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1.
Phytother Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837315

RESUMO

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

2.
Molecules ; 29(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38792269

RESUMO

Quercetin, a flavonoid polyphenol found in many plants, has garnered significant attention due to its potential cancer chemoprevention. Our previous studies have shown that acetyl modification of the hydroxyl group of quercetin altered its antitumor effects in HepG2 cells. However, the antitumor effect in other cancer cells with different gene mutants remains unknown. In this study, we investigated the antitumor effect of quercetin and its methylated derivative 3,3',4',7-O-tetramethylquercetin (4Me-Q) and acetylated derivative 3,3',4',7-O-tetraacetylquercetin (4Ac-Q) on two human breast cancer cells, MCF-7 (wt-p53, caspase-3-ve) and MDA-MB-231 (mt-p53, caspase-3+ve). The results demonstrated that 4Ac-Q exhibited significant cell proliferation inhibition and apoptosis induction in both MCF-7 and MDA-MB-231 cells. Conversely, methylation of quercetin was found to lose the activity. The human apoptosis antibody array revealed that 4Ac-Q might induce apoptosis in MCF-7 cells via a p53-dependent pathway, while in MDA-MB-231 cells, it was induced via a caspase-3-dependent pathway. Furthermore, an evaluation using a superoxide inhibitor, MnTBAP, revealed 4Ac-Q-induced apoptosis in MCF-7 cells in a superoxide-independent manner. These findings provide valuable insights into the potential of acetylated quercetin as a new approach in cancer chemoprevention and offer new avenues for health product development.


Assuntos
Apoptose , Neoplasias da Mama , Proliferação de Células , Quercetina , Humanos , Quercetina/farmacologia , Quercetina/análogos & derivados , Quercetina/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Acetilação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Metilação , Feminino , Proliferação de Células/efeitos dos fármacos , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proteína Supressora de Tumor p53/metabolismo , Caspase 3/metabolismo
3.
Food Funct ; 15(9): 4852-4861, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38573228

RESUMO

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.


Assuntos
Dieta Hiperlipídica , Mitocôndrias , Resultado da Gravidez , Resveratrol , Útero , Animais , Resveratrol/farmacologia , Feminino , Gravidez , Camundongos , Dieta Hiperlipídica/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Útero/metabolismo , Útero/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo
4.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38139286

RESUMO

Quercetin forms complexes with various metals due to its structural attributes. It predominantly exhibits chelating activity at the 3-hydroxy/4-carbonyl group. Previously, coordination in synthetically obtained quercetin-zinc (II) complexes has been limited to this group. However, the expanded coordination observed in quercetin-iron complexes has opened avenues for diverse applications. Thus, synthesizing novel quercetin-zinc complexes with different coordination positions is a significant advance. In our study, we not only synthesized and comprehensively characterized a new quercetin-zinc (II) complex, Zn-Q, but also evaluated the structure and bioactivity of chelate complexes (Q+Zn) derived from co-treatment in cell culture mediums. The structure of the new compound Zn-Q was comprehensively characterized using 1D 1H and 2D correlation spectroscopy (COSY), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometer (ESI-MS), and X-ray diffraction analysis (XRD) analysis. Subcellular localization and absorption of these zinc (II) complexes were determined using the ZnAF-2 DA zinc ion fluorescence probe. Throughout the experiments, both Zn-Q and Q+Zn exhibited significant antioxidant, cell growth inhibitory, and anticancer effects