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1.
Dig Liver Dis ; 56(1): 92-97, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37659917

RESUMO

BACKGROUND: Emerging clinical evidence has been discovered associating Inflammatory bowel disease (IBD) with Henoch-Schönlein purpura (HSP) and immune thrombocytopenia (ITP). However, it is unclear whether a cause-effect relationship exists between them. We aimed to examine the casual effect of IBD on the risk of HSP and ITP. METHODS: Based on summary statistics from International IBD Genetics (IIBDG) Consortium and FinnGen study, a two-sample Mendelian randomization study was carried out to determine whether IBD including ulcerative colitis (UC) and Crohn's disease (CD) is causally related to HSP, ITP or secondary thrombocytopenia. To support the results, a variety of sensitivity analyses were performed. RESULTS: Significant causal relationships between IBD and HSP (odds ratios = 1.20, 95% confidence interval: 1.07-1.36, adjusted P = 0.006) and ITP (odds ratios =1.22, 95% confidence interval: 1.08-1.38, adjusted P = 0.006) were found. Both genetically predicted UC and CD were positively related with ITP, while CD alone may be responsible for the higher risk of HSP. Besides, no significant association was observed between IBD and secondary thrombocytopenia. CONCLUSIONS: The results of this Mendelian randomization study supported the causal association of IBD with HSP and ITP. Taken together, our findings may present implications for management of IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Vasculite por IgA , Doenças Inflamatórias Intestinais , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/genética , Análise da Randomização Mendeliana , Vasculite por IgA/complicações , Vasculite por IgA/genética , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Doença de Crohn/genética , Colite Ulcerativa/complicações , Colite Ulcerativa/genética
2.
Food Chem ; 426: 136621, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37354582

RESUMO

A rapid and selective sorbent for the enrichment of dibutyl phthalate (DBP) from water and Chinese Baijiu samples was established using magnetic surface molecularly imprinted polymers (MSMIPs) combined with gas chromatography-mass spectrometer (GC-MS). The MSMIPs were synthesized using a magnetic nanosphere material with silica layer, increasing the polymer surface area as a carrier. Compared with the traditional methods, the addition of magnetic microspheres simplified the process of food substrate purification and significantly shortened the pre-concentration time. The MSMIPs adsorption conforms to the Freundlich isotherm model as multilayer adsorption on an inhomogeneous surface and the pseudo-second-order model. The developed MSMIPs combined with GC-MS method showed good linearity in DBP concentration range of 0.02-1.0 mg L-1 with low LOD (0.0054 mg L-1) and LOQ (0.018 mg L-1), and obtained good recoveries in real samples (95.2-97.2%) with RSD < 5.0% (n = 9), which were consistent with those from Chinese national standard method.


Assuntos
Impressão Molecular , Nanoestruturas , Dibutilftalato , Polímeros Molecularmente Impressos , Impressão Molecular/métodos , Adsorção , Fenômenos Magnéticos , Extração em Fase Sólida/métodos
3.
Cancer Biol Med ; 21(4)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38164734

RESUMO

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells. One of the most exciting advances within this field is the targeting of neoantigens, which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells. Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment, early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors. Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens. Consequently, personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences. This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines, and also discusses challenges and future perspectives for this innovative approach, particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.


Assuntos
Antígenos de Neoplasias , Vacinas Anticâncer , Imunoterapia , Neoplasias , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Antígenos de Neoplasias/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Medicina de Precisão/métodos , Animais
4.
Anal Chim Acta ; 1231: 340392, 2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36220287

