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1.
Drug Dev Res ; 84(4): 703-717, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36896715

RESUMO

A series of thioether pleuromutilin derivatives containing 1,2,4-triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). The results of time-kill study and postantibiotic effect study indicated that compound 72 could inhibit the growth of MRSA quickly (-2.16 log10 CFU/mL) and showed certain postantibiotic effect (PAE) time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.30 and 1.35 h) against MRSA. Furthermore, the binding mode between compound 72 and 50S ribosome of MRSA was explored by molecular docking and five hydrogen bonds were formed between compound 72 and 50S ribosome.


Assuntos
Antibacterianos , Compostos Policíclicos , Simulação de Acoplamento Molecular , Antibacterianos/química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Pleuromutilinas
2.
Molecules ; 28(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37175382

RESUMO

Two series of pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). 6-chloro-4-amino-1-R-1H-pyrazolo[3,4-d]pyrimidine or 4-(6-chloro-1-R-1H-pyrazolo[3,4-d]pyrimidine-4-yl)amino-phenylthiol were connected to pleuromutilin. A diverse array of substituents was introduced at the N-1 position of the pyrazole ring. The in vitro antibacterial activities of these semisynthetic derivatives were evaluated against two standard strains, Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, Staphylococcus aureus (S. aureus), ATCC 29213 and two clinical S. aureus strains (144, AD3) using the broth dilution method. Compounds 12c, 19c and 22c (MIC = 0.25 µg/mL) manifested good in vitro antibacterial ability against MRSA which was similar to that of tiamulin (MIC = 0.5 µg/mL). Among them, compound 22c killed MRSA in a time-dependent manner and performed faster bactericidal kinetics than tiamulin in time-kill curves. In addition, compound 22c exhibited longer PAE than tiamulin, and showed no significant inhibition on the cell viability of RAW 264.7, Caco-2 and 16-HBE cells at high doses (≤8 µg/mL). The neutropenic murine thigh infection model study revealed that compound 22c displayed more effective in vivo bactericidal activity than tiamulin in reducing MRSA load. The molecular docking studies indicated that compound 22c was successfully localized inside the binding pocket of 50S ribosomal, and four hydrogen bonds played important roles in the binding of them.


Assuntos
Diterpenos , Staphylococcus aureus Resistente à Meticilina , Compostos Policíclicos , Infecções Estafilocócicas , Animais , Camundongos , Humanos , Staphylococcus aureus , Simulação de Acoplamento Molecular , Células CACO-2 , Testes de Sensibilidade Microbiana , Antibacterianos/química , Diterpenos/química , Compostos Policíclicos/farmacologia , Pirimidinas/farmacologia , Pirimidinas/química , Infecções Estafilocócicas/tratamento farmacológico , Pleuromutilinas
3.
Fa Yi Xue Za Zhi ; 39(3): 271-275, 2023 Jun 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37517015

RESUMO

OBJECTIVES: To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother. METHODS: For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother. RESULTS: When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship. CONCLUSIONS: The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.


Assuntos
Mães , Paternidade , Feminino , Humanos , Masculino , Criança , Genótipo , Pai
4.
Yi Chuan ; 43(10): 938-948, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702706

RESUMO

The genetic structure differences in population is one of the key elements in medical research involving multi-population samples. A set of ancestry-informative single nucleotide polymorphisms (AI-SNPs) can be utilized to analyze genetic component of a population, infer ancestral origin of individuals and pre-filter samples to reduce the impact of population genetic structure differences on medical research. However, most of the published studies were focused on revealing the differences between populations of continents or regions of a continent. In this paper, AI-SNPs were screened by calculating FST value in each pair of five East Asian populations: Japanese in Tokyo (JPT), Han Chinese in Beijing (CHB), Southern Han Chinese (CHS), Chinese Dai in Xishuangbanna (CDX) and Kinh in Ho Chi Minh City (KHV) in the 1000 Genomes Project phase 3 (GRCh37.p13) to analyze differences in subcontinent populations. The results demonstrate that the five East Asian populations in our study were assigned to three clusters: JPT, CHB and CHS, CDX and KHV. A set of AI-SNPs can be used for analysis of individual genetic composition and selection of representative individuals. Individuals with over 80% population representative genetic components have good representativeness of a population. This paper demonstrated the practical value of the method, which was performed to verify the ancestral composition and select representative samples with a panel of screened AI-SNPs by FST value, thereby reducing the influence of genetic structure differences in subcontinent populations on population-related medical research.


