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1.
Aquat Toxicol ; 230: 105702, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33264694

RESUMO

Although substantial knowledge of mercury toxicity in fish has been assembled; until now, studies investigating the toxic impacts in Nile tilapia (Oreochromis niloticus) following dietary exposure to organic methyl mercury (MeHg) are less prolific. Accordingly, the current study aimed to evaluate the impacts of MeHg on neurobehavioral and immune integrity in Nile tilapia after dietary exposure. Two hundred and twenty-five juvenile Nile tilapia (19.99 ± 0.33 g) were allocated into five groups in triplicates (15 fish/replicate). G1, G2, G3, G4, and G5. O. niloticus were fed corresponding basal diets containing 0, 0.5, 1, 1.5, and 2 mg/kg diet MeHg chloride (MeHgCl) daily for 30 days, zero value represented the control G1 group. The results showed that MeHg induced significant alterations in O. niloticus behavior, the swimming behavior was significantly decreased, while scratching, biting, and fin tugging behaviors were significantly augmented. Moreover; chasing, mouth pushing, and butting behaviors were significantly increased in all the exposed groups. MeHg significantly decreased brain acetylcholine esterase (AChE) and serum immunoglobulin M (IgM) levels in all the exposed groups. Meanwhile, serum levels of lysozyme (LYZ), nitric oxide (NO), superoxide dismutase (SOD) malondialdehyde (MDA), protein carbonyl (PCO), and 8 hydroxy 2 deoxyguanosine (8OH2dG) were significantly elevated in all the exposed groups except for serum reduced glutathione (GSH) content was significantly decreased implying oxidative stress (OS), lipid peroxidation (LPO), protein, DNA damage and impaired immune response of the exposed tilapia. MeHg significantly altered transcriptional expression of immune-related genes including (TNF-α, IL-1ß, and IL-8, and IL-10) in all the exposed groups. From the obtained outcomes, the present research is the premier to investigate that dietary MeHg exposure in O. niloticus significantly induced neurobehavioral and immune defense impairments in a dose-related manner. This study exhibits that dietary MeHg may pose a potential threat to the O. niloticus populations.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ciclídeos , Exposição Dietética/efeitos adversos , Compostos de Metilmercúrio/toxicidade , Poluentes Químicos da Água/toxicidade , Ração Animal/análise , Animais , Biomarcadores/sangue , Encéfalo/imunologia , Encéfalo/patologia , Ciclídeos/imunologia , Ciclídeos/metabolismo , Citocinas/genética , Exposição Dietética/análise , Relação Dose-Resposta a Droga , Glutationa/sangue , Imunoglobulina M/sangue , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Superóxido Dismutase/sangue
2.
Biochemistry (Mosc) ; 85(10): 1178-1190, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33202203

RESUMO

NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca2+ in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. In this review, basic mechanisms of NETosis, as well as its role in the pathogenesis of some diseases including COVID-19 are discussed.


Assuntos
/imunologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , /virologia , Cálcio/metabolismo , Cromatina/metabolismo , Histonas/metabolismo , Humanos , Mitocôndrias/metabolismo , NADPH Oxidases/metabolismo , Neutrófilos/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo
3.
J Environ Pathol Toxicol Oncol ; 39(3): 213-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865913

RESUMO

Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/imunologia , Asma/metabolismo , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/citologia , Feminino , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória , Triterpenos/administração & dosagem
4.
J Environ Pathol Toxicol Oncol ; 39(3): 247-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865916

RESUMO

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Citocinas/sangue , Linfoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ascite/metabolismo , Ascite/patologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/imunologia
5.
Front Immunol ; 11: 1582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793223

RESUMO

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Hiperglicemia/imunologia , Síndrome Metabólica/imunologia , Obesidade/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal , Humanos , Sistema Imunitário/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/imunologia
6.
Ecotoxicol Environ Saf ; 205: 111157, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829211

