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(1) Background: Particulate methane monooxygenase (pMMO) has a strong dependence on the natural electron transfer path and is prone to denaturation, which results in its redox activity centers being unable to transfer electrons with bare electrodes directly and making it challenging to observe an electrochemical response; (2) Methods: Using methanobactin (Mb) as the electron transporter between gold electrodes and pMMO, a bionic interface with high biocompatibility and stability was created. The Mb-AuNPs-modified functionalized gold net electrode as a working electrode, the kinetic behaviors of pMMO bioelectrocatalysis, and the effect of Mb on pMMO were analyzed. The CV tests were performed at different scanning rates to obtain electrochemical kinetics parameters. (3) Results: The values of the electron transfer coefficient (α) and electron transfer rate constant (ks) are relatively large in test environments containing only CH4 or O2. In contrast, in the test environment containing both CH4 and O2, the bioelectrocatalysis of pMMO is a two-electron transfer process with a relatively small α and ks; (4) Conclusions: It was inferred that Mb formed the complex with pMMO. More importantly, Mb not only played a role in electron transfer but also in stabilizing the enzyme structure of pMMO and maintaining a specific redox state. Furthermore, the continuous catalytic oxidation of natural substrate methane was realized.
Assuntos
Ouro , Imidazóis , Nanopartículas Metálicas , Oligopeptídeos , Oxigenases , Ouro/química , Cobre/química , Nanopartículas Metálicas/química , Oxirredução , Minerais , Metano/química , EletrodosRESUMO
BACKGROUND: Allergic reactions to crustacean products have been increasing owing to the rising consumption. Tropomyosin (TM) is the main crustacean allergen; it has a coiled-coil structure, which shows stability to various food processing methods. Crustacean processed products have been used in several food products, thereby causing greater difficulties in detecting TM in these products. We aimed to develop an assay based on high-performance liquid chromatography-tandem mass spectrometry for the accurate and reproducible quantification of crustacean TM in foods. RESULTS: The three peptides IQLLEEDLER, LAEASQAADESER, and IVELEEELR were selected as peptide markers, and the peptide IVELEEELR was selected as the quantitative marker. Extraction conditions and enzymatic digestion conditions were completely optimized. The extraction solution of Tris-hydrochloric acid buffer (50 mmol L-1 , pH 7.4) containing 1 mol L-1 potassium chloride and the enzymatic treatment at 1:15 ratio (enzyme/protein, m/m) for 13 h showed excellent efficiency. The method exhibited a good linear relationship, with the qualified coefficient of determination (R2 = 0.9994) in the wide range of 1 to 1000 µg L-1 . The accuracy was validated based on spiked recovery at three spiking levels (12.5, 25.0, and 50.0 µg kg-1 , TM/matrix) in blank matrices that included chicken sausages, beef balls, and egg-milk biscuits. The recoveries ranged from 91% to 109% with qualified relative standard deviations <15% with the limit of quantification (of 1.6 mg kg-1 , TM/matrix). CONCLUSION: This new approach can be used for the qualitative and quantitative detection of crustacean TM in various food matrices. © 2021 Society of Chemical Industry.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Crustáceos/química , Espectrometria de Massas em Tandem/métodos , Tropomiosina/química , Sequência de Aminoácidos , Animais , Contaminação de Alimentos/análise , Peptídeos/química , Frutos do Mar/análiseRESUMO
WHAT IS KNOWN AND OBJECTIVE: Aristolochic acid (AA) is an abundant compound in Aristolochia plants and various natural herbs. In the 1990s, a slimming formula used in Belgium that contains Aristolochia fangchi was reported to cause kidney damage and bladder cancer, and aristolochic acid nephropathy (AAN) is now well recognized worldwide. In October 2017, researchers reported an AA signature that is closely associated with hepatocellular carcinoma (HCC) worldwide. COMMENT: There are differing opinions on the toxicity of AA, and different countries have taken different measures to address the issue. There is a lack of clarity on the causal role of AA in hepatocarcinogenesis and on the potential underlying mechanisms for the reported nephrotoxicity and carcinogenicity. The toxicity of AA differs depending on gender and age, and other risk factors that could explain the variability in the toxicity of AA remain to be identified. WHAT IS NEW AND CONCLUSION: Whether preparations containing AA, such as many Chinese medicines, should be used remains controversial, and this issue warrants further investigation before definite conclusions can be drawn.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Carcinoma Hepatocelular/induzido quimicamente , Nefropatias/induzido quimicamente , Neoplasias Hepáticas/induzido quimicamente , Fatores Etários , Ácidos Aristolóquicos/administração & dosagem , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Nefropatias/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Fatores de Risco , Fatores SexuaisRESUMO
