Adriana Franco Paes Leme

Laboratório Nacional de Ciência e Tecnologia do Bioetanol

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Co-Authors

Romênia R. Domingues

Laboratório Nacional de Ciência e Tecnologia do Bioetanol

Daniela Campos Granato

Brazilian Biosciences National Laboratory

Bianca Alves Pauletti

Brazilian Biosciences National Laboratory

Alan Roger Santos‐Silva

Universidade Estadual de Campinas (UNICAMP)

Carolina Moretto Carnielli

Brazilian Biosciences National Laboratory

Márcio Ajudarte Lopes

Universidade Estadual de Campinas (UNICAMP)

Ana Carolina Prado Ribeiro

Instituto do Câncer do Estado de São Paulo

Thaís Bianca Brandão

Instituto do Câncer do Estado de São Paulo

Jaime Aparecido Cury

Universidade Estadual de Campinas (UNICAMP)

Sami Yokoo

Brazilian Biosciences National Laboratory

Cooperative Institutions

Universidade Estadual de Campinas (UNICAMP)

454

Universidade de São Paulo

326

Brazilian Center for Research in Energy and Materials

236

Brazilian Biosciences National Laboratory

192

Laboratório Nacional de Ciência e Tecnologia do Bioetanol

171

Universidade Estadual Paulista (Unesp)

104

Hospital de Clínicas da Unicamp

Instituto Butantan

Universidade de Ribeirão Preto

Universidade Federal do Rio de Janeiro

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Identification of Novel Interaction between ADAM17 (a Disintegrin and Metalloprotease 17) and Thioredoxin-1

Journal of Biological Chemistry (2012)

Annelize Zambon Barbosa Aragão Maria Luiza Caldas Nogueira Daniela Campos Granato Fernando Moreira Simabuco Rodrigo V. Honorato

Identification

10.1074/jbc.m112.364513

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Citations (39)

Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival

Molecular & Cellular Proteomics (2023)

Carolina Moretto Carnielli Thayná Melo de Lima Morais Fábio Malta de Sá Patroni Ana Carolina Prado Ribeiro Thaís Bianca Brandão

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site-specific N-glycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue N-glycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.

Glycoproteomics

Glycomics

Glycome

Glycobiology

10.1016/j.mcpro.2023.100586

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Citations (16)

MASS SPECTROMETRY-BASED PROTEOME PROFILE DIFFERENTIATES ADENOID CYSTIC CARCINOMA FROM POLYMORPHOUS ADENOCARCINOMA

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology (2019)

Felipe Paiva Fonseca Sara Ferreira dos Santos Costa CAROLINA SOARES CARNEIRO MACEDO Adriana Franco Paes Leme Hélder Antônio Rebelo Pontes

Adenoid Cystic Carcinoma

Proteome

Laser capture microdissection

UniProt

10.1016/j.oooo.2019.06.641

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Citations (0)

Abstract 15141: Machine Learning-Driven Serum Metabolomics: Insights Into the Transition to Early-Stage Heart Failure With Preserved Ejection Fraction

Circulation (2022)

Marcos Rodrigo Alborghetti Renato A. Hortegal Jose Pereira Mariana Grizante Renato Cancellier

Introduction: Metabolomics has emerged as a powerful tool in providing readouts of early disease states before clinical manifestation. Here we used the predictive power of Unsupervised Hierarchical Clustering Analysis (UHCA) and Automated Machine Learning (AutoML) algorithms to identify serum metabolic panels in a population at risk of developing HFpEF. Methods: We studied 215 subjects staged as non-HF, pre-HFpEF and early-stage HFpEF(es-HFpEF). We evaluated clinical, laboratory, echocardiographic, and NMR-based metabolomics of blood serum data. UHCA and AutoML were used to explore metabolic fingerprints potentially related to clinical features or HFpEF. We used Metabolite Set Enrichment Analysis to explore biochemical pathways. Results: The UHCA identified three major patients (P) and two metabolites (M) clusters (Figure). The P clusters were associated with HFpEF stages, cardiac remodeling, diastolic dysfunction, and sex (Pearson Chi-square, p < 0.05) and M clusters with glycine and serine metabolism and urea cycle pathways (FDR-adjusted p-value < 0.002). Considering non-HFpEF and es-HFpEF groups, AUROC mean for feature subset combinations was 0.897 and the highest AUROC (0.995) combined metabolites, clinical, laboratory and echo features. Of the 64 models trained that included metabolites as input, serine (25), uridine (17), 2-oxoglutarate (14), citrate (14), 2-aminobutyrate (13) and taurine (13) were observed more frequently with feature importance value greater than zero. The metabolites with higher sum values of feature importance were serine (0.173), uridine (0.131), 2-aminobutyrate (0.123), choline (0.098) and dimethylamine (0.087). Conclusions: This study revealed characteristic metabolite profiles in the sera of patients at risk of developing HFpEF. These metabolite panels can add information for classificatory algorithms development and contribute to the understanding of HFpEF pathophysiology.

