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1.
BMC Cancer ; 24(1): 961, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107726

RESUMO

BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients. METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated. RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa. CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.


Assuntos
Biomarcadores Tumorais , Exossomos , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Exossomos/genética , Exossomos/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Regulação Neoplásica da Expressão Gênica , Idoso , Perfilação da Expressão Gênica/métodos , Curva ROC , Antígeno CA-19-9/sangue
2.
Virol J ; 21(1): 113, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760812

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. METHOD: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. RESULTS: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. CONCLUSION: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Anticorpos Antivirais/sangue , China/epidemiologia , Fazendeiros , Fazendas , Vison/virologia , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Phlebovirus/classificação , Filogenia , RNA Viral/genética , Febre Grave com Síndrome de Trombocitopenia/transmissão , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/epidemiologia
3.
Dysphagia ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096333

RESUMO

This study aimed to develop the Dysphagia Handicap Index-Chinese Mandarin (DHI-CM) and to assess its reliability and validity. This prospective study was conducted in China with individuals who speak Mandarin. The DHI-CM was developed according to a five-stage process. 264 patients with oropharyngeal dysphagia (OD) and 187 healthy individuals completed the study. Reliability was assessed using Cronbach's α and test-retest reliability. Differences between healthy participants and patients with OD were analyzed for instrument validity. Convergent and concurrent validity were assessed using the Swallowing Quality of Life Questionnaire (SWAL-QoL) and Functional Oral Intake Scale (FOIS), respectively. The Content Validity Index (CVI) was used to assess content validity. Exploratory and Confirmatory Factor Analyses (EFA and CFA, respectively) were used to assess structural validity. The Cronbach's alpha was > 0.9 for the total score and every individual subscale. The Pearson and intraclass correlation coefficients were both > 0.8. The patients with OD showed significantly higher scores in the DHI-CM and its subscales than the healthy individuals. Significant correlations were found between most subscales of the DHI-CM and both the SWAL-QoL and FOIS. The CVI of the DHI-CM was 0.892 and ranged between 0.878 and 1.000 for the subscales. The EFA identified three components that explained 24.33%, 23.99%, and 22.73% of the variance, respectively. The scale showed good structural validity through CFA. Conclusions. The DHI-CM demonstrated good reliability and validity among Mandarin-speaking Chinese adults.

4.
J Mol Cell Cardiol ; 174: 88-100, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36473288

RESUMO

Pro-inflammatory and reparative macrophages are crucial in clearing necrotic myocardium and promoting cardiac repair after myocardial infarction (MI), respectively. Extracellular adenosine has been demonstrated to modulate macrophage polarization through adenosine receptors. However, the role of intracellular adenosine in macrophage polarization has not been explored and adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels. Here, we aimed to elucidate the role of ADK in macrophage polarization and its subsequent impact on MI. We demonstrated that ADK was upregulated in bone marrow-derived macrophages (BMDMs) after IL-4 treatment and was highly expressed in the infarct area at day 7 post-MI, especially in macrophages. Compared with wild-type mice, myeloid-specific Adk knockout mice showed increased infarct size, limited myofibroblast differentiation, reduced collagen deposition and more severe cardiac dysfunction after MI, which was related to impaired reparative macrophage phenotype in MI tissue. We found that ADK deletion or inhibition significantly decreased the expression of reparative genes, such as Arg1, Ym1, Fizz1, and Cd206 in BMDMs after IL-4 treatment. The increased intracellular adenosine due to Adk deletion inhibited transmethylation reactions and decreased the trimethylation of H3K4 in BMDMs after IL-4 treatment. Mechanistically, we demonstrated that Adk deletion suppressed reparative macrophage phenotype through decreased IRF4 expression, which resulted from reduced levels of H3K4me3 on the Irf4 promotor. Together, our study reveals that ADK exerts a protective effect against MI by promoting reparative macrophage polarization through epigenetic mechanisms.


