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1.
PLoS One ; 16(7): e0254167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214123

RESUMO

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Dexametasona/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Inflamação/prevenção & controle , SARS-CoV-2 , Viremia/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Biomarcadores , COVID-19/sangue , COVID-19/diagnóstico por imagem , Dexametasona/farmacologia , Endotélio Vascular/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Masculino , Oxigênio/sangue , Projetos Piloto , Carga Viral , Viremia/sangue
2.
Toxins (Basel) ; 13(6)2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067285

RESUMO

Recent studies have revealed that the gut microbiota plays a crucial role in maintaining a healthy, as well as diseased condition. Various organs and systems, including the kidney, are affected by the gut microbiota. While the impacts of the gut microbiota have been reported mainly on chronic kidney disease, acute kidney injury (AKI) is also affected by the intestinal environment. In this review, we discussed the pathogenesis of AKI, highlighting the relation to the gut microbiota. Since there is no established treatment for AKI, new treatments for AKI are highly desired. Some kinds of gut bacteria and their metabolites reportedly have protective effects against AKI. Current studies provide new insights into the role of the gut microbiota in the pathogenesis of AKI.


Assuntos
Injúria Renal Aguda/etiologia , Microbioma Gastrointestinal/fisiologia , Injúria Renal Aguda/terapia , Animais , Disbiose , Ácidos Graxos Voláteis/fisiologia , Hemodinâmica , Humanos , Inflamação/prevenção & controle
3.
J Nanobiotechnology ; 19(1): 173, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: covidwho-1266489

RESUMO

BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Biomimética , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Portadores de Fármacos , Inflamação/prevenção & controle , Nanopartículas , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Humanos , Inflamação/complicações , SARS-CoV-2/isolamento & purificação
4.
FASEB J ; 35(7): e21699, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151459

RESUMO

FUT2, a protein that uses l-fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l-fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l-fucose on the restoration of epithelial barrier function in both the DSS-induced colitis mouse model and LPS-stimulated Caco-2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS-induced colitis was significantly reduced by l-fucose. Restoration of epithelial barrier function by l-fucose was detected. Direct l-fucose-mediated protection of tight junctions was observed in Caco-2 cells. Moreover, exogenous l-fucose promoted the exogenous metabolic pathway of l-fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l-fucose on barrier function. The severity of colitis was not improved by l-fucose in Fut2 knockout mice. Therefore we conclude that exogenous l-fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.


Assuntos
Colite/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Fucose/farmacologia , Fucosiltransferases/fisiologia , Inflamação/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Sulfato de Dextrana/toxicidade , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
J Food Sci ; 86(7): 3265-3276, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34160066

RESUMO

Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-ß, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Fibrose/prevenção & controle , Hiperuricemia/tratamento farmacológico , Inflamação/prevenção & controle , Nefropatias/tratamento farmacológico , Animais , Fibrose/etiologia , Fibrose/patologia , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Inflamação/etiologia , Inflamação/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Ácido Oxônico/toxicidade , Ratos , Ratos Sprague-Dawley
6.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068193

RESUMO

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1ß, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.


Assuntos
Anti-Inflamatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Inflamação/prevenção & controle , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Animais , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Edema/prevenção & controle , Heme Oxigenase-1/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Proteínas de Membrana/genética , Camundongos , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
J Nanobiotechnology ; 19(1): 173, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112203

RESUMO

BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Biomimética , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Portadores de Fármacos , Inflamação/prevenção & controle , Nanopartículas , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Humanos , Inflamação/complicações , SARS-CoV-2/isolamento & purificação
8.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066125

