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1.
Chem Biol Interact ; 329: 109220, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32763245

RESUMO

The sepsis is considered as serious clinic-pathological condition related with high rate of morbidity and mortality in critical care settings. In the proposed study, the hydrazides derivatives N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) were investigated against the LPS-induced sepsis in rodents. The NCHDH and NTHDH markedly improved the physiological sign and symptoms associated with the sepsis such as mortality, temperature, and clinical scoring compared to negative control group, which received only LPS (i.p.). The NCHDH and NTHDH also inhibited the production of the NO and MPO compared to the negative control. Furthermore, the treatment control improved the histological changes markedly of all the vital organs. Additionally, the Masson's trichrome and PAS (Periodic Acid Schiff) staining also showed improvement in the NCHDH and NTHDH treated group in contrast to LPS-induced group. The antioxidants were enhanced by the intervention of the NCHDH and NTHDH and the level of the MDA and POD were attenuated marginally compared to the LPS-induced group. The hematology study showed marked improvement and the reversal of the LPS-induced changes in blood composition compared to the negative control. The synthetic function of the liver and kidney were preserved in the NCHDH and NTHDH treated group compared to the LPS-induced group. The NCHDH and NTHDH markedly enhanced the Nrf2, HO-1 (Heme oxygenase-1), while attenuated the Keap1 and TRPV1 expression level as compared to LPS treated group. Furthermore, the NCHDH and NTHDH treatment showed marked increased in the mRNA expression level of the HSP70/90 proteins compared to the negative control.


Assuntos
Hidrazinas/farmacologia , Insuficiência de Múltiplos Órgãos/etiologia , Sepse/etiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Heme Oxigenase-1/metabolismo , Hidrazinas/química , Hidrazinas/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/mortalidade , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Sepse/tratamento farmacológico , Sepse/mortalidade , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
2.
Life Sci ; 257: 118130, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710950

RESUMO

BACKGROUND AND OBJECTIVES: Sepsis is a life-threatening organ dysfunction syndrome arising from uncontrolled inflammatory responses. Liver injury is a crucial factor for the prognosis of sepsis. Camptothecins (CPTs) have been reported to suppress the inflammatory response induced by sepsis. G2, a CPT-bile acid conjugate, has been demonstrated the property of liver targeting in our previous research. This study aimed to research the effects of G2 on liver injury induced by cecal ligation and puncture (CLP). METHODS: C57BL/6 mice were subjected to CLP surgery, and effects of G2 on liver damage and survival rates of CLP-induced mice were evaluated. To detect the related markers of hepatic injury or neutrophil infiltration, inflammatory cytokines and protein levels, hematoxylin-eosin staining assay, corresponding Detection Kits assay, ELISA and Western blot analysis were performed. RESULTS: Intraperitoneal administration of G2 reduced liver injury and enhanced the survival rates in mice with sepsis. Treatment with G2 decreased the levels of hepatic injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of mice induced by CLP. The hepatic level of neutrophil infiltration marker myeloperoxidase (MPO) was reduced in G2 administration group. And the levels of serum inflammatory cytokines, including Tumor Necrosis Factor-α (TNFα), Interleukin-6 (IL-6) and IL-1ß, were decreased by G2. Furthermore, the results of Western blot analysis indicated that G2 suppressed the up-regulation of NF-κB p-P65 and p-IκBα. It suggested that G2 suppressed the activation of NF-κB signaling pathway. CONCLUSION: G2 alleviated sepsis-induced liver injury via inhibiting the NF-κB signaling pathway.


Assuntos
Ácidos e Sais Biliares/uso terapêutico , Camptotecina/uso terapêutico , Hepatopatias/etiologia , NF-kappa B/metabolismo , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/administração & dosagem , Western Blotting , Camptotecina/administração & dosagem , Citocinas/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Hepatopatias/metabolismo , Hepatopatias/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo
3.
Chem Biol Interact ; 329: 109210, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32726580

