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1.
Phys Chem Chem Phys ; 26(10): 8177-8182, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38380533

RESUMO

The problem of poisoning on the surface of catalysts used in CO oxidation reactions, such as Pt, needs to be solved. In this work, we constructed lattice-matched C2N/Pt(111) catalysts with different configurations (top/fcc/hcp) and found that, within the confined space between the cover and the substrate, the adsorption energy of CO is reduced by 0.35 eV to 0.43 eV, while the adsorption of other reactants O/O2 is strengthened and the adsorption energy of the product CO2 is positive, indicating that the constraint effect produced by C2N and Pt(111) is beneficial to CO oxidation, when compared to the pure Pt(111). Our work suggests that the C2N cover not only protects the Pt surface under harsh conditions but also allows gaseous molecules CO and O2 to approach the Pt surface through a facile intercalation process, with enhanced surface reactivity for CO oxidation and reduced catalyst poisoning.

2.
Behav Brain Res ; 458: 114737, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-37924850

RESUMO

Aggressive behavior can have serious physical, psychological, and social consequences. However, little is known about the personality and neurological antecedents underlying aggressive behavior in children. The objective of this study was to investigate the relationship between self-esteem, aggression, and brain structure (i.e., cortical thickness and surface area) in a population of healthy children (N = 78; 9-12 years; mean age: 9.95 ± 0.90 years). The results revealed that self-esteem showed a negative association with aggression and significantly predicted aggressive behavior. No gender differences were found in aggression and its neural correlates. We performed the cortical parcellation method to further explore the neural foundations underlying the association of self-esteem with aggression. Children with higher aggression had increased cortical thickness in four clusters after multiple comparison correction: right medial orbitofrontal cortex, right lateral orbitofrontal cortex, right superior frontal gyrus, and left insula. In a mediation analysis, cortical thickness in the right medial orbitofrontal cortex contributed to the effect of self-esteem on aggression. These findings extend our understanding of morphological correlates of aggression in children, suggesting that an increased cortical thickness in childhood is a potential mechanism linking low self-esteem to aggression.


Assuntos
Agressão , Córtex Pré-Frontal , Humanos , Criança , Autoimagem , Personalidade , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética
4.
Front Nutr ; 10: 1210726, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388634

RESUMO

The reward system has been proven to be contributed to the vulnerability of obesity. Previous fMRI studies have shown abnormal functional connectivity of the reward system in obesity. However, most studies were based on static index such as resting-state functional connectivity (FC), ignoring the dynamic changes over time. To investigate the dynamic neural correlates of obesity susceptibility, we used a large, demographically well-characterized sample from the Human Connectome Project (HCP) to determine the relationship of body mass index (BMI) with the temporal variability of FC from integrated multilevel perspectives, i.e., regional and within- and between-network levels. Linear regression analysis was used to investigate the association between BMI and temporal variability of FC, adjusting for covariates of no interest. We found that BMI was positively associated with regional FC variability in reward regions, such as the ventral orbitofrontal cortex and visual regions. At the intra-network level, BMI was positively related to the variability of FC within the limbic network (LN) and default mode network (DMN). At the inter-network level, variability of connectivity of LN with DMN, frontoparietal, sensorimotor, and ventral attention networks showed positive correlations with BMI. These findings provided novel evidence for abnormal dynamic functional interaction between the reward network and the rest of the brain in obesity, suggesting a more unstable state and over-frequent interaction of the reward network and other attention and cognitive networks. These findings, thus, provide novel insight into obesity interventions that need to decrease the dynamic interaction between reward networks and other brain networks through behavioral treatment and neural modulation.

5.
Phys Chem Chem Phys ; 25(17): 12420-12425, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37096319

RESUMO

The technique of CO2 capture and separation using charge-modulated sorbent materials holds promise for reducing CO2 emissions. Density functional theory with long-range dispersion correction has been used to study the adsorption of CO2, H2, CH4, and N2 on BC3 nanosheets with/without charge injections. We find that CO2 is weakly adsorbed on pristine BC3, but injection of 3 negative charges (3 e) can change the adsorption to chemical adsorption. Removing the charge results in the release of CO2 without any energy barrier. A high capacity of 4.30 × 1014 cm-2 can be achieved with 5 e charge injection, and CO2 molecules could automatically desorb after charge removal. Additionally, negatively charged BC3 exhibits high selectivity for separating CO2 from other industrial gases such as CH4, H2, and N2. Our findings provide useful guidance for the development of switchable CO2 capture and storage materials.

