Publications by authors named "P Silva"

3,901 Publications

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The miR-200-Zeb1 axis regulates key aspects of β-cell function and survival in vivo.

Mol Metab 2021 Jun 8:101267. Epub 2021 Jun 8.

Institute of Molecular Health Sciences (IMHS), ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland; Competence Center Personalized Medicine, ETH Zurich, Voltastrasse 24, 8044 Zurich, Switzerland; Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. Electronic address:

Objective: The miR-200-Zeb1 axis regulates the epithelial-to-mesenchymal transition (EMT), differentiation, and resistance to apoptosis. A better understanding of these processes in diabetes is highly relevant as β-cell dedifferentiation and apoptosis contribute to loss of functional β-cell mass and diabetes progression, while EMT promotes loss of β-cell identity in in vitro expansion of human islets. While the miR-200 family has previously been identified as a regulator of β-cell apoptosis in vivo, studies focusing on Zeb1 are lacking. The aim of this study was thus to investigate the role of Zeb1 in β-cell function and survival in vivo.

Methods: miR-200 and Zeb1 are involved in a double-negative feedback loop. We characterized a mouse model in which miR-200 binding sites in the Zeb1 3'UTR are mutated (Zeb1), leading to a physiologically relevant upregulation of Zeb1 mRNA expression. The role of Zeb1 was investigated in this model via metabolic tests and analysis of isolated islets. Further insights into the distinct contributions of the miR-200 and Zeb1 branches of the feedback loop were obtained by crossing the Zeb1 allele into a background of miR-141∼200c overexpression.

Results: Mild Zeb1 derepression in vivo led to broad transcriptional changes in islets affecting β-cell identity, EMT, insulin secretion, cell-cell junctions, the unfolded protein response (UPR), and the response to ER stress. Aggregation and insulin secretion of dissociated islets of mice homozygous for the Zeb1 mutation (Zeb1) were impaired, and Zeb1 islets were resistant to thapsigargin-induced ER stress ex vivo. Zeb1 mice had increased circulating proinsulin levels but no overt metabolic phenotype, reflecting the strong compensatory ability of islets in maintaining glucose homeostasis.

Conclusions: This study points to the importance of the miR-200-Zeb1 axis in regulating key aspects of β-cell function and survival. A better understanding of this axis is highly relevant in developing therapeutic strategies for inducing β-cell redifferentiation, as well as maintaining β-cell identity in in vitro islet expansion.
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http://dx.doi.org/10.1016/j.molmet.2021.101267DOI Listing
June 2021

A Physiological behavior and tolerance of Lactuca sativa to lead nitrate and silver nitrate heavy metals.

Braz J Biol 2021 4;82:e237604. Epub 2021 Jun 4.

Centro Universitário Cesmac, Programa de Pós-graduação em Análise de Sistemas Ambientais, Maceió, AL. Brasil.

This study goal to evaluate the effects of different concentrations of lead (Pb) and silver (Ag) on germination, initial growth and anatomical alterations of Lactuca sativa L. Plants use various mechanisms to reduce the impacts caused by anthropic action, such as xenobiotic elements of soils and water contaminated by heavy metals. These metals were supplied as lead nitrate and silver nitrate and the following treatments were established: control for both metals, maximum dose of heavy metals, for arable soils, allowed by the National Council of the Environment (Ag = 25 mg. Kg-1, Pb = 180 mg. Kg-1), double (Ag = 50 mg. Kg-1, Pb = 360 mg. Kg-1) and triple (Ag = 75 mg. Kg-1, Pb = 540 mg. Kg -1) of this dosage. Vigor and germination tests of the seeds and possible anatomical changes in the leaves and roots of lettuce plants were performed. The species showed a high capacity to germinate under Pb and Ag stress, and the germination was never completely inhibited; however, the germination decreased with increasing Pb concentrations, but not under Ag stress. The use of increasing doses of metals reduced seed vigor and increased chlorophyll content. An increase in biomass was also observed in plants from treatments submitted to Pb. The phytotoxic effects of metals were more pronounced at 15 days after sowing. Anatomically, L. sativa was influenced by metal concentrations, and had a reduction of up to 79.9% in root epidermis thickness at the highest Pb concentration, although some structures did not suffer significant changes. The results suggest that L. sativa presents tolerance to high concentrations of heavy metals, showing possible mechanisms to overcome the stress caused by these metals. In this research lettuce possibly used the mechanism of exclusion of metals retaining Pb and Ag in the roots preserving the photosynthetic apparatus in the aerial part of the plants. In general, the chemical element Pb was more toxic than Ag, in these experimental conditions.
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http://dx.doi.org/10.1590/1519-6984.237604DOI Listing
June 2021

Genome profiling of fluoroquinolone-resistant uropathogenic Escherichia coli isolates from Brazil.

Braz J Microbiol 2021 Jun 8. Epub 2021 Jun 8.

Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.