RESUMO

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. In in vivo study, male C57BL/6J wild type (WT) and endothelial-specific conditional PPARγ knockout mice were gavage fed with 0.7 g/kg/day ethanol or volume-matched water daily for 8 weeks. From the 7th week, 3 mg/kg/day GW9662 (a selective PPARγ antagonist) was intraperitoneally given for two weeks. Cerebral ischemia/reperfusion (I/R) injury and expression of manganese superoxide dismutase (MnSOD) and adhesion molecules, neutrophil infiltration, and microglial activation in the cerebral cortex before and following a 90 min unilateral middle cerebral artery occlusion (MCAO)/24 h reperfusion were evaluated. In in vitro study, the impact of chronic alcohol exposure on expression of PPARγ and MnSOD in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs) was measured. PPARγ and MnSOD were significantly upregulated in the cerebral cortex of ethanol-fed WT mice and low-concentration ethanol-exposed C57BL/6J MBMVECs. GW9662 significantly inhibited alcohol-induced upregulation of MnSOD. Eight-week ethanol feeding significantly reduced cerebral I/R injury and alleviated the post-ischemic inflammatory response (upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin, microglial activation, and neutrophil infiltration). Treatment with GW9662 and endothelial-specific conditional knockout of PPARγ did not alter cerebral I/R injury and the inflammatory response in the control mice but abolish the neuroprotective effect in ethanol-fed mice. In addition, GW9662 and endothelial-specific conditional knockout of PPARγ diminished the inhibitory effect of LAC on the post-ischemic expression of adhesion molecules and neutrophil infiltration. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing the post-ischemic inflammation via activation of PPARγ.


Assuntos
Anti-Inflamatórios/farmacologia , Etanol/administração & dosagem , Inflamação/prevenção & controle , Fármacos Neuroprotetores/farmacologia , PPAR gama/fisiologia , Traumatismo por Reperfusão/complicações , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Inflamação/etiologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
Crit Care ; 25(1): 178, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034789

RESUMO

A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient's inflammatory response.


Assuntos
COVID-19/tratamento farmacológico , Cuidados Críticos/métodos , Dexametasona/uso terapêutico , Inflamação/prevenção & controle , Insuficiência Respiratória/tratamento farmacológico , COVID-19/complicações , Dexametasona/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Insuficiência Respiratória/virologia , Resultado do Tratamento
10.
Am J Gastroenterol ; 116(6): 1124-1147, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34003176

RESUMO

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.


Assuntos
Infecções por Clostridium , Antibacterianos/uso terapêutico , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Diarreia/prevenção & controle , Humanos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/prevenção & controle , Recidiva
11.
Crit Care ; 25(1): 178, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1243817

RESUMO

A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient's inflammatory response.


Assuntos
COVID-19/tratamento farmacológico , Cuidados Críticos/métodos , Dexametasona/uso terapêutico , Inflamação/prevenção & controle , Insuficiência Respiratória/tratamento farmacológico , COVID-19/complicações , Dexametasona/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Insuficiência Respiratória/virologia , Resultado do Tratamento
12.
J Int Soc Sports Nutr ; 18(1): 39, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039357

RESUMO

BACKGROUND: Taurine has become a popular supplement among athletes attempting to improve performance. While the effectiveness of taurine as an ergogenic aid remains controversial, this paper summarizes the current evidence regarding the efficacy of taurine in aerobic and anaerobic performance, metabolic stress, muscle soreness, and recovery. METHODS: Google Scholar, Web of Science, and MedLine (PubMed) searches were conducted through September 2020. Peer-reviewed studies that investigated taurine as a single ingredient at dosages of < 1 g - 6 g, ranging from 10 to 15 min-to-2 h prior to exercise bout or chronic dose (7 days- 8 weeks) of consumption were included. Articles were excluded if taurine was not the primary or only ingredient in a supplement or food source, not published in peer-reviewed journals, if participants were older than 50 years, articles published before 1999, animal studies, or included participants with health issues. A total of 19 studies met the inclusion criteria for the review. RESULTS: Key results include improvements in the following: VO2max, time to exhaustion (TTE; n = 5 articles), 3 or 4 km time-trial (n = 2 articles), anaerobic performance (n = 7 articles), muscle damage (n = 3 articles), peak power (n = 2 articles), recovery (n = 1 article). Taurine also caused a change in metabolites: decrease in lactate, creatine kinase, phosphorus, inflammatory markers, and improved glycolytic/fat oxidation markers (n = 5 articles). Taurine dosing appears to be effective at ~ 1-3 g/day acutely across a span of 6-15 days (1-3 h before an activity) which may improve aerobic performance (TTE), anaerobic performance (strength, power), recovery (DOMS), and a decrease in metabolic markers (creatine kinase, lactate, inorganic phosphate). CONCLUSIONS: Limited and varied findings prohibit definitive conclusions regarding the efficacy of taurine on aerobic and anaerobic performance and metabolic outcomes. There are mixed findings for the effect of taurine consumption on improving recovery from training bouts and/or mitigating muscle damage. The timing of taurine ingestion as well as the type of exercise protocol performed may contribute to the effectiveness of taurine as an ergogenic aid. More investigations are needed to better understand the potential effects of taurine supplementation on aerobic and anaerobic performance, muscle damage, metabolic stress, and recovery.


