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The growing use of nanomaterials has sparked significant interest in assessing the insect toxicities of nanoparticles. The silkworm, as an economically important insect, serves as a promising model for studying how insects respond to harmful substances. Here, we conducted a comprehensive investigation on the impact of graphene oxide (GO) on silkworms using a combination of physiological and transcriptome analyses. GO can enter the midguts and posterior silk glands of silkworms. High GO concentrations (> 25â¯mg/L) significantly (P < 0.01) inhibited larval growth. Additionally, GO (> 5â¯mg/L) significantly reduced the cocooning rate, and GO (> 15â¯mg/L) hindered oviduct development and egg laying in silkworms. GO increased the reactive oxygen species content and regulated catalase activity, suggesting that it may affect insect growth by regulating reactive oxygen detoxification. The transcriptome data analysis showed that 35 metabolism-related genes and 20 ribosome biogenesis-related genes were differentially expressed in response to GO, and their expression levels were highly correlated. Finally, we propose that a Ribosome biogenesis-Metabolic signaling network is involved in responses to GO. The research provides a new perspective on the molecular responses of insects to GO.
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Bombyx , Grafite , Larva , Espécies Reativas de Oxigênio , Transcriptoma , Animais , Grafite/toxicidade , Bombyx/efeitos dos fármacos , Bombyx/genética , Bombyx/crescimento & desenvolvimento , Transcriptoma/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/genética , Espécies Reativas de Oxigênio/metabolismo , Feminino , Perfilação da Expressão GênicaRESUMO
Selective neuronal vulnerability to protein aggregation is found in many neurodegenerative diseases including Alzheimer's disease (AD). Understanding the molecular origins of this selective vulnerability is, therefore, of fundamental importance. Tau protein aggregates have been found in Wolframin (WFS1)-expressing excitatory neurons in the entorhinal cortex, one of the earliest affected regions in AD. The role of WFS1 in Tauopathies and its levels in tau pathology-associated neurodegeneration, however, is largely unknown. Here we report that WFS1 deficiency is associated with increased tau pathology and neurodegeneration, whereas overexpression of WFS1 reduces those changes. We also find that WFS1 interacts with tau protein and controls the susceptibility to tau pathology. Furthermore, chronic ER stress and autophagy-lysosome pathway (ALP)-associated genes are enriched in WFS1-high excitatory neurons in human AD at early Braak stages. The protein levels of ER stress and autophagy-lysosome pathway (ALP)-associated proteins are changed in tau transgenic mice with WFS1 deficiency, while overexpression of WFS1 reverses those changes. This work demonstrates a possible role for WFS1 in the regulation of tau pathology and neurodegeneration via chronic ER stress and the downstream ALP. Our findings provide insights into mechanisms that underpin selective neuronal vulnerability, and for developing new therapeutics to protect vulnerable neurons in AD.
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Doença de Alzheimer , Tauopatias , Doença de Alzheimer/patologia , Animais , Lisossomos/metabolismo , Camundongos , Camundongos Transgênicos , Neurônios/patologia , Agregados Proteicos , Tauopatias/patologiaRESUMO
Hyperlipidemia is an important factor in the induction of cardiovascular diseases. However, the molecular mechanisms underlying the vascular injury involved in hyperlipidemia remains unclear. This study aimed to investigate the Notch pathway of endothelial progenitor cells (EPCs) in reendothelialization after vascular injury and to explore the involvement of Notch pathway in the senescence of EPCs. Our results demonstrated that high-fat diet (HFD) treatment inhibited reendothelialization after vascular injury in the mice model. In vitro studies showed that 7-ketocholesterol (7-keto) stimulation induced senescence in the isolated EPCs from mice. In addition, 7-keto markedly upregulated the protein expression of Notch1 and Delta-like ligand 4 and induced the transport of notch intracellular domain (NICD) to the nucleus. Mechanistically, treatment with NICD inhibitor reduced the senescence of the EPCs stimulated by cholesterol. In summary, our results showed that HFD treatment caused the disruption of reendothelialization after vascular injury in the mouse model. In vitro studies indicated that 7-keto-induced senescence of EPCs was at least via the activation of the Notch1 pathway. Mechanistic data suggested that 7-keto may activate the Notch1 pathway by regulating the generation and transport of NICD to the nucleus. Future investigations are warranted to confirm the role of Notch1 in the dysfunction of EPCs during obesity.
