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1.
Nutrients ; 13(12)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34959851

RESUMO

This article focuses on how nutrition may help prevent and/or assist with recovery from the harmful effects of strenuous acute exercise and physical training (decreased immunity, organ injury, inflammation, oxidative stress, and fatigue), with a focus on nutritional supplements. First, the effects of ketogenic diets on metabolism and inflammation are considered. Second, the effects of various supplements on immune function are discussed, including antioxidant defense modulators (vitamin C, sulforaphane, taheebo), and inflammation reducers (colostrum and hyperimmunized milk). Third, how 3-hydroxy-3-methyl butyrate monohydrate (HMB) may offset muscle damage is reviewed. Fourth and finally, the relationship between exercise, nutrition and COVID-19 infection is briefly mentioned. While additional verification of the safety and efficacy of these supplements is still necessary, current evidence suggests that these supplements have potential applications for health promotion and disease prevention among athletes and more diverse populations.


Assuntos
Antioxidantes/uso terapêutico , Atletas , Suplementos Nutricionais , Exercício Físico/imunologia , Estresse Oxidativo , Resistência Física , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Inflamação/epidemiologia , Inflamação/imunologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Resistência Física/efeitos dos fármacos , Resistência Física/imunologia , SARS-CoV-2/imunologia , Ciências da Nutrição e do Esporte
2.
Trends Endocrinol Metab ; 32(11): 875-889, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34593305

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin (Ang)-converting enzyme 2 (ACE2), which is highly expressed in host cells. The cytokine storm observed in patients with COVID-19 contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasis, and death. Growth and differentiation factor 15 (GDF15), which belongs to the transforming growth factor-ß (TGF-ß) superfamily of proteins, has a pivotal role in the development and progression of diseases because of its role as a metabolic regulator. In COVID-19, GDF15 activity increases in response to tissue damage. GDF15 appears to be a strong predictor of poor outcomes in patients critically ill with COVID-19 and acts as an 'inflammation-induced central mediator of tissue tolerance' via its metabolic properties. In this review, we examine the potential properties of GDF15 as an emerging modulator of immunity in COVID-19 in association with iron metabolism. The virus life cycle in host cell provides potential targets for drug therapy.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Endotélio Vascular/imunologia , Fator 15 de Diferenciação de Crescimento/imunologia , Ferro/metabolismo , Apoptose/imunologia , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/imunologia , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Fatores Imunológicos/uso terapêutico , Estresse Oxidativo/imunologia , Prognóstico , Piroptose/imunologia , SARS-CoV-2
4.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445774

RESUMO

Polyethyleneimine (PEI) induced immune responses were investigated in human bronchial epithelial (hBE) cells and mice. PEI rapidly induced ATP release from hBE cells and pretreatment with glutathione (GSH) blocked the response. PEI activated two conductive pathways, VDAC-1 and pannexin 1, which completely accounted for ATP efflux across the plasma membrane. Moreover, PEI increased intracellular Ca2+ concentration ([Ca2+]i), which was reduced by the pannexin 1 inhibitor, 10Panx (50 µM), the VDAC-1 inhibitor, DIDS (100 µM), and was nearly abolished by pretreatment with GSH (5 mM). The increase in [Ca2+]i involved Ca2+ uptake through two pathways, one blocked by oxidized ATP (oATP, 300 µM) and another that was blocked by the TRPV-1 antagonist A784168 (100 nM). PEI stimulation also increased IL-33 mRNA expression and protein secretion. In vivo experiments showed that acute (4.5 h) PEI exposure stimulated secretion of Th2 cytokines (IL-5 and IL-13) into bronchoalveolar lavage (BAL) fluid. Conjugation of PEI with ovalbumin also induced eosinophil recruitment and secretion of IL-5 and IL-13 into BAL fluid, which was inhibited in IL-33 receptor (ST2) deficient mice. In conclusion, PEI-induced oxidative stress stimulated type 2 immune responses by activating ATP-dependent Ca2+ uptake leading to IL-33 secretion, similar to allergens derived from Alternaria.