RESUMO

Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluated the effect of tempol on inflammation and oxidative damage induced by acute exposure to cigarette smoke in vivo. Male C57BL/6 mice (n = 32) were divided into 4 groups (n = 8 each): 1) control group exposed to ambient air (GC), 2) animals exposed to cigarette smoke for 5 days (CSG), mice treated 3) prior or 4) concomitantly with tempol (50 mg/kg/day) and exposed to cigarette smoke for 5 days. The results showed that the total number of leukocytes and neutrophils increased in the respiratory tract and lung parenchyma of mice exposed to cigarette smoke. Likewise, MPO levels and activity as well as lipid peroxidation and lung protein nitration and carbonylation also increased. Administration of tempol before or during exposure to cigarette smoke inhibited all the above parameters. Tempol also reduced the pulmonary expression of the inflammatory cytokines Il-6, Il-1ß and Il-17 to basal levels and of Tnf-α by approximately 50%. In contrast, tempol restored Il-10 and Tgf-ß levels and enhanced the expression of Nrf2-associated genes, such as Ho-1 and Gpx2. Accordingly, total GPx activity increased in lung homogenates of tempol-treated animals. Taken together, our results show that tempol protects mouse lungs from inflammation and oxidative damage resulting from exposure to cigarette smoke, likely through reduction of leukocyte infiltration and increased transcription of some of the Nrf2-controlled genes.


Assuntos
Óxidos N-Cíclicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fumar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/química , Interleucina-10/genética , Interleucina-10/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Nitritos/análise , Peroxidase/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Marcadores de Spin , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
4.
Ecotoxicol Environ Saf ; 201: 110869, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32585490

RESUMO

Chromium (Cr) contamination is a potential threat to the agricultural soil. Arbuscular mycorrhizal (AM) fungi have potential to remediate the heavy metal polluted soils. It was hypothesized that Cr phytoremediation potentiality of AM fungi could be enhanced in combination with saprophytic filamentous fungi and soil amendment. Tomato plants were raised in Cr polluted technosol amended with compost, inoculated with mixed-culture of AM fungi and Aspergillus terreus. It was found that, triple treatment (soil amendment with compost along with AM fungi and A. terreus inoculation) enhanced biomass production (up to 315%), fruit setting (up to 49%), photosynthetic pigments (up to 214%) and carbohydrate content (up to 400%) whereas reduced the proline (up to 76.5%), catalase (up to 34.2%), peroxidase (up to 58.9%) and root membrane permeability (up to 74.2%). The effect of AM fungi with compost amendment was additive, while it was synergistic with A. terreus. AM fungi enhanced the extraction of Cr from the substrate, but retained in the mycorrhizal root, thereby reduced the translocation into shoot and in fruit, Cr translocation was undetectable. At the end of experiment Cr content in the substrate was significantly decreased (up to 37.9%). Soil amendment with compost along with AM fungi and A. terreus inoculation can be used for reclamation of Cr polluted soils at field scale.


Assuntos
Aspergillus/fisiologia , Cromo/farmacocinética , Lycopersicon esculentum/metabolismo , Micorrizas/fisiologia , Poluentes do Solo/farmacocinética , Biodegradação Ambiental , Biomassa , Metabolismo dos Carboidratos , Catalase/metabolismo , Compostagem , Lycopersicon esculentum/enzimologia , Peroxidase/metabolismo , Raízes de Plantas/metabolismo , Prolina/metabolismo
5.
Chem Biol Interact ; 327: 109181, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32569593

RESUMO

Acute pancreatitis (AP) is a sudden pancreatic inflammation accompanied by an excessive reactive oxygen species production that provokes inflammation. The present study investigated whether carvedilol can protect against l-arginine induced AP in a rat model and studied the mechanisms associated with its protection. Rats were divided into four groups: a control group, an AP group (injected with 2 doses of l-arginine 250 mg/100 g body weight at 1 h interval, intraperitoneally) on the 22nd day of the experiment, a carvedilol group (10 mg/kg, orally) for 21 successive days, and finally a carvedilol + AP group. It was found that pretreatment with carvedilol decreased α-amylase and lipase activities as well as C-reactive protein (CRP) and malondialdehyde levels; on the other hand, it improved the reduced glutathione (GSH) level and catalase (CAT) activity. In addition, carvedilol markedly decreased all of the following biomarkers: nuclear factor kappa B (NF-κB p65), p38 mitogen-activated protein kinases (P38-MAPK), signal transducer and activator of transcription 1 (STAT1-α), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), myeloperoxidase (MPO), and phospholipase A2 (PLA2) levels that was induced by l-arginine. Finally, carvedilol noticeably down regulated the pancreatitis associated protein (PAP2) and the pancreas platelets activating factor (PAF) genes expression. In conclusion: carvedilol protected against l-arginine induced AP in rats, via the inhibition of cellular oxidative stress and inflammatory pathways that contributed to pancreas injury.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carvedilol/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pancreatite/tratamento farmacológico , Animais , Arginina , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Glutationa/metabolismo , Hidrolases/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Peroxidase/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
6.
Chemosphere ; 259: 127258, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32585458