RESUMO

The fungicide carbendazim (CBM) has been applied all around the world but its potential adverse effects other than its recognized activity as endocrine disruptor in non target organisms have been scarcely studied. The aims of this work were (1) to use a battery of biomarkers that can reflect potential negative effects such as oxidative stress, genotoxicity, neurotoxicity or altered immune response; and (2) to examine biomarkers of detoxification by analyzing the gene expression of cytochrome P4501A1 (CYP1A1) and the multi-xenobiotic resistance protein P-glycoprotein (P-gp) in the freshwater fish Jenynsia multidentata exposed to environmentally relevant concentrations of CBM during 24 h. Fish exposed to 5 µg/L showed inhibition of GST activity and an increase of TBARs contents in gills, the organ of direct contact with waterborne contaminants. Genotoxicity - measured in peripheral blood-was evidenced by the increases of micronuclei frequency when fish were exposed to 5, 10 and 100 µg/L CBM and of nuclear abnormalities (NA) frequency at 0.05, 0.5, 5, 10 and 100 µg/L CBM. The expression inhibition of interleukin (IL-1ß) and tumor necrosis factor a (TNF-α) at 10, and 5 and 10 µg/L CBM, respectively, indicated an altered immune response. The expression of CYP1A1 was down regulated in liver at 10 µg/L and of P-gp at 5 µg/L CBM, indicating a possible slow on CBM metabolization. On the other hand, in gills CYP1A1 decreased at 5 and 10 µg/L while P-gp was induced at 5 and 100 µg/L CBM. Overall, most of these significant effects were detected below 10 µg/L CBM, in a range of realistic concentrations in aquatic ecosystems worldwide.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Ciprinodontiformes/metabolismo , Citocinas/metabolismo , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ciprinodontiformes/genética , Ciprinodontiformes/imunologia , Citocromo P-450 CYP1A1/genética , Ecossistema , Água Doce/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia
7.
Ecotoxicol Environ Saf ; 205: 111161, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853865

RESUMO

The present study was implemented to evaluate oxidative stress, immune response, Nrf2 and NF-κB signaling molecules related genes expression of Rhynchocypris lagowski living in biofloc technology (BFT) system and exposed to waterborne ammonia. According to the differences of C:N ratios, the experiment was divided into four groups: C:N 10.8:1 (control group), C:N 15:1, C:N 20: 1 and C:N 25:1. The results demonstrated that BFT can effectively regulate water quality and promote growth, and the C:N 20:1 group has the most significant effect (P < 0.05). Besides, significant increases in immune enzymes (lysozyme, complement C3, C4, immunoglobulin M and nitric oxide synthase) and anti-inflammatory factor (IL-2) activity of R. lagowski were emerged in the treatment C:N 20:1 after the 56-d growth experiment and the challenging trial (P < 0.05). Comparing the antioxidant status of R. lagowski in liver and gut before and after ammonia stress: superoxide dismutase, total antioxidant capacity and catalase activity in treatments C:N 20:1 were significant increased (P < 0.05), while the level of malondialdehyde was marked lower than that in control. Meanwhile, treatment C:N 20:1 considerably upregulated Nrf2 signaling molecules related genes and significantly down-regulated the expression of pro-inflammatory factor gene in NF-κB signaling pathway compared with the control (P < 0.05). These results indicated that BFT could enhance growth, antioxidant and immune response and regulate Nrf2 and NF-κB related genes expression in R. lagowski, with most excellent effects in fish given C:N 20:1 group.


Assuntos
Amônia/toxicidade , Aquicultura , Cyprinidae/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/imunologia , Citocinas/metabolismo , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo/imunologia , Transdução de Sinais , Superóxido Dismutase/metabolismo
8.
Ecotoxicol Environ Saf ; 205: 111186, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853868

RESUMO

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 µg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion () in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction.