False Discovery Rate

10.1161/circ.146.suppl_1.15141

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MOESM2 of Mapping N-linked glycosylation of carbohydrate-active enzymes in the secretome of Aspergillus nidulans grown on lignocellulose

Figshare (2016)

Marcelo Rubio Mariane Paludetti Zubieta João Franco Cairo Felipe Calzado Adriana Franco Paes Leme

Additional file 2: Table S1. Identified proteins and spectrum counts.

Aspergillus nidulans

10.6084/m9.figshare.c.3599441_d1

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Analysis of the subproteomes of proteinases and heparin‐binding toxins of eight Bothrops venoms

PROTEOMICS (2009)

Adriana Franco Paes Leme Eduardo S. Kitano Maria F. Furtado Richard H. Valente Antônio Carlos Martins de Camargo

Viperid snakes show the most complex snake-venom proteomes and offer an intriguing challenge in terms of understanding the nature of their components and the pathological outcomes of envenomation characterized by local and systemic effects. In this work, the venom complexity of eight Bothrops species was analyzed by 2-DE, and their subproteomes of proteinases were explored by 2-D immunostaining and 2-D gelatin zymography, demonstrating the diversity of their profiles. Heparin, a highly sulfated glycosaminoglycan released from mast cells, is involved in anti-coagulant and anti-inflammatory processes. Here, we explored the hypothesis that heparin released upon envenomation could interact with toxins and interfere with venom pathogenesis. We first identified the Bothrops venom subproteome of toxins that bind with high-affinity for heparin as composed of mainly serine proteinases and C-type lectins. Next, we explored the Bothrops jararaca toxins that bind to heparin under physiological conditions and identified a relationship between the subproteomes of proteinases, and that of heparin-binding toxins. Only the non-bound fraction, composed mainly of metalloproteinases, showed lethal and hemorrhagic activities, whereas the heparin-bound fraction contained mainly serine proteinases associated with coagulant and fibrinogenolytic activities. These data suggest that heparin binding to B. jararaca venom components in vivo has a minor protective effect to venom toxicity.

Bothrops jararaca

Bothrops

10.1002/pmic.200800484

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Citations (42)

Extracellular Vesicles from Different Sources of Mesenchymal Stromal Cells Have Distinct Effects on Lung and Distal Organs in Experimental Sepsis

International Journal of Molecular Sciences (2023)

Natália G. Blanco NAOMY SOL FERNANDES MACHADO Lígia Lins de Castro Mariana A. Antunes Christina Maeda Takiya

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.

Extracellular vesicles

10.3390/ijms24098234

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Citations (10)

Effect of 10% carbamide peroxide bleaching on sound and artificial enamel carious lesions

Brazilian Dental Journal (2009)

Cristiane Franco Pinto Adriana Franco Paes Leme Vanessa Cavalli Marcelo Giannini

This study evaluated the effect of 10% carbamide peroxide (CP) bleaching on Knoop surface microhardness (KHN) and morphology of sound enamel and enamel with early artificial caries lesions (CL) after pH-cycling model (pHcm). Human dental enamel blocks were randomly divided into 6 groups (n=10): 1 - sound enamel bleached (S) with CP (Rembrandt/Den-Mat); 2 - S and submitted to pHcm; 3 - CL bleached with CP; 4 - CL stored in artificial saliva and submitted to pHcm; 5 - CL treated with placebo gel and submitted to pHcm; 6 - CL bleached with CP and submitted to pHcm. Enamel blocks with known initial KHN values were demineralized (groups 3 to 6) and submitted to 12 day pHcm (groups 2, 4, 5 and 6). After demineralization and treatments, KHN was determined and the specimens were examined using scanning electron microscopy (SEM). Data were analyzed statistically by ANOVA and Tukey's test at 5% significance level. The results showed that among CL groups (3 to 6) only the group 3 presented remineralization after treatments. S groups (1 and 2) showed higher KHN and presented less formation of porosities on enamel surface than CL groups after treatments. In conclusion, bleaching procedures on enamel with CL did not exacerbate the demineralization, but should be indicated with caution.

Knoop hardness test

Carbamide peroxide

Tooth Whitening

10.1590/s0103-64402009000100008

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Citations (39)

Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study

PLoS neglected tropical diseases (2017)

José Xavier‐Neto Murilo de Carvalho Bruno dos Santos Pascoalino Alisson C. Cardoso Ângela Maria Sousa Costa

The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5–9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes.

Zika Virus

10.1371/journal.pntd.0005363

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Citations (111)

Proteomic analysis of human dental cementum and alveolar bone

Journal of Proteomics (2013)

Cristiane R. Salmon Daniela M. Tomazela Karina Gonzáles Silvério Brian L. Foster Adriana Franco Paes Leme

Periodontal fiber

Proteome

Dental cementum

10.1016/j.jprot.2013.08.016

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Citations (96)