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1.
Anal Biochem ; : 114412, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34656613

RESUMO

Nuclear Magnetic Resonance (NMR) based metabolomic analysis of whole saliva has provided potential diagnostic biomarkers for numerous human diseases contributing to a better understanding of their mechanisms. However, a comprehensive interpretation of the significance of metabolites in whole, parotid, and submandibular/sublingual saliva subtypes is still missing. Precision and reproducibility of sample preparation is an essential step. Here, we present a simple and efficient protocol for saliva 1H NMR metabolic profiling. This procedure has been specifically designed and optimized for the identification and quantification of low concentration metabolites (as low as 1.1 µM) and is suitable for all the saliva subtypes.

2.
Brain ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297092

RESUMO

Misfolding and aggregation of α-synuclein are specific features of Parkinson's disease and other neurodegenerative diseases defined as synucleinopathies. Parkinson's disease progression has been correlated with the formation and the extracellular release of α-synuclein aggregates, as well as with their spreading from neuron to neuron. Therapeutic interventions in the initial stages of Parkinson's disease require a clear understanding of the mechanisms by which α-synuclein disrupts the physiological synaptic and plastic activity of the basal ganglia. For this reason, here we have identified two early time points to clarify how the intrastriatal injection of α-synuclein preformed fibrils in rodents, via retrograde transmission, induces time-dependent electrophysiological and behavioral alterations. We found that intrastriatal α-synuclein preformed fibrils perturb the firing rate of dopaminergic neurons of the substantia nigra pars compacta while the discharge of putative GABAergic cells of the substantia nigra pars reticulata is unchanged. The α-synuclein-induced dysregulation of nigrostriatal function also impairs, in a time-dependent manner, the two main forms of striatal synaptic plasticity, long-term potentiation and long-term depression. We also observed an increased glutamatergic transmission measured as an augmented frequency of spontaneous excitatory synaptic currents. These changes in neuronal function in the substantia nigra pars compacta and striatum were observed before overt neuronal death occurred. In an additional set of experiments, we were able to rescue α-synuclein-induced alterations of motor function, striatal synaptic plasticity, and increased spontaneous excitatory synaptic currents by a sub-chronic treatment with L-Dopa, a precursor of dopamine widely used in the therapy of Parkinson's disease, clearly demonstrating that a dysfunctional dopamine system plays a critical role in the early phases of the disease.

3.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202728

RESUMO

The prognosis of patients with oral squamous carcinoma (OSCC) largely depends on the stage at diagnosis, the 5-year survival rate being approximately 30% for advanced tumors. Early diagnosis, including the detection of lesions at risk for malignant transformation, is crucial for limiting the need for extensive surgery and for improving disease-free survival. Saliva has gained popularity as a readily available source of biomarkers (including cytokines) useful for diagnosing specific oral and systemic conditions. Particularly, the close interaction between oral dysplastic/neoplastic cells and saliva makes such fluid an ideal candidate for the development of non-invasive and highly accurate diagnostic tests. The present review has been designed to answer the question: "Is there evidence to support the role of specific salivary cytokines in the diagnosis of OSCC?" We retrieved 27 observational studies satisfying the inclusion and exclusion criteria. Among the most frequent cytokines investigated as candidates for OSCC biomarkers, IL-6, IL-8, TNF-α are present at higher concentration in the saliva of OSCC patients than in healthy controls and may therefore serve as basis for the development of rapid tests for early diagnosis of oral cancer.


Assuntos
Biomarcadores , Carcinoma de Células Escamosas/metabolismo , Citocinas/metabolismo , Neoplasias Bucais/metabolismo , Saliva/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Escamosas/diagnóstico , Humanos , Biópsia Líquida/métodos , Neoplasias Bucais/diagnóstico , Prognóstico
4.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064250

RESUMO

The members of the Lemur Tyrosine Kinases (LMTK1-3) subfamily constitute a group of three membrane-anchored kinases. They are known to influence a wide variety of key cellular events, often affecting cell proliferation and apoptosis. They have been discovered to be involved in cancer, in that they impact various signalling pathways that influence cell proliferation, migration, and invasiveness. Notably, in the context of genome-wide association studies, one member of the LMTK family has been identified as a candidate gene which could contribute to the development of prostate cancer. In this review, of published literature, we present evidence on the role of LMTKs in human prostate cancer and model systems, focusing on the complex network of interacting partners involved in signalling cascades that are frequently activated in prostate cancer malignancy. We speculate that the modulators of LMTK enzyme expression and activity would be of high clinical relevance for the design of innovative prostate cancer treatment.