Assuntos
Genética Populacional , Polimorfismo de Nucleotídeo Único , Povo Asiático , Frequência do Gene , Estruturas Genéticas , Genótipo , Humanos
5.
Electrophoresis ; 41(1-2): 123-130, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674686

RESUMO

A novel micro matrix solid phase dispersion method was successfully used for the extraction of quaternary alkaloids in Phellodendri chinensis cortex. The elution of target compounds was accomplished with sodium hexanesulfonate as the eluent solvent. A neutral ion pair was formed between ion-pairing reagent and positively charged alkaloids in this process, which was beneficial for selectively extraction of polar alkaloids. Several parameters were optimized and the optimal conditions were listed as follows: silica gel as the sorbent, silica to sample mass ratio of 1:1, the grinding time of 1 min. The exhaustive elution of targets was achieved by 200 µL methanol/water (9:1) containing 150 mM sodium hexane sulfonate at pH 4.5. The method validation covered linearity, recovery, precision of intraday and interday, limits of detection, limits of quantitation, and repeatability. This established method was rapid, simple, environmentally friendly, and highly sensitive.


Assuntos
Berberina , Medicamentos de Ervas Chinesas/química , Quinolizinas , Extração em Fase Sólida/métodos , Berberina/análise , Berberina/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Modelos Lineares , Phellodendron/química , Plantas Medicinais/química , Quinolizinas/análise , Quinolizinas/isolamento & purificação , Reprodutibilidade dos Testes
6.
J Sep Sci ; 42(23): 3579-3588, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617304

RESUMO

The quantification of three alkaloids is important because quantitative study is a means of assessing the reliability of the experimental method, and three alkaloids of peimine, peiminine, and peimisine are main active ingredients in Chinese Pharmacopoeia 2015. An effective method based on the matrix solid-phase dispersion microextraction was developed for the extraction of alkaloid compounds in Fritillariae Thunbergii Bulbus. Target analytes were analyzed by capillary electrophoresis coupled with quadrupole time-of-flight mass spectrometry. The optimized experimental condition was that 50 mg Fritillariae Thunbergii Bulbus was blended homogeneously with 10 mg citric acid for 5 min. Two hundred microliters of water acidized by 1 mol/L hydrochloric acid (pH = 4.5) was selected to elute tested alkaloids. The results demonstrated that the investigated method had low limits of detection (1.32-1.59 ng/mL), good recoveries (86.63-98.12%), and reproducibility (relative standard deviations of peak areas < 0.87%). The proposed matrix solid-phase dispersion microextraction coupled with capillary electrophoresis combined with quadrupole time-of-flight mass spectrometry was successfully applied for the extraction of alkaloids in plants.


Assuntos
Alcaloides/análise , Alcaloides/isolamento & purificação , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Eletroforese Capilar/métodos , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Cevanas/análise , Cevanas/isolamento & purificação , Limite de Detecção
7.
Phytochem Anal ; 30(6): 710-719, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264752

RESUMO

INTRODUCTION: The main active components in hawthorn leaves possess various biological activities such as anti-inflammatory, antioxidant, and hypolipidemic effects. Therefore, it is necessary to develop an effective and reliable extraction method to extract these active compounds from hawthorn leaves. OBJECTIVE: To establish a simple, rapid, and sensitive method for extraction and determination of polyphenolic compounds from hawthorn leaves. METHODS: In this study, a microwave-assisted reaction and extraction (MARE) combined with ultra-high-performance liquid chromatography with ultraviolet detector method was established to extract and determine the polyphenolic compounds in hawthorn leaves. The solid reagent aqueous solutions were applied as extraction solvents, preventing the use of organic solvents. The target analytes were identified by quadrupole time-of-flight tandem mass spectrometry. Several experimental parameters that can significantly affect the extraction efficiency were evaluated and optimised. RESULTS: The optimal conditions were as follows: 0.1 g of sodium carbonate was used as solid reagent, the amount of sodium borate was set at 0.01 g, extraction time was 10 min, extraction temperature was set at 50°C, pH value was adjusted to 7. The validation experiments demonstrated that the method had high sensitivity with the limits of detection in the range 26.5-37.7 ng/mL. The average recoveries ranged from 80.22% to 93.27%. CONCLUSION: In this work, the proposed MARE method was successfully applied to extract and determine polyphenolic compounds in hawthorn leaf samples. Compared with other reported methods, the present method was faster, greener, and more sensitive.


