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The present study aimed to investigate the alterations in functional interaction between hippocampal CA1 and medial entorhinal cortex (MEC) after moderate traumatic brain injury (TBI) in C57BL/6J mice, and the possible beneficial effects of comprehensive exercise (CE). Following TBI, two microelectrodes were implanted into CA1 and MEC for extracellular recording. We found a clear synchronization of neuronal firing in CA1 and MEC, particularly within 100 Hz and peaked at 20-30 Hz range. TBI induced a significant reduction (P < 0.001) of the coherences of firing between 20-40 Hz frequency band. The mean power spectral densities (PSD) of all group mice in MEC were steadily larger than the values in CA1 in both 20-40 Hz and 56-100 Hz ranges. TBI induced significant and consistent increases of averaged 20-40 Hz or 56-100 Hz PSD (P < 0.001 or P < 0.01) in both CA1 and MEC. Injured mice displayed more varied firing patterns, and showed increased burst frequency (BF), burst duration (BD), inter-spike intervals (ISI) and inter-burst interval (IBI). Injured mice also showed worsened neurological function, sleep, gait performance, and working memory. CE facilitated the restoration of aforementioned electrophysiological characteristics and functional deficits in TBI mice. These results suggest that the beneficial effects of CE on TBI functional deficits may be partly attributed to improved neuronal network interaction between CA1 and MEC.
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Lesões Encefálicas Traumáticas , Córtex Entorrinal , Animais , Camundongos , Camundongos Endogâmicos C57BL , Hipocampo , Redes Neurais de ComputaçãoRESUMO
The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
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Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Recuperação de Função Fisiológica , Inibidores do Fator de Necrose TumoralRESUMO
Vasculogenic mimicry (VM) refers to the process by which highly aggressive tumor cells mimic endothelial cells to form vessel-like structures that aid in supplying enough nutrients to rapidly growing tumors. Histone deacetylases (HDACs) regulate the expression and activity of numerous molecules involved in cancer initiation and progression. Notably, HDAC3 is overexpressed in the majority of carcinomas. However, thus far, no data are available to support the role of HDAC3 in VM. In this study, we subjected glioma specimens to immunohistochemical and histochemical double-staining methods and found that VM and HDAC3 expression were related to the pathological grade of gliomas. The presence of VM correlated with HDAC3 expression in glioma tissues. The formation of tubular structures, as determined by the tube formation assay to evaluate VM, was impaired in U87MG cells when transfected by siRNA or treated with an HDAC3 inhibitor. Importantly, the expression of VM-related molecules such as MMP-2/14 and laminin5γ2 was also affected when HDAC3 expression was altered. Furthermore, U87MG cells were treated with a phosphoinositide 3-kinase (PI3K) inhibitor or/and ERK inhibitor and found that the PI3K and ERK signaling pathways play key roles in VM; whereas, in VM, the two signaling pathways did not act upstream or downstream from each other. Taken together, our findings showed that HDAC3 contributed to VM in gliomas, possibly through the PI3K/ERK-MMPs-laminin5γ2 signaling pathway, which could potentially be a novel therapeutic target for gliomas.
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Glioma/enzimologia , Histona Desacetilases/metabolismo , Neovascularização Patológica/enzimologia , Adulto , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Glioma/irrigação sanguínea , Histona Desacetilases/genética , Humanos , Laminina/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
The effects of dietary addition of yeast Rhodotorula benthica (R. benthica) D30 which isolated from local sea mud at levels of 0 (control), 10(5), 10(6) and 10(7) CFU/g feed on the growth performance, digestive enzyme activity, immunity and disease resistance of juvenile sea cucumber Apostichopus japonicus were investigated. It was shown that dietary addition of R. benthica D30 significantly increased the growth rates of sea cucumbers (p < 0.05). The amylase activity, cellulase activity and alginase activity were increased for the animals from three probiotics treated groups. And with the supplemented concentration increased, the values of those digestive enzyme activities increased as well. Dietary addition of R. benthica D30 at the level of 10(7) CFU significantly increased the lysozyme, phagocytic and total nitric oxide synthase activity of A. japonicus (p < 0.05). While, the highest values of the phenoloxidase and alkaline phosphatase activity were found in sea cucumbers fed with R. benthica D30 at the level of 10(6) CFU. Whereas adding R. benthica D30 to diet had no significant effects on the total coelomocyte counts and acid phosphatase activity of A. japonicus (p > 0.05). It was observed that adding R. benthica D30 could significantly decrease the cumulative mortality of sea cucumbers. The present study demonstrated that dietary addition of R. benthica D30 could increase growth performance and some digestive enzyme activities, improve immunity and disease resistance of A. japonicus. And the medium (10(6) CFU) and high (10(7) CFU) additional levels showed better effects. It suggests that yeast R. benthica D30 could be a good probiotic for aquaculture.
