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Article ; Online: Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury.

Gonzatti, Michelangelo Bauwelz / Freire, Beatriz Marton / Antunes, Maísa Mota / de Menezes, Gustavo Batista / Talbot, Jhimmy / Peron, Jean Pierre Schatzmann / Basso, Alexandre Salgado / Keller, Alexandre Castro

iScience

2023 Volume 26, Issue 10, Page(s) 107947

Abstract: Invariant Natural Killer T (iNKT) cell activation by α-galactosylceramide (αGC) potentiates cytotoxic immune responses against tumors. However, αGC-induced liver injury is a limiting factor for iNKT-based immunotherapy. Although adrenergic receptor ... ...

Abstract	Invariant Natural Killer T (iNKT) cell activation by α-galactosylceramide (αGC) potentiates cytotoxic immune responses against tumors. However, αGC-induced liver injury is a limiting factor for iNKT-based immunotherapy. Although adrenergic receptor stimulation is an important immunosuppressive signal that curbs tissue damage induced by inflammation, its effect on the antitumor activity of invariant Natural Killer T (iNKT) cells remains unclear. We use mouse models and pharmacological tools to show that the stimulation of the sympathetic nervous system (SNS) inhibits αGC-induced liver injury without impairing iNKT cells' antitumoral functions. Mechanistically, SNS stimulation prevents the collateral effect of TNF-α production by iNKT cells and neutrophil accumulation in hepatic parenchyma. Our results suggest that the modulation of the adrenergic signaling can be a complementary approach to αGC-based immunotherapy to mitigate iNKT-induced liver injury without compromising its antitumoral activity.
Language	English
Publishing date	2023-09-16
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107947
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Article ; Online: Zoledronic Acid Modulates Cytokine Expression and Mitigates Bone Loss during the Development of Induced Apical Periodontitis in a Mice Model.

Maia, Caroline Andrade / Chaves, Hebertt Gonzaga Dos Santos / Benetti, Francine / de Menezes, Gustavo Batista / Antunes, Maísa Mota / Pinto, Karem Paula / Silva, Emmanuel João Nogueira Leal / Sobrinho, Antônio Paulino Ribeiro / Tavares, Warley Luciano Fonseca

Journal of endodontics

2023

Abstract: Introduction: Bisphosphonates are antiresorptive drugs used worldwide to treat systemic bone pathologies. This study aimed to assess the impact of zoledronic acid on the progression of induced apical periodontitis and the expression of cytokines ... ...

Abstract	Introduction: Bisphosphonates are antiresorptive drugs used worldwide to treat systemic bone pathologies. This study aimed to assess the impact of zoledronic acid on the progression of induced apical periodontitis and the expression of cytokines interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) in a mouse model. Methods: Sixteen female isogenic BALB/c mice 6 weeks of age were distributed into 2 groups: mice with induced apical periodontitis (the AP group, n = 8) and mice with induced apical periodontitis treated with zoledronic acid (the AP-ZA group, n = 8). The AP-ZA group received a dose of 125 μg/kg zoledronic acid diluted in sterile saline solution administered intraperitoneally once a week for 4 weeks before pulp exposure, whereas the AP group received only saline solution. Pulp exposures were performed on the maxillary first molars for the induction of apical periodontitis, and mice were euthanized after 7 and 21 days. The jaws were collected; scanned using micro-computed tomographic imaging; and processed for polymerase chain reaction analysis of IL-1β, IL-10, IL-6, and TNF-α. The Student t test was performed for parametric data, and Mann-Whitney U tests were used for nonparametric data. The level of significance was set at 5%. Results: Micro-computed tomographic imaging revealed higher bone resorption in the AP group compared with the AP-ZA group at both time points (P < .05). Real-time polymerase chain reaction demonstrated higher TNF-α expression in the AP group at both time points and higher IL-6 and IL-1β expression in the AP group at the 7- and 21-day time points, respectively, compared with the AP-ZA group (P < .05). No differences were observed regarding IL-10 expression between the groups. Conclusions: Zoledronic acid had significant anti-inflammatory and antiresorptive effects on apical periodontitis in mice.
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	752412-2
ISSN	1878-3554 ; 0099-2399
ISSN (online)	1878-3554
ISSN	0099-2399
DOI	10.1016/j.joen.2023.08.010
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Article ; Online: Maternal chronic caffeine intake impairs fertility, placental vascularization and fetal development in mice.

