Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Span J Psychol ; 27: e2, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38311914

ABSTRACT

The main goal of the present research is to develop and validate the Perceived Economic Inequality Scale (PEIS), an instrument measuring individuals' perceptions of economic inequality at the national level. The study was conducted on a representative sample of the Italian population (N = 1,446, 51% women). The factorial structure of the scale was assessed through cross-validated exploratory-confirmatory factor analyses. To inspect the PEIS psychometric properties, item and correlation analyses were performed. The results showed that the PEIS is a valid and reliable unidimensional measure of perceived economic inequality at the national level. Further support of the PEIS construct validity was provided by the correlation of the scale score with the perceived wage gap and ideological beliefs like the economic system justification, social dominance orientation, meritocratic beliefs, and participants' political orientation. Crucially, multigroup confirmatory factor analysis supported configural, metric, and scalar invariances of the scale across socio-demographic groups. The PEIS allows researchers to assess the subjective component of economic inequality by also serving as a useful tool for unpacking the psychological correlates of perceived inequality.


Subject(s)
Motivation , Humans , Female , Male , Surveys and Questionnaires , Psychometrics , Factor Analysis, Statistical , Reproducibility of Results
2.
Span. j. psychol ; 27: e2, Feb. 2024. tab, graf
Article in English | IBECS | ID: ibc-230532

ABSTRACT

The main goal of the present research is to develop and validate the Perceived Economic Inequality Scale (PEIS), an instrument measuring individuals’ perceptions of economic inequality at the national level. The study was conducted on a representative sample of the Italian population (N = 1,446, 51% women). The factorial structure of the scale was assessed through cross-validated exploratory-confirmatory factor analyses. To inspect the PEIS psychometric properties, item and correlation analyses were performed. The results showed that the PEIS is a valid and reliable unidimensional measure of perceived economic inequality at the national level. Further support of the PEIS construct validity was provided by the correlation of the scale score with the perceived wage gap and ideological beliefs like the economic system justification, social dominance orientation, meritocratic beliefs, and participants’ political orientation. Crucially, multigroup confirmatory factor analysis supported configural, metric, and scalar invariances of the scale across socio-demographic groups. The PEIS allows researchers to assess the subjective component of economic inequality by also serving as a useful tool for unpacking the psychological correlates of perceived inequality. (AU)


Subject(s)
Humans , Male , Female , Motivation , Social Perception , Psychometrics , Factor Analysis, Statistical , Perception , Surveys and Questionnaires , Reproducibility of Results
3.
PLoS One ; 19(2): e0298222, 2024.
Article in English | MEDLINE | ID: mdl-38412193

ABSTRACT

Understanding lay theories on the causes of economic inequality is the first step to comprehending why people tolerate, justify, or react against it. Accordingly, this paper aims to develop and validate with two cross-sectional studies the Attributions for Cross-Country Inequality Scale (ACIS), which assesses how people explain cross-country economic inequality-namely, the uneven distribution of income and wealth between poor and rich countries. After selecting and adapting items from existing scales of attributions for poverty and wealth, in Study 1, we tested the factorial structure of this initial pool of items in three countries with different levels of economic development and inequality, namely, Italy (n = 246), the UK (n = 248), and South Africa (n = 228). Three causal dimensions emerged from the Exploratory Factor Analysis: "rich countries" (blaming the systematic advantage of and exploitation by rich countries), "poor countries" (blaming the dispositional inadequacy and faults of poor countries), and "fate" (blaming destiny and luck). The retained items were administered in Study 2 to three new samples from Italy (n = 239), the UK (n = 249), and South Africa (n = 248). Confirmatory Factor Analysis (CFA) corroborated the factorial structure of the ACIS, and Multi-Group CFA supported configural and metric invariances of the scale across countries. In addition, we show internal consistency and construct validity of the scale: the scale correlates with relevant constructs (e.g., beliefs about cross-country inequality and ideological orientation) and attitudes toward relevant policies related to international redistribution and migration. Overall, the scale is a valid instrument to assess causal attribution for cross-national inequality and is reliable across countries. By focusing on resource distribution from an international perspective, this scale will allow researchers to broaden the discussion on economic inequality to a global level.