Assuntos
Trifosfato de Adenosina/imunologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Imunidade/efeitos dos fármacos , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Polietilenoimina/farmacologia , Alérgenos/imunologia , Animais , Cálcio/imunologia , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Imunidade/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/imunologia , RNA Mensageiro/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia
5.
J Dermatol Sci ; 103(1): 33-40, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34158211

RESUMO

BACKGROUND: Hair follicle undergoes a growth cycle under the regulation of dermal papilla cells. Due to their enormous roles, these fibroblast cells have been used in various in vitro studies as a screening model to evaluate the effect of hair growth regulating agents. OBJECTIVE: In the current study, we aim to check the hair growth potential effect of Argan press cake (APC) extracted using 50 or 80 % aqueous ethanol on human hair follicle dermal papilla cells (HFDPCs) and to determine the molecular mechanism. METHODS: APC were applied to HFDPCs, then cell proliferation assays, mitochondrial biogenesis assay, and oxidative stress assay were assessed. DNA microarray was performed from the cells treated with our samples and minoxidil. Validation of the results was done using Quantitative Real-Time PCR with primers for hair-growth related genes. GC/MS analysis was used to determine the compounds contained in APC 50 and 80 %. RESULTS: APC enhanced cell proliferation along with the stimulation of the ATP content. Additionally, APC had an anti-oxidant activity against H2O2 mediated oxidative stress preventing dermal papilla cell senescence. Consistent with this, global gene profiling analysis showed an activation of hair growth-related pathway, and a downregulation of inflammation- and oxidative stress-related genes by APC extracts. GC/MS analysis revealed that these extracts contained pure fatty acids, derived sugar chains, and pure compounds including tocopherols, squalene, and spinasterol. CONCLUSION: Taken together, here we showed that APC extracts had an effect on stimulating hair growth while inhibiting the inflammation and the oxidative stress of HFDPCs and thus can potentially contribute to an anti-hair loss drug development.


Assuntos
Alopecia/tratamento farmacológico , Folículo Piloso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sapotaceae/química , Alopecia/imunologia , Antioxidantes , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Folículo Piloso/imunologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Extratos Vegetais/uso terapêutico
6.
Front Immunol ; 12: 649502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968042

RESUMO

Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autoanticorpos/metabolismo , Estresse Oxidativo/imunologia , Pênfigo/imunologia , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Casos e Controles , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Linhagem Celular , Desmogleína 3/imunologia , Desmogleína 3/metabolismo , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Estresse Oxidativo/efeitos dos fármacos , Pênfigo/sangue , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , alfa Catenina/metabolismo
7.
Vet Immunol Immunopathol ; 237: 110265, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33989854

RESUMO

Severe equine asthma is characterized by airway hyperresponsiveness, neutrophilic inflammation and structural alterations of the lower airways. In asthmatic horses with neutrophilic inflammation, there is insensitivity to corticosteroids characterized by the persistence of neutrophils within the airways with therapy. We hypothesized that hypoxia or oxidative stress in the microenvironment of the lung contributes to this insensitivity of neutrophils to corticosteroids in asthmatic horses. Blood neutrophils isolated from horses with severe asthma (N = 8) and from healthy controls (N = 8) were incubated under different cell culture conditions simulating hypoxia and oxidative stress and, in the presence, or absence of dexamethasone. The pro-inflammatory gene and protein expression of neutrophils were studied. In both groups, pyocyanin-induced oxidative stress increased the mRNA expression of IL-8, IL-1ß, and TNF-α. While IL-1ß and TNF-α were downregulated by dexamethasone under these conditions, IL-8 was not. Simulated hypoxic conditions did not enhance pro-inflammatory gene expression in neutrophils from either group of horses. In conclusion, oxidative stress but not hypoxia may contribute to corticosteroid insensitivity via a selective gene regulation pathway. Equine neutrophil responses were similar in both heathy and asthmatic horses, indicating that it is not specific to asthmatic inflammation.


