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1.
Sci Total Environ ; 913: 169648, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38159772

RESUMO

Global warming has led to an increase in extreme weather and climate phenomena, including floods and heatwaves. Marine heatwaves have frightening consequences for coastal benthic communities around the world. Each species exhibits a natural range of thermal tolerance and responds to temperature variations through behavioral, physiological, biochemical, and molecular adjustments. Physiological stress leading to disease and mass mortality appears when tolerance thresholds are exceeded. Sessile species are therefore particularly affected by these phenomena. Among these sessile species, marine sponges are important members of coral reef ecosystems. To better understand the sponge thermal stress response, we tested the response of demosponge Chondrosia reniformis (Nardo, 1847) to three different temperatures (8 °C, 24 °C and 30 °C) during two exposure periods of time (4 and 14 h). Histological studies of whole parts of the sponge, biochemical analyses (Defense enzymes) and gene expression levels of some target genes were undertaken in this study. The exposure to cold temperature (8 °C) resulted in inhibition of antioxidant enzymes and less modification in the gene expression level of the heat shock proteins (HSPs). These latter were strongly upregulated after exposure to a temperature of 24 °C for 4 h. However, exposure to 30 °C at both periods of time resulted in indication of HSP, antioxidant enzymes, the gene involved in the apoptosis process (Bcl-2: B-cell lymphoma 2), the gene involved in inflammation (TNF: Tumor Necrosis Factor), as well as the aquaporin gene, involved in H2O2 permeation. Moreover, the normal organization of the whole organism was disrupted by the extension and fusion of choanocyte chambers and alteration of the pinacoderm. Interestingly, exposure to sublethal temperatures may show that this sponge has an adaptation threshold temperature. These insights into the adaptation mechanisms of sponges contribute to better management and conservation of sponges and to the prediction of ecosystem trajectories with future climate change.


Assuntos
Ecossistema , Poríferos , Animais , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Estresse Fisiológico/fisiologia
2.
Ecol Evol ; 12(1): e8494, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35136554

RESUMO

Despite the strategic localization of Tunisia in the Mediterranean Sea, no phylogeographic study on sponges has been investigated along its shores. The demosponge Chondrosia reniformis, descript only morphologically along Tunisian coasts, was chosen to estimate the influence of natural oceanographic and biogeographic barriers on its genetic differentiation and its Phylogeography. The cytochrome oxidase subunit I (COI) gene was amplified and analyzed for 70 Mediterranean Chondrosia reniformis, collected from eight localities in Tunisia. Polymorphism results revealed high values of haplotype diversity (H d) and very low nucleotide diversity (π). Thus, these results suggest that our sponge populations of C. reniformis may have undergone a bottleneck followed by rapid demographic expansion. This suggestion is strongly confirmed by the results of neutrality tests and "mismatch distribution." The important number of haplotypes between localities and the high genetic differentiation (F st ranged from 0.590 to 0.788) of the current C. reniformis populations could be maintained by the limited gene flow Nm (0.10-0.18). Both haplotype Network and the biogeographic analysis showed a structured distribution according to the geographic origin. C. reniformis populations are subdivided into two major clades: Western and Eastern Mediterranean. This pattern seems to be associated with the well-known discontinuous biogeographic area: the Siculo-Tunisian Strait, which separates two water bodies circulating with different hydrological, physical, and chemical characteristics. The short dispersal of pelagic larvae of C. reniformis and the marine bio-geographic barrier created high differentiation among populations. Additionally, it is noteworthy to mention that the "Mahres/Kerkennah" group diverged from Eastern groups in a single sub-clade. This result was expected, the region Mahres/Kerkennah, presented a particular marine environment.

