RESUMO
Alzheimer's disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer's disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer's disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer's disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue.
Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Peptídeos beta-Amiloides/metabolismo , Transcriptoma , Hipocampo/metabolismo , Camundongos Transgênicos , Perfilação da Expressão Gênica , Tecido Adiposo Branco/metabolismoRESUMO
BACKGROUND: Hepatic encephalopathy-induced hyperammonemia alters astrocytic glutamate metabolism in the brain, which is involved in cognitive decline. To identify specific therapeutic strategies for the treatment of hepatic encephalopathy, various molecular signaling studies, such as non-coding RNA functional study, have been conducted. However, despite several reports of circular RNAs (circRNAs) in the brain, few studies of circRNAs in hepatic encephalopathy-induced neuropathophysiological diseases have been conducted. METHODS: In this study, we performed RNA sequencing to identify whether the candidate circRNA cirTmcc1 is specifically expressed in the brain cortex in a bile duct ligation (BDL) mouse model of hepatic encephalopathy. RESULTS: Based on transcriptional and cellular analysis, we investigated the circTmcc1-dysregulation-induced changes in the expression of several genes that are associated with intracellular metabolism and astrocyte function. We found that the circTmcc1 binds with the NF-κB p65-CREB transcriptional complex and regulates the expression of the astrocyte transporter EAAT2. Furthermore, circTmcc1 contributed to the secretion of proinflammatory mediators and glutamate metabolism in astrocytes and subsequently modulated an improvement in spatial memory by mediating neuronal synaptic plasticity. CONCLUSIONS: Thus, circTmcc1 may be a promising circRNA candidate for targeted interventions to prevent and treat the neuropathophysiological complications that occur due to hepatic encephalopathy.
Assuntos
Encefalopatia Hepática , NF-kappa B , RNA Circular , Animais , Camundongos , Astrócitos/metabolismo , Ductos Biliares/metabolismo , Modelos Animais de Doenças , Glutamatos/metabolismo , Encefalopatia Hepática/etiologia , Ligadura/efeitos adversos , NF-kappa B/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Memória EspacialRESUMO
BACKGROUND: The disadvantages and complications of computed tomography (CT) can be minimized if CT is performed in rib fracture patients with high probability of intra-thoracic and intra-abdominal injuries and CT is omitted in rib fracture patients with low probability of intra-thoracic and intra-abdominal injuries. This study aimed to evaluate the factors that can identify patients with rib fractures with intra-thoracic and intra-abdominal injuries in the emergency department among patients with rib fracture. METHODS: This retrospective observational study included adult patients (age ≥ 18 years) diagnosed with rib fracture on chest radiography prior to chest CT due to blunt chest trauma in the emergency department who underwent chest CT from January 2016 to February 2021. The primary outcomes were intra-thoracic and intra-abdominal injuries that could be identified on a chest CT. Multivariate logistic regression analysis was performed. RESULTS: Among the characteristics of rib fractures, the number of rib fractures was greater (5.0 [3.0-7.0] vs. 2.0 [1.0-3.0], p < 0.001), bilateral rib fractures were frequent (56 [20.1%] vs. 12 [9.8%], p = 0.018), and lateral and posterior rib fracture was more frequent (lateral rib fracture: 160 [57.3%] vs. 25 [20.5%], p < 0.001; posterior rib fracture: 129 [46.2%] vs. 21 [17.2%], p < 0.001), and displacement was more frequent (99 [35.5%] vs. 6 [6.6%], p < 0.001) in the group with intra-thoracic and intra-abdominal injuries than in the group with no injury. The number of rib fractures (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.16-1.78; p = 0.001), lateral rib fracture (aOR, 2.80; 95% CI, 1.32-5.95; p = 0.008), and posterior rib fracture (aOR, 3.18; 95% CI, 1.45-6.94; p = 0.004) were independently associated with intra-thoracic and intra-abdominal injuries. The optimal cut-off for the number of rib fractures on the outcome was three. The number of rib fractures ≥ 3 (aOR, 3.01; 95% CI, 1.35-6.71; p = 0.007) was independently associated with intra-thoracic and intra-abdominal injuries. CONCLUSION: In patients with rib fractures due to blunt trauma, those with lateral or posterior rib fractures, those with ≥ 3 rib fractures, and those requiring O2 supplementation require chest CT to identify significant intra-thoracic and intra-abdominal injuries in the emergency department.
Assuntos
Traumatismos Abdominais , Fraturas das Costelas , Traumatismos Torácicos , Ferimentos não Penetrantes , Adulto , Humanos , Adolescente , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/epidemiologia , Fraturas das Costelas/complicações , Traumatismos Torácicos/diagnóstico por imagem , Traumatismos Torácicos/epidemiologia , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/complicações , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Serviço Hospitalar de Emergência , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/epidemiologiaRESUMO
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.
