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Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their endothelial properties and acquire mesenchymal characteristics. Dual-specific protein phosphatase 22 (DUSP22) inactivates various protein kinases and transcription factors by dephosphorylating serine/threonine residues: hence, it plays a key role in many diseases. The aim of this study was to explore the functional role of DUSP22 in EndMT. In the transforming growth factor-ß-induced EndMT model in human umbilical vein endothelial cells (HUVECs), we observed a downregulation of DUSP22 expression. This DUSP22 deficiency could aggravate EndMT. Conversely, the overexpression of DUSP22 could ameliorate EndMT. We used signaling pathway inhibitors to verify our results and found that DUSP22 could regulate EndMT through the smad2/3 and the mitogen-activated protein kinase (MAPK) signaling pathways. In summary, DUSP22 ameliorates EndMT in HUVECs in vitro through the smad2/3 and MAPK signaling pathways.
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Sistema de Señalización de MAP Quinasas , Fosfoproteínas Fosfatasas , Humanos , Regulación hacia Abajo , Fosfatasas de Especificidad Dual/genética , Transición Endotelial-Mesenquimatosa , Células Endoteliales de la Vena Umbilical Humana , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genéticaRESUMEN
Objective: Gastrointestinal bleeding (GIB) post acute myocardial infarction (AMI) is a severe clinical condition with a poor prognosis. The purpose of the study was to evaluate the rate of in-hospital mortality in patients with GIB post-AMI and to identify the potential risk factors of this situation. Methods: In this single-center retrospective study, a total of 154 patients diagnosed with AMI who subsequently suffered GIB were enrolled from October 2013 to December 2021. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality. Results: Among the 154 subjects included in the final analysis, the mean age was 65.58 ± 11.20 years, and 104 (67.53%) were males. GIB occurred in 11 patients after thrombolytic therapy, 50 patients after percutaneous coronary intervention (PCI), and 93 patients during drug conservative treatment. A total of 41 patients died in the hospital. The in-hospital mortality rate of the thrombolysis group, PCI group, and drug conservative treatment group was 27.27% (3/11), 28.00% (14/50), and 25.81% (24/93), respectively. There was no difference in the in-hospital mortality among the three groups. The multivariate logistic regression analysis showed that the peak levels of TnI (OR 1.07, 95% CI 1.02-1.12, P = 0.011), condition of cardiogenic shock after admission (OR 14.52, 95% CI 3.36-62.62, P < 0.001), and the use of the mechanical ventilator (OR 8.14, 95% CI 2.03-32.59, P = 0.003) were significantly associated with in-hospital mortality. Conclusion: Regardless of the treatment strategy for AMI, once GIB occurred, the prognosis was poor. High in-hospital mortality in patients with GIB post-AMI was independently associated with the peak levels of TnI, condition of cardiogenic shock, and the use of a mechanical ventilator.
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Oxidative RNA damage has been found to be associated with age-related diseases and 8-oxo-7,8-dihydroguanosine (8-oxoGsn) is a typical marker of oxidative modification of RNA. Urine tests are a feasible non-invasive diagnostic modality. The present study aimed to assess whether the measurement of urinary 8-oxoGsn could represent a potential early maker in mild cognitive impairment (MCI) of frail patients with cardiovascular disease (CVD). In this cross-sectional study performed in China from September 2018 to February 2019. Urinary 8-oxoGsn was measured in frail (Fried phenotype: 3-5) in patients with CVD and was adjusted by urinary creatinine (Cre) levels. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE) and participants were classified into non-MCI (≥24) and MCI (<24) groups. Univariate and multivariate logistic regression models were used to determine the relationship between 8-oxoGsn/Cre and MCI. Receiver operating characteristic (ROC) curve analysis was used to assess the 8-oxoGsn/Cre ratio in relation to MCI in frail patients with CVD. A total of 106 elderly patients were enrolled in this study. The mean age of participants was 77.9 ± 6.8 years, the overall prevalence of MCI was 22.6% (24/106), and 57.5% (61/106) of participants were women. In the multivariate logistic regression analysis, urinary 8-oxoGsn/Cre was independently associated with MCI (odds ratio [OR] = 1.769, 95% confidence interval [CI] = 1.234-2.536, P = 0.002), after adjusting for age, sex, education level, marital status, and serum prealbumin levels. The area under the ROC curve was 0.786 (0.679-0.893) (P < 0.001), and the optimal cut-off value was 4.22 µmol/mol. The urinary 8-oxoGsn/Cre ratio showed a sensitivity of 87.5% and a specificity of 69.5%. The present study suggests the urinary 8-oxoGsn/Cre ratio may be a useful indicator for the early screening of MCI in frail patients with CVD. CLINICAL TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
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Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear. Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE. Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P < 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174-6.098, P < 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112-3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014-6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate. Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B. Trial Registration: ChiCTR1800017204; 07/18/2018.
