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1.
BMC Public Health ; 24(1): 790, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481210

RESUMO

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.


Assuntos
COVID-19 , Saúde Mental , Humanos , Universidades , Reprodutibilidade dos Testes , Ansiedade , COVID-19/epidemiologia , Psicometria , Inquéritos e Questionários
2.
Mol Syst Biol ; 15(12): e8983, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31885201

RESUMO

Arrayed CRISPR-based screens emerge as a powerful alternative to pooled screens making it possible to investigate a wide range of cellular phenotypes that are typically not amenable to pooled screens. Here, we describe a solid-phase transfection platform that enables CRISPR-based genetic screens in arrayed format with flexible readouts. We demonstrate efficient gene knockout upon delivery of guide RNAs and Cas9/guide RNA ribonucleoprotein complexes into untransformed and cancer cell lines. In addition, we provide evidence that our platform can be easily adapted to high-throughput screens and we use this approach to study oncogene addiction in tumor cells. Finally demonstrating that the human primary cells can also be edited using this method, we pave the way for rapid testing of potential targeted therapies.


Assuntos
Edição de Genes/instrumentação , Neoplasias/genética , RNA Guia de Cinetoplastídeos/farmacologia , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Predisposição Genética para Doença , Ensaios de Triagem em Larga Escala , Humanos , Fenótipo , Transfecção
7.
Contraception ; 132: 110372, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38237672

RESUMO

OBJECTIVES: The study aimed to evaluate the impact of a structured subdermic implant training program on healthcare providers and its effect on the integration of this contraceptive method into patient counselling. STUDY DESIGN: The study was a longitudinal experiment with an intervention group, assessing changes at three points: before the training, immediately after, and six months later. The training consisted of a four-hour session combining theory and practical application, conducted by experts in contraception. RESULTS: Out of the participants, 376 healthcare professionals (a 34.3% response rate) completed the training and subsequent questionnaires. Post-training, there was an increase in the inclusion of the implant in contraceptive advice and a rise in the monthly number of implants. Knowledge about the implant, including insertion, positioning, removal, and replacement, significantly improved after six months (p<0.05), particularly among general practitioners. CONCLUSIONS: The training program successfully enhanced knowledge and handling of the contraceptive implant, leading to its increased recommendation by healthcare providers and selection by patients. Theoretical and practical training in contraception should be compulsory for healthcare providers involved in contraceptive counselling. IMPLICATIONS: A training program that includes lectures, video material, and hands-on demonstrations is effective for developing skills in administering the subdermic implant and its integration into contraceptive counselling. Such training should be regular and required for all healthcare professionals providing contraceptive advice.


Assuntos
Anticoncepção , Anticoncepcionais , Humanos , Seguimentos , Espanha , Anticoncepção/métodos , Aconselhamento/métodos
8.
Children (Basel) ; 11(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38671598

RESUMO

Advances in technology and artificial intelligence (smart healthcare) open up a range of possibilities for precision intervention in the field of health sciences. The objectives of this study were to analyse the functionality of using supervised (prediction and classification) and unsupervised (clustering) machine learning techniques to analyse results related to the development of functional skills in patients at developmental ages of 0-6 years. We worked with a sample of 113 patients, of whom 49 were cared for in a specific centre for people with motor impairments (Group 1) and 64 were cared for in a specific early care programme for patients with different impairments (Group 2). The results indicated that in Group 1, chronological age predicted the development of functional skills at 85% and in Group 2 at 65%. The classification variable detected was functional development in the upper extremities. Two clusters were detected within each group that allowed us to determine the patterns of functional development in each patient with respect to functional skills. The use of smart healthcare resources has a promising future in the field of early care. However, data recording in web applications needs to be planned, and the automation of results through machine learning techniques is required.