6.
Cereb Cortex ; 33(11): 7163-7174, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36748995

RESUMO

Delay discounting (DD) refers to a phenomenon that humans tend to choose small-sooner over large-later rewards during intertemporal choices. Steep discounting of delayed outcome is related to a variety of maladaptive behaviors and is considered as a transdiagnostic process across psychiatric disorders. Previous studies have investigated the association between brain structure (e.g. gray matter volume) and DD; however, it is unclear whether the intracortical myelin (ICM) influences DD. Here, based on a sample of 951 healthy young adults drawn from the Human Connectome Project, we examined the relationship between ICM, which was measured by the contrast of T1w and T2w images, and DD and further tested whether the identified associations were mediated by the regional homogeneity (ReHo) of brain spontaneous activity. Vertex-wise regression analyses revealed that steeper DD was significantly associated with lower ICM in the left temporoparietal junction (TPJ) and right middle-posterior cingulate cortex. Region-of-interest analysis revealed that the ReHo values in the left TPJ partially mediated the association of its myelin content with DD. Our findings provide the first evidence that cortical myelination is linked with individual differences in decision impulsivity and suggest that the myelin content affects cognitive performances partially through altered local brain synchrony.


Assuntos
Imageamento por Ressonância Magnética , Bainha de Mielina , Adulto Jovem , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Comportamento Impulsivo , Substância Cinzenta/diagnóstico por imagem
7.
Neurobiol Stress ; 22: 100511, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36632310

RESUMO

Perceived stress, which refers to people's evaluation of a stressful event and their ability to cope with it, has emerged as a stable predictor for physical and mental health outcomes. Increasing evidence has suggested the buffering effect of social support on perceived stress. Although previous studies have investigated the brain structural features (e.g., gray matter volume) associated with perceived stress, less is known about the association between perceived chronic stress and intra-cortical myelin (ICM), which is an important microstructure of brain and is essential for healthy brain functions, and the role of social support in this association. Using a sample of 1076 healthy young adults drawn from the Human Connectome Project, we quantified the ICMby the contrast of T1w and T2w images and examined its association with perceived chronic stress during the last month and social support. Behavioral results showed that perceived chronic stress was negatively associated with both emotional support and instrumental support. Vertex-wise multiple regression analyses revealed that higher level of perceived chronic stress was significantly associated with lower ICM content of a cluster in the right supramarginal gyrus (rSMG). Interestingly, the emotional support, but not the instrumental support, significantly mediated the association of perceived chronic stress with ICM in the rSMG. Overall, the present study provides novel evidence for the cortical myelination of perceived chronic stress in humans and highlights the essential role of the rSMG in perceived chronic stress and emotional support.