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Aquicultura , Probióticos/farmacologia , Rhodotorula/química , Stichopus/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta , Digestão/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Probióticos/administração & dosagem , Stichopus/enzimologia , Stichopus/crescimento & desenvolvimento , Stichopus/imunologiaRESUMO
Thus far, little is known about whether jackfruit flake, a byproduct of jackfruit, can be used as a fermentation substrate to obtain value-added products through microbial fermentation. Here, jackfruit flake puree was fermented by three different ways: spontaneous fermentation (JF), inoculated with LAB (JFL), inoculated co-fermentation with LAB and yeast (JFC). In contrast to JF, the total polyphenol and flavonoid content and syndrome-associated enzyme inhibition are significantly increased in JFC at the end of fermentation. Electronic tongue analysis revealed that the JFC was significantly lower in astringency and higher in bitterness. 41 volatile compounds were identified during fermentation by HS-SPME-GC-MS, and JFC was richer in honey, rose, and fruity flavors. A total of 290 compounds were screened for discriminative pre- and post-fermentation differential metabolites by non-target metabolomics analysis. These results provide a potential reference for the conversion of jackfruit waste into functional products using fermentation.
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In this study, a new fermented food was developed using pineapple by-products and whey protein (2.6%) as raw materials through the co-fermentation of autochthonous lactic acid bacteria and yeast. To better understand the fermentation mechanism and the impact of microorganisms on the entire fermentation system, we tracked the changes in carbohydrate and amino acid profiles, organoleptic quality and microbial community during the fermentation process. Compared with unfermented samples, dietary fiber and free amino acids increased significantly as fermentation proceeded. The fermented samples were significantly lower in astringency and bitterness and significantly higher in sourness, umami and richness. The fermented products were richer in volatile compounds with floral, cheesy, fruity and other flavors. Relevant analyses showed that the core microbial community was highly correlated with the quality attributes of the fermented products. Microorganisms such as Lactococcus, Weissella, Hanseniaspora, Saccharomyces and Lachancea contributed significantly to the fermented products.
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An ethanol/(NH4)2SO4 biphasic (aqueous two-phase) system was designed to effectively separate antioxidant peptides from Xuanwei ham, and its potential to prevent ultraviolet A-induced damage to skin cells was explored. Optimization via single factor experiments and response surface methodology revealed that under 20 % ethanol aqueous solution (w/w), 25.5 % (NH4)2SO4 aqueous solution (w/w), and pH 8.80 conditions, the optimal extraction ratio was 59.0 ± 1.73 %. In vitro antioxidant activity and cellular assays showed that the peptide purified in the upper phase exhibited strong antioxidant activity, increasing the viability of HaCat cells damaged by UVA irradiation from 56.14 ± 1.05 % to 66.3 ± 1.76 %. We used an in silico peptide screening strategy and identified 10 with potential antioxidant activity, emphasizing the important role of amino acids Pro, Gly, and Ala in antioxidant activity.
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Antioxidantes , Citoproteção , Antioxidantes/química , Peptídeos/farmacologia , Peptídeos/química , Água , Etanol/químicaRESUMO
Dry-cured hams contain abundant bioactive peptides with significant potential for the development of functional foods. However, the limited bioavailability of food-derived bioactive peptides has hindered their utilization in health food development. Moreover, there is insufficient regulatory information regarding bioactive peptides and related products globally. This review summarizes diverse bioactive peptides derived from dry-cured ham and by-products originating from various countries and regions. The bioactivity, preparation techniques, bioavailability, and metabolic stability of these bioactive peptides are described, as well as the legal and regulatory frameworks in various countries. The primary objectives of this review are to dig deeper into the functionality of dry-cured ham and provide theoretical support for the commercialization of bioactive peptides from food sources, especially the dry-cured ham.