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INTRODUCTION: Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells. METHODS: Cell viability and IC50 dose for TQ and TRAIL, alone and in combination, were determined using the MTT method. ELISA evaluated the expression levels of 8-Hydroxy-2'-deoxyguanosine. The apoptosis rate was assessed by flow cytometry, ELISA cell death assay, and caspase 8 activity assays. The mRNA and protein evaluation of candidate genes, including survivin, Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP, were accomplished before and after the treatment using qRT-PCR and Western blot analysis, respectively. RESULTS: Our results showed that TQ synergistically increased TRAIL's cell toxic effects as follows: TQ plus TRAIL > TRAIL > TQ. TQ could sensitize the HepG2 cells against the TRAIL-induced apoptosis and amplify the caspase 8 activity. This outcome is achieved by decreasing the mRNA and protein expression levels of anti-apoptotic genes. CONCLUSIONS: Our findings suggest that TQ can sensitize the human HCC cell line HepG2 against TRAIL by inducing the death receptor pathway. Moreover, these agents' combinational therapy might promise a therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with HCC.
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Apoptosis , Benzoquinonas/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Daño del ADN , Neoplasias Hepáticas/tratamiento farmacológico , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Benzoquinonas/uso terapéutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/fisiopatología , ADN/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatología , Estrés OxidativoRESUMEN
[This corrects the article DOI: 10.3389/fcell.2020.00602.].
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As a serious metabolic disease, diabetes causes series of complications that seriously endanger human health. The liver is a key organ for metabolizing glucose and lipids, which substantially contributes to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Exogenous fibroblast growth factor 1 (FGF1) has a great potential for the treatment of diabetes. Receptor of advanced glycation end products (RAGE) is a receptor for advanced glycation end products that involved in the development of diabetes-triggered complications. Previous study has demonstrated that FGF1 significantly ameliorates diabetes-mediated liver damage (DMLD). However, whether RAGE is involved in this process is still unknown. In this study, we intraperitoneally injected db/db mice with 0.5 mg/kg FGF1. We confirmed that FGF1 treatment not only significantly ameliorates diabetes-induced elevated apoptosis in the liver, but also attenuates diabetes-induced inflammation, then contributes to ameliorate liver dysfunction. Moreover, we found that diabetes triggers the elevated RAGE in hepatocytes, and FGF1 treatment blocks it, suggesting that RAGE may be a key target during FGF1 treatment of diabetes-induced liver injury. Thus, we further confirmed the role of RAGE in FGF1 treatment of AML12 cells under high glucose condition. We found that D-ribose, a RAGE agonist, reverses the protective role of FGF1 in AML12 cells. These findings suggest that FGF1 ameliorates diabetes-induced hepatocyte apoptosis and elevated inflammation via suppressing RAGE pathway. These results suggest that RAGE may be a potential therapeutic target for the treatment of DMLD.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Factor 1 de Crecimiento de Fibroblastos/farmacología , Inflamación/tratamiento farmacológico , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Apoptosis , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Frailty increases the adverse outcomes of clinical heart failure; however, the relationship between frailty and stage-B heart failure (SBHF) remains unknown. We aimed to explore the epidemiology and predictive value of frailty in older adults with SBHF. METHODS: A prospective cohort of SBHF inpatients aged 65 years or older who were hospitalized between September 2018 and February 2019 and were followed up for 6 months were included. SBHF was defined as systolic abnormality, structural abnormality (left ventricular enlargement, left ventricular hypertrophy, wall motion abnormalities, valvular heart disease), or prior myocardial infarction. Frailty was assessed by the Fried frailty phenotype. Multivariable Cox proportional hazards regression was used to explore the independent risk and prognostic factors. RESULTS: Data of 443 participants (age: 76.1 ± 6.79 years, LVEF: 62.8 ± 4.92%, men: 225 [50.8%], frailty: 109 [24.6%]) were analyzed. During the 6-month follow-up, 83 (18.7%) older SBHF inpatients experienced all-cause mortality or readmission, and 29 (6.5%) of them developed clinical HF. Frail individuals had a 1.78-fold (95%CI: 1.02-3.10, P = 0.041) higher risk of 6-month mortality or readmission and a 2.83-fold (95%CI 1.24-6.47, P = 0.014) higher risk of developing clinical HF, independent of age, sex, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide level. CONCLUSIONS: Frailty is common in older SBHF inpatients and should be considered to help identify individuals with an increased risk of mortality or readmission, and developing clinical HF. TRIAL REGISTRATION: ChiCTR1800017204 .