RESUMO

In this study, a ZrO2/nitrogen-doped three-dimensional porous carbon (ZrO2/N-3DPC) nanocomposite was manufactured to fabricate an effective electrochemical sensor for the detection of ultra-trace mercury ion (Hg2+). The synthesized N-3DPC had an open pore structure, large specific surface area and enough continuous mass transfer channels, which can facilitate the diffusion and transmission of electrons and ions at the sensing interface, providing an effective adhesion platform for electrochemical deposition of ZrO2 nanoparticles. Benefiting from the synergistic effect of ZrO2 and N-3DPC, the developed electrochemical sensor had good adsorption and catalytic performance for Hg2+ with a wider linear range of 0.1-220 µg L-1 and a lower detection limit of 0.062 µg L-1. Meanwhile, the sensor exhibited remarkable repeatability, reproducibility, stability and anti-interference, and was further applied to detect Hg2+ in seafood and tap water with satisfactory recoveries (97.1-103.1%) and lower relative standard deviation (≤4.3%). The proposed strategy of electrochemical sensing detection of Hg2+ provides a new idea and direction for the research of ZrO2/N-3DPC nanocomposite in the field of analysis and detection, which is also of great significance to ensure foods, environmental safety and human health.


Assuntos
Técnicas Eletroquímicas , Mercúrio , Nanocompostos , Carbono/química , Técnicas Eletroquímicas/instrumentação , Humanos , Íons/química , Íons/isolamento & purificação , Mercúrio/isolamento & purificação , Nanocompostos/química , Nitrogênio/química , Porosidade , Reprodutibilidade dos Testes , Água/química
5.
Tohoku J Exp Med ; 257(4): 283-289, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35598971

RESUMO

We evaluated the protective effect of epifriedelinol against breast cancer and postulated an underlying mechanism. Breast cancer was induced by a single dose of 50 mg/kg 7,12-Dimethylbenanthracene (DMBA), and rats were treated with 100 or 200 mg/kg (i.p.) epifriedelinol for 4 weeks. We then evaluated the effect of epifriedelinol on tumor growth, oxidative stress and serum inflammatory cytokine levels in DMBA-induced breast cancer. Protein and mRNA levels were determined using western blotting and quantitative reverse transcription polymerase chain reaction, respectively. The tumor volume and weight were significantly (p < 0.01) decreased in the epifriedelinol-treated group compared to the negative control group. Epifriedelinol decreased the altered levels of oxidative stress and serum inflammatory cytokines in rats with DMBA-induced breast cancer. Protein levels of PI3K, AKT and mTOR and mRNA levels of PI3K, AKT, Map3k1, Erbb2 and Pdk1 were decreased in the mammary tissue of epifriedelinol-treated rats with DMBA-induced breast cancer. Apoptosis was significantly induced in the epifriedelinol-treated group compared to the negative control group. In conclusion, epifriedelinol ameliorates DMBA-induced breast cancer by regulating the PI3K/AKT pathway.


Assuntos
Neoplasias da Mama , Ácido Oleanólico/análogos & derivados , Fosfatidilinositol 3-Quinases , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Feminino , Ácido Oleanólico/farmacologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
6.
Nanomaterials (Basel) ; 12(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35407335

RESUMO

We demonstrate the growth of ultra-thin (~5 nm) indium ytterbium oxide (In-Yb-O) thin film using a simple vacuum-free aqueous solution approach for the first time. The influences of Yb addition on the microstructural, chemical, optical, and electrical properties of In2O3 are well investigated. The analyses indicate that Yb dopant could suppress oxygen vacancy defects effectively owing to the lower standard electrode potential, lower electronegativity, and stronger metal-oxide bond strength than that of In. The optimized In-Yb-O thin-film transistors (TFTs) exhibit excellent electrical performance (mobility of 8 cm2/Vs and on/off ratio of ~108) and enhanced stability. The triumph of In-Yb-O TFTs is owing to the high quality In2O3 matrix, the remarkable suppressor of Yb, and the nanometer-thin and atomically smooth nature (RMS: ~0.26 nm) of channel layer. Therefore, the eco-friendly water-induced ultra-thin In-Yb-O channel provides an excellent opportunity for future large-scale and cost-effective electronic applications.