8.
BMC Pulm Med ; 23(1): 19, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647106

RESUMO

BACKGROUND: Severe influenza, especially influenza pneumonia, causes large numbers of deaths each year. Some patients who develop severe influenza have no known risk factors. In this study we investigated risk factors for mortality of patients with influenza A-related pneumonia who have different basic conditions. We also evaluated the power of pneumonia severity assessment tools in Chinese patients hospitalized with influenza A-related pneumonia. Together, these results could provide a basis for a screening method that has improved ability for the early identification of critical patients who will have poor prognoses in clinical practice. METHODS: This single-center, retrospective case-control study included 152 adult patients with severe influenza over six influenza seasons. Data for diagnoses and demographics, as well clinical data, laboratory findings, treatment methods, 30-day and 60-day outcomes of the patients were collected. Patients who had any of the risk factors for severe influenza were included in the high-risk group, and those that had no known risk factors were included in the low-risk group. RESULTS: The PSI, CURB-65 and PIRO-CAP tools all underestimated the mortality rate of patients hospitalized with influenza A-related pneumonia, and this underestimate was more pronounced for low-risk patients. D-dimer (Odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.001-1.106, p = 0.045) and direct bilirubin (OR = 1.143, 95%CI 1.049-1.246, p = 0.002) were independent risk factors for mortality of patients with influenza A-related pneumonia. When used in combination with ferritin and D-dimer, the area under receiver operator characteristic curve (AUCROC) was 0.851 (95%CI 0.780-0.922, p < 0.001), 0.840 (95%CI 0.763-0.916, p < 0.001) and 0.829 (95%CI 0.748-0.911, p < 0.001) for PSI, CURB-65 and PIRO-CAP, respectively, which was higher than that obtained using PSI, CURB-65 and PIRO-CAP alone. CONCLUSIONS: The findings demonstrate that currently used community-acquired pneumonia (CAP) scoring systems could underestimate the risk of influenza A-related pneumonia mortality. D-dimer was shown to be an independent risk factor of mortality for influenza A-related pneumonia in hospitalized patients, and a combination of D-dimer with ferritin could improve the predictive value of PSI, CURB-65 and PIRO-CAP for adverse prognoses of patients with influenza A-related pneumonia.


Assuntos
Infecções Comunitárias Adquiridas , Influenza Humana , Pneumonia , Adulto , Humanos , Estudos Retrospectivos , Influenza Humana/complicações , Estudos de Casos e Controles , Índice de Gravidade de Doença , Pneumonia/diagnóstico , Fatores de Risco , Prognóstico
9.
J Environ Sci (China) ; 126: 321-332, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36503760

RESUMO

Sludge is the by-product of wastewater treatment process. Multisource sludge can be defined as sludge from different sources. Based on the sludge properties of five typical cities in the Yangtze River basin, including Jiujiang, Wuhu, Lu'an, Zhenjiang and Wuhan, this study investigated and summarized the characteristic variations and distribution differences of multiple indicators and substances from municipal sludge, dredged sludge, and river and lake sediments. The results demonstrated pH of multisource sludge was relatively stable in the neutral range. Organic matter and water content among municipal sludge were high and varied considerably between different wastewater treatment plants. Dredged sludge had an obviously higher sand content and wider particle distribution, which could be considered for graded utilization depending on its size. The nutrients composition of river and lake sediments was usually stable and special, with lower nitrogen and phosphorus content but higher potassium levels. The sources of heavy metals and persistent organic pollutants in multisource sludge were correlated, generally much higher among municipal sludge than dredged sludge and river and lake sediments, which were the most important limitation for final land utilization. Despite various properties of multisource sludge, the final fate and destination have some overall similarities, which need to be supplemented and improved by standards and laws. The study provided a preliminary analysis of suitable technical routes for municipal sludge, dredged sludge, river and lake sediments based on their different characteristics respectively, which was of great significance for multisource sludge co-treatment and disposal in the future of China.


Assuntos
Rios , Esgotos , Lagos , Cidades , Fósforo
10.
J Mass Spectrom ; 57(12): e4899, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36517208

RESUMO

Oseltamivir phosphate is widely used to treat and prevent influenza, and is available in the form of capsules, powder for oral suspension, pediatric solutions, and granules. Because of the amino group, oseltamivir is easy to react with the excipients of the formulation to generate drug-excipient interaction impurities. In this research, two degradation products in a commercial oseltamivir phosphate powder for oral suspension due to interaction between API and citrate were investigated. They were characterized to be 3-((-6-acetamido-3-(ethoxycarbonyl)-5-(pentan-3-yloxy)cyclohex-3-en-1-yl)carbamoyl)-3-hydroxypentanedioic acid and 2-(2-((-6-acetamido-3-(ethoxycarbonyl)-5-(pentan-3-yloxy)cyclohex-3-en-1-yl)amino)-2-oxoethyl)-2-hydroxysuccinic acid by MS and NMR, respectively. Furthermore, the formation mechanisms of these impurities were verified, and the method of analysis of covariance was used to assess the rate of impurities' degradation. HIGHLIGHTS: Two excipient interaction degradation products in commercial oseltamivir phosphate powder for oral suspension were studied and elucidated in detail via LC-MS/MS and NMR. The incompatibility risk of pH conditioners such as citrate and citric acid with formulations that contain an amino group was disclosed in this article. Analysis of covariance was demonstrated to assess the impact of various formulations and preparation techniques on the rate of impurity degradation.


