Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 266
Filtrar
1.
J Immunol ; 206(8): 1752-1764, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811103

RESUMO

Macrophages play an important role in the pathogenesis of systemic lupus erythematosus-associated diffuse alveolar hemorrhage (DAH). The immunomodulation of macrophage responses might be a potential approach for the prevention and treatment of DAH. Erythropoietin (EPO) could regulate macrophage bioactivities by binding to the EPO receptor expressing on macrophages. This study assessed the effects of EPO on DAH protection using an immune-mediated DAH murine model with macrophages as the major contributor. A DAH murine model was established in female C57BL/6 mice by an i.p. injection of pristane. We found that EPO administration alleviates DAH by reducing pulmonary macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. EPO drove macrophages to the anti-inflammatory phenotype in the primary murine bone marrow-derived macrophages and macrophages cell line RAW 264.7 with LPS, IFN-γ, and IL-4 in vitro. Moreover, EPO treatment increases the expression of EPOR and decreases the expression of miR-494-3p, resulting in increased phosphorylation of JAK2 and STAT3. In conclusion, EPO can be a potential therapeutic agent in DAH by reducing cell apoptosis and regulating macrophage polarization through the EPOR/JAK2/STAT3 axis. Further studies are also needed to validate the direct target of miR-494-3p in regulating JAK2/STAT3 signaling transduction.

2.
J Neural Eng ; 18(5): 056012, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33821810

RESUMO

OBJECTIVE: Electroencephalogram (EEG) signals suffer inevitable interference from artifacts during the acquisition process. These artifacts make the analysis and interpretation of EEG data difficult. A major source of artifacts in EEGs is ocular activity. Therefore, it is important to remove ocular artifacts before further processing the EEG data. APPROACH: In this study, an automatic ocular artifact removal (AOAR) method for EEG signals is proposed based on non-negative matrix factorization (NMF) and empirical mode decomposition (EMD). First, the amplitude of EEG data was normalized in order to ensure its non-negativity. Then, the normalized EEG data were decomposed into a set of components using NMF. The components containing ocular artifacts were extracted automatically through the fractal dimension. Subsequently, the temporal activities of these components were adaptively decomposed into some intrinsic mode functions (IMFs) by EMD. The IMFs corresponding to ocular artifacts were removed. Finally, the de-noised EEG data were reconstructed. MAIN RESULTS: The proposed method was tested against seven other methods. In order to assess the effectiveness and reliability of the AOAR method in processing EEG data, experiments on ocular artifact removal were performed using simulated EEG data. Experimental results indicated that the proposed method was superior to the other methods in terms of root mean square error, signal-to-noise ratio (SNR) and correlation coefficient, especially in cases with a lower SNR. To further evaluate the potential applications of the proposed method in real life, the proposed method and others were applied to preprocess real EEG data recorded from children with and without attention-deficit/hyperactivity disorder (ADHD). After artifact rejection, the event-related potential feature was extracted for classification. The AOAR method was best at distinguishing the children with ADHD from the others. SIGNIFICANCE: These results indicate that the proposed AOAR method has excellent prospects for removing ocular artifacts from EEG data.

3.
Theranostics ; 11(9): 4403-4420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754068

RESUMO

Rationale: In breast cancer, high intratumor DNA methylation heterogeneity can lead to drug-resistant, metastasis and poor prognosis of tumors, which increases the complexity of cancer diagnosis and treatment. However, most studies are limited to average DNA methylation level of individual CpGs and ignore heterogeneous DNA methylation patterns of cell subpopulations within the tumor. Thus, quantifying the variability in DNA methylation pattern in sequencing reads is valuable for understanding intratumor heterogeneity. Methods: We performed Reduced Representation Bisulfite Sequencing and RNA sequencing for tumor core and tumor periphery regions within one breast tumor. By developing a method named "epialleJS" based on Jensen-Shannon divergence, we detected the differential epialleles between tumor core and tumor periphery (CPDEs). We then explored the correlation between intratumor methylation heterogeneity and hypoxic microenvironment in TCGA breast cancer cohort. Results: More than 70% of CPDEs had higher epipolymorphism in tumor core than tumor periphery, and these CPDEs had lower methylation in tumor core. The CPDEs with lower methylation in tumor core may associate with hypoxic tumor microenvironment. Moreover, we identified a signature of five hypoxia-related DNA methylation markers which can predict the prognosis of breast cancer patients, including a CpG site cg15190451 in gene SLC16A5. Furthermore, immunohistochemical analysis confirmed that the expression of SLC16A5 was associated with clinicopathological characteristics and survival of breast cancer patients. Conclusions: The analysis of intratumor DNA methylation heterogeneity based on epialleles reveals that disordered methylation patterns in tumor core are associated with hypoxic microenvironment, which provides a framework for understanding biological heterogeneous behavior and guidance for developing effective treatment schemes for breast cancer patients.