Assuntos
Lemur/genética , Neoplasias da Próstata/genética , Proteínas Tirosina Quinases/genética , Animais , Humanos , Masculino , Transdução de Sinais/genética
5.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673424

RESUMO

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells. In vitro, Pol λ can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol λ. Pol λ associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol λ in the maintenance of telomeres by the ALT mechanism.


Assuntos
Aminopeptidases/metabolismo , DNA Polimerase beta/metabolismo , Quadruplex G , Serina Proteases/metabolismo , Homeostase do Telômero , Proteínas de Ligação a Telômeros/metabolismo , Linhagem Celular Tumoral , Humanos , Complexos Multiproteicos , Proteína de Replicação A/metabolismo , Telômero/química , Telômero/metabolismo
7.
J Fungi (Basel) ; 7(2)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578728

RESUMO

The previously described decapeptide AKVTMTCSAS (killer peptide, KP), derived from the variable region of a recombinant yeast killer toxin-like anti-idiotypic antibody, proved to exert a variety of antimicrobial, antiviral, and immunomodulatory activities. It also showed a peculiar self-assembly ability, likely responsible for the therapeutic effect in animal models of systemic and mucosal candidiasis. The present study analyzed the biological and structural properties of peptides derived from KP by substitution or deletion of the first residue, leaving unchanged the remaining amino acids. The investigated peptides proved to exert differential in vitro and/or in vivo anti-Candida activity without showing toxic effects on mammalian cells. The change of the first residue in KP amino acidic sequence affected the conformation of the resulting peptides in solution, as assessed by circular dichroism spectroscopy. KP-derivatives, except one, were able to induce apoptosis in yeast cells, like KP itself. ROS production and changes in mitochondrial transmembrane potential were also observed. Confocal and transmission electron microscopy studies allowed to establish that selected peptides could penetrate within C. albicans cells and cause gross morphological alterations. Overall, the physical and chemical properties of the first residue were found to be important for peptide conformation, candidacidal activity and possible mechanism of action. Small antimicrobial peptides could be exploited for the development of a new generation of antifungal drugs, given their relative low cost and ease of production as well as the possibility of devising novel delivery systems.

8.
Behav Neurol ; 2020: 8216758, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282006

RESUMO

Background: Progressive increase of an aging population in Western countries will result in a growth of stroke prevalence. As many stroke survivors chronically show severe disability, increase in economic, social, and medical burden could be expected in the future. Objective and subjective measures of poststroke recovery are necessary to obtain predictive information, to improve the treatments, and to better allocate resources. Aim: To explore a measure of the temporal dimension of poststroke recovery, to search for predictive association with multiple clinical variables, and to improve tailoring of poststroke treatments. Method: In this observational monocentric cohort study, 176 poststroke inpatients at their first cerebrovascular event were consecutively enrolled. A novel measure based on the time needed to reach the main milestones of motor recovery was proposed. Moreover, two commonly used outcome measures, a measure of global functioning (Functional Independence Measure (FIM™)) and a measure of neurological poststroke deficit (Fugl-Meyer scale), were collected for the investigations of possible predictors. Results: The patients showed a substantial increase in Fugl-Meyer and FIM scores during the rehabilitative treatment. The acquisition of three milestones was significantly associated with female sex (autonomous standing), length of stay and Fugl-Meyer initial score (autonomous walking), and Fugl-Meyer initial score (functional arm). These findings provided quantitative data on motor milestone reacquisition in a sample of poststroke patients. It also demonstrated the value of the Fugl-Meyer score in predicting the acquisition of two motor milestones, relevant for daily life activities. Conclusion: Systematic recording of the timescale of poststroke recovery showed that motor milestone reacquisition happens, on average and when attainable, in less than 30 days in our sample of patients. The present study underscores the importance of the Fugl-Meyer score as a possible predictor for better improvement in reacquisition times of milestone functional recovery.

9.
Cell Death Dis ; 11(11): 980, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191398

RESUMO

miR-205 plays important roles in the physiology of epithelia by regulating a variety of pathways that govern differentiation and morphogenesis. Its aberrant expression is frequently found in human cancers, where it was reported to act either as tumor-suppressor or oncogene depending on the specific tumor context and target genes. miR-205 expression and function in different cell types or processes are the result of the complex balance among transcription, processing and stability of the microRNA. In this review, we summarize the principal mechanisms that regulate miR-205 expression at the transcriptional and post-transcriptional level, with particular focus on the transcriptional relationship with its host gene. Elucidating the mechanisms and factors regulating miR-205 expression in different biological contexts represents a fundamental step for a better understanding of the contribution of such pivotal microRNA to epithelial cell function in physiology and disease, and for the development of modulation strategies for future application in cancer therapy.