Subject(s)
Income , Poverty , Humans , Cross-Sectional Studies , Policy , South Africa , Socioeconomic Factors
4.
Cogn Emot ; : 1-16, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37724804

ABSTRACT

Social learning plays a prominent role in shaping individual preferences. The vicarious approach-avoidance effect consists of developing a preference for attitudinal objects that have been approached over objects that have been avoided by another person (model). In two experiments (N = 448 participants), we explored how the vicarious approach-avoidance effect is affected by agency (model's voluntary choice) and identification with the model. The results consistently revealed vicarious approach-avoidance effects in preference, as indicated by the semantic differential and the Implicit Association Test. Agency increased the size of the preference assessed through the semantic differential but did not significantly impact preference in the Implicit Association Test. Identification with the model had no significant impact on the vicarious approach-avoidance effect. Theoretical and practical implications of the results are discussed.

5.
Psychol Methods ; 28(3): 580-599, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36913286

ABSTRACT

Big Data can bring enormous benefits to psychology. However, many psychological researchers show skepticism in undertaking Big Data research. Psychologists often do not take Big Data into consideration while developing their research projects because they have difficulties imagining how Big Data could help in their specific field of research, imagining themselves as "Big Data scientists," or for lack of specific knowledge. This article provides an introductory guide for conducting Big Data research for psychologists who are considering using this approach and want to have a general idea of its processes. By taking the Knowledge Discovery from Database steps as the fil rouge, we provide useful indications for finding data suitable for psychological investigations, describe how these data can be preprocessed, and list some techniques to analyze them and programming languages (R and Python) through which all these steps can be realized. In doing so, we explain the concepts with the terminology and take examples from psychology. For psychologists, familiarizing with the language of data science is important because it may appear difficult and esoteric at first approach. As Big Data research is often multidisciplinary, this overview helps build a general insight into the research steps and a common language, facilitating collaboration across different fields. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Big Data , Psychology , Humans , Psychology/methods
6.
Neurol Sci ; 44(2): 529-538, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36197578

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has forced significant changes in clinical practice. Psychologists and neuropsychologists had to modify their settings to assess patients' abilities, switching from an in-person modality to a remote setting by using video calling platforms. Consequently, this change brought about the need for new normative data tailored to remote settings. AIM AND METHODS: The study aimed to develop normative data for the online assessment of neuropsychological memory tests and to compare it with the published norms obtained in standard settings. Two hundred and four healthy Italian volunteers performed three verbal memory tests through the Google Meet platform: the Digit Span (Backward and Forward), the Rey Auditory Verbal Learning, and the Verbal Paired Associated Learning Test. RESULTS: This research provides specific norms that consider the influence of demographic characteristics. Their comparison with published norms shows a medium to high agreement between systems. The present study provides a reference for the clinical use of neuropsychological instruments to assess verbal memory in a remote setting and offers specific recommendations.


Subject(s)
COVID-19 , Pandemics , Humans , Memory/physiology , Neuropsychological Tests , Verbal Learning/physiology
7.
Neurol Sci ; 43(9): 5243-5249, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35581425

ABSTRACT

INTRODUCTION: Neuropsychological assessment of cognitive functioning is a crucial part of clinical care: diagnosis, treatment planning, treatment evaluation, research, and prediction of long-term outcomes. The Equivalent Score (ES) method is used to score numerous neuropsychological tests. The ES0 and the ES4 are defined respectively by the outer tolerance limit and the median. The intermediate ESs are commonly calculated using a z-score approach even when the distribution of neuropsychological data is typically non-parametric. To calculate more accurate ESs, we propose that the intermediate ESs need to be calculated based on a non-parametric rank subdivision of the distribution of the adjusted scores. MATERIAL AND METHODS: We make three simulations to explain the differences between the classical z-score approach, the rank-based approach, and the direct subdivision of the dependent variable. RESULTS: The results show that the rank procedure permits dividing the region between ES0 and ES4 into three areas with the same density. The z-score procedure is quite similar to the direct subdivision of the dependent variable and different from the rank subdivision. CONCLUSIONS: By subdividing intermediate ESs using the rank-subdivision, neuropsychological tests can be scored more accurately, also considering that the two essential points for diagnosis (ES = 0 and ES = 4) remain the same. Future normative data definition should consider the best procedure for scoring with ES.


