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Publicações Científicas e Culturais 22795
Recursos Educacionais 447
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Exposições ocupacionais a HIV e HBV em ambientes odontológicos: revisão sistemática, avaliação da qualidade dos registros de acidentes biológicos e análise descritiva com modelagem por clusters
(Universidade Federal de Minas Gerais, 2025-12-09) Ana Carolina Marques Medeiros
Occupational accidents involving exposure to biological materials constitute an important public health problem, particularly in dental practice, where the intensive use of sharp instruments, close proximity to the oral cavity, and the dynamics of clinical procedures increase the risk of contact with potentially infectious fluids. Among the most relevant hazards are the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV), whose potential for seroconversion underscores the need for continuous surveillance and evidence-based prevention strategies. This doctoral thesis was structured around three complementary methodological approaches, which resulted in independent and interconnected scientific products. The first approach consisted of a global systematic review with meta-analysis aimed at estimating the incidence of occupational HIV seroconversion among healthcare workers exposed to biological materials. The search was conducted in six international bibliographic databases and grey literature, with the protocol registered on the PROSPERO platform. Observational studies were included, and quantitative syntheses were performed using random-effects models, stratified according to type of exposure, use of post-exposure prophylaxis (PEP), and completeness of clinical follow-up, in addition to assessments of risk of bias and certainty of evidence. The results indicated a low incidence of occupational HIV seroconversion, with rare events even following percutaneous exposures, high consistency across studies, and no seroconversion among individuals who used PEP, in contrast to higher, although still rare, rates among those with indication but without PEP use. The second approach corresponded to an evaluation of the quality of information recorded in notification forms for accidents involving exposure to biological material in the Sistema de Informação de Agravos de Notificação (Sinan), referring to dental settings in the municipality of Belo Horizonte between 2006 and 2019. The attributes of completeness, internal consistency, and duplicity were analyzed according to guidelines of the Ministério da Saúde. The analysis showed no duplicate records and high completeness of mandatory variables. However, essential clinical and care-related variables, such as laboratory testing, post-exposure management, and case evolution, exhibited predominantly poor or very poor completeness, as well as relevant inconsistencies, particularly in the “Evolução do caso” field, indicating limitations of the system for infection risk assessment and adequate follow-up of exposed workers. The third approach involved a descriptive observational study based on the same dataset, with characterization of reported exposures and application of the TwoStep Cluster method to identify risk profiles. Exposures occurred predominantly via the percutaneous route during clinical procedures, with incomplete use of personal protective equipment and frequent gaps in the documentation of laboratory tests and post-exposure follow-up. Cluster analysis identified two distinct profiles, one characterized by lower biological risk and another associated with mucosal and non-intact skin exposures, a higher proportion of positive or unknown sources, and less adequate protective barriers, with no recorded seroconversions to HIV, HBV, or HCV. The study was approved by the Comitês de Ética em Pesquisa da Universidade Federal de Minas Gerais (approval no. 6.097.439) and the Secretaria Municipal de Saúde de Belo Horizonte (approval no. 6.161.565).