Assuntos
Crataegus/química , Micro-Ondas , Folhas de Planta/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Polifenóis/análise , Reprodutibilidade dos Testes
8.
Electrophoresis ; 39(17): 2218-2227, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29869395

RESUMO

A rapid, simple, and efficient sample extraction method based on micro-matrix-solid-phase dispersion (micro-MSPD) was applied to the extraction of polyphenols from pomegranate peel. Five target analytes were determined by ultra-HPLC coupled with Q-TOF/MS. Carbon molecular sieve (CMS) was firstly used as dispersant to improve extraction efficiency in micro-MSPD. The major micro-MSPD parameters, such as type of dispersant, amount of dispersant, grinding time, and the type and the volume of elution solvents, were studied and optimized. Under optimized conditions, 26 mg of pomegranate peel was dispersed with 32.5 mg of CMS, the grinding time was selected as 90 s, the dispersed sample was eluted with 100 µL of methanol. Results showed that the proposed method was of good linearity for concentrations of analytes against their peak areas (coefficient of determination r2 > 0.990), the LOD was as low as 3.2 ng/mL, and the spiking recoveries were between 88.1 and 106%. Satisfactory results were obtained for the extraction of gallic acid, punicalagin A, punicalagin B, catechin, and ellagic acid from pomegranate peel sample, which demonstrated nice reliability and high sensitivity of this approach.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lythraceae/química , Espectrometria de Massas/métodos , Polifenóis/isolamento & purificação , Extração em Fase Sólida/métodos , Carbono/química , Limite de Detecção , Modelos Lineares , Extratos Vegetais/química , Polifenóis/análise , Polifenóis/química , Reprodutibilidade dos Testes
9.
Cancer Cell Int ; 18: 124, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186040

RESUMO

BACKGROUND: Growing evidence suggests that MiRNAs play essential roles in the initiation and progression of colorectal cancer (CRC). The aberrant expression of miR-384 has been reported in some cancers. However, the role and mechanism of miR-384 in CRC proliferation remains unknown. METHODS: The expression of miR-384 was detected in CRC and their paired normal tissues by real-time PCR. In vivo and in vitro assays were conducted to confirm the role of miR-384 in the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that AKT3 was the target gene of miR-384. Finally, Spearman's correlation analyses was carried out to analyze the relationship between miR-384 expression and AKT3 expression in CRC. RESULTS: MiR-384 was down­regulated in CRC tissues. The in vivo and vitro functional assays verified that the ectopic upregulation of miR-384 inhibited the proliferation of CRC and the inhibition of miR-384 promoted the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro functional assays confirmed AKT3 as the target gene of miR-384. The expression of miR-384 was negatively correlated with the expressions of AKT3. CONCLUSION: Our study verified that miR-384 could significantly suppress the proliferation of CRC by directing targeting AKT3.

10.
J Minim Invasive Gynecol ; 24(2): 305-308, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27867049

RESUMO

STUDY OBJECTIVE: To demonstrate the efficacy of electronic reminders for follow-up hysterosalpingography (HSG) after Essure hysteroscopic sterilization in an urban tertiary care hospital obstetrics and gynecology practice. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Obstetrics and gynecology practice at a university-affiliated urban tertiary care teaching hospital. PATIENTS: Two hundred and fifty patients who underwent Essure hysteroscopic sterilization between June 2011 and July 2014. INTERVENTION: Implementation of electronic reminders for the office staff. MEASUREMENTS AND MAIN RESULTS: Two hundred and fifty of 259 patients (96.5%) underwent Essure hysteroscopic sterilization and successful placement of coils into bilateral Fallopian tubes. Among these 250 patients, 135 (54%) returned for HSG at 3 months post-Essure as advised at the time of procedure. The use of electronic reminders prompted another 45 patients (18%) to return for HSG, improving the total post-Essure follow-up rate to 72%. CONCLUSION: Electronic reminders for the office staff of an urban tertiary care hospital's obstetrics and gynecology practice is an effective method for improving the rate of post-Essure HSG.


