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  1. Article: Frequency determination of breast tumor-reactive CD4 and CD8 T cells in humans: unveiling the antitumor immune response.

    Pinho, Mariana Pereira / Patente, Thiago Andrade / Flatow, Elizabeth Alexandra / Sallusto, Federica / Barbuto, José Alexandre Marzagão

    Oncoimmunology

    2019  Volume 8, Issue 8, Page(s) 1607674

    Abstract: As cancer immunotherapy gains importance, the determination of a patient's ability to react to his/her tumor is unquestionably relevant. Though the presence of T cells that recognize specific tumor antigens is well established, the total frequency of ... ...

    Abstract As cancer immunotherapy gains importance, the determination of a patient's ability to react to his/her tumor is unquestionably relevant. Though the presence of T cells that recognize specific tumor antigens is well established, the total frequency of tumor-reactive T cells in humans is difficult to assess, especially due to the lack of broad analysis techniques. Here, we describe a strategy that allows this determination, in both CD4 and CD8 compartments, using T cell proliferation induced by tumor cell-lysate pulsed dendritic cells as the readout. All 12 healthy donor tested had circulating CD4 and CD8 tumor cell-reactive T cells. The detection of these T cells, not only in the naïve but also in the memory compartment, can be seen as an evidence of tumor immunosurveillance in humans. As expected, breast cancer patients had higher frequencies of blood tumor-reactive T cells, but with differences among breast cancer subtypes. Interestingly, the frequency of blood tumor-reactive T cells in patients did not correlate to the frequency of infiltrating tumor-reactive T cells, highlighting the danger of implying a local tumor response from blood obtained data. In conclusion, these data add T cell evidence to immunosurveillance in humans, confirm that immune parameters in blood may be misleading and describe a tool to follow the tumor-specific immune response in patients and, thus, to design better immunotherapeutic approaches.
    Language English
    Publishing date 2019-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2019.1607674
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Acetate Improves the Killing of

    Machado, Marina Gomes / Patente, Thiago Andrade / Rouillé, Yves / Heumel, Severine / Melo, Eliza Mathias / Deruyter, Lucie / Pourcet, Benoit / Sencio, Valentin / Teixeira, Mauro Martins / Trottein, François

    Frontiers in immunology

    2022  Volume 13, Page(s) 773261

    Abstract: Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota with a known role in immune regulation. Acetate, the major SCFA, is described to disseminate to distal organs such as lungs where it can arm sentinel cells, including ... ...

    Abstract Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota with a known role in immune regulation. Acetate, the major SCFA, is described to disseminate to distal organs such as lungs where it can arm sentinel cells, including alveolar macrophages, to fight against bacterial intruders. In the current study, we explored mechanisms through which acetate boosts macrophages to enhance their bactericidal activity. RNA sequencing analyses show that acetate triggers a transcriptomic program in macrophages evoking changes in metabolic process and immune effector outputs, including nitric oxide (NO) production. In addition, acetate enhances the killing activity of macrophages towards
    MeSH term(s) Acetates/pharmacology ; Animals ; Biomarkers ; Cytotoxicity, Immunologic/drug effects ; Disease Models, Animal ; Disease Susceptibility ; Gene Knockdown Techniques ; Glycolysis ; Host-Pathogen Interactions/immunology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Macrophages, Alveolar/physiology ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide/metabolism ; Oxygen Consumption ; Pneumococcal Infections/etiology ; Pneumococcal Infections/metabolism ; RNA, Small Interfering/genetics ; Streptococcus pneumoniae/immunology
    Chemical Substances Acetates ; Biomarkers ; Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Small Interfering ; Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2022-01-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.773261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes.

    Admoni, Sharon Nina / Santos-Bezerra, Daniele Pereira / Perez, Ricardo Vesoni / Patente, Thiago Andrade / Monteiro, Maria Beatriz / Cavaleiro, Ana Mercedes / Parisi, Maria Candida / Moura Neto, Arnaldo / Pavin, Elizabeth Joao / Queiroz, Marcia Silva / Nery, Marcia / Correa-Giannella, Maria Lucia

    Diabetes & vascular disease research

    2019  Volume 16, Issue 3, Page(s) 297–299

    Abstract: Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the ...