Assuntos
MicroRNAs/fisiologia , Diferenciação Celular , Humanos
10.
Pharmacol Res ; 160: 105185, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32891865

RESUMO

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR), whose activation requires a proteolytic cleavage in the extracellular domain exposing a tethered ligand, which binds to the same receptor thus stimulating Gαq/11-, Gαi/o- and Gα12-13 proteins. PAR1, activated by serine proteases and matrix metalloproteases, plays multifaceted roles in neuroinflammation and neurodegeneration, in stroke, brain trauma, Alzheimer's diseases, and Parkinson's disease (PD). Substantia nigra pars compacta (SNpc) is among areas with highest PAR1 expression, but current evidence on its roles herein is restricted to mechanisms controlling dopaminergic (DAergic) neurons survival, with controversial data showing PAR1 either fostering or counteracting degeneration in PD models. Since PAR1 functions on SNpc DAergic neurons activity are unknown, we investigated if PAR1 affects glutamatergic transmission in this neuronal population. We analyzed PAR1's effects on NMDARs and AMPARs by patch-clamp recordings from DAergic neurons from mouse midbrain slices. Then, we explored subunit composition of PAR1-sensitive NMDARs, with selective antagonists, and mechanisms underlying PAR1-induced NMDARs modulation, by quantifying NMDARs surface expression. PAR1 activation inhibits synaptic NMDARs in SNpc DAergic neurons, without affecting AMPARs. PAR1-sensitive NMDARs contain GluN2B/GluN2D subunits. Moreover, PAR1-mediated NMDARs hypofunction is reliant on NMDARs internalization, as PAR1 stimulation increases NMDARs intracellular levels and pharmacological limitation of NMDARs endocytosis prevents PAR1-induced NMDARs inhibition. We reveal that PAR1 regulates glutamatergic transmission in midbrain DAergic cells. This might have implications in brain's DA-dependent functions and in neurological/psychiatric diseases linked to DAergic dysfunctions.

11.
Metabolites ; 10(8)2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32781584

RESUMO

The detection of salivary molecules associated with pathological and physiological alterations has encouraged the search of novel and non-invasive diagnostic biomarkers for oral health evaluation. While genomic, transcriptomic, and proteomic profiles of human saliva have been reported, its metabolic composition is a topic of research: metabolites in submandibular/sublingual saliva have never been analyzed systematically. In this study, samples of whole, parotid, and submandibular/sublingual saliva from 20 healthy donors, without dental or periodontal diseases, were examined by nuclear magnetic resonance. We identified metabolites which are differently distributed within the three saliva subtypes (54 in whole, 49 in parotid, and 36 in submandibular/sublingual saliva). Principal component analysis revealed a distinct cluster for whole saliva and a partial overlap for parotid and submandibular/sublingual metabolites. We found exclusive metabolites for each subtype: 2-hydroxy-3-methylvalerate, 3-methyl-glutarate, 3-phenylpropionate, 4-hydroxyphenylacetate, 4-hydroxyphenyllactate, galactose, and isocaproate in whole saliva; caprylate and glycolate in submandibular/sublingual saliva; arginine in parotid saliva. Salivary metabolites were classified into standard and non-proteinogenic amino acids and amines; simple carbohydrates; organic acids; bacterial-derived metabolites. The identification of a salivary gland-specific metabolic composition in healthy people provides the basis to invigorate the search for salivary biomarkers associated with oral and systemic diseases.

12.
Nat Commun ; 11(1): 4342, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859892

RESUMO

Magmatic systems play a crucial role in enriching the crust with volatiles and elements that reside primarily within the Earth's mantle, including economically important metals like nickel, copper and platinum-group elements. However, transport of these metals within silicate magmas primarily occurs within dense sulfide liquids, which tend to coalesce, settle and not be efficiently transported in ascending magmas. Here we show textural observations, backed up with carbon and oxygen isotope data, which indicate an intimate association between mantle-derived carbonates and sulfides in some mafic-ultramafic magmatic systems emplaced at the base of the continental crust. We propose that carbon, as a buoyant supercritical CO2 fluid, might be a covert agent aiding and promoting the physical transport of sulfides across the mantle-crust transition. This may be a common but cryptic mechanism that facilitates cycling of volatiles and metals from the mantle to the lower-to-mid continental crust, which leaves little footprint behind by the time magmas reach the Earth's surface.

