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Article: The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review.

Fiestas Solórzano, Victor Edgar / de Lima, Raquel Curtinhas / de Azeredo, Elzinandes Leal

2022 Volume 11, Issue 10

Abstract: Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping ... ...

Abstract	Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied.
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11101179
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antiviral and Virucidal Activities of

de Lima, Raquel Curtinhas / Valente, Ligia Maria Marino / Familiar Macedo, Débora / de-Oliveira-Pinto, Luzia Maria / Dos Santos, Flavia Barreto / Mazzei, José Luiz / Siani, Antonio Carlos / Nunes, Priscila Conrado Guerra / de Azeredo, Elzinandes Leal

Viruses

2024 Volume 16, Issue 3

Abstract: ... Uncaria ... ...

Abstract	Uncaria tomentosa
MeSH term(s)	Cat's Claw ; Chikungunya virus ; Plant Extracts/pharmacology ; Plants, Medicinal ; Antiviral Agents/pharmacology ; Chikungunya Fever/drug therapy
Chemical Substances	Plant Extracts ; Antiviral Agents
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030369
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Analysis of a Routinely Used Commercial Anti-Chikungunya IgM ELISA Reveals Cross-Reactivities with Dengue in Brazil: A New Challenge for Differential Diagnosis?

Lima, Monique da Rocha Queiroz / de Lima, Raquel Curtinhas / de Azeredo, Elzinandes Leal / Dos Santos, Flavia Barreto

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 5

Abstract: In Brazil, chikungunya emerged in 2014, and by 2016, co-circulated with other arbovirosis, such as dengue and zika. ELISAs (Enzyme-Linked Immunosorbent Assays) are the most widely used approach for arboviruses diagnosis. However, some limitations include ...

Abstract	In Brazil, chikungunya emerged in 2014, and by 2016, co-circulated with other arbovirosis, such as dengue and zika. ELISAs (Enzyme-Linked Immunosorbent Assays) are the most widely used approach for arboviruses diagnosis. However, some limitations include antibody cross reactivities when viruses belong to the same genus, and sensitivity variations in distinct epidemiological scenarios. As chikungunya virus (CHIKV) is an alphavirus, no serological cross reactivity with dengue virus (DENV) should be observed. Here, we evaluated a routinely used chikungunya commercial IgM (Immunoglobulin M) ELISA test (Anti-Chikungunya IgM ELISA, Euroimmun) to assess its performance in confirming chikungunya in a dengue endemic area. Samples (
Language	English
Publishing date	2021-04-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11050819
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Article ; Online: Miconia albicans (Melastomataceae) to treat Chikungunya viral infection: An effectual symptom-driven ethnomedicinal repurposing of an anti-inflammatory species?

do Nascimento, Sarah Neves / Mazzei, José Luiz / Tostes, João Batista de Freitas / Nakamura, Marcos Jun / Valente, Ligia Maria Marino / de Lima, Raquel Curtinhas / Nunes, Priscila Conrado Guerra / de Azeredo, Elzinandes Leal / Berrueta, Luis Angel / Gallo, Blanca / Siani, Antonio Carlos

Journal of ethnopharmacology

2023 Volume 318, Issue Pt A, Page(s) 116875

Abstract: Ethnopharmacological relevance: Miconia albicans (MA) is consumed all over the Brazilian territory as a remedy to treat rheumatoid arthritis and has been increasingly used to alleviate the deleterious symptoms caused by Chikungunya virus (CHIKV).: Aim ...