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Manipulação de Alimentos , Produtos da Carne , Peptídeos , Animais , Produtos da Carne/análise , Manipulação de Alimentos/métodos , Disponibilidade Biológica , Suínos , Humanos , Alimento Funcional , Estabilidade ProteicaRESUMO
As a traditional fermented meat product, dry-cured Xuanwei ham could be a rich source of bioactive peptides. This study intended to investigate the transepithelial transport and cytoprotection of antioxidant peptides isolated from simulated gastrointestinal digestion of Xuanwei ham. Through ultrafiltration and gel filtration chromatography after simulated digestion, five new antioxidative cell-penetrating peptides (CPPs) with 16-27 amino acid residues were identified, and protective effects of the pretreatment with GHYTEGAELVDSVLDVVRK (GK-19) and TDEFQLHTNVNDGTEFGGSIYQK (TK-23) on H2O2-induced damaged HepG2 cells were investigated. The results showed that the peptide TK-23 at 0.5 mg mL-1 showed a good antioxidant activity through upregulating the activity of antioxidant enzymes (CAT, SOD and GR) and decreasing the MDA level in H2O2-induced damaged HepG2 cells with a better protective effect compared to GSH. Our observations of novel antioxidant CPPs with 16-27 amino acid residues could enrich the antioxidative CPP database, and these findings could provide data support for further study of CPPs.
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Antioxidantes , Citoproteção , Antioxidantes/química , Peróxido de Hidrogênio , Peptídeos/química , DigestãoRESUMO
In this study, we developed an ultrasound-assisted alkaline method for extracting black soldier fly larvae protein (BSFLP). The effects of ultrasound-assisted extraction on the nutritional value, structural characteristics, and techno-functional properties of BSFLP were compared with those using the conventional hot alkali method. The results showed that ultrasound-assisted extraction significantly increased the extraction ratio of BSFLP from 55.40% to 80.37%, but reduced the purity from 84.19% to 80.75%. The BSFLP extracted by ultrasound-assisted extraction met the amino acid requirements for humans proposed by the Food and Agriculture Organization in 2013, and ultrasound-assisted extraction did not alter the limiting amino acids of the BSFLP. The ultrasound-assisted extraction increased the in vitro protein digestibility from 82.97% to 99.79%. Moreover, ultrasound-assisted extraction obtained BSFLP with a more ordered secondary structure and more loosely porous surface morphology, without breaking the peptide bonds. By contrast, the conventional hot alkaline method hydrolyzed BSFLP into smaller fragments. The effect of ultrasound-assisted extraction on the structure of BSFLP improved the solubility and emulsion capacity of BSFLP, but reduced its foaming properties. In conclusion, the results of this study suggest that ultrasound-assisted alkaline extraction could be a suitable method for extracting BSFLP and improving its nutritional value, and structural and functional properties. The findings obtained in this study could promote the wider application of BSFLP in food industry.
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Dípteros , Animais , Humanos , Larva , Aminoácidos/metabolismo , Alimentos , Valor NutritivoRESUMO
Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.
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Tratamento Farmacológico da COVID-19 , Ligusticum/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/virologia , Configuração de Carboidratos , Sequência de Carboidratos , Medicamentos de Ervas Chinesas , Humanos , Polissacarídeos/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificaçãoRESUMO
Obesity is a major global health problem determined by heredity and environment, and its incidence is increasing yearly. In recent years, increasing evidence linking obesity to the gut microbiota has been reported. Gut microbiota management has become a new method of obesity treatment. However, the complex interactions among genetics, environment, the gut microbiota, and obesity remain poorly understood. In this review, we summarize the characteristics of the gut microbiota in obesity, the mechanism of obesity induced by the gut microbiota, and the influence of genetic and environmental factors on the gut microbiota and obesity to provide support for understanding the complex relationship between obesity and microbiota. At the same time, the prospect of obesity research related to the gut microbiota is proposed.