13.
JMIR Mhealth Uhealth ; 8(6): e16165, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32357123

RESUMO

BACKGROUND: Childhood obesity prevention is a public health priority in industrialized countries. The Reggio Emilia Local Health Authority has implemented a program involving primary and secondary prevention as well as the care of obese children. There are many health-promoting mobile apps, but few are targeted to children and very few are sponsored by public health agencies. OBJECTIVE: The goal of the research was to describe the process and tools adopted to cocreate a mobile app sponsored by the Reggio Emilia Local Health Authority to be installed in parents' phones aimed at promoting child health and preventing obesity. METHODS: After stakeholder mapping, a consulting committee including relevant actors, stakeholders, and users was formed. Key persons for childhood obesity prevention were interviewed, focus groups with parents and pediatricians were conducted, and community reporting storytelling was collected. The results of these activities were presented to the consulting committee in order to define the functionalities and contents of the mobile app. RESULTS: Three key trends emerged from community reporting: being active, playing, and being outdoors; time for oneself, family, and friends; and the pressures of life and work and not having time to be active and socialize. In focus groups, interviews, and labs, mothers showed a positive attitude toward using an app to manage their children's weight, while pediatricians expressed concerns that the app could increase their workload. When these findings were explored by the consulting committee, four key themes were extracted: strong relationships with peers, family members, and the community; access to safe outdoor spaces; children's need for age-appropriate independence; and professional support should be nonjudgmental and stigma-free. It should be a dialogue that promotes family autonomy. The app functions related to these needs include the following: (1) newsletter with anticipatory guidance, recipes, and vaccination and well-child visit reminders; (2) regional map indicating where physical activity can be done; (3) information on how to manage emergencies (eg, falls, burns, fever); (4) module for reinforcing the counseling intervention conducted by pediatricians for overweight children; and (5) a function to build a balanced daily diet. CONCLUSIONS: The pilot study we conducted showed that cocreation in health promotion is feasible, with the consulting committee being the key co-governance and cocreation tool. The involvement of stakeholders in this committee made it possible to expand the number of persons and institutions actively contributing to the project.


Assuntos
Aplicativos Móveis , Criança , Feminino , Humanos , Obesidade , Projetos Piloto , Projetos de Pesquisa , Smartphone
14.
Front Psychol ; 11: 738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425853

RESUMO

Objective: Divergent thinking (DT) has attracted research interest because of its potential role in early diagnosis and rehabilitation programs for patients affected by neurodegenerative diseases. Recently, DT has received even more attention because of its proven relationship with cognitive reserve (CR) and the possibility of a standardized assessment. However, few studies have investigated this ability in dementia patients, and even less is known about patients affected by Mild Cognitive Impairment (MCI). Thus, this study aims to investigate DT abilities in MCI patients. Methods: A total of 25 MCI patients and 25 healthy controls subjects (HC; from a random selection of 50) matched for age, gender, and educational level were enrolled. General cognitive functioning was measured by the Montreal Cognitive Assessment (MoCA), while the Abbreviated Torrance Test for Adults (ATTA) was selected to measure DT. Results: MANOVA analysis did not reveal any significant differences in DT abilities between MCI patients and HC except for the figural indicator score. A logistic hierarchical regression analysis revealed that the figural indicator score added an 8% of accuracy in the prediction of the group variable over the general cognition measure (MoCA). Conclusion: MCI patients seem to perform significantly worse than HC only in the figural DT score and this evidence has significant practical implications. First, that figural DT seemed to decrease even earlier than verbal DT and could therefore be taken into account for early diagnosis of MCI patients. On the contrary, the sparing of all the other DT skills (such as verbal DT skills, fluency, flexibility, originality, and elaboration) may suggest that, given its relationship with CR, verbal DT could instead be considered a possible target for prevention or early cognitive stimulation interventions.