3.
Sci Adv ; 7(33)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34380619

RESUMO

Coronavirus disease 2019 (COVID-19) continues to burden society worldwide. Despite most patients having a mild course, severe presentations have limited treatment options. COVID-19 manifestations extend beyond the lungs and may affect the cardiovascular, nervous, and other organ systems. Current treatments are nonspecific and do not address potential long-term consequences such as pulmonary fibrosis, demyelination, and ischemic organ damage. Cell therapies offer great potential in treating severe COVID-19 presentations due to their customizability and regenerative function. This review summarizes COVID-19 pathogenesis, respective areas where cell therapies have potential, and the ongoing 89 cell therapy trials in COVID-19 as of 1 January 2021.

4.
Compr Psychiatry ; 106: 152227, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33639332

RESUMO

BACKGROUND: Against the backdrop of 10 years of civil war in Syria, with millions of refugees, this study aimed to explore sense of community coherence and the acculturation strategies of separation and competition as factors that might explain mental-health problems among adolescent Syrian refugees in Greece. METHODS: Data were gathered from 173 adolescents aged 13-18 (M = 15.85; SD = 1.49); female adolescents accounted for 60.7% of the sample. Participants filled out a self-reported questionnaire regarding internalizing and externalizing problems, as well as posttraumatic stress disorder (PTSD). They were also asked about their sense of community coherence, their use of different acculturation strategies, and sociodemographic factors (i.e., gender, age, amount of time spent in the camp, and parents' education), as well as contextual factors such as exposure to war events, appraisal of danger, and whether they had received aid from various organizations. RESULTS: The female adolescents reported a stronger sense of community coherence and that they had received more aid from organizations than the male adolescents reported receiving. The male adolescents reported more externalizing problems. Exposure and appraisal of danger, as well as sense of community coherence and the use of the acculturation strategies of separation and competition all significantly explained the various mental-health problems. CONCLUSIONS: This article underscores the significance of gender, community coherence, and acculturation strategies in the prediction of mental health. It presents the results of this research in the context of the salutogenic and acculturation models.


Assuntos
Refugiados , Transtornos de Estresse Pós-Traumáticos , Aculturação , Adolescente , Feminino , Grécia , Humanos , Masculino , Saúde Mental , Síria
5.
Data Brief ; 30: 105640, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32420428

RESUMO

The data presented in this paper stand as supplementary information of the associated article "Karyological characterization of the common chameleon (Chamaeleo chamaeleon) provides insights on the evolution and diversification of sex chromosomes in Chamaeleonidae" [1]. This work provides (i) raw experimental data on the karyology of the common chameleon Chamaeleo chamaeleon and (ii) the results of bioinformatic analysis on sex-specific and repeated DNA sequences found in the same species. The karyological information here presented includes traditional staining method (Giemsa staining) and sequential C-banding + fluorochromes performed on Tunisian samples of the species. The sequence data include the alignments of the isolated DNA sequences with homologous sequences found in squamate Short Read Archives (SRAs) and the results of searches in public nucleic acid databases.

6.
Nucleic Acids Res ; 48(9): 5183-5195, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315033

RESUMO

To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.


Assuntos
Edição de Genes/métodos , Retroelementos , Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Sobrevivência Celular , Endodesoxirribonucleases , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas , Mutação , RNA
7.
Zoology (Jena) ; 141: 125738, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32291142

RESUMO

Chameleons display high karyological diversity in chromosome number (from 2n = 20 to 62), morphology, heterochromatin distribution and location of specific chromosomal markers, making them unique study models in evolutionary cytogenetics. However, most available cytogenetic data are limited to the description of the chromosome number and morphology. Concerning sex chromosomes, our knowledge is limited to ZZ/ZW and Z1Z1Z2Z2/Z1Z2W systems in the genus Furcifer and the isolation of sex-linked, male-specific, sequences in Chamaeleo calyptratus, but the putative XY chromosomes have still to be identified in Chamaeleo and the conservation of male heterogamety in the genus needs confirmation from other species. In this study we performed a molecular and a cytogenetic analysis on C. chamaeleon, using standard, banding methods and molecular cytogenetics to provide a throughout karyological characterization of the species and to identify and locate the putative XY chromosomes. We confirm that the chromosome formula of the species is 2n = 24, with 12 metacentric macrochromosomes, 12 microchromosomes and NORs on the second chromosome pair. Heterochromatin was detected as weak C-bands on centromeric regions, differently from what was previously reported for C. calyptratus. Fluorescence in situ hybridization (FISH) showed the occurrence of interspersed telomeric signals on most macrochromosomes, suggesting that ancient chromosome fusions may have led to a reduction of the chromosome number. Using a combination of molecular and FISH analyses, we proved that male specific Restriction site-Associated DNA sequences (RADseq) isolated in C. calyptratus are conserved in C. chamaeleon and located the putative XY chromosomes on the second chromosome pair. We also identified different transposable elements in the focal taxa, which are highly interspersed on most chromosome pairs.