Assuntos
Asma/veterinária , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Doenças dos Cavalos/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Animais , Asma/tratamento farmacológico , Asma/imunologia , Células Cultivadas , Quimiocinas/biossíntese , Quimiocinas/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças dos Cavalos/imunologia , Cavalos , Hipóxia/imunologia , Hipóxia/metabolismo , Hipóxia/veterinária , Mediadores da Inflamação/metabolismo , Interleucina-17/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Piocianina/farmacologia
8.
Front Immunol ; 12: 649591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995368

RESUMO

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Patológica/tratamento farmacológico , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Imiquimode/administração & dosagem , Imiquimode/toxicidade , Interleucina-17/imunologia , Interleucina-17/metabolismo , Queratinócitos , Masculino , Camundongos , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia
9.
Front Immunol ; 12: 670574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995406

RESUMO

Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex during Cryptococcus neoformans (Cn) infection. To better understand the role of neutrophils in acute pulmonary cryptococcosis, we analyzed neutrophil heterogeneity by single-cell transcriptional analysis of immune cells in the lung of Cn-infected mice from a published dataset. We identified neutrophils by reference-based annotation and identified two distinct neutrophil subsets generated during acute Cn infection: A subset with an oxidative stress signature (Ox-PMN) and another with enhanced cytokine gene expression (Cyt-PMN). Based on gene regulatory network and ligand-receptor analysis, we hypothesize that Ox-PMNs interact with the fungus and generate ROS, while Cyt-PMNs are longer-lived neutrophils that indirectly respond to Cn-derived ligands and cytokines to modulate cell-cell communication with dendritic cells and alveolar macrophages. Based on the data, we hypothesized that, during in vivo fungal infection, there is a division of labor in which each activated neutrophil becomes either Ox-PMN or Cyt-PMN.


Assuntos
Criptococose/imunologia , Pneumopatias Fúngicas/imunologia , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Animais , Criptococose/metabolismo , Cryptococcus neoformans/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Pneumopatias Fúngicas/metabolismo , Camundongos , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/imunologia , Análise de Célula Única
10.
Adv Protein Chem Struct Biol ; 125: 51-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33931144

RESUMO

Mitochondria, conserved intracellular organelles best known as the powerhouse of cells for generating ATP, play an important role in apoptosis. Oxidative stress can induce mitochondrial dysfunction and activate mitochondria-mediated apoptotic cell death. TRPM2 is a Ca2+-permeable cation channel that is activated by pathologically relevant concentrations of reactive oxygen species (ROS) and one of its well-recognized roles is to confer susceptibility to ROS-induced cell death. Increasing evidence from recent studies supports TRPM2 channel-mediated cell death as an important cellular mechanism linking miscellaneous oxidative stress-inducing pathological factors to associated diseased conditions. In this chapter, we will discuss the role of the TRPM2 channel in neurons in the brain and pancreatic ß-cells in mediating mitochondrial dysfunction and cell death, focusing mainly on apoptotic cell death, that are induced by pathological stimuli implicated in the pathogenesis of neurodegenerative diseases, ischemic stroke and diabetes.


Assuntos
Apoptose/imunologia , Diabetes Mellitus/imunologia , AVC Isquêmico/imunologia , Mitocôndrias/imunologia , Doenças Neurodegenerativas/imunologia , Estresse Oxidativo/imunologia , Canais de Cátion TRPM/imunologia , Animais , Cálcio/imunologia , Diabetes Mellitus/patologia , Humanos , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/patologia , AVC Isquêmico/patologia , Mitocôndrias/patologia , Doenças Neurodegenerativas/patologia , Neurônios/imunologia , Neurônios/patologia
11.
Clin Immunol ; 227: 108754, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33964432