Particulate methane monooxygenase (pMMO) is a characteristic membrane-bound metalloenzyme of methane-oxidizing bacteria that can catalyze the bioconversion of methane to methanol. However, in order to achieve pMMO-based continuous methane-to-methanol bioconversion, the problems of reducing power in vitro regeneration and pMMO stability need to be overcome. Methanobactin (Mb) is a small copper-chelating molecule that functions not only as electron carrier for pMMO catalysis and pMMO protector against oxygen radicals, but also as an agent for copper acquisition and uptake. In order to improve the activity and stability of pMMO, methanobactin-Cu (Mb-Cu)-modified gold nanoparticle (AuNP)-pMMO nanobiohybrids were straightforwardly synthesized via in situ reduction of HAuCl4 to AuNPs in a membrane fraction before further association with Mb-Cu. Mb-Cu modification can greatly improve the activity and stability of pMMO in the AuNP-pMMO nanobiohybrids. It is shown that the Mb-Cu-modified AuNP-pMMO nanobiohybrids can persistently catalyze the conversion of methane to methanol with hydroquinone as electron donor. The artificial heterogeneous nanobiohybrids exhibited excellent reusability and reproducibility in three cycles of catalysis, and they provide a model for achieving hydroquinone-driven conversion of methane to methanol.
Assuntos
Proteínas de Bactérias/química , Enzimas Imobilizadas/química , Ouro/química , Imidazóis/química , Nanopartículas Metálicas/química , Methylosinus trichosporium/enzimologia , Oligopeptídeos/química , Oxigenases/química , Estabilidade EnzimáticaRESUMO
Inorder to brought S-naproxen into small intestine, an optically pure (S)-naproxen starch ester was produced by lipase through enantio-selective trans-esterification of racemic naproxen methyl ester with pretreatment starch in solvent system. With carefully selection of the reaction medium (isooctane), lipase (Carica Papaya Lipase, CPL) and the reaction mode (intermittent opening), a high conversion rate (48.6%) and enantiomeric excess of product (99.6%) was obtained. The slow release macromolecular (S)-Naproxen had been synthesized to improve the efficacy of racemic naproxen and overcome its side effects. The enanitomeric ratio of CPL (E=52.5) was higher than CRL (E=22) and greatly influenced by the byproduct methyl alcohol. The intermittent opening reaction mode was the effective way to remove the inhibition of methyl alcohol and to improve the enantio-selectivity of CPL. S-naproxen starch was confirmed by HPLC and 1H NMR. This method may also apply to preparation the other optically pure 2-phenylpropionic acid derivatives. S-naproxen starch was a new optically pure derivatives possessing emulsifying and slow release properties would be widely applied to the food, pharmaceutical and biomedical industries.
Assuntos
Carica/enzimologia , Lipase/química , Naproxeno/análogos & derivados , Naproxeno/síntese química , Amido/química , Catálise , Esterificação , Naproxeno/química , Solventes/química , EstereoisomerismoRESUMO
Pinoresinol diglucoside (PD), a typical marker compound in Ecommia ulmoides Oliv., is an important and natural antihypertensive drug. A selective, sensitive, and rapid liquid chromatography tandem mass spectrometric (LC-MS/MS) analytical method was developed for the determination of PD in rats. After simple protein precipitation with acetonitrile, chromatographic separation of PD was conducted using a reversed-phase ZORBAX SB C18 analytical column (4.6mm × 150 mm, 5 µm particles) with a mobile phase of 10mM ammonium acetate-methanol-acetic acid (50:50:0.15, v/v/v) and quantified by selected reaction monitoring mode under positive electrospray ionization condition. The chromatographic run time was 3.4 min for each sample, in which the retention times of PD and the internal standard were 2.87 and 2.65 min, respectively. The calibration curves were linear over the range of 1.00~3000 ng/mL and the lower limit of quantification was 1.00 ng/mL in rat plasma. The precision expressed by relative standard deviations were <8.9% for intra-batch precision and <2.0% for inter-batch precision, and the intra- and inter-batch accuracy by relative error was within the range of -3.9% ~7.3%, which met acceptable criteria. The LC-MS/MS method was successfully applied to investigate the pharmacokinetics and oral bioavailability of PD in rats, with the bioavailability being only 2.5%.