15.
J Neurosci Methods ; 340: 108741, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311374

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) that contributes to the main motor symptoms of the disease. At present, even if several advancements have been done in the last decades, the molecular and cellular mechanisms involved in the pathogenesis are far to be fully understood. Accordingly, the establishment of reliable in vitro experimental models to investigate the early events of the pathogenesis represents a key issue in the field. However, to mimic and reproduce in vitro the complex neuronal circuitry involved in PD-associated degeneration of DAergic neurons still remains a highly challenging issue. Here we will review the in vitro PD models used in the last 25 years of research, ranging from cell lines, primary rat or mice neuronal cultures to the more recent use of human induced pluripotent stem cells (hiPSCs) and, finally, the development of 3D midbrain organoids.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doença de Parkinson , Células-Tronco Pluripotentes , Animais , Linhagem Celular , Neurônios Dopaminérgicos , Humanos , Camundongos , Ratos , Substância Negra
16.
Data Brief ; 29: 105355, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32190721

RESUMO

The presented data were obtained with the lipocalin allergen Mus m 1.0102 and its cysteine mutants MM-C138A, MM-C157A and MM-C138,157A, whose structural features and unfold reversibility investigations are presented in the research article entitled "The allergen Mus m 1.0102: cysteine residues and molecular allergology" [1]. The data were obtained by means of a Dynamic Light Scattering-based thermal stability assay, a Fluorescence-based ligand-binding assay and a basophil degranulation test, and describe proteins' fold stability, ligand binding ability and allergenic potential, respectively. Analysis of the collected data produced the temperatures corresponding to the onset of the protein unfolding, the dissociation constants for N-Phenyl-1-naphthylamine ligand and the profiles of ß-hexosaminidase release from RBL SX-38 cells, sensitized with the serum of selected allergic patients and incubated with increasing antigens concentrations. These data allow for comparison of the lipocalin allergen Mus m 1.0102 with its conserved cysteines mutants and, with regard to their potential application in allergy diagnostics and immunotherapy, they contribute to the process of recombinant allergen characterization and standardization.

17.
Prev Med ; 134: 106024, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32061684

RESUMO

Childhood obesity is a major public health problem in industrialized countries. The aim of this study was to estimate the risk of obesity at age 5 based on BMI categories at age 3 and changes in BMI z-score from birth to 3 years of age. In this population-based study BMI data of 5173 children were collected at ages 3 and 5 and were linked to information relative to birth weight. The prevalence of obesity at age 5 was 3.8%. The risk of obesity for children born large for gestational age was 6.5%, while it was 18.6% for children overweight at age 3 and 62% for children who were obese at 3. An increase in BMI z-score from birth to 3 years increases the risk of obesity at age 5 (OR for increase of one standard deviation 2.8%; 95% CI: 2.46-3.20), but adjusting for BMI z-score at age 3, the effect of trajectory disappears (OR 1.08 95% CI: 0.9-1.29). In other words, if one targeted early preventive interventions to 3-year-olds affected by overweight/obesity (only 9.8% of the study cohort), one could possibly address 71% of children potentially affected by obesity at age 5.


Assuntos
Peso ao Nascer , Índice de Massa Corporal , Obesidade Pediátrica/epidemiologia , Pré-Escolar , Feminino , Humanos , Itália/epidemiologia , Masculino , Sobrepeso/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco
18.
Mol Immunol ; 120: 1-12, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32044430

RESUMO

Mus m 1.0102 is a member of the mouse Major Urinary Protein family, belonging to the Lipocalins superfamily. Major Urinary Proteins (MUPs) are characterized by highly conserved structural motifs. These include a disulphide bond, involved in protein oxidative folding and protein structure stabilization, and a free cysteine residue, substituted by serine only in the pheromonal protein Darcin (MUP20). The free cysteine is recognized as responsible for the onset of inter- or intramolecular thiol/disulphide exchange, an event that favours protein aggregation. Here we show that the substitution of selected cysteine residues modulates Mus m 1.0102 protein folding, fold stability and unfolding reversibility, while maintaining its allergenic potency. Recombinant allergens used for immunotherapy or employed in allergy diagnostic kits require, as essential features, conformational stability, sample homogeneity and proper immunogenicity. In this perspective, recombinant Mus m 1.0102 might appear reasonably adequate as lead molecule because of its allergenic potential and thermal stability. However, its modest resistance to aggregation renders the protein unsuitable for pharmacological preparations. Point mutation is considered a winning strategy. We report that, among the tested mutants, C138A mutant acquires a structure more resistant to thermal stress and less prone to aggregation, two events that act positively on the protein shelf life. Those features make that MUP variant an attractive lead molecule for the development of a diagnostic kit and/or a vaccine.