RESUMO

Recently, a continuous increase in environmental pollution has been observed. Despite wide-scale efforts to reduce air pollutant emissions, the problem is still relevant. Exposure to elevated levels of airborne particles increased the incidence of respiratory diseases. PM10 constitute the largest fraction of air pollutants, containing particles with a diameter of less than 10 µm, metals, pollens, mineral dust and remnant material from anthropogenic activity. The natural airway defensive mechanisms against inhaled material, such as mucus layer, ciliary clearance and macrophage phagocytic activity, may be insufficient for proper respiratory function. The epithelium layer can be disrupted by ongoing oxidative stress and inflammatory processes induced by exposure to large amounts of inhaled particles as well as promote the development and exacerbation of obstructive lung diseases. This review draws attention to the current state of knowledge about the physical features of PM10 and its impact on airway epithelial cells, and obstructive pulmonary diseases.


Assuntos
Asma/imunologia , Imunidade Inata/imunologia , Inflamação/imunologia , Estresse Oxidativo/imunologia , Material Particulado/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Mucosa Respiratória/imunologia , Poluentes Atmosféricos , Poluição do Ar , Poluição do Ar em Ambientes Fechados , Asma/metabolismo , Asma/fisiopatologia , Progressão da Doença , Células Epiteliais/metabolismo , Humanos , Inflamação/metabolismo , Padrões Moleculares Associados a Patógenos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptores de Reconhecimento de Padrão/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Mucosa Respiratória/metabolismo , Mucosa Respiratória/fisiopatologia
12.
Eur J Immunol ; 51(7): 1748-1761, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33811758

RESUMO

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-ß to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-ß precursor to its mature form, TGF-ß. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.


Assuntos
Antígenos/imunologia , Apoptose/imunologia , Estresse Oxidativo/imunologia , Linfócitos T Reguladores/imunologia , Animais , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Proteína Smad3/imunologia , Superóxido Dismutase/imunologia , Fator de Crescimento Transformador beta/imunologia , Regulação para Cima/imunologia
13.
Fish Shellfish Immunol ; 113: 106-117, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33826938

RESUMO

Catalase, a key enzyme in the antioxidant defense grid of organisms, scavenges free radicals to curtail their harmful effects on the host, supporting proper immune function. Herein, we report the identification and characterization of a catalase homolog from Amphiprion clarkii (ClCat), followed by its functional characterization. An open reading frame was identified in the cDNA sequence of ClCat at 1581 bp, which encodes a protein of 527 amino acids (aa) with a molecular mass of 60 kDa. In silico analyses of ClCat revealed characteristic features of the catalase family and a lack of a signal peptide. Multiple sequence alignment of ClCat indicated the conservation of functionally important residues among its homologs. According to phylogenetic analysis, ClCat was of vertebrate origin, positioned within the teleost clade. During native conditions, ClCat mRNA was highly expressed in blood, followed by the liver and kidney. Moreover, significant changes in ClCat transcription were observed after stimulation with LPS, poly I:C, and Vibrio harveyi, in a time-dependent manner. Recombinant ClCat (rClCat) was characterized, and its peroxidase activity was determined. Furthermore, the optimum temperature and pH for rClCat were determined to be 30-40 °C and pH 7, respectively. Oxidative stress tolerance and chromatin condensation assays indicated enhanced cell survival and reduced apoptosis, resulting from reactive oxygen species scavenging by rClCat. The DNA-protective function of rClCat was further confirmed via a metal-catalyzed oxidation assay. Taken together, our findings propose that rClCat plays an essential role in maintaining cellular oxidative homeostasis and host immune protection.