Assuntos
Anti-Hipertensivos/sangue , Anti-Hipertensivos/farmacocinética , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Lignanas/sangue , Lignanas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Disponibilidade Biológica , Calibragem , Cromatografia Líquida de Alta Pressão/normas , Cromatografia de Fase Reversa/normas , Estabilidade de Medicamentos , Injeções Intravenosas , Lignanas/administração & dosagem , Modelos Lineares , Masculino , Ratos Wistar , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem/normasRESUMO
Starch, lipids, and proteins are essential biological macromolecules that play a crucial role in providing energy and nutrition to our bodies. Interactions between these macromolecules have been shown to impact starch digestibility. Understanding and controlling starch digestibility is a key area of research. Investigating the mechanisms behind the interactions of these three components and their influence on starch digestibility is of significant practical importance. Moreover, these interactions can result in the formation of resistant starch, which can be fermented by gut microbiota in the colon, leading to various health benefits. While current research has predominantly focused on the digestive properties of starch in the small intestine, there is a notable gap in understanding the colonic microbial fermentation phase of resistant starch. The benefits of fermentation of resistant starch in the colon may outweigh its glucose-lowering effect in the small intestine. Thus, it is crucial to study the fermentation behavior of resistant starch in the colon. This paper investigates the impact of interactions among starch, lipids, and proteins on starch digestion, with a specific focus on the fermentation phase of indigestible carbohydrates in the colon. Furthermore, valuable insights are offered for guiding future research endeavors.
Assuntos
Microbiota , Amido , Amido Resistente , Fermentação , Lipídeos , ColoRESUMO
A common epitope (AGSFDHKKFFKACGLSGKST) of parvalbumin from 16 fish species was excavated using bioinformatics tools combined with the characterization of fish parvalbumin binding profile of anti-single epitope antibody in this study. A competitive enzyme-linked immunosorbent assay (ELISA) based on the common epitope was established with a limit of detection of 10.15 ng/mL and a limit of quantification of 49.29 ng/mL. The developed ELISA exhibited a narrow range (71% to 107%) of related cross-reactivity of 15 fish parvalbumin. Besides, the recovery, the coefficient of variations for the intra-assay and the inter-assay were 84.3% to 108.2%, 7.4% to 13.9% and 8.5% to 15.6%. Our findings provide a novel idea for the development of a broad detection method for fish allergens and a practical tool for the detection of parvalbumin of economic fish species in food samples.
Assuntos
Ensaio de Imunoadsorção Enzimática , Epitopos , Proteínas de Peixes , Peixes , Parvalbuminas , Animais , Parvalbuminas/imunologia , Parvalbuminas/análise , Ensaio de Imunoadsorção Enzimática/métodos , Peixes/imunologia , Epitopos/imunologia , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Alérgenos/imunologia , Alérgenos/análiseRESUMO
Fucoidan is a native sulfated polysaccharide mainly isolated from brown seaweed, with diverse pharmacological activities, such as anti-inflammatory and antifibrosis. Hyperuricemia (HUA) is a common metabolic disease worldwide and mainly causes hyperuricemic nephropathy, including chronic kidney disease and end-stage renal fibrosis. The present study investigated the protective function of fucoidan in renal fibrosis and its pharmacological mechanism. The renal fibrotic model was established with the administration of potassium oxonate for 10 weeks. The protein levels of related factors were assessed in HUA mice by an enzyme-linked immunosorbent assay (ELISA) and western blotting. The results showed that fucoidan significantly reduced the levels of serum uric acid, blood urea nitrogen (BUN), α-smooth muscle actin (α-SMA), and collagen I, and improved kidney pathological changes. Furthermore, renal fibrosis had been remarkably elevated through the inhibition of the epithelial-to-mesenchymal transition (EMT) progression after fucoidan intervention, suppressing the Janus kinase 2 (JAK2) signal transducer and activator of transcription protein 3 (STAT3) signaling pathway activation. Together, this study provides experimental evidence that fucoidan may protect against hyperuricemia-induced renal fibrosis via downregulation of the JAK2/STAT3 signaling pathway.