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Células Progenitoras Endoteliais/metabolismo , Hipercolesterolemia/metabolismo , Animais , Senescência Celular , Humanos , Masculino , CamundongosRESUMO
BACKGROUND/AIMS: The aim of present study was to test the hypothesis that preconditioning with sodium hydrosulfide (NaHS) could enhance the capacity of migration, adhesion and proliferation of endothelial progenitor cells (EPCs) in vitro, and also could improve the efficacy of EPCs transplantation for re-endothelialization in nude mice with carotid artery injury. The paper further addressed the underlying mechanisms. METHODS: EPCs were isolated from peripheral blood mononuclear cells of healthy male volunteers and the markers of EPCs were analyzed by flow cytometry. Thereafter, different concentrations of NaHS (25, 50, 100, 200 and 500 uM) were used for preconditioning EPCs. In vitro and in vivo migration, adhesion and proliferation as well as nitric oxide (NO) production of EPCs were evaluated. Carotid artery injury model was produced in nude mice and thereafter, NaHS-preconditioned EPCs were transplanted in order to evaluate their capacity of re-endothelialization. RESULTS: Cellular immuno-staining showed that isolated cells expressed the key markers of EPCs. In vitro, EPCs proliferation rates and NO production were gradually increased in a NaHS-concentration dependent manner, while these benefits were blocked at a concentration of 500 uM NaHS. Similarly, the migration and adhesion rates of EPCs were also increased the most prominently at a concentration of 200 µM NaHS. In vivo, compared to the control group, treatment with NaHS-preconditioned EPCs significantly enhanced the capacity of re-endothelialization of EPCs. Fluorescent microscope revealed that there were more EPCs homing to the injury vessels in the NaHS-preconditioned EPCs group than the non-preconditioned group. With the administration of AMPK or eNOS inhibitors respectively, the above benefits of NaHS-preconditioning were abrogated. CONCLUSION: These results suggested that NaHS-preconditioning enhanced the biological function and re-endothelialization of EPCs through the AMPK/eNOS signaling pathway.
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Lesões das Artérias Carótidas/terapia , Proliferação de Células/efeitos dos fármacos , Células Progenitoras Endoteliais/transplante , Sulfeto de Hidrogênio/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Animais , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/veterinária , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Masculino , Camundongos , Camundongos Nus , Microscopia de Fluorescência , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: To evaluate association of 24 h-systolic blood pressure (SBP) variability and obstructive sleep apnea (OSA) as defined by the apnea-hypopnea index ≥5/h; and association of 24 h-SBP variability and prevalent cardiovascular disease (CVD) in OSA patients. METHODS: Participants underwent polysomongraphy to evaluate the presence of OSA, and 24 h-ambulatory blood pressure monitoring was applied to evaluate 24 h-SBP variability as indexed by weighted 24 h-standard deviation (SD) of SBP. Between-group differences were evaluated in participants with and without OSA. Participants with OSA were divided into high and low 24 h-SBP variability groups and between-group differences were evaluated. RESULTS: Mean age of 384 participants was 50 years old and 42.2% had OSA. Mean 24 h-systolic/diastolic BP were 130/78 mmHg, with mean weighted 24 h-SD of systolic/diastolic BP were 12.9/7.3 mmHg. Compared to those without OSA, OSA participants had higher clinic-, 24 h-, daytime- and nighttime-SBP, and weighted 24 h, daytime- and nighttime-SD of SBP. Age, prevalent CVD and OSA, usage of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker and diuretic were significantly associated with 24 h-SBP variability. In OSA patients, compared to those with low variability, participants with high variability had higher weighted 24 h, daytime- and nighttime-SD of SBP. After adjusted for covariates including clinic-SBP and 24 h-SBP, per 1-SD increment weighted 24 h-SD of SBP was associated with 21% increased prevalent CVD. CONCLUSIONS: Patients with newly-diagnosed OSA have higher 24 h-SBP variability compared to those without OSA; in OSA patients, increased 24 h-SBP variability is associated with increased prevalence of CVD.