Assuntos
Catalase/imunologia , Doenças dos Peixes/imunologia , Peixes/imunologia , Regulação da Expressão Gênica/genética , Imunidade Inata/genética , Animais , Antioxidantes/fisiologia , DNA/imunologia , Doenças dos Peixes/microbiologia , Regulação da Expressão Gênica/fisiologia , Lipopolissacarídeos/administração & dosagem , Estresse Oxidativo/imunologia , Poli I-C/administração & dosagem , Vibrio/fisiologia , Vibrioses/imunologia , Vibrioses/microbiologia , Vibrioses/veterinária
14.
Front Immunol ; 12: 651191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912174

RESUMO

Microbiome composition and function have been implicated as contributing factors in the pathogenesis of autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis and autoimmune hepatitis (AIH). Furthermore, dysbiosis of gut microbiome is associated with impaired barrier function and mucosal immune dysregulation. However, mechanisms by which gut microbiome contributes to the ADs and whether antioxidant treatment can restore gut homeostasis and ameliorate the disease outcome are not known. This study was, therefore, focused on examining the involvement of gut microbiome and host responses in the pathogenesis of SLE using unique female mouse models (C57BL/6, MRL+/+ and MRL/lpr) of 6 and 18 weeks with varying degrees of disease progression. Fecal microbiome diversity and composition, gut oxidative stress (OS), barrier function and inflammation, as well as systemic autoimmunity were determined. Interestingly, each mouse strain had distinct bacterial community as revealed by ß-diversity. A lower Firmicutes/Bacteroidetes ratio in 6-week-old MRL/lpr mice was observed, evidenced by decrease in Peptostreptococcaceae under Firmicutes phylum along with enrichment of Rikenellaceae under Bacteroidetes phylum. Additionally, we observed increases in colonic OS [4-hydroxynonenal (HNE)-adducts and HNE-specific immune complexes], permeability changes (lower tight junction protein ZO-2; increased fecal albumin and IgA levels) and inflammatory responses (increased phos-NF-κB, IL-6 and IgG levels) in 18-week-old MRL/lpr mice. These changes were associated with markedly elevated AD markers (antinuclear and anti-smooth muscle antibodies) along with hepatic portal inflammation and severe glomerulonephritis. Notably, antioxidant N-acetylcysteine treatment influenced the microbial composition (decreased Rikenellaceae; increased Akkeransiaceae, Erysipelotrichaceae and Muribaculaceae) and attenuated the systemic autoimmunity in MRL/lpr mice. Our data thus show that gut microbiome dysbiosis is associated with increased colonic OS, barrier dysfunction, inflammatory responses and systemic autoimmunity markers. These findings apart from delineating a role for gut microbiome dysbiosis, also support the contribution of gut OS, permeability changes and inflammatory responses in the pathogenesis of ADs.


Assuntos
Disbiose/complicações , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/patologia , Lúpus Eritematoso Sistêmico/imunologia , Animais , Modelos Animais de Doenças , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/patologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Lúpus Eritematoso Sistêmico/microbiologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , Estresse Oxidativo/imunologia , Permeabilidade
15.
Food Funct ; 12(9): 4176-4198, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33861291

RESUMO

Herein, polyphenols were extracted from Pinus koraiensis bark and characterized. Besides, the in vitro antioxidant activity, inhibition effect on cancer cells and the activity of the immune system were investigated. The results showed that the main component of Pinus koraiensis bark was 3,5,7,3',5'-pentahydroxydihydroflavone. PKB polyphenols demonstrated a high antioxidant activity during in vitro investigation. In vivo immunological function studies on oxidatively injured mice revealed that Pinus koraiensis bark polyphenols effectively improved the survival status of irradiated mice. PKBP also increased the spleen and thymus index of mouse immunoregulatory organs. The results indicated that the phagocytic ability of mononuclear macrophages was increased. Comparing the cell distribution of the PKBP administered group and the model group, the PKBP-administered group reduced the cells arrested in the G1 phase, while the number of cells increased in the S and G2 phases. PKBP effectively protected the mouse immune system and reduced the immune suppression caused by radiation. These findings also confirmed that oxidative damaged cells induced by radiation could be repaired. PKBP had the highest inhibitory activity on colon cancer cells HT29, breast cancer cells MFC-7, gastric cancer cells BGC-823 and cervical cancer HeLa and HT29 cancer cells. PKB polyphenols could effectively induce the production of DNA-Ladder fragments and cause DNA damage in cancer cells. PKBP also blocked the cycle of cancer cells in the G2 phase, stopped cell division and induced cancer cell apoptosis. Analysis of cell apoptosis by Annexin V-FTIC/PI double staining indicated that PKBP inhibited HT29 cancer cell proliferation.