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Fragilidad , Insuficiencia Cardíaca , Anciano , Anciano de 80 o más Años , Femenino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Pacientes Internos , Masculino , Readmisión del Paciente , Pronóstico , Estudios Prospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD). METHODS: A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ≥65 years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves. RESULTS: Of all the subjects enrolled, 51.0% were male and the mean age was 75.32 ± 6.52 years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p = 0.004; HR: 3.67, 95% CI: 1.83-7.39, p < 0.001). Adding hsCRP to the frailty model resulted in a significant increase in the area under the ROC curve from 0.74 (95% CI: 0.70-0.77) to 0.77 (95% CI: 0.71-0.84) (p = 0.0132) and a net reclassification index of 7.9% (95% CI: 1.96%-12.56%, p = 0.012). CONCLUSION: Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1 year. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
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Enfermedades Cardiovasculares , Fragilidad , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Pacientes Internos , Masculino , Factores de RiesgoRESUMEN
DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.
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Benzofuranos/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Disfunción Cognitiva/etiología , Dendritas/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Hipocampo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Células PC12 , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Sinapsis/efectos de los fármacosRESUMEN
Objective: To evaluate the prognostic value of frailty in gerontal pre-clinical heart failure (stage B heart failure, SBHF) inpatients. Background: The association between frailty and SBHF remains unknown. Methods: We conducted a subgroup analysis of a prospective observational cohort study on frailty. The previous study recruited 1,000 elderly inpatients who were consecutively admitted to a tertiary referral hospital in Beijing, China, from September 2018 to February 2019. The outcomes were all-cause death or readmission at 1-year follow-up. SBHF was diagnosed for asymptomatic cardiac structural or functional abnormalities. Frailty was assessed using the Comprehensive Geriatric Assessment-Frailty Index (CGA-FI). Results: Overall, 531 inpatients aged ≥65 years were deemed to have SBHF and followed up for 1 year. Of them, 34.5% exhibited frailty. During the follow-up period, all-cause death or readmission occurred in 157 (29.5%) participants. Of these participants, 36.6% (67/183) and 25.9% (90/348) belonged to the frail and non-frail groups, respectively (χ2 = 6.655, P = 0.010). Frailty, defined by the CGA-FI, rather than Fried frailty phenotype, could independently predict 1-year all-cause death or readmission (hazard ratio, 1.56; 95% confidence interval, 1.03-2.35; P = 0.034) and was more suitable for predicting all-cause death or readmission than N-terminal pro-B-type natriuretic peptide in female SBHF inpatients aged 80 years or over(AUCCGA-FI vs. AUCNT-proBNP 0.654 vs. 0.575, P = 0.017). Conclusions: Frailty is highly prevalent even among SBHF inpatients aged ≥65 years. The CGA-FI can independently predict 1-year all-cause death or readmission, rather than Fried frailty phenotype. Frailty in gerontal SBHF inpatients deserves more attention. Clinical Trial registration: ChiCTR1800017204; date of registration: 07/18/2018.
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PURPOSE: To study the effects of chronic-simulated night shift work using the rat model and examines if a particular sleep supplement mode could be better in alleviating the effects. METHODS: The male Wistar rats were randomly divided into the control (CTL: 8 rats) and night shift work (NW: 24 rats) groups of rats. Based on the sleep supplement strategy, the NW group was further segregated into three subgroups (8 rats each); late sleep supplement group (LSS), early sleep supplement group (ESS), and intermittent sleep supplement group (ISS). Sleep deprivation was achieved using the standard small-platform-over water method. Parameters such as animal body weight and food intake were measured daily. The intraperitoneal glucose tolerance test, fasting plasma insulin concentration, insulin resistance index and insulin sensitivity were measured twice, in the 4th and 8th weeks of the study. Plasma corticosterone concentration and pathological changes in islets (insulitis) were measured at the end of the 8th week. RESULTS: In NW group, night work resulted in a gain of body weight and albeit lower than that of the CTL group. NW rats also had higher food intake, showed impaired glucose metabolism and higher plasma corticosterone concentration. The sleep supplement experiments suggested that compared to the other modes, intermittent sleep supplement had significantly low changes in the body weight, glucose metabolism and the islet cells. CONCLUSION: Similar to previous studies, we also found that night shift work adversely impacts the body weight and glucose metabolism in rats. However, upon evaluating different sleep supplement strategies, we found the intermittent sleep supplement strategy to be most effective.
