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Metabolic syndromes (e.g., obesity) are characterized by insulin resistance, chronic inflammation, impaired glucose metabolism, and dyslipidemia. Recently, patients with metabolic syndromes have experienced not only metabolic problems but also neuropathological issues, including cognitive impairment. Several studies have reported blood-brain barrier (BBB) disruption and insulin resistance in the brain of patients with obesity and diabetes. Adenosine, a purine nucleoside, is known to regulate various cellular responses (e.g., the neuroinflammatory response) by binding with adenosine receptors in the central nervous system (CNS). Adenosine has four known receptors: A1R, A2AR, A2BR, and A3R. These receptors play distinct roles in various physiological and pathological processes in the brain, including endothelial cell homeostasis, insulin sensitivity, microglial activation, lipid metabolism, immune cell infiltration, and synaptic plasticity. Here, we review the recent findings on the role of adenosine receptor-mediated signaling in neuropathological issues related to metabolic imbalance. We highlight the importance of adenosine signaling in the development of therapeutic solutions for neuropathological issues in patients with metabolic syndromes.
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Adenosina , Síndrome Metabólica , Receptores Purinérgicos P1 , Humanos , Adenosina/metabolismo , Receptores Purinérgicos P1/metabolismo , Animais , Síndrome Metabólica/metabolismo , Transdução de Sinais , Doenças do Sistema Nervoso/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Barreira Hematoencefálica/metabolismo , Resistência à Insulina/fisiologiaRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disease worldwide and is accompanied by memory deficits, personality changes, anxiety, depression, and social difficulties. For treatment of AD, many researchers have attempted to find medicinal resources with high effectiveness and without side effects. Oligonol is a low molecular weight polypeptide derived from lychee fruit extract. We investigated the effects of oligonol in 5 × FAD transgenic AD mice, which developed severe amyloid pathology, through behavioral tests (Barnes maze, marble burying, and nestle shredding) and molecular experiments. Oligonol treatment attenuated blood glucose levels and increased the antioxidant response in the livers of 5 × FAD mice. Moreover, the behavioral score data showed improvements in anxiety, depressive behavior, and cognitive impairment following a 2-month course of orally administered oligonol. Oligonol treatment not only altered the circulating levels of cytokines and adipokines in 5 × FAD mice, but also significantly enhanced the mRNA and protein levels of antioxidant enzymes and synaptic plasticity in the brain cortex and hippocampus. Therefore, we highlight the therapeutic potential of oligonol to attenuate neuropsychiatric problems and improve memory deficits in the early stage of AD.
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Doença de Alzheimer , Doenças Neurodegenerativas , Camundongos , Animais , Antioxidantes/farmacologia , Doença de Alzheimer/patologia , Encéfalo , Fígado , Camundongos Transgênicos , Transtornos da Memória/tratamento farmacológicoRESUMO
We investigated whether cigarette smoking and dietary acid load (DAL) are associated with a risk of chronic obstructive pulmonary disease (COPD) in healthy, middle-aged Korean men. Healthy men without diagnosed chronic disease (aged 40-64 years) from the KNHANES-VI (2013-2015) were included in the analysis (n = 774) and were subdivided by smoking status and DAL levels, as estimated using the quartile of net endogenous acid production (NEAP). The current smokers tended to have a higher risk of COPD than the never-smokers before and after adjustment. When divided by the DAL quartile, the Q4 group tended to have a higher risk of COPD than the Q1 group. Additionally, the current smokers with lower (Q2), modest (Q3), and the highest NEAP scores (Q4) showed risks of COPD that were more than fourfold higher than those of the never-smokers with the lowest NEAP scores (Q1). The ex-smokers with higher NEAP scores (Q3 and Q4) showed risks of COPD that were more than fourfold higher than those of the Q1 group. Interestingly, the risk of COPD was also more than sixfold higher in the never-smokers with the highest NEAP scores compared to that in the Q1 group. The NEAP scores and smoking status synergistically increased the risk of COPD in healthy, middle-aged Korean men. This suggests that DAL levels are an important factor in the prevention and management of COPD.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Fumar Cigarros/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Receptores Proteína Tirosina Quinases , República da Coreia/epidemiologia , Fumantes , População do Leste Asiático , Dieta , Ácidos , AdultoRESUMO