Assuntos
Adenosina Quinase , Infarto do Miocárdio , Camundongos , Animais , Adenosina Quinase/genética , Adenosina Quinase/metabolismo , Interleucina-4/genética , Macrófagos/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Fenótipo , Camundongos Knockout , Camundongos Endogâmicos C57BL
5.
Biochem Biophys Res Commun ; 665: 152-158, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37163935

RESUMO

Uridine has formerly been shown to alleviate obesity and hepatic lipid accumulation. N-carbamoyl aspartate (NCA) provides carbon atoms to uridine in de novo pyrimidine biosynthesis pathway. However, whether NCA is involved in the lipid metabolism remains elusive. Here we showed that NCA supplementation significantly decreased (P < 0.05) serum cholesterol (CHOL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels of mice, and significantly increased (P < 0.05) relative mRNA expression of genes related to the synthesis of pyrimidine nucleotides and polyunsaturated fatty acids. Besides, supplemented with NCA significantly decreased body weight and area under the curve (AUC), and increased body temperature in the high-fat diet fed mice. For further, relative protein expression of uridine monophosphate synthase (UMPS), sterol regulatory element-binding protein 1(SREBP-1) and phosphorylated hormone-sensitive triglyceride lipase (P-HSL) in the liver, and uncoupling protein 1 (UCP-1) in interscapular brown adipose tissue (iBAT) also showed upregulated in the high-fat diet fed mice. Thus, NCA promoted de novo synthesis of pyrimidine and polyunsaturated fatty acid, and reduced body weight by stimulating high-fat diet-induced thermogenesis of iBAT.


Assuntos
Tecido Adiposo Marrom , Ácido Aspártico , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Ácido Aspártico/metabolismo , Peso Corporal , Termogênese/genética , Dieta Hiperlipídica/efeitos adversos , Pirimidinas/farmacologia , Uridina/metabolismo
6.
J Environ Manage ; 330: 117214, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36623386

RESUMO

A park that had used reclaimed water as the sole water supply for fourteen years, was selected to analyze the distribution, sources and risks of 16 priority polycyclic aromatic hydrocarbons (PAHs) in waters and sediments. The effects of phytoremediation were investigated in waterbodies classified as phytoremediation, transitional and non-phytoremediation areas. Diagnostic ratio (DR) and principal component analysis (PCA) were used to analyze the sources of PAHs, while risk quotient (RQ) was used as risk assessment tool. Results showed that ∑PAH concentrations in sediments ranged from 29.4 to 1245.6 ng‧g-1, with average of 354.3 ng‧g-1, corresponding to a moderate pollution level. The concentration of PAHs in water ranged from 10.6 to 326.3 ng‧L-1, with average of 147.2 ng‧L-1, corresponding to a low pollution level. The ∑PAHs in sediments showed a downward trend from northwest to southeast along with the water flow direction, with average values of 459.5, 362.9 and 246.1 ng‧L-1 in the upstream, midstream and downstream, respectively. In contrast, PAH concentrations in water were consistent with recreational activities in the urban park area. There were 95% of water samples and 72% of sediment samples obtaining the Ant/(Ant + Phe) > 0.1 and Flu/(Flu + Pyr) > 0.5, indicating that coal combustion was the major source of PAHs in both the water and sediment. The RQ∑PAH(NCs) values in water and sediment were all between 1 and 800, while RQ∑PAH(MPCs) reached equal to 0, suggesting that ∑PAHs presented a low ecological risk. Acenaphthene accounted for 28.4% of RQ(NCs), and became the most risk PAH in water column. Aquatic plants effectively removed high-ring PAHs from water and middle-ring PAHs from sediments, reducing the overall risks posed by PAHs.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Água/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Medição de Risco , China , Sedimentos Geológicos
7.
Langmuir ; 35(43): 14133-14140, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31573206

RESUMO

The sliding behavior of anisotropic surfaces is a crucial property to their applications from fundamental research to practical fields. Herein, we propose a theoretical model for analyzing the sliding behavior based on the concept of adhesion energy. Surface Evolver simulation is conducted to determine the adhesion energy per unit area. The microgrooved surfaces are fabricated and characterized to validate the proposed theory. It is found that the apparent contact angle measured along the direction parallel to the strips increases with the increase of microgroove width, while the corresponding sliding angles exhibit an opposite trend. The adhesion energy per unit area has a constant value regardless of the droplet volume. The different sliding behaviors of anisotropic surfaces along the perpendicular and parallel directions are attributed to the difference in the corresponding adhesion energies per unit area. The proposed model is expected to be used for predicting the sliding behavior of anisotropic surfaces.