Subject(s)
Cognition , Cognition/physiology , Humans , Neuropsychological Tests
8.
Article in English | MEDLINE | ID: mdl-36612816

ABSTRACT

Background: This study aimed to identify clusters of long COVID-19 symptoms using latent class analysis and investigate the psychological factors involved in the onset of this syndrome. Method: Five hundred and six subjects recovering from COVID-19 completed a series of standardized questionnaires to evaluate the personality traits, alexithymia, and post-traumatic stress. Results: Five classes were identified: Brain fog (31.82%), No symptoms (20.95%), Sensory disorders (18.77%), Breath impairment (17.59%), and Multiple disorders (10.87%). Women reported post-COVID-19 respiratory symptoms and multiple disorders to a greater extent than men. Hospitalized subjects were more likely to report persistent symptoms after COVID-19 than asymptomatic or home-treated subjects. Antagonism, hyperarousal, and difficulty identifying emotions significantly predicted post COVID-19 symptoms. Conclusions: These findings open new questions for research on long COVID-19 and how states of emotional dysregulation can alter the physiological processes of the body and contribute to the onset of organic pathologies.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Male , Humans , Female , Post-Acute COVID-19 Syndrome , Stress Disorders, Post-Traumatic/psychology , Latent Class Analysis , COVID-19/epidemiology , Affective Symptoms
9.
Psychiatry Res ; 308: 114353, 2022 02.
Article in English | MEDLINE | ID: mdl-34968807

ABSTRACT

High rates of post-traumatic stress disorder (PTSD) symptoms have been found among patients with more severe COVID-19-related symptoms, and hospitalization is generally recognized as a risk factor for developing PTSD. Furthermore, other personality characteristics may increase the risk of developing post-traumatic stress symptoms following a COVID-19 infection. This study aimed to assess personality traits, alexithymia, dissociation, anxiety, and depression in patients who have recovered from COVID-19 and the impact of these variables on the presence of post-traumatic stress symptoms. Five hundred and six participants completed a battery of standardized questionnaires. All the scales used in this study are valid and reliable measures of their respective constructs. Results showed that high levels of alexithymia, dissociation, anxiety, and depression statistically significantly predicted the three main clusters of PTSD symptoms (avoidance, intrusion, and hyperarousal) in individuals who have recovered from COVID-19. Furthermore, negative affectivity and psychoticism significantly predicted PTSD symptoms in our sample. Finally, individuals hospitalized by COVID-19 are more at risk of developing intrusion and hyperarousal symptoms than those who never needed hospital care. Our findings are a valuable contribution in identifying the main risk factors of psychological distress related to COVID-19 to address the long-term mental health needs of people who have experienced the disease.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Cross-Sectional Studies , Hospitalization , Humans , SARS-CoV-2 , Stress Disorders, Post-Traumatic/epidemiology
10.
Mol Ther ; 29(1): 86-102, 2021 01 06.
Article in English | MEDLINE | ID: mdl-33010230

ABSTRACT

Chronic granulomatous disease (CGD) is a rare inherited disorder due to loss-of-function mutations in genes encoding the NADPH oxidase subunits. Hematopoietic stem and progenitor cell (HSPC) gene therapy (GT) using regulated lentiviral vectors (LVs) has emerged as a promising therapeutic option for CGD patients. We performed non-clinical Good Laboratory Practice (GLP) and laboratory-grade studies to assess the safety and genotoxicity of LV targeting myeloid-specific Gp91phox expression in X-linked chronic granulomatous disease (XCGD) mice. We found persistence of gene-corrected cells for up to 1 year, restoration of Gp91phox expression and NADPH oxidase activity in XCGD phagocytes, and reduced tissue inflammation after LV-mediated HSPC GT. Although most of the mice showed no hematological or biochemical toxicity, a small subset of XCGD GT mice developed T cell lymphoblastic lymphoma (2.94%) and myeloid leukemia (5.88%). No hematological malignancies were identified in C57BL/6 mice transplanted with transduced XCGD HSPCs. Integration pattern analysis revealed an oligoclonal composition with rare dominant clones harboring vector insertions near oncogenes in mice with tumors. Collectively, our data support the long-term efficacy of LV-mediated HSPC GT in XCGD mice and provide a safety warning because the chronic inflammatory XCGD background may contribute to oncogenesis.