Assuntos
Hiperuricemia , Laminaria , Insuficiência Renal Crônica , Camundongos , Animais , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Ácido Úrico/metabolismo , Laminaria/metabolismo , Rim/metabolismo , Fibrose , Polissacarídeos/metabolismo , Transdução de Sinais , Insuficiência Renal Crônica/metabolismoRESUMO
OBJECTIVE: To investigate the constituents of the Annona squamosa and evaluate their anti-tumor activity. METHOD: The compounds were isolated and purified by various column chromatography. Their structures were elucidated by spectral data analysis. Their anti-tumor activity was assayed by SRB method. RESULT: Eleven compounds were obtained from the 95% EtOH extract. The structures were determined as: annosquamosin C(1),15, 16-epoxy-17-hydroxy-ent-kau-ran-19-oic acid (2),16,17-dihydroxy-ent-kau-ran-19-oic acid(3), annosquamosin A(4), ent-kaur-16-en-19-oic acid (5), 19-nor-ent-kauran4-ol-17-oic acid (6),16-hydroxy ent-kau ran-19-oic acid (7), ent-15beta-hydroxy-kaur-16-en-19-oic acid (8), annosquamosin B (9), ent-16beta, 17-dihydroxykauran-19-al (10), 16, 17-dihydroxy-ent-kauran-19-oic acid me thyl ester (11). Compounds 1,2,3,5,9 showed different inhibitory activities against 95-D lung cancer cells,the effect of compound 5 was strongest with the IC50 value 7.78 micromol x L(-1); Compounds 2, 5, 9 showed inhibitory activities against A2780 ovarian cancer cells, the effects of compounds 2 and 9 were strong with the IC50 values being 0.89, 3.10 micromol x L(-1), respectively. CONCLUSION: Compound 2 was firstly isolated from this family, while compound 8 and 10 were first found from this genus and the title species, respectively. The in vitro anti-tumor test showed compound 5 significantly inhibited 95-D lung cancer cells and compounds 2 and 9 exhibited remarkbale activity against A2780 ovarian cancer cells.
Assuntos
Annona/química , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Casca de Planta/químicaRESUMO
Molecular simulation is a new technology to analyze the interaction between molecules. This review mainly summarizes the application of molecular simulation technology in the food industry. This technology has been employed to assess structural changes of biomolecules, the interaction between components, and the mechanism of physical and chemical property alterations. These conclusions provide a deeper understanding of the molecular interaction mechanism in foods, break through the limitations of scientific experiments and avoid blind and time-consuming scientific research. In this paper, the advantages and development trends of molecular simulation technology in the food research field are described. This methodology can be used to contribute to further studies of the mechanism of molecular interactions in food, confirm experimental results and provide new ideas for research in the field of food sciences.
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Accumulating evidence points to a critical role of the brain gut axis as an important paradigm for many central nervous system diseases. Recent studies suggest that propolis has obvious neuroprotective properties and functionality in regulating intestinal bacteria flora, hinting at a potential key effect at both terminals of this axis regulation. However, currently no clear evidence confirms the effects of propolis on alcohol-induced depression. Here, we establish an alcoholic depression model with C57BL/6J mice and demonstrate that treatment with propolis protects against alcohol-induced depressive symptoms by behavioral tests. In addition, propolis attenuates the injury of nerve cells in the hippocampal region and restores the serum levels of brain-derived neurotrophic factor (BDNF) and dopamine (DA) in mice with alcohol-induced depression. Pathology and biotin tracer assays show that propolis repairs the intestinal leakage caused by alcohol. Additionally, propolis treatment increases the expression levels of intestinal intercellular tight junctions' (TJs') structural proteins Claudin-1, Occludin and zona occludens-1 (ZO-1), as well as the activation state of the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway, which is closely related to the intestinal permeability. Furthermore, propolis can reduce the levels of pro-inflammatory, lipopolysaccharide (LPS) and fatty-acid-binding protein 2 (FABP2), suggesting the significance of the inflammatory response in alcoholic depression. Collectively, our findings indicate that propolis exerted an improving effect on alcohol-induced depressive symptoms by ameliorating brain gut dysfunction.
Assuntos
Própole , Animais , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Etanol/metabolismo , Etanol/toxicidade , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Própole/farmacologia , Própole/uso terapêuticoRESUMO
The gut-liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman's correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.