Paula, Thais de Merici Domingues E / Cardoso, Lucas Carvalho / Felicioni, Fernando / Caldeira-Brant, Andre Lucas / Santos, Thais Garcia / Castro-Oliveira, Hortencia / Menezes, Gustavo Batista / Bloise, Enrrico / Chiarini-Garcia, Helio / de Almeida, Fernanda Radicchi Campos Lobato

Reproductive toxicology (Elmsford, N.Y.)

2023 Volume 121, Page(s) 108471

Abstract: Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake ... ...

Abstract	Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake and the effects on fetal growth. Female Swiss mice received, via gavage, caffeine doses (either 60, 120 or 240 mg/kg/day) seven days before mating until gestational days-(GD) 11.5 or 17.5. Fetal biometrical parameters were assessed, and placentae were either submitted to histomorphometrical or molecular evaluation of angiogenesis (placental growth factor-1[PlGF-1]), apoptosis (Caspase-3) and proliferation (Ki-67) markers (evaluated in Swiss dams) and to intravital microscopy (evaluated in C57BL/6 dams). Caffeine exposed fetuses exhibited intrauterine growth restriction in a sex-dependent manner, with greater commitment of female fetuses (P < 0.05). In addition, placentae from dams that received 120 mg/kg/day showed less irrigation by maternal blood and greater development of fetal vasculature, characterized by higher number of larger vessels (P < 0.05). Although no effects on apoptosis (Caspase-3) and angiogenesis (PlGF-1) were observed, dams treated with 60 mg/kg/day showed greater placental cell proliferation (Ki-67 staining) at GD 11.5 (P < 0.05). The group treated with 240 mg/kg/day exhibited only one pregnant dam for each gestational age, suggesting that this high caffeine consumption may compromise fertility. Taken together, even in the doses currently ingested by many pregnant women, caffeine has detrimental effects on placental vasculature and fetal development in mice. Therefore, our results strongly suggest that caffeine consumption in human pregnancies greater than the recommended doses should be avoided.
Language	English
Publishing date	2023-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	639342-1
ISSN	1873-1708 ; 0890-6238
ISSN (online)	1873-1708
ISSN	0890-6238
DOI	10.1016/j.reprotox.2023.108471
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Article ; Online: DIY: "Do Imaging Yourself" - Conventional microscopes as powerful tools for in vivo investigation.

Antunes, Maísa Mota / Carvalho, Érika de / Menezes, Gustavo Batista

The international journal of biochemistry & cell biology

2017 Volume 94, Page(s) 1–5

Abstract: Intravital imaging has been increasingly employed in cell biology studies and it is becoming one of the most powerful tools for in vivo investigation. Although some protocols can be extremely complex, most intravital imaging procedures can be performed ... ...

Abstract	Intravital imaging has been increasingly employed in cell biology studies and it is becoming one of the most powerful tools for in vivo investigation. Although some protocols can be extremely complex, most intravital imaging procedures can be performed using basic surgery and animal maintenance techniques. More importantly, regular confocal microscopes - the same that are used for imaging immunofluorescence slides - can also acquire high quality intravital images and movies after minor adaptations. Here we propose minimal adaptations in stock microscopes that allow major improvements in different fields of scientific investigation.
MeSH term(s)	Animals ; Biomedical Research/instrumentation ; Biomedical Research/trends ; Cell Biology/instrumentation ; Cell Biology/trends ; Humans ; Immune System/diagnostic imaging ; Intravital Microscopy/instrumentation ; Intravital Microscopy/trends ; Mice ; Microscopy, Confocal/instrumentation ; Microscopy, Confocal/trends ; Microscopy, Video/instrumentation ; Microscopy, Video/trends
Language	English
Publishing date	2017-11-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2017.11.004
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Article ; Online: Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice.

Lacerda, Débora Romualdo / Nunes-Silva, Albená / Silveira, Ana Letícia Malheiros / Costa, Kátia Anunciação / Rodrigues, Débora Fernandes / Moraes, Michele Macedo / Pinho, Vanessa / Menezes, Gustavo Batista / Teixeira, Mauro Martins / Wanner, Samuel Penna / Soares, Danusa Dias / Ferreira, Adaliene Versiani Matos

Nutrition (Burbank, Los Angeles County, Calif.)

2023 Volume 115, Page(s) 112092

Abstract: Objectives: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. ...

Abstract	Objectives: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. Methods: Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. Results: In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b Conclusions: These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.
Language	English
Publishing date	2023-05-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/j.nut.2023.112092
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Article ; Online: Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice

Nutrition. 2023 Nov., v. 115 p.112092-

2023

Abstract: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because ... ...