9.
Behav Sci (Basel) ; 14(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38540476

RESUMO

The repercussions of the pandemic caused by the SARS-CoV-2 coronavirus over recent years have posed an unprecedented challenge for the whole of society, affecting the well-being of everyone. Among all the variables affected in relation to well-being, Anxiety, Emotional Intelligence, and Effective Personality (Self-Esteem, Academic Self-Realisation, Resolute Self-Efficacy, Social Self-Realisation) have been highlighted. The aim of this study is to assess the evolution of those variables across three temporal phases: pre-pandemic, during the pandemic, and up until the end of the study in April 2022. A study was conducted during these temporal phases with three cohorts from Spanish Universities. The cohorts were formed of people assessed for Anxiety (660 pre-pandemic, 460 during the pandemic, and 311 at the end of the study), Emotional Intelligence (355 pre-pandemic, 91 during the pandemic, 311 at the end of the study), and Effective Personality (708 pre-pandemic, 174 in 2018, 311 at the end of the study). Anxiety was assessed with the State-Trait Anxiety Inventory, Emotional Intelligence with the Trait Meta-Mood Scale and TMMS-24, and Effective Personality with the Cuestionario Personalidad Eficaz-Universidad (the Effective Personality Questionnaire-University). The results showed a rise in the state of anxiety during COVID-19, with a subsequent reduction two years into the pandemic; however, anxiety rates remained higher than before the pandemic. Emotional intelligence increased in the emotional attention factor, but diminished as regards both clarity and regulation. Effective Personality was at lower levels for all factors (Self-Esteem, Academic Self-Realisation, Resolute Self-Efficacy, Social Self-Realisation). The main conclusion was the need for assistance with the dimensions under study, in order to improve the well-being of university students after the serious effects caused by COVID-19.

10.
J Biol Chem ; 287(47): 39554-63, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23019333

RESUMO

ADAMTSs (a disintegrin and metalloprotease with thrombospondin domains) are a family of enzymes with both proteolytic and protein interaction functions, which have been implicated in distinct pathologies. In this work, we have investigated the putative role of ADAMTS-12 in inflammation by using a mouse model deficient in this metalloprotease. Control and mutant mice were subjected to different experimental conditions to induce colitis, endotoxic sepsis, and pancreatitis. We have observed that Adamts12-deficient mice exhibit more severe inflammation and a delayed recovery from these challenges compared with their wild-type littermates. These changes are accompanied by an increase in inflammatory markers including several cytokines, as assessed by microarray expression analysis and proteomic-based approaches. Interestingly, the clinical symptoms observed in Adamts12-deficient mice are also concomitant with an elevation in the number of neutrophils in affected tissues. Finally, isolation and in vitro culture of human neutrophils demonstrate that the presence of ADAMTS-12 induces neutrophil apoptosis. On the basis of these results, we propose that ADAMTS-12 is implicated in the inflammatory response by modulating normal neutrophil apoptosis.


Assuntos
Proteínas ADAM/metabolismo , Colite/enzimologia , Endotoxemia/enzimologia , Neutrófilos/enzimologia , Pancreatite/enzimologia , Proteínas ADAM/genética , Proteínas ADAM/imunologia , Proteínas ADAMTS , Animais , Apoptose/genética , Apoptose/imunologia , Colite/genética , Colite/metabolismo , Colite/patologia , Endotoxemia/genética , Endotoxemia/imunologia , Endotoxemia/metabolismo , Endotoxemia/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Humanos , Inflamação/enzimologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Camundongos , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Pancreatite/genética , Pancreatite/imunologia , Pancreatite/patologia
11.
Eur J Investig Health Psychol Educ ; 13(3): 595-612, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36975398

RESUMO

BACKGROUND: The passage through university is a complex experience that can heighten personal susceptibility to eating disorders. The objective of this research is to determine how gender, age, course, educational faculty, and body mass index (BMI) can influence the risk of eating disorders among university students. METHOD: A transversal and descriptive study is conducted with a sample of 516 Spanish students (57.2% female, 42.8% male; Mage = 21.7, SDage = 4.1) following 26 university degrees. The Inventory Eating Disorder-Reference criterion (EDI-3-RF) was administered to the students. Contingency tables were used between categorical variables with the chi-squared statistic, at a significance level of p < 0.05. The Student t-test was used for two independent samples and a one-way ANOVA test with the post hoc Bonferroni test for more than two groups. Pearson's correlation and a simple linear regression analysis were used to analyze the relationship between the variables in its quantitative version. RESULTS: It was found that the female students enrolled in the second year presented a greater obsession with thinness and body dissatisfaction (p = 0.029; d = 0.338); the male students practiced more physical exercise to control their weight (p = 0.003); and that students under the age of twenty (p < 0.010; d = 0.584) and students from both the Health (p = 0.0.13) and Law (p = 0.021) educational faculties showed greater bulimic behavior (d = 0.070). More females are underweight (z = 2.8), and more men are overweight (z = 2.4). Normal-weight students scored significantly higher in thinness obsession (p = 0.033). Overweight students scored significantly higher on thinness obsession (p < 0.001) and body dissatisfaction (p < 0.001). Obese students scored significantly higher on body dissatisfaction (p = 0.04). CONCLUSIONS: The data obtained in this study, reinforce the hypothesis that the female gender, at an age within the limits of early adolescence, in the first year of the degree courses, with specific university qualifications, and a high BMI constituted factors that could provoke an eating disorder. Consequently, it is necessary to implement preventive measures adapted to the circumstances of each university student.