Subject(s)
Genetic Therapy , Genetic Vectors/genetics , Granulomatous Disease, Chronic/complications , Granulomatous Disease, Chronic/therapy , Hematologic Neoplasms/etiology , Lentivirus/genetics , Animals , Disease Models, Animal , Genetic Therapy/adverse effects , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Granulomatous Disease, Chronic/genetics , Humans , Mice , NADPH Oxidase 2/genetics , NADPH Oxidase 2/metabolism , Time Factors , Treatment Outcome
11.
Eur J Psychol ; 15(3): 595-613, 2019 Sep.
Article in English | MEDLINE | ID: mdl-33680148

ABSTRACT

The previous research attempts to reduce the influence of the belief bias on deductive thinking have often been unsuccessful and, when they succeeded, they failed to replicate. In this paper, we propose a new way to see an old problem. Instead of considering the analytical abilities of the respondent, we focus on the communicative characteristics of the experimental task. By changing the pragmatics into play through a subtle manipulation of the instruction of the syllogism problem, we obtained a strong improvement in the accuracy of the performance in both untrained and trained in logic respondents. We suggest that current models of deductive thinking should be broadened to consider also communicative understanding as part of the processing of the problem.

12.
Mol Ther Methods Clin Dev ; 11: 9-28, 2018 Dec 14.
Article in English | MEDLINE | ID: mdl-30320151

ABSTRACT

Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for ß-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of ß-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for ß-thalassemia.

13.
Hum Gene Ther Clin Dev ; 28(1): 17-27, 2017 03.
Article in English | MEDLINE | ID: mdl-28319446

ABSTRACT

GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Ex vivo gene therapy of patient bone-marrow CD34+ cells is an alternative treatment. In order to prepare for a marketing authorization application in the European Union, preclinical safety studies in mice were requested by the European Medicines Agency (EMA). A pilot study and a main biodistribution study were performed according to Good Laboratory Practice (GLP) at the San Raffaele Telethon Institute for Gene Therapy test facility. In the main study, human umbilical cord blood (UCB)-derived CD34+ cells were transduced with gamma-retroviral vector used in the production of GSK2696273. Groups of 10 male and 10 female NOD-SCID gamma (NSG) mice were injected intravenously with a single dose of transduced- or mock-transduced UCB CD34+ cells, and they were observed for 4 months. Engraftment and multilineage differentiation of blood cells was observed in the majority of animals in both groups. There was no significant difference in the level of chimerism between the two groups. In the gene therapy group, vector was detectable in lymphohemopoietic and nonlymphohemopoietic tissues, consistent with the presence of gene-modified human hematopoietic donor cells. Given the absence of relevant safety concerns in the data, the nonclinical studies and the clinical experience with GSK2696273 supported a successful application for market authorization in the European Union for the treatment of ADA-SCID patients, for whom no suitable human leukocyte antigen-matched related donor is available.


Subject(s)
Adenosine Deaminase/deficiency , Agammaglobulinemia/therapy , Genetic Therapy , Genetic Vectors/therapeutic use , Laboratories/standards , Severe Combined Immunodeficiency/therapy , Adenosine Deaminase/genetics , Agammaglobulinemia/genetics , Animals , Drug Evaluation, Preclinical , Female , Gene Transfer Techniques , Humans , Male , Mice , Mice, Inbred NOD , Mice, SCID , Severe Combined Immunodeficiency/genetics , Tissue Distribution
14.
Mol Med ; 22: 809-820, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27900389

ABSTRACT

OBJECTIVE: The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute. METHODS: We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and ptx3-deficient mice. RESULTS: Ptx3 expression was up-regulated three-five days after injury and restricted to the extracellular matrix. Cellular debris and leukocytes persisted in the muscle of ptx3-deficient mice for a long time after wild-type animals had healed. ptx3-deficient macrophages expressed receptors involved in apoptotic cell clearance and engulfed dead cells in vitro. Accumulation of cell debris in a pro-inflammatory microenvironment was not sufficient to elicit autoantibodies. CONCLUSION: PTX3 generated in response to muscle injury prompts the clearance of debris and the termination of the inflammatory response.