Assuntos
Evolução Biológica , Cariótipo , Lagartos/genética , Cromossomos Sexuais/genética , Animais , Sequência de Bases , Análise Citogenética , Código de Barras de DNA Taxonômico , Feminino , Masculino , Reação em Cadeia da Polimerase/métodos
8.
Nucleic Acids Res ; 47(22): 11956-11962, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31713635

RESUMO

There is increasing demand for single-stranded DNA (ssDNA) of lengths >200 nucleotides (nt) in synthetic biology, biological imaging and bionanotechnology. Existing methods to produce high-purity long ssDNA face limitations in scalability, complexity of protocol steps and/or yield. We present a rapid, high-yielding and user-friendly method for in vitro production of high-purity ssDNA with lengths up to at least seven kilobases. Polymerase chain reaction (PCR) with a forward primer bearing a methanol-responsive polymer generates a tagged amplicon that enables selective precipitation of the modified strand under denaturing conditions. We demonstrate that ssDNA is recoverable in ∼40-50 min (time after PCR) with >70% yield with respect to the input PCR amplicon, or up to 70 pmol per 100 µl PCR reaction. We demonstrate that the recovered ssDNA can be used for CRISPR/Cas9 homology directed repair in human cells, DNA-origami folding and fluorescent in-situ hybridization.


Assuntos
DNA de Cadeia Simples/síntese química , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Proteína 9 Associada à CRISPR/metabolismo , Reparo do DNA/efeitos dos fármacos , DNA de Cadeia Simples/química , Marcação de Genes/métodos , Células HEK293 , Humanos , Metanol/química , Metanol/farmacologia , Mutagênese Sítio-Dirigida/métodos , Polímeros/química , Fatores de Tempo
9.
Artigo em Inglês | MEDLINE | ID: mdl-31635399

RESUMO

: The present study aimed to explore the coping resources and mental health of women who have fled Syria to a neighboring European country. To that end, we examined the roles of sociodemographic factors, situational factors, and personal and community sense of coherence (SOC and ComSOC, respectively) in mental-health outcomes. One hundred and eleven refugee women aged 19-70 filled out self-reported questionnaires during August 2018 in a refugee camp in Greece. The questionnaires asked the participants for demographic information (i.e., age, level of education level, and time spent in the camp) and also addressed the situational factors of having received aid from various organizations, appraisal of danger during the war in Syria, and exposure to war experiences, as well as the coping resources of SOC and ComSOC. The results show that time spent in the camp, appraisal of danger, SOC, and ComSOC all play significant roles in predicting the variance of various mental-health outcomes. Together, those factors predict 56% of anxiety, 53% of depression, and 58% of somatization. SOC was also found to mediate the relationships between time spent in the camp and outcome variables, as well as the relationships between the appraisal of danger and the outcome variables. This indicates that SOC is crucial for good adaptation. These results will be discussed in light of the salutogenic theory.