Urinary tract infections (UTIs) are a major public health concern in both community and hospital settings worldwide. Uropathogenic Escherichia coli (UPEC) is the main causative agent of UTI and increasingly associated with antibiotic resistance. Herein, we report the draft genome sequence of 9 fluoroquinolone-resistant UPEC isolates from Brazil and examine selected major phenotypic features, such as antimicrobial resistance profile, phylogroup, serotype, sequence type (ST), virulence genes, and resistance marks. Besides the quinolone resistance, beta-lactams, ESBL production, aminoglycosides, and tetracycline resistance were observed. High prevalence of 20 virulence genes was detected in all isolates, such as those encoding type 1 fimbriae, acid tolerance system, and hemolysin E, particularly within E. coli B2 phylogroup, as ST131 and ST1193 strains, among other genomic analyses as genomic islands, resistance plasmids, and integron identification.
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http://dx.doi.org/10.1007/s42770-021-00513-3DOI Listing
June 2021

Evaluation of Exposure to Toluene and Xylene in Gasoline Station Workers.

Adv Prev Med 2021 20;2021:5553633. Epub 2021 May 20.

Technical Area of Environment, Work and Cancer, Prevention and Surveillance Coordination, National Cancer Institute José Alencar Gomes da Silva (INCA), Rua Marquês de Pombal 125, 5º Andar-Centro, Rio de Janeiro CEP 20230-240, Brazil.

The main volatile organic compounds found at gasoline stations are benzene, toluene, ethylbenzene, and xylene isomers (BTEX). They cause several harmful effects on human health. Regulatory Norm 7 (1978) provides that, in Brazil, biological monitoring of toluene and xylene is carried out by measuring the urinary metabolites hippuric acid (HA) and methylhippuric acid (MHA), respectively. The objective of this study was to assess the exposure to toluene and xylene and to identify related signs and symptoms in gasoline station workers. A cross-sectional epidemiological study was conducted with workers occupationally exposed to fuels. These gasoline station workers were divided into two groups: 94 workers exposed mainly by inhalation (convenience store workers (CSWs)) and 181 workers exposed by inhalation and dermal route (filling station attendants (FSAs)). A comparison group was formed by 119 workers not occupationally exposed to fuels (office workers (OWs)). Workers exposed to fuels had higher average levels of these exposure biomarkers (HA and MHA), which were also higher in convenience store workers than in filling station attendants. In addition, individuals exposed to the solvents present in gasoline had altered mood/depression, cramps, dizziness, drowsiness, headaches, irritability/nervousness, weakness, weight loss, and other symptoms more frequently and had higher urinary levels of HA and MHA compared to the comparison group. Gasoline station workers showed high levels of HA and MHA, reflecting high occupational exposure to the solvents toluene and xylene present in gasoline, demonstrating that changes in the current legislation and in the work environment are necessary to ensure better health protection for these workers.
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http://dx.doi.org/10.1155/2021/5553633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159630PMC
May 2021

Factors Affecting Predominantly Peripheral Lesion Identification and Grading.

Transl Vis Sci Technol 2021 Jun;10(7)

Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, USA.

Purpose: The purpose of this study was to determine factors affecting predominantly peripheral lesion (PPL) grading, such as qualitative versus quantitative assessment, device type, and severity of diabetic retinopathy (DR) in ultrawide field color images (UWF-CIs).

Methods: Patients with DR had UWF-CI qualitatively graded for PPL using standardized techniques and had hemorrhages/microaneurysms (H/Mas) individually annotated for quantitative PPL grading on two different ultrawide field devices.

Results: Among 791 eyes of 481 patients, 38.2% had mild nonproliferative DR (NPDR), 34.7% had moderate NPDR, and 27.1% had severe NPDR to proliferative DR (PDR). The overall agreement between qualitative and quantitative PPL grading was moderate (ĸ = 0.423, P < 0.001). Agreement rates were fair in eyes with mild NPDR (ĸ = 0.336, P < 0.001) but moderate in eyes with moderate NPDR (ĸ = 0.525, P < 0.001) and severe NPDR-PDR (ĸ = 0.409, P < 0.001). Increasing thresholds for quantitative PPL determination improved agreement rates, with peak agreements at H/Ma count differences of six for mild NPDR, five for moderate NPDR, and nine for severe NPDR-PDR. Based on ultrawide field device type (California = 412 eyes vs. 200Tx = 379 eyes), agreement between qualitative and quantitative PPL grading was moderate for all DR severities in both devices (ĸ = 0.369-0.526, P < 0.001) except for mild NPDR on the 200Tx, which had poor agreement (ĸ = 0.055, P = 0.478).

Conclusions: Determination of PPL varies between standard qualitative and quantitative grading and is dependent on NPDR severity, device type, and magnitude of lesion differences used for quantitative assessment.

Translational Relevance: Prior UWF studies have not accounted for imaging and grading factors that affect PPL, such factors need to be reviewed when assessing thresholds for DR progression rates.
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http://dx.doi.org/10.1167/tvst.10.7.6DOI Listing
June 2021