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Pressão Sanguínea , Doenças Cardiovasculares/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Prevalência , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Sístole , Fatores de TempoRESUMO
Background: Allergen immunotherapy (AIT) is still the only treatment that may affect the natural cause of allergic disease. This study is to investigate whether an accelerated up-dosing scheme for subcutaneous allergen immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract is as safe as the standard 3-strengths dose-escalation scheme in children with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma in China. Methods: In this multicenter, open label, randomized controlled trial, the children aged 5-14 years were randomized 1:1 either to One Strength group or the Standard group. The dose escalation scheme for patients in the One Strength group included 6 injections of strength 3, whereas the Standard group comprised 14 injections using strength 1, 2, and 3. All treatment-emergent adverse events (TEAEs) were recorded and analyzed. The 5-point Likert scale was used to assess tolerability (ChiCTR2100050311). Results: Overall, 101 children were included in the Safety Set (One Strength group: 50 vs. Standard group: 51). A total of 26 TEAEs were reported for 15 children. TEAEs related to AIT occurred in 10 % of the children in the One Strength group and 11.8 % of the Standard group. The number of systemic adverse reactions was comparable in both groups (One Strength: 5 vs. Standard: 4). No serious TEAEs was recorded for either group. 90.0 % of patients in the One Strength group reached the maintenance dose without an interventional dose adjustment due to adverse events, compared to 78.4 % in the Standard group. All patients who completed the dose-escalation phase reached the recommended maintenance dose of 1.0 ml of strength 3.Investigators and patients rated the tolerability of the One Strength regimen slightly better than the Standard scheme. Conclusions: This exploratory study suggests that the accelerated One Strength dose-escalation scheme is comparable in safety and tolerability to the Standard regimen. However, due to the preliminary nature and small sample size, further research with larger sample sizes and robust study designs is necessary for confirmation.
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Accurate reconstruction of the brain activities from electroencephalography and magnetoencephalography (E/MEG) remains a long-standing challenge for the intrinsic ill-posedness in the inverse problem. In this study, to address this issue, we propose a novel data-driven source imaging framework based on sparse Bayesian learning and deep neural network (SI-SBLNN). Within this framework, the variational inference in conventional algorithm, which is built upon sparse Bayesian learning, is compressed via constructing a straightforward mapping from measurements to latent sparseness encoding parameters using deep neural network. The network is trained with synthesized data derived from the probabilistic graphical model embedded in the conventional algorithm. We achieved a realization of this framework with the algorithm, source imaging based on spatio-temporal basis function (SI-STBF), as backbone. In numerical simulations, the proposed algorithm validated its availability for different head models and robustness against distinct intensities of the noise. Meanwhile, it acquired superior performance compared to SI-STBF and several benchmarks in a variety of source configurations. Additionally, in real data experiments, it obtained the concordant results with the prior studies.