    Abstract Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27-42] years old; diabetes duration: 21 [15-27] years; HbA1c: 8.3% [7.4-9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17-0.90; p  = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.
    MeSH term(s) Adult ; Autonomic Nervous System/physiopathology ; Cardiovascular System/physiopathology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/enzymology ; Diabetes Mellitus, Type 1/genetics ; Diabetic Neuropathies/diagnosis ; Diabetic Neuropathies/enzymology ; Diabetic Neuropathies/genetics ; Diabetic Neuropathies/physiopathology ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Glutathione Peroxidase/genetics ; Humans ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Risk Assessment ; Risk Factors
    Chemical Substances phospholipid-hydroperoxide glutathione peroxidase (EC 1.11.1.12) ; Glutathione Peroxidase (EC 1.11.1.9)
    Language English
    Publishing date 2019-01-01
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2250793-0
    ISSN 1752-8984 ; 1479-1641
    ISSN (online) 1752-8984
    ISSN 1479-1641
    DOI 10.1177/1479164118820641
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals.

    Perez, Ricardo Vessoni / Machado, Cleide Guimarães / Santos-Bezerra, Daniele Pereira / Admoni, Sharon Nina / Patente, Thiago Andrade / Monteiro, Maria Beatriz / Cavaleiro, Ana Mercedes / Queiroz, Márcia Silva / Nery, Márcia / Corrêa-Giannella, Maria Lúcia

    Gene

    2019  Volume 703, Page(s) 120–124

    Abstract: Aims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) ... ...

    Abstract Aims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4.
    Methods: A cross-sectional case-control study included 288 individuals (61% women, 34[±11] years old, diabetes duration of 22[±9] years, mean [±SD]) sorted according to DR stages: absence of DR (ADR), non-proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed.
    Results: The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38-13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11-0.80, p = 0.017) in female T1D individuals.
    Conclusion: The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication.
    MeSH term(s) Adult ; Age of Onset ; Case-Control Studies ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/genetics ; Diabetic Retinopathy/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Glutamate-Cysteine Ligase/genetics ; Glutathione Peroxidase/genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult
    Chemical Substances phospholipid-hydroperoxide glutathione peroxidase (EC 1.11.1.12) ; Glutathione Peroxidase (EC 1.11.1.9) ; GCLC protein, human (EC 6.3.2.2) ; Glutamate-Cysteine Ligase (EC 6.3.2.2)
    Language English
    Publishing date 2019-04-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2019.04.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals

    Perez, Ricardo Vessoni / Machado, Cleide Guimarães / Santos-Bezerra, Daniele Pereira / Admoni, Sharon Nina / Patente, Thiago Andrade / Monteiro, Maria Beatriz / Cavaleiro, Ana Mercedes / Queiroz, Márcia Silva / Nery, Márcia / Corrêa-Giannella, Maria Lúcia

    Gene. 2019 June 30, v. 703

    2019  

    Abstract: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in ... ...

    Abstract Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4.A cross-sectional case-control study included 288 individuals (61% women, 34[±11] years old, diabetes duration of 22[±9] years, mean [±SD]) sorted according to DR stages: absence of DR (ADR), non-proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed.The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38–13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11–0.80, p = 0.017) in female T1D individuals.The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication.
    Keywords alleles ; allelic variation ; antioxidants ; case-control studies ; diabetic retinopathy ; females ; fluorescence ; genotyping ; glutathione ; insulin-dependent diabetes mellitus ; oxidative stress ; pathogenesis ; quantitative polymerase chain reaction ; regression analysis ; risk factors ; single nucleotide polymorphism ; women
    Language English
    Dates of publication 2019-0630
    Size p. 120-124.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2019.04.015
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Macrophage inflammatory state in Type 1 diabetes: triggered by NLRP3/iNOS pathway and attenuated by docosahexaenoic acid.

    Davanso, Mariana Rodrigues / Crisma, Amanda Rabello / Braga, Tárcio Teodoro / Masi, Laureane Nunes / do Amaral, Cátia Lira / Leal, Vinícius Nunes Cordeiro / de Lima, Dhêmerson Souza / Patente, Thiago Andrade / Barbuto, José Alexandre / Corrêa-Giannella, Maria L / Lauterbach, Mario / Kolbe, Carl Christian / Latz, Eicke / Camara, Niels Olsen Saraiva / Pontillo, Alessandra / Curi, Rui

    Clinical science (London, England : 1979)

    2021  Volume 135, Issue 1, Page(s) 19–34

    Abstract: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by insulin-producing pancreatic β-cell destruction and hyperglycemia. While monocytes and NOD-like receptor family-pyrin domain containing 3 (NLRP3) are associated with T1D ... ...