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BACKGROUND: A comprehensive geriatric assessment (CGA) of elderly patients is useful for detecting the patients vulnerabilities. Exercise and early rehabilitation, nutritional intervention, traditional Chinese medicine (TCM), standardized medication guidance, and patient education can, separately, improve and even reverse the physical frailty status. However, the effect of combining a CGA and multi-disciplinary management on frailty in elderly patients remains unclear. The present study assessed the effects of a CGA and multi-disciplinary management on elderly patients with frailty in China. METHODS: In this study, 320 in patients with frailty ≥70 years old will be randomly divided into an intervention group and a control group. The intervention group will be given routine management, a CGA and multi-disciplinary management involving rehabilitation exercise, diet adjustment, multi-drug evaluation, acupoint massage in TCM and patient education for 12 months, and the control group will be followed up with routine management for basic diseases. The primary outcomes are the Fried phenotype and short physical performance battery (SPPB). The secondary outcomes are the clinical frailty scale (CFS), non-elective hospital readmission, basic activities of daily living (BADL), 5-level European quality of life 5 dimensions index (EQ-5D), nutrition risk screening-2002 (NRS-2002), medical insurance expenses, fall events, and all-cause mortality. In addition, a cost-effectiveness study will be carried out. DISCUSSION: This paper outlines the protocol for a randomized, single-blind, parallel multi-center clinical study. This protocol, if beneficial, will demonstrate the interaction of various intervention strategies, will help improve elderly frailty patients, and will be useful for clinicians, nurses, policymakers, public health authorities, and the general population. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR1900022623. Registered on April 19, 2019, http://www.chictr.org.cn/showproj.aspx?proj=38141.
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Atención Integral de Salud/métodos , Anciano Frágil , Fragilidad/rehabilitación , Evaluación Geriátrica/métodos , Servicios de Salud para Ancianos , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , China , Terapia por Ejercicio/métodos , Femenino , Humanos , Masculino , Medicina Tradicional China/métodos , Terapia Nutricional/métodos , Estado Nutricional , Grupo de Atención al Paciente , Educación del Paciente como Asunto/métodos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del TratamientoRESUMEN
OBJECTIVE: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease. PATIENTS AND METHODS: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry. RESULTS: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84-7.01] vs 3.21 [2.13-5.03] µM; p<0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01-4.38, p=0.046). Dose-response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08-1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01-1.45, p for trend 0.04). CONCLUSION: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.
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Enfermedades Cardiovasculares/epidemiología , Trastornos del Conocimiento/epidemiología , Anciano Frágil/estadística & datos numéricos , Microbioma Gastrointestinal/fisiología , Metilaminas/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores , Enfermedades Cardiovasculares/sangre , Estudios Transversales , Femenino , Evaluación Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Diabetes significantly induces cognitive dysfunction. Neuronal apoptosis is the main cause of diabetes-induced cognitive decline (DICD). Apoptosis signal-regulating kinase 1 (ASK1) and endoplasmic reticulum (ER) stress are remarkably activated by diabetes. The role and relationship of ASK1-JNK1/2 signaling and ER stress in DICD have not yet been elucidated. In this study, we used db/db mice as the DICD animal model and confirmed that db/db mice displayed cognitive decline with inferior learning and memory function. Diabetes significantly induced morphological and structural changes, excessive neuronal apoptosis, Aß1 - 42 large deposition, and synaptic dysfunction in the hippocampus. Mechanistic studies found that diabetes significantly triggered ASK1-JNK1/2 signaling activation and increased ER stress in the hippocampus. Moreover, diabetes enhanced the formation of the IRE1α-TRAF2-ASK1 complex, which promotes the crosstalk of ER stress and the ASK1-JNK1/2 pathway during DICD. Furthermore, 4-PBA treatment blocked high glucose (HG)-induced ASK1-JNK1/2 signaling activation, and excessive apoptosis in vitro. Inhibiting ASK1 via siRNA remarkably ameliorated the HG-induced increase in p-IRE1α and associated apoptosis in SH-SY5Y cells, suggesting that ASK1 is essential for the assembly and function of the proapoptotic kinase activity of the IRE1α signalosome. In summary, ER stress and ASK1-JNK1/2 signaling play causal roles in DICD development, which has crosstalk through the formation of the IRE1α-TRAF2-ASK1 complex.