Abstract	Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b⁺F480– was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.
Keywords	adipose tissue ; blood serum ; carbohydrates ; chemokines ; diet ; epididymis ; exercise ; free fatty acids ; homeostasis ; inflammation ; interleukin-10 ; interleukin-13 ; interleukin-4 ; interleukin-6 ; ligands ; lipolysis ; myeloperoxidase ; necrosis ; neoplasms ; neutrophils ; Cytokines ; Obesity ; High-refined carbohydrate diet
Language	English
Dates of publication	2023-11
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/j.nut.2023.112092
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The neonatal liver hosts a spontaneously occurring neutrophil population, exhibiting distinct spatial and functional characteristics from adults.

da Silva Júnior, Wanderson Ferreira / de Freitas Lopes, Maria Alice / Antunes, Maísa Mota / de Oliveira Costa, Karen Marques / Diniz, Ariane Barros / Lanza Nakagaki, Brenda Naemi / de Miranda, Camila Dutra Moreira / de Castro Oliveira, Hortência Maciel / Reis, Alesandra Corte / Libreros, Stephania / de Paula, Cristina Maria Pinto / Rezende, Rafael Machado / Menezes, Gustavo Batista

Journal of leukocyte biology

2024

Abstract: The elusive nature of the liver immune system in newborns remains an important challenge, casting a shadow over our understanding of how to effectively treat and prevent diseases in children. Therefore, deeper exploration into the intricacies of neonatal ...

Abstract	The elusive nature of the liver immune system in newborns remains an important challenge, casting a shadow over our understanding of how to effectively treat and prevent diseases in children. Therefore, deeper exploration into the intricacies of neonatal immunology might be crucial for improved pediatric healthcare. Using liver intravital microscopy, we unveiled a significant population of granulocytes in the hepatic parenchyma of fetuses and newborns. Utilizing high-dimensional immunophenotyping, we showed dynamic alterations predominantly in granulocytes during neonatal development. Liver intravital microscopy from birth through adulthood captures real-time dynamics, showing a substantial presence of Ly6G + cells that persisted significantly up to 2 weeks of age. Using CyTOF, we characterized neonatal Ly6G + cells as neutrophils, confirmed by morphology and immunohistochemistry. Surprisingly, the embryonic liver hosts a distinct population of neutrophils established as early as the second gestational week, challenging conventional notions about their origin. Additionally, we observed that embryonic neutrophils occupy preferentially the extravascular space, indicating their early establishment within the liver. Hepatic neutrophils in embryos and neonates form unique cell clusters, persisting during the initial days of life, while reduced migratory capabilities in neonates are observed, potentially compensating with increased reactive oxygen species (ROS) release in response to stimuli. Finally, in vivo imaging of acute neutrophil behavior in a newborn mouse, subjected to focal liver necrosis, unveils that neonatal neutrophils exhibit a reduced migratory response. The study provides unprecedented insights into the intricate interplay of neutrophils within the liver, shedding light on their functional and dynamic characteristics during development.
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiae082
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Article ; Online: Antimicrobial and antibiofilm activity of highly soluble polypyrrole against methicillin-resistant Staphylococcus aureus.

Rosa, Danillo Sales / Oliveira, Samily Aquino de Sá / Souza, Renata de Faria Silva / de França, Chirles Araujo / Pires, Isabelle Caroline / Tavares, Márcio Rennan Santos / de Oliveira, Helinando Pequeno / da Silva Júnior, Fernando Antônio Gomes / Moreira, Maria Aparecida Scatamburlo / de Barros, Mariana / de Menezes, Gustavo Batista / Antunes, Maísa Mota / Azevedo, Vasco Ariston de Carvalho / Naue, Carine Rosa / da Costa, Mateus Matiuzzi

Journal of applied microbiology

2024 Volume 135, Issue 4

Abstract: Aims: The purpose was to evaluate the antimicrobial activity of highly soluble polypyrrole (Hs-PPy), alone or combined with oxacillin, as well as its antibiofilm potential against methicillin-resistant Staphylococcus aureus strains. Furthermore, the in ... ...