Macrophages are the major primary immune cells that mediate the inflammatory response. In this process, long non-coding RNAs (lncRNAs) play an important, yet largely unknown role. Therefore, utilizing several publicly available RNA sequencing datasets, we predicted and selected lncRNAs that are differentially expressed in M1 or M2 macrophages and involved in the inflammatory response. We identified SUGCT-AS1, which is a human macrophage-specific lncRNA whose expression is increased upon M1 macrophage stimulation. Conditioned media of SUGCT-AS1-depleted M1 macrophages induced an inflammatory phenotype of vascular smooth muscle cells, which included increased expression of inflammatory genes (IL1B and IL6), decreased contractile marker proteins (ACTA2 and SM22α), and increased cell migration. Depletion of SUGCT-AS1 promoted the expression and secretion of proinflammatory cytokines, such as TNF, IL1B, and IL6, in M1 macrophages, and transcriptomic analysis showed that SUGCT-AS1 has functions related to inflammatory responses and cytokines. Furthermore, we found that SUGCT-AS1 directly binds to hnRNPU and regulates its nuclear-cytoplasmic translocation. This translocation of hnRNPU altered the proportion of the MALT1 isoforms by regulating the alternative splicing of MALT1, a mediator of NF-κB signaling. Overall, our findings suggest that lncRNAs can be used for future studies on macrophage regulation. Moreover, they establish the SUGCT-AS1/hnRNPU/MALT1 axis, which is a novel inflammatory regulatory mechanism in macrophages.
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RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Interleucina-6/genética , Processamento Alternativo , Proteínas Contráteis , Citocinas/genética , MacrófagosRESUMO
Recent evidence indicates that the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, is associated with metabolic disorders such as diabetes and obesity. Various circular RNAs (circRNAs) have been found in brain tissues and recent studies have suggested that circRNAs are related to neuropathological mechanisms in the brain. However, there is a lack of interest in the involvement of circRNAs in metabolic imbalance-related neuropathological problems until now. Herein we profiled and analyzed diverse circRNAs in mouse brain cell lines (Neuro-2A neurons, BV-2 microglia, and C8-D1a astrocytes) exposed to obesity-related in vitro conditions (high glucose, high insulin, and high levels of tumor necrosis factor-alpha, interleukin 6, palmitic acid, linoleic acid, and cholesterol). We observed that various circRNAs were differentially expressed according to cell types with many of these circRNAs conserved in humans. After suppressing the expression of these circRNAs using siRNAs, we observed that these circRNAs regulate genes related to inflammatory responses, formation of synaptic vesicles, synaptic density, and fatty acid oxidation in neurons; scavenger receptors in microglia; and fatty acid signaling, inflammatory signaling cyto that may play important roles in metabolic disorders associated with neurodegenerative diseases.
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Doenças Neurodegenerativas , RNA Circular , Humanos , Camundongos , Animais , RNA Circular/genética , RNA Circular/metabolismo , Neurônios/metabolismo , Doenças Neurodegenerativas/genética , Astrócitos/metabolismo , Obesidade/genéticaRESUMO
To overcome the limitations of brown adipose tissue (BAT) imaging with MRI and PET/CT, near-infrared (NIR) fluorescence imaging has been utilized in living animals because it is highly sensitive, noninvasive, nonradioactive, and cost-effective. To date, only a few NIR fluorescent dyes for detecting BAT have been reported based on the structure-inherent targeting strategy. Among them, IR-786, a commercial cyanine dye, was used firstly for quantitative NIR imaging of BAT perfusion in 2003. Owing to the high cytotoxicity, poor water solubility, and strong nonspecific background uptake of IR-786, the chemical structure of IR-786 should be redesigned to be more hydrophilic and less toxic so that it can show more BAT-specific accumulation. Here, we developed a BAT-specific NIR dye, BF800-AM, by incorporating the tyramine linker in the original structure of IR-786. After modifying the physicochemical properties of IR-786, in vivo results showed significant uptake of the newly designed BF800-AM in the BAT with improved signal-to-background ratio. Additional in vivo studies using mouse tumor models revealed that BF800-AM targeting to BAT is independent of tumor tissues, as distinct from IR-786 showing uptake in both tissues. Therefore, BF800-AM can be used for improved noninvasive visualization of BAT mass and activity in living animals.