12.
Am J Pathol ; 178(2): 718-23, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21281804

RESUMO

Pemphigus is considered an autoimmune bullous skin disorder associated with IgG against the desmosomal components, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). This concept is supported by the in vitro and in vivo pathogenicity of anti-Dsg3/Dsg1 IgG and the mucosal blistering phenotype of mice with a genetic deficiency of Dsg3. Mice deficient for another desmosomal adhesion molecule, desmocollin 3 (Dsc3), show a similar pemphigus phenotype, and we investigated the pathogenicity of Dsc3-reactive IgG autoantibodies that were identified previously in a subset of patients with atypical pemphigus. We here demonstrate that IgG against Dsc3 causes loss of adhesion of epidermal keratinocytes. Specifically, IgG against Dsc3 was purified from Dsc3-reactive pemphigus sera by affinity column chromatography using recombinant human Dsc3. Affinity purified IgG was functionally active and did not only react with recombinant Dsc3 but also with epidermis and cultured human keratinocytes. Moreover, Dsc3-reactive IgG induced loss of adhesion of epidermal keratinocytes in a dispase-based keratinocyte dissociation assay that was reversed on pre-adsorption with human Dsc3 but not Dsg3. These findings demonstrate that IgG autoantibodies against an additional component of the desmosomes, Dsc3, induce loss of keratinocyte adhesion and thus may contribute to blister formation in pemphigus.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Desmocolinas/imunologia , Imunoglobulina G/imunologia , Queratinócitos/patologia , Pênfigo/sangue , Pênfigo/imunologia , Animais , Especificidade de Anticorpos/imunologia , Adesão Celular/imunologia , Cromatografia de Afinidade , Haplorrinos , Humanos , Camundongos , Pênfigo/patologia , Proteínas Recombinantes/imunologia
13.
Front Psychol ; 13: 764926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222180

RESUMO

BACKGROUND/OBJECTIVE: Social skills are essential in adolescence, both for their relational dimension and for their influence on other areas of adolescent life, so it is essential to include Social skills in the formal education of students. METHOD: This paper presents the results of an experimental mixed factorial design pilot study in which an Interpersonal Skills Training Program for Adolescents (PEHIA) was applied. The convenience sample consisted of 51 adolescents. An evaluation was carried out before and after the intervention, using the CEDIA (Adolescent Interpersonal Difficulties Assessment Questionnaire) and SAS-A (Social Anxiety Scale for Adolescents) questionnaires. RESULTS: The mixed factorial ANOVA show significant differences in the overall measures and in most of the subscales of both questionnaires, indicating that PEHIA is effectiveness, at least in the short term. CONCLUSIONS: The results obtained in assertiveness, interpersonal relationships and public speaking suggest that the program is feasible and shows promising results in reducing anxiety. However, a larger scale study should be conducted.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33477831

RESUMO

Mindfulness-based interventions (MBI) are a recognized effective psychological practice characterized by attention control, awareness, acceptance, non-reactivity, and non-judgmental thinking obtained through the practice of meditation. They have been shown to be useful in reducing stress and enhancing well-being in different contexts. In this research, the effectiveness of an MBI was evaluated on variables that can promote successful job performance such as mindfulness trait, positive and negative affect, forgiveness, personality strengths and satisfaction with life. The intervention was carried out through a smartphone application called "Aire Fresco" (Fresh Air) during 14 days in the middle of the quarantine produced by the Covid-19 pandemic. The study sample was composed of 164 Spanish people who were distributed in two groups: control group and experimental group, which were evaluated before and after the intervention. The MANCOVA performed showed an overall positive effect of the intervention on the variables evaluated. The different ANCOVAs carried out showed that the intervention was beneficial in increasing mindfulness trait, reducing negative affect or increasing life satisfaction, among others. Our study is, as far as we know, the first to demonstrate the effectiveness of a brief intervention in mindfulness conducted using a smartphone application in Spanish.