8.
Nutrients ; 16(16)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39203897

RESUMO

γ-Aminobutyric acid (GABA) is a widely distributed non-protein amino acid that serves as a crucial inhibitory neurotransmitter in the brain, regulating various physiological functions. As a result of its potential benefits, GABA has gained substantial interest in the functional food and pharmaceutical industries. The enzyme responsible for GABA production is glutamic acid decarboxylase (GAD), which catalyzes the irreversible decarboxylation of glutamate. Understanding the crystal structure and catalytic mechanism of GAD is pivotal in advancing our knowledge of GABA production. This article provides an overview of GAD's sources, structure, and catalytic mechanism, and explores strategies for enhancing GABA production through fermentation optimization, metabolic engineering, and genetic engineering. Furthermore, the effects of GABA on the physiological functions of animal organisms are also discussed. To meet the increasing demand for GABA, various strategies have been investigated to enhance its production, including optimizing fermentation conditions to facilitate GAD activity. Additionally, metabolic engineering techniques have been employed to increase the availability of glutamate as a precursor for GABA biosynthesis. By fine-tuning fermentation conditions and utilizing metabolic and genetic engineering techniques, it is possible to achieve higher yields of GABA, thus opening up new avenues for its application in functional foods and pharmaceuticals. Continuous research in this field holds immense promise for harnessing the potential of GABA in addressing various health-related challenges.


Assuntos
Biotecnologia , Fermentação , Glutamato Descarboxilase , Engenharia Metabólica , Ácido gama-Aminobutírico , Ácido gama-Aminobutírico/biossíntese , Ácido gama-Aminobutírico/metabolismo , Glutamato Descarboxilase/metabolismo , Engenharia Metabólica/métodos , Biotecnologia/métodos , Animais , Humanos , Engenharia Genética , Ácido Glutâmico/metabolismo
9.
Front Biosci (Landmark Ed) ; 29(2): 70, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38420793

RESUMO

BACKGROUND: The number of older people in the world is increasing year by year; studies have shown that more than 90% of cardiovascular disease occurs in the older people population, indicating that aging is one of the major risks involved in the development of cardiovascular disease. Therefore, retarding the development of cardiac aging is an important strategy to prevent aging-related cardiovascular diseases. METHODS: In the current study, we examined the anti-cardiovascular aging potential of canthaxanthin in vitro and in vivo experiments. For this, a model of cardiomyocyte senescence induced by D-galactose was established, which was used to investigate the canthaxanthin's effect on cardiac premature aging. RESULTS: We found that canthaxanthin obviously mitigated the cardiomyocyte senescence in vitro. Further mechanistic studies revealed that canthaxanthin seems to alleviate cardiomyocyte senescence by regulating the autophagy process. Furthermore, the effects of canthaxanthin on cardiovascular senescence were further evaluated. We also observed that canthaxanthin mitigated cardiac aging and fibrosis in the aged mice model. CONCLUSIONS: To sum up, the current work showed that canthaxanthin could obviously alleviate cardiac premature aging, indicating that canthaxanthin could be used as a biologically active molecule for the treatment of cardiac aging and fibrosis.