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Tecido Adiposo Marrom , Neoplasias , Animais , Camundongos , Tecido Adiposo Marrom/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imageamento por Ressonância Magnética/métodosRESUMO
Diabetes contributes to the onset of various diseases, including cancer and cardiovascular and neurodegenerative diseases. Recent studies have highlighted the similarities and relationship between diabetes and dementia as an important issue for treating diabetes-related cognitive deficits. Diabetes-related dementia exhibits several features, including blood-brain barrier disruption, brain insulin resistance, and Aß over-accumulation. High-mobility group box1 (HMGB1) is a protein known to regulate gene transcription and cellular mechanisms by binding to DNA or chromatin via receptor for advanced glycation end-products (RAGE) and toll-like receptor 4 (TLR4). Recent studies have demonstrated that the interplay between HMGB1, RAGE, and TLR4 can impact both neuropathology and diabetic alterations. Herein, we review the recent research regarding the roles of HMGB1-RAGE-TLR4 axis in diabetes-related dementia from several perspectives and emphasize the importance of the influence of HMGB1 in diabetes-related dementia.
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Demência , Diabetes Mellitus , Proteína HMGB1 , Resistência à Insulina , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Proteína HMGB1/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). METHODS: This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan-Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. RESULTS: Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001-1.005; p = 0.042). CONCLUSIONS: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.
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Receptores de Lipopolissacarídeos/sangue , Fragmentos de Peptídeos/sangue , Pró-Calcitonina/sangue , Sepse , Choque Séptico , Biomarcadores/sangue , Humanos , Prognóstico , Sepse/diagnóstico , Sepse/mortalidade , Choque Séptico/diagnóstico , Choque Séptico/mortalidadeRESUMO
Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol's effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.
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We investigated association between epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients and clinical outcomes in Korea. This nationwide retrospective cohort study included 5621 discharged patients with COVID-19, extracted from the Korea Disease Control and Prevention Agency (KDCA) database. We compared clinical data between survivors (n = 5387) and non-survivors (n = 234). We used logistic regression analysis and Cox proportional hazards model to explore risk factors of death and fatal adverse outcomes. Increased odds ratio (OR) of mortality occurred with age (≥ 60 years) [OR 11.685, 95% confidence interval (CI) 4.655-34.150, p < 0.001], isolation period, dyspnoea, altered mentality, diabetes, malignancy, dementia, and intensive care unit (ICU) admission. The multivariable regression equation including all potential variables predicted mortality (AUC = 0.979, 95% CI 0.964-0.993). Cox proportional hazards model showed increasing hazard ratio (HR) of mortality with dementia (HR 6.376, 95% CI 3.736-10.802, p < 0.001), ICU admission (HR 4.233, 95% CI 2.661-6.734, p < 0.001), age ≥ 60 years (HR 3.530, 95% CI 1.664-7.485, p = 0.001), malignancy (HR 3.054, 95% CI 1.494-6.245, p = 0.002), and dyspnoea (HR 1.823, 95% CI 1.125-2.954, p = 0.015). Presence of dementia, ICU admission, age ≥ 60 years, malignancy, and dyspnoea could help clinicians identify COVID-19 patients with poor prognosis.