Abstract	Ethnopharmacological relevance: Miconia albicans (MA) is consumed all over the Brazilian territory as a remedy to treat rheumatoid arthritis and has been increasingly used to alleviate the deleterious symptoms caused by Chikungunya virus (CHIKV). Aim of the study: To investigate the effect of MA leaf and stem hydroethanolic extracts (LE and SE, respectively), their fractions enriched in triterpene acids or polyphenols as well isolated constituents, on CHIKV hosted in Vero cells. Materials and methods: Polyphenol profiles of LE and SE were dereplicated by HPLC-DAD-ESI-MS/MS, aided by standards. Polyphenol-rich (LEx and SEx) and triterpenic acid-rich (LOH and SOH) fractions were obtained in Amberlite XAD-4 and alkalinized 95% ethanol (EtOH) extraction, respectively. TPC and TFC were assessed by colorimetric methods. Three representative flavonoids and two triterpenic acids were quantified by HPLC. CHIKV load suppression was evaluated in Vero cells by real-time qRT‒PCR at noncytotoxic concentrations. Results: Fifteen flavonoids were characterized in LE and SE. LEx presented isoquercitrin, quercitrin, rutin (0.49-1.51%) and quercetin. The TPC was 48 and 62 mg QE/g extract, and the TFC was 11.93 and 0.76 mg QE/g extract for LEx and SEx, respectively. LOH presented ursolic (15.3%) and oleanolic (8.0%) acids. A reduction (91-97%) in the CHIKV load was produced by the triterpene fraction, quercitrin and quercetin; the latter maintained the activity down to one twentieth of the tolerated concentration. Conclusion: M. albicans contains flavonoids and triterpenic acids that are effective against CHIKV, which might justify its use to alleviate sequelae of CHIKV infection. However, further investigations on the species and its active constituents are needed.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Chikungunya virus ; Chikungunya Fever/drug therapy ; Vero Cells ; Melastomataceae ; Quercetin/pharmacology ; Tandem Mass Spectrometry ; Flavonoids/pharmacology ; Polyphenols/pharmacology ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Triterpenes/pharmacology ; Triterpenes/therapeutic use
Chemical Substances	Quercetin (9IKM0I5T1E) ; Flavonoids ; Polyphenols ; Plant Extracts ; Anti-Inflammatory Agents ; Triterpenes
Language	English
Publishing date	2023-07-12
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.116875
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Article ; Online: Pro-Inflammatory Profile of Children Exposed to Maternal Chikungunya Virus Infection during the Intrauterine Period: A One-Year Follow-Up Study.

Faustino, Renan / Carvalho, Fabiana Rabe / Medeiros, Thalia / Familiar-Macedo, Débora / Vianna, Renata Artimos de Oliveira / Leite, Paulo Emílio Côrrea / Pereira, Isabela Resende / Cardoso, Claudete Aparecida Araújo / De Azeredo, Elzinandes Leal / Silva, Andrea Alice

Viruses

2022 Volume 14, Issue 9

Abstract: Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to ... ...

Abstract	Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated.
MeSH term(s)	Becaplermin ; Chemokine CCL3 ; Chemokine CCL4 ; Chikungunya Fever ; Chikungunya virus ; Cross-Sectional Studies ; Cytokines ; Female ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunoglobulin M ; Infant ; Infant, Newborn ; Interleukin-6 ; Interleukin-7 ; Male ; Tumor Necrosis Factor-alpha
Chemical Substances	Chemokine CCL3 ; Chemokine CCL4 ; Cytokines ; Immunoglobulin M ; Interleukin-6 ; Interleukin-7 ; Tumor Necrosis Factor-alpha ; Becaplermin (1B56C968OA) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2022-08-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14091881
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pro-Inflammatory Profile of Children Exposed to Maternal Chikungunya Virus Infection during the Intrauterine Period: A One-Year Follow-Up Study

Viruses. 2022 Aug. 26, v. 14, no. 9

2022

Abstract	Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated.
Keywords	Chikungunya fever ; Chikungunya virus ; children ; cross-sectional studies ; immune response ; interleukin-6 ; interleukin-7 ; males ; maternal exposure ; viremia
Language	English
Dates of publication	2022-0826
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14091881
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Miconia albicans (Melastomataceae) to treat Chikungunya viral infection: An effectual symptom-driven ethnomedicinal repurposing of an anti-inflammatory species?

do Nascimento, Sarah Neves / Mazzei, José Luiz / de Freitas Tostes, João Batista / Nakamura, Marcos Jun / Valente, Ligia Maria Marino / de Lima, Raquel Curtinhas / Guerra Nunes priscila, Priscila Conrado / de Azeredo, Elzinandes Leal / Berrueta, Luis Angel / Gallo, Blanca / Siani, Antonio Carlos

Journal of Ethnopharmacology. 2023 July 12, p.116875-

2023 , Page(s) 116875–

Abstract: Miconia albicans (MA) is consumed all over the Brazilian territory as a remedy to treat rheumatoid arthritis and has been increasingly used to alleviate the deleterious symptoms caused by Chikungunya virus (CHIKV). To investigate the effect of MA leaf ... ...

