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BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.
Assuntos
Insuficiência Cardíaca , Subunidade alfa do Fator 1 Induzível por Hipóxia , Transportadores de Ácidos Monocarboxílicos , Condicionamento Físico Animal , Simportadores , Animais , Masculino , Ratos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/etiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Miócitos Cardíacos/metabolismo , Ratos Sprague-Dawley , Simportadores/metabolismo , Simportadores/genética , Regulação para CimaRESUMO
Mycotoxins cause significant harm to human health, so it is imperative to develop a highly sensitive and easy-to-operate method for the detection of mycotoxins. Herein, a fluorescence-based magnetic separation immunoassay for simultaneous detection of mycotoxins fumonisin B1 and zearalenone is established. The method employed high fluorescent upconversion-nanoparticles(UCNPs) conjugated with biotinylated antigens as upconversion fluoroscent probes. Magnetic nanoparticles(MNPs) immobilized with monoclonal antibodies are used as immune-capture probes. Highly sensitive detection of FB1 and ZEN was achieved based on the luminescence properties of UCNPs and the separation effects of MNPs. The results showed a robust linear correlation between the enhanced fluorescence emission intensity and the logarithmic concentrations of FB1 and ZEN under the optimal conditions (R2(FB1) = 0.9965, R2(ZEN) = 0.9976), and the linear ranges were 0.05-5 ng mL-1. Furthermore, the limits of detection (LOD) were 0.016 ng mL-1 for FB1 and 0.012 ng mL-1 for ZEN. The standard addition method was used to determine the content of FB1 and ZEN in the samples to evaluate the accuracy of the process. The average recoveries were 89.48% to 113.69% and 85.97% to 113.82%, respectively. Compared with the other five mycotoxins, this method had high selectivity. It is expected that the multi-component simultaneous detection can be further realized by using the multicolor labeling characteristics of UCNPs.
Assuntos
Micotoxinas , Zearalenona , Imunofluorescência , Contaminação de Alimentos/análise , Fumonisinas , Humanos , Imunoensaio , Limite de Detecção , Fenômenos Magnéticos , Micotoxinas/análiseRESUMO
The design and fabrication of a surface-enhanced Raman scattering (SERS) aptasensor for simultaneous detection of zearalenone (ZEN) and ochratoxin A (OTA) in wheat and corn samples is described. The capture and reporter probes were SH-cDNA-modified gold nanorods and SH-Apt-modified Au@Ag core-shell nanoparticles, respectively. After recognizing OTA and ZEN aptamers and complementary strands (SH-cDNA), the reporter probe generated a strong SERS signal. The preferred binding of OTA and ZEN aptamers to OTA and ZEN, respectively, caused reporter probes to release the capture probes, resulting in a linear decrease in SERS intensity. The detection of OTA showed good linearity with an R2 value of 0.986, which could be maintained across a wide concentration range (0.01 to 100 ng/mL), with the limit of detection of 0.018 ng/mL. For detection of ZEN, good linearity with an R2 value of 0.987 could be maintained across a wide concentration range (0.05 to 500 ng/mL), with 0.054 ng/mL as the limit of detection. Good accuracy (relative standard deviation < 4.2%) during mycotoxin determination as well as excellent quantitative recoveries (96.0-110.7%) during the analysis of spiked real samples was achieved. The proposed SERS aptasensor exhibited excellent performance in the detection of OTA and ZEN in real food samples. Hence, by simply changing the aptamer, this new model can be applied to the detection of multiple mycotoxins in the food industry.
Assuntos
Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Micotoxinas/análise , Nanotubos/química , Ocratoxinas/análise , Zearalenona/análise , Aptâmeros de Nucleotídeos/química , Grão Comestível/química , Contaminação de Alimentos/análise , Ouro/química , Ácidos Nucleicos Imobilizados/química , Limite de Detecção , Micotoxinas/química , Ocratoxinas/química , Reprodutibilidade dos Testes , Prata/química , Análise Espectral Raman , Triticum/química , Zea mays/química , Zearalenona/químicaRESUMO
Introduction: In the evolving field of neurophysiological research, visual light flicker stimulation is recognized as a promising non-invasive intervention for cognitive enhancement, particularly in sleep-deprived conditions. Methods: This study explored the effects of specific flicker frequencies (40 Hz and 20-30 Hz random flicker) on alertness recovery in sleep-deprived rats. We employed a multidisciplinary approach that included behavioral assessments with the Y-maze, in vivo electrophysiological recordings, and molecular analyses such as c-FOS immunohistochemistry and hormone level measurements. Results: Both 40 Hz and 20-30 Hz flicker significantly enhanced behavioral performance in the Y-maze test, suggesting an improvement in alertness. Neurophysiological data indicated activation of neural circuits in key brain areas like the thalamus and hippocampus. Additionally, flicker exposure normalized cortisol and serotonin levels, essential for stress response and mood regulation. Notably, increased c-FOS expression in brain regions related to alertness and cognitive functions suggested heightened neural activity. Discussion: These findings underscore the potential of light flicker stimulation not only to mitigate the effects of sleep deprivation but also to enhance cognitive functions. The results pave the way for future translational research into light-based therapies in human subjects, with possible implications for occupational health and cognitive ergonomics.