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COVID-19/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Adulto JovemRESUMO
Dementia accompanied by memory loss is considered one of the most common neurodegenerative diseases worldwide, and its prevalence is gradually increasing. Known risk factors for dementia include genetic background, certain lifestyle and dietary patterns, smoking, iron overload, insulin resistance, and impaired glucose metabolism in the brain. Here, we review recent evidence on the regulatory role of lipocalin 2 (LCN2) in dementia from various perspectives. LCN2 is a neutrophil gelatinase-associated protein that influences diverse cellular processes, including the immune system, iron homeostasis, lipid metabolism, and inflammatory responses. Although its functions within the peripheral system are most widely recognized, recent findings have revealed links between LCN2 and central nervous system diseases, as well as novel roles for LCN2 in neurons and glia. Furthermore, LCN2 may modulate diverse pathological mechanisms involved in dementia. Taken together, LCN2 is a promising therapeutic target with which to address the neuropathology of dementia.
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Encéfalo/metabolismo , Demência/metabolismo , Resistência à Insulina/fisiologia , Ferro/metabolismo , Lipocalina-2/metabolismo , Doenças Neuroinflamatórias/metabolismo , Demência/diagnóstico , Homeostase/fisiologia , Humanos , Metabolismo dos Lipídeos/fisiologia , Doenças Neuroinflamatórias/diagnósticoRESUMO
Glucagon-like peptide-1 (GLP-1), an incretin hormone, plays an important role in regulating glucose homeostasis. In this study, the applicability of circulating GLP-1 levels as an early indicator of metabolic syndrome (MetS) risk was examined. Women without diagnosed diseases were grouped according to their number of MetS risk factors (MetS RFs) (no RFs as Super-healthy, n = 61; one or two RFs as MetS risk carriers, n = 60; 3 ≤ RFs as MetS, n = 19). The circulating GLP-1 levels and homeostasis model assessment insulin resistance (HOMA-IR) scores were significantly higher in the MetS group than in the other two groups. The GLP-1 levels correlated positively with adiposity, HOMA-IR, blood pressure, and high sensitivity C-reactive protein (hs-CRP), but not with fasting glucose and lipid profiles, whose significances were maintained after adjustments for age, smoking and drinking habits, menopausal status, and total calorie intake. The GLP-1 levels also increased proportionally with the number of MetS RFs. In the MetS group, the GLP-1 levels were much higher in individuals with obesity (body mass index ≥ 25 kg/m2). In conclusion, the circulating GLP-1 level may be applicable as a potential early indicator of MetS risk in women without diagnosed diseases. Further study with a large population is needed to confirm the conclusion.
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Peptídeo 1 Semelhante ao Glucagon/sangue , Síndrome Metabólica/diagnóstico , Medição de Risco/métodos , Adiposidade , Adulto , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Proteína C-Reativa/análise , Diagnóstico Precoce , Jejum/sangue , Feminino , Homeostase , Humanos , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Valor Preditivo dos Testes , República da Coreia , Adulto JovemRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a rapid accumulation of amyloid ß (Aß) protein in the hippocampus, which impairs synaptic structures and neuronal signal transmission, induces neuronal loss, and diminishes memory and cognitive functions. The present study investigated the impact of neuregulin 1 (NRG1)-ErbB4 signaling on the impairment of neural networks underlying hippocampal long-term potentiation (LTP) in 5xFAD mice, a model of AD with greater symptom severity than that of TG2576 mice. Specifically, we observed parvalbumin (PV)-containing hippocampal interneurons, the effect of NRG1 on hippocampal LTP, and the functioning of learning and memory. We found a significant decrease in the number of PV interneurons in 11-month-old 5xFAD mice. Moreover, synaptic transmission in the 5xFAD mice decreased at 6 months of age. The 11-month-old transgenic AD mice showed fewer inhibitory PV neurons and impaired NRG1-ErbB4 signaling than did wild-type mice, indicating that the former exhibit the impairment of neuronal networks underlying LTP in the hippocampal Schaffer-collateral pathway. In conclusion, this study confirmed the impaired LTP in 5xFAD mice and its association with aberrant NRG1-ErbB signaling in the neuronal network.