RESUMO

This is the first study to investigate the reduction mechanism of Tl (III) to Tl(I) in the presence of plants, especially rice. Smaller plant density could effectively reduce the content of organic acids in the hydroponic system to keep the stability of Tl(III). As the plant density was reduced from 40 seedlings to 10 seedlings in 100 mL Tl(III) solution, the content of oxalate was declined to one-third of the original, and the ratio of Tl(III)/total Tl was increased from 39.6% to 81.0% in the first 2 h treatment. Then the differences in antioxidant capacity of rice exposed to the two Tl species were studied. The contents of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide anion (O2˙-) of rice roots exposed to Tl(III) were all higher than those to Tl(I). Meanwhile, the catalase (CAT) activity was significantly depressed and peroxidase (POD) was increased by Tl(III), whereas superoxide dismutase (SOD) showed a rise in both Tl(I) and Tl(III) with no significant difference between them. The expression of metallothionein gene OsMT1a to Tl(I) was upregulated to 255.5 times of Tl(III) though OsMT2c was downregulated to 0.39 times of Tl(III). Overall, the different responses in metallothionein gene expression and antioxidative enzyme activation might result in more ROS accumulation to rice roots by Tl(III) treatment than those by Tl(I).


Assuntos
Metalotioneína/genética , Oryza/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tálio/toxicidade , Antioxidantes/metabolismo , Catalase/metabolismo , Peróxido de Hidrogênio/metabolismo , Hidroponia , Malondialdeído/metabolismo , Metalotioneína/metabolismo , Oryza/genética , Oryza/metabolismo , Peroxidase/metabolismo , Peroxidases/metabolismo , Raízes de Plantas/metabolismo , Plântula/metabolismo , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
7.
Proc Natl Acad Sci U S A ; 117(27): 15827-15836, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571911

RESUMO

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br, 81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.


Assuntos
Membrana Basal/metabolismo , Bromo/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Peroxidase/metabolismo , Animais , Biópsia , Bromatos/metabolismo , Brometos , Células Cultivadas , Colágeno Tipo IV/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Iminas/metabolismo , Rim/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteômica
8.
Leg Med (Tokyo) ; 46: 101724, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32516737

RESUMO

Hypochlorous acid, produced by myeloperoxidase upon neutrophil activation, can oxidize various compounds and exert antimicrobial activity in vivo. To elucidate the mechanisms underlying the reactions of the unsaturated phosphatidylcholines, which abound in cell membranes, with hypochlorous acid, we identified and examined phosphatidylcholine chlorination and oxidation products formed under various reaction conditions. We first investigated the products of unsaturated phosphatidylcholine and hypochlorous acid reaction with respect to hypochlorite concentration and reaction time. Next, we examined the lipids extracted postmortem from human abscesses. For all the analyses, we used liquid chromatography-quadrupole time-of-flight mass spectrometry. Various compounds, including phosphatidylcholine chlorohydrin and phosphatidylcholine hydroxide/epoxide, were detected. Oxidized phosphatidylcholines were mainly detectable upon reaction with low concentrations of sodium hypochlorite, whereas chlorinated phosphatidylcholines formed in the presence of higher concentrations. In human abscesses, oxidized phosphatidylcholines were detected in the cases with high procalcitonin concentration, whereas chlorinated phosphatidylcholines were undetected. The detections of oxidized phosphatidylcholines in human tissues might indicate previous exposure to hypochlorous acid in septic cases. Our results provide insight into the mechanisms underlying pathogen survival following inflammation associated with neutrophil activation and topical myeloperoxidase release and show postmortem biomarkers candidates for sepsis.


