RESUMO
Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below -7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG's inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.
RESUMO
Water-soluble fluorescent chemosensors for lead ion are highly desirable in environmental detection and bioimagery. Based on a water-soluble pillar[5]arene WP5 and imidazolium terminal functionalized 2,2'-bibenzimidazole derivative BIHB, we report a host-guest charge transfer assembly BIHB-2WP5 for sensitive and selective detection of Pb2+ in pure aqueous media. As a result of its high electron-rich cavity, WP5 can bind electron-deficiency guest BIHB with various host/guest stoichiometry to easily tune the microtopography of assembly from nanoparticle to nanocube. In view of the good biocompatibility and sensitivity, the supramolecular assembly BIHB-2WP5 was used as a fluorescent probe for the detection of Pb2+ in living cells and a smartphone Pb2+ detection device was constructed for the in situ test.
RESUMO
BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.
RESUMO
BACKGROUND AND AIM: The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. METHODS: The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). RESULTS: After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. CONCLUSIONS: This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.
Assuntos
Ácidos e Sais Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células T Matadoras Naturais , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/cirurgia , Células T Matadoras Naturais/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/cirurgia , Ácidos e Sais Biliares/metabolismo , Masculino , Humanos , Feminino , Colecistectomia , Modelos Animais de Doenças , Camundongos , Hepatectomia , Pessoa de Meia-Idade , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Imunidade Celular , Recidiva Local de Neoplasia/prevenção & controle , Interferon gama/metabolismo , Fatores de Risco , IdosoRESUMO
BACKGROUND Percutaneous coronary intervention (PCI), a therapeutic approach to coronary heart disease, significantly alleviates symptoms of coronary heart disease (CHD) and substantially improves quality of life. This study aimed to investigate the effect of home cardiac rehabilitation (HCR) on patients after PCI. MATERIAL AND METHODS We randomly divided 106 patients after PCI into an Intervention group (n=52) and a Control group (n=53). Left ventricular ejection fraction (LVEF), blood pressure, blood glucose, and low-density lipoprotein were measured in both groups before hospital discharge and after 3 months of engaging in the intervention. Patients were assessed using the short-form health survey (SF-12) scale and Hospital Anxiety and Depression Scale (HADS) scale. RESULTS After 3 months of HCR intervention, SF-12 scores of patients in the Intervention group were significantly higher compared to patients in the Control group (physical component summary (PCS): 47.46±9.86 vs 43.28±8.21; and Mental Component Summary (MCS): 50.68±9.82 vs 48.26±9.69) (P.
Assuntos
Reabilitação Cardíaca , Doença das Coronárias , Intervenção Coronária Percutânea , Humanos , Qualidade de Vida , Bem-Estar Psicológico , Volume Sistólico , Função Ventricular Esquerda , Doença das Coronárias/tratamento farmacológicoRESUMO
Four pairs of neolignan enantiomers (±)-1- (±)-4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+)-2 and (±)-3 exerted protective activities against H2O2-induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications.
Assuntos
Crataegus , Lignanas , Neuroblastoma , Humanos , Lignanas/farmacologia , Frutas/química , Crataegus/química , Peróxido de Hidrogênio/farmacologiaRESUMO
Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/patologia , Triterpenos Pentacíclicos/metabolismo , ObesidadeRESUMO
Fenpyroximate is an efficient, broad-spectrum phenoxypyrazole acaricide which is used for controlling various mites. In this study, we measured the levels of terminal fenpyroximate residues in citrus fruits, and estimated the dietary intake risks posed by fenpyroximate. To this end, a QuEChERS analytical method was used in combination with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine the residual levels of fenpyroximate and its Z-isomer (Z-fenpyroximate) in citrus fruits collected from 12 fields under good agricultural practices (GAPs). The average recoveries of fenpyroximate in whole fruits and citrus flesh were 104-110% and 92-109%, respectively, with corresponding RSDs of 1-4% and 1-3%. The average recoveries of Z-fenpyroximate were 104-113% and 90-91%, respectively, with RSDs of 1-2% in both cases. Each limit of quantification (LOQ) was 0.01 mg kg-1. Fifteen days after application with 56 mg kg-1, the terminal residues of fenpyroximate in whole fruits and citrus flesh were <0.010-0.18 mg kg-1 and <0.010-0.063 mg kg-1, respectively; the corresponding values for total fenpyroximate (the sum of fenpyroximate and Z-fenpyroximate) were <0.020-0.19 and <0.020-0.053 mg kg-1. The levels of terminal fenpyroximate residues in citrus fruit were less than the maximum residue limits (MRLs) specified in all the existing international standards. In addition, the risk quotients RQc and RQa were both less than 100%, indicating that the long-term and short-term dietary intake risks posed to Chinese consumers by fenpyroximate in citrus fruit are both acceptable after a 15-day harvest interval.