Assuntos
Macrófagos Alveolares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Superóxidos/metabolismo , Poluentes Atmosféricos/toxicidade , Animais , Antioxidantes/metabolismo , Cinza de Carvão/toxicidade , Peróxido de Hidrogênio/metabolismo , Inflamação , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Oxirredução , Estresse Oxidativo/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
9.
Mol Immunol ; 126: 40-45, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32750537

RESUMO

Oxidative stress-related injury is a negative state caused by the imbalance between oxidation and antioxidant effects in the internal environment of the body. Oxidative stress has been confirmed to be an important factor in aging and a variety of diseases and the inhibition of inappropriate oxidative stress responses are important for maintaining normal physiological functions. Recently, considerable attention has been focused on specialized pro-resolving mediators(SPMs). SPMs are endogenous mediators derived from polyunsaturated fatty acids, which have multiple protective effects such as anti-inflammation, pro-resolution, and promoting tissue damage repair, etc. Moreover, the role of SPMs on oxidative stress has been extensively researched and provides a possible treatment method. In the current study, we review the positive role of SPMs in oxidative stress-related disease and outline the possible involved mechanism, thus providing the theoretical support for a better understanding of the roles of SPMs in oxidative stress and the theoretical basis for finding targets for the oxidative stress-related diseases.


Assuntos
Anti-Inflamatórios/metabolismo , Ácidos Graxos Insaturados/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Animais , Anti-Inflamatórios/imunologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/imunologia , Humanos , Espécies Reativas de Oxigênio/metabolismo
10.
Mol Immunol ; 126: 73-86, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771671

RESUMO

Natural killer enhancing factor (NKEF) of peroxiredoxin family is an important innate immune molecule with having anti-oxidant activity. Although this gene has already been studied in a few fish species, it is yet to be identified and functionally characterised in Indian major carps. In the present study, the complete NKEF-B cDNA of rohu, Labeo rohita was cloned that encoded a putative protein of 197 amino acids. The phylogenetic study showed that L. rohita NKEF-B (LrNKEF-B) is closely related to NKEF-B of Cyprinus carpio and Danio rerio species. Tissue-specific expression of LrNKEF-B gene revealed the highest transcript level in the liver tissue. In the ontogeny study, the highest level of the expression was observed in milt and at 18 h post-development. The expression pattern of this gene was also studied in various pathogen models viz., Gram-negative bacteria (Aeromonas hydrophila), ectoparasite (Argulus siamensis) and a dsRNA viral analogue (poly I:C) in the liver and anterior kidney tissues of L. rohita juveniles. During A. hydrophila infection, the increase in expression of transcripts was observed at 3 h post-infection in both liver (15-fold) and anterior kidney (8-fold). In A. siamensis infection, the expression gradually increased up to 3 d post-infection in the anterior kidney, whereas in liver 3-fold up-regulation was noticed at 12 h post-infection. Similarly, during poly I:C stimulation, up-regulation of NKEF-B transcript was observed in anterior kidney from 1 h to 24 h post-stimulation and down-regulated afterwards whereas, the transcript level increased gradually from 6 h to 15 d post-stimulation in liver tissue. In vitro exposure to concanavalin, A and formalin-killed A. hydrophila upregulated NKEF-B gene expression in anterior kidney and peripheral blood leukocytes of L. rohita, however, down-regulated the same in the splenic leukocytes. A recombinant protein of LrNKEF-B (rLrNKEF-B) of 22 kDa was produced and it showed anti-oxidant activity by protecting supercoiled DNA and reducing insulin disulfide bonds. The minimum bactericidal concentration of this recombinant protein was found to be 4.54 µM against A. hydrophila and Staphylococcus aureus. Interestingly, rLrNKEF-B showed relative percent survival of 72.6 % in A. hydrophila challenged L. rohita, and the survival was found to be associated with a high level of expression of different cytokines, anti-oxidant genes and perforin in the rLrNKEF-B treated L. rohita. An indirect ELISA assay for estimation of NKEF was developed in L. rohita, and the concentrations of NKEF-B increased with time periods post A. hydrophila challenge viz., 0 h (42.56 ng/mL), 12 h (174 ng/mL) and 48 h (370 ng/mL) in rohu serum. Our results suggest a crucial role of LrNKEF-B in innate immunity against biotic stress and oxidative damage and also having antibacterial activity.