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Mapeamento Encefálico , Magnetoencefalografia , Humanos , Mapeamento Encefálico/métodos , Teorema de Bayes , Magnetoencefalografia/métodos , Eletroencefalografia/métodos , Redes Neurais de Computação , Algoritmos , Fenômenos Eletromagnéticos , EncéfaloRESUMO
Biodegradable plastic is considered one of the most promising alternatives to agricultural mulch. However, the impact of biodegradable microplastics on agricultural ecosystems is still lacking. We conducted a controlled experiment with polylactic acid microplastics (PLA MPs) to examine the effects of biodegradable plastic on soil properties, corn growth, the microbial community and hotspots of enzyme activity. The results showed that PLA MPs in soil significantly reduced the soil pH value but increased the soil C:N ratio. High levels of PLA MPs significantly reduced the biomass of plant shoots and roots as well as chlorophyll, leaf C and N and root N contents. PLA MPs increased bacterial abundance but decreased the abundance of dominant fungal taxa. As the level of PLA MPs increased, the soil bacterial community structure became more complex, while the fungal community became more singular. The results of the in situ zymogram showed that low levels of PLA MPs increased the hotspots of enzyme activity. The effect of PLA MPs on enzyme activity hotspots was regulated by a combination of soil properties and microbial diversity. Generally, the addition of PLA MPs at high concentrations will have a negative impact on soil characteristics, soil microbials and plant growth in a short period of time. Therefore, we should be aware of the potential risks of biodegradable plastic to agricultural ecosystems.
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Plásticos Biodegradáveis , Microbiota , Microplásticos , Plásticos/toxicidade , Poliésteres , Solo , Microbiologia do SoloRESUMO
Background: The incidence of thyroid carcinoma (THCA), the most common endocrine tumor, is continuously increasing worldwide. Although the overall prognosis of THCA is good, patients with distant metastases exhibit a mortality rate of 5-20%. Methods: To improve the diagnosis and overall prognosis of patients with thyroid cancer, we screened specific candidate neoantigen genes in early- and late-stage THCA by analyzing the transcriptome and somatic cell mutations in this study. Results: The top five early-stage neoantigen-related genes (NRGs) were G protein-coupled receptor 4 [GPR4], chondroitin sulfate proteoglycan 4 [CSPG4], teneurin transmembrane protein 1 [TENM1], protein S 1 [PROS1], and thymidine kinase 1 [TK1], whereas the top five late-stage NRGs were cadherin 6 [CDH6], semaphorin 6B [SEMA6B], dysferlin [DYSF], xenotropic and polytropic retrovirus receptor 1 [XPR1], and ABR activator of RhoGEF and GTPase [ABR]. Subsequently, we used machine learning models to verify their ability to screen NRGs and analyze the correlations among NRGs, immune cell types, and immune checkpoint regulators. The use of candidate antigen genes resulted in a better diagnostic model (the area under the curve [AUC] value of the early-stage group [0.979] was higher than that of the late-stage group [0.959]). Then, a prognostic model was constructed to predict NRG survival, and the 1-, 3- and 5-year AUC values were 0.83, 0.87, and 0.86, respectively, which were closely related to different immune cell types. Comparison of the expression trends and mutation frequencies of NRGs in multiple tumors revealed their potential for the development of broad spectrum therapeutic drugs. Conclusion: In conclusion, the candidate NRGs identified in this study could potentially be used as therapeutic targets and diagnostic biomarkers for the development of novel broad spectrum therapeutic agents.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Exoma , Transcriptoma , Neoplasias da Glândula Tireoide/genéticaRESUMO
Accurate reconstruction of cortical activation from electroencephalography and magnetoencephalography (E/MEG) is a long-standing challenge because of the inherently ill-posed inverse problem. In this paper, a novel algorithm under the empirical Bayesian framework, source imaging with smoothness in spatial and temporal domains (SI-SST), is proposed to address this issue. In SI-SST, current sources are decomposed into the product of spatial smoothing kernel, sparseness encoding coefficients, and temporal basis functions (TBFs). Further smoothness is integrated in the temporal domain with the employment of an underlying autoregressive model. Because sparseness encoding coefficients are constructed depending on overlapped clusters over cortex in this model, we derived a novel update rule based on fixed-point criterion instead of the convexity based approach which becomes invalid in this scenario. Entire variables and hyper parameters are updated alternatively in the variational inference procedure. SI-SST was assessed by multiple metrics with both simulated and experimental datasets. In practice, SI-SST had the superior reconstruction performance in both spatial extents and temporal profiles compared to the benchmarks.