Assuntos
Antioxidantes , Neoplasias/patologia , Pinus/química , Polifenóis/química , Polifenóis/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular , Sobrevivência Celular , Feminino , Sequestradores de Radicais Livres/farmacologia , Radicais Livres , Humanos , Macrófagos/imunologia , Masculino , Camundongos , Estrutura Molecular , Oxirredução , Estresse Oxidativo/imunologia , Fagocitose , Casca de Planta/química , Polifenóis/isolamento & purificação , Baço/citologia
16.
Oxid Med Cell Longev ; 2021: 5545330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897941

RESUMO

Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of the disease. In this disorder, when the blood flow is compromised by ruptures or blocked arteries, sudden death of neurons is observed as a result of a lack of oxygen and nutrients. Numerous severe problems and frequent complications also exist in stroke patients; therefore, there is an urgent need to develop new therapeutic, diagnostic, and prognostic methods for the disease. At present, the diagnosis of stroke is based on a neurological examination, medical history, and neuroimaging, due to the fact that rapid and noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress and inflammation are considered key factors in stroke pathogenesis. Oxygen free radicals are responsible for oxidation of lipids, proteins, and DNA/RNA, which in turn contributes to oxidative damage of the brain. Toxic products of the oxidation reactions act cytostatically on the cell by damaging cell membranes and leading to neuronal death by apoptosis or necrosis. Thus, it seems that redox/inflammatory biomarkers might be used in the diagnosis of the disease. Nowadays, saliva is of increasing interest in clinical laboratory medicine. Redox biomarkers could be obtained easily, noninvasively, cheaply, and stress-free from saliva. This minireview is aimed at presenting the current knowledge concerning the use of salivary biomarkers of oxidative stress and inflammation in the diagnosis and prognosis of stroke.


Assuntos
Biomarcadores/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Saliva/metabolismo , Acidente Vascular Cerebral/diagnóstico , Humanos , Saliva/citologia , Acidente Vascular Cerebral/patologia
17.
J Invest Dermatol ; 141(8): 2037-2048.e4, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33676948

RESUMO

Inflammatory diseases, including psoriasis, are characterized by changes in redox regulation. The MTH1 prevents the incorporation of oxidized nucleotides during DNA replication. Using MTH1 small-molecule inhibitors, we found induced apoptosis through 8-oxodeoxyguanosine triphosphate accumulation and DNA double-strand breaks after oxidative stress in normal and malignant keratinocytes. In psoriasis, we detected increased MTH1 expression in lesional skin and PBMCs compared with that in the controls. Using the imiquimod psoriasis mouse model, we found that MTH1 inhibition diminished psoriatic histological characteristics and normalized the levels of neutrophils and T cells in the skin and skin-draining lymph nodes. The inhibition abolished the expression of T helper type 17‒associated cytokines in the skin, which was in line with decreased levels of IL-17-producing γδ T cells in lymph nodes. In human keratinocytes, MTH1 inhibition prevented the upregulation of IL-17‒downstream genes, which was independent of ROS-induced apoptosis. In conclusion, our data support MTH1 inhibition using small molecules suitable for topical application as a promising therapeutic approach to psoriasis.


Assuntos
Enzimas Reparadoras do DNA/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Psoríase/tratamento farmacológico , Pele/patologia , Administração Cutânea , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Biópsia , Linhagem Celular Tumoral , Enzimas Reparadoras do DNA/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imiquimode/administração & dosagem , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Monoéster Fosfórico Hidrolases/metabolismo , Cultura Primária de Células , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia
18.
J Neuroimmunol ; 354: 577545, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33756415