Assuntos
Citrus , Resíduos de Praguicidas , Cromatografia Líquida de Alta Pressão , Citrus/química , Espectrometria de Massas em Tandem/métodos , Resíduos de Praguicidas/análiseRESUMO
Isoxaflutole and atrazine are representative pesticides for weed control in corn fields. Formulations containing these two pesticides have been registered in China, and their residues may threaten food safety and human health. In this study, a method for simultaneous determination of isoxaflutole, atrazine, and their metabolites in fresh corn, corn kernels, and corn straw was established based on modified QuEChERS pre-treatment and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The linearity of seven compounds was good (R2 ≥ 0.9912), and the matrix effect was 48.5-77.1%. At four spiked levels of 0.01, 0.02, 0.05, and 0.5 mg kg-1, all compounds' average recovery was 76% to 116%, with relative standard deviation (RSD) less than 18.9%. Field experiments were conducted in Liaoning, Heilongjiang, Inner Mongolia, Shanxi, Beijing, and Yunnan provinces to study the terminal residues. The terminal residues of all compounds were below the LOQ (0.01 mg kg-1) in fresh corn and corn kernels, and atrazine residues in corn straw ranged from <0.05 mg kg-1 to 0.17 mg kg-1. Finally, a dietary risk assessment was conducted based on residues from field trials, food consumption, and acceptable daily intake (ADI). For all populations, the chronic dietary risk probability (RQc) of atrazine was between 0.0185% and 0.0739%, while that of isoxaflutole was 0.0074-0.0296%, much lower than 100%. The results may provide scientific guidance for using isoxaflutole and atrazine in corn field ecosystems.
Assuntos
Atrazina , Resíduos de Praguicidas , Praguicidas , Humanos , Cromatografia Líquida de Alta Pressão , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Zea mays/química , Ecossistema , China , Praguicidas/análise , Medição de RiscoRESUMO
BACKGROUND: Evidence for the efficacy of combined PD-1 and HER2 blockade with chemotherapy on progression-free and overall survival in HER2-positive gastro-oesophageal cancer is scarce. The first interim analysis of the randomised, phase 3 KEYNOTE-811 study showed a superior objective response with pembrolizumab compared with placebo when added to trastuzumab plus fluoropyrimidine and platinum-based chemotherapy. Here, we report results from protocol-specified subsequent interim analyses of KEYNOTE-811. METHODS: The randomised, phase 3 KEYNOTE-811 trial involved 168 medical centres in 20 countries worldwide. Patients aged 18 years or older with locally advanced or metastatic HER2-positive gastro-oesophageal junction adenocarcinoma, without previous first-line treatment, were randomly assigned (1:1) by an integrated interactive voice-response and web-response system to intravenous pembrolizumab 200 mg or placebo, both to be combined with standard chemotherapy (fluoropyrimidine and platinum-based therapy) plus trastuzumab every 3 weeks for up to 35 cycles or until disease progression, unacceptable toxic effects, or investigator or participant-initiated withdrawal. Randomisation used a block size of four and was stratified by region, PD-L1 status, and chemotherapy. Dual primary endpoints were progression-free and overall survival, analysed by intention to treat. Safety was assessed in all randomly assigned patients who received at least one dose of study treatment according to the treatment received. KEYNOTE-811 is registered with ClinicalTrials.gov (NCT03615326) and is active but not recruiting. FINDINGS: Between Oct 5, 2018, and Aug 6, 2021, 698 patients were assigned to pembrolizumab (n=350) or placebo (n=348). 