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Mapeamento Encefálico , Magnetoencefalografia , Algoritmos , Teorema de Bayes , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Fenômenos Eletromagnéticos , Humanos , Magnetoencefalografia/métodosRESUMO
Electromagnetic source imaging (ESI) requires solving a highly ill-posed inverse problem. To seek a unique solution, traditional ESI methods impose various forms of priors that may not accurately reflect the actual source properties, which may hinder their broad applications. To overcome this limitation, in this article, a novel data-synthesized spatiotemporally convolutional encoder-decoder network (DST-CedNet) method is proposed for ESI. The DST-CedNet recasts ESI as a machine learning problem, where discriminative learning and latent-space representations are integrated in a CedNet to learn a robust mapping from the measured electroencephalography/magnetoencephalography (E/MEG) signals to the brain activity. In particular, by incorporating prior knowledge regarding dynamical brain activities, a novel data synthesis strategy is devised to generate large-scale samples for effectively training CedNet. This stands in contrast to traditional ESI methods where the prior information is often enforced via constraints primarily aimed for mathematical convenience. Extensive numerical experiments as well as analysis of a real MEG and epilepsy EEG dataset demonstrate that the DST-CedNet outperforms several state-of-the-art ESI methods in robustly estimating source signals under a variety of source configurations.
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L.P. Li, J.W. Liang and H.J. Fu. An update on the association between traumatic brain injury and Alzheimer's disease: Focus on Tau pathology and synaptic dysfunction. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating conditions that have long-term consequences on individual's cognitive functions. Although TBI has been considered a risk factor for the development of AD, the link between TBI and AD is still in debate. Aggregation of hyperphosphorylated tau and intercorrelated synaptic dysfunction, two key pathological elements in both TBI and AD, play a pivotal role in mediating neurodegeneration and cognitive deficits, providing a mechanistic link between these two diseases. In the first part of this review, we analyze the experimental literatures on tau pathology in various TBI models and review the distribution, biological features and mechanisms of tau pathology following TBI with implications in AD pathogenesis. In the second part, we review evidences of TBI-mediated structural and functional impairments in synapses, with a focus on the overlapped mechanisms underlying synaptic abnormalities in both TBI and AD. Finally, future perspectives are proposed for uncovering the complex relationship between TBI and neurodegeneration, and developing potential therapeutic avenues for alleviating cognitive deficits after TBI.
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Doença de Alzheimer , Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Doença de Alzheimer/complicações , Lesões Encefálicas Traumáticas/complicações , Humanos , Sinapses , Proteínas tauRESUMO
Researchers have explored the influence of visual working memory (VWM) load on visual perception in the past decade. One of their key findings is that a high VWM load leads to reduced visual detection sensitivity to incoming visual stimuli. However, recent studies imply that persistent sensory processing continues after the memory array is offset. It is possible that the impaired visual detection is due to the sensory load of the residual sensory processing of the memory array (sensory load account) rather than the working memory load of the VWM task (VWM load account). We performed four experiments to examine the impacts on visual detection. Experiment 1 manipulated the retention time of the memory array while keeping the VWM load constant, revealing reduced visual detection along with retention time. Experiments 2 and 3 manipulated the VWM load while maintaining a constant sensory load, and visual detection was not affected. Experiment 4 affirmed that the findings in Experiments 1-3 were reliable. Together, the results of the current study suggest that the residual sensory load, rather than the VWM load of the VWM task, impairs visual detection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Memória de Curto Prazo , Percepção Visual , HumanosRESUMO