4.
Exp Cell Res ; 402(1): 112552, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711329

RESUMO

Endothelial dysfunction is an early step in the development of atherosclerotic cardiovascular disease. Iron overload can lead to excessive mitochondrial reactive oxygen species (mtROS) production, resulting in mitochondrial dysfunction and vascular endothelial cell (EC) damage. Mitoferrin 2 (Mfrn2) is an iron transporter in the inner mitochondrial membrane. This study aimed to assess whether Mfrn2 and mitochondrial iron overload were involved in atherosclerosis progression and to explore the potential mechanism. We observed significant upregulation of Mfrn2 in the arteries of high-fat diet (HFD)-fed Apolipoprotein E-/- (ApoE-/-) mice and in TNF-α-induced mouse aortic endothelial cells (MAECs). Mfrn2 gene silencing inhibited mitochondrial iron overload, stabilized mitochondrial membrane potential and improved mitochondrial function in TNF-α-induced MAECs. Vascular EC-specific knockdown of Mfrn2 in ApoE-/- mice markedly decreased atherosclerotic lesion formation and the levels of ICAM-1 in aortas and reduced monocyte infiltration into the vascular wall. Furthermore, TNF-α increased the binding of 14-3-3 epsilon (ε) and Mfrn2, preventing Mfrn2 degradation and leading to mitochondrial iron overload in ECs, while 14-3-3ε overexpression increased Mfrn2 stability by inhibiting its ubiquitination. Together, our results reveal that Mfrn2 deficiency attenuates endothelial dysfunction by decreasing iron levels within the mitochondria and mitochondrial dysfunction. These findings may provide new insights into preventive and therapeutic strategies against vascular endothelial dysfunction in atherosclerotic disease.

5.
J Neural Eng ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706292

RESUMO

OBJECTIVE: Electroencephalogram (EEG) signals are inevitably interfered by artifacts during the acquisition process. These artifacts make analysis and interpretation of EEG data difficult. A major source of artifacts in EEG is the ocular activity. Therefore, it is important to remove the ocular artifacts before further processing the EEG data. APPROACH: In this study, we proposed an automatic ocular artifacts removal (AOAR) method for EEG signals based on non-negative matrix factorization (NMF) and empirical mode decomposition (EMD). First, the amplitude of EEG data was normalized in order to ensure the non-negativity of EEG data. Then, the normalized EEG data were decomposed into a set of components using NMF. The components containing ocular artifacts were extracted automatically through fractal dimension. Subsequently, the temporal activities of these components were adaptively decomposed into some intrinsic mode functions (IMFs) by EMD. The IMFs corresponding to ocular artifacts were removed. Finally, the denoised EEG data were reconstructed. MAIN RESULTS: The proposed method was tested against the other seven methods. In order to assess the effectiveness and reliability of the AOAR method in processing EEG data, experiments on ocular artifacts removal were performed using semi-simulated EEG data. Experimental results indicated that the proposed method was superior to other methods in terms of root mean squared error, signal noise rate and correlation coefficient, especially in the cases with lower signal noise rate. To further evaluate the application potentials of the proposed method in real life, the proposed method with the counterparts were applied to preprocess the real EEG data recorded from children with and without attention-deficit/hyperactivity disorder (ADHD). After artifacts rejection, the ERP feature was extracted for classification. The AOAR performed the best for distinguishing the ADHD children from others. SIGNIFICANCE: These results indicate that the proposed AOAR method has great prospects in removing ocular artifacts from EEG.

