing , Neoplasias Ósseas/genética , Endoglina/genética , Humanos , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Proteômica , Receptores de Fatores de Crescimento , Sarcoma de Ewing/patologia , Transdução de Sinais
8.
Br J Clin Pharmacol ; 88(9): 4220-4223, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35491467

RESUMO

It is not clear if platelet responses are sustained after thrombopoietin receptor agonist (ar-TPO) withdrawal in paediatric patients. A multicentre retrospective observational study was performed in children with chronic immune thrombopenia (cITP) to describe ar-TPO tapering and withdrawal in patients who had achieved a sustained complete response to ar-TPOs. Ten patients (eltrombopag n = 6, romiplostim n = 4) were included. Treatment withdrawal was performed after a mean tapering time of 7.6 months. Two patients relapsed (median follow-up time of 24 months). Slow tapering and withdrawal of ar-TPOs can be safely performed in cITP paediatric patients after achieving a sustained complete response.


Assuntos
Fármacos Hematológicos , Púrpura Trombocitopênica Idiopática , Receptores de Trombopoetina , Benzoatos/uso terapêutico , Plaquetas , Criança , Fármacos Hematológicos/uso terapêutico , Humanos , Hidrazinas/uso terapêutico , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico
9.
Nat Commun ; 12(1): 5356, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531368

RESUMO

Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably 'silent' genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or its activating polo-like kinase 1 (PLK1) can be employed to induce fatal genomic instability and tumor regression. We find that the EwS-specific oncogenic transcription factor EWSR1-FLI1 hijacks PRC1, which physiologically safeguards controlled cell division, through binding to a proximal enhancer-like GGAA-microsatellite, thereby promoting tumor growth and poor clinical outcome. Via integration of transcriptome-profiling and functional in vitro and in vivo experiments including CRISPR-mediated enhancer editing, we discover that high PRC1 expression creates a therapeutic vulnerability toward PLK1 inhibition that can repress even chemo-resistant EwS cells by triggering mitotic catastrophe.Collectively, our results exemplify how aberrant PRC1 activation by a dominant oncogene can confer malignancy but provide opportunities for targeted therapy, and identify PRC1 expression as an important determinant to predict the efficacy of PLK1 inhibitors being used in clinical trials.


Assuntos
Apoptose/genética , Proteínas de Ciclo Celular/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Sarcoma de Ewing/genética , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Criança , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Estimativa de Kaplan-Meier , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Terapêutica com RNAi/métodos , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/terapia , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
11.
Sci Rep ; 11(1): 9096, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907274

RESUMO

Notch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of ß-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise ß-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters ß-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit ß-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.


Assuntos
Receptores Notch/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Núcleo Celular/metabolismo , Células HCT116 , Células HEK293 , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptores Notch/genética , Transcrição Gênica , beta Catenina/genética , Proteínas rab5 de Ligação ao GTP/metabolismo
12.
Eur J Immunol ; 51(5): 1182-1194, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33521935

RESUMO

Stringent regulation of the inflammatory response is crucial for normal tissue regeneration. Here, we analyzed the role of Toll-like receptor 3 (TLR3) in pancreatic regeneration after acute pancreatitis (AP). AP was induced by caerulein treatment in mice with global TLR3 deficiency (TLR3OFF ) or in mice re-expressing TLR3 exclusively in the myeloid cell lineage (TLR3Mye ). Compared to WT mice, TLR3OFF mice had a markedly increased formation of acinar-to-ductal metaplasia (ADM) that persisted until day 7 after initiation of AP. Pancreatic tissue of WT mice was completely regenerated after 5 days with no detectable ADM structures. The enhancing effect of TLR3-deficiency on ADM formation was closely linked with an increased and prolonged accumulation of macrophages in pancreata of TLR3OFF mice. Importantly, the phenotype of TLR3OFF mice was rescued in TLR3Mye mice, demonstrating the causative role of myeloid cell selective TLR3 signaling. Moreover, in vitro stimulation of macrophages through TLR3 initiated cell death by a caspase-8-associated mechanism. Therefore, these findings provide evidence that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after AP. Notably, resolution of inflammation after AP was associated with macrophage sensitivity to TLR3-mediated cell death.


