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BACKGROUND: Clinical observations on the potential of pre-hospital antiplatelet therapy in preventing ARDS have been inconsistent. To further the correlation between antiplatelet therapy and ARDS, we conducted a meta-analysis to evaluate the effects of pre-hospital antiplatelet therapy on subjects with ARDS. METHODS: A literature search in major data banks was performed. We included prospective and retrospective cohorts, case-control trials, and randomized controlled trials that compared the ARDS incidence in subjects with or without pre-hospital antiplatelet agents. RESULTS: Meta-analysis of 7 studies (a total of 30,291 subjects) showed significantly lower odds of ARDS in the pre-hospital antiplatelet therapy group compared with subjects with no pre-hospital antiplatelet therapy (odds ratio 0.68, 95% CI 0.56-0.83; P < .001). However, ARDS mortalities in the hospital and ICUs were not affected. CONCLUSIONS: These findings indicated that pre-hospital antiplatelet therapy was associated with a reduced rate of ARDS but had no effect on the mortality in the subjects at high risk.
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Inibidores da Agregação Plaquetária , Síndrome do Desconforto Respiratório , Aspirina , Hospitais , Humanos , Incidência , Estudos Prospectivos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/epidemiologia , Estudos RetrospectivosRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0208799.].
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This study was designed to examine the potential involvement of reactive oxygen species in skeletal muscle dysfunction linked with stretching in a mouse model and to explore the effects of combined antioxidant intake on peripheral leukocyte apoptosis following eccentrically-biased downhill runs in human subjects. In the mouse model, diaphragmatic muscle was stretched by 30% of its optimal length, followed by 5-min contraction. Muscle function and extracellular reactive oxygen species release was measured ex vivo. In human models, participants performed two trials of downhill running either with or without antioxidant supplementation, followed by apoptotic assay of inflammatory cells in the blood. The results showed that stretch led to decreased muscle function and prominent ROS increase during muscle contraction. In human models, we observed an elevation in circulating leukocyte apoptosis 24-48 hours following acute downhill runs. However, there is an attenuated leukocyte apoptosis following the second bout of downhill run. Interestingly, the combination of ascorbic acid (vitamin C) and α-tocopherol (vitamin E) supplementation attenuated the decrease in B-cell lymphoma 2 (Bcl-2) at 24 hours following acute downhill running. These data collectively suggest that significant ROS formation can be induced by muscle-lengthening associated with eccentric exercise, which is accompanied by compromised muscle function. The combination of antioxidants supplementation appears to have a protective role via the attenuation of decrease in anti-apoptotic protein.
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Apoptose/imunologia , Leucócitos/imunologia , Músculo Esquelético/imunologia , Doenças Musculares/imunologia , Condicionamento Físico Animal , Espécies Reativas de Oxigênio/imunologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Leucócitos/patologia , Masculino , Camundongos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , Oxirredução/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Vitamina E/farmacologiaRESUMO
The overproduction of reactive oxygen species (ROS) has been implicated in the development of various chronic and degenerative diseases such as cancer, respiratory, neurodegenerative, and digestive diseases. Under physiological conditions, the concentrations of ROS are subtlety regulated by antioxidants, which can be either generated endogenously or externally supplemented. A combination of antioxidant-deficiency and malnutrition may render individuals more vulnerable to oxidative stress, thereby increasing the risk of cancer occurrence. In addition, antioxidant defense can be overwhelmed during sustained inflammation such as in chronic obstructive pulmonary diseases, inflammatory bowel disease, and neurodegenerative disorders, cardiovascular diseases, and aging. Certain antioxidant vitamins, such as vitamin D, are essential in regulating biochemical pathways that lead to the proper functioning of the organs. Antioxidant supplementation has been shown to attenuate endogenous antioxidant depletion thus alleviating associated oxidative damage in some clinical research. However, some results indicate that antioxidants exert no favorable effects on disease control. Thus, more studies are warranted to investigate the complicated interactions between ROS and different types of antioxidants for restoration of the redox balance under pathologic conditions. This review highlights the potential roles of ROS and nutritional antioxidants in the pathogenesis of several redox imbalance-related diseases and the attenuation of oxidative stress-induced damages.