Assuntos
Abscesso/diagnóstico , Abscesso/metabolismo , Ácido Hipocloroso/metabolismo , Lipídeos/análise , Fosfatidilcolinas/metabolismo , Biomarcadores/metabolismo , Membrana Celular/metabolismo , Cromatografia Líquida , Medicina Legal/métodos , Halogenação , Humanos , Ácido Hipocloroso/química , Espectrometria de Massas , Ativação de Neutrófilo , Oxirredução , Peroxidase/metabolismo , Fosfatidilcolinas/química
9.
Aquat Toxicol ; 225: 105548, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32593115

RESUMO

Natural algaecides are more likely to be specific and biodegradable, and may offer an environmentally friendly method for control of cyanobacterial blooms. We explored, for the first time, the potential for watermelon peel aqueous extract (WMPAE) to control the growth of the harmful blue-green alga Aphanizomenon flos-aquae. The growth inhibition and several physiological parameters of A. flos-aquae, in response to WMPAE, were analyzed. Results showed that WMPAE significantly inhibited the growth of A. flos-aquae in a concentration-dependent way. The highest inhibition reached 94 % after 3 days' treatment with 6 g L-1 of WMPAE and a significant effect was obtained with lower doses and shorter times as well. The cell viability decreased quickly, cell shape changed, and intracellular structural damage occurred. At the same time, the antioxidant enzymes (superoxide dismutase SOD, catalase CAT and peroxidase POD) and malondialdehyde (MDA) levels all increased significantly, indicating that WMPAE between 2-6 g L-1 induced severe oxidative stress and damage to A. flos-aquae. Moreover, production of the four pigments chlorophyll a (Chl a), carotenoids, phycocyanin (PC), and allophycocyanin (APC) were all stimulated, though photosynthesis of A. flos-aquae was clearly inhibited. The maximum quantum yield of photosystem II (Fv/Fm) and the effective quantum yield of photosystem II ( Fv'/Fm') declined sharply, suggesting the decreased photosystem capacity of A. flos-aquae to convert light energy into chemical energy. In addition, non-photochemical quenching (NPQ) of A. flos-aquae increased after a very short time exposure to WMPAE, and decreased significantly with prolonged exposure time, which indicated the failure of photo protection mechanisms. These results suggest that the loss of cell viability, and increases in oxidative stress, and damage to intracellular structure and photosynthetic systems might be the mechanisms for the inhibitory effects. Our results suggested that WMPAE could be a novel and effective approach for controlling the growth of A. flos-aquae in aquatic environments.


Assuntos
Aphanizomenon/fisiologia , Citrullus/efeitos dos fármacos , Extratos Vegetais/toxicidade , Poluentes Químicos da Água/toxicidade , Antioxidantes/farmacologia , Aphanizomenon/química , Catalase/metabolismo , Clorofila A , Citrullus/metabolismo , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Fotossíntese/efeitos dos fármacos , Superóxido Dismutase/metabolismo
10.
Clin Sci (Lond) ; 134(12): 1475-1489, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32538435

RESUMO

Sphingosine-1-phosphate (S1P) is a pleiotropic lysosphingolipid derived from the metabolism of plasma membrane lipids. The interaction between S1P and its ubiquitously expressed G-protein-coupled receptors (S1PR1-5) is crucial in many pathophysiological processes. Emerging evidence suggested a potential role for S1P receptors in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the present study, we investigated the effects of three different S1P receptors modulators (FTY720, SEW2871 and TY52156) in a recognized rat model of experimental autoimmune vasculitis (EAV). The effects of treatments were evaluated with clinico-pathological parameters including hematuria, proteinuria, crescent formation, pulmonary hemorrhage, etc. In vitro functional studies were performed in a Jurkat T-cell line following stimulations of serum from myeloperoxidase-AAV patients. We found that only the FTY720 treatment significantly alleviated hematuria and proteinuria, and diminished glomerular crescent formation, renal tubulointerstitial lesions and pulmonary hemorrhage in EAV. The attenuation was accompanied by less renal T-cell infiltration, up-regulated mRNA of S1PR1 and down-regulated IL-1ß in kidneys, but not altered circulating ANCA levels, suggesting that the therapeutic effects of FTY720 were B-cell independent. Further in vitro studies demonstrated that FTY720 incubation could significantly inhibit the proliferation, adhesion, and migration, and increase apoptosis of T cells. In conclusion, the S1P modulator FTY720 could attenuate EAV through the reduction and inhibition of T cells, which might become a novel treatment of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Cloridrato de Fingolimode/uso terapêutico , Peroxidase/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Anticorpos/imunologia , Apoptose , Feminino , Cloridrato de Fingolimode/farmacologia , Hematúria/complicações , Humanos , Células Jurkat , Rim/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteinúria/complicações , Ratos Endogâmicos WKY , Transdução de Sinais
11.
Am J Trop Med Hyg ; 103(1): 520-527, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32431271