Assuntos
Perdão , Atenção Plena , Aplicativos Móveis , Satisfação Pessoal , Smartphone , Afeto , COVID-19 , Humanos , Pandemias , Espanha
15.
Artigo em Inglês | MEDLINE | ID: mdl-34444510

RESUMO

The scientific literature on mental health has found an association between physical activity and emotional wellbeing and recommends active leisure activities as a way of keeping stress under control. The purpose of this research study is to analyze the level of anxiety, the symptoms of depression and the level of self-esteem of people practicing speleology, as well as possible gender differences. This paper also attempts to understand whether self-esteem is associated with the presence of symptoms of depression in speleologists and whether anxiety has a mediating effect. We conduct a cross-sectional and descriptive research study with a sampling of 105 adult speleologists. The results reveal that the total mediation model is applicable, as self-esteem has a significant indirect association with depression through trait anxiety, as well as a partial mediation model that is applicable through state anxiety. This means that speleologists with high levels of self-esteem, who appreciate and value themselves adequately, reveal lower levels of trait anxiety, and this negatively influences their levels of depression (that is, a lower level of depressive symptoms). At the same time, speleologists with high levels of self-esteem, who appreciate and value themselves adequately, also reveal lower levels of state anxiety, which again has a negative impact on their levels of depression (with fewer symptoms of depression). Emotions such as anxiety, self-esteem, depression and their collateral effects are international topics of interest, which are relevant for people from all sporting backgrounds; therefore, value should be placed on supporting and carrying out further research into this topic.


Assuntos
Ansiedade , Depressão , Adulto , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Humanos , Autoimagem , Fatores Sexuais
16.
Artigo em Inglês | MEDLINE | ID: mdl-32121514

RESUMO

Currently, teaching in higher education is being heavily developed by learning management systems that record the learning behaviour of both students and teachers. The use of learning management systems that include project-based learning and hypermedia resources increases safer learning, and it is proven to be effective in degrees such as nursing. In this study, we worked with 120 students in the third year of nursing degree. Two types of blended learning were applied (more interaction in learning management systems with hypermedia resources vs. none). Supervised learning techniques were applied: linear regression and k-means clustering. The results indicated that the type of blended learning in use predicted 40.4% of student learning outcomes. It also predicted 71.9% of the effective learning behaviors of students in learning management systems. It therefore appears that blended learning applied in Learning Management System (LMS) with hypermedia resources favors greater achievement of effective learning. Likewise, with this type of Blended Learning (BL) a larger number of students were found to belong to the intermediate cluster, suggesting that this environment strengthens better results in a larger number of students. BL with hypermedia resources and project-based learning increase students´ learning outcomes and interaction in learning management systems. Future research will be aimed at verifying these results in other nursing degree courses.


Assuntos
Instrução por Computador/métodos , Bacharelado em Enfermagem/métodos , Aprendizagem , Estudantes de Enfermagem/psicologia , Adulto , Avaliação Educacional , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Educacionais , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-32630314

RESUMO

As entrepreneurial interest is believed to represent a causal factor increasing entrepreneurship, research has begun to explore how family systems affect youth entrepreneurial interests. In the present study, we attempt to identify different types of family influence on the entrepreneurial interests of young people. A questionnaire was used to obtain data from 1633 Spanish adolescents (15 to 18 years old) and another questionnaire was used to obtain data from 839 parents. Principal component analysis identified unique family types and revealed that they have differential associations to entrepreneurial interest among youth. These findings reaffirm the influence of family on the entrepreneurial ecosystem and the promotion of an entrepreneurial family culture. This study further suggests that early attention should focus on the detection of entrepreneurial interest among youth so that actions can be implemented in the families to incentivize an entrepreneurial family culture.


Assuntos
Ecossistema , Empreendedorismo , Pais , Adolescente , Humanos , Espanha , Inquéritos e Questionários
18.
BMC Biochem ; 7: 9, 2006 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-16566820

RESUMO

BACKGROUND: We have previously described the identification and characterization of polyserase-1 and polyserase-2, two human serine proteases containing three different catalytic domains within the same polypeptide chain. Polyserase-1 shows a complex organization and it is synthesized as a membrane-bound protein which can generate three independent serine protease domains as a consequence of post-translational processing events. The two first domains are enzymatically active. By contrast, polyserase-2 is an extracellular glycosylated protein whose three protease domains remain embedded in the same chain, and only the first domain possesses catalytic activity. RESULTS: Following our interest in the study of the human degradome, we have cloned a human liver cDNA encoding polyserase-3, a new protease with tandem serine protease domains in the same polypeptide chain. Comparative analysis of polyserase-3 with the two human polyserases described to date, revealed that this novel polyprotein is more closely related to polyserase-2 than to polyserase-1. Thus, polyserase-3 is a secreted protein such as polyserase-2, but lacks additional domains like the type II transmembrane motif and the low-density lipoprotein receptor module present in the membrane-anchored polyserase-1. Moreover, analysis of post-translational mechanisms operating in polyserase-3 maturation showed that its two protease domains remain as integral parts of the same polypeptide chain. This situation is similar to that observed in polyserase-2, but distinct from polyserase-1 whose protease domains are proteolytically released from the original chain to generate independent units. Immunolocalization studies indicated that polyserase-3 is secreted as a non-glycosylated protein, thus being also distinct from polyserase-2, which is a heavily glycosylated protein. Enzymatic assays indicated that recombinant polyserase-3 degrades the alpha-chain of fibrinogen as well as pro-urokinase-type plasminogen activator (pro-uPA). Northern blot analysis showed that polyserase-3 exhibits a unique expression pattern among human polyserases, being predominantly detected in testis, liver, heart and ovary, as well as in several tumor cell lines. CONCLUSION: These findings contribute to define the growing group of human polyserine proteases composed at present by three different proteins. All of them share a complex structural design with several catalytic units in a single polypeptide but also show specific features in terms of enzymatic properties, expression patterns and post-translational maturation mechanisms.