Assuntos
Senilidade Prematura , Doenças Cardiovasculares , Humanos , Animais , Camundongos , Idoso , Cantaxantina/farmacologia , Senilidade Prematura/patologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/patologia , Envelhecimento , Miócitos Cardíacos , Fibrose , Senescência Celular
10.
Reprod Toxicol ; 124: 108530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38159578

RESUMO

The reproductive system is a primary target organ for zearalenone (ZEN, a widespread fusarium mycotoxin) to exert its toxic effects, including decreased antioxidant capacity and aggravated inflammatory response. These ZEN-induced reproductive abnormalities are partially caused by the declining levels of nicotinamide adenine dinucleotide (NAD+), which results in an imbalance in lipid/glucose metabolism. Accordingly, the present study aimed to investigate whether supplements of nicotinamide mononucleotide (NMN, a NAD+ precursor) in female mice could protect against ZEN-induced reproductive toxicity. In this study, thirty female mice were randomly divided into three groups that were intragastrically administered with i) 0.5% DMSO (the Ctrl group), ii) 3 mg/(kg bw.d) ZEN (the ZEN group), or iii) ZEN + 500 mg/(kg bw.d) NMN (the ZEN/NMN group) for two weeks. The results revealed that, compared with the Ctrl group, animals exposed to ZEN exhibited reproductive toxicity, such as decreased antioxidant capacity and aggravated inflammatory response in reproductive tissues. These effects were strongly correlated with lower activities in key glycolytic enzymes (e.g., ALDOA and PGK), but increased expressions in key lipid-synthesis genes (e.g., LPIN1 and ATGL). These changes contribute to lipid accumulation, specifically for diacylglycerols (DAGs). Furthermore, these ZEN-induced changes were linked with disturbed NAD+ synthesis/degradation, and subsequently decreased NAD+ levels. Notably, NMN supplements in mice protected against these ZEN-induced reproductive abnormalities by boosting NAD+ levels. Herein, the present findings demonstrate that potential strategies to enhance NAD+ levels can protect against ZEN-induced reproductive toxicity.


Assuntos
Antioxidantes , Zearalenona , Camundongos , Feminino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Zearalenona/toxicidade , NAD/metabolismo , Metabolismo dos Lipídeos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Genitália/metabolismo , Glicólise , Lipídeos
11.
Math Biosci Eng ; 21(4): 5521-5535, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38872546

RESUMO

Early diagnosis of abnormal electrocardiogram (ECG) signals can provide useful information for the prevention and detection of arrhythmia diseases. Due to the similarities in Normal beat (N) and Supraventricular Premature Beat (S) categories and imbalance of ECG categories, arrhythmia classification cannot achieve satisfactory classification results under the inter-patient assessment paradigm. In this paper, a multi-path parallel deep convolutional neural network was proposed for arrhythmia classification. Furthermore, a global average RR interval was introduced to address the issue of similarities between N vs. S categories, and a weighted loss function was developed to solve the imbalance problem using the dynamically adjusted weights based on the proportion of each class in the input batch. The MIT-BIH arrhythmia dataset was used to validate the classification performances of the proposed method. Experimental results under the intra-patient evaluation paradigm and inter-patient evaluation paradigm showed that the proposed method could achieve better classification results than other methods. Among them, the accuracy, average sensitivity, average precision, and average specificity under the intra-patient paradigm were 98.73%, 94.89%, 89.38%, and 98.24%, respectively. The accuracy, average sensitivity, average precision, and average specificity under the inter-patient paradigm were 91.22%, 89.91%, 68.23%, and 95.23%, respectively.


Assuntos
Algoritmos , Arritmias Cardíacas , Eletrocardiografia , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Humanos , Arritmias Cardíacas/classificação , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Eletrocardiografia/métodos , Sensibilidade e Especificidade , Aprendizado Profundo , Reprodutibilidade dos Testes , Bases de Dados Factuais
12.
Heliyon ; 10(1): e23675, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187229