Assuntos
Adaptação Psicológica , Recursos em Saúde , Campos de Refugiados , Refugiados/psicologia , Adulto , Idoso , Europa (Continente) , Feminino , Grécia , Humanos , Saúde Mental , Pessoa de Meia-Idade , Senso de Coerência , Inquéritos e Questionários , Síria/etnologia , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30841587

RESUMO

Bedouin society has undergone rapid changes over the past decade. The younger generation of Bedouin women is better educated, which has enabled them to enter different professions, increased their incomes and elevated their social status. We examined the sense of coherence (SOC) and its components of meaningfulness, manageability and comprehensibility as well as the use of coping strategies among Bedouin women from three age groups. We also investigated the coping resources and strategies before determining the relationships between these variables in the three groups. One hundred ninety-six women participated in the study. Differences were found mostly between the oldest age group (61 years and older) and the two younger groups (21⁻40 and 41⁻60 years old). The oldest women reported less meaningfulness and used less positive reframing, planning, humor and acceptance. In terms of coping strategies, venting was used more by the youngest group whereas behavioral disengagement was used more by the oldest group. In the younger groups, SOC and its components were positively correlated with the use of coping strategies that are considered to be adaptive and with emotional support. However, the correlations between these factors were negative among the oldest group, which points to non-adaptive coping strategies used by these women. These results are discussed in light of the salutogenic, stress-appraisal and coping theories.


Assuntos
Árabes , Percepção , Senso de Coerência , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
11.
Egypt Heart J ; 70(4): 353-359, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30591754

RESUMO

BACKGROUND: Two-dimensional (2D) speckle-tracking strain imaging is a novel method for assessment of regional myocardial deformation that uses tracking of acoustic speckles or kernels rather than Doppler myocardial velocities. It has been suggested that Left atrial (LA) strain as measured by 2D speckle tracking can be used to evaluate dynamic LA function. OBJECTIVE: To study the relation between left atrial deformation and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). STUDY DESIGN: 30 patients with stable coronary artery disease (SCAD) with coronary artery stenosis (>50%) who were admitted for elective coronary angiography at Ain Shams University hospitals and AlAzhar University hospitals were included in the study. Measurements of conventional echocardiographic parameters as well as LA strain and strain rate parameters were obtained, Syntax (SX) score was calculated for all patients. RESULTS: Patients were categorized into 3 groups: low Syntax score of <23 (Group I), moderate syntax score 23-32 (Group II) and high syntax score of ≥33 (Group III). Peak atrial longitudinal strain (PALS) (Group I: 29.80 ±â€¯4.48, Group II: 22.44 ±â€¯1.42, Group III: 19.53 ±â€¯4.46; p < 0.001) and Peak atrial contraction strain (PACS) (Group I: 13.43 ±â€¯4.05, Group II: 10.84 ±â€¯2.47, Group III: 7.19 ±â€¯0.71; p < 0.022) were significantly lower in high syntax group. Significant negative correlation was found between SX score level and LA strain parameters (PALS and PACS) (r = 0.861; p < 0.001). CONCLUSION: Left atrial deformation analysis by 2D Speckle tracking Doppler Echocardiography can predict the severity of coronary affection in patients with stable CAD.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30577448

RESUMO

Elderly Bedouin men in southern Israel are a unique traditional population living in remote unrecognized villages and experiencing rapid social transition, in addition to deep poverty and political tension. In this study, we aimed to explore stressful events, as self-defined by the participants, and the ways in which these men have coped with those stressful events. This study involved 12 men, aged 69⁻74, who participated in in-depth narrative interviews during which they were asked about transformative stressful events in their lives and how they had managed, understood, and utilized human capital, meaning-making, and other methods of coping. Analysis of the interviews revealed several themes: (a) the definition of stressful events within the cultural context, (b) the use of human capital to overcome those events, (c) the transformation of experience from hindsight into a didactic narrative that can be used to assign meaning to past events, which can then be passed on to the next generation, and (d) cultural transition as a catalyst for the creation of new understandings of events. This paper sheds new light on how elderly indigenous Bedouin men self-define stressful situations within a complex and unstable cultural context. This specific context, can help us to gain insight into how indigenous impoverished older men in similar contexts may self-define their stress and coping, based on the types of generalization accepted in qualitative research. The methodological contribution of this work lies in its use of narrative to culturally contextualize phenomenological meaning structures. Its theoretical contribution lies in its examination of the concept of stress within a specific cultural context.