Assuntos
Expressão Gênica , Células Mieloides/metabolismo , Pancreatite/genética , Pancreatite/metabolismo , Receptor 3 Toll-Like/genética , Doença Aguda , Animais , Biomarcadores , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Células Mieloides/imunologia , Pancreatite/imunologia , Pancreatite/patologia , Regeneração/genética , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo
13.
Epigenomics ; 12(22): 1949-1955, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33245684

RESUMO

Aim: To determine the role of single nucleotide polymorphisms (SNPs) in noncoding RNAs in childhood acute lymphoblastic leukemia (ALL) subtypes. Materials & methods: We screened all SNPs in 130 pre-miRNA genes to assess their role in the susceptibility of the most common subtypes of ALL: hyperdiploid and ETV6-RUNX1. Results: In two independent cohorts, we found a significant association between rs10406069 in miR-5196 and the risk of developing hyperdiploid ALL. This observation could be explained by the impact of the SNP on miR-5196 expression and in turn, in its target genes. Indeed, rs10406069 was associated with expression changes in SMC1A, a gene involved in sister chromatin cohesion. Conclusion: rs10406069 in miR-5196 may have a relevant role in hyperdiploid ALL risk.


Assuntos
MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Pré-Escolar , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core , Diploide , Feminino , Regulação Leucêmica da Expressão Gênica , Técnicas de Genotipagem , Humanos , Lactente , Masculino , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética
14.
Sci Rep ; 10(1): 9654, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541781

RESUMO

Several studies have shown that over 70 different microRNAs are aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC), affecting proliferation, apoptosis, metabolism, EMT and metastasis. The most important genetic alterations driving PDAC are a constitutive active mutation of the oncogene Kras and loss of function of the tumour suppressor Tp53 gene. Since the MicroRNA 34a (Mir34a) is a direct target of Tp53 it may critically contribute to the suppression of PDAC. Mir34a is epigenetically silenced in numerous cancers, including PDAC, where Mir34a down-regulation has been associated with poor patient prognosis. To determine whether Mir34a represents a suppressor of PDAC formation we generated an in vivo PDAC-mouse model harbouring pancreas-specific loss of Mir34a (KrasG12D; Mir34aΔ/Δ). Histological analysis of KrasG12D; Mir34aΔ/Δ mice revealed an accelerated formation of pre-neoplastic lesions and a faster PDAC development, compared to KrasG12D controls. Here we show that the accelerated phenotype is driven by an early up-regulation of the pro-inflammatory cytokines TNFA and IL6 in normal acinar cells and accompanied by the recruitment of immune cells. Our results imply that Mir34a restrains PDAC development by modulating the immune microenvironment of PDAC, thus defining Mir34a restauration as a potential therapeutic strategy for inhibition of PDAC development.


Assuntos
Carcinoma Ductal Pancreático/patologia , Regulação para Baixo , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Animais , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Interleucina-6/metabolismo , Camundongos , Neoplasias Pancreáticas/genética , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de RNA , Fator de Necrose Tumoral alfa/metabolismo
15.
Nanomaterials (Basel) ; 10(6)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575636

RESUMO

Neodymium is a key rare-earth element applied to modern devices. The purpose of this study is the development of a hybrid biomaterial based on chitosan (CS) and manganese ferrite (MF) for the recovery of Nd(III) ions from the aqueous phase. The preparation of the beads was performed in two stages; first, MF particles were obtained by the assessment of three temperatures during the co-precipitation synthesis, and the best nano-MF crystallites were incorporated into CS to obtain the hybrid composite material (CS-MF). The materials were characterized by FTIR, XRD, magnetization measurements, and SEM-EDX. The adsorption experiments included pH study, equilibrium study, kinetics study, and sorption-desorption reusability tests. The results showed that for MF synthesis, 60 °C is an appropriate temperature to obtain MF crystals of ~30 nm with suitable magnetic properties. The final magnetic CS-MF beads perform maximum adsorption at pH 4 with a maximum adsorption capacity of 44.29 mg/g. Moreover, the material can be used for up to four adsorption-desorption cycles. The incorporation of MF improves the sorption capacity of the neat chitosan. Additionally, the magnetic properties enable its easy separation from aqueous solutions for further use. The material obtained represents an enhanced magnetic hybrid adsorbent that can be applied to recover Nd(III) from aqueous solutions.