Assuntos
Carpas/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Imunidade Inata , Peroxirredoxinas/imunologia , Aeromonas hydrophila/imunologia , Animais , Arguloida/imunologia , Carpas/genética , Carpas/microbiologia , Carpas/parasitologia , Clonagem Molecular , Doenças dos Peixes/sangue , Doenças dos Peixes/microbiologia , Doenças dos Peixes/parasitologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Rim Cefálico/enzimologia , Rim Cefálico/imunologia , Fígado/enzimologia , Fígado/imunologia , Estresse Oxidativo/imunologia , Peroxirredoxinas/genética , Filogenia , Poli I-C/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Staphylococcus aureus/imunologia
11.
Eur J Pharmacol ; 882: 173329, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32615182

RESUMO

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Diabetes Mellitus/imunologia , Melatonina/farmacologia , Obesidade/imunologia , Pneumonia Viral/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/epidemiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Pulmão , Melatonina/uso terapêutico , Obesidade/epidemiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
12.
Toxicol Lett ; 331: 152-158, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522579

RESUMO

Chronic exposure to n-hexane, a widely used solvent in industry, causes sensorimotor neuropathy, which is mainly mediated by its toxic metabolite, 2,5-hexanedione (HD). However, the mechanisms remain unclear. This study is designed to investigate whether nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in HD-induced neurotoxicity. Results showed that HD intoxication significantly elevated NLRP3 expression, caspase-1 activation and interleukin-1ß (IL-1ß) maturation in the spinal cord of rats, indicating NLRP3 inflammasome activation. Glibenclamide, a sulfonylurea inhibitor of NLRP3 inflammasome, reduced HD-induced NLRP3 inflammasome activation, which was associated with mitigated gasdermin D (GSDMD) cleavage, neurofilament protein L (NF-L) reduction and demyelination as well as axon degeneration in the spinal cord of rats. Subsequently, we found that inhibition of NLRP3 inflammasome by glibenclamide suppressed microglial activation and M1 polarization and simultaneously recovered M2 polarization in HD-intoxicated rats. Furthermore, glibenclamide treatment reduced the contents of malondialdehyde (MDA) as well as elevated glutathione (GSH) levels and total-antioxidative capacity in the spinal cord of HD-intoxicated rats, indicating attenuated oxidative stress. Collectively, our findings suggested that NLRP3 inflammasome activation contributed to HD-induced neurotoxicity by enhancing microglial M1 polarization and oxidative damage. Inhibition of NLRP3 inflammasome by glibenclamide might a potential avenue to combat n-hexane-induced neuropathy.


Assuntos
Glibureto/farmacologia , Hexanonas/toxicidade , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Masculino , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/imunologia , Ratos Sprague-Dawley , Medula Espinal/imunologia , Medula Espinal/metabolismo
13.
PLoS One ; 15(6): e0234484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511271