Assuntos
Adaptação Psicológica , Árabes/psicologia , Estresse Psicológico/etnologia , Idoso , Características Culturais , Humanos , Entrevistas como Assunto , Israel/epidemiologia , Masculino , Resolução de Problemas , Pesquisa Qualitativa
13.
Zookeys ; (775): 131-147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057476

RESUMO

Marmorana (Murella) muralis is known as an endemic species of Sicily Island, which is introduced in many European countries. Here, M. (M.) muralis is recorded from the north of Tunisia. In order to confirm the identification of samples collected from several localities, shell morphology, details of genital organs and two mitochondrial markers (COI and 16S) were investigated. The results of the molecular study, as well as the morphological and anatomical studies confirm the identification of all Tunisian samples as M. (M.) muralis. The analysis of mitochondrial markers shows a low divergence between Sicilian and Tunisian samples suggesting a recent introduction of M. (M.) muralis to the North of Tunisia. The comparison of morphological characters of M. (M.) muralis with shell characters of Murella nicollei described by Pallary (1926) confirms that the latter should be considered as synonym of M. (M.) muralis.


Résumé Marmorana (Murella) muralis est connue comme une espèce endémique de l'île de Sicile qui est actuellement introduite dans plusieurs pays européens. Dans la présente étude, nous enregistrons, la présence de M. (M.) muralis dans différentes localités du Nord de la Tunisie. Dans le but de valider l'authenticité des spécimens collectés de différentes localités, la morphologie de la coquille, l'anatomie de l'appareil génital ainsi que deux marqueurs mitochondriaux (COI et 16S) ont été analysés. Les résultats de l'étude moléculaire ainsi que ceux de l'étude morphologique et anatomique confirment qu'il s'agit bien de l'espèce Sicilienne M. (M.) muralis. L'analyse des deux marqueurs mitochondriaux montre une faible divergence entre les populations Sicilienne et Tunisienne suggérant ainsi une récente introduction de cette espèce en Tunisie. La comparaison des critères morphologiques de l'espèce M. (M.) muralis avec les critères de la coquille de l'espèce Murella nicollei décrite par Pallary (1926) confirme que cette dernière doit être considérée comme synonyme de l'espèce M. (M.) muralis.

14.
Curr Psychiatry Rep ; 20(5): 36, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29732528

RESUMO

PURPOSE OF REVIEW: Bipolar disorder (BD) medical comorbidity presents significant clinical and public health concerns with serious impact on health. The aim of this article is to present an updated narrative review of original research articles (case control, longitudinal cohort, and cross-sectional studies) and meta-analyses published in English language journals from January 2013 to May 2017 focusing on general medical comorbidity in BD, including the added risks of iatrogenic factors relevant to the treatment of BD. RECENT FINDINGS: We found numerous patterns of association between BD and various medical disorders involving multiple organ systems. One pattern indicated reciprocal increase in the rate of each comorbid condition, such as an increased rate of BD in asthma or migraine, and likewise an increase in the rate of asthma or migraine in patients with BD. A second pattern was a predominantly unidirectional increase in the rate of BD in patients with certain medical disorders, such as multiple sclerosis or cerebellar diseases. A third pattern was a predominantly unidirectional increased rate of medical disorders in patients with BD. One study suggested the potential involvement of genetic mechanisms for the association between BD and migraine. Most of the studies had cross-sectional or retrospective designs, and many relied on analysis of large administrative databases inviting multiple potential biases. Our review highlights the association between BD and a variety of medical disorders. Further research is needed to elucidate the potential underlying etiopathological mechanisms that contribute to observed comorbidities. The results of this review also emphasize the need for comprehensive screening for medical disorders in BD and for adoption of an integrated model of care to address these complex comorbidities.