Assuntos
Doenças Neurodegenerativas , RNA Circular , Humanos , Camundongos , Animais , RNA Circular/genética , RNA Circular/metabolismo , Neurônios/metabolismo , Doenças Neurodegenerativas/genética , Astrócitos/metabolismo , Obesidade/genéticaRESUMO
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.
Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Interleucina-6/genética , Processamento Alternativo , Proteínas Contráteis , Citocinas/genética , MacrófagosRESUMO
Metabolic syndromes, including obesity, cause neuropathophysiological changes in the brain, resulting in cognitive deficits. Only a few studies explored the contribution of non-coding genes in these pathophysiologies. Recently, we identified obesity-linked circular RNAs (circRNA) by analyzing the brain cortices of high-fat-fed obese mice. In this study, we scrutinized a conserved and neuron-specific circRNA, circTshz2-2, which affects neuronal cell cycle and spatial memory in the brain. Transcriptomic and cellular analysis indicated that circTshz2-2 dysregulation altered the expression of cell division-related genes and induced cell cycle arrest at the G2/M phase of the neuron. We found that circTshz2-2 bound to the YY1 transcriptional complex and suppressed Bdnf transcription. Suppression of circTshz2-2 increased BDNF expression and reduced G2/M checkpoint proteins such as Cyclin B2 and CDK1 through BDNF/TrkB signaling pathway, resulting in cell cycle arrest and neurite elongation. Inversely, overexpression of circTshz2-2 decreased BDNF expression, induced cell cycle proteins, and shortened the neurite length, indicating that circTshz2-2 regulates neuronal cell cycle and structure. Finally, we showed that circTshz2-2 affects spatial memory in wild-type and obese mice. Our data have revealed potential regulatory roles of obesity-related circTshz2-2 on the neuronal cell cycle and memory function providing a novel link between metabolic syndromes and cognitive deficits.
Assuntos
RNA Circular , Memória Espacial , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Camundongos , Neurônios/metabolismo , Obesidade/genética , RNA Circular/genéticaRESUMO
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.
Assuntos
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
The incidence of dementia is steadily increasing worldwide. The risk factors for dementia are diverse, and include genetic background, environmental factors, sex differences, and vascular abnormalities. Among the subtypes of dementia, diabetes-related dementia is emerging as a complex type of dementia related to metabolic imbalance, due to the increase in the number of patients with metabolic syndrome and dementia worldwide. Thyroid hormones are considered metabolic regulatory hormones and affect various diseases, such as liver failure, obesity, and dementia. Thyroid dysregulation affects various cellular mechanisms and is linked to multiple disease pathologies. In particular, hypothyroidism is considered a critical cause for various neurological problems-such as metabolic disease, depressive symptoms, and dementia-in the central nervous system. Recent studies have demonstrated the relationship between hypothyroidism and brain insulin resistance and dyslipidemia, leading to diabetes-related dementia. Therefore, we reviewed the relationship between hypothyroidism and diabetes-related dementia, with a focus on major features of diabetes-related dementia such as insulin resistance, neuronal dysfunction, and dyslipidemia.
Assuntos
Demência , Diabetes Mellitus , Dislipidemias , Hipotireoidismo , Resistência à Insulina , Demência/etiologia , Dislipidemias/complicações , Feminino , Humanos , Hipotireoidismo/complicações , MasculinoRESUMO
Hepatic encephalopathy (HE) is a chronic metabolic disease accompanied by neuropathological and neuropsychiatric features, including memory deficits, psychomotor dysfunction, depression, and anxiety. Alzheimer's disease (AD), the most common neurodegenerative disease, is characterized by tau hyperphosphorylation, excessive amyloid beta (Aß) accumulation, the formation of fibrillary tangles, hippocampus atrophy, and neuroinflammation. Recent studies have suggested a positive correlation between HE and AD. Some studies reported that an impaired cholesterol pathway, abnormal bile acid secretion, excessive ammonia level, impaired Aß clearance, astrocytic dysfunction, and abnormal γ-aminobutyric acid GABAergic neuronal signaling in HE may also be involved in AD pathology. However, the mechanisms and related genes involved in AD-like pathology in the HE brain are unclear. Thus, we compared the cortical transcriptome profile between an HE mouse model, bile duct ligation (BDL), and an AD mouse model, the 5×FAD. Our study showed that the expression of many genes implicated in HE is associated with neuronal dysfunction in AD mice. We found changes in various protein-coding RNAs, implicated in synapses, neurogenesis, neuron projection, neuron differentiation, and neurite outgrowth, and non-coding RNAs possibly associated with neuropathology. Our data provide an important resource for further studies to elucidate AD-like pathophysiology in HE patients.