Abstract	Miconia albicans (MA) is consumed all over the Brazilian territory as a remedy to treat rheumatoid arthritis and has been increasingly used to alleviate the deleterious symptoms caused by Chikungunya virus (CHIKV). To investigate the effect of MA leaf and stem hydroethanolic extracts (LE and SE, respectively), their fractions enriched in triterpene acids or polyphenols as well isolated constituents, on CHIKV hosted in Vero cells. Polyphenol profiles of LE and SE were dereplicated by HPLC-DAD-ESI-MS/MS, aided by standards. Polyphenol-rich (LEx and SEx) and triterpenic acid-rich (LOH and SOH) fractions were obtained in Amberlite XAD-4 and alkalinized 95% ethanol (EtOH) extraction, respectively. TPC and TFC were assessed by colorimetric methods. Three representative flavonoids and two triterpenic acids were quantified by HPLC. CHIKV load suppression was evaluated in Vero cells by real-time qRT‒PCR at noncytotoxic concentrations. Fifteen flavonoids were characterized in LE and SE. LEx presented isoquercitrin, quercitrin, rutin (0.49–1.51%) and quercetin. The TPC was 48 and 62 mg QE/g extract, and the TFC was 11.93 and 0.76 mg QE/g extract for LEx and SEx, respectively. LOH presented ursolic (15.3%) and oleanolic (8.0%) acids. A reduction (91–97%) in the CHIKV load was produced by the triterpene fraction, quercitrin and quercetin; the latter maintained the activity down to one twentieth of the tolerated concentration. M. albicans contains flavonoids and triterpenic acids that are effective against CHIKV, which might justify its use to alleviate sequelae of CHIKV infection. However, further investigations on the species and its active constituents are needed.
Keywords	Chikungunya virus ; Miconia albicans ; amberlite ; colorimetry ; complications (disease) ; ethanol ; isoquercitrin ; leaves ; polyphenols ; quercetin ; quercitrin ; rheumatoid arthritis ; rutin ; traditional medicine ; triterpenoids ; Phenolic compounds ; Triterpene acids ; Antiviral activity
Language	English
Dates of publication	2023-0712
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.116875
Database	NAL-Catalogue (AGRICOLA)

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Article: Subsets of Cytokines and Chemokines from DENV-4-Infected Patients Could Regulate the Endothelial Integrity of Cultured Microvascular Endothelial Cells.

Cipitelli, Marcio da Costa / Paiva, Iury Amancio / Badolato-Corrêa, Jéssica / Marinho, Cíntia Ferreira / Fiestas Solórzano, Victor Edgar / da Costa Faria, Nieli Rodrigues / de Azeredo, Elzinandes Leal / de Souza, Luiz José / da Cunha, Rivaldo Venâncio / de-Oliveira-Pinto, Luzia Maria

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 5

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2022-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11050509
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Comparative Analysis of Circulating Levels of SARS-CoV-2 Antibodies and Inflammatory Mediators in Healthcare Workers and COVID-19 Patients.

de-Oliveira-Pinto, Luzia Maria / Fiestas Solórzano, Victor Edgar / de Lourdes Martins, Maria / Fernandes-Santos, Caroline / Damasco, Paula Hesselberg / de Siqueira, Marilda Agudo Mendonça Teixeira / Dias, Helver Gonçalves / Pauvolid-Corrêa, Alex / Damasco, Paulo Vieira / de Azeredo, Elzinandes Leal

Viruses

2022 Volume 14, Issue 3

Abstract: Advances in knowledge of the pathophysiology of COVID-19 have been acquired; however, the host factors that could explain the mild and severe forms of the disease are not fully understood. Thus, we proposed to evaluate anti-SARS-CoV-2 antibodies and the ... ...