Assuntos
Histerossalpingografia/métodos , Histeroscopia/métodos , Sistemas de Alerta , Esterilização Tubária/métodos , Adulto , Assistência ao Convalescente/métodos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Sistemas de Alerta/instrumentação , Sistemas de Alerta/estatística & dados numéricos , Estudos Retrospectivos , Esterilização Reprodutiva/métodos , Estados Unidos/epidemiologia , População Urbana
11.
ACS Infect Dis ; 10(6): 1980-1989, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38703116

RESUMO

In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy of these synthesized compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 µg/mL), compound 14 exhibited potency in inhibiting MRSA growth (MIC = 0.0625 µg/mL) in these derivatives. Meanwhile, the time-killing kinetics further demonstrated that compound 14 could efficiently inhibit the MRSA growth. After exposure at 4 × MIC, the postantibiotic effect (PAE) of compound 14 was 1.29 h. Additionally, in thigh-infected mice, compound 14 exhibited a more potent antibacterial efficacy (-1.78 ± 0.28 log10 CFU/g) in reducing MRSA load compared to tiamulin (-1.21 ± 0.23 log10 CFU/g). Moreover, the MTT assay on RAW 264.7 cells demonstrated that compound 14 (8 µg/mL) had no significant cytotoxicity. Docking studies indicated the strong affinity of compound 14 toward the 50S ribosomal subunit, with a binding free energy of -9.63 kcal/mol. Taken together, it could be deduced that compound 14 was a promising candidate for treating MRSA infections.


Assuntos
Antibacterianos , Diterpenos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Pleuromutilinas , Compostos Policíclicos , Infecções Estafilocócicas , Tiazóis , Compostos Policíclicos/farmacologia , Compostos Policíclicos/química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/síntese química , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Tiazóis/farmacologia , Tiazóis/química , Tiazóis/síntese química , Infecções Estafilocócicas/tratamento farmacológico , Desenho de Fármacos , Células RAW 264.7
12.
Zool Res ; 45(3): 691-703, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38766750

RESUMO

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.


Assuntos
Anestésicos Gerais , Encéfalo , Oligodendroglia , Oligodendroglia/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Anestésicos Gerais/efeitos adversos , Anestésicos Gerais/toxicidade , Síndromes Neurotóxicas/etiologia , Humanos
13.
J Pharm Biomed Anal ; 180: 113071, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31931323

RESUMO

The zirconium metal-organic framework (Zr-MOF) was used as a novel and effective adsorbent material for the enrichment of five phenylurea herbicides (fenuron, monuron, diuron, linuron and pencycuron) in natural products. The target analytes were determined by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Some crucial experimental parameters, such as type of adsorbents, amount of adsorbent, type of eluent solvents and adsorption capacity were investigated and optimized. Under the optimum extraction conditions, the enrichment factors of fenuron, monuron, diuron, linuron and pencycuron were 90, 128, 148, 204 and 295 times, respectively. A good linearity was obtained in different concentration levels of target analytes with the determination coefficients (r2) larger than 0.993. In addition, the limits of detection varied from 0.05 to 0.36 ng/mL and the recoveries of the analytes were in the range of 85.19-99.13 %. The results demonstrated that the proposed miniaturized solid-phase extraction procedure coupled with Zr-MOF could become an effective tool to analyze phenylurea herbicides and would have the vast application prospect for the extraction of pesticide residue and more organic pollutants from Hawthorn, Dendrobii Officinalis Caulis and Salviae Miltiorrhizae Radix et Rhizoma samples.


Assuntos
Poluentes Ambientais/análise , Herbicidas/análise , Estruturas Metalorgânicas/química , Resíduos de Praguicidas/análise , Compostos de Fenilureia/análise , Zircônio/química , Cromatografia Líquida de Alta Pressão/métodos , Crataegus/química , Dendrobium/química , Espectrometria de Massas/métodos , Salvia miltiorrhiza/química , Extração em Fase Sólida/métodos
14.
Food Chem ; 303: 125394, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473455

RESUMO

A simple and effective vesicle based ultrasonic-assisted extraction (UAE) method was developed for extraction of active compounds in functional food. The target analytes were determined by ultra-high performance liquid chromatography with ultraviolet detector. Surfactant vesicle was adopted as extraction solvent. Different operating conditions including the type and concentration of vesicle, extraction time and solid to liquid ratio were investigated by single-factor experiments and response surface methodology. Optimized experimental conditions were 1% (w/v) of DTAB/SDS vesicle, 20 min of extraction time and 160 mg/mL of solid to liquid ratio. The proposed method provided good linearity in the linear range of 10-1000 µg/mL with regression coefficients larger than 0.999, low limits of detection of 27.64-55.67 ng/mL, good precision with relative standard deviations below 0.35%, and satisfactory recoveries of 83.84-90.92% for tested saponins. Consequently, the proposed vesicle based UAE method was well suited for the extraction of saponins in Panax notoginseng.