RESUMO
Fructose has been reported to acutely elevate the circulating fibroblast growth factor 21 (FGF21) levels, which ultimately causes FGF21 resistance. FGF21 resistance is suggested to result in lipid metabolism disorder. Nicotinamide riboside (NR) can alleviate lipid metabolism disorder in mice. It is unknown whether NR supplementation would alleviate lipid metabolism disorder in high-fructose exposed mice via improving FGF21 resistance. In this study, C57BL/6J mice were given 20% fructose solution for free drinking with the supplementation of NR in 400 mg kg-1 day-1. The results showed that NR supplementation decreased the serum and hepatic lipid profile levels. The increase of lipid droplets in the liver and the size of adipose cells in WAT induced by a high-fructose diet were alleviated by the addition of NR. NR supplementation increased the NAD+/NADH ratio and activated the SIRT1/NF-κB pathway. The down-regulation of NF-κB is accompanied by a decrease in inflammation, which may increase the expression of the FGF21 receptor complex, namely KLB and FGFR, then restore its downstream signaling cascade, including ERK phosphorylation and EGR1 and c-FOS expression, and ultimately improve FGF21 resistance. With the FGF21 function recovery, hepatic PGC-1α expression was up-regulated, and hepatic SREBP-1c expression was down-regulated, resulting in decreased lipogenesis. Furthermore, restoration of the FGF21 signaling pathway also led to increased expression of ATGL and HSL in WAT, which promotes lipolysis. In conclusion, we found that NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the regulation of inflammation mediated by the SIRT1/NF-κB signaling pathway.
Assuntos
Frutose , Transtornos do Metabolismo dos Lipídeos , Niacinamida , Animais , Camundongos , Tecido Adiposo Branco/metabolismo , Frutose/efeitos adversos , Inflamação/metabolismo , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacologiaRESUMO
Oxidative stress injury (OSI) occurs in many cardiovascular diseases, and the OSI of endothelial cells is the main pathological basis of these diseases. Tectorigenin has an effect on oxidative stress in fibroblasts, keratinocytes, and neuroblastoma. This study attempted to reveal the effect of Tectorigenin on OSI in endothelial cells. An OSI cell model was firstly established by treating human umbilical vein endothelial cells (HUVECs) with H2O2. The H2O2-induced HUVECs were further pre-treated with Tectorigenin or PI3K inhibitor. Then the viability and apoptosis of HUVECs were evaluated using MTT, Hochest 33258 staining and TUNEL staining. Lactate dehydrogenase (LDH) leakage, enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) level were measured through colorimetric assays. The expressions of apoptosis-related factors and the activation of the PI3K/Akt pathway in HUVECs were detected by RT-qPCR or Western blot. Tectorigenin had no inhibiting effect on the viability of HUVECs at the concentrations of 0.1, 0.5, 0.5, 1, and 10 µmol/L. Tectorigenin reversed the H2O2 induced-destruction of HUVECs morphology. Tectorigenin increased the viability and decreased the apoptosis of H2O2-induced HUVECs. Tectorigenin increased Bcl-2 expression and the enzyme activities of SOD and GSH-Px, but decreased LDH leakage, MDA level, and the expressions of Bax and Cleaved Caspase-3 in H2O2-induced HUVECs. Furthermore, Tectorigenin increased the ratios of p-PI3K to PI3K and p-Akt to Akt in H2O2-induced HUVECs. PI3K inhibitor had an opposite effect of Tectorigenin on the OSI in H2O2-induced HUVECs and its effect was further reversed by Tectorigenin. Tectorigenin protected HUVECs against H2O2-induced OSI via PI3K/Akt pathway.