RESUMO

Postmenopausal osteoporosis is the most common type of osteoporosis in women. To date, little is known about their transcriptome signatures, although biomarkers from peripheral blood mononuclear cells are attractive for postmenopausal osteoporosis diagnoses. Here, we performed bulk RNA sequencing of 206 samples (124 postmenopausal osteoporosis and 82 normal samples) and described the clinical phenotypic characteristics of postmenopausal women. We then highlighted the gene set enrichment analyses between the extreme T-score group and the heathy control group, revealing that some immune-inflammatory responses were enhanced in postmenopausal osteoporosis, with representative pathways including the mitogen-activated protein kinase (NES = 1.6, FDR <0.11) pathway and B_CELL_RECEPTOR (NES = 1.69, FDR <0.15) pathway. Finally, we developed a combined risk prediction model based on lasso-logistic regression to predict postmenopausal osteoporosis, which combined eleven genes (PTGS2, CXCL16, NECAP1, RPS23, SSR3, CD74, IL4R, BTBD2, PIGS, LILRA2, MAP3K11) and three pieces of clinical information (age, procollagen I N-terminal propeptide, ß isomer of C-terminal telopeptide of type I) and provided the best prediction ability (AUC = 0.97). Taken together, this study filled a gap in the large-scale transcriptome signature profiles and revealed the close relationship between immune-inflammatory responses and postmenopausal osteoporosis, providing a unique perspective for understanding the occurrence and development of postmenopausal osteoporosis.

13.
Analyst ; 138(12): 3372-5, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23666563

RESUMO

An in situ electrochemical method of cell viability, which integrated cell culture, pretreatment and detection in a cell culture dish, was developed. The method significantly improved the electrochemical response of cells, simplified the operation process, reduced the experiment time, avoided the use of trypsin, and was applied in the study of the effectiveness of antitumor drugs on tumor suppression.


Assuntos
Eletroquímica/métodos , Antineoplásicos/farmacologia , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Células MCF-7 , Fatores de Tempo
14.
Math Biosci Eng ; 20(7): 13415-13433, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37501494

RESUMO

For wearable electrocardiogram (ECG) acquisition, it was easy to infer motion artifices and other noises. In this paper, a novel end-to-end ECG denoising method was proposed, which was implemented by fusing the Efficient Channel Attention (ECA-Net) and the cycle consistent generative adversarial network (CycleGAN) method. The proposed denoising model was optimized by using the ECA-Net method to highlight the key features and introducing a new loss function to further extract the global and local ECG features. The original ECG signal came from the MIT-BIH Arrhythmia Database. Additionally, the noise signals used in this method consist of a combination of Gaussian white noise and noises sourced from the MIT-BIH Noise Stress Test Database, including EM (Electrode Motion Artifact), BW (Baseline Wander) and MA (Muscle Artifact), as well as mixed noises composed of EM+BW, EM+MA, BW+MA and EM+BW+MA. Moreover, corrupted ECG signals were generated by adding different levels of single and mixed noises to clean ECG signals. The experimental results show that the proposed method has better denoising performance and generalization ability with higher signal-to-noise ratio improvement (SNRimp), as well as lower root-mean-square error (RMSE) and percentage-root-mean-square difference (PRD).


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Eletrocardiografia/métodos , Teste de Esforço , Razão Sinal-Ruído
15.
Int J Cardiol ; 372: 6-14, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513282

RESUMO

BACKGROUND: Timely and appropriate transformation of macrophage phenotypes from proinflammatory to anti-inflammatory is essential for cardiac repair after myocardial infarction (MI). Chemokine-like receptor 1 (CMKLR1), which is expressed on macrophages, is regulated by proinflammatory and anti-inflammatory stimuli. However, the contribution of CMKLR1 to macrophage phenotypic transformation and the role it plays in modulating cardiac repair after MI remain unclear. METHODS: CMKLR1 knockout (CMKLR1-/-) mice were generated by CRISPR/Cas-mediated genome engineering. A model of murine MI was induced by permanent ligation along the left anterior descending artery. Cardiac function was evaluated by echocardiography. Infarct size and collagen deposition were detected by Masson's trichrome staining. Cardiac macrophages were obtained by fluorescence-activated cell sorting. The protein and mRNA expression of associated molecules was determined by Western blotting and qRT-PCR. RESULTS: We demonstrated that macrophages highly expressed CMKLR1 and accumulated in murine infarcted hearts during the anti-inflammatory reparative phase of MI. CMKLR1 deficiency impaired cardiac function, increased infarct size, induced maladaptive cardiac remodeling, and decreased long-term survival after MI. Furthermore, CMKLR1 deficiency impeded macrophage phenotypic transformation from M1 to M2 in vivo and in vitro. In addition, we demonstrated that CMKLR1 signaling through the PI3K/Akt/mTOR pathway stimulated C/EBPß activation while simultaneously limiting NF-κB activation, thereby promoting anti-inflammatory and prohibiting proinflammatory macrophage polarization. CONCLUSIONS: Our results reveal that CMKLR1 deficiency impedes macrophage phenotypic transformation and cardiac repair after MI involving the PI3K/AKT/mTOR pathway. CMKLR1 may thus represent a potential therapeutic target for MI.