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Aim: Skeletal muscle subjected to hypoxia followed by reoxygenation is susceptible to injury and subsequent muscle function decline. This phenomenon can be observed in the diaphragm during strenuous exercise or in pulmonary diseases such as chronic obstructive pulmonary diseases (COPD). Previous studies have shown that PO2 cycling or hypoxic preconditioning (HPC), as it can also be referred to as, protects muscle function via mechanisms involving reactive oxygen species (ROS). However, this HPC protection has not been fully elucidated in aged pulmonary TNF-α overexpressing (Tg+) mice (a COPD-like model). We hypothesize that HPC can exert protection on the diaphragms of Tg+ mice during reoxygenation through pathways involving ROS/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/extracellular signal regulated kinase (ERK), as well as the downstream activation of mitochondrial ATP-sensitive potassium channel (mitoKATP) and inhibition of mitochondrial permeability transition pore (mPTP). Methods: Isolated Tg+ diaphragm muscle strips were pre-treated with inhibitors for ROS, PI3K, Akt, ERK, or a combination of mitoKATP inhibitor and mPTP opener, respectively, prior to HPC. Another two groups of muscles were treated with either mitoKATP activator or mPTP inhibitor without HPC. Muscles were treated with 30-min hypoxia, followed by 15-min reoxygenation. Data were analyzed by multi-way ANOVA and expressed as means ± SE. Results: Muscle treated with HPC showed improved muscle function during reoxygenation (n = 5, p < 0.01). Inhibition of ROS, PI3K, Akt, or ERK abolished the protective effect of HPC. Simultaneous inhibition of mitoKATP and activation of mPTP also diminished HPC effects. By contrast, either the opening of mitoKATP channel or the closure of mPTP provided a similar protective effect to HPC by alleviating muscle function decline, suggesting that mitochondria play a role in HPC initiation (n = 5; p < 0.05). Conclusion: Hypoxic preconditioning may protect respiratory skeletal muscle function in Tg+ mice during reoxygenation through redox-sensitive signaling cascades and regulations of mitochondrial channels.
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The pathogenesis of chronic obstructive pulmonary disease (COPD) is a multifaceted process involving the alteration of pulmonary vasculature. Such vascular remodeling can be associated with inflammation, shear stress, and hypoxia-conditions commonly seen in patients with lung diseases. Particularly, the overproduction of reactive oxygen species (ROS) in the diseased lungs contributes greatly to pulmonary vascular remodeling. ROS play an important role in vascular homeostasis, yet excessive ROS can alter pulmonary vasculature and impair lung function, as implicated in COPD at all stages. Increased inflammatory cell infiltration and endothelial dysfunction both correspond to the severity of COPD. As a byproduct of vascular remodeling, pulmonary hypertension negatively affects the long-term survival rate of COPD patients. While there is currently no cure for COPD, several treatment options have focused on alleviating COPD symptoms. Interventions such as long-term oxygen therapy, endothelium-targeted treatment, and pharmacological therapies show promising results in improving the life span of COPD patients and attenuating the progression of pulmonary hypertension. In this chapter, we aim to discuss the contributing factors of pulmonary vascular remodeling in COPD with an emphasis on the ROS, as well as potential redox treatments for COPD-related vascular remodeling.
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Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Remodelação Vascular , Animais , Antioxidantes/farmacologia , Progressão da Doença , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipóxia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
As one of the most commonly diagnosed cancers worldwide, colorectal adenocarcinoma often occurs sporadically in individuals aged 50 or above and there is an increase among younger patients under 50. Routine screenings are recommended for this age group to improve early detection. The multifactorial etiology of colorectal cancer consists of both genetic and epigenetic factors. Recently, studies have shown that the development and progression of colorectal cancer can be attributed to aberrant expression of microRNA. Reactive oxygen species (ROS) that play a key role in cancer cell survival, can also lead to carcinogenesis and cancer exacerbations. Given the rapid accumulating knowledge in the field, an updated review regarding microRNA and ROS in colorectal cancer is necessary. An extensive literature search has been conducted in PubMed/Medline databases to review the roles of microRNAs and ROS in colorectal cancer. Unique microRNA expression in tumor tissue, peripheral blood, and fecal samples from patients with colorectal cancer is outlined. Therapeutic approaches focusing on microRNA and ROS in colorectal cancer treatment is also delineated. This review aims to summarize the newest knowledge on the pathogenesis of colorectal cancer in the hopes of discovering novel diagnostic biomarkers and therapeutic techniques.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Dano ao DNA , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Genéticos , Estresse OxidativoRESUMO
Checkpoint kinase 2 (CHK2) and cell division cycle 25C (CDC25C) are two proteins involved in the DNA damage response pathway, playing essential roles in maintaining genome integrity. As one of the major hallmarks of abnormal cellular division, genomic instability occurs in most cancers. In this study, we identified the functional expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer, as well as its association with breast cancer survival. Tissue microarray analysis using immunohistochemistry was constructed to identify the expression of pCHK2-Thr68 and pCDC25C-Ser216 in 292 female breast cancer patients. The relationship among protein expression, clinicopathological factors (e.g., human epidermal growth factor receptor 2 (HER 2), tumor size, tumor-node-metastasis (TNM) classification), and overall survival of the breast cancer tissues were analyzed using Pearson's χ-square (χ²) test, Fisher's exact test, multivariate logistic regression and Kaplan-Meier survival analysis. Significantly higher expressions of pCHK2-Thr68 and pCDC25C-Ser216 were observed in the nucleus of the breast cancer cells compared to the paracancerous tissue (pCHK2-Thr68, 20.38% vs. 0%; pCDC25C-Ser216, 82.26% vs. 24.24%). The expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer showed a positive linear correlation (p = 0.026). High expression of pCHK2-Thr68 was associated with decreased patient survival (p = 0.001), but was not an independent prognostic factor. Our results suggest that pCHK2-Thr68 and pCDC25C-Ser216 play important roles in breast cancer and may be potential treatment targets.