Assuntos
Citoproteção/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Peróxido de Hidrogênio/toxicidade , Isoflavonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismoRESUMO
Chinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Cardiotônicos/farmacologia , Dioscorea/química , Doxorrubicina/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína 2 Associada à Farmacorresistência Múltipla/genética , Rizoma/química , Animais , Biomarcadores , Cardiotônicos/química , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Cromatografia Líquida de Alta Pressão , Doxorrubicina/efeitos adversos , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
In the present study, the influence of lipid emulsion on the allergenicity of digestion products of fish parvalbumin (PV) was investigated, which was initially subjected to simulated gastric/intestinal digestion both under emulsified and non-emulsified conditions. The release of ß-hexosaminidase (ß-hex), histamine (His), tryptase (TPS), interleukin 4 (IL-4), and IL-13 in RBL cells was decreased by 79.32, 26.19, 41.67, 53.95 and 54.40%, respectively, following stimulation with the gastric digestion products of PV. Whereas, lipid emulsified digestion products of PV (e-PV) significantly enhanced the release of active mediators and cytokines. The digestion products of emulsified PV at 180 min resulted in a higher release of ß-hex (197.60%), His (12.18%), TPS (38.85%), IL-4 (48.19%) and IL-13 (59.40%), as compared to that of PV. However, no obvious differences in the release of active substances and cytokines were noted between intestinal digestion products of PV and intestinal digestion products of emulsified PV. In the mouse model studies, digested PV products reduced the anaphylactic scores, whereas e-PV manifested a higher level of allergic symptoms. Moreover, mice treated with 50% e-PV had significantly higher levels of specific IgE (32.56%), total IgE (16.67%) and total IgG1 (5.15%) than those treated with 50% PV. Mice treated with 50% e-PV had significantly higher levels of His (8.50%) and TPS (10.07%) compared with mice treated with 50% PV. Lipid emulsions altered the digestibility of PV in gastrointestinal digestion and enhanced the allergenicity of PV digestion products at the cellular levels, subsequently posing a higher risk of allergic reactions in susceptible individuals.
Assuntos
Alérgenos/imunologia , Digestão , Emulsões , Linguados , Hipersensibilidade Alimentar/imunologia , Parvalbuminas/metabolismo , Anafilaxia , Animais , Citocinas , Duodeno/patologia , Feminino , Histamina , Imunoglobulina E , Imunoglobulina G , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Baço/patologia , Triptases , beta-N-Acetil-HexosaminidasesRESUMO
In this study, the effect of enzymatic cross-linking of shrimp tropomyosin (TM) with tyrosinase and caffeic acid (TM-Tyr/CA) on the allergic response were assessed using in vitro and in vivo models. The RBL-2H3 and KU812 cell lines were employed to evaluate the changes in the stimulation abilities of TM-Tyr/CA that showed significant inhibition of mediators and cytokines. The digestibility of cross-linked TM was improved and the recognitions of IgG/IgE were markedly reduced, as revealed by western blotting. TM-Tyr/CA decreased anaphylactic symptoms, and hindered the levels of IgG1, IgE, histamine, tryptase and mouse mast-cell protease-1 (mMCP-1) in mice sera. Cross-linked TM downregulated the production of interleukin (IL)-4, IL-5, and IL-13 by 51.36, 12.24 and 20.55%, respectively, whereas, IL-10 and IFN-γ were upregulated by 20.71 and 19.0%. TM-Tyr/CA showed reduced allergenicity and may have preventive effect in relieving TM induced allergic response via immunosuppression and positive modulation of T-helper (Th)1/Th2 immunobalance.
Assuntos
Ácidos Cafeicos/química , Monofenol Mono-Oxigenase/metabolismo , Penaeidae/imunologia , Células Th1/citologia , Células Th2/citologia , Tropomiosina/metabolismo , Animais , Linhagem Celular , Histamina/sangue , Hipersensibilidade , Imunoglobulina E/sangue , Camundongos , Alimentos Marinhos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
BACKGROUND: Cancer metastasis is the main obstacle to increasing the lifespan of cancer patients. Epithelial-to-mesenchymal transition (EMT) plays a significant role in oncogenic processes, including tumor invasion, intravasation, and micrometastasis formation, and is especially critical for cancer invasion and metastasis. The extracellular matrix (ECM) plays a crucial role in the occurrence of EMT corresponding to the change in adhesion between cells and matrices. CONCLUSION: SPOCK1 is a critical regulator of the ECM and mediates EMT in cancer cells. This suggests an important role for SPOCK1 in tumorigenesis, migration and invasion. SPOCK1 is a critical regulator of some processes involved in cancer progression, including cancer cell proliferation, apoptosis and migration. Herein, the functions of SPOCK1 in cancer progression are expounded, revealing the association between SPOCK1 and EMT in cancer metastasis. SPOCK1 is a positive downstream regulator of transforming growth factor-ß, and SPOCK1-mediated EMT regulates invasion and metastasis through the Wnt/ß-catenin pathway and PI3K/Akt signaling pathway. It is of significance that SPOCK1 may be an attractive prognostic biomarker and therapeutic target in cancer treatment.