Assuntos
Alérgenos/química , Alérgenos/imunologia , Proteínas/química , Proteínas/imunologia , Alérgenos/genética , Substituição de Aminoácidos , Animais , Linhagem Celular , Cisteína/química , Humanos , Testes Imunológicos , Ligantes , Camundongos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Conformação Proteica , Dobramento de Proteína , Estabilidade Proteica , Estrutura Secundária de Proteína , Proteínas/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Epidemiol Prev ; 44(5-6 Suppl 1): 153-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33415958

RESUMO

OBJECTIVES: to explain differences in effectiveness of paediatrician-led motivational interviewing (MI) in decreasing body mass index (BMI) between children of mothers with low or high education level. DESIGN: secondary analysis of a randomised control trial. SETTING AND PARTICIPANTS: individually randomized controlled trial previously conducted from 2011 to 2013 in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy). Eligible participants included in the trial were 372 (187 in the MI group and 185 in the control group) overweight children (BMI percentile >= 85th and < 95th) aged between 4 and 7 years, residing in the province of Reggio Emilia and under the care of paediatrician for >= 12 months. The intervention included 5 MI sessions based on the transtheoretical model of addiction and behavioural change delivered at 1, 4, 7, and 12 months after the baseline visit, when families had to define specific goals in changing physical activity (PA) and diet behaviours. MAIN OUTCOME MEASURES: primary: BMI score variation (ΔBMI) from baseline to 12 months; secondary: percentage of changes in parent-reported PA and dietary behaviours. RESULTS: a significant effect of MI on ΔBMI in children whose mothers had high education level (ΔBMI = -0.62; 95%CI -0.92;-0.32) were observed. Children of women with high education level in MI group had more improvements in set unstructured PA, decreasing screen time and sweet snacks consumption, while children with less educated mothers had improvements in consuming more vegetable soup and less desserts, sweet snacks, and sugary beverages. Highly educated mothers chose for their children to drink fewer sugary beverages and to increase PA. Less educated mothers most frequently chose as goals having breakfast, eating more fruit and vegetables, eating fewer snacks, and having less screen time. Overall achievement was similar in the two strata for diet goals, but higher for PA goals in the high education level stratum. CONCLUSIONS: MI intervention was not effective in reducing BMI in children of mothers with low education level. This does appear to be weakly or not associated with goal choices and achievement within MI, it is rather an effect of unmeasured behaviours which possibly mediate association between MI and BMI reduction.


Assuntos
Escolaridade , Obesidade Pediátrica , Índice de Massa Corporal , Criança , Dieta , Feminino , Humanos , Lactente , Itália/epidemiologia , Mães , Sobrepeso , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/prevenção & controle
20.
Front Immunol ; 10: 1092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156639

RESUMO

Chemokine receptor CXCR4, its ligand stromal cell-derived factor-1 (CXCL12) and the decoy receptor atypical chemokine receptor 3 (ACKR3, also named CXCR7), are involved in the guidance of migrating cells in different anatomical districts. Here, we investigated the role of the ACKR3 zebrafish ortholog ackr3b in the vascularization process during embryonic development. Bioinformatics and functional analyses confirmed that ackr3b is a CXCL12-binding ortholog of human ACKR3. ackr3b is transcribed in the endoderm of zebrafish embryos during epiboly and is expressed in a wide range of tissues during somitogenesis, including central nervous system and somites. Between 18 somite and 26 h-post fertilization stages, the broad somitic expression of ackr3b becomes restricted to the basal part of the somites. After ackr3b knockdown, intersomitic vessels (ISVs) lose the correct direction of migration and are characterized by the presence of aberrant sprouts and ectopic filopodia protrusions, showing downregulation of the tip/stalk cell marker hlx1. In addition, ackr3b morphants show significant alterations of lateral dorsal aortae formation. In keeping with a role for ackr3b in endothelial cell guidance, CXCL12 gradient generated by ACKR3 expression in CHO cell transfectants guides human endothelial cell migration in an in vitro cell co-culture chemotaxis assay. Our results demonstrate that ackr3b plays a non-redundant role in the guidance of sprouting endothelial cells during vascular development in zebrafish. Moreover, ACKR3 scavenging activity generates guidance cues for the directional migration of CXCR4-expressing human endothelial cells in response to CXCL12.


Assuntos
Movimento Celular/genética , Quimiocina CXCL12/metabolismo , Células Endoteliais/metabolismo , Receptores CXCR/metabolismo , Transdução de Sinais/genética , Animais , Animais Geneticamente Modificados , Células CHO , Células COS , Chlorocebus aethiops , Cricetulus , Desenvolvimento Embrionário/genética , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Fisiológica/genética , Receptores CXCR/genética , Transfecção , Peixe-Zebra/embriologia
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