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Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Quinase do Ponto de Checagem 2/biossíntese , Fosfatases cdc25/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Quinase do Ponto de Checagem 2/genética , Dano ao DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica/genética , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Metástase Linfática/patologia , Análise em Microsséries , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/genética , Fosfatases cdc25/genéticaRESUMO
It is well known that regular exercise can benefit health by enhancing antioxidant defenses in the body. However, unaccustomed and/or exhaustive exercise can generate excessive reactive oxygen species (ROS), leading to oxidative stress-related tissue damages and impaired muscle contractility. ROS are produced in both aerobic and anaerobic exercise. Mitochondria, NADPH oxidases and xanthine oxidases have all been identified as potential contributors to ROS production, yet the exact redox mechanisms underlying exercise-induced oxidative stress remain elusive. Interestingly, moderate exposure to ROS is necessary to induce body's adaptive responses such as the activation of antioxidant defense mechanisms. Dietary antioxidant manipulation can also reduce ROS levels and muscle fatigue, as well as enhance exercise recovery. To elucidate the complex role of ROS in exercise, this review updates on new findings of ROS origins within skeletal muscles associated with various types of exercises such as endurance, sprint and mountain climbing. In addition, we will examine the corresponding antioxidant defense systems as well as dietary manipulation against damages caused by ROS.
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No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·ß) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs.
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Alpha-1-antitrypsin (AAT) deficiency is a heritable disease that is commonly associated with complications in the respiratory and hepatic systems. AAT acts as a regulatory enzyme that primarily inhibits neutrophil elastase activity thus protecting tissues from proteolytic damage after inflammation. This paper provides a historical review of the discovery, classification, phenotypic expression, and treatment of AAT deficiency. While its pattern of inheritance has been long understood, the underlying mechanism between AAT deficiency and related diseases remains to be elucidated. Most commonly, AAT deficiency is associated with the development of emphysema in the lungs as well as various liver injuries. Cigarette smoke has been shown to be particularly detrimental in AAT deficient individuals during the development of lung disease. Therefore, understanding familial history may be beneficial when educating patients regarding lifestyle choices. While numerous AAT deficient phenotypes exist in the human populations, only specific variants have been proven to markedly predispose individuals to lung and liver disorders. The exact relationship between AAT levels and the aforementioned diseases is an essential area of further research. It is imperative that clinicians and researchers alike strive to standardize diagnostic criteria and develop safe and effective therapies for this genetic disease.
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Insuficiência Hepática/genética , Enfisema Pulmonar/genética , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Expressão Gênica , Insuficiência Hepática/complicações , Insuficiência Hepática/tratamento farmacológico , Insuficiência Hepática/história , História do Século XX , História do Século XXI , Humanos , Elastase de Leucócito/metabolismo , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Pulmão/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Neutrófilos/patologia , Fenótipo , Enfisema Pulmonar/complicações , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/história , Fatores de Risco , Fumar/fisiopatologia , Inibidores da Tripsina/uso terapêutico , alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/uso terapêutico , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Deficiência de alfa 1-Antitripsina/históriaRESUMO
Asthma and chronic obstructive pulmonary disease (COPD) have both been historically associated with significant morbidity and financial burden. These diseases can be induced by several exogenous factors, such as pathogen-associated molecular patterns (PAMPs) (e.g., allergens and microbes). Endogenous factors, including reactive oxygen species, and damage-associated molecular patterns (DAMPs) recognized by toll-like receptors (TLRs), can also result in airway inflammation. Asthma is characterized by the dominant presence of eosinophils, mast cells, and clusters of differentiation (CD)4(+) T cells in the airways, while COPD typically results in the excessive formation of neutrophils, macrophages, and CD8(+) T cells in the airways. In both asthma and COPD, in the respiratory tract, TLRs are the primary proteins of interest associated with the innate and adaptive immune responses; hence, multiple treatment options targeting TLRs are being explored in an effort to reduce the severity of the symptoms of these disorders. TLR-mediated pathways for both COPD and asthma have their similarities and differences with regards to cell types and the pro-inflammatory cytotoxins present in the airway. Because of the complex TLR cascade, a variety of treatments have been used to minimize airway hypersensitivity and promote bronchodilation. Although unsuccessful at completely alleviating COPD and severe asthmatic symptoms, new studies are focused on possible targets within the TLR cascade to ameliorate airway inflammation.
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An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer's disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aß) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aß overproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aß plaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.