Assuntos
Infarto do Miocárdio , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Macrófagos/metabolismo , Serina-Treonina Quinases TOR , Fenótipo , Quimiocinas/metabolismo , Miocárdio/metabolismo , Camundongos Endogâmicos C57BL
16.
Front Biosci (Landmark Ed) ; 28(12): 367, 2023 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-38179737

RESUMO

BACKGROUND: Vascular endothelial dysfunction is an early phenotype of aging-related vascular dysfunction. Delaying vascular aging and preventing cardiovascular disease are major public health problems that urgently need to be solved. Scientists have studied various drugs to prevent the occurrence and progress of cardiovascular disease, but progress has been slow. Here, the antisenescence and anti-endothelial damage of canthaxanthin (CX, which is an active molecule from food) has been studied. METHODS: This study was performed by adding CX to a model of cell senescence and oxidative damage induced by hydrogen peroxide. Cellular senescence markers (e.g., p16, p21, and p53) and oxidative damage markers (e.g., reactive oxygen species, nitric oxide, malondialdehyde, superoxide dismutase) were evaluated by the enzyme-linked immunosorbent assay, laser scanning confocal microscopy, and Western blotting. RESULTS: We found that CX downregulated the expression level of senescence-associated molecules, and significantly reduced the oxidative damage of vascular endothelial cells. These observations showed that CX effectively alleviated the senescence of vascular endothelial cells. Furthermore, CX treatment reduced the expression levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1ß. Finally, in vivo, CX significantly alleviated vascular senescence. CONCLUSIONS: The current study shows that CX has potential application value for treating vascular aging or endothelial cell senescence.


Assuntos
Cantaxantina , Doenças Cardiovasculares , Camundongos , Animais , Cantaxantina/farmacologia , Células Endoteliais , Envelhecimento , Senescência Celular/genética , Estresse Oxidativo , Inflamação
17.
Eur J Pharm Biopharm ; 189: 189-201, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37364749

RESUMO

Brexpiprazole (BPZ), which is approved for the treatment of schizophrenia and major depressive disorder, has the potential to meet diverse clinical needs. This study aimed to develop a long-acting injectable (LAI) formulation of BPZ that could provide sustained therapeutic benefits. A library of BPZ prodrugs was screened through esterification, and BPZ laurate (BPZL) was identified as an optimal candidate. To achieve stable aqueous suspensions, a pressure- and nozzle size-controlled microfluidization homogenizer was utilized. The pharmacokinetics (PK) profiles, considering dose and particle size modulation, were investigated following a single intramuscular injection in beagles and rats. BPZL treatment resulted in sustained plasma concentrations above the median effective concentration (EC50) for 2 âˆ¼ 3 weeks, without exhibiting an initial burst release. Histological examination of foreign body reaction (FBR) in rats revealed the morphological evolution of an inflammation-mediated drug depot, confirming the sustained release mechanism of BPZL. These findings provide strong support for the further development of a ready-to-use LAI suspension of BPZL, which could potentially enhance treatment outcomes, improve patient adherence, and address the clinical challenges associated with long-term regimens of schizophrenia spectrum disorders (SSD).