Accumulating evidence has shown that endothelial progenitor cell-derived exosomes (EPC-Exos) can ameliorate myocardial fibrosis. The purpose of the present study was to investigate the effects of EPC-Exos-derived microRNAs (miRNAs) on myocardial infarction (MI). A miRNA-Seq dataset of miRNAs differentially expressed between EPCs and exosomes was collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the miRNA expression indicated by miRNA-Seq. Immunofluorescence, cell proliferation, and angiogenesis assays were employed to investigate the effects of miRNAs on cardiac fibroblasts (CFs) in vitro. Interactions between miRNAs and their respective targets were examined via immunoblotting, qRT-PCR, and luciferase reporter assays. An MI rat model was constructed, and various staining and immunohistochemical assays were performed to explore the mechanisms underlying the miRNA-mediated effects on MI. miR-363-3p and miR-218-5p were enriched in EPC-Exos, and miR-218-5p and miR-363-3p mimic or inhibitor enhanced or suppressed CF proliferation and angiogenesis, respectively. miR-218-5p and miR-363-3p regulated p53 and junction-mediating and regulatory protein (JMY) by binding to the promoter region of p53 and the 3' untranslated region of JMY. Additionally, treatment of CFs with Exo-miR-218-5p or Exo-miR-363-3p upregulated p53 and downregulated JMY expression, promoted mesenchymal-endothelial transition, and inhibited myocardial fibrosis. Administration of exosomes containing miR-218-5p mimic or miR-363-3p mimic ameliorated left coronary artery ligation-induced MI and restored myocardial tissue integrity in the MI model rats. In summary, these results show that the protective ability of EPC-Exos against MI was mediated by the shuttled miR-218-5p or miR-363-3p via targeting of the p53/JMY signaling pathway.
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Células Progenitoras Endoteliais/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Animais , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transfecção , Proteína Supressora de Tumor p53/metabolismoRESUMO
The disruption of endothelial homeostasis is the hallmark of coronary artery disease (CAD) and psychological disorders such as anxiety/depression. Xinkeshu (XKS), a traditional Chinese patent medicine, plays an essential role in CAD and psychological condition; however, the mechanisms underlying the effects of XKS on the endothelial function and endogenous endothelium-repair capacity in CAD patients with anxiety/depression remain elusive. In this study, endothelial function and endothelial progenitor cell- (EPC-) mediated reendothelialization capacity were compared among age-matched healthy subjects, CAD patients with or without anxiety/depression. Besides, CAD patients with anxiety/depression received 1-month XKS treatment. Anxiety/depression symptoms were evaluated by Generalized Anxiety Disorder 7-item (GAD-7)/Patient Health Questionnaire-9 (PHQ-9) score, endothelial function was tested by flow mediated dilation (FMD) measurement, and EPC-mediated reendothelialization capacity was evaluated by a carotid artery injury model in nude mouse (n = 6) with the injection of XKS-incubated EPCs from CAD patients with anxiety/depression. The results showed that FMD and EPC-mediated reendothelialization capacity of CAD patients with anxiety/depression were compromised compared to healthy subjects and CAD patients without anxiety/depression. After 1 month of XKS treatment, FMD increased from 4.29 ± 1.65 to 4.87 ± 1.58% (P < 0.05) in CAD patients with anxiety/depression, whereas it remained unchanged in the controls. Moreover, XKS decreased GAD-7 and PHQ-9 scores. Meanwhile, incubating XKS enhanced in vivo reendothelialization capacity and in vitro apoptosis of EPCs from CAD patients with anxiety/depression, which was associated with the upregulation of CXC-chemokine receptor 7 (CXCR7) and inhibition of phosphorylation of p38 signaling. CXCR7 knockdown abolished the beneficial effects of XKS, which was rescued by p38 inhibitor SB203580. Our data demonstrate for the first time that XKS improves endothelial function and enhances EPC-mediated reendothelialization through CXCR7/p38/cleaved casepase-3 signaling and provides novel insight into the detailed mechanism of XKS in maintaining endothelial homeostasis in CAD patients with anxiety/depression.