Assuntos
Desempenho Atlético/fisiologia , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/administração & dosagem , Taurina/administração & dosagem , Glicemia/metabolismo , Regulação da Temperatura Corporal , Cálcio/metabolismo , Metabolismo Energético , Humanos , Inflamação/prevenção & controle , Ácido Láctico/sangue , Metabolismo dos Lipídeos , Força Muscular , Mialgia/prevenção & controle , Estresse Oxidativo , Consumo de Oxigênio , Substâncias para Melhoria do Desempenho/farmacocinética , Taurina/farmacocinética
13.
Trials ; 22(1): 338, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971938

RESUMO

BACKGROUND: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI. METHODS: The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months. DISCUSSION: Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620266 . Registered on August 8, 2018.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Vaccinium myrtillus , Avena , Método Duplo-Cego , Tolerância ao Exercício , Humanos , Inflamação/diagnóstico , Inflamação/prevenção & controle , Lipídeos , Infarto do Miocárdio/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Suécia
14.
J Food Sci ; 86(6): 2736-2752, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963555

RESUMO

Defatted walnut kernel with pellicle (WKP) is an industrial byproduct during walnut oil extraction, which is rich in protein and polyphenols. WKP was hydrolyzed by simulated gastrointestinal digestion to obtain WKP hydrolysates (WKPHs). Results showed the protein recovery and hydrolysis degree of WKPH were 82.15 and 10.36%. The total phenol contents in WKP and WKPH were 4.90 and 40.70 mg gallic acid equivalent/g, respectively. The antiaging activity of WKPH was evaluated using a d-gal-induced aging mouse model. Results showed that WKPHs could recover the activities of SOD and T-AOC and the content of MDA in tissues and serum of the aging mice. The histological morphology of liver and kidney sections and the immunohistochemistry of TNF-α, IL-1ß, and IL-6 in liver were observed. WKPH could effectively protect the tissue structure of the liver and kidney and reduce the inflammatory expression of liver in aging mice. The polypeptides and polyphenols in WKPH were further analyzed. Fifty polypeptides were identified and 12 of these peptides had Leu-Arg at the C-terminal. Forty-two polyphenols were detected, and most phenolic compounds belonged to ellagitannins. This study provided a theoretical basis for the improved processing and high-value utilization of walnut byproducts. PRACTICAL APPLICATION: Defatted walnut kernel with pellicle was hydrolyzed by simulated gastrointestinal digestion to obtain its hydrolysates. The hydrolysates have good antiaging activity in vivo. Fifty polypeptides were identified and 12 of these peptides had Leu-Arg at the C-terminal. Forty-two polyphenols were detected, and most phenolic compounds belonged to ellagitannins. This study could provide a theoretical basis for high-value utilization of walnut byproducts.


Assuntos
Envelhecimento/efeitos dos fármacos , Digestão , Galactose/toxicidade , Inflamação/prevenção & controle , Juglans/química , Peptídeos/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Trato Gastrointestinal , Masculino , Camundongos
15.
J Int Soc Sports Nutr ; 18(1): 36, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001168