564 (81%) were male and 134 (19%) were female. At the third interim analysis, 286 (82%) of 350 patients in the pembrolizumab group and 304 (88%) of 346 in the placebo group who received treatment had discontinued treatment, mostly due to disease progression. At the second interim analysis (median follow-up 28·3 months [IQR 19·4-34·3] in the pembrolizumab group and 28·5 months [20·1-34·3] in the placebo group), median progression-free survival was 10·0 months (95% CI 8·6-11·7) in the pembrolizumab group versus 8·1 months (7·0-8·5) in the placebo group (hazard ratio [HR] 0·72, 95% CI 0·60-0·87; p=0·0002). Median overall survival was 20·0 months (17·8-23·2) versus 16·9 months (15·0-19·8; HR 0·87 [0·72-1·06]; p=0·084). At the third interim analysis (median follow-up 38·4 months [IQR 29·5-44·4] in the pembrolizumab group and 38·6 months [30·2-44·4] in the placebo group), median progression-free survival was 10·0 months (8·6-12·2) versus 8·1 months (7·1-8·6; HR 0·73 [0·61-0·87]), and median overall survival was 20·0 months (17·8-22·1) versus 16·8 months (15·0-18·7; HR 0·84 [0·70-1·01]), but did not meet prespecified criteria for significance and will continue to final analysis. Grade 3 or worse treatment-related adverse events occurred in 204 (58%) of 350 patients in the pembrolizumab group versus 176 (51%) of 346 patients in the placebo group. Treatment-related adverse events that led to death occurred in four (1%) patients in the pembrolizumab group and three (1%) in the placebo group. The most common treatment-related adverse events of any grade were diarrhoea (165 [47%] in the pembrolizumab group vs 145 [42%] in the placebo group), nausea (154 [44%] vs 152 [44%]), and anaemia (109 [31%] vs 113 [33%]). INTERPRETATION: Compared with placebo, pembrolizumab significantly improved progression-free survival when combined with first-line trastuzumab and chemotherapy for metastatic HER2-positive gastro-oesophageal cancer, specifically in patients with tumours with a PD-L1 combined positive score of 1 or more. Overall survival follow-up is ongoing and will be reported at the final analysis. FUNDING: Merck Sharp & Dohme.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Humanos , Masculino , Feminino , Trastuzumab , Antígeno B7-H1 , Adenocarcinoma/patologia , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Método Duplo-CegoRESUMO
To assess the potential risks posed to the environment and human health, analyzing pesticide residues in proso millet is important. This paper aimed to develop a modified QuEChERS method with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the analysis of 54 pesticide residues in proso millet. Parameters including the mobile phase of the instrument, the acidity of the extraction solvent, and the type of absorbents were optimized to provide satisfactory performance. The method was validated concerning linearity, limit of quantification (LOQ), matrix effect, accuracy, and precision. In detail, the linearity of the matrix-matched calibration curve was acceptable with correlation coefficients (R2) higher than 0.99. The mean recovery was in the range of 86% to 114% with relative standard deviations (RSDs) ≤ 20% (n = 5). The LOQ was determined to be 0.25-10 µg/kg. The developed method was feasible for the determination of multiple pesticide residues in proso millet.