15.
Hum Gene Ther ; 27(10): 813-829, 2016 10.
Article in English | MEDLINE | ID: mdl-27431943

ABSTRACT

In order to support the clinical application of hematopoietic stem cell (HSC) gene therapy for mucopolysaccharidosis I (MPS I), biosafety studies were conducted to assess the toxicity and tumorigenic potential, as well as the biodistribution of HSCs and progenitor cells (HSPCs) transduced with lentiviral vectors (LV) encoding the cDNA of the alpha-iduronidase (IDUA) gene, which is mutated in MPS I patients. To this goal, toxicology and biodistribution studies were conducted, employing Good Laboratory Practice principles. Vector integration site (IS) studies were applied in order to predict adverse consequences of vector gene transfer and to obtain HSC-related information. Overall, the results obtained in these studies provided robust evidence to support the safety and tolerability of high-efficiency LV-mediated gene transfer and above-normal IDUA enzyme expression in both murine and human HSPCs and their in vivo progeny. Taken together, these investigations provide essential safety data to support clinical testing of HSC gene therapy in MPS I patients. These studies also underline criticisms associated with the use of currently available models, and highlight the value of surrogate markers of tumorigenicity that may be further explored in the future. Notably, biological evidence supporting the efficacy of gene therapy on MPS I disease and its feasibility on patients' HSCs were also generated, employing clinical-grade LVs. Finally, the clonal contribution of LV-transduced HSPCs to hematopoiesis along serial transplantation was quantified in a minimum of 200-300 clones, with the different level of repopulating cells in primary recipients being reflected in the secondary.


Subject(s)
Genetic Therapy/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Iduronidase/genetics , Mucopolysaccharidosis I/therapy , Animals , Gene Expression Regulation, Enzymologic , Gene Transfer Techniques/adverse effects , Genetic Therapy/methods , Genetic Vectors/adverse effects , Hematopoietic Stem Cells/enzymology , Humans , Iduronidase/adverse effects , Iduronidase/therapeutic use , Lentivirus/genetics , Mice , Mucopolysaccharidosis I/genetics
16.
PLoS One ; 10(6): e0128094, 2015.
Article in English | MEDLINE | ID: mdl-26039259

ABSTRACT

Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.


Subject(s)
Cell Lineage , Forkhead Transcription Factors/metabolism , Muscle, Skeletal/injuries , Muscle, Skeletal/pathology , Regeneration , Satellite Cells, Skeletal Muscle/pathology , T-Lymphocytes/immunology , Animals , Antigens, CD/metabolism , Cell Differentiation , Cell Proliferation , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/immunology
17.
PLoS One ; 8(3): e59308, 2013.
Article in English | MEDLINE | ID: mdl-23555016

ABSTRACT

Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils' necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P<0.05) and F.A. (P<0.05) compared with young muscles. After acute damage T2-rt increased in otherwise healthy young muscles with a peak at day 3, followed by a progressive decrease to basal values. F.A. dropped 24 hours after injury and afterward increased above the basal level in the regenerated muscle (from day 7 to day 15) returning to the basal value at the end of the follow up period. The ADC displayed opposite kinetics. T2-rt positively correlated with the number of infiltrating leucocytes retrieved by immunomagnetic bead sorting from the tissue (r = 0.92) and with the damage/infiltration score (r = 0.88) while F.A. correlated with the extent of tissue regeneration evaluated at various time points after injury (r = 0.88). Our results indicate that multiparametric MRI is a sensitive and informative tool for monitoring inflammatory and structural muscle changes in living experimental animals; particularly, it allows identifying the increase of T2-rt and F.A. as common events reflecting inflammatory infiltration and muscle regeneration in the transient response of the tissue to acute injury and in the persistent adaptation to aging.