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BACKGROUND: The clinical symptoms and adverse events caused by pacemaker battery depletion are not uncommon, but it is easy to miss or misdiagnose them clinically. To raise the level of awareness towards this clinical situation, we report two cases. CASE PRESENTATION: We described two cases of pacemaker battery depletion. Case 1 was an 83-year-old male manifesting chest pain and dyspnea. Automatic reprogramming after pacemaker battery depletion resulted in pacemaker syndrome. While case 2 was an 80-year-old female with complete atrioventricular heart block and torsade de pointes, due to complete depletion of pacemaker battery. In addition, we introduce a method that can easily identify the depletion of the pacemaker battery, which has clinical promotion value of a certain degree. CONCLUSIONS: Those cases emphasize that serious morbidity can arise from pacemaker battery depletion, even in the early stages. Therefore, early detection and diagnosis is especially important.
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Bloqueo Atrioventricular/etiología , Dolor en el Pecho/etiología , Disnea/etiología , Suministros de Energía Eléctrica/efectos adversos , Falla de Equipo , Marcapaso Artificial/efectos adversos , Torsades de Pointes/etiología , Anciano de 80 o más Años , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/terapia , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/terapia , Remoción de Dispositivos , Disnea/diagnóstico , Disnea/terapia , Resultado Fatal , Femenino , Humanos , Masculino , Torsades de Pointes/diagnóstico , Torsades de Pointes/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6 months in elderly inpatients with cardiovascular disease (CVD). METHODS: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P < 0.001) and a lower education level (P < 0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at 6 months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P = 0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P = 0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to 6 months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69). CONCLUSIONS: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.
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Enfermedades Cardiovasculares , Fragilidad , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Cognición , Femenino , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Pacientes Internos , Masculino , Readmisión del Paciente , Estudios ProspectivosRESUMEN
Type-2 diabetes (T2D) is a common metabolic disorder, which causes several physiological and pathological complications. Spleen is regarded as an important organ, which regulates immune system and iron metabolism in the body. Precious few studies have been conducted to explore the pathological and deleterious roles of diabetes on spleen. In our current study, we have explored and confirmed the pathological effects of diabetes on spleen in db/db experimental mice model. In our current study, 0.5 mg/kg fibroblast growth factor 1 (FGF1) dose was intraperitoneally administrated to db/db mice. We found that diabetes evidently induced spleen enlargement and fibrosis progression in the db/db mice. Additionally, our studies demonstrate that iron has hugely deposited in the spleen in db/db mice. Several studies have documented that diabetes largely disrupts the inflammatory cells distribution, immune homeostasis, proliferation and oxidative stress with the down-regulation of anti-inflammatory cytokines and antioxidant activities. Moreover, we have observed that FGF1 administration significantly reversed the deleterious effect of diabetes on spleen enlargement and dysfunction. In summary, these substantial findings clearly demonstrate that diabetes plays deleterious roles in maintaining the spleen structure and functions. Therefore, our investigations suggest that FGF1 can effectively prevent diabetes-mediated splenomegaly progression.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Factor 1 de Crecimiento de Fibroblastos/uso terapéutico , Inflamación/patología , Estrés Oxidativo , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/etiología , Animales , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Factor 1 de Crecimiento de Fibroblastos/administración & dosificación , Factor 1 de Crecimiento de Fibroblastos/farmacología , Fibrosis , Inflamación/complicaciones , Hierro/metabolismo , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
BACKGROUND: Diabetes induces central nervous system damage, leading to cognitive decline. Fibroblast growth factor 1 (FGF1) has dual function of neuroprotection and normalizing hyperglycemia. To date, the precise mechanisms and potential treating strategies of FGF1 for diabetes-induced cognitive decline (DICD) hasn't been fully elucidated. METHODS: In this study, db/db mice were used as DICD animal model. We found that diabetes remarkably suppressed FGF1 expression in hippocampus. Thus, exogenous FGF1 had been treated for db/db mice and SH-SY5Y cells. RESULTS: FGF1 significantly ameliorates DICD with better spatial learning and memory function. Moreover, FGF1 blocked diabetes-induced morphological structure change, neuronal apoptosis and Aß1-42 deposition and synaptic dysfunction in hippocampus. But normalizing glucose may not the only contributed factor for FGF1 treating DICD with evidencing that metformin-treated db/db mice has a inferior cognitive function than that in FGF1 group. Current mechanistic study had found that diabetes inhibits cAMP-response element binding protein (CREB) activity and subsequently suppresses brain derived neurotrophic factor (BDNF) level via coordinately regulating PERK signaling and PI3K/AKT signaling in hippocampus, which were reversed by FGF1. CONCLUSION: We conclude that FGF1 exerts its neuroprotective role and normalizing hyperglycemia effect, consequently ameliorates DICD, implying FGF1 holds a great promise to develop a new treatment for DICD. Video abstract.