Assuntos
Excipientes , Oseltamivir , Humanos , Criança , Oseltamivir/química , Excipientes/química , Pós , Cromatografia Líquida , Espectrometria de Massas em Tandem , Contaminação de Medicamentos , Fosfatos , Citratos
11.
Front Psychol ; 13: 992245, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312178

RESUMO

A growing body of evidence suggests that engagement in episodic future thinking (EFT) could reduce delay discounting rates. However, little is known about whether individual differences in the ability of EFT are associated with differences in delay discounting in young adults. In the present study, this association was tested in healthy college students (n = 106, 19.98 ± 1.56 years), and the neural basis underlying this association was also examined using voxel-based morphometry (VBM) method. Behavioral analysis indicated that individual differences in EFT ability can significantly negatively predict discounting rates. VBM analysis first revealed that the EFT score positively correlated with gray matter volume (GMV) of a cluster in hippocampus, while negatively correlated with GMV of a cluster in rostral anterior cingulate cortex. We also found the GMV of a cluster in the mPFC was positively correlated with delay discounting. ROI analysis further revealed that individual differences in delay discounting could be reliably predicted by the GMV in the hippocampus and mPFC. The final mediation analysis showed that the GMV of the hippocampus plays a significant mediating role in the association between EFT and delay discounting, and the indirect effect of the hippocampal GMV accounts for 33.2% of the total effect. Our results suggest that individuals' EFT ability may be an important determinant of differences in delay discounting, and highlight the hippocampal structure as a neural biomarker for explaining the association between EFT ability and delay discounting.

12.
Int Immunopharmacol ; 111: 108855, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35905560

RESUMO

Retinoblastoma is a most frequently occurring primary intraocular tumor in infancy and children, highlighting the requirement to find and develop novel and more effective therapeutic approaches. Wedelolactone (WDL), a nature compound isolated from E. prostrata, exhibits multiple biological activities through regulating various signaling pathways; however, its potential influences on retinoblastoma progression are still unknown, and thus was investigated in our study, as well as the underlying mechanisms. Here, we found that WDL treatments significantly reduced the proliferation of retinoblastoma cells by inducing apoptosis and pyroptosis through increasing Caspase-3, Caspase-1, gasdermin E (GSDME) and gasdermin D (GSDMD) activation. Mitochondrial impairment and reactive oxygen species (ROS) generation were considerably up-regulated in WDL-incubated retinoblastoma cells through a dose-dependent manner. Notably, we found that ROS scavenge significantly abolished the function of WDL to provoke apoptosis and pyroptosis in retinoblastoma cell lines, revealing that ROS was required for WDL to perform its anti-cancer role in retinoblastoma. Moreover, our in vivo experiments indicated that WDL administration significantly reduced the tumor growth in the established retinoblastoma mouse models with undetectable toxicity. Collectively, these findings highlighted the potential of WDL to inhibit the growth and induce cell death of retinoblastoma in vitro and in vivo, and thereby showed promise as a therapeutic agent for the treatment of retinoblastoma.


Assuntos
Neoplasias da Retina , Retinoblastoma , Animais , Apoptose , Cumarínicos , Camundongos , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico
13.
Neuroscience ; 482: 53-63, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34923040

RESUMO

Academic self-concept, which can be defined as one's beliefs about their academic ability, plays an important role in students' future academic achievement. Here, we examined the neuroanatomical substrates underlying academic self-concept in 92 school-aged children (9.90 ± 0.85 years, 41 girls) using voxel-based morphometry of images obtained by structural magnetic resonance imaging. Our results revealed a significant positive correlation between academic self-concept and achievement 1 year after assessment. Whole-brain regression analyses found that gray matter volume in the right dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC) was negatively associated with academic self-concept. Region of interest analyses further showed that regional gray matter volume in the right DLPFC could significantly predict achievement 1 year after assessment. Notably, mediation analyses suggested that regional gray matter volume in the right DLPFC mediated the effect of academic self-concept on students' future academic achievement.