Assuntos
Transtorno Bipolar/epidemiologia , Comorbidade , Saúde Global , Humanos
15.
Zookeys ; (712): 1-27, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29134034

RESUMO

In order to clarify the systematic position of Helix latastei Letourneux in Letourneux & Bourguignat, 1887, and Helix latasteopsis Letourneux & Bourguignat, 1887, a comprehensive approach using morphological and molecular methods is presented. The investigation of the genital organs of both species showed that they belong to the genus Xerocrassa Monterosato, 1892 with two very small dart sacs and a few tubiform glandulae mucosae. In our phylogenetic analysis using the mitochondrial markers COI, 16S and the nuclear cluster 5.8-ITS2-28S, the results of the anatomical research were confirmed. Thus, the genus Ereminella Pallary, 1919, which is based on H. latastei, becomes a junior synonym of Xerocrassa. A review of the genus-level taxa Xerobarcana Brandt, 1959, and Xeroregima Brandt, 1959, showed that these should also be considered as synonyms of Xerocrassa. A third species, Helix lacertara Bourguignat, 1863 from Algeria was found to be closely related to X. latastei based on its shell morphology. A map showing the distribution of the three species treated is supplied.


RésuméUne étude basée sur des approches morphologiques et moléculaires a été réalisée dans le but de clarifier la position systématique de deux espèces Helix latastei Letourneux 1887 et Helix latasteopsis Letourneux & Bourguignat, 1887. L'examen des organes génitaux a montré des critères typiques du genre Xerocrassa Monterosato, 1892 avec la présence de deux petits "Dart Sac" et des glandes digitiformes à mucus. Les résultats de l'analyse phylogénétique de deux gènes mitochondriaux (COI et 16S) et un gène nucléaire 5.8S-ITS2-28S ont confirmé les résultats de l'étude anatomique. Par conséquent, le genre Ereminella Pallary, 1919, qui a été basé sur Helix latastei est donc un synonyme du genre Xerocrassa. La révision de deux genres Xerobarcana Brandt, 1959 et Xeroregima Brandt, 1959, suggère que ces deux genres sont aussi des synonymes du genre Xerocrassa. L'examen de la coquille de l'espèce Algérienne Helix lacertara Bourguignat, 1863 a montré une forte ressemblance avec X. latastei, ce qui nous a permis, ainsi, de la classer dans le genre Xerocrassa. Une carte montrant la distribution des trois espèces a été fournie.

16.
Autoimmunity ; 49(6): 366-372, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27494076

RESUMO

The aim of this study was to assess the relationships between five different splice isoforms of VEGF mRNA and its plasma levels in individuals treated for autoimmune thyroid diseases (AITD); mainly Graves' disease (GD) and Hashimoto's thyroiditis (HT). In a population from Tunisia, levels of thyroid hormones and antibodies were quantified simultaneously with plasma VEGF and VEGF mRNA isoforms after a period of 6 months of patients' treatment. Plasma VEGF was measured in 110 AITD patients (21 GD and 89 HT patients). VEGF isoforms (VEGF121, VEGF165, VEGF145 and VEGF189 pro-angiogenic isoforms and VEGF165b anti-angiogenic isoform) in peripheral blood mononuclear cells were quantified in 71 patients (20 GD and 51 HT patients) and 86 healthy controls. Decreased levels of VEGF189 mRNA were observed in AITD compared to controls. VEGF165 was increased in GD patients compared to controls and the VEGF165b was increased in HT patients compared to GD. We observed increased levels of VEGF165b in hypothyroid AITD patients after treatment. We have also shown that the VEGF145 isoform levels were determined by FT4 in all patients and by the thyroid status after 6 months of treatment only in HT patients. An association was observed for VEGF165 mRNA levels with anti-TPO antibodies in all patients. Finally, FT4 was associated with VEGF plasma levels but only in healthy controls. In conclusion, this descriptive study highlights the specificity of VEGF mRNA isoforms in AITD, a fact underlining the need for novel clinical trials and the development of personalised theranostic approaches.


Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doença de Graves/genética , Doença de Graves/imunologia , Neovascularização Patológica/genética , RNA Mensageiro/genética , Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Processamento Alternativo , Autoanticorpos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Biomarcadores , Estudos de Casos e Controles , Feminino , Doença de Graves/diagnóstico , Doença de Graves/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento do Endotélio Vascular/sangue
17.
Immunol Invest ; 45(4): 284-97, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27100882

RESUMO

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Cytokines IL-1B and IL-4 play a role in the pathogenesis of AITD. This study was conducted on Tunisian patients with GD or HT to investigate the association of IL-1B and IL-4 gene polymorphisms with the risk and the prognosis of AITD. A total of 358 healthy controls and 341 patients with AITDs (249 HT and 92 GD) were genotyped for IL-1B+3953C/T and IL-4 intron 3 VNTR polymorphisms. A significant association was found between IL-1B+3953C/T polymorphism and GD or HT, both in the dominant and additive models. The IL-1B+3953T allele was associated with GD (p = 0.0003, OR = 1.93, CI = 1.34-2.78) and HT (p = 0.009, OR = 1.43, CI = 1.09-1.88). The IL-4 VNTR polymorphism was associated only with HT risk both in additive (p = 0.03, OR = 0.31, CI = 0.11-0.86) and recessive (p = 0.03, OR = 3.04, CI = 1.13-8.17) models. No significant association was found between IL-1B+3953C/T polymorphism and change in the serum concentrations of TSH and FT4 in GD and HT patients. In HT patients, the IL-1B+3953T allele (p = 0.009, OR = 0.42, CI = 0.22-0.83) and the IL-1B+3953T/T genotype (p = 0.03, OR = 0.21, CI = 0.04-1.07) were more frequent in the absence than in the presence of an anti-TPO antibody. The proportion of HT patients with the P1P2 genotype of the IL-4 gene was significantly higher in the absence than in the presence of the anti-TPO antibody (p = 0.04, OR = 0.39, CI = 0.17-0.89). These preliminary results suggest that IL-1B and IL-4 gene polymorphisms may be associated with GD and HT susceptibility and may represent prognostic factors for predicting the severity of HT.


Assuntos
Interleucina-1beta/genética , Interleucina-4/genética , Tireoidite Autoimune/genética , Adulto , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Polimorfismo Genético , Risco , Tireotropina/sangue , Tunísia
18.
Autoimmunity ; 49(4): 229-35, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26955881

RESUMO

Autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto thyroiditis (HT), are complex multifactorial diseases. Vascular endothelial growth factor (VEGF) is implicated in various inflammatory diseases, especially autoimmune diseases. Our aim was to elucidate the relationships between plasma VEGF levels and four genome-wide association study-identified single nucleotide polymorphisms (SNPs) related to VEGF with AITD in Tunisian patients. A total of 364 healthy controls and 389 patients with AITD were genotyped for the SNPs rs6921438, rs4416670, rs6993770 and rs10738760. Levels of thyroid hormones and antibodies were quantified simultaneously with plasma VEGF after a period of six months of treatment. We found that the minor alleles of rs10738760 and rs6921438 are associated with the presence of GD. A allele of rs10738760 polymorphism is associated with increased plasma levels of free tri-iodothyronin (FT3) while no relationship was found with circulating VEGF plasma levels after six months of treatment. We also showed that the T allele of rs4416670 polymorphism was associated with increased risk of hyperthyroidism in patients treated for six months, independently of their initial diagnosis. There was no significant association between the SNPs and the risk for HT compared with controls. This study shows that AITD are influenced by 3 SNPs linked to VEGF circulating levels. Whereas rs10738760 appeared specific to GD and FT3 production after six months of treatment, rs6921438 and rs4416670 were implicated in the risk for GD. This study opens new ways to test pharmacogenomics concepts in the future especially in GD in which recurrence prognosis is still challenging.