Assuntos
Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Dimerização , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Serina Endopeptidases/genética , Homologia Estrutural de Proteína , Distribuição Tecidual
19.
Gene ; 283(1-2): 49-62, 2002 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-11867212

RESUMO

ADAMTS (A Disintegrin And Metalloproteinase domain, with ThromboSpondin type-1 modules) is a recently described family of zinc-dependent proteases which play important roles in a variety of normal and pathological conditions, including arthritis and cancer. In this work, we report the identification and cloning of cDNAs encoding seven new human ADAMTSs. These novel enzymes have been called ADAMTS-13, -14, -15, -16, -17, -18, and -19. All of them show a domain organization similar to that of previously characterized family members, consisting of a signal sequence, a propeptide, a metalloproteinase domain, a disintegrin-like domain, a cysteine-rich region, and a variable number of TS-1 repeats. Expression analysis revealed that these ADAMTS genes are mainly expressed in fetal tissues, especially in lung (ADAMTS14, ADAMTS16, ADAMTS17, ADAMTS18, and ADAMTS19), kidney (ADAMTS14, ADAMTS15, and ADAMTS16), and liver (ADAMTS13, ADAMTS15 and ADAMTS18). Reverse transcriptase--polymerase chain reaction analysis also revealed the expression of some of these new ADAMTSs in different human adult tissues, such as prostate (ADAMTS13, ADAMTS17, and ADAMTS18), and brain (ADAMTS13, ADAMTS16, ADAMTS17, and ADAMTS18). High levels of ADAMTSs transcripts were also observed in some tumor biopsies and cells lines, including osteosarcomas (ADAMTS19), melanoma and colon carcinoma cells (ADAMTS13). Chromosomal location analysis indicated that the seven identified ADAMTS genes are dispersed in the human genome mapping to 9q34, 10q21, 11q25, 5p15, 15q24, 16q23, and 5q31, respectively. According to these results, together with a comparative analysis of ADAMTSs in other eukaryotic organisms, we conclude that these enzymes, with at least 18 distinct members encoded within the human genome, represent an example of a widely expanded protease family during metazoan evolution.


Assuntos
Proteínas ADAM/genética , Desintegrinas/genética , Metaloendopeptidases/genética , Trombospondina 1/genética , Proteínas ADAMTS , Adulto , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/genética , Domínio Catalítico , Mapeamento Cromossômico , Clonagem Molecular , Cisteína/genética , DNA Complementar/química , DNA Complementar/genética , Drosophila melanogaster/genética , Feminino , Expressão Gênica , Genoma Humano , Humanos , Masculino , Metaloendopeptidases/química , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Isoformas de Proteínas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos
20.
Oncotarget ; 5(5): 1253-64, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24457941

RESUMO

Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Besides this structural function, fibulins also play crucial roles in different biological events, including tumorigenesis. To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we performed different in vitro assays using two breast cancer cell lines: the poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data indicate that this interaction promotes anti-tumor effects in breast cancer cells. To assess the in vivo relevance of this interaction, we induced tumors in nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical staining of breast cancer samples allowed the detection of both ADAMTS-12 and fibulin-2 in the connective tissue surrounding tumor area in less aggressive carcinomas. However, both proteins are hardly detected in more aggressive tumors. These data and survival analysis plots of breast cancer patients suggest that concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker in breast cancer diagnosis.


Assuntos
Proteínas ADAM/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas ADAM/análise , Proteínas ADAM/genética , Proteínas ADAMTS , Animais , Neoplasias da Mama/química , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/genética , Movimento Celular , Proliferação de Células , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Camundongos , Invasividade Neoplásica , Prognóstico , Esferoides Celulares , Carga Tumoral , Microambiente Tumoral
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