    Abstract Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by insulin-producing pancreatic β-cell destruction and hyperglycemia. While monocytes and NOD-like receptor family-pyrin domain containing 3 (NLRP3) are associated with T1D onset and development, the specific receptors and factors involved in NLRP3 inflammasome activation remain unknown. Herein, we evaluated the inflammatory state of resident peritoneal macrophages (PMs) from genetically modified non-obese diabetic (NOD), NLRP3-KO, wild-type (WT) mice and in peripheral blood mononuclear cells (PBMCs) from human T1D patients. We also assessed the effect of docosahexaenoic acid (DHA) on the inflammatory status. Macrophages from STZ-induced T1D mice exhibited increased inflammatory cytokine/chemokine levels, nitric oxide (NO) secretion, NLRP3 and iNOS protein levels, and augmented glycolytic activity compared to control animals. In PMs from NOD and STZ-induced T1D mice, DHA reduced NO production and attenuated the inflammatory state. Furthermore, iNOS and IL-1β protein expression levels and NO production were lower in the PMs from diabetic NLRP3-KO mice than from WT mice. We also observed increased IL-1β secretion in PBMCs from T1D patients and immortalized murine macrophages treated with advanced glycation end products and palmitic acid. The present study demonstrated that the resident PMs are in a proinflammatory state characterized by increased NLRP3/iNOS pathway-mediated NO production, up-regulated proinflammatory cytokine/chemokine receptor expression and altered glycolytic activity. Notably, ex vivo treatment with DHA reverted the diabetes-induced changes and attenuated the macrophage inflammatory state. It is plausible that DHA supplementation could be employed as adjuvant therapy for treating individuals with T1D.
    MeSH term(s) Adult ; Animals ; Anti-Inflammatory Agents/pharmacology ; Cells, Cultured ; Cytokines/metabolism ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/enzymology ; Diabetes Mellitus, Experimental/immunology ; Diabetes Mellitus, Type 1/chemically induced ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/enzymology ; Diabetes Mellitus, Type 1/immunology ; Docosahexaenoic Acids/pharmacology ; Female ; Humans ; Inflammation/chemically induced ; Inflammation/drug therapy ; Inflammation/enzymology ; Inflammation/immunology ; Inflammation Mediators/metabolism ; Macrophage Activation/drug effects ; Macrophages, Peritoneal/drug effects ; Macrophages, Peritoneal/enzymology ; Macrophages, Peritoneal/immunology ; Male ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Pregnancy ; Signal Transduction ; Streptozocin ; Mice
    Chemical Substances Anti-Inflammatory Agents ; Cytokines ; Inflammation Mediators ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Nlrp3 protein, mouse ; Docosahexaenoic Acids (25167-62-8) ; Streptozocin (5W494URQ81) ; NOS2 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39)
    Language English
    Publishing date 2021-01-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20201348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

    Soares, Jaine L S / Fernandes, Fernanda Pereira / Patente, Thiago Andrade / Monteiro, Maria B / Parisi, Maria C / Giannella-Neto, Daniel / Corrêa-Giannella, Maria L / Pontillo, Alessandra

    Clinical immunology (Orlando, Fla.)

    2017  Volume 187, Page(s) 46–49

    Abstract: Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of ... ...

    Abstract Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adult ; Apoptosis Regulatory Proteins/genetics ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/metabolism ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/genetics ; Female ; Gain of Function Mutation ; Genetic Predisposition to Disease ; Humans ; Inflammasomes/genetics ; Male ; Middle Aged ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Prospective Studies ; Retrospective Studies ; Serum Albumin/metabolism ; Stress, Physiological ; Young Adult
    Chemical Substances Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Blood Glucose ; Inflammasomes ; NLRP1 protein, human ; Serum Albumin ; glycated serum albumin
    Language English
    Publishing date 2017-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2017.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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