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  1. Article ; Online: Biochanin A as a modulator of the inflammatory response: An updated overview and therapeutic potential.

    Felix, Franciel Batista / Vago, Juliana Priscila / Beltrami, Vinícius Amorim / Araújo, Jessica Maria Dantas / Grespan, Renata / Teixeira, Mauro Martins / Pinho, Vanessa

    Pharmacological research

    2022  Volume 180, Page(s) 106246

    Abstract: Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, ... ...

    Abstract Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.
    MeSH term(s) Genistein/pharmacology ; Genistein/therapeutic use ; Humans ; Inflammation/drug therapy ; Isoflavones ; Phytochemicals/pharmacology ; Phytotherapy
    Chemical Substances Isoflavones ; Phytochemicals ; Genistein (DH2M523P0H) ; biochanin A (U13J6U390T)
    Language English
    Publishing date 2022-05-10
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2022.106246
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

    Magalhaes, Giselle Santos / Gregorio, Juliana Fabiana / Beltrami, Vinicius Amorim / Felix, Franciel Batista / Oliveira-Campos, Livia / Bonilha, Caio Santos / Righetti, Renato Fraga / Tibério, Iolanda de Fátima Lopes Calvo / De Sousa, Frederico B / Rezende, Barbara Maximino / Teixeira-Carvalho, Andréa / Santos, Robson As / Campagnole-Santos, Maria José / Rodrigues-Machado, Maria da Gloria / Teixeira, Mauro Martins / Pinho, Vanessa

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2024  

    Abstract: Objective: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact ...

    Abstract Objective: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.
    Methods: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.
    Results: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4
    Conclusion: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
    Language English
    Publishing date 2024-04-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-024-01880-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis.

    Felix, Franciel Batista / Dias, Julia / Vago, Juliana Priscila / Martins, Débora Gonzaga / Beltrami, Vinícius Amorim / Fernandes, Débora de Oliveira / Menezes Dos Santos, Anna Clara Paiva / Queiroz-Junior, Celso Martins / de Sousa, Lirlândia Pires / Amaral, Flávio Almeida / Soriani, Frederico Marianetti / Teixeira, Mauro Martins / Pinho, Vanessa

    Pharmacological research

    2023  Volume 188, Page(s) 106640

    Abstract: Inflammation resolution is an active process that involves cellular events such as apoptosis and efferocytosis, which are key steps in the restoration of tissue homeostasis. Hepatocyte growth factor (HGF) is a growth factor mostly produced by mesenchymal- ...

    Abstract Inflammation resolution is an active process that involves cellular events such as apoptosis and efferocytosis, which are key steps in the restoration of tissue homeostasis. Hepatocyte growth factor (HGF) is a growth factor mostly produced by mesenchymal-origin cells and has been described to act via MET receptor tyrosine kinase. The HGF/MET axis is essential for determining the progression and severity of inflammatory and immune-mediated disorders. Here, we investigated the effect of blocking the HGF/MET signalling pathway by PF-04217903 on the resolution of established models of neutrophilic inflammation. In a self-resolving model of gout induced by MSU crystals, HGF expression on periarticular tissue peaked at 12 h, the same time point that neutrophils reach their maximal accumulation in the joints. The HGF/MET axis was activated in this model, as demonstrated by increased levels of MET phosphorylation in neutrophils (Ly6G
    MeSH term(s) Humans ; Neutrophils ; Hepatocyte Growth Factor/metabolism ; Hepatocyte Growth Factor/pharmacology ; Hepatocyte Growth Factor/therapeutic use ; Lipopolysaccharides/pharmacology ; Inflammation/metabolism ; Apoptosis ; Proto-Oncogene Proteins c-met/metabolism ; Homeostasis
    Chemical Substances Hepatocyte Growth Factor (67256-21-7) ; Lipopolysaccharides ; Proto-Oncogene Proteins c-met (EC 2.7.10.1) ; HGF protein, human
    Language English
    Publishing date 2023-01-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2022.106640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Therapeutic treatment with phosphodiesterase-4 inhibitors alleviates kidney injury and renal fibrosis by increasing MMP-9 in a doxorubicin-induced nephrotoxicity mouse model.