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Ansiedade/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Doença da Artéria Coronariana/psicologia , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Vascular dysfunction is a key hallmark of hypertension and related cardiovascular outcomes. As a well-known hemodynamic disease, hypertension is characterized by abnormal ventricular-vascular interactions. Complementing non-invasive systemic hemodynamics in hypertensive vascular risk assessment is of promising significance. We aimed to investigate the effects of abnormal hemodynamic states other than elevated blood pressure on vascular damage and establish a united index of systemic hemodynamics for generalized vascular risk evaluation. Non-invasive systemic hemodynamics, assessed by impedance cardiography, was compared among blood pressure stages. Vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Systemic hemodynamics was obtained from a total of 88 enrollees with a mean (±SD) systolic blood pressure 140 (±17) mm Hg, and aged 17 to 91 years. Both stroke systemic vascular resistance index and left stroke work index exhibited a significant alteration among blood pressure stages (p < 0.001; p = 0.01, respectively), whereas heterogeneous hemodynamic and vascular function subsets existed within similar blood pressure. In addition, blood pressure categories failed to recognize between-group differences in endothelial dysfunction (p = 0.88) and arterial stiffness (p = 0.26). An increase in myocardial contractility and a parallel decrease in afterload was associated with the decline of vascular dysfunction. Systemic Hemodynamic Index (SHI), as a surrogate marker, demonstrated a significantly negative correlation with vascular damage index (VDI, r = -0.49, p < 0.001). These findings illustrate that systemic hemodynamics underlying hypertensives provides more vascular information. The SHI/VDI score may be a feasible tool for cardiovascular function assessment.
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Acute myocardial infarction (MI) is a common cardiovascular disease with high mortality. In this study, an injectable thermosensitive hydrogel of chitosan (CS)/dextran (DEX)/ß-glycerophosphate (ß-GP) loaded with umbilical cord mesenchymal stem cells (UCMSCs) was prepared for MI treatment. The good biocompatibility of hydrogels was confirmed by 3T3 cells and HUVECs culture study in vitro. HUVECs encapsulated in the hydrogels showed a cell delivery ability. Furthermore, the results indicated that hydrogel could encapsulate most of UCMSCs and the cells exhibited good viability in CS/ 1.0DEX/ß-GP hydrogels. The expression of cardiac markers of cTnI and Cx43 and signaling pathways of p-Akt and p-ERK1/2 were studied, and it showed that UCMSCs differentiate towards myocardium and has a great potential for therapeutic use of cardiac repair. In conclusion, the thermosensitive hydrogel of CS/1.0 DEX/ß-GP loaded UCMSCs was a promising candidate as cell delivery vehicle for cardiac repair to reconstitute damaged myocardium.
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Quitosana/química , Dextranos/química , Glicerofosfatos/química , Hidrogéis/química , Células 3T3 , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Conexina 43/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Reologia , Transdução de Sinais/efeitos dos fármacos , Alicerces Teciduais/química , Troponina I/metabolismoRESUMO
Although previous data showed that remote ischemic preconditioning (RIPC) has beneficial effect on blood pressure (BP) reduction, the efficacy of RIPC-induced decline in BP and the favorable humoral factors in hypertension is elusive. This present study is performed to evaluate whether RIPC reduces BP, improves microvascular endothelial function and increases circulating hSDF-1α generation in hypertension. Fifteen hypertensive patients received 3 periods of 5-min inflation/deflation of the forearm with a cuff on the upper arm daily for 30 days. Clinic and 24-h ambulatory blood pressure monitoring (ABPM) were examined before and after the end of this procedure. Microvascular endothelial function was measured by finger reactive hyperemia index (RHI) using the Endo-PAT 2000 device. The circulating hSDF-1α level was tested by ELISA. RIPC significantly decreased systolic BP (139.13 ± 6.68 versus 131.45 ± 7.45 mmHg) and diastolic BP (89.67 ± 4.98 versus 83.83 ± 6.65 mmHg), meanwhile 24-h ambulatory systolic and diastolic BP dropped from 136.33 ± 9.10 mmHg to 131.33 ± 7.12 mmHg and 87.60 ± 6.22 mmHg to 82.47 ± 4.47 mmHg respectively. RHI was improved (1.95 ± 0.34 versus 2.47 ± 0.44). Plasma hSDF-1α level was markedly increased after RIPC (1585.86 ± 167.17 versus 1719.54 ± 211.17 pg/ml). The increase in hSDF-1α level was associated with the fall in clinic and 24-h ABPM and rise in RHI. The present data suggests that RIPC may be a novel alternative or complementary intervention means to treat hypertension and protect endothelial function.