Assuntos
Doença de Alzheimer , Encefalopatia Hepática , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encefalopatia Hepática/metabolismo , Doenças Neurodegenerativas/metabolismo , Transcriptoma , Encéfalo/metabolismo , Modelos Animais de Doenças , Camundongos TransgênicosRESUMO
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.
Assuntos
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
Thyroid hormone (TH) contributes to multiple cellular mechanisms in the liver, muscle cells, adipose tissue, and brain, etc. In particular, the liver is an important organ in TH metabolism for the conversion of thyronine (T4) into triiodothyronine (T3) by the deiodinase enzyme. TH levels were significantly decreased and thyroid-stimulating hormone (TSH) levels were significantly increased in patients with liver failure compared with normal subjects. Among liver failure diseases, hepatic encephalopathy (HE) deserves more attention because liver damage and neuropathologies occur simultaneously. Although there is numerous evidence of TH dysregulation in the HE model, specific mechanisms and genetic features of the thyroid glands in the HE model are not fully understood. Here, we investigated the significantly different genes in the thyroid glands of a bile duct ligation (BDL) mouse model as the HE model, compared to the thyroid glands of the control mouse using RNA sequencing. We also confirmed the alteration in mRNA levels of thyroid gland function-related genes in the BDL mouse model. Furthermore, we evaluated the increased level of free T4 and TSH in the BDL mouse blood. Thus, we emphasize the potential roles of TH in liver metabolism and suggest that thyroid dysfunction-related genes in the HE model should be highlighted for finding the appropriate solution for an impaired thyroid system in HE.
Assuntos
Encefalopatia Hepática , Glândula Tireoide , Animais , Ductos Biliares/metabolismo , Ductos Biliares/cirurgia , Modelos Animais de Doenças , Humanos , Ligadura , Fígado/metabolismo , Camundongos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Tireotropina/metabolismo , TranscriptomaRESUMO
OBJECTIVE: Clinical research on drug intoxication is necessary for appropriate action in emergency departments (EDs). However, currently, there are no evident biomarkers for predicting adverse events (AEs) in patients with drug intoxication. We aimed to evaluate the prognostic value of serum lactate concentrations and lactate kinetics for AEs such as cardiogenic or respiratory failure in patients admitted to the ED with acute drug overdose. METHODS: We conducted a single-center retrospective study by reviewing the prospective suicide registry of patients visiting the ED. The primary outcome was composite AEs at any point during the ED visit or hospital stay. RESULTS: A total of 566 patients with acute drug overdose were enrolled in this study. Of these, 62 patients had AEs, whereas 363 patients did not, yielding an AE rate of 14.6%. The median 0 h lactate concentrations in the AE and non-AE groups were 2.7 [2.1-5.1] mmol/L and 2.1 [1.4-2.9] mmol/L, respectively (p < 0.001). The median 6 h lactate concentrations in the AE and non-AE groups were 2.0 [1.5-3.9] mmol/L and 1.3 [0.9-2.2] mmol/L, respectively (p < 0.001). The area under the curve of lactate at 0 h for predicting AEs was 0.705 (95% CI: 0.659-0.748). The optimal lactate cutoff point was 4.2 mmol/L (37.1% sensitivity, 92.8% specificity). Multivariable analysis using a stepwise backward method showed that the 0 h lactate concentration was associated with AEs in acute drug intoxication after adjusting for confounders (adjusted OR of 0 h lactate, 1.47; 95% CI, 1.23-1.77). However, the 6 h lactate concentrations, lactate clearance, and delta lactate levels did not predict the outcomes. CONCLUSION: Lactate concentrations and kinetics in patients admitted to the ED with an acute drug overdose exhibited limited prognostic utility in predicting AEs and should be interpreted with caution when considered for clinical decision-making.
Assuntos
Overdose de Drogas/sangue , Serviço Hospitalar de Emergência , Lactatos/sangue , Adulto , Feminino , Humanos , Lactatos/farmacocinética , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: The early detection and treatment of sepsis and septic shock patients in emergency departments are critical. Ischemia modified albumin (IMA) is a biomarker produced by ischemia and oxygen free radicals which are related to the pathogenesis of sepsis-induced organ dysfunction. This study aimed to investigate whether IMA was associated with short-term mortality in quick sequential organ failure assessment (qSOFA)-positive sepsis or septic shock patients screened by the sepsis management program. METHOD: From September 2019 to April 2020, patients who arrived at the emergency departments with qSOFA-positive sepsis or septic shock were included in this retrospective observational study. RESULTS: Among 124 patients analyzed, IMA was higher in the non-surviving group than in the surviving group (92.6 ± 8.1 vs. 86.8 ± 6.2 U/mL, p < 0.001). The area under the receiver operating characteristics curve was 0.703 (95% CI: 0.572-0.833, p < 0.001). The optimal IMA cutoff was 90.45 (sensitivity 60.9%, specificity 79.2%). IMA values were independently associated with 28-day mortality in the multivariate Cox proportional hazard model (adjusted hazard ratio (aHR) = 1.16, 95% CI: 1.06-1.27, p < 0.01). CONCLUSIONS: In this study, we showed that IMA in the emergency departments was associated with 28-day mortality in qSOFA-positive sepsis and septic shock patients. Further studies are needed to evaluate the clinical value of IMA as a useful biomarker in large populations and multicenter institutions.