RESUMO

BACKGROUND: Elite athletes may suffer from impaired immune function and gastro-intestinal (GI) symptoms, which may affect their health and may impede their performance. These symptoms may be reduced by multi-strain probiotic supplementation. Therefore, the aim of the current study is to examine the effects of probiotic supplementation on aerobic fitness characteristics, inflammatory markers and incidence and severity of GI symptoms in elite cyclists. METHODS: Twenty-seven male cyclists, ranked elite or category 1 level competitions, were randomly assigned to a multi-strain probiotic-supplemented group (E, n = 11) or placebo group (C, n = 16). All participants visited the laboratory at the beginning of the study and following 90 d of supplementation/placebo. Prior to testing, all participants completed a GI symptoms questionnaire and underwent physical and medical examination, and anthropometric measurements. Venous blood was drawn for inflammatory markers analysis. The cyclists then underwent maximal oxygen consumption (VO2max) test and time-to-fatigue (TTF) test at 85 % of maximal power, 3 h following the VO2max test. All testing procedures were repeated after 90 d of probiotic / placebo treatment (double blind design). RESULTS: Lower incidence of nausea, belching, and vomiting (P < 0.05) at rest, and decreased incidence of GI symptoms during training were found in E group vs. C Group, respectively (∆GI -0.27 ± 0.47 % vs. 0.08 ± 0.29 %, P = 0.03), no significant changes were observed in the incidence of total overall GI symptoms (∆GI -5.6 ± 14.7 % vs. 2.6 ± 11.6 %, P = 0.602) Mean rate of perceived exertion (RPE) values during the TTF were lower in E group (∆RPE: -0.3 ± 0.9 vs. 0.8 ± 1.5, P = 0.04). No significant changes were measured between and within groups in VO2max and TTF values, mean levels of C-reactive protein (CRP), IL-6-and tumor necrosis factor alpha (TNFα) values following treatment. CONCLUSIONS: Probiotics supplementation may have beneficial effects on GI symptoms in elite cyclists. Future studies, using higher doses and during different training seasons, might help understanding the effects of probiotic supplementation on elite athletes' health and performance. TRIAL REGISTRATION: NIH clinicaltrial.gov #NCT02756221 Registered 25 April 2016.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Suplementos Nutricionais , Gastroenteropatias/prevenção & controle , Inflamação/prevenção & controle , Probióticos/administração & dosagem , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Gastroenteropatias/fisiopatologia , Humanos , Inflamação/fisiopatologia , Interleucina-6/sangue , Masculino , Fadiga Muscular , Consumo de Oxigênio , Condicionamento Físico Humano/fisiologia , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
16.
Life Sci ; 279: 119655, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34043988

RESUMO

Psoriasis is a chronic inflammatory disorder of the skin and is characterized by hyper-dividing keratinocytes. This hyper-proliferation of keratinocytes is due to the high level of inflammatory cytokines. In this study, we evaluated the effect of topically applied Baricitinib, JAK1/2 inhibitor on chronic 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis model in mice. To our knowledge, this is the first report evaluating the topical route of administration of Baricitinib in the context of psoriasis in vivo. TPA-induced inflammation was induced by the topical application of TPA in both ears. Thirty minutes before the application of TPA, the inner and outer surface of each ear was treated with Baricitinib for 6 days. Topical application of Baricitinib inhibited the expression of inflammation markers up-regulated by TPA. Besides, Baricitinib substantially reduced ear swelling, infiltration of leukocytes, the proliferation of epidermal cells, and angiogenesis of the dermal layer. The results suggest that Baricitinib significantly reduced phosphorylation of STAT3 and STAT1 levels in turn attenuating the downstream expression of inflammatory cytokines. Collectively, these results suggest that Baricitinib can be a potential therapeutic through topical route for psoriasis progresses.


Assuntos
Azetidinas/administração & dosagem , Inflamação/prevenção & controle , Psoríase/prevenção & controle , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Pele/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Acetato de Tetradecanoilforbol/toxicidade , Administração Tópica , Animais , Carcinógenos/toxicidade , Inflamação/induzido quimicamente , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Psoríase/patologia , Pele/patologia
17.
Life Sci ; 279: 119641, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34043992

RESUMO

AIMS: Apigenin (4',5,7-trihydroxyflavone) is one of the subclasses of flavonoids and has various pharmacological effects. The present work was carried out to study the effect of apigenin on ethylene glycol-induced kidney damage in male Wistar rats. MAIN METHODS: We evaluated the effects of apigenin orally administrated in normal and urolithiatic rats. Animals were assigned to nine groups in random: normal control; apigenin alone (0.005, 0.01, and 0.02 g/kg bw); urolithiatic control (0.75% ethylene glycol and 1.0% ammonium chloride in drinking water); apigenin (0.005, 0.01, and 0.02 g/kg bw) plus ethylene glycol and ammonium chloride; and cystone (0.75 g/kg bw) plus ethylene glycol and ammonium chloride. At the end of 28th day of treatment, animals were sacrificed for biochemical and histopathological assays. KEY FINDINGS: Our results indicated that the apigenin treatment decreased the formation of urinary stones in urolithiatic rats. Also, apigenin reduced the generation of malondialdehyde and enhanced antioxidant enzymes activities in the kidney homogenate of rats. It also caused a significant decrease in the calcium oxalate crystals numbers in urinary sample of rats with ethylene glycol-induced hyperoxaluria. These findings were supported by histopathological examinations. SIGNIFICANCE: Based on the results obtained, apigenin attenuate ethylene glycol-related kidney damage in male Wistar rats. Although the underlying mechanism of apigenin effect has not been determined, reduction of urinary levels of stone-producing constituents, antioxidant activities, and inhibition of TGF-ß signaling may be involved.