6.
Chemosphere ; 271: 129740, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33736212

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) has been well acknowledged for its endocrine disruption and associated metabolic diseases, leading to the search for safer industrial alternatives including di-isononyl phthalate (DINP). However, safety data for the latter chemical has been relatively scarce particularly regarding potential damage to the kidney at low doses. Five-week-old ICR male mice were exposed to vehicle, DEHP or DINP (0.05 and 4.8 mg/kg bw) daily via gavage for 5 weeks. We observed increased levels of reactive oxygen species and malondialdehyde, decreased levels of reduced glutathione, in the kidney at higher dose for both chemicals suggestive of oxidative damage. Elevated levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 of the kidney further suggested inflammatory status as a result of phthalate exposure in both high dose groups. Targeted lipidomics demonstrated greatest changes in the kidney induced by high dose of DEHP, although DINP also induced significant changes in phospholipids diacylglycerides that are associated with lipid accumulation in glomerular podocytes and inflammatory responses. Our data suggest that oxidative stress may be involved in both DEHP- and DINP-induced renal lipidomic disruption and continue to question the suitability of DINP as proper DEHP substitute.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/toxicidade , Rim , Lipidômica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
7.
Front Immunol ; 12: 609406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746953

RESUMO

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function. Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance. Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity. Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.

8.
J Affect Disord ; 284: 229-237, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33618206

RESUMO

BACKGROUND: Individuals with generalized anxiety disorder (GAD) tend to worry exaggeratedly and uncontrollably about various daily routines. Previous studies have demonstrated that the GAD patients exhibited widespread alternations in both functional networks (FN) and structural networks (SN). However, the simultaneous alternations of the topological organization of FN, SN, as well as their couplings in GAD still remain unknown. METHODS: Using multimodal approach, we constructed FN from resting-state functional magnetic imaging (R-fMRI) data and SN from diffusion magnetic resonance imaging (dMRI) data of 32 adolescent GAD patients and 25 healthy controls (HC). Graph theory analysis was employed to investigate the topological properties of FN, SN, and FN-SN coupling. RESULTS: Compared to HC, the GAD patients showed disruptions in global (i.e., decreased clustering coefficient, global, and local efficiency) and subnetwork (i.e., reduced intermodular connections, rich club, and feeder connections) levels in FN. Abnormal global level properties (i.e., increased characteristic path length and reduced global efficiency) were also observed in SN. Altered FN-SN couplings in normalized characteristic path length and feeder connections were identified in the GAD patients. The identified network measures were correlated with anxiety severity in the GAD patients. LIMITATIONS: The sample size of the current study is small and the cross-sectional nature can not infer causal relationship. CONCLUSIONS: Our findings identified GAD-related topological alternations in both FN and SN, together with the couplings between FN and SN, providing us with a novel perspective for understanding the pathophysiological mechanisms of GAD.

9.
Mar Drugs ; 19(2)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562511

RESUMO

Fucoxanthin (FX), a natural carotenoid found in seaweed with multiple functional activities, is unstable with a poor water solubility that limits its utilization. This study aimed to improve FX's stability and bioavailability via the nano-encapsulation of FX in polyvinylpyrrolidone (PVP)-coated FX@PVP nanoparticles (NPs). The FX@PVP NPs were evaluated in terms of their morphology, stability, encapsulation efficiency (EE), loading capacity (LC), and in vitro release to optimize the encapsulation parameters, and a 1:8 FX:PVP ratio was found to perform the best with the highest EE (85.50 ± 0.19%) and LC (10.68 ± 0.15%) and improved FX stability. In addition, the FX@PVP NPs were shown to effectively deliver FX into Caco-2 cancer cells, and the accumulation of FX in these cancer cells showed pro-oxidative activities to ameliorate H2O2-induced damage and cell death. The FX@PVP NPs could potentially become a new therapeutical approach for targeted cancer treatment.