Subject(s)
Aging , Diffusion Tensor Imaging/methods , Muscle, Skeletal/pathology , Regeneration/physiology , Sarcopenia/pathology , Animals , Cardiotoxins , Cell Movement , Female , Homeostasis/physiology , Leukocytes/cytology , Mice , Muscle, Skeletal/injuries , Myofibrils/pathology , Sarcopenia/chemically induced , Sarcopenia/physiopathology
18.
J Immunol ; 188(12): 6267-77, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22573810

ABSTRACT

The aim of this study was to verify whether macrophages influence the fate of transplanted mesoangioblasts--vessel-associated myogenic precursors--in a model of sterile toxin-induced skeletal muscle injury. We have observed that in the absence of macrophages, transplanted mesoangioblasts do not yield novel fibers. Macrophages retrieved from skeletal muscles at various times after injury display features that resemble those of immunoregulatory macrophages. Indeed, they secrete IL-10 and express CD206 and CD163 membrane receptors and high amounts of arginase I. We have reconstituted the muscle-associated macrophage population by injecting polarized macrophages before mesoangioblast injection: alternatively activated, immunoregulatory macrophages only support mesoangioblast survival and function. This action depends on the secretion of IL-10 in the tissue. Our results reveal an unanticipated role for tissue macrophages in mesoangioblast function. Consequently, the treatment of muscle disorders with mesoangioblasts should take into consideration coexisting inflammatory pathways, whose activation may prove crucial for its success.


Subject(s)
Interleukin-10/metabolism , Macrophages/metabolism , Muscle Fibers, Skeletal/cytology , Muscle, Skeletal/injuries , Pericytes/cytology , Stem Cells/cytology , Animals , Blotting, Western , Cell Differentiation , Cell Separation , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Fluorescent Antibody Technique , Interleukin-10/immunology , Macrophages/immunology , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/metabolism , Pericytes/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Stem Cell Transplantation , Stem Cells/metabolism
19.
Antioxid Redox Signal ; 15(8): 2161-74, 2011 Oct 15.
Article in English | MEDLINE | ID: mdl-21294652

ABSTRACT

High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and thioredoxin. HMGB1, a protein thiol, weakly expressed in healthy muscles, increases during regeneration in parallel with the antioxidant response in both fibers and leukocytes. A reduced environment may be important to maintain HMGB1 bioactivity. Indeed, oxidation abrogates both muscle stem cell migration in response to HMGB1 and their ability to differentiate into myofibers in vitro. We propose that the early antioxidant response in regenerating muscle limits HMGB1 oxidation, thus allowing successful muscle regeneration.


Subject(s)
HMGB1 Protein/metabolism , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Antioxidants/metabolism , Blotting, Western , Cell Differentiation/physiology , Cells, Cultured , Female , Fluorescent Antibody Technique , HMGB1 Protein/genetics , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscle, Skeletal/physiology , Muscle, Skeletal/ultrastructure , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Regeneration/genetics , Regeneration/physiology , Reverse Transcriptase Polymerase Chain Reaction , SKP Cullin F-Box Protein Ligases/genetics , SKP Cullin F-Box Protein Ligases/metabolism , Satellite Cells, Skeletal Muscle/cytology , Satellite Cells, Skeletal Muscle/metabolism , Tripartite Motif Proteins , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
20.
Ann N Y Acad Sci ; 1209: 83-90, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20958320

ABSTRACT

High-mobility group box-1 (HMGB1) is a prototypical endogenous signal that links tissue necrosis and wound healing. Extracellular HMGB1 has apparently contrasting biological actions: it sustains inflammation (with the possible establishment of autoimmunity or of self-maintaining tissue damage) while activating and recruiting stem cells, which foster tissue repair. However, little is known about the role environmental cues play in the extracellular functions of HMGB1. The skeletal muscle is an optimal tissue model to help us unravel these underlying molecular events. Here, sterile injury triggers a potent inflammatory response that includes infiltration by inflammatory leukocytes and the parallel activation, proliferation, and fusion of muscle-specific stem cells. Recent data suggest that the regulation of environmental redox is critical for the bioactivity of HMGB1, which is extremely sensitive to oxidation. Moreover, data suggest a potential role for infiltrating alternatively activated macrophages to influence the outcome of inflammatory responses to sterile skeletal muscle necrosis.


Subject(s)
HMGB1 Protein/physiology , Muscle, Skeletal/injuries , Animals , Base Sequence , DNA Primers , Humans , Macrophages/cytology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Stem Cells/cytology
SELECTION OF CITATIONS
SEARCH DETAIL
...