RESUMO

The microbial communities residing in the child gut are thought to play an important role in child growth, although the relationship is not well understood. We examined a cohort of young children from Mirzapur, Bangladesh, prospectively over 18 months. Four fecal markers of environmental enteropathy (EE) (high levels of alpha-1-antitrypsin, calprotectin, myeloperoxidase, and neopterin) were examined and anthropometric measures obtained from a cohort of 68 children. The 16S rRNA gene of bacterial DNA was sequenced from stool samples and used to estimate amplicon sequence variants (ASVs). We age-matched children with poor growth to children with normal growth within 1 month and compared the change in abundance and diversity of ASVs over time. Elevated EE markers and poor linear growth in children were associated with changes in microbial communities in the gut. There were increased amounts of Escherichia/Shigella and Proteobacteria and decreased amounts of Prevotella associated with poorly growing children consistent with the mounting evidence supporting the relationship between intestinal inflammation, child growth, and changes in gut microbiota composition. Future research is needed to investigate this association among young children in low- and middle-income countries.


Assuntos
Microbioma Gastrointestinal/genética , Transtornos do Crescimento/microbiologia , Enteropatias/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Neopterina/metabolismo , Peroxidase/metabolismo , alfa 1-Antitripsina/metabolismo , Bangladesh/epidemiologia , Biomarcadores , Estudos de Casos e Controles , Pré-Escolar , Escherichia , Fezes/química , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/metabolismo , Humanos , Lactente , Inflamação , Enteropatias/epidemiologia , Masculino , Prevotella , Proteobactérias , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Shigella
12.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(3): 290-293, 2020 Apr 26.
Artigo em Chinês | MEDLINE | ID: mdl-32468792

RESUMO

OBJECTIVE: To evaluate the effects of Cu2+ and Cd2+ at different concentrations on superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activity in Oncomelania hupensis. METHODS: Cu2+- and Cd2+-containing solutions were prepared at 7 concentrations, and O. hupensis snails were exposed to the solutions for 24 h, of 15 snails in each concentration. Then, the snail body was collected following removal of the snail shell and homogenated, and the SOD, CAT and POS activities were detected in the supernatants. RESULTS: With the increase of the Cu2+ concentration, the SOD activity appeared a rise followed by a reduction in O. hupensis snails, and the CTA activity appeared a decline-rise-decline tendency, while the POD activity showed a tendency towards rise followed by decline. With the increase of the Cd2+ concentration, the SOD activity appeared a rise followed by a reduction in O. hupensis snails, and the CTA activity appeared a decline- rise- decline tendency, while the POD activity showed a decline-rise-decline tendency. CONCLUSIONS: Exposure to Cu2+ and Cd2+ at high concentrations results in a decline in the activity of SOD, CAT and POD in O. hupensis at the same time.