Assuntos
Sucesso Acadêmico , Encéfalo/patologia , Criança , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem
14.
Front Cardiovasc Med ; 9: 1053697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620624

RESUMO

Background: Most deaths from coronary artery disease (CAD) are due to acute myocardial infarction (AMI). There is an urgent need for early AMI detection, particularly in patients with stable CAD. 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of cardiovascular diseases, while little research examined 5mC regulators in CAD to AMI progression. Method: Two datasets (GSE59867 and GSE62646) were downloaded from Gene Expression Omnibus (GEO) database, and 21 m5C regulators were extracted from previous literature. Dysregulated 5mC regulators were screened out by "limma." The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm were employed to identify hub 5mC regulators in CAD to AMI progression, and 43 clinical samples (Quantitative real-time PCR) were performed for expression validation. Then a logistic model was built to construct 5mC regulator signatures, and a series of bioinformatics algorithms were performed for model validation. Besides, 5mC-associated molecular clusters were studied via unsupervised clustering analysis, and correlation analysis between immunocyte and 5mC regulators in each cluster was conducted. Results: Nine hub 5mC regulators were identified. A robust model was constructed, and its prominent classification accuracy was verified via ROC curve analysis (area under the curve [AUC] = 0.936 in the training cohort and AUC = 0.888 in the external validation cohort). Besides, the clinical effect of the model was validated by decision curve analysis. Then, 5mC modification clusters in AMI patients were identified, along with the immunocyte infiltration levels of each cluster. The correlation analysis found the strongest correlations were TET3-Mast cell in cluster-1 and TET3-MDSC in cluster-2. Conclusion: Nine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD.

15.
Sci Total Environ ; 801: 149609, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34419907

RESUMO

Sewage sludge was rich in pollutants such as heavy metals, nutrients and persistent organic pollutants. Anaerobic digestion can effectively degrade the pollutants while achieving sludge stabilization and reduction. This study took a sludge treatment plant located in Anhui Province, China as a case study, investigating the variations of multiple substances and particle size distribution during sludge anaerobic digestion-solar drying-land utilization process. The results demonstrated anaerobic digestion had a positive effect on the removal of heavy metals, nutrients and persistent organic pollutants, for polycyclic aromatic hydrocarbons, antibiotics and disinfection by-products with 41.38%, 62.26% and 68.68%, respectively, which were related to their molecular weight and structure. Large amounts of heavy metals would flow away with liquid digestate, in which Cr and Hg were the most and least, 90.44% and 41.95% respectively. The degradation of extracellular polymers in this process led to a decrease in particle size distribution, which caused the deterioration of sludge dewatering performance. Nutrients and water content increased and decreased respectively during solar drying along with the volatilization of organic matter under high temperature, which was beneficial for the final sludge product to subsequent land utilization. No significant correlation was demonstrated between heavy metals and sludge properties besides electrical conductivity. The study provided a new thinking on the variations of different substances and the way of actual treatment and disposal from the perspective of sludge anaerobic digestion-solar drying-land utilization process, which had a considerable significance for the further promotion and application of anaerobic digestion process in China's engineering community.


Assuntos
Metais Pesados , Esgotos , Anaerobiose , Nutrientes , Tamanho da Partícula , Eliminação de Resíduos Líquidos
16.
Medicine (Baltimore) ; 100(19): e25870, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106637

RESUMO

INTRODUCTION: Intra-arterial chemotherapy (IAC) has been used successfully for unilateral and bilateral eye disease with advanced or less advanced intraocular disease and of children as young as 3 months of age. In this study, we expanded the use of IAC to eyes of two infants with very low birthweight (birth weight of 1000-1500 g) and retinoblastoma. PATIENT CONCERNS: The ophthalmologists refused to give patients intravenous chemotherapy (IVC), considering the risk of IVC because of the low body weight. DIAGNOSIS: Two patients were diagnosed unilateral eye retinoblastoma at 31 days old and 27 days old respectively when newborn fundus screening. INTERVENTIONS: Chemotherapeutic agents were injected into the ophthalmic artery during the four IAC session. The two patients' oculars were preserved due to calcification during follow-up periods to the final IAC. OUTCOMES: Complications included eyelid edema in the patient #1 and neutropenia in both patients. No fever, sepsis and other systemic toxic effects were observed. After two successful IAC treatment for each patient, their oculars were all preserved without serious complications. LESSONS: Our center for the first time reported the management of retinoblastoma in very low birthweight infants with especially challenging and we recommend this to be useful to the patient community.