Assuntos
Doenças Autoimunes/sangue , Doenças Autoimunes/genética , Polimorfismo Genético , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/genética , Fatores de Crescimento do Endotélio Vascular/sangue , Fatores de Crescimento do Endotélio Vascular/genética , Alelos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Biomarcadores , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Doença de Graves/sangue , Doença de Graves/genética , Doença de Hashimoto/sangue , Doença de Hashimoto/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/terapia
19.
J Appl Toxicol ; 36(6): 863-71, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26857037

RESUMO

The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors (ERs), aromatase B (Aro-B) protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line (U251MG) transfected with different zebrafish ER subtypes (ERα, ERß1 and ERß2) was also used. Embryos were exposed either to estradiol (E2 ), Cd, E2 +Cd or E2 +Cd+Zn for 72 h and cells were exposed to the same treatments for 30 h. Our results show that E2 treatment promoted the transcriptional activation of ERs and increased Aro-B expression, at both the protein and mRNA levels. Although exposure to Cd, does not affect the studied parameters when administered alone, it significantly abolished the E2 -stimulated transcriptional response of the reporter gene for the three ER subtypes in U251-MG cells, and clearly inhibited the E2 induction of Aro-B in radial glial cells of zebrafish embryos. These inhibitory effects were accompanied by a significant downregulation of the expression of esr1, esr2a, esr2b and cyp19a1b genes compared to the E2 -treated group used as a positive control. Zn administration during simultaneous exposure to E2 and Cd strongly stimulated zebrafish ERs transactivation and increased Aro-B protein expression, whereas mRNA levels of the three ERs as well as the cyp19a1b remained unchanged in comparison with Cd-treated embryos. In conclusion, our results clearly demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced E2 antagonism can be reversed, at the protein level, by Zn supplement. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Encéfalo/efeitos dos fármacos , Intoxicação por Cádmio/prevenção & controle , Cádmio/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Zinco/uso terapêutico , Animais , Animais Geneticamente Modificados , Aromatase/genética , Aromatase/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Cádmio/química , Intoxicação por Cádmio/embriologia , Intoxicação por Cádmio/metabolismo , Intoxicação por Cádmio/veterinária , Linhagem Celular , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Antagonistas de Estrogênios/química , Antagonistas de Estrogênios/toxicidade , Estrogênios/agonistas , Estrogênios/química , Estrogênios/metabolismo , Doenças dos Peixes/embriologia , Doenças dos Peixes/metabolismo , Doenças dos Peixes/patologia , Doenças dos Peixes/prevenção & controle , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genes Reporter/efeitos dos fármacos , Humanos , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/química , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Poluentes Químicos da Água/antagonistas & inibidores , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/agonistas , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Zigoto/efeitos dos fármacos , Zigoto/metabolismo , Zigoto/patologia
20.
Food Chem ; 196: 58-65, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26593465

RESUMO

The question asked in the present work was how to differentiate between contamination of field samples with and GM plants contained sequences provided from this bacterium in order to avoid false positives in the frame of the detection and the quantification of GMO. For this, new set of primers and corresponding TaqMan Minor Groove Binder (MGB) probes were designed to target Agrobacterium sp. using the tumor-morphology-shooty gene (TMS1). Final standard curves were calculated for each pathogen by plotting the threshold cycle value against the bacterial number (log (colony forming units) per milliliter) via linear regression. The method designed was highly specific and sensitive, with a detection limit of 10CFU/ml. No significant cross-reaction was observed. Results from this study showed that TaqMan real-time PCR, is potentially an effective method for the rapid and reliable quantification of Agrobacterium sp. in samples containing GMO or non GMO samples.


Assuntos
Agrobacterium/química , Bactérias/química , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Agrobacterium/genética , Bactérias/genética , Plantas Geneticamente Modificadas/genética
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