Assuntos
Cádmio , Cobre , Oxirredutases , Caramujos , Animais , Cádmio/toxicidade , Catalase/metabolismo , Cobre/toxicidade , Ativação Enzimática/efeitos dos fármacos , Íons/toxicidade , Oxirredutases/metabolismo , Peroxidase/metabolismo , Caramujos/efeitos dos fármacos , Caramujos/enzimologia , Superóxido Dismutase/metabolismo
13.
Ecotoxicol Environ Saf ; 200: 110747, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460052

RESUMO

The presence of surfactants may affect the bioavailability of polycyclic aromatic hydrocarbons. A hydroponic experiment was conducted to investigate the response of Hydrocharis dubia (Bl.) Backer to different concentrations of linear alkylbenzene sulfonate (LAS), naphthalene (NAP) and their mixture (0.5, 5, 10, and 20 mg/L) for 14 days and 28 days. The results showed that LAS had a greater toxic effect on H. dubia growth than NAP at treatment concentrations of 0.5-20 mg/L. The combined effect of LAS and NAP was damaging to H. dubia at concentrations of LAS + NAP ≥5 + 5 mg/L. When LAS + NAP ≥10 + 10 mg/L, the underground parts of H. dubia suffered more significant damage than the aboveground parts. Under the treatments with LAS, NAP and their mixture, H. dubia experienced oxidative stress. Soluble proteins and antioxidant enzymes were the main substances protecting H. dubia from LAS stress, and superoxide dismutase (SOD) and peroxidase (POD) were the main protective enzymes. When exposed to NAP, H. dubia growth was stimulated and promoted at the same time. In the short-term treatment (14 d), catalase (CAT) activity was sensitive to NAP stimulation, and soluble proteins and SOD were the main protective substances produced. Soluble sugars, SOD and ascorbate peroxidase (APX) played important protective roles during the longer exposure time (28 d). The physiological response of H. dubia exposed to the combined toxicants was weaker than the response to exposure to individual toxicants. The responses of SOD and CAT activity were positive in the short term (14 d), and these were the main protective enzymes. As the exposure time increased (28 d), the plant antioxidant system responded negatively.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Hydrocharitaceae/efeitos dos fármacos , Naftalenos/toxicidade , Tensoativos/toxicidade , Ácidos Alcanossulfônicos/antagonistas & inibidores , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Sinergismo Farmacológico , Hydrocharitaceae/enzimologia , Hydrocharitaceae/metabolismo , Naftalenos/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo
14.
Ecotoxicol Environ Saf ; 200: 110732, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460049

RESUMO

This paper reports the role of exogenous glycine betaine (25 and 50 mM GB at a rate of 50 mL per plant) in enhancing NaCl-stress tolerance in common bean (Phaseolus vulgaris L.). Irrigating plants by simulated saline water, containing 0, 50 and 100 mM sodium chloride (NaCl), significantly reduced the growth dynamics, photosynthetic pigments (i.e., Chl a, Chl b, and carotenoids), membrane stability index (MSI), relative water content (RWC), and pod yield. While, malondialdehyde (MDA), endogenous proline, and glutathione contents, electrolyte leakage (EL), antioxidant defense system, and Na+ accumulation markedly increased upon exposure to NaCl-stress. However, the application of exogenous GB significantly improved salt tolerance of common bean as it increased the antioxidant defense including both enzymatic (i.e., peroxidase, superoxide dismutase, and catalase) and nonenzymatic (i.e., proline and glutathione) agents. Consequently, MSI, RWC, EL, and photosynthetic pigments have been improved recording significantly higher values than the control. Moreover, the pod yield increased by 29.8 and 59.4% when plants grown under 50 and 100 mM NaCl, respectively, were sprayed with 25 mM GB. Our results show that GB-induced slat tolerance in common bean plants mainly depends on the osmoregulation effect of GB and to a lesser extent on its antioxidant capacity. Foliar application of GB significantly reduced the accumulation of Na+ and at the same time induced K+ uptake maintaining a higher K+/Na+ ratio. Despite some changes in the activities of antioxidant enzymes induced by the application of GB, no consistent contribution in the salt tolerance could be cited in this study. Therefore, we suggest that salt tolerance is largely unrelated to the antioxidant defense ability of GB in common bean. While the potential role of GB in ameliorating salt tolerance is mainly due to the adjustment of ions uptake through limiting Na+ uptake and alternatively increasing K+ accumulation in plant tissues.