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Microbioma Gastrointestinal , Disbiose , Humanos , ObesidadeRESUMO
This study evaluated for the first time the feasibility of mild preheating treatment of broccoli florets combined with lactic acid bacteria fermentation for enhancing sulforaphane yield in broccoli puree. The optimum preheating condition for in-pack processing of broccoli florets was 3 min treatment at 65 °C increasing sulforaphane yield in broccoli puree by â¼5 times compared to untreated broccoli. Preheating of broccoli florets in-pack (65 °C per 3 min) combined with lactic acid bacteria fermentation further enhanced the sulforaphane content by â¼16 times compared to untreated broccoli. The sulforaphane content of the preheated-fermented puree remained stable (â¼94% retention) for two weeks at 4 °C. The results indicate that a combination of judicious heat treatment of broccoli florets with lactic acid bacteria fermentation enables production of safe and high sulforaphane content broccoli products with potential health benefits.
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Brassica , Isotiocianatos/metabolismo , Ácido Láctico/farmacologia , Lactobacillales/metabolismo , Culinária , Fermentação/efeitos dos fármacos , Temperatura Alta , Humanos , SulfóxidosRESUMO
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of gastrointestinal tract in the world, and the long-term prognosis for ESCC patients still remains dismal due to the lack of effective early diagnosis biomarkers. MATERIALS AND METHODS: Western blot and immunochemistry were used to determine the expression of PRR11 in 201 clinicopathologically characterized ESCC specimens. The effects of PRR11 on stem cell-like traits and tumorigenicity were examined by tumor sphere formation assay and SP assays in vitro and by a tumorigenesis model in vivo. The mechanism by which PRR11 mediated Wnt/ß-catenin signaling was explored using luciferase reporter, immuno-chemistry, and real time-PCR (RT-PCR) assays. RESULTS: We found that PRR11 was markedly upregulated, at the level of both transcription and translation, in ESCC cell lines as compared with normal esophageal epithelial cells (NECCs). Immunohistochemical analysis showed that 69.2% paraffin-embedded archival ESCC specimens exhibited high levels of PRR11 expression, and multivariate analysis revealed that PRR11 upregulation might be an independent prognostic indicator for the survival of patients with ESCC. Furthermore, overexpression of PRR11 dramatically enhanced, whereas inhibition of PRR11 reduced the capability of cancer stem cell (CSC)-like phenotypes and tumorigenicity of ESCC cells both in vitro and in vivo. Mechanically, we demonstrated PRR11-enhanced tumorigenicity of ESCC cells via activating Wnt/ß-catenin signaling, and PRR11 expression is found to be significantly correlated with ß-catenin nuclear location in ESCC. CONCLUSION: Our findings suggest that the PRR11 might represent a novel and valuable prognostic marker for ESCC progression and play a role during the development and progression of this malignancy.
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BACKGROUND: Glioma is the most lethal primary brain tumor, the survival rate still isn't improved in the past decades. It's essential to study the regulatory mechanism of glioma progression, hoping to find new therapy targets or methods. The family of tripartite motif (TRIM) containing proteins are E3 ubiquitination ligases, which play critical role in various tumor progression. METHODS: Cell proliferation and invasion were analyzed by colony formation assay, soft agar growth assay, BrdU incorporation assay and transwell invasion assay. Luciferase reporter analysis was used to analyze NF-κB pathway activity. RESULTS: We found TRIM31 was upregulated in glioma cells and tissues, its overexpression significantly promoted glioma cell proliferation and invasion, while its knockdown significantly inhibited glioma cell proliferation and invasion. Mechanism analysis found TRIM31 promoted NF-κB pathway activity and increased its targets expression. NF-κB inhibition reversed the phenotype caused by TRIM31, confirming TRIM31 promoted glioma progression through activating NF-κB pathway. Using clinical specimens found TRIM31 expression was positively correlative with NF-κB activity. CONCLUSION: This study found TRIM31 promoted glioma proliferation and invasion through activating NF-κB activity.