RESUMO

Inflammation plays a crucial role in the defense response of the innate immune system against pathogen infection. In this study, we selected 4 compounds for their potential or proven anti-inflammatory and/or anti-microbial properties to test on our in vitro model of bacteria-infected THP-1-derived macrophages. We first compared the capacity of sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) to induce the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of the antioxidant, anti-inflammatory response pathways. Next, we performed a comparative evaluation of the antioxidant and anti-inflammatory efficacies of the 4 selected compounds. THP-1-derived macrophages and LPS-stimulated macrophages were treated with each compound and expression levels of genes coding for inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified by RT-qPCR. Moreover, expression levels of genes coding for M1 (IL-23, CCR7, IL-1ß, IL-6, and TNF-α) and M2 (PPARγ, MRC1, CCL22, and IL-10) markers were determined in classically-activated M1 macrophages treated with each compound. Finally, the effects of each compound on the intracellular bacterial survival of gram-negative E. coli and gram-positive S. aureus in THP-1-derived macrophages and PBMC-derived macrophages were examined. Our data confirmed the anti-inflammatory and antioxidant effects of SFN, WG, and DMF on LPS-stimulated THP-1-derived macrophages. In addition, SFN or WG treatment of classically-activated THP-1-derived macrophages reduced expression levels of M1 marker genes, while SFN or DMF treatment upregulated the M2 marker gene MRC1. This decrease in expression of M1 marker genes may be correlated with the decrease in intracellular S. aureus load in SFN- or DMF-treated macrophages. Interestingly, an increase in intracellular survival of E. coli in SFN-treated THP-1-derived macrophages that was not observed in PBMC-derived macrophages. Conversely, OTZ exhibited pro-oxidant and proinflammatory properties, and affected intracellular survival of E. coli in THP-1-derived macrophages. Altogether, we provide new potential therapeutic alternatives in treating inflammation and bacterial infection.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/imunologia , Estresse Oxidativo/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Fumarato de Dimetilo/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/imunologia , Flavanonas/farmacologia , Humanos , Inflamação/imunologia , Isotiocianatos/farmacologia , Leucócitos Mononucleares , Ativação de Macrófagos/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Estresse Oxidativo/imunologia , Pirazinas/farmacologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/efeitos dos fármacos , Células THP-1 , Tionas , Tiofenos
14.
Nutrients ; 12(6)2020 May 27.
Artigo em Inglês | MEDLINE | ID: covidwho-381976

RESUMO

The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.


Assuntos
Infecções por Coronavirus , Dieta , Sistema Imunitário/imunologia , Inflamação/imunologia , Nutrientes/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral , Antioxidantes , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Inflamação/prevenção & controle , Estado Nutricional/imunologia , Pneumonia Viral/imunologia
15.
Chemosphere ; 255: 127040, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416398

RESUMO

There is growing concern that microplastics (MPs), which act as carriers of other organic contaminants, are mistakenly ingested by aquatic organisms, consequently causing unpredictable adverse effects. In this study, zebrafish larvae (6 d post fertilization) were exposed to either 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), polystyrene microplastics (PS-MPs) or their combination for 7 d to evaluate the effects of the presence of PS-MPs on the bioaccumulation and immunomodulation of F-53B. PS-MPs greatly promoted the sorption of F-53B, which reduced the bioavailability and bioaccumulation of F-53B in zebrafish larvae. F-53B, PS-MPs, or their mixture significantly reduced the body weight of zebrafish larvae. Combined exposure of PS-MPs and F-53B resulted in a significant reduction in superoxide dismutase (SOD) and lysozyme activity, indicating the occurrence of oxidative stress and inflammatory response in zebrafish larvae. The content of malondialdehyde (MDA) and immunoglobulin M (IgM) was not affected by F-53B or PS-MPs, but significantly increased in their combined exposure. Furthermore, co-exposure of F-53B and PS-MPs significantly upregulated the transcripts of pro-inflammatory cxcl-clc and il-1ß genes and increased the levels of iNOS protein in zebrafish larvae. In addition, enhanced protein expression of NF-κB paralleled the upregulation in the expression of most immune-related genes, suggesting NF-κB pathway was mechanistically involved in these responses. Collectively, the presence of MPs decreased F-53B bioaccumulation, but induced inflammatory stress in larval zebrafish. These findings highlight the health risks of co-contamination of MPs and F-53B in aquatic environments.


Assuntos
Alcanossulfonatos/toxicidade , Bioacumulação , Microplásticos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Alcanossulfonatos/metabolismo , Animais , Disponibilidade Biológica , Larva/efeitos dos fármacos , Larva/imunologia , Larva/metabolismo , Malondialdeído/metabolismo , Microplásticos/metabolismo , Estresse Oxidativo/imunologia , Poliestirenos/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/imunologia
16.
Nutrients ; 12(6)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471251

RESUMO

The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.