10.
FASEB J ; 35(2): e21367, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33508160

RESUMO

Millions of human deaths occur annually due to chronic kidney disease, caused by diabetic kidney disease (DKD). Despite having effective drugs controlling the hyperglycemia and high blood pressure, the incidence of DKD is increasing, which indicates the need for the development of novel therapies to control DKD. In this article, we discussed the recent advancements in the basic innate immune mechanisms in renal tissues triggered under the diabetes environment, leading to the pathogenesis and progression of DKD. We also summarized the currently available innate immune molecules-targeting therapies tested against DKD in clinical and preclinical settings, and highlighted additional drug targets that could potentially be employed for the treatment of DKD. The improved understanding of the disease pathogenesis may open avenues for the development of novel therapies to rein in DKD, which consequently, can reduce morbidity and mortality in humans in the future.

11.
Free Radic Biol Med ; 165: 137-151, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33497799

RESUMO

AIMS: Tissue engineering aims to improve the longevity of prosthetic heart valves. However, the optimal cell source has yet to be determined. This study aimed to establish a mechanistic rationale supporting the suitability of human adventitial pericytes (APCs). METHODS AND RESULTS: APCs were immunomagnetically sorted from saphenous vein leftovers of patients undergoing coronary artery bypass graft surgery and antigenically characterized for purity. Unlike bone marrow-derived mesenchymal stromal cells (BM-MSCs), APCs were resistant to calcification and delayed osteochondrogenic differentiation upon high phosphate (HP) induction, as assessed by cytochemistry and expression of osteogenic markers. Moreover, glycolysis was activated during osteogenic differentiation of BM-MSCs, whereas APCs showed no increase in glycolysis upon HP challenge. The microRNA-132-3p (miR-132), a known inhibitor of osteogenesis, was found constitutively expressed by APCs and upregulated following HP stimulation. The anti-calcific role of miR-132 was further corroborated by in silico analysis, luciferase assays in HEK293 cells, and transfecting APCs with miR-132 agomir and antagomir, followed by assessment of osteochondrogenic markers. Interestingly, treatment of swine cardiac valves with APC-derived conditioned medium conferred them with resistance to HP-induced osteogenesis, with this effect being negated when using the medium of miR-132-silenced APCs. Additionally, as an initial bioengineering step, APCs were successfully engrafted onto pericardium sheets, where they proliferated and promoted aortic endothelial cells attraction, a process mimicking valve endothelialization. CONCLUSIONS: Human APCs are resistant to calcification compared with BM-MSCs and convey the anti-calcific phenotype to heart valves through miR-132. These findings may open new important avenues for prosthetic valve cellularization.

12.
PLoS One ; 16(1): e0245209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444408

RESUMO

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/virologia , /fisiopatologia , Quercetina/farmacologia , Bases de Dados Factuais , Bases de Dados Genéticas , Humanos , Simulação de Acoplamento Molecular , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , /isolamento & purificação
13.
Bioorg Chem ; 108: 104561, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33349457

RESUMO

Although targeted therapy for renal cell carcinoma (RCC) has achieved good therapeutic effects in clinic, a considerable number of patients develop drug resistance over time. So, there is still an urgent need to develop new drugs for RCC treatment. As LSD1 is considered as a promising drug target in diverse cancers, including RCC, we tried to find new LSD1 inhibitor using drug repurposing strategy from a compound library, and fenoldopam, an FDA-approved drug, was identified as a potent LSD1 inhibitor with IC50 = 0.8974 µM in a reversible manner. Molecular docking predicted that fenoldopam occupied the FAD cavity of LSD1, forming hydrogen bonds with surrounding residues. Moreover, fenoldopam inactivated LSD1 and performed antiproliferative activity against ACHN cells and promoted cells apoptosis in vitro. Taken together, fenoldopam was identified as a novel LSD1 inhibitor firstly, and may serve as a new skeleton for RCC therapy.