7.
Food Chem ; 381: 132225, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35114624

RESUMO

A molecularly imprinted sensor for highly sensitive and selective determination of dibutyl phthalate (DBP) was fabricated by combining multi-walled carbon nanotubes (MWCNTs) and Au nanoparticles (AuNPs) with surface molecularly imprinted polymer (SMIPs). The MWCNTs and AuNPs were designed to modify the electrode surface to accelerate the electron transfer rate and enhance the chemical stability. SMIPs were synthesized using SiO2 microspheres as carriers. By loading SMIPs capable of identifying DBP on the surface of modified electrodes of MWCNTs and AuNPs, an electrochemical sensor for detecting DBP was successfully constructed. After optimizing the experimental conditions, the modified electrode SiO2-COOH@MIP/AuNPs/MWCNTs/GCE can recognize DBP in the range of 10-7g L-1 to 10-2g L-1, and the detection limit achieved to 5.09 × 10-9 g L-1 (S/N = 3). The results demonstrate that the proposed MIP electrochemical sensor may be a promising candidate electrochemical strategy for detecting DBP in complex samples.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Impressão Molecular , Nanotubos de Carbono , Técnicas Biossensoriais/métodos , Dibutilftalato , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro , Limite de Detecção , Impressão Molecular/métodos , Dióxido de Silício
8.
J Nanobiotechnology ; 20(1): 51, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078480

RESUMO

In this study, a thermo-sensitive molecularly imprinted fluorescence sensor was developed for the specific detection of ß-Lactoglobulin (ß-LG) allergen in milk products. The metal-organic frameworks (MIL-100) with a high specific surface area was coated on the surface of upconversion micro-particles (UCMPs). As the core, an imprinted polymer layer allowing for swelling and shrinking with response to temperature was prepared, which exhibited high adsorption and mass transfer capabilities for ß-LG allergen. The fluorescence intensity of UCMPs@MIL-100@MIP decreased linearly with the concentration of ß-LG in the range of 0.1-0.8 mg mL-1, and the limit of detection was 0.043 mg mL-1. The imprinting factor reached 3.415, which indicated that excellent specificity of the UCMPs@MIL-100@MIP for ß-LG allergen. In the analysis of ß-LG allergen in actual milk samples, the proposed UCMPs@MIL-100@MIP fluorescence sensor produced reliable and accurate results (recovery: 86.0-98.4%, RSD: 2.8-6.8%), closely related to the results of standard HPLC method (correlation coefficient: 0.9949), indicating that its feasibility in the detection of ß-LG allergen.


Assuntos
Impressão Molecular , Animais , Alérgenos , Lactoglobulinas , Limite de Detecção , Leite
9.
Biosens Bioelectron ; 197: 113755, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740119

RESUMO

A hydrophobic carboxyl functionalized phosphonium-based ionic liquid (IL) ((5-carboxypentyl) triphenylphosphonium bis (trifluoromethyl)sulfonyl) amide, TPP-HA[TFSI]) was synthesized through a simple hydrothermal approach. Based on the π-π and cation-π interactions with multi-wall carbon nanotubes (MWCNTs), a TPP-HA[TFSI]@MWCNTs hybrid was prepared to immobilize hemoglobin (Hb) to fabricate a simple and effective electrochemical sensing platform for the detection of methyl parathion (MP) in vegetables. Spectroscopic and electrochemical results show that TPP-HA[TFSI]@MWCNTs substrate synergistically provided a good biocompatible microenvironment for Hb, and the hydrophobicity of TPP-HA[TFSI] and the π-π interaction and hydrogen bonding between TPP-HA[TFSI]@MWCNTs, Hb and nafion (NF) were conducive to maintain the stability and integrity of the modified electrode interface. The TPP-HA[TFSI]@MWCNTs with large surface area and high conductivity promoted the exposure of the electroactive center of Hb and the direct electron transfer between Hb and the electrode, which effectively amplified the electrochemical signal and improved the sensitivity of MP detection. The constructed electrochemical sensing platform had a wider linear range (2-14 ng mL-1) and a lower detection limit (0.62 ng mL-1) for MP, and had acceptable repeatability, reproducibility, stability and anti-interference ability. This results indicated that the phosphonium-based ILs functionalized MWCNTs was an effective substrate for the immobilization of biological components, which have broad prospect in the construction of electrochemical sensing interfaces.