Assuntos
Betaína/farmacologia , Phaseolus/efeitos dos fármacos , Potássio/metabolismo , Tolerância ao Sal , Sódio/metabolismo , Antioxidantes/metabolismo , Transporte Biológico/efeitos dos fármacos , Catalase/metabolismo , Cátions , Glutationa/metabolismo , Malondialdeído/análise , Osmorregulação/efeitos dos fármacos , Peroxidase/metabolismo , Phaseolus/química , Phaseolus/enzimologia , Phaseolus/metabolismo , Fotossíntese/efeitos dos fármacos , Potássio/análise , Prolina/metabolismo , Sódio/análise , Superóxido Dismutase/metabolismo
15.
Invest Ophthalmol Vis Sci ; 61(5): 26, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32416603

RESUMO

Purpose: IFN-stimulated gene (ISG) 15 is a type 1 IFN-induced protein and known to modify target proteins in a manner similar to ubiquitylation (protein conjugation by ISG15 is termed ISGylation). We sought to determine the role of ISG15 and its underlying mechanisms in corneal innate immune defense against Pseudomonas aeruginosa keratitis. Methods: ISG15 expression in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR and Western blot analysis. Gene knockout mice were used to define the role of ISG15 signaling in controlling the severity of P. aeruginosa keratitis, which was assessed with photographing, clinical scoring, bacterial counting, myeloperoxidase assay, and quantitative PCR determination of cytokine expression. Integrin LFA-1 inhibitor was used to assess its involvement of ISG15 signaling in P. aeruginosa-infected corneas. Results: Heat-killed P. aeruginosa induced ISG15 expression in cultured HCECs and accumulation in the conditioned media. Isg15 deficiency accelerated keratitis progress, suppressed IFNγ and CXCL10, and promoted IL-1ß while exhibiting no effects on IFNα expression. Moreover, exogenous ISG15 protected the corneas of wild-type mice from P. aeruginosa infection while markedly reducing the severity of P. aeruginosa keratitis in type 1 IFN-receptor knockout mice. Exogenous ISG15 increased bacteriostatic activity of B6 mouse corneal homogenates, and inhibition of LFA-1 exacerbated the severity of and abolished protective effects of ISG15 on P. aeruginosa keratitis. Conclusions: Type 1 INF-induced ISG15 regulates the innate immune response and greatly reduces the susceptibility of B6 mouse corneas to P. aeruginosa infection in an LFA-1-dependent manner.


Assuntos
Úlcera da Córnea/imunologia , Citocinas/fisiologia , Infecções Oculares Bacterianas/imunologia , Imunidade Inata/fisiologia , Infecções por Pseudomonas/imunologia , Ubiquitinas/fisiologia , Animais , Carga Bacteriana , Western Blotting , Células Cultivadas , Úlcera da Córnea/metabolismo , Úlcera da Córnea/fisiopatologia , Citocinas/metabolismo , Epitélio Anterior/metabolismo , Infecções Oculares Bacterianas/metabolismo , Infecções Oculares Bacterianas/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peroxidase/metabolismo , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologia
16.
JCI Insight ; 5(11)2020 06 04.
Artigo em Inglês | MEDLINE | ID: covidwho-116202

RESUMO

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.


Assuntos
Ácidos Nucleicos Livres/metabolismo , Infecções por Coronavirus/metabolismo , Armadilhas Extracelulares/metabolismo , Histonas/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citrulinação , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Respiração Artificial , Índice de Gravidade de Doença
17.
JCI Insight ; 5(11)2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32329756

RESUMO

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.


Assuntos
Ácidos Nucleicos Livres/metabolismo , Infecções por Coronavirus/metabolismo , Armadilhas Extracelulares/metabolismo , Histonas/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citrulinação , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Respiração Artificial , Índice de Gravidade de Doença
18.
Nat Commun ; 11(1): 2031, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341348

RESUMO

Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming "swarms" to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida. We find that neutrophil swarming over Candida clusters delays germination through the action of MPO and NADPH oxidase, and restricts fungal growth through NET release within the swarm. In comparison with neutrophils from healthy subjects, those from patients with chronic granulomatous disease produce larger swarms against Candida, but their release of NETs is delayed, resulting in impaired control of fungal growth. We also show that granulocyte colony-stimulating factors (GCSF and GM-CSF) enhance swarming and neutrophil ability to restrict fungal growth, even during treatment with chemical inhibitors that disrupt neutrophil function.