Assuntos
Panicum , Resíduos de Praguicidas , Praguicidas , Humanos , Praguicidas/análise , Resíduos de Praguicidas/análise , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
The technology of carbon capture, utilization, and storage (CCUS) is an important component of carbon neutral technology systems. To confirm the carbon storage potential of CO2 foamed concrete (CFC), this study addressed the principle of carbon storage in CFC materials. It is apparent that carbon storage of CFC materials includes carbon fixation in concrete skeletons and carbon storage in CFC bubbles. The carbon fixation of CFC skeletons is realized by CO2 mineralization. As the concrete skeleton in CFC is in the CO2 atmosphere, the carbonation of CFC materials or CO2 mineralization is more complete. Research shows that the carbonation rate of CFC materials can reach almost 30% after acidification, foaming with high CO2 pressure and curing in the atmosphere. The carbonation rate is higher than the rate in concrete curing with CO2. A mathematical model was established to calculate carbon fixation capacity in CFC materials, and the carbon fixation and storage capacity in CFC material were estimated. The results showed that more than 99% carbon storage of CFC was realized by the chemical carbonization of the concrete skeleton. Comparatively, the potential of carbon storage in the bubble of CFC was small. In this study, carbon storage capacity was divided into three categories, i.e., theoretical maximum capacity, relative reliable capacity, and expected capacity or potential. The carbonation rate for theoretical maximum capacity was 100%, when all the concrete was considered to be carbonated. As the carbonation rate of concrete during the whole life cycle is approximately 55% all over the world, 50% was set as the carbonation rate for relative reliable capacity calculation. If at high temperatures, CO2 curing with high pressure or accessory ingredients applied to silicate concrete can improve carbonation rate to be over 80%, when the carbon storage capacity is considered to be expected capacity or potential. In 2017-2021, the theoretical maximum capacity of carbon storage was 3.623×109 t CO2 in China, with 7.25×108 t·a-1. The relative reliable capacity was 3.75×108 t·a-1, and the expected capacity was 5.80×108 t·a-1. If the carbonation rate was 30%, the carbon storage of concrete produced annually in China during the whole life cycle reached 2.18×108 t, which was more than the carbon sink of Daxing'anling forest for one year. In coal electricity integrated mining areas and large thermal, metallurgical, cement chemical, and other high-energy consuming enterprises, CFC has a good prospect of development to promote the recycling of solid waste and waste gas. Meanwhile, it is pointed out that the stability of CFC before solidification is a technical problem to be solved in the next step.
RESUMO
Myclobutanil residue poses a potential threat to consumers' health. This work aims to investigate the degradation behavior, residue levels, processing factors (PFs) and dietary risk of myclobutanil in tomato. Myclobutanil was analyzed using a modified quick, easy, cheap, effective, rugged, safe (QuEChERS) method combined with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS), and average recoveries ranged from 82% to 102% with relative standard deviations RSDs ≤ 9.1%. After spraying myclobutanil miscible oil under field conditions, the initial concentration of myclobutanil was 0.055 mg/kg, and its dissipation followed the first-order kinetics equation with a half-life of 2.88 days. Myclobutanil was mainly present in the tomato skin, and its concentration was about four times that in the whole tomato. The initial concentration of myclobutanil in raw tomato was 0.100 mg/kg. After washing, peeling, homogenization, simmering and canning, the residual level of myclobutanil decreased to 0.067 mg/kg, 0.023 mg/kg, 0.013 mg/kg, 0.044 mg/kg and 0.041 mg/kg, respectively. Although the procedure of simmering led to an increase in myclobutanil concentration, the PFs were all less than 1 in the whole process, showing that the processing procedure significantly decreased the residual level of myclobutanil canned tomato paste in comparison with the raw agricultural commodity. Washing, peeling, and homogenization played critical roles in reducing pesticide residues. The residues of myclobutanil during the processing of tomato pose low dietary exposure risks to consumers in China, which were acceptable. However, the acute and chronic risk quotient for children revealed that it was necessary to monitor the dietary exposure of pesticide residues for children closely.