    Costa, Walyson Coelho / Beltrami, Vinícius Amorim / Campolina-Silva, Gabriel Henrique / Queiroz-Junior, Celso Martins / Florentino, Rodrigo M / Machado, Jéssica Rayssa / Martins, Débora Gonzaga / Gonçalves, William Antonio / Barroso, Lívia Corrêa / Freitas, Katia Michelle / de Souza-Neto, Fernando Pedro / Félix, Franciel Batista / da Silva, Rafaela Fernandes / Oliveira, Cleida Aparecida / Câmara, Niels Olsen Saraiva / Rachid, Milene Alvarenga / Teixeira, Mauro Martins / Rezende, Barbara Maximino / Pinho, Vanessa

    International immunopharmacology

    2023  Volume 115, Page(s) 109583

    Abstract: Nephrotic syndrome (NS) is associated with kidney dysfunction and is an important cause of morbidity and mortality in industrialized countries. Here, we evaluated the effects of the phosphodiesterase-4 (PDE-4) inhibitors rolipram and roflumilast on a ... ...

    Abstract Nephrotic syndrome (NS) is associated with kidney dysfunction and is an important cause of morbidity and mortality in industrialized countries. Here, we evaluated the effects of the phosphodiesterase-4 (PDE-4) inhibitors rolipram and roflumilast on a doxorubicin-induced NS model. Early-stage rolipram treatment preserved glomerular filtration barrier function, as indicated by reduced serum protein and albumin loss and the prevention of hypercholesterolemia. These effects were associated with reduced glomerular and tubular lesions and abrogated renal cell apoptosis. In addition, rolipram treatment reduced inflammation, which was characterized by a decrease in macrophage accumulation and reduced levels of CCL2 and TNF in the kidneys. Rolipram also reduced renal fibrosis, which was associated with decreased α-smooth muscle actin (α-SMA) area and increased metalloproteinase 9 (MMP9) activity in renal tissue. Late-stage rolipram or roflumilast treatment preserved glomerular filtration barrier function, as characterized by reduced serum albumin loss, decreased proteinuria, and the prevention of hypercholesterolemia. Importantly, only roflumilast treatment was associated with a reduction in glomerular and tubular lesions at this time point. In addition, both rolipram and roflumilast reduced renal tissue fibrosis and MMP9 activity in renal tissue.
    MeSH term(s) Mice ; Animals ; Phosphodiesterase 4 Inhibitors/therapeutic use ; Phosphodiesterase 4 Inhibitors/pharmacology ; Rolipram/pharmacology ; Rolipram/therapeutic use ; Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism ; Matrix Metalloproteinase 9 ; Hypercholesterolemia ; Kidney/metabolism ; Kidney Diseases/chemically induced ; Kidney Diseases/drug therapy ; Disease Models, Animal ; Fibrosis
    Chemical Substances Phosphodiesterase 4 Inhibitors ; Rolipram (K676NL63N7) ; Roflumilast (0P6C6ZOP5U) ; Cyclic Nucleotide Phosphodiesterases, Type 4 (EC 3.1.4.17) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2023-01-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2022.109583
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation.

    Gonçalves, William Antonio / Rezende, Barbara Maximino / de Oliveira, Marcos Paulo Esteves / Ribeiro, Lucas Secchim / Fattori, Victor / da Silva, Walison Nunes / Prazeres, Pedro Henrique Dias Moura / Queiroz-Junior, Celso Martins / Santana, Karina Talita de Oliveira / Costa, Walyson Coelho / Beltrami, Vinícius Amorim / Costa, Vivian Vasconcelos / Birbrair, Alexander / Verri, Waldiceu A / Lopes, Fernando / Cunha, Thiago Mattar / Teixeira, Mauro Martins / Amaral, Flávio Almeida / Pinho, Vanessa

    Frontiers in immunology

    2020  Volume 10, Page(s) 3120

    Abstract: Joint pain is a distressing symptom of arthritis, and it is frequently persistent even after treatments which reduce local inflammation. Continuous production of algogenic factors activate/sensitize nociceptors in the joint structures and contribute to ... ...