Assuntos
Candida albicans/crescimento & desenvolvimento , Neutrófilos/citologia , Neutrófilos/microbiologia , Sistemas CRISPR-Cas , Candidíase/microbiologia , Linhagem Celular , Armadilhas Extracelulares/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Doença Granulomatosa Crônica/microbiologia , Humanos , Processamento de Imagem Assistida por Computador , Análise em Microsséries , NADPH Oxidases/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
19.
J Oleo Sci ; 69(4): 377-390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32249265

RESUMO

Colletotrichum nymphaeae is the causal agent of strawberry anthracnose, which is one of the most important disease affecting strawberry plant in Iran. This research aimed to apply the selected plant essential oils (EOs) such as Achillea millefolium, Mentha longifolia, and Ferula kuma to the management of strawberry anthracnose disease under in vitro, in vivo, and greenhouse conditions. In vitro tests indicated that all the EOs and fungicide were able to inhibit mycelial growth and conidial germination of the pathogen. Scanning electron microscopy (SEM) revealed that EOs significantly suppressed the mycelia growth and caused a change in morphology of fungal mycelia. The severity of strawberry anthracnose disease was significantly (p ≤ 0.05) reduced by all EOs under in vivo and greenhouse conditions. Results of all experiments showed that M. longifolia EO was the best EO to control C. nymphaeae. Also, EOs almost reduced weight loss and preserved firmness, ascorbic acid, total phenol, antioxidant activity (DPPH), and enzyme peroxidase activity in treated fruit. Moreover, EOs preserved the sensory quality of strawberry fruit during the storage period so that there were no significant differences between treatments (EOs) in their appearance, flavor, odor attributes, and overall evaluation compared to the control. Our results indicate that EOs are excellent bio-fungicides for the management of strawberry anthracnose.


Assuntos
Qualidade dos Alimentos , Fragaria/microbiologia , Fungicidas Industriais , Mentha/química , Óleos Voláteis , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Óleos Vegetais , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Colletotrichum/patogenicidade , Fragaria/metabolismo , Peroxidase/metabolismo , Fenóis/metabolismo
20.
Ecotoxicol Environ Saf ; 197: 110599, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32304919

RESUMO

Hydroponic experiment was conducted to investigate the biochemical responses and accumulation behaviour of cadmium (Cd) in aquatic fern, Ceratopteris pteridoides, under four different levels of exposure. Plants were grown in 10 µM (CdT1), 20 µM (CdT2), 40 µM (CdT3) and 60 µM (CdT4) concentrations of Cd for 12 consecutive days and Cd accumulation in different plant parts, cell levels and growth medium was estimated. In C. pteridoides, Cd removal kinetics was best described by pseudo-second-order kinetic model. Increased accumulation of Cd in the plants was detected in a concentration dependent manner with maximum under 60 µM of Cd (CdT4) exposure (191.38 mg kg-1, 186.19 mg kg-1 and 1316.34 mg kg-1 in leaves, stems and roots, respectively). Cell wall of C. pteridoides is identified as crucial Cd storage site with the highest (28-69%) accumulation followed by organelles (14-44%) and soluble fraction (6-46%). Increased leaf proline, malondialdehyde (MDA) and protein content with significant reduction (P < 0.05) in chlorophyll concentration and upregulation of antioxidant enzymes catalase (CAT), guaiacol peroxidase (POD) and superoxide dismutase (SOD) reveals the presence of Cd resistance mechanism in C. pteridoides. Calculated higher (>1) bioconcentration factor (BCF) and lower (<1) translocation factor (TF) values evinced the suitability of C. pteridoides in Cd phytostabilization rather than phytoextraction.


Assuntos
Cádmio/farmacocinética , Pteridaceae/metabolismo , Antioxidantes/metabolismo , Transporte Biológico , Cádmio/toxicidade , Catalase/metabolismo , Parede Celular/metabolismo , Clorofila/metabolismo , Hidroponia , Malondialdeído/metabolismo , Peroxidase/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Pteridaceae/efeitos dos fármacos , Pteridaceae/enzimologia , Superóxido Dismutase/metabolismo
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