Assuntos
Fracionamento Químico/métodos , Panax notoginseng/química , Saponinas/isolamento & purificação , Ultrassom , Cromatografia Líquida de Alta Pressão , Saponinas/análise
15.
J Chromatogr A ; 1602: 150-159, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30961967

RESUMO

A rapid and effective method was successfully established for the extraction and determination of chlorogenic acid, protocatechuic acid, malic acid, caffeic acid and gallic acid in fruit (chaenomeles speciosa) via matrix solid-phase dispersion (MSPD) microextraction combined with ultra-high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Several major extraction parameters were investigated and optimized, such as the type of sorbent, the amount of sorbent, the grinding time, the type and concentration of the eluting solvent. The optimal extraction conditions were obtained by using 20 mg of calix[8]arene as dispersing adsorbent, selecting 60 s as the appropriate grinding time and applying 250 mM of 1-dodecyl-3-methylimidazolium bromide as eluent solvent. Moreover, the calibration curves of the analytes were in the range of 0.01-500 µg/mL with the determination coefficients (r2) higher than 0.9995. The limits of detection and limits of quantification were in the range of 0.202-1.056 ng/mL and 0.674-3.521 ng/mL, respectively. The recoveries of the target compounds at two spiked levels were between 82.19 and 113.36%. Furthermore, this method had acceptable reproducibility (RSD ≤ 3.84%). The proposed approach combined the advantages of MSPD microextraction with UHPLC-Q-TOF/MS, and could be applicable for the analysis organic acids in fruit.


Assuntos
Calixarenos/química , Ácidos Carboxílicos/isolamento & purificação , Frutas/química , Líquidos Iônicos/química , Microextração em Fase Sólida/métodos , Adsorção , Íons/análise , Limite de Detecção , Modelos Lineares , Padrões de Referência , Reprodutibilidade dos Testes , Solventes/química , Espectrometria de Massas em Tandem , Fatores de Tempo
16.
Onco Targets Ther ; 12: 8105-8115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632063

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Studies have demonstrated that epigenetic modifications play essential roles in the development of CRC. ADHFE1 is a differentially expressed gene that has been reported to be hypermethylated in CRC. However, the role and mechanism of ADHFE1 in the proliferation of CRC remain unclear. MATERIALS AND METHODS: ADHFE1 expression was analyzed in CRC tissues by IHC and qRT-PCR, and the relationship between ADHFE1 expression and the clinicopathological parameters was analyzed. Cell proliferation were assessed by the in vitro and in vivo experimental models. GSEA assay was performed to explore the mechanism of ADHFE1 in the proliferation of CRC. Flow cytometry and Western blot were used to detect the activation of the cell cycle signaling. Bisulfite genomic sequence (BSP) assay was used to test the methylation degree of ADHFE1 gene promoter in CRC tissues. RESULTS: Here, we verified that ADHFE1 was down-regulated and hypermethylated in CRC tissues. The down-regulation of ADHFE1 was correlated with poor differentiation and advanced TNM stage of CRC patients. And ADHFE1 expression restored when the CRC cell line SW620 was treated with the demethylating agent 5-Aza-CdR. Overexpression of ADHFE1 inhibited the proliferation of CRC, while ADHFE1 knockdown promoted the proliferation of CRC cells in vitro and in vivo. Moreover, ADHFE1 overexpression could induce a significant G1-S cell cycle arrest in CRC cells and vice versa. CONCLUSION: Hypermethylation of ADHFE1 might promote cell proliferation by modulating cell cycle progression in CRC, potentially providing a new therapeutic target for CRC patients.

17.
Am J Cancer Res ; 9(5): 1061-1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218112

RESUMO

Slingshot phosphatase 3 (SSH3) is a member of the SSH phosphatase family that regulates actin filament dynamics. However, its role in cancer metastasis is relatively unclear compared to that of SSH1. Here, we showed that SSH3 was upregulated in colorectal cancer (CRC). Of note, SSH3 was upregulated in the tumor thrombus and lymph node metastasis compared with that in paired primary CRC tissues. High SSH3 expression was associated with the aggressive phenotype of CRC and may be an independent prognostic factor for the poor survival of patients with CRC. SSH3 significantly enhanced the invasion and metastasis of CRC cells in vitro and in vivo. Moreover, SSH3 regulated the remodeling of actin, which is involved in the cytoskeleton signaling pathway, through its interaction with LIMK1/Rac1 and subsequently promoted CRC cell invasion and metastasis. Our data elucidate an important role for SSH3 in the progression of CRC, and SSH3 may be considered a potential therapeutic target for CRC.