Assuntos
Antineoplásicos/uso terapêutico , Recém-Nascido de muito Baixo Peso , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Infusões Intra-Arteriais , Artéria Oftálmica
17.
Transl Pediatr ; 10(12): 3194-3201, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35070833

RESUMO

BACKGROUND: This study aimed to analyze the angiographic characteristics of kaposiform hemangioendothelioma (KHE) and investigate the value of transcatheter arterial embolization (TAE) therapy. METHODS: The clinical data of infants diagnosed with KHE at the department from June 2013 to June 2020 were retrospectively analyzed. Of these, 34 infants received TAE therapy. The efficacy of the treatment was evaluated 4 weeks after the therapy. The angiographic characteristics were analyzed by comparing them with the angiographic characteristics of infantile hemangioma (IH), and the times of TAE therapy and the platelet level after each TAE therapy in infants with KHE were summarized. RESULTS: The present study showed that the capillary blush of KHE was irregular with an obscure boundary and nonuniform distribution. Many fine feeding arteries were present. The diameter of the feeding arteries was disproportionate to the volume of the tumor blush. The normal arteries were usually embedded in the tumor blush. The angiography of common IH in infants also showed tumor blush, but it was usually round with a clear boundary and uniform staining, and was distributed on 1 side of the normal arterial trunk. The infants with KHE received TAE therapy for 2 to 5 times/case, with a total of 104.0 times, with an average of 3.1±0.8/case. Among which, the platelets continued to decline for 9 times after TAE therapy and the platelets increased to ≥100×109/L in 7.8±3.2 days for 95 times after TAE therapy, The average relapse time was 30.0±15.9 days. CONCLUSIONS: The feeding arteries of KHE were numerous and fine and were not easily embolized. The application of TAE may rapidly improve the platelet level, but the long-term effect is poor.

18.
Am J Physiol Heart Circ Physiol ; 320(2): H867-H880, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356961

RESUMO

Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. ß2-Adrenergic receptor (ß2AR) is a novel and key target for EPC homing. Here, we proposed that attenuated ß2AR signaling contributes to EPCs dysfunction, whereas enhanced ß2AR signaling restores EPCs' functions in hypertension. EPCs derived from hypertensive patients exhibited reduced cell number, impaired in vitro migratory and adhesion abilities, and impaired re-endothelialization after transplantation in nude mice with carotid artery injury. ß2AR expression of EPCs from hypertensive patients was markedly downregulated, whereas the phosphorylation of the p38 mitogen-activated protein kinase (p38-MAPK) was elevated. The cleaved caspase-3 levels were elevated in EPCs. The overexpression of ß2AR in EPCs from hypertensive patients inhibited p38-MAPK signaling, whereas it enhanced in vitro EPC proliferation, migration, and adhesion and in vivo re-endothelialization. The ß2AR-mediated effects were attenuated by treating the EPCs with a neutralizing monoclonal antibody against ß2AR, which could be partially antagonized by the p38-MAPK inhibitor SB203580. Moreover, shear stress stimulation, a classic nonpharmacological intervention, increased the phosphorylation levels of ß2AR and enhanced the in vitro and in vivo functions of EPCs from hypertensive patients. Collectively, the current investigation demonstrated that impaired ß2AR/p38-MAPK/caspase-3 signaling at least partially reduced the re-endothelialization capacity of EPCs from hypertensive patients. Restoration of ß2AR expression and shear stress treatment could improve their endothelial repair capacity by regulating the p38-MAPK/caspase-3 signaling pathway. The clinical significance of ß2AR in endothelium repair still requires further investigation.NEW & NOTEWORTHY Impaired ß2-adrenergic receptor (ß2AR) expression with an elevation of p38-MAPK/caspase-3 signaling at least partially contributes to the decline of re-endothelialization capacity of late endothelial progenitor cells (EPCs) from hypertensive patients. ß2AR gene transfer and shear stress treatment improve the late EPC-mediated enhancement of the re-endothelialization capacity in hypertensive patients through activating ß2AR/p38-MAPK/caspase-3 signaling. The present study is the first to reveal the potential molecular mechanism of the impaired endothelium-reparative capacity of late EPCs in hypertension after vascular injury and strongly suggests that ß2AR is a novel and crucial therapeutic target for increasing EPC-mediated re-endothelialization capacity in hypertension.