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Envelhecimento/patologia , Doença de Alzheimer/patologia , Região CA1 Hipocampal/patologia , Potenciação de Longa Duração/fisiologia , Rede Nervosa/patologia , Neurônios/patologia , Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Região CA1 Hipocampal/metabolismo , Cognição/fisiologia , Modelos Animais de Doenças , Feminino , Interneurônios/metabolismo , Interneurônios/patologia , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Transgênicos , Rede Nervosa/metabolismo , Neuregulina-1/metabolismo , Neurônios/metabolismo , Parvalbuminas/metabolismo , Receptor ErbB-4/metabolismo , Transdução de Sinais/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
PURPOSE: Differentiation between radiation-induced necrosis and tumor recurrence is crucial to determine proper management strategies but continues to be one of the central challenges in neuro-oncology. We hypothesized that hyperpolarized 13C MRI, a unique technique to measure real-time in vivo metabolism, would distinguish radiation necrosis from tumor on the basis of cell-intrinsic metabolic differences. The purpose of this study was to explore the feasibility of using hyperpolarized [1-13C]pyruvate for differentiating radiation necrosis from brain tumors. PROCEDURES: Radiation necrosis was initiated by employing a CT-guided 80-Gy single-dose irradiation of a half cerebrum in mice (n = 7). Intracerebral tumor was modeled with two orthotopic mouse models: GL261 glioma (n = 6) and Lewis lung carcinoma (LLC) metastasis (n = 7). 13C 3D MR spectroscopic imaging data were acquired following hyperpolarized [1-13C]pyruvate injection approximately 89 and 14 days after treatment for irradiated and tumor-bearing mice, respectively. The ratio of lactate to pyruvate (Lac/Pyr), normalized lactate, and pyruvate in contrast-enhancing lesion was compared between the radiation-induced necrosis and brain tumors. Histopathological analysis was performed from resected brains. RESULTS: Conventional MRI exhibited typical radiographic features of radiation necrosis and brain tumor with large areas of contrast enhancement and T2 hyperintensity in all animals. Normalized lactate in radiation necrosis (0.10) was significantly lower than that in glioma (0.26, P = .004) and LLC metastatic tissue (0.25, P = .00007). Similarly, Lac/Pyr in radiation necrosis (0.18) was significantly lower than that in glioma (0.55, P = .00008) and LLC metastasis (0.46, P = .000008). These results were consistent with histological findings where tumor-bearing brains were highly cellular, while irradiated brains exhibited pathological markers consistent with reparative changes from radiation necrosis. CONCLUSION: Hyperpolarized 13C MR metabolic imaging of pyruvate is a noninvasive imaging method that differentiates between radiation necrosis and brain tumors, providing a groundwork for further clinical investigation and translation for the improved management of patients with brain tumors.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Isótopos de Carbono , Imageamento por Ressonância Magnética/métodos , Necrose/etiologia , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Animais , Encéfalo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Camundongos , Transplante de NeoplasiasRESUMO
Resveratrol is a natural polyphenol that has anti-aging and anti-inflammatory properties against stress condition. It is reported that resveratrol has beneficial functions in various metabolic and central nervous system (CNS) diseases, such as obesity, diabetes, depression, and dementia. Recently, many researchers have emphasized the connection between the brain and gut, called the gut-brain axis, for treating both CNS neuropathologies and gastrointestinal diseases. Based on previous findings, resveratrol is involved in glucagon-like peptide 1 (GLP-1) secreted by intestine L cells, the patterns of microbiome in the intestine, the 5-hydroxytryptamine (5-HT) level, and CNS inflammation. Here, we review recent evidences concerning the relevance and regulatory function of resveratrol in the gut-brain axis from various perspectives. Here, we highlight the necessity for further study on resveratrol's specific mechanism in the gut-brain axis. We present the potential of resveratrol as a natural therapeutic substance for treating both neuropathology and gastrointestinal dysfunction.