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Alzheimer's disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors, accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the brain. At the cellular and molecular levels, the neuronal cellular milieu of the AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, and reduced overall metabolic capacity, which lead to abnormal neural network activity and impaired neuroplasticity, thus accelerating the formation of extracellular senile plaques and intracellular neurofibrillary tangles. The current absence of effective pharmacological therapies for AD points to the urgent need to investigate the benefits of non-pharmacological approaches such as physical exercise. Despite the evidence that regular physical activity can improve metabolic dysfunction in the AD state, inhibit different pathophysiological molecular pathways associated with AD, influence the pathological process of AD, and exert a protective effect, there is no clear consensus on the specific biological and molecular mechanisms underlying the advantages of physical exercise. Here, we review how physical exercise improves crucial molecular pathways and biological processes associated with metabolic disorders in AD, including glucose metabolism, lipid metabolism, Aß metabolism and transport, iron metabolism and tau pathology. How metabolic states influence brain health is also presented. A better knowledge on the neurophysiological mechanisms by which exercise improves AD metabolism can contribute to the development of novel drugs and improvement of non-pharmacological interventions.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Emaranhados Neurofibrilares/metabolismo , Encéfalo/metabolismoRESUMO
The illegal addition of melamine (MEL) into pet foods and infant milk powder has caused great concern among people. In this study, a point-of-care testing (POCT) method was developed by combining stimuli-responsive deoxyribonucleic acid (DNA) hydrogels with microfluidic chips to achieve portable and sensitive detection of MEL. With the MEL aptamer (MA) acting as a cross-linker, DNA hydrogel-coated gold nanoparticles (AuNPs) served as a basis for colorimetric detection and quantitative analysis. In the presence of MEL, it competitively binds to the aptamer, causing disintegration of the DNA hydrogels and a release of the coated AuNPs, making it possible to visually detect and quantitatively measure the MEL. Under optimal conditions, the detection range of MEL using DNA hydrogels was 0.1-100 µM and the limit of detection (LOD) was 42 nM. This portable, sensitive, and user-friendly field test equipment was developed to avoid the use of non-portable laboratory instruments. Furthermore, we combined microfluidic chips with the properties of DNA hydrogels, making it possible to quantitatively detect MEL by taking photos and analyzing the gray value using software in accordance with the different colors of copolymerization solutions after the reaction. The detection range of MEL using the microfluidic chip-based method was 0.2-50 µM, and the LOD was 37 nM. Neither trained operators nor large-scale instruments are needed for using this method to conduct portable and sensitive field detection of the targets, which highlights the methods excellent potential in food security, clinical tests, environmental monitoring, and other aspects.
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Ouro , Nanopartículas Metálicas , DNA , Humanos , Hidrogéis , Microfluídica , Pós , TriazinasRESUMO
Fumonisin (FB) is a common mycotoxin in corn, wheat, oats, and their related products. FB1 is the most predominant among fumonisins and is responsible for severe food contamination that may have deleterious effects on public health. Therefore, the demand for achieving sensitive detection of FB1 is becoming more and more pressing. In the present study, a creative biosensor for FB1 detection was developed based on fluorescence resonance energy transfer between upconversion nanoparticles (UCNPs) and graphene oxide (GO) with catalytic hairpin assembly (CHA) target recycling and amplification. In the presence of FB1, UCNPs were bound to the CHA amplification products away from the GO surface. Simultaneously, a strong fluorescence signal was produced at 980 nm (near-infrared light). The correlation between the concentration of FB1 and the fluorescence intensity exhibited a high relevance (R2 = 0.9971) ranging from 0.032 to 500 ng mL-1, and the method reached a considerably low limit of detection (0.0121 ng mL-1). It could be applied for the detection of FB1 in corn, oats, and infant supplements. The sensitive detection of FB1 proves the application potential of this method on food safety detection. This biosensor can enable high-throughput fungal toxin detection by allowing the use of various aptamers.
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Técnicas Biossensoriais , Fumonisinas , Micotoxinas , Nanopartículas , Grafite , Humanos , Micotoxinas/análise , Zea maysRESUMO
T-2 toxin is one of class A trichothecene mycotoxins produced by Fusarium, presenting genotoxic, cytotoxicity, and immunotoxicity for animals and humans. Therefore, It is urgent to establish a rapid test method with high sensitivity, good selectivity and reliability. In this research, by adjusting the synthesis conditions, a kind of NH2-UiO-66 with high quenching efficiency was screened out. On this basis, we constructed a novel fluorescence sensor via Cy3-labeled aptamer (Cy3-aptamer). With the help of π-π interaction, hydrogen bond and coordination, NH2-UiO-66 could adsorb and quench the fluorescence of Cy3-aptamer based on FRET and PET. In the presence of T-2 toxin, it recognized and bound to Cy3-aptamer, leading to the disintegration of the NH2-UiO-66/Cy3-aptamer compound. As the energy transfer process was blocked, the fluorescence intensity was restored, enabling a highly sensitive response to T-2 toxin. There was a good linear correlation between fluorescence intensity and T-2 toxin concentration in the range of 0.5-100 ng ml -1. The LOD of this fluorescence aptasensor was 0.239 ng ml-1 (S/N = 3). Besides, the recoveries of milk and beer were 89.86-108.99% (RSD = 2.0-2.6%) and 92.31-111.51% (RSD = 2.3-2.9%), respectively. The fluorescence aptasensor exhibited advantages of excellent analytical performance, convenient operation procedure and good selectivity. Predictably, the aptasensor was supposed to detect antibiotics and other pollutants, describing an intriguing blueprint and potential application prospect in food safety, biochemical sensing and environmental conservation.