Assuntos
Apigenina/farmacologia , Etilenoglicol/toxicidade , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Urolitíase/tratamento farmacológico , Animais , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Ratos , Ratos Wistar , Urolitíase/induzido quimicamente , Urolitíase/metabolismo , Urolitíase/patologia
18.
Food Funct ; 12(8): 3476-3492, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900330

RESUMO

Bifidobacterium longum (B. longum) species are widely used to prevent and treat ulcerative colitis (UC). In this study, phylogenetic and pan-genomic characterization of 122 B. longum strains was performed on the basis of 936 core genes; among these, four strains from different branches of the phylogenetic tree were selected for an evaluation of anti-inflammatory and immune modulatory activities in a DSS-induced colitis mouse model. Among the tested B. longum strains (B. longum FBJ20M1, B. longum FGDLZ8M1, B. longum FGSZY16M3, and B. longum FJSWXJ2M1), B. longum FGDLZ8M1 was found to most effectively alleviate colitis by reducing the expression of pro-inflammatory cytokines, restoring the colon length, and maintaining the mucosal integrity. The anti-inflammatory mechanisms of B. longum FGDLZ8M1 were related to the inhibition of NF-κB signaling. Genomic analysis indicated that these protective effects of B. longum FGDLZ8M1 may be related to specific genes associated with carbohydrate transport and metabolism and defense mechanisms (e.g., tolerance to bile salts and acids). Correlation analysis indicated that gastrointestinal transit tolerance was the most strongly associated factor. Our findings may contribute to the rapid screening of lactic acid bacterial strains with UC-alleviating effects.


Assuntos
Bifidobacterium longum/fisiologia , Colite Ulcerativa/terapia , Animais , Anti-Inflamatórios , Bifidobacterium longum/classificação , Bifidobacterium longum/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/imunologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Filogenia
19.
Nutrients ; 13(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808480

RESUMO

Chronic inflammation is a risk factor for colorectal cancer, and inflammatory cytokines secreted from inflammatory cells and active oxygen facilitate tumorigenesis. Intestinal bacteria are thought to regulate tumorigenesis. The longer the breastfeeding period, the lower is the risk of inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on colitis-associated tumorigenesis. An inflammatory colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with azoxymethane (AOM: 12 mg/kg body weight). On weeks 2 and 4, 2% dextran sulfate sodium (DSS) was administered to mice for 7 days through drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed weight loss, diarrhea, intestinal shortening, increased number of colon tumors, proliferating tumorigenesis, increased inflammation score, fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-tumor areas. Inflammation and tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress tumor formation in the large intestine by regulating the intestinal environment and ameliorating inflammation, suggesting its therapeutic potential for treatment of inflammation and colitis-associated tumorigenesis.


Assuntos
Colite/induzido quimicamente , Neoplasias do Colo/etiologia , Microbioma Gastrointestinal , Lactobacillus rhamnosus/fisiologia , Leite Humano/microbiologia , Carcinogênese , Colite/complicações , Neoplasias do Colo/prevenção & controle , Sulfato de Dextrana/toxicidade , Humanos , Inflamação/prevenção & controle , Lactobacillus rhamnosus/classificação , Masculino , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia
20.
Biochem Biophys Res Commun ; 556: 65-71, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839416

RESUMO

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Benzoatos/metabolismo , Ácido Gálico/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Plantas Medicinais/metabolismo , Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apolipoproteínas E/deficiência , Aterosclerose/patologia , Aterosclerose/prevenção & controle , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Células Espumosas/citologia , Células Espumosas/efeitos dos fármacos , Células Espumosas/imunologia , Células Espumosas/metabolismo , Ácido Gálico/administração & dosagem , Ácido Gálico/metabolismo , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/prevenção & controle , Células RAW 264.7 , Regulação para Cima/efeitos dos fármacos , Peixe-Zebra/metabolismo
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