16.
JCI Insight ; 5(10)2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32434991

RESUMO

Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3ß, as well as YAP1 and phosphorylated ß-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/ß-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients.


Assuntos
Neoplasias Experimentais/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteína Neuronal da Síndrome de Wiskott-Aldrich/deficiência , Animais , Humanos , Camundongos , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Neuronal da Síndrome de Wiskott-Aldrich/metabolismo
17.
Environ Pollut ; 264: 114409, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32387997

RESUMO

Rare earth elements (REE) present multiple applications in technological devices but also drawbacks (scarcity and water contaminant). The current study aims to valorise the banana wastes - banana rachis (BR), banana pseudo-stem (BPS) and banana peel (BP) as sustainable adsorbent materials for the recovery of REE (Nd3+, Eu3+, Y3+, Dy3+ and Tb3+). The adsorbent materials were characterized using analytical techniques such as: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential and scanning electron microscopy with energy dispersive X-ray probe. The adsorption performance and mechanisms were studied by pH dependence, equilibrium isotherms, kinetics, thermodynamics, ion-exchange and desorption evaluation. The results show good adsorption capacities for the three materials, highlighting BR that presents ∼100 mg/g for most of the REE. The adsorption process (100 mg REE/L) reaches the 60% uptake in 8 min and the equilibrium within 50 min. On the other hand, the thermodynamic study indicates that the adsorption is spontaneous and exothermic (ΔH° < 40 kJ/mol). The adsorption mechanism is based on the presence of carboxylic groups that induce electrostatic interactions and facilitate the surface nucleation of REE microcrystals coupled to an ion exchange process as well as the presence of other oxygen containing groups that establish weak intermolecular forces. The recovery of REE from the adsorbent (∼97%) is achieved using EDTA as desorbing solution. This research indicates that banana waste and particularly BR is a new and promising renewable bioresource to recover REE with high adsorption capacity and moderated processing cost.


Assuntos
Musa , Poluentes Químicos da Água/análise , Adsorção , Biomassa , Concentração de Íons de Hidrogênio , Cinética , Lignina , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
18.
Gastroenterology ; 159(2): 575-590, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32325086

RESUMO

BACKGROUND & AIMS: Studies are needed to determine the mechanism by which Barrett's esophagus (BE) progresses to esophageal adenocarcinoma (EAC). Notch signaling maintains stem cells in the gastrointestinal tract and is dysregulated during carcinogenesis. We explored the relationship between Notch signaling and goblet cell maturation, a feature of BE, during EAC pathogenesis. METHODS: We measured goblet cell density and levels of Notch messenger RNAs in BE tissues from 164 patients, with and without dysplasia or EAC, enrolled in a multicenter study. We analyzed the effects of conditional expression of an activated form of NOTCH2 (pL2.Lgr5.N2IC), conditional deletion of NOTCH2 (pL2.Lgr5.N2fl/fl), or loss of nuclear factor κB (NF-κB) (pL2.Lgr5.p65fl/fl), in Lgr5+ (progenitor) cells in L2-IL1B mice (which overexpress interleukin 1 beta in esophagus and squamous forestomach and are used as a model of BE). We collected esophageal and stomach tissues and performed histology, immunohistochemistry, flow cytometry, transcriptome, and real-time polymerase chain reaction analyses. Cardia and forestomach tissues from mice were cultured as organoids and incubated with inhibitors of Notch or NF-kB. RESULTS: Progression of BE to EAC was associated with a significant reduction in goblet cell density comparing nondysplastic regions of tissues from patients; there was an inverse correlation between goblet cell density and levels of NOTCH3 and JAG2 messenger RNA. In mice, expression of the activated intracellular form of NOTCH2 in Lgr5+ cells reduced goblet-like cell maturation, increased crypt fission, and accelerated the development of tumors in the squamocolumnar junction. Mice with deletion of NOTCH2 from Lgr5+ cells had increased maturation of goblet-like cells, reduced crypt fission, and developed fewer tumors. Esophageal tissues from in pL2.Lgr5.N2IC mice had increased levels of RelA (which encodes the p65 unit of NF-κB) compared to tissues from L2-IL1B mice, and we found evidence of increased NF-κB activity in Lgr5+ cells. Esophageal tissues from pL2.Lgr5.p65fl/fl mice had lower inflammation and metaplasia scores than pL2.Lgr5.N2IC mice. In organoids derived from pL2-IL1B mice, the NF-κB inhibitor JSH-23 reduced cell survival and proliferation. CONCLUSIONS: Notch signaling contributes to activation of NF-κB and regulates differentiation of gastric cardia progenitor cells in a mouse model of BE. In human esophageal tissues, progression of BE to EAC was associated with reduced goblet cell density and increased levels of Notch expression. Strategies to block this pathway might be developed to prevent EAC in patients with BE.


Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Carcinogênese/patologia , Neoplasias Esofágicas/patologia , Células Caliciformes/patologia , Receptores Notch/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Idoso , Animais , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/genética , Biópsia , Carcinogênese/genética , Diferenciação Celular/genética , Estudos Transversais , Modelos Animais de Doenças , Progressão da Doença , Mucosa Esofágica/citologia , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Esofagoscopia , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/patologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Estudos Prospectivos , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Receptores Notch/genética , Transdução de Sinais
19.
Int J Biol Macromol ; 154: 937-953, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32194123

RESUMO

In this research paper, the utilization of the magnetic calcium alginate/carboxymethyl chitosan/Ni0.2Zn0.2Fe2.6O4 (CA/CMC/Ni0.2Zn0.2Fe2.6O4) was investigated for the simultaneous aqueous adsorption of Nd (III), Tb (III), and Dy (III). The magnetic products were characterized by FE-SEM, EDX, XRD, FT-IR, TGA, and VSM techniques. The saturation magnetization value for Ni0.2Zn0.2Fe2.6O4 and CA/CMC/Ni0.2Zn0.2Fe2.6O4 was found to be 45.87 and 14.14 emu/g, respectively. Using RSM, a quadratic polynomial equation was obtained to predict the adsorption efficiency of each ion. Under the conditions of pH = 5.5, adsorbent dosage of 0.1 g, initial concentration of 30 mg/L, and contact time of 53 min predicted by RSM, the adsorption efficiencies of Nd (III), Tb (III), and Dy (III) were respectively 95.72, 96.17, and 99.44%. The isotherm and kinetic data were respectively fitted well with Freundlich and pseudo-second-order (PSO) models. The desorption of the loaded ions was effectively carried out by 0.2 M HNO3, and the adsorbent was consecutively utilized with 2.54, 1.63, and 1.16% decrease in adsorption efficiency for Nd (III), Tb (III), and Dy (III), respectively, after the forth cycle. Additionally, the adsorption behavior of the CA/CMC/Ni0.2Zn0.2Fe2.6O4 towards Nd (III), Tb (III), and Dy (III) was studied by using a fixed-bed column technique.


Assuntos
Alginatos/química , Quitosana/análogos & derivados , Nanopartículas de Magnetita/química , Metais Terras Raras/química , Adsorção , Quitosana/química , Cinética , Nanoporos , Pós/química , Purificação da Água
20.
Molecules ; 25(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168823

RESUMO

Removal of heavy metals from wastewater is mandatory in order to avoid water pollution of natural reservoirs. In the present study, layered double hydroxide (LDH) materials were evaluated for removal of zinc from aqueous solutions. Materials thus prepared were impregnated with cyanex 272 using the dry method. These materials were characterized through X-ray diffraction (XRD), Fourier transform infrared (FTIR), and thermal analysis. Batch shaking adsorption experiments were performed in order to examine contact time and extraction capacity in the removal process. Results showed that the equilibrium time of Zn (II) extraction is about 4 h for Mg2Al-CO3 and Mg2Al-CO3-cyanex 272, 6 h for Zn2Al-CO3, and 24 h for Zn2Al-CO3-cyanex 272. The experimental equilibrium data were tested for Langmuir, and Freundlich isotherm models. Correlation coefficients indicate that experimental results are in a good agreement with Langmuir's model for zinc ions. Pseudo-first, second-order, Elovich, and intraparticular kinetic models were used to describe kinetic data. It was determined that removal of Zn2+ was well-fitted by a second-order reaction kinetic. A maximum capacity of 280 mg/g was obtained by Zn2Al-CO3-cyanex 272.


Assuntos
Hidróxidos/química , Ácidos Fosfínicos/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Zinco/isolamento & purificação , Adsorção , Humanos , Cinética , Modelos Estatísticos , Águas Residuárias/química
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