Assuntos
Infecções por Coronavirus , Dieta , Sistema Imunitário/imunologia , Inflamação/imunologia , Nutrientes/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral , Antioxidantes , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Inflamação/prevenção & controle , Estado Nutricional/imunologia , Pneumonia Viral/imunologia
17.
Clin Immunol ; 215: 108410, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-38673

RESUMO

Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.


Assuntos
Infecções por Coronavirus/genética , Epigênese Genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Viremia/genética , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Antígeno CD11a/genética , Antígeno CD11a/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/imunologia , Metilação de DNA , Progressão da Doença , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Ligação Proteica , Receptores KIR/genética , Receptores KIR/imunologia , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Viremia/complicações , Viremia/epidemiologia , Viremia/imunologia
18.
Clin Immunol ; 215: 108410, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32276140

RESUMO

Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.


Assuntos
Infecções por Coronavirus/genética , Epigênese Genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Viremia/genética , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Antígeno CD11a/genética , Antígeno CD11a/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/imunologia , Metilação de DNA , Progressão da Doença , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Ligação Proteica , Receptores KIR/genética , Receptores KIR/imunologia , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Viremia/complicações , Viremia/epidemiologia , Viremia/imunologia
19.
Sci Rep ; 10(1): 6449, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296107

RESUMO

Hypoxia (HYPX) induced-overload Ca2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca2+ permeable TRPM2 channel was gated by ADP-ribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 µM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl2 (200 µM and 24 hours) incubation was used. HYPX-induced intracellular Ca2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H2O2 and ADPR. RSV treatment improved intracellular Ca2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1ß and TNF-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn2+, apoptosis, cell death, PARP-1, TRPM2 expression, caspase -3 and -9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.


Assuntos
Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Resveratrol/farmacologia , Canais de Cátion TRPM/metabolismo , Adenosina Difosfato Ribose/metabolismo , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/imunologia , Linhagem Celular Tumoral , Cobalto/toxicidade , Células HEK293 , Humanos , Peróxido de Hidrogênio/metabolismo , Hipóxia Encefálica/tratamento farmacológico , Hipóxia Encefálica/imunologia , Hipóxia Encefálica/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurônios/citologia , Neurônios/imunologia , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Resveratrol/uso terapêutico
20.
Sci Rep ; 10(1): 6493, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32300192

RESUMO

The current study aims to evaluate the antioxidant, cytotoxicity activities and suppression of LPS-induced oxidative stress production and characterization of phytochemicals in Solanum sisymbriifolium leaf extracts. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity of the leaves of S. sisymbriifolium extracted with solvents of various polarities viz. water: ethanol, ratio 50: 50; ethyl acetate and dichloromethane, was assessed. The cytotoxicity of the extracts was determined using the [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] (MTT) assay on RAW 264.7 macrophage (Murine) cells and real-time cell analysis (RTCA) xCELLigence system was used for determining cell viability. Cell-based detection of reactive oxygen species (ROS) was investigated utilizing a 2',7'-Dichlorodihydrofluorescein diacetate (H2DCF-DA) assay. The DPPH and ABTS scavenging activity results of extracts revealed a dose-dependent response with significantly lower activity in both DPPH and ABTS. The superoxide dismutase (SOD) enzyme activity was then evaluated and extracts displayed a high SOD enzyme activity with 90-50% activity. Cytotoxicity results revealed that S. sisymbriifolium extracts were not toxic to RAW 264.7 macrophage cells at the tested concentrations. All three extracts decreased the production of ROS in macrophage cells. Phytochemical analysis using Fourier-transform infrared spectroscopy (FTIR) indicated the presence of metabolite functional groups which may be responsible for the antioxidant activity. The current study indicates that S. sisymbriifolium contains phytochemicals that scavenge free radicals, with less toxicity, and suppresses the LPS-induced ROS production in RAW 264.7 macrophage cells.


Assuntos
Depuradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Solanum/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Depuradores de Radicais Livres/isolamento & purificação , Lipopolissacarídeos/imunologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade
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