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Biomarkers are valuable tools for the prediction of mortality in patients with sepsis. However, the use of a single biomarker to predict patient outcomes is challenging owing to the complexity and redundancy of the immune response to infections.We aimed to conduct a prospective observational analysis to investigate the prognostic value of pentraxin 3, interleukin 6, procalcitonin, and lactate combined in predicting the 28-day mortality rate in patients with sepsis or septic shock (nâ=â160; sepsis, 78; sepsis shock, 82). Two methods (the frequency sum of values above the cutoff, and the multivariate logistic regression model) were used to assess the prognostic value of the biomarker combination.In the receiver operating characteristic curve analyses, the combination of the 4 biomarkers was better than the Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality rate, regardless of whether the frequency sum of values above the cutoff or the multivariate logistic model was used for the analysis. The addition of the SOFA score to the biomarker combination did not result in a better performance for the prediction of mortality.The combined biomarker approach showed good performance in predicting 28-day all-cause mortality among patients diagnosed with either sepsis or septic shock according to the Sepsis-3 definitions. Furthermore, it was superior to the SOFA score in predicting mortality.
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Biomarcadores/sangue , Escores de Disfunção Orgânica , Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Lactatos/sangue , Masculino , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Componente Amiloide P Sérico/metabolismoRESUMO
Glucagon-like peptide-1 (GLP-1) is a hormone mainly secreted from enteroendocrine L cells. GLP-1 and its receptor are also expressed in the brain. GLP-1 signaling has pivotal roles in regulating neuroinflammation and memory function, but it is unclear how GLP-1 improves memory function by regulating neuroinflammation. Here, we demonstrated that GLP-1 enhances neural structure by inhibiting lipopolysaccharide (LPS)-induced inflammation in microglia with the effects of GLP-1 itself on neurons. Inflammatory secretions of BV-2 microglia by LPS aggravated mitochondrial function and cell survival, as well as neural structure in Neuro-2a neurons. In inflammatory condition, GLP-1 suppressed the secretion of tumor necrosis factor-alpha (TNF-α)-associated cytokines and chemokines in BV-2 microglia and ultimately enhanced neurite complexity (neurite length, number of neurites from soma, and secondary branches) in Neuro-2a neurons. We confirmed that GLP-1 improves neurite complexity, dendritic spine morphogenesis, and spine development in TNF-α-treated primary cortical neurons based on altered expression levels of the factors related to neurite growth and spine morphology. Given that our data that GLP-1 itself enhances neurite complexity and spine morphology in neurons, we suggest that GLP-1 has a therapeutic potential in central nervous system diseases.
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Encefalite/imunologia , Peptídeo 1 Semelhante ao Glucagon/imunologia , Animais , Morte Celular , Células Cultivadas , Citocinas/imunologia , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Microglia/imunologia , Neurônios/imunologia , Ratos Sprague-DawleyRESUMO
BACKGROUND: This study investigated the clinical value of interleukin-6 (IL-6), pentraxin 3 (PTX3), and procalcitonin (PCT) in patients with sepsis and septic shock diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). METHODS: Serum levels of IL-6, PTX3, and PCT were measured in 142 enrolled subjects (51 with sepsis, 46 with septic shock, and 45 as controls). Follow-up IL-6 and PTX3 levels were measured in patients with initial septic shock within 24 h of hospital discharge. Optimal cut-off values were determined for sepsis and septic shock, and prognostic values were evaluated. RESULTS: Serum IL-6 levels could discriminate sepsis (area under the curve [AUC], 0.83-0.94, P < 0.001; cut-off value, 52.60 pg/mL, 80.4% sensitivity, 88.9% specificity) from controls and could distinguish septic shock (AUC, 0.71-0.89; cut-off value, 348.92 pg/mL, 76.1% sensitivity, 78.4% specificity) from sepsis. Twenty-eight-day mortality was significantly higher in the group with high IL-6 (≥ 348.92 pg/mL) than in the group with low IL-6 (< 348.92 pg/mL) (P = 0.008). IL-6 was an independent risk factor for 28-day mortality among overall patients (hazard ratio, 1.0004; 95% confidence interval, 1.0003-1.0005; p = 0.024). In septic shock patients, both the initial and follow-up PTX3 levels were consistently significantly higher in patients who died than in those who recovered (initial p = 0.004; follow-up P < 0.001). CONCLUSIONS: The diagnostic and prognostic value of IL-6 was superior to those of PTX3 and PCT for sepsis and septic shock.