Assuntos
Lesões das Artérias Carótidas/prevenção & controle , Proliferação de Células , Células Progenitoras Endoteliais/metabolismo , Hipertensão/metabolismo , Reepitelização , Receptores Adrenérgicos beta 2/metabolismo , Animais , Apoptose , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Estudos de Casos e Controles , Caspase 3/metabolismo , Adesão Celular , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Células Progenitoras Endoteliais/transplante , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipertensão/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Ann Transl Med ; 8(20): 1318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209898

RESUMO

BACKGROUND: Physiological fluid shear stress has been shown to have a beneficial impact on vascular homeostasis. Endothelial progenitor cells (EPCs) make a significant contribution to maintaining endothelial integrity. Therefore, we hypothesised that shear stress-induced endothelium protection plays a role in hydrogen sulphide (H2S) production and up-regulation of cystathionine γ-lyase (CSE) expression in EPCs. METHODS: Human EPC-derived CSE activity was detected by colorimetric assay, and H2S production was evaluated by membrane adsorption method. Cell proliferation, migration, and adhesion were assessed by MTT, Transwell, and endothelial cell-mediated adhesion assays, respectively. Real-time polymerase chain reaction (RT-PCR) was carried out to analyse gene expression. Protein expression was analysed by western blot. RESULTS: Human EPCs were treated with shear stress levels of 5-25 dyn/cm2 for up to 3 h, and 25 dyn/cm2 for up to 24 h. H2S production and CSE mRNA expression in the EPCs were increased by shear stress in a dose-dependent manner in vitro. Likewise, time-dependent shear stress also significantly enhanced CSE protein expression. Compared to static condition, shear stress improved EPCs proliferation, migration and adhesion capacity. Knockdown of CSE expression by small interfering RNA substantially eliminated the shear stress-induced above functions of human EPCs in vitro. CONCLUSIONS: This study gives new insight into the regulatory effect of physiological shear stress on the CSE/H2S system in human EPCs. Our findings may contribute to the development of vascular protective research, although the relevant evidence is admittedly indirect.

20.
Infect Drug Resist ; 13: 4147-4154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244244

RESUMO

PURPOSE: To predict the risk of hospital deaths in patients with hospital-acquired pneumonia (HAP) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) infection. PATIENTS AND METHODS: A total of 366 patients who were diagnosed with HAP caused by MDR-AB infection were enrolled between January 2013 and December 2016. The sociological characteristics and clinical data of these cases were collected. Univariate and multivariate logistic analyses were used to explore the risk factors of hospital deaths before medication and after drug withdrawal. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to assess the predictive effectiveness of the models with or without the adjustment. RESULTS: Hospital deaths occurred in 142 cases (38.80%). The results showed that acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores before medication and after drug withdrawal were associated with the risk of hospital deaths. Adjusting the covariants including the age, autoimmune disease, venous cannula, transfer of patients from other hospitals, and APACHE II score at admission, then no differences were discovered in predicting the hospital deaths between adjusted APACHE II and adjusted SOFA scores before medication (AUC: 0.808 vs 0.803, P =0.614) and after drug withdrawal (AUC: 0.876 vs 0.878, P =0.789). CONCLUSION: Before medication or after drug withdrawal, the adjusted APACHE II and adjusted SOFA scores all performed well in determining the predictive effectiveness of the hospital deaths in patients with HAP caused by MDR-AB infection, indicating that the appropriate infection control may reduce the occurrence of nosocomial deaths and improve the prognosis.

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