18.
J Chromatogr A ; 1537: 10-20, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29336808

RESUMO

A simple and effective method of miniaturized solid-phase extraction (mini-SPE) was developed for the simultaneous purification and enrichment of macrolide antibiotics (MACs) (i.e. azithromycin, clarithromycin, erythromycin, lincomycin and roxithromycin) from honey and skim milk. Mesoporous MCM-41 silica was synthesized and used as sorbent in mini-SPE. Several key parameters affecting the performance of mini-SPE procedure were thoroughly investigated, including sorbent materials, amount of sorbent and elution solvents. Under the optimized condition, satisfactory linearity (r2 > 0.99), acceptable precision (RSDs, 0.3-7.1%), high sensitivity (limit of detection in the range of 0.01-0.76 µg/kg), and good recoveries (83.21-105.34%) were obtained. With distinct advantages of simplicity, reliability and minimal sample requirement, the proposed mini-SPE procedure coupled with ultrahigh performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry could become an alternative tool to analyze the residues of MACs in complex food matrixes.


Assuntos
Análise de Alimentos/métodos , Mel/análise , Macrolídeos/isolamento & purificação , Leite/química , Dióxido de Silício/química , Extração em Fase Sólida/métodos , Animais , Antibacterianos/análise , Antibacterianos/isolamento & purificação , Bovinos , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Macrolídeos/análise , Reprodutibilidade dos Testes , Solventes/análise , Espectrometria de Massas em Tandem
19.
Food Chem ; 262: 118-128, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29751898

RESUMO

In this study, dispersive micro solid phase extraction (DMSPE) combined with ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method was established to extract and determine sudan dyes and their metabolites in real samples. The crown ether microfunctionalized multi-walled carbon nanotubes (MWCNTs) was applied as the sorbent in DMSPE procedure. Several experimental parameters that can effect the extraction performance of the DMSPE method were investigated separately by a univariate method. The validation data showed that the limits of detection were in the range of 0.084-13.13 µg/kg, the mean recoveries were ranged from 80.15 to 103.58% for six samples. Compared with other published methods, the proposed method was more effective, more time-saving and more eco-friendly. Finally, the developed method was successfully applied to enrich and detect sudan dyes and their metabolites in real samples.


Assuntos
Compostos Azo/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Corantes/isolamento & purificação , Análise de Alimentos/métodos , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Compostos Azo/análise , Corantes/análise , Éteres de Coroa/química , Limite de Detecção , Nanotubos de Carbono/química
20.
J Chromatogr A ; 1561: 1-12, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-29807708

RESUMO

Mycotoxins are a group of secondary fungi metabolites present in foods that cause adverse effects in humans and animals. The objective of this study was to develop and validate a reliable and sensitive method to determine the presence of fumonisin B1, aflatoxin B1, ochratoxin B, T-2 toxin, ochratoxin A and zearalenone. A rapid, effective process, which involves microwave-assisted dispersive micro-solid phase extraction (MA-d-µ-SPE), has been proposed for the extraction and detection of 6 mycotoxins in peach seed, milk powder, corn flour and beer sample matrixes, for subsequent analysis by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Several experimental parameters (type of dispersant, concentration of dispersant, vortex time, type of desorption solvent and pH) affecting the extraction efficiency were systematically studied and optimized. The optimum extraction conditions involved immersing 2.5 µg/mL of nano zirconia (as dispersant) in a 5 mL sample solution. After 2 min of extraction by vigorous shaking, the target analytes were desorbed by 100 µL of chloroform at pH 4.5. The results indicated good linearity in the range of 0.0074-3.6 µg/mL (r ≥ 0.9982), low limits of detection (0.0036-0.033 µg/kg for solid samples and 0.0022-0.017 ng/mL for beer), acceptable reproducibility (relative standard deviation (RSD%) 2.08-2.76% for retention time and 3.51-4.59% for peak area, n = 3), and satisfactory spiked recoveries (84.27-104.96%) for studied mycotoxins in sample matrixes, which demonstrated that MA-d-µ-SPE coupled with UHPLC-Q-TOF/MS is a useful tool for analysis of multi-mycotoxin.


Assuntos
Análise de Alimentos/métodos , Nanopartículas Metálicas/química , Micro-Ondas , Micotoxinas/análise , Micotoxinas/isolamento & purificação , Microextração em Fase Sólida/métodos , Zircônio/química , Cerveja/análise , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem/métodos
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