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Proteína C-Reativa/análise , Interleucina-6/sangue , Pró-Calcitonina/sangue , Sepse/diagnóstico , Componente Amiloide P Sérico/análise , Choque Séptico/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Sepse/mortalidade , Sepse/patologia , Índice de Gravidade de Doença , Choque Séptico/mortalidade , Choque Séptico/patologiaRESUMO
Obesity is a globally widespread metabolic disorder, characterized by immoderate fat accumulation in the body. There are different types of body fats such as white adipose tissue (WAT), which stores surplus energy in the body, and brown adipose tissue (BAT) which utilize energy to produce heat during metabolism. BAT acts many beneficial functions in metabolic disorders including type 2 diabetes and obesity. Recent studies have investigated methods for promoting the fat browning process of WAT in obesity because of various reasons such as the improvement of insulin resistance, and weight loss. Among natural polyphenolic compounds, resveratrol has been highlighted due to its anti-oxidant and anti-obesity as well as anti-inflammation and anti-cancer properties. Recent studies have paid a lot of attention to that resveratrol may act as a fat browning activator, involved in the secretion of many myokines and adipokines. Here, we reviewed the role of resveratrol in fat browning and also the association between resveratrol and adipokines/myokines in the fat browning process. Our review may provide novel insight into the role of resveratrol in fat browning, leading to the maintenance of a healthy weight against obesity.
Assuntos
Adipocinas/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , HumanosRESUMO
Hyperglycemia-induced oxidative stress triggers severe vascular damage and induces an inflammatory vascular state, and is, therefore, one of the main causes of atherosclerosis. Recently, interest in the natural compound Carpinus turczaninowii has increased because of its reported antioxidant and anti-inflammatory properties. We investigated whether a C. turczaninowii extract was capable of attenuating high glucose-induced inflammation and arterial damage using human aortic vascular smooth muscle cells (hASMCs). mRNA expression levels of proinflammatory response [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], endoplasmic reticulum (ER) stress [CCAAT-enhancer-binding proteins (C/EBP) homologous protein (CHOP)], and adenosine monophosphate (AMP)-protein activated kinase α2 (AMPK α2)], and DNA damage [phosphorylated H2.AX (p-H2.AX)] were measured in hASMCs treated with the C. turczaninowii extracts (1 and 10 µg/mL) after being stimulated by high glucose (25 mM) or not. The C. turczaninowii extract attenuated the increased mRNA expression of IL-6, TNF-α, and CHOP in hASMCs under high glucose conditions. The expression levels of p-H2.AX and AMPK α2 induced by high glucose were also significantly decreased in response to treatment with the C. turczaninowii extract. In addition, 15 types of phenolic compounds including quercetin, myricitrin, and ellagic acid, which exhibit antioxidant and anti-inflammatory properties, were identified in the C. turczaninowii extract through ultra-performance liquid chromatography-quadrupole-time of flight (UPLC-Q-TOF) mass spectrometry. In conclusion, C. turczaninowii may alleviate high glucose-induced inflammation and arterial damage in hASMCs, and may have potential in the treatment of hyperglycemia-induced atherosclerosis.