14.
Cell Signal ; 80: 109900, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33370582

RESUMO

Low shear stress (LSS) plays a critical role in the development of atherosclerotic plaques and vascular inflammation. Previous studies have reported Akt phosphorylation induced by LSS. However, the mechanism and role of Akt activation remains unclear in LSS-induced endothelial dysfunction. In this study, our results demonstrated the increased phosphorylation of IKKε, TBK1 and Akt in HUVECs exposed to LSS. Furthermore, IKKε silencing using small interfering RNAs significantly reduced LSS-induced Akt phosphorylation. In contrast, silencing of TBK1 or inhibition of PI3K and mTORC2 had no effect on LSS-induced Akt phosphorylation. Notably, Akt inhibition markedly diminished LSS-induced expression of ICAM-1, VCAM-1 and MCP-1, as well as LSS-induced IRF3 phosphorylation and nuclear translocation, without affecting the activation of NF-κB and STAT1. Moreover, endothelial cell specific Akt overexpression mediated by adeno-associated virus markedly increased intimal ICAM-1 and IRF3 expression at LSS area of partially ligated carotid artery in mice. In brief, our findings suggest that LSS-induced Akt phosphorylation is positively regulated by IKKε and promotes IRF3 activation, leading to endothelial inflammation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33226850

RESUMO

Aims: To ascertain if human pericytes produce SPARC (acronym for Secreted Protein Acidic and Cysteine Rich), a matricellular protein implicated in the regulation of cell proliferation, migration, and cell-matrix interactions; clarify if SPARC expression in cardiac pericytes is modulated by hypoxia; and determine the functional consequences of SPARC silencing. Results: Starting from the recognition that the conditioned media (CM) of human pericytes promote proliferation and migration of cardiac stromal cells, we screened candidate mediators by mass-spectrometry analysis. Of the 14 high-confidence proteins (<1% FDR) identified in the bioactive fractions of the pericyte CM, SPARC emerged as the top-scored matricellular protein. SPARC expression was validated using ELISA and found to be upregulated by hypoxia/starvation in pericytes that express platelet-derived growth factor receptor α (PDGFRα). This subfraction is acknowledged to play a key role in extracellular matrix remodeling. Studies in patients with acute myocardial infarction showed that peripheral blood SPARC correlates with the levels of creatine kinase Mb, a marker of cardiac damage. Immunohistochemistry analyses of infarcted hearts revealed that SPARC is expressed in vascular and interstitial cells. Silencing of SPARC reduced the pericyte ability to secrete collagen1a1, without inhibiting the effects of CM on cardiac and endothelial cells. These data indicate that SPARC is enriched in the bioactive fraction of the pericyte CM, is induced by hypoxia and ischemia, and is essential for pericyte ability to produce collagen. Innovation: This study newly indicates that pericytes are a source of the matricellular protein SPARC. Conclusion: Modulation of SPARC production by pericytes may have potential implications for postinfarct healing.

16.
Aging (Albany NY) ; 122020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232280

RESUMO

Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11b+Ly6G+ and CD11b+Ly6G- populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11b+Ly6G-, but not the CD11b+Ly6G+ compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11b+Ly6G- population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11b+Ly6G- population.

17.
Brain Behav Immun ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157258

RESUMO

Over-activation of the innate immune system constitutes a risk factor for the development of nervous system disorders but may reduce the severity of these disorders by inducing tolerance effect. Here, we studied the tolerance-inducing effect and properties of innate immune stimulation on chronic social defeat stress (CSDS)-induced behavioral abnormalities in mice. A single injection of the innate immune enhancer lipopolysaccharide (LPS) one day before stress exposure prevented CSDS-induced impairment in social interaction and increased immobility time in the tail suspension test and forced swimming test. This effect was observed at varying doses (100, 500, and 1000 µg/kg) and peaked at 100 µg/kg. A single LPS injection (100 µg/kg) either one or five but not ten days before stress exposure prevented CSDS-induced behavioral abnormalities. A second LPS injection ten days after the first LPS injection, or a 2 × or 4 × LPS injections ten days before stress exposure also induced tolerance against stress-induced behavioral abnormalities. Our results furthermore showed that a single LPS injection one day before stress exposure skewed the neuroinflammatory response in the hippocampus and prefrontal cortex of CSDS-exposed mice toward an anti-inflammatory phenotype. Inhibiting the central innate immune response by pretreatment with minocycline or PLX3397 abrogated the tolerance-inducing effect of LPS preconditioning on CSDS-induced behavioral abnormalities and neuroinflammatory responses in the brain. These results provide evidence for a prophylactic effect of innate immune stimulation on stress-induced behavioral abnormalities via changes in microglial activation, which may help develop novel strategies for the prevention of stress-induced psychological disorders.