Regulatory/inflammatory cellular response discrimination in operational tolerance
(Universidade Federal de Minas Gerais, 2019) Priscila Carmona; Yordanka Medina-Armenteros; Amanda Cabral; Sandra Maria Monteiro; Simone Gonçalves Fonseca; Ana Maria Caetano de Faria; Francine Lemos; David Saitovitch; Irene de Lourdes Noronha; Jorge Kalil; Verônica Coelho
Background Antigen-specific cellular response is essential in immune tolerance. We tested whether antigen-specific cellular response is differentially modulated in operational tolerance (OT) in renal transplantation with respect to critical antigenic challenges in allotransplantation—donor antigens, pathogenic antigens and self-antigens. Methods We analysed the profile of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines for the antigen-specific response directed to these three antigen groups, by Luminex. Results We showed that, in contrast to chronic rejection and healthy individuals, OT gives rise to an immunoregulatory deviation in the cellular response to donor human leucocyte antigen DR isotype peptides, while preserving the pro-inflammatory response to pathogenic peptides. Cellular autoreactivity to the N6 heat shock protein 60 (Hsp60) peptide also showed a REG profile in OT, increasing IL4, IL-5, IL-10 and IL-13. Conclusions The REG shift of donor indirect alloreactivity in OT, with inhibition of interleukin (IL)-1B, IL-8, IL-12, IL-17, granulocyte colony-stimulating factor, Interferon-γ and monocyte chemoattractant protein-1, indicates that this may be an important mechanism in OT. In addition, the differential REG profile of cellular response to the Hsp60 peptide in OT suggests that REG autoimmunity may also play a role in human transplantation tolerance. Despite cross-reactivity of antigen-specific T cell responses, a systemic functional antigen-specific discrimination takes place in OT.
Compartmentalized gut lymph node drainage dictates adaptive immune responses
(Universidade Federal de Minas Gerais, 2019) Daria Esterházy; Maria Cecilia Campos Canesso; Luka Mesin; Paul Muller; Tiago Bruno Rezende de Castro; Ainsley Lockhart; Mahmoud ElJalby; Ana Maria Caetano de Faria; Daniel Mucida
The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure of this balance leads to conditions such as inflammatory bowel diseases, food allergies and invasive gastrointestinal infections1. Multiple immune mechanisms are therefore in place to maintain tissue integrity, including balanced generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively1,2,3,4. The gut-draining lymph nodes (gLNs) are key sites for orchestrating adaptive immunity to luminal perturbations5,6,7. However, it is unclear how they simultaneously support tolerogenic and inflammatory reactions. Here we show that gLNs are immunologically specific to the functional gut segment that they drain. Stromal and dendritic cell gene signatures and polarization of T cells against the same luminal antigen differ between gLNs, with the proximal small intestine-draining gLNs preferentially giving rise to tolerogenic responses and the distal gLNs to pro-inflammatory T cell responses. This segregation permitted the targeting of distal gLNs for vaccination and the maintenance of duodenal pTreg cell induction during colonic infection. Conversely, the compartmentalized dichotomy was perturbed by surgical removal of select distal gLNs and duodenal infection, with effects on both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory intestinal responses is in part resolved by discrete gLN drainage, and encourage antigen targeting to specific gut segments for therapeutic immune modulation.
Cell-free dna as a biomarker of aging
(Universidade Federal de Minas Gerais, 2018-12-20) Yee Voan Teo; Miriam Capri; Cristina Morsiani; Grazia Pizza; Ana Maria Caetano Faria; Claudio Franceschi; Nicola Neretti
Cell-free DNA (cfDNA) is present in the circulating plasma and other body fluids and is known to originate mainly from apoptotic cells. Here, we provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. In addition, we detected a relative cfDNA loss at several genomic locations, such as transcription start and termination sites, 5′UTR of L1HS retrotransposons and dimeric AluY elements with age. Our results also revealed age and deteriorating health status correlate with increased enrichment of signals from cells in different tissues. In conclusion, our results show that the sequencing of circulating cfDNA from human blood plasma can be used as a noninvasive methodology to study age-associated changes to the epigenome in vivo.
Aberrant methylation patterns in colorectal cancer: a meta-analysis
(Universidade Federal de Minas Gerais, 2017) Danielle Fernandes Durso; Maria Giulia Bacalini; Ítalo Faria do Valle; Chiara Pirazzini; Massimiliano Bonafé; Gastone Castellani; Ana Maria Caetano Faria; Claudio Franceschi; Paolo Garagnani; Christine Nardini
Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon. To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group [1], through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing -regardless of the level of cellular control- their role in the complex of alterations involved in tumorigenesis. These findings were finally validated in an independent cohort from The Cancer Genome Atlas (TCGA).

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