RESUMO

BACKGROUND: Inflammation along with oxidative stress alters neuroplasticity which might contribute to neurodegeneration in Parkinson's disease (PD). OBJECTIVES: We aimed to explore the correlation of inflammatory-oxidative and neurotrophic changes in PD and their association with clinical staging and motor severity. METHODS: Serum oxidative markers, pro and anti-inflammatory cytokines and BDNF levels were estimated by spectrophotometric and ELISA techniques. RESULTS: Redox-Inflammatory and neurotrophic markers significantly altered in PD and strongly correlated with motor severity and stagings of PD. CONCLUSION: This study establishes a link between peripheral immune-neurotrophic markers and disease severity in PD. This can lead to novel future therapeutics.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Inflamação , Estresse Oxidativo , Doença de Parkinson , Idoso , Fator Neurotrófico Derivado do Encéfalo/sangue , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/imunologia , Doença de Parkinson/imunologia , Doença de Parkinson/metabolismo , Índice de Gravidade de Doença
19.
Ann Transplant ; 26: e929279, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707409

RESUMO

Coronavirus disease 19 (COVID-19) has been an ongoing pandemic since December 2019. Unfortunately, kidney transplant recipients are a high-risk group during the disease course, and scientific data are still limited in this patient group. Beyond the dosage of immunosuppressive drugs, pharmacological immunosuppression may also alter the infection response in the COVID-19 course. The effects of immunosuppressive agents on the development and process of infection should not be decided only by determining how potent they are and how much they suppress the immune system; it is also thought that the direct effect of the virus, increased oxidative stress, and cytokine storm play a role in the pathogenesis of COVID-19 disease. There are data about immunosuppressive drugs like calcineurin inhibitors (CNI) or mammalian target of rapamycin inhibitors (mTORi) therapy related to their beneficial effects during any infection course. Limited data suggest that the use of CNI or mTORi may have beneficial effects on the process. In this hypothetical review, the probable impacts of CNI and mTORi on the pathogenesis of the COVID-19 were investigated.


Assuntos
COVID-19/imunologia , Inibidores de Calcineurina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , COVID-19/diagnóstico , Inibidores de Calcineurina/farmacologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Rejeição de Enxerto/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/virologia , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
20.
Front Immunol ; 12: 649693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746988

RESUMO

Dysregulated neutrophil activation contributes to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Neutrophil-derived reactive oxygen species (ROS) and granule proteases are implicated in damage to and destruction of host tissues in both conditions (cartilage in RA, vascular tissue in SLE) and also in the pathogenic post-translational modification of DNA and proteins. Neutrophil-derived cytokines and chemokines regulate both the innate and adaptive immune responses in RA and SLE, and neutrophil extracellular traps (NETs) expose nuclear neoepitopes (citrullinated proteins in RA, double-stranded DNA and nuclear proteins in SLE) to the immune system, initiating the production of auto-antibodies (ACPA in RA, anti-dsDNA and anti-acetylated/methylated histones in SLE). Neutrophil apoptosis is dysregulated in both conditions: in RA, delayed apoptosis within synovial joints contributes to chronic inflammation, immune cell recruitment and prolonged release of proteolytic enzymes, whereas in SLE enhanced apoptosis leads to increased apoptotic burden associated with development of anti-nuclear auto-antibodies. An unbalanced energy metabolism in SLE and RA neutrophils contributes to the pathology of both diseases; increased hypoxia and glycolysis in RA drives neutrophil activation and NET production, whereas decreased redox capacity increases ROS-mediated damage in SLE. Neutrophil low-density granulocytes (LDGs), present in high numbers in the blood of both RA and SLE patients, have opposing phenotypes contributing to clinical manifestations of each disease. In this review we will describe the complex and contrasting phenotype of neutrophils and LDGs in RA and SLE and discuss their discrete roles in the pathogenesis of each condition. We will also review our current understanding of transcriptomic and metabolomic regulation of neutrophil phenotype in RA and SLE and discuss opportunities for therapeutic targeting of neutrophil activation in inflammatory auto-immune disease.


Assuntos
Artrite Reumatoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Progressão da Doença , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo
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