18.
Anal Chem ; 92(23): 15297-15305, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33185440

RESUMO

Oxidative stress is a state of stress injury, which leads to the pathogenesis of most neurodegenerative diseases. Moreover, this is also one of the main reasons for the loss of dopaminergic neurons and the abnormal content of dopamine (DA). In the past decades, a number of studies have found that acetaminophen (AP) is metabolized and distributed in the brain when it is used as a neuroprotective compound. In this context, we proposed an electrochemical sensor based on 9-(4-(10-phenylanthracen-9-yl)phenyl)-9H-carbazole with the goal of diagnosing these two drugs in the body. Carbazole groups can easily be formed into large π-conjugated systems by electropolymerization. The introduction of anthracene exactly combined the carbazole group to establish an efficient electron donor-acceptor pattern, which enhanced π-π interaction with the electrode surface and charge transporting ability. The diagnostic platform showed good sensing activity toward the oxidation of DA and AP. The detection range for DA and AP is from 0.2 to 300 µM and from 0.2 to 400 µM, respectively. The simultaneous detection range is from 0.5 to 250 µM, which is wider than most reports. After a series of electrochemical assessments were determined, the sensor was finally developed to the analysis of pharmaceutical and human serum, displaying a meaningful potential in clinical evaluation.

19.
Sensors (Basel) ; 20(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007915

RESUMO

A design scheme of multi-element sensor which included electrical resistivity probes, multiple Cl- selective electrodes, and a steel corrosion monitoring system was proposed in this work. Embedding this multi-element sensor in concrete enables the real-time and non-destructive monitoring of internal electrical resistivity, free Cl- (Clf) contents in the concrete pore solution at different depths, and steel corrosion parameters. Based on the monitoring data obtained by the multi-element sensor, the freezing-thawing (F-T) damage degree, the Clf diffusion coefficient, the quantitative relation between F-T damage degree and Clf diffusion coefficient, the initiation period of steel corrosion, and the critical content related to steel corrosion are determined. To conclude, the multi-element sensor provides key durability parameters for the establishment of the Clf diffusion model, the assessment of health condition, and the prediction of service life of concrete under the coexistence of the F-T cycle and Cl-.

20.
J Sci Food Agric ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063326

RESUMO

BACKGROUND: Oxidized phlorotannin can be used as a protein crosslinking agent to produce high-quality fish gel products. Phlorotannin can be easily induced to form quinone compounds in an oxidizing environment, while o-quinone has been proven to be a reactive, electrophilic intermediate that easily reacts with proteins to form rigid molecular crosslinking networks. The objective of this study was to investigate the synergistic effects of ultraviolet A (UVA) irradiation (1 h, 15 W m-2 ) and various concentrations of Laminaria japonica phlorotannin extracts (PTE) on the gel properties of grass carp myofibrillar protein (MP). RESULTS: UVA treatment and PTE could synergistically improve the MP gel properties more than PTE alone (P < 0.05). At 625 mmol kg-1 MP PTE alone, the gel strength and cooking yield reached 3.10 ± 0.16 g cm and 47.45 ± 0.35%, respectively, while with the same level of PTE plus UVA they became 4.26 ± 0.19 g cm and 53.89 ± 1.54%, respectively. The three-dimensional network structure of the gel (with PTE + UVA) showed higher connectivity and tightness than that of the control group (no treatment). CONCLUSIONS: The synergistic effects of PTE and UVA could effectively induce crosslinking of grass carp MP, which could lead to an improvement of MP gel quality. These findings would provide a new technical approach to produce high-quality protein gel products in the fish processing industry. © 2020 Society of Chemical Industry.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...