Assuntos
Técnicas Biossensoriais , Líquidos Iônicos , Metil Paration , Nanotubos de Carbono , Técnicas Eletroquímicas , Hemoglobinas , Reprodutibilidade dos Testes
10.
Front Psychol ; 13: 1063569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36600717

RESUMO

A questionnaire survey was conducted among 600 visitors to the region using Qingyuan Mountain, a 5A picturesque location in Quanzhou City, Fujian Province, as the research site. A total of 489 valid questionnaires were received. The links between cultural involvement, cultural experience, cultural identity, cultural confidence, and cultural loyalty were experimentally examined using a structural equation modeling technique. The results showed that cultural experience was a mediating factor in the processes of the influence of cultural involvement on cultural identity and the influence of cultural involvement on cultural confidence, but the influence of cultural involvement on cultural identity and the influence of cultural involvement on cultural confidence were not supported. The study accordingly condenses theoretical contributions to academia and management insights for businesses.

11.
Front Surg ; 9: 1037215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684294

RESUMO

The hormone receptor (HR) status and human epidermal growth hormone receptor 2 (HER2) status of patients with breast cancer may change following neoadjuvant chemotherapy (NAC). We retrospectively analyzed the clinical data of 294 patients with stage II/III breast cancer to evaluate the clinical significance and prognostic value of receptor transformation after NAC in breast cancer patients. Pathological complete response after NAC was achieved in 10.7% of patients. HR, estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 conversion rates were 9.2%, 6.5%, 13.0%, 4.4%, and 33.7%, respectively. Patients with stable HR (P = 0.01) and HER2 (P = 0.048) expression had more favorable overall survival (OS). Low or reduced Ki-67 expression was associated with better disease-free survival (DFS) (P < 0.001) and OS (P < 0.01). Multivariate analysis showed that the number of lymph nodes after NAC, HR conversion, and radiotherapy were independent prognostic factors for overall survival. HR conversion implied a higher risk of death [hazard ratio, 2.56 (95% confidence interval: 1.19-5.51); P = 0.016]. Patients with HR conversion after NAC who received endocrine therapy had better DFS (P = 0.674) and OS (P = 0.363) than those who did not receive endocrine therapy, even if the HR changed from positive to negative. In conclusion, pathological testing should be performed before and after NAC, and even patients with HR conversion after NAC might benefit from endocrine therapy.

12.
Foods ; 10(11)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34828878

RESUMO

Food allergies have seriously affected the life quality of some people and even endangered their lives. At present, there is still no effective cure for food allergies. Avoiding the intake of allergenic food is still the most effective way to prevent allergic diseases. Therefore, it is necessary to develop rapid, accurate, sensitive, and reliable analysis methods to detect food allergens from different sources. Aptamers are oligonucleotide sequences that can bind to a variety of targets with high specificity and selectivity, and they are often combined with different transduction technologies, thereby constructing various types of aptamer sensors. In recent years, with the development of technology and the application of new materials, the sensitivity, portability, and cost of fluorescence sensing technology have been greatly improved. Therefore, aptamer-based fluorescence sensing technology has been widely developed and applied in the specific recognition of food allergens. In this paper, the classification of major allergens and their characteristics in animal and plant foods were comprehensively reviewed, and the preparation principles and practical applications of aptamer-based fluorescence biosensors are summarized. In addition, we hope that this article can provide some strategies for the rapid and sensitive detection of allergens in food matrices.

13.
Food Res Int ; 148: 110578, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507726

RESUMO

Food allergies are one of the major health concerns worldwide and have been increasing at an alarming rate in recent times. The elimination of food allergenicity has been an important issue in current research on food. Irradiation is a typical nonthermal treatment technology that can effectively reduce the allergenicity of food, showing great application prospects in improving the quality and safety of foods. In this review, the mechanism and remarkable features of irradiation in the elimination of food allergens are mainly introduced, and the research progress on reducing the allergenicity of animal foods (milk, egg, fish and shrimp) and plant foods (soybean, peanut, wheat and nuts) using irradiation is summarized. Furthermore, the influencing factors for irradiation in the elimination of food allergens are analyzed and further research directions of irradiation desensitization technology are also discussed. This article aims to provide a reference for promoting the application of irradiation technology in improving the safety of foods.