Abstract	Aims: The purpose was to evaluate the antimicrobial activity of highly soluble polypyrrole (Hs-PPy), alone or combined with oxacillin, as well as its antibiofilm potential against methicillin-resistant Staphylococcus aureus strains. Furthermore, the in silico inhibitory mechanism in efflux pumps was also investigated. Methods and results: Ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and two reference strains were used. Antimicrobial activity was determined by broth microdilution, and the combination effect with oxacillin was evaluated by the checkerboard assay. The biofilm formation capacity of MRSA and the interference of Hs-PPy were evaluated. The inhibitory action of Hs-PPy on the efflux pump was evaluated in silico through molecular docking. Hs-PPy showed activity against the isolates, with inhibitory action between 62.5 and 125 µg ml-1 and bactericidal action at 62.5 µg ml-1, as well as synergism in association with oxacillin. The isolates ranged from moderate to strong biofilm producers, and Hs-PPy interfered with the formation of this structure, but not with mature biofilm. There was no in silico interaction with the efflux protein EmrD, the closest homolog to NorA. Conclusions: Hs-PPy interferes with biofilm formation by MRSA, has synergistic potential, and is an efflux pump inhibitor.
MeSH term(s)	Methicillin-Resistant Staphylococcus aureus ; Anti-Bacterial Agents/pharmacology ; Polymers/pharmacology ; Pyrroles/pharmacology ; Molecular Docking Simulation ; Oxacillin/pharmacology ; Anti-Infective Agents/pharmacology ; Biofilms ; Microbial Sensitivity Tests
Chemical Substances	Anti-Bacterial Agents ; polypyrrole (30604-81-0) ; Polymers ; Pyrroles ; Oxacillin (UH95VD7V76) ; Anti-Infective Agents
Language	English
Publishing date	2024-03-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1358023-1
ISSN	1365-2672 ; 1364-5072
ISSN (online)	1365-2672
ISSN	1364-5072
DOI	10.1093/jambio/lxae072
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Article ; Online: Corrigendum: Susceptibility to infections during acute liver injury depends on transient disruption of liver macrophage niche.

Lopes, Mateus Eustáquio / Nakagaki, Brenda Naemi / Mattos, Matheus Silvério / Campolina-Silva, Gabriel Henrique / Meira, Raquel de Oliveira / Paixão, Pierre Henrique de Menezes / Oliveira, André Gustavo / Faustino, Lucas D / Gonçalves, Ricardo / Menezes, Gustavo Batista

Frontiers in immunology

2022 Volume 13, Page(s) 1038067

Abstract: This corrects the article DOI: 10.3389/fimmu.2022.892114.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2022.892114.].
Language	English
Publishing date	2022-10-14
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1038067
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Article ; Online: Susceptibility to Infections During Acute Liver Injury Depends on Transient Disruption of Liver Macrophage Niche.

Frontiers in immunology

2022 Volume 13, Page(s) 892114

Abstract: Kupffer cells are the primary liver resident immune cell responsible for the liver firewall function, including clearance of bacterial infection from the circulation, as they are strategically positioned inside the liver sinusoid with intimate contact ... ...

Abstract	Kupffer cells are the primary liver resident immune cell responsible for the liver firewall function, including clearance of bacterial infection from the circulation, as they are strategically positioned inside the liver sinusoid with intimate contact with the blood. Disruption in the tissue-resident macrophage niche, such as in Kupffer cells, can lead to a window of susceptibility to systemic infections, which represents a significant cause of mortality in patients with acetaminophen (APAP) overdose-induced acute liver injury (ALI). However, how Kupffer cell niche disruption increases susceptibility to systemic infections in ALI is not fully understood. Using a mouse model of ALI induced by APAP overdose, we found that Kupffer cells upregulated the apoptotic cell death program and were markedly reduced in the necrotic areas during the early stages of ALI, opening the niche for the infiltration of neutrophils and monocyte subsets. In addition, during the resolution phase of ALI, the remaining tissue macrophages with a Kupffer cell morphology were observed forming replicating cell clusters closer to necrotic areas devoid of Kupffer cells. Interestingly, mice with APAP-induced liver injury were still susceptible to infections despite the dual cellular input of circulating monocytes and proliferation of remaining Kupffer cells in the damaged liver. Therapy with bone marrow-derived macrophages (BMDM) was shown to be effective in occupying the niche devoid of Kupffer cells following APAP-induced ALI. The rapid BMDM migration to the liver and their positioning within necrotic areas enhanced the healing of the tissue and restored the liver firewall function after BMDM therapy. Therefore, we showed that disruption in the Kupffer cell niche and its impaired function during acute liver injury are key factors for the susceptibility to systemic bacterial infections. In addition, modulation of the liver macrophage niche was shown to be a promising therapeutic strategy for liver injuries that reduce the Kupffer cell number and compromise the organ function.
MeSH term(s)	Acetaminophen/adverse effects ; Humans ; Kupffer Cells/metabolism ; Liver ; Macrophages ; Monocytes ; Necrosis/metabolism
Chemical Substances	Acetaminophen (362O9ITL9D)
Language	English
Publishing date	2022-07-28
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.2022.892114
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