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Cães , Animais , Ratos , Suspensões , Transtorno Depressivo Maior/tratamento farmacológico , Injeções Intramusculares , Inflamação/tratamento farmacológico , Preparações de Ação Retardada
18.
Sci Total Environ ; 888: 164069, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37207778

RESUMO

To illustrate the evolution process, environmental feature and phytoremediation effect of phosphorus (P) in waterbodies with long-term replenishment by reclaimed water (RW), an urban waterbody using RW as the sole supply was selected as a case study. The concentration and distribution of soluble reactive phosphate (SRP), dissolved organic P (DOP) and particulate P (PP) in water column, as well as organic P (OP), inorganic P (IP), exchangeable P (Ex-P), BD-P (redox-sensitive P), NaOH-P (P bound to Fe and Al oxyhydroxides) and HCl-P (P bound to Ca) in sediment were investigated. Results showed that the seasonal average concentrations of total phosphorus (TPw) in water column ranged from 0.048 to 0.130 mg∙L-1, with the highest in summer and the lowest in winter. P in water column was predominantly present in dissolved state, with the similar proportions of SRP and DOP. SRP decreased apparently in midstream, where the phytoremediation was applied extensively. PP content obviously increased in non-phytoremediation area in downstream, due to visitor activity and sediment resuspension. Total phosphorus (TPs) in sediments was between 352.9 and 1331.3 mg∙kg-1, with average 365.7 mg∙kg-1 of IP and 382.8 mg∙kg-1 of OP. Among IP, HCl-P had the highest proportion, followed by BD-P, NaOH-P and Ex-P. OP was significantly higher in phytoremediation areas than that in non-phytoremediation areas. Coverage of aquatic plants was positively correlated with TP, OP, BAP, while it was negatively correlated with BD-P. Hydrophyte stabilized and conserved active P in sediment and prevented release of active P. Moreover, hydrophyte increased NaOH-P and OP contents in sediment through regulating the abundance of phosphorus-solubilizing bacteria (PSB), such as Lentzea and Rhizobium. Four sources were identified through two multivariate statistical models. RW and runoff were the dominant sources of P accounting for 52.09 %, which mainly contributed to P in sediment especially IP.

19.
Analyst ; 137(14): 3230-3, 2012 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-22606685

RESUMO

Two electrochemical signals of the MCF-7 cell were simultaneously detected by using multiwall carbon nanotubes and room temperature ionic liquid composite film modified electrode. The signal at +0.726 V due to the oxidation of xanthine and guanine, was obviously improved. And the signal at +1.053 V due to the oxidation of hypoxanthine and adenine was found for the first time. This two-signal electrochemical method is credible to detect cell viability and proliferation.


Assuntos
Eletroquímica/métodos , Catálise , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Eletroquímica/instrumentação , Eletrodos , Humanos , Nanotubos de Carbono/química , Temperatura
20.
Physiol Meas ; 43(8)2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35882225

RESUMO

Objective.With the improvement of living standards, heart disease has become one of the common diseases that threaten human health. Electrocardiography (ECG) is an effective way of diagnosing cardiovascular diseases. With the rapid growth of ECG examinations and the shortage of cardiologists, accurate and automatic arrhythmias classification has become a research hotspot. The main purpose of this paper is to improve accuracy in detecting abnormal ECG patterns.Approach.A hybrid 1D Resnet-GRU method, consisting of the Resnet and gated recurrent unit (GRU) modules, is proposed to implement classification of arrhythmias from 12-lead ECG recordings. In addition, the focal Loss function is used to solve the problem of unbalanced datasets. Based on the proposed 1D Resnet-GRU model, we use class-discriminative visualization to improve interpretability and transparency as an additional step. In this paper, the Grad-CAM++ mechanism has been employed to the trained network model and generate thermal images superimposed on raw signals to explore underlying explanations of various ECG segments.Main results.The experimental results show that the proposed method can achieve a high score of 0.821 (F1-score) in classifying 9 kinds of arrythmias, and Grad-CAM++ not only provides insight into the predictive power of the model, but is also consistent with the diagnostic approach of the arrhythmia classification.Significance.The proposed method can effectively select and integrate ECG features to achieve the goal of end-to-end arrhythmia classification by using 12-lead ECG signals, which can serve a promising and useful way for automatic arrhythmia classification, and can provide an explainable deep leaning model for clinical diagnosis.


Assuntos
Aprendizado Profundo , Processamento de Sinais Assistido por Computador , Algoritmos , Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Humanos , Redes Neurais de Computação
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