Assuntos
Serviço Hospitalar de Emergência , Sepse/mortalidade , Albumina Sérica Humana/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , República da Coreia , Estudos Retrospectivos , Sensibilidade e Especificidade , Choque Séptico/mortalidadeRESUMO
OBJECTIVE: This study aimed to describe the timely strategies used to prevent the spread of the emerging coronavirus disease 2019 (COVID-19) and present the activities performed in a regional base hospital in South Korea, from the identification of the index patient until the pandemic declaration. METHODS: This is a descriptive study detailing the step-by-step guidelines implemented to manage COVID-19 in a regional tertiary base hospital from January to March 2020. We described our three-phase response to the COVID-19 outbreak as per the national and global quarantine procedures applied during each critical event and highlighted the activities implemented from the perspective of public health crisis preparedness involving emerging infectious diseases. RESULTS: During the COVID-19 outbreak in Korea, we improved and implemented a rapid and flexible screening system for visiting patients using patient history and radiological testing and created a separate isolation zone for patients under investigation. This active identification-isolation strategy has been effectively applied in the COVID-19 outbreak. CONCLUSIONS: The step-by-step enforced strategies to prevent the spread of COVID-19, though not perfect, adequately reduced the risk of transmission of the highly contagious infectious disease in the hospital while maintaining the emergency medical system.
Assuntos
COVID-19/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Serviço Hospitalar de Emergência/normas , Guias como Assunto , Pandemias , Centros de Atenção Terciária/normas , COVID-19/epidemiologia , Humanos , República da Coreia/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
Hepatic encephalopathy (HE) is one of the main consequences of liver disease and is observed in severe liver failure and cirrhosis. Recent studies have provided significant evidence that HE shows several neurological symptoms including depressive mood, cognitive dysfunction, impaired circadian rhythm, and attention deficits as well as motor disturbance. Liver disease is also a risk factor for the development of diabetes mellitus. Diabetic encephalopathy (DE) is characterized by cognitive dysfunction and motor impairment. Recent research investigated the relationship between metabolic changes and the pathogenesis of neurological disease, indicating the importance between metabolic organs and the brain. Given that a diverse number of metabolites and changes in the brain contribute to neurologic dysfunction, HE and DE are emerging types of neurologic disease. Here, we review significant evidence of the association between HE and DE, and summarise the common risk factors. This review may provide promising therapeutic information and help to design a future metabolic organ-related study in relation to HE and DE.
Assuntos
Encéfalo/patologia , Diabetes Mellitus/patologia , Encefalopatia Hepática/patologia , Fígado/patologia , Animais , Disfunção Cognitiva/patologia , HumanosRESUMO
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.
Assuntos
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
Diabetes-induced dementia is an emerging neurodisorder all over the world. The prevalence rates of dementia and diabetes have been gradually increasing worldwide. Diabetes has been known to lead to oxidative stress, inflammation aggravation, and hyperglycemia conditions in the brain. Various diabetic implications cause the lower secretion of brain-derived neurotrophic factor (BDNF) and the increase of receptor for advanced glycation end products (RAGE), ultimately leading to both cerebrovascular dysfunction and cognitive decline. Here, we summarized the significant evidences highlighting the specific mechanisms between BDNF and RAGE and cerebrovascular dysfunction and memory function and how these relate to diabetes-induced dementia. Especially, we review that the association between BDFN and RAGE in neuroinflammation, the reduction of long-term potentiation, and the vascular implications in brain.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/irrigação sanguínea , Artérias Cerebrais/metabolismo , Cognição , Demência Vascular/metabolismo , Complicações do Diabetes/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Glicemia/metabolismo , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular , Demência Vascular/epidemiologia , Demência Vascular/fisiopatologia , Demência Vascular/psicologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/psicologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Potenciação de Longa Duração , Memória , Fatores de Risco , Transdução de SinaisRESUMO
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.
Assuntos
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
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
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.