Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Torres, Diego José Lira; Arruda, Tiago Ribeiro de; Barros, Michelle da Silva; Gonçales, Juliana Prado; Soares, Ana Karine de Araújo; Oliveira, Kamila Kássia dos Santos; Moreira, Leyllane Rafael; Medeiros, Carolina de Araújo; Cavalcanti, Maria da Gloria Aureliano Melo; Martins, Sílvia Marinho; Carrazzone, Cristina de Fátima Velloso; Oliveira, Wilson de; Lannes-Vieira, Joseli; Lorena, Virgínia Maria Barros de

doi:10.1016/j.imbio.2021.152166

Cited by 4 publications

(9 citation statements)

References 32 publications

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“…erefore, we can refer to the framework of IAsTE to simplify the corpus structure, starting from English at the beginning, and gradually adding French, Russian, Arabic, and Spanish terminology translations. Add term definitions, sources, authors, related literature, and reference sources for term translation, enrich term entries, and improve the quality of terms and term translation [16].…”

Section: E Starting Point Of the Researchmentioning

confidence: 99%

A Study on the Impact of International Translation Levels Based on Multiple Correlation Analysis

Zheng

2022

Mathematical Problems in Engineering

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Since my country’s accession to the World Trade Organization, the opening up of the financial industry has gradually deepened, and the banking industry has gradually developed into an international trend. In the development of international financial business, especially when banks carry out deposits and loans, international communication is a must. Indispensably, the international language of English is very important at this time. For the unique features of the language of financial English, the frequently used skills and common difficulties in Chinese-English translation are summarized in this paper, and financial English is analyzed from the aspects of laws and characteristics.

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Section: E Starting Point Of the Researchmentioning

confidence: 99%

A Study on the Impact of International Translation Levels Based on Multiple Correlation Analysis

Zheng

2022

Mathematical Problems in Engineering

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“…While there is a predominance of anti-inflammatory cytokines in the IND form, cardiac impairment is evidenced by greater production of pro-inflammatory cytokines, especially TNF. [14][15][16][17][18][19][20][21][22][23] Initially, we evaluated cytokine production among carriers only in the culture condition with only PBMCs. Our data indicate an increase in TNF in patients with severe Chagas heart disease (CARD2) compared to those with mild Chagas heart disease (CARD1) and NEG.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17]19 Our group measured the levels of TNF and its soluble receptors, sTNFR1 and sTNFR2, in the serum of 132 chronic carriers clinics. 20 It is essential to highlight the complexity of the immune response in the disease; TNF plays a critical role and may influence other markers (Table 2). On the other hand, our data show that PBMCs from carriers with the CARD2 form produce smaller amounts of IL-4 when compared to non-infectious heart disease (idiopathic).…”

Section: Discussionmentioning

confidence: 99%

“…This cytokine binds to its receptors, TNFR1 and TNFR2, which also participate in immunopathology associated with cardiac damage or regulation. 20,21 Understanding the immunological mechanisms involved in the chronic clinical forms of Chagas disease can contribute to the search for immune biomarkers and serve as therapeutic targets since cytokines such as TNF contribute to the inflammatory process of the infection. Thus, we aimed to study the Th1/Th2 profile cytokines in culture supernatants of peripheral blood mononuclear cells from carriers with different clinical forms of Chagas disease treated with two anti-TNF biologics, Adalimumab (ADA) and Etanercept (ETA), isolated or associated with Benznidazole (BZ), the drug of choice for the etiological treatment in Brazil.…”

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TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease

Torres,

dos Santos Oliveira,

da Silva Barros

et al. 2024

Parasite Immunology

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Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]‐4 and IL‐10) and inflammatory (TNF, interferon‐gamma [IFN‐γ], IL‐2 and IL‐6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms—IND (n = 13) mild heart form—CARD1 (n = 13) and severe cardiac form—CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN‐γ increased in the CARD2 group after treatment with ETA relative to ADA. IL‐4 had its levels decreased when treated by both drugs. IL‐2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL‐2/TNF and increased IL‐4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.

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“…Increased TNF and soluble TFNR1 (sTNFR1) serum levels, biomarkers of systemic inflammatory diseases, are detected in chronic CD patients regardless of clinical forms. (39) Severity of CCC is correlated with high serum levels of proinflammatory (IL-6, IL-17, IFNγ, TNF) and regulatory (IL-4, IL-10, TGFβ) cytokines, chemokines (CCL2, CCL3, CCL5), and the inflammatory mediators NO. (9,10,11,40) Although most evidence lacks causal correlation, these data suggest that CCC is associated with a systemic inflammatory profile.…”

Section: Pathogenic Mechanisms and Modulatory Preclinical Strategy Te...mentioning

confidence: 99%

Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach*

Lannes‐Vieira

2022

Mem. Inst. Oswaldo Cruz

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Chagas disease (CD), caused by infection by the protozoan parasite Trypanosoma cruzi, presents as main clinical manifestation the chronic chagasic cardiomyopathy (CCC). CCC afflicts millions of people, mostly in Latin America, and vaccine and effective therapy are still lacking. Comprehension of the host/parasite interplay in the chronic phase of T. cruzi infection may unveil targets for rational trait-based therapies to improve CCC prognosis. In the present viewpoint, I critically summarise a collection of data, obtained by our network of collaborators and other groups on CCC and preclinical studies on pathogenesis, targeting identification for intervention and the use of drugs with immunomodulatory properties to improve CCC. In the last two decades, models combining mouse lineages and T. cruzi strains allowed replication of crucial clinical, histopathological, and immunological traits of CCC. This condition includes conduction changes (heart rate changes, arrhythmias, atrioventricular blocks, prolongation of the QRS complex and PR and corrected QT intervals), ventricular dysfunction and heart failure, CD8-enriched myocarditis, tissue remodeling and progressive fibrosis, and systemic inflammatory profile, resembling "cytokine storm". Studies on Chagas' heart disease pathogenesis begins to unveil the molecular mechanisms underpinning the inflammation-related cardiac tissue damage, placing IFNγ, TNF and NFκB signaling as upstream regulators of miRNAs and mRNAs associated with critical biological pathways as cell migration, inflammation, tissue remodeling and fibrosis, and mitochondrial dysfunction. Further, data on preclinical trials using hypothesis-based tools, targeting parasite and inflammationrelated alterations, opened paths for multi-therapeutic approaches in CCC. Despite the long path taken using experimental CD models replicating relevant aspects of CCC and testing new therapies and therapeutic schemes, these findings may get lost in translation, as conceptual and economical challenges, underpinning the valley of death across preclinical and clinical trials. It is hoped that such difficulties will be overcome in the near future.

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Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Cited by 4 publications

References 32 publications

A Study on the Impact of International Translation Levels Based on Multiple Correlation Analysis

A Study on the Impact of International Translation Levels Based on Multiple Correlation Analysis

TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease

Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach*

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