Assuntos
Resíduos de Praguicidas , Solanum lycopersicum , Criança , Humanos , Cromatografia Líquida , Exposição Dietética , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To summarize and discuss the guiding role of endoscopic ultrasound (EUS) in selecting endoscopic treatments for submucosal tumors (SMTs) in the upper gastrointestinal tract. METHODS: A retrospective investigation was conducted on 156 SMT patients who received endoscopic resection guided by EUS in the endoscopy center of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2019 to September 2021. Next, the size, pathological type, and distribution of lesions were analyzed; the correlation of the tumor origin with distribution of lesions and selection of treatments was explored; and the consistency of preoperative EUS diagnosis and postoperative pathological diagnosis was summarized and analyzed. RESULTS: The tumor diameters of the included SMT patients ranged from 0.3 to 4 cm, with a mean diameter of 0.95 cm; the lesions were mostly located in the esophagus, gastric fundus or fundic cardia and gastric body. As for the pathological types, liomyoma was the most common tumor in the esophagus, liomyoma and mesenchymoma were mainly located in the fundic cardia and gastric body, and heterotopic pancreas was mostly discovered in the gastric sinus. Among 38 esophageal SMT patients, some with lesions originating from muscularis mucosa and submucosa under EUS mainly underwent endoscopic submucosal dissection (ESD) and endoscope band ligation (EBL); while others with lesions originated from muscularis propria mainly received submucosal tunneling endoscopic resection (STER). Of 115 gastric SMT patients under EUS, some with lesion origins from the muscularis mucosa and submucosa mainly underwent endoscopic submucosal excavation (ESE), while others from muscularis propria mainly underwent ESE, ESD, and endoscopic full-thickness resection (EFTR). Besides, 3 duodenal SMT patients with lesion origins from submucosa and muscularis propria under EUS were given ESD and ESE, respectively. Additionally, 121 cases showed a consistency between the EUS diagnosis and the postoperative pathological nature, and the consistency rate was 84.6%. CONCLUSION: Clarifying the origin layer, size, growth pattern, and pathological nature of the lesion through preoperative EUS can guide the precise selection of endoscopic treatments, thereby ensuring a safe, effective, and complete surgical outcomes and reducing complications.
Assuntos
Neoplasias , Trato Gastrointestinal Superior , Humanos , Estudos Retrospectivos , Endossonografia , EndoscopiaRESUMO
As a valuable traditional Chinese herbal medicine, Radix Astragali has attracted much attention due to its extensive pharmacological activities. In this study, density functional theory (DFT) was used thermodynamically and kinetically in detail to predict the antioxidant activity and reaction mechanisms involved in the free radical scavenging reactions of three representative isoflavonoids (formononetin, calycosin, and calycosin-7-glucoside) extracted from Radix Astragali. Three main mechanisms, including hydrogen atom transfer (HAT), proton transfer after electron transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were examined by calculating the thermodynamic parameters. It was found that HAT is the predominant mechanism in the gas phase, while SPLET is supported in the solvent environment. The isoflavonoids' order of antioxidant activity was estimated as: calycosin > calycosin-7-glucoside > formononetin. For the calycosin compound, the result revealed the feasibility of double HAT mechanisms, which involve the formation of stable benzodioxazole with significantly reduced energy in the second H+/e- reaction. In addition, the potential energy profiles and kinetic calculations show that the reaction of â¢OH into the 3'-OH site of calycosin has a lower energy barrier (7.2 kcal/mol) and higher rate constant (4.55 × 109 M-1 s-1) compared with other reactions in the gas phase.
Assuntos
Medicamentos de Ervas Chinesas , Flavonas , Antioxidantes/farmacologia , Prótons , Modelos Teóricos , Hidrogênio , Glucosídeos , TermodinâmicaRESUMO
In this study, a magnetic deep eutectic solvent coupled with dispersive liquid-liquid microextraction using high-performance liquid chromatography (MDES-DLLME-HPLC) was developed to detect strobilurin fungicides. The green hydrophobic MDES synthesized by methyltrioctylammonium chloride, ferric chloride, and heptanoic acid was used as an extraction solvent, which was dispersed by vortex and separated by an external magnetic field. The use of toxic solvents was avoided, and the separation time was reduced. The best experimental results were obtained through single factor and response surface optimization. The method had a good linear relationship with R2 > 0.996. The limit of detection (LOD) ranged from 0.001 to 0.002 mg L-1. The extraction recoveries were 81.9-108.9%. The proposed method was rapid and green, and it has been successfully applied to detection of strobilurin fungicides in water, juice, and vinegar.
RESUMO
Spirotetramat is a potential tetronic acid pesticide for controlling various pests with piercing-sucking mouthparts. To clarify its dietary risk on cabbage, we established an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and then investigated the residual levels of spirotetramat and its four metabolites in cabbage collected from field experiments under good agricultural practices (GAPs). The average recoveries of spirotetramat and its metabolites in cabbage were 74~110%, while the relative standard deviation (RSD) was 1~6%, and the limit of quantitation (LOQ) was 0.01 mg kg-1. The terminal residue of spirotetramat was in the range of <0.05~0.33 mg kg-1, the chronic dietary risk (RQc) was 17.56%, and the acute dietary risk (RQa) was 0.025~0.049%, which means an acceptable dietary intake risk. This study provides data to guide on the use of spirotetramat and to establish the maximum residue limits (MRLs) of spirotetramat on cabbage.
Assuntos
Brassica , Resíduos de Praguicidas , Cromatografia Líquida de Alta Pressão , Brassica/química , Espectrometria de Massas em Tandem , Medição de Risco , Resíduos de Praguicidas/análiseRESUMO
Estrogen-related receptor ß (ESRRB) is a member of the orphan nuclear receptor family and mediates stem cell self-renewal and early embryonic development. Previous studies have also reported that ESRRB plays a role in the development and progression of breast cancer and prostate cancer. In this study, we observed that ESRRB was highly expressed in cervical cancer and was associated with disease progression. Knocking out ESRRB using CRISPR/Cas9 gene editing in cervical cancer cells induced cell-cycle arrest at the transition from the G0-G1 phase to the S phase, resulting in inhibition of cell proliferation in vitro and reduced tumor growth in vivo. Conversely, ectopic expression of ESRRB significantly promoted the proliferation of cervical cancer cells. ESRRB activated transcription of SMAD7, a TGFß pathway inhibitor, which blocked phosphorylation and nuclear translocation of SMAD2/3 to the nucleus, thereby downregulating CDKN1A and upregulating CCNA2 and MYC. In turn, MYC transactivated ESRRB and upregulated SMAD7, thus forming a positive feedback loop with ESRRB. Together, these findings identify the tumor-promoting function of ESRRB in cervical cancer and reveal a mechanism by which ESRRB stimulates cell proliferation to promote cancer progression. SIGNIFICANCE: The ESRRB/SMAD7/MYC-positive feedback loop inhibits TGFß signaling to activate cell-cycle progression and promote proliferation in cervical cancer, thereby driving tumor growth.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Proliferação de Células , Receptores de Estrogênio , Transdução de Sinais , Fator de Crescimento Transformador beta , Neoplasias do Colo do Útero/genéticaRESUMO
Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.
Assuntos
Medicamentos de Ervas Chinesas , Cloreto de Metileno , Absorção Cutânea , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/químicaRESUMO
A simple, green extraction method of dithiocarbamate (DTC) pesticides in food samples was developed using adhesive tapes and a green deep eutectic solvent (DES). A rapid and convenient determination and distinction method of DTC pesticides was established using tyrosinase inhibition assay. First, DTC pesticides were extracted by pasting and peeling off the adhesive tape, then eluted by the DES synthesized from xylitol and ethylene glycol. Second, determination of DTC pesticides was conducted by inhibiting the activity of tyrosinase which can catalyze the oxidation of catechol. Less colored products were generated in the reaction system (tyrosinase, catechol, and 4-aminoantipyrine), leading to weak absorbance. In addition, different DTC pesticides (ziram, propineb, zineb, mancozeb, thiram, metiram, and ferbam) were successfully distinguished by sensor arrays (tyrosinase, phenolic compounds, and 4-aminoantipyrine) through principal component analysis. The limit of detection was found to be 0.2 µg kg-1, and the limit of quantification was 0.6 µg kg-1. The recoveries ranging from 89.4% to 103.8% were obtained in vegetable, fruit, and cereal, with a relative standard deviation of less than 4.2%. The method is simple, rapid, and convenient and shows good application prospects in the determination of pesticides in a variety of food samples.