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Braço/irrigação sanguínea , Pressão Sanguínea , Quimiocina CXCL12/sangue , Endotélio Vascular/fisiopatologia , Hipertensão/terapia , Precondicionamento Isquêmico/métodos , Oclusão Terapêutica , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fluxo Sanguíneo Regional , Método Simples-Cego , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
A new operating approach by reducing the aeration time while keeping high intensity was evaluated for enhanced nutrients removal and maintenance of granular stability. Three aerobic granular sequencing batch reactors (SBR) performing simultaneous nitrification, denitrification and phosphorus removal (SNDPR) were run at different aeration time (120, 90, and 60â¯min). Aerobic granules could remain their integrity and stability over long-term operation under high aeration intensity and different time, and shorter aeration time favored the retention of biomass, better settleability, and more production of extracellular polymeric substances (EPS). Besides, efficient and stable reactor performance for carbon and phosphorus were achieved, especially, enhanced nitrogen removal was obtained due to reduction of aeration time. Further exploration revealed that the aeration time shaped the bacterial community in terms of diversity, composition, as well as the distribution of functional groups involving carbon, nitrogen and phosphorus removal.
Assuntos
Reatores Biológicos , Desnitrificação , Fósforo/isolamento & purificação , Nitrificação , Nitrogênio , Esgotos , Eliminação de Resíduos LíquidosRESUMO
INTRODUCTION: Previous studies have shown that endothelial cell senescence is involved in cardiovascular diseases such as cardiac fibrosis, atherosclerosis and heart failure. Accumulating evidence indicates that apelin exerts protective effects on ageing-related endothelial dysfunction. In this study, we aim to investigate the role of the apelin/APJ axis in angiotensin II (AngII)-induced endothelium senescence and its associated mechanisms. MATERIAL AND METHODS: Senescence-related ß-gal activity assay and western blot were used to evaluate human umbilical vein endothelial cell (HUVEC) senescence. In addition, DCFH-DA staining was carried out to detect the generation of reactive oxygen species (ROS). A validated, high-sensitivity real-time quantitative telomeric repeat amplification protocol (RQ-TRAP) was applied to determine telomerase activity in HUVECs, and a CCK-8 assay was employed to measure cellular viability. RESULTS: AngII induced an increase in SA-ß-Gal-positive cells and upregulation on expression of P21 and PAI-1 compared to the control group (p < 0.05), while apelin against this process (p < 0.05). The protective effects were attenuated when APJ, AMPK and SIRT1 expression was knocked down (p < 0.05). Furthermore, apelin reduced AngII-induced ROS generation and enhanced telomerase activity in HUVECs (p < 0.05), which contributed to increased HUVEC viability as assessed by the CCK-8 assay (p < 0.05). CONCLUSIONS: The apelin/APJ axis improved AngII-induced HUVEC senescence via the AMPK/SIRT1 signaling pathway, and the underlying mechanisms might be associated with reduced ROS production and enhanced telomerase activity.