Abstract	Advances in knowledge of the pathophysiology of COVID-19 have been acquired; however, the host factors that could explain the mild and severe forms of the disease are not fully understood. Thus, we proposed to evaluate anti-SARS-CoV-2 antibodies and the inflammatory response of different groups of individuals, including healthcare workers (HCW), sick and dead COVID-19 patients and also recovered patients to contribute to this knowledge gap. Our objective is to relate the clinical evolution of these individuals with the level of detection and functionality of specific antibodies and with the production of inflammatory mediators. As main findings, IgA and IgG anti-SARS-CoV-2 were detected in asymptomatic HCW. IFN-γ and TNF-α levels were higher in symptomatic HCWs than patients with COVID-19 and those who died. Patients who died had higher levels of IL-6, IL-10, and CCL2/MCP-1. We found an imbalance between antiviral and pro-inflammatory mediators in the groups, in which IFN-γ and TNF-α seem to be more associated with protection and IL-6 and CCL2/MCP-1 with pathology. Our work is pioneering the Brazilian population and corroborates data from people from other countries.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Health Personnel ; Humans ; Inflammation Mediators ; SARS-CoV-2
Chemical Substances	Antibodies, Viral ; Inflammation Mediators
Language	English
Publishing date	2022-02-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14030455
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Chikungunya Virus Multiepitope Recombinant Protein Expressed from the Binary System Insect Cell/Recombinant Baculovirus Is Useful for Laboratorial Diagnosis of Chikungunya

Silva, Leonardo Assis da / Lima, Monique da Rocha Queiroz / de Camargo, Brenda Rabello / Guimarães, Dyeferson Kened da Silva Coelho / Barbastefano, Anabele Azevedo Lima / Lima, Raquel Curtinhas de / Damasco, Paulo Vieira / Cunha, Rivaldo Venâncio da / de Souza, Luiz José / de Azeredo, Elzinandes Leal / de-Oliveira-Pinto, Luzia Maria / Nagata, Tatsuya / Ardisson-Araújo, Daniel M. P. / dos Santos, Flavia Barreto / Morais Ribeiro, Bergmann

Microorganisms. 2022 July 18, v. 10, no. 7

2022

Abstract: Chikungunya virus (CHIKV) is an arbovirus currently distributed worldwide, causing a disease that shares clinical signs and symptoms with other illnesses, such as dengue and Zika and leading to a challenging clinical differential diagnosis. In Brazil, ... ...

Abstract	Chikungunya virus (CHIKV) is an arbovirus currently distributed worldwide, causing a disease that shares clinical signs and symptoms with other illnesses, such as dengue and Zika and leading to a challenging clinical differential diagnosis. In Brazil, CHIKV emerged in 2014 with the simultaneous introduction of both Asian and East/Central/South African (ECSA) genotypes. Laboratorial diagnosis of CHIKV is mainly performed by molecular and serological assays, with the latter more widely used. Although many commercial kits are available, their costs are still high for many underdeveloped and developing countries where the virus circulates. Here we described the development and evaluation of a multi-epitope recombinant protein-based IgG-ELISA (MULTREC IgG-ELISA) test for the specific detection of anti-CHIKV antibodies in clinical samples, as an alternative approach for laboratorial diagnosis. The MULTREC IgG-ELISA showed 86.36% of sensitivity and 100% of specificity, and no cross-reactivity with other exanthematic diseases was observed. The recombinant protein was expressed from the binary system insect cell/baculovirus using the crystal-forming baculoviral protein polyhedrin as a carrier of the target recombinant protein to facilitate recovery. The crystals were at least 10 times smaller in size and had an amorphous shape when compared to the polyhedrin wild-type crystal. The assay uses a multi-epitope antigen, representing two replicates of 18 amino acid sequences from the E2 region and a sequence of 17 amino acids from the nsP3 region of CHIKV. The recombinant protein was highly expressed, easy to purify and has demonstrated its usefulness in confirming chikungunya exposure, indeed showing a good potential tool for epidemiological surveillance.
Keywords	Baculoviridae ; Chikungunya virus ; antigens ; arboviruses ; cross reaction ; dengue ; insects ; monitoring ; recombinant proteins ; Brazil
Language	English
Dates of publication	2022-0718
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10071451
Database	NAL-Catalogue (AGRICOLA)

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