    Abstract Joint pain is a distressing symptom of arthritis, and it is frequently persistent even after treatments which reduce local inflammation. Continuous production of algogenic factors activate/sensitize nociceptors in the joint structures and contribute to persistent pain, a challenging and difficult condition to treat. TNF is a crucial cytokine for the pathogenesis of several rheumatic diseases, and its inhibition is a mainstay of treatment to control joint symptoms, including pain. Here, we sought to investigate the inflammatory changes and the role of TNF in dorsal root ganglia (DRG) during persistent hypernociception after the resolution of acute joint inflammation. Using a model of antigen-induced arthritis, the peak of joint inflammation occurred 12-24 h after local antigen injection and was characterized by an intense influx of neutrophils, pro-inflammatory cytokine production, and joint damage. We found that inflammatory parameters in the joint returned to basal levels between 6 and 8 days after antigen-challenge, characterizing the resolving phase of joint inflammation. Mechanical hyperalgesia was persistent up to 14 days after joint insult. The persistent nociception was associated with the inflammatory status of DRG after cessation of acute joint inflammation. The late state of neuroinflammation in the ipsilateral side was evidenced by gene expression of TNF, TNFR2, IL-6, IL-1β, CXCL2, COX2, and iNOS in lumbar DRG (L3-L5) and leukocyte adhesion in the lumbar intumescent vessels between days 6 and 8. Moreover, there were signs of resident macrophage activation in DRG, as evidenced by an increase in Iba1-positive cells. Intrathecal or systemic injection of etanercept, an agent clinically utilized for TNF neutralization, at day 7 post arthritis induction, alleviated the persistent joint hyperalgesia by specific action in DRG. Our data suggest that neuroinflammation in DRG after the resolution of acute joint inflammation drives continuous neural sensitization resulting in persistent joint nociception in a TNF-dependent mechanism.
    MeSH term(s) Animals ; Arthralgia/etiology ; Arthralgia/metabolism ; Arthralgia/pathology ; Biomarkers ; Biopsy ; Disease Models, Animal ; Disease Susceptibility ; Ganglia, Spinal/metabolism ; Gene Expression ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Male ; Mice ; Nociception ; Spinal Cord ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Biomarkers ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2020-01-20
    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.2019.03120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice

    Pimenta, Jordane Clarisse / Beltrami, Vinícius Amorim / Oliveira, Bruna Da Silva / Queiroz-Junior, Celso Martins / Barsalini, Jéssica / Teixeira, Danielle Cunha / de Souza-Costa, Luiz Pedro / Lima, Anna Luiza Diniz / Machado, Caroline Amaral / Parreira, Bárbara Zuccolotto Schneider Guimarães / Santos, Felipe Rocha da Silva / Costa, Pedro Augusto Carvalho / Lacerda, Larisse De Souza Barbosa / Gonçalves, Matheus Rodrigues / Chaves, Ian de Meira / Couto, Manoela Gonzaga Gontijo Do / Costa, Victor Rodrigues de Melo / Nóbrega, Natália Ribeiro Cabacinha / Silva, Bárbara Luísa /
    Fonseca, Talita / Resende, Filipe / Wnuk, Natália Teixeira / Umezu, Hanna L. / Campolina-Silva, Gabriel / Andrade, Ana Cláudia dos Santos Pereira / Santana de Aguiar, Renato / Costa, Guilherme Mattos Jardim / Guimarães, Pedro Pires Goulart / da Silva, Glauber Santos Ferreira / Vieira, Luciene Bruno / Pinho, Vanessa / Teixeira, Antônio Lúcio / Teixeira, Mauro Martins / De Miranda, Aline Silva / Costa, Vivian Vasconcelos

    bioRxiv

    Abstract: The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing ... ...

    Abstract The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10^3 to 3x105 PFU/30 uL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10^4 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.
    Keywords covid19
    Language English
    Publishing date 2024-01-10
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.01.10.575003
    Database COVID19

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  7. Article ; Online: Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice

    Pimenta, Jordane Clarisse / Beltrami, Vinicius Amorim / Oliveira, Bruna Da Silva / Queiroz-Junior, Celso Martins / Barsalini, Jessica / Teixeira, Danielle Cunha / Souza-Costa, Luiz Pedro / Lima, Anna Luiza Diniz / Machado, Caroline Amaral / Parreira, Barbara Zuccolotto Schneider Guimaraes / Santos, Felipe Rocha da Silva / Costa, Pedro Augusto Carvalho / Lacerda, Larisse De Souza Barbosa / Goncalves, Mateus Rodrigues / Chaves, Ian de Meira / Couto, Manoela Gonzaga Gontijo / Costa, Victor Rodrigues de Melo / Nobrega, Natalia Ribeiro Cabacinha / Silva, Barbara Luisa /
    Fonseca, Talita / Resende, Filipe / Wnuk, Natalia Teixeira / Umezu, Hanna L / Campolina-Silva, Gabriel / Andrade, Ana Claudia / Santana de Aguiar, Renato / Costa, Guilherme Mattos Jardim / Guimaraes, Pedro Pires / Silva, Glauber Santos Ferreira / Vieira, Luciene Bruno / Pinho, Vanessa / Teixeira, Antonio Lucio / Teixeira, Mauro Martins / Miranda, Aline Silva / Costa, Vivian Vasconcelos

    bioRxiv

    Abstract: The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing ... ...

    Abstract The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10^3 to 3x105 PFU/30 uL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10^4 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.
    Keywords covid19
    Language English
    Publishing date 2024-01-10
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.01.10.575003
    Database COVID19

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