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This research was aimed to explore correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease (AD).This study was a case-control study. Two hundred eleven AD hospitalized patients were selected as the AD group and 241 subjects were selected as the control group. PCR-RFLP was used to detect three loci (rs7755, rs3211956, and rs10499859) of CD36 gene and ApoE genotype. Chi-square test and univariate nonconditional logistic regression analysis were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI). The haplotypes were constructed using SHEsis online software and the correlation between haplotypes and AD was analyzed. Meanwhile, differences of 3 alleles of ApoE and 6 genotypes (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4) were compared between AD and control groups.The frequencies of rs7755 genotype (χâ=â10.780, Pâ=â.005) and allele (χâ=â10.549, Pâ=â.001) were statistically different between 2 groups. The genotype frequency of rs3211956 was statistically different between AD and control groups (χâ=â10.119, Pâ=â.006). For the rs7755 locus, GG genotype (OR: 2.013, 95% CI: 1.098-3.699) was an independent risk factor for AD compared with AA genotype. In the dominant model, the risk to develop AD in AG/GG genotype was 1.686 times higher than AA genotype. For the rs3211956 locus, compared with TT genotype, GT genotype (OR: 0.536, 95% CI: 0.340-0.846) was a protective factor for AD after adjusting various physiological and biochemical factors. In the dominant model, the risk of GT/GG genotype to develop AD was reduced by 41.6%. For ApoE gene, the distribution differences of E2/E3 (χâ=â9.216, Pâ=â.002), E3/E4 (χâ=â7.728, Pâ=â.005), and E4/E4 had statistical significance between the 2 groups. The frequencies of allele E2 (χâ=â9.359, Pâ=â.002) and E4 (χâ=â13.995, Pâ<â.001) were statistically significant between AD and control groups.The rs7755 and rs3211956 loci polymorphisms of CD36 gene and genotype E2/E3, E3/E4, E4/E4 of ApoE gene, and E2 and E4 alleles were statistically related with AD.
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Doença de Alzheimer/genética , Apolipoproteínas E/genética , Antígenos CD36/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The basic helix-loop-helix myogenic regulatory factors play critical roles in skeletal myogenesis. Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear. In this study, we used BEF (spontaneously immortalized bovine embryonic fibroblast that shows myogenic differentiation by overexpression of MyoD) and C2C12 cells to investigate the function of MRF4. Ectopic expressions of MRF4 did not stimulate myogenic differentiation in the BEF and C2C12 cells, but did show a marked increase of cell proliferation, upregulation of cyclin E, and downregulation of p21WAF1. Furthermore, MRF4 was found to induce degradation of the MyoD protein, which acts as a transcriptional activator for p21WAF1, and thus indicates that MRF4 accelerates cell proliferation by suppressing MyoD-dependent p21WAF1 expression. However, forced expression of MyoD in the MRF4-overexpressing cells inhibited cell proliferation and partially induced myogenic differentiation, which suggests that MyoD is a potential negative intercessor of MRF4 in the regulation of the cell cycle. Taken together, these results indicate that MRF4 and MyoD play competitive roles in myogenesis by stimulating cell proliferation and differentiation, respectively.
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Células Musculares/citologia , Células Musculares/fisiologia , Desenvolvimento Muscular/fisiologia , Proteína MyoD/metabolismo , Mioblastos/citologia , Mioblastos/fisiologia , Fatores de Regulação Miogênica/metabolismo , Transdução de Sinais/fisiologia , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , CamundongosRESUMO
A new type of cobalt(II)-doped carbon dots (CCDs) have been fabricated and used successfully for sensing Cr(VI) ions on the basis of photoluminescence quenching. The structural characterization of as-obtained CCDs was thoroughly performed by transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) and X-ray photoelectron (XPS) spectroscopy. The optical properties were also determined by absorption and fluorescence spectra. By recording 3D fluorescence spectrum, a unique intra-particle Förster resonance energy transfer (FRET) system was investigated. In addition, fluorescence quenching of CCDs was observed in the presence of Cr(VI) ions due to inner filter effect. A good linear relationship between the concentration of Cr(VI) ions and fluorescent intensity was obtained in the range from 5µM to 125µM (R2=0.99), and the limit of detection was calculated as 1.17µM (0.12ppm for Cr(VI)). Importantly, this method was capable of rapidly detecting Cr(VI) ions in tap water and fish samples, which may be helpful in risk reduction of intake Cr(VI) contamination from water and seafood.