Assuntos
Hipersensibilidade Alimentar , Alérgenos , Animais , Arachis , Hipersensibilidade Alimentar/prevenção & controle , Nozes , Alimentos Marinhos
14.
J Agric Food Chem ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133167

RESUMO

In this study, the rhodamine 6G hydrazide (R6GH) complex was synthesized to develop an "off-on" output platform for fluorescence and visual dual-mode analysis of lead(II) (Pb2+). The prepared R6GH complex using the heat to reflux reaction of rhodamine 6G (R6G) and hydrazine hydrate was characterized through FT-IR, MS, 1H NMR, and 13C NMR and demonstrated to have good fluorescence stability and reversibility. The microenvironment for Pb2+ detection has been optimized in detail. Under the optimal conditions, the "off-on" R6GH-based fluorescence output platform showed a good response to Pb2+ in the concentration range of 0.05-6.0 µM (R2 = 0.9851) with a limit of detection (LOD) of 0.02 µM. Furthermore, at three spiked Pb2+ levels in the selected agricultural (tap water, soil) and food (fish, shrimp) samples, the developed R6GH-based fluorescence assays obtained a significant recovery range of 84.0-102.0% (RSD < 5.0%, n = 3), which had a good correlation with the results from ICP-MS (R2 = 0.9915). The developed R6GH immobilized paper-based array sensor can reach the lower LOD (2.5 µM) for Pb2+ through the naked eye. By combining with LAB analysis, a good linear response was obtained in the Pb2+ concentration range of 1.0-50.0 µM. These results indicated that the developed R6GH probe had great application potential in accurate detection of fluorescence and rapid visual and semiquantitative screening for Pb2+.

15.
Foods ; 9(11)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172006

RESUMO

A variety of contaminants in food is an important aspect affecting food safety. Due to the presence of its trace amounts and the complexity of food matrix, it is very difficult to effectively separate and accurately detect them. The magnetic metal-organic framework (MMOF) composites with different structures and functions provide a new choice for the purification of food matrix and enrichment of trace targets, thus providing a new direction for the development of new technologies in food safety detection with high sensitivity and efficiency. The MOF materials composed of inorganic subunits and organic ligands have the advantages of regular pore structure, large specific surface area and good stability, which have been thoroughly studied in the pretreatment of complex food samples. MMOF materials combined different MOF materials with various magnetic nanoparticles, adding magnetic characteristics to the advantages of MOF materials, which are in terms of material selectivity, biocompatibility, easy operation and repeatability. Combined with solid phase extraction (SPE) technique, MMOF materials have been widely used in the food pretreatment. This article introduced the new preparation strategies of different MMOF materials, systematically summarizes their applications as SPE adsorbents in the pretreatment of food contaminants and analyzes and prospects their future application prospects and development directions.

16.
Nanomaterials (Basel) ; 10(5)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403325

RESUMO

Carbon quantum dots (CQDs) with stable physicochemical properties are one of theemerging carbon nanomaterials that have been studied in recent years. In addition to the excellentoptical properties such as photoluminescence, photobleaching resistance and light stability, thismaterial also has favorable advantages of good biocompatibility and easy functionalization, whichmake it an ideal raw material for constructing sensing equipment. In addition, CQDs can combinedwith other kinds of materials to form the nanostructured composites with unique properties, whichprovides new insights and ideas for the research of many fields. In the field of food analysis,emerging CQDs have been deeply studied in food composition analysis, detection and monitoringtrace harmful substances and made remarkable research progress. This article introduces andcompares the various methods for CQDs preparation and reviews its related sensing applicationsas a new material in food components analysis and food safety inspection in recent years. It isexpected to provide a significant guidance for the further study of CQDs in the field of foodanalysis and detection. CQDs; synthesis; fluorescent sensing; food analysis.

17.
Foods ; 9(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331265

RESUMO

Acrylamide (AA) is produced by high-temperature processing of high carbohydrate foods, such as frying and baking, and has been proved to be carcinogenic. Because of its potential carcinogenicity, it is very important to detect the content of AA in foods. In this paper, the conventional instrumental analysis methods of AA in food and the new rapid immunoassay and sensor detection are reviewed, and the advantages and disadvantages of various analysis technologies are compared, in order to provide new ideas for the development of more efficient and practical analysis methods and detection equipment.

18.
J Pharm Pharmacol ; 72(1): 29-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31617221

RESUMO

OBJECTIVES: Arctigenin (ARG) has been proved to inhibit the viability of hepatocellular carcinoma (HCC) via inducing apoptosis. However, the precise mechanism remains unknown. The present study was aimed to further investigate the mechanism of ARG against HCC in vitro and in vivo. METHODS: Arctigenin was applied in vitro and in vivo. Western blotting, immunohistochemistry, etc., were used to investigate the mechanisms. KEY FINDINGS: The time-dependent enhancement of Bax/Bcl-2 ratio, cytochrome c release, Fas and FasL levels, caspase cascade activation and the loss in the mitochondrial out membrane potential indicated that both intrinsic and extrinsic apoptotic pathways were triggered by ARG. Moreover, Jun NH2-terminal kinase (JNK) and p38 phosphorylated time-dependently. And inhibition of the phosphorylation of either p38 or JNK led to a significant reduction in HepG2 apoptosis, owing to the crucial roles of p38 and JNK played in regulating the apoptosis pathways. In addition, ARG increased the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine almost reversed ARG-induced JNK and p38 activation, and dramatically decreased cell apoptosis. In vivo, ARG increased the cell apoptosis in tumour tissues, and p-p38, p-JNK and Bax were significantly upregulated. CONCLUSIONS: Our findings demonstrated that ARG induced apoptosis in HCC via ROS-mediated mitogen-activated protein kinases apoptosis pathway.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Furanos/farmacologia , Lignanas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Ativação Enzimática , Células Hep G2 , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cell Death Dis ; 9(6): 619, 2018 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-29795311

RESUMO

Cancer cells frequently adapt fundamentally altered metabolism to support tumorigenicity and malignancy. Epigenetic and metabolic networks are closely interactive, in which DNA methyltransferases (DNMTs) play important roles. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (EBV-LMP1) is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis because it can trigger multiple cell signaling pathways that promote cell transformation, proliferation, immune escape, invasiveness, epigenetic modification, and metabolic reprogramming. Our current findings reveal for the first time that LMP1 not only upregulates DNMT1 expression and activity, but also promotes its mitochondrial translocation. This induces epigenetic silencing of pten and activation of AKT signaling as well as hypermethylation of the mtDNA D-loop region and downregulation of oxidative phosphorylation (OXPHOS) complexes, consequently, leading to metabolic reprogramming in NPC. Furthermore, we demonstrate that grifolin, a natural farnesyl phenolic compound originated from higher fungi, is able to attenuate glycolytic flux and recover mitochondrial OXPHOS function by inhibiting DNMT1 expression and activity as well as its mitochondrial retention in NPC cells. Therefore, our work establishes a mechanistic connection between epigenetics and metabolism in EBV-positive NPC and provides further evidence for pathological classification based on CpG island methylator phenotype (CIMP) in EBV-associated malignancies. In addition, grifolin might be a promising lead compound in the intervention of high-CIMP tumor types. The availability of this natural product could hamper tumor cell metabolic reprogramming by targeting DNMT1.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Proteínas da Matriz Viral/metabolismo , Aerobiose , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1/genética , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Terpenos/farmacologia
20.
Front Pharmacol ; 8: 294, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28588496

RESUMO

A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2ß), Tmax, and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 µg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control group (tiamulin). In conclusion, 10% enrofloxacin enteric-coated granules had significant potential for treating APP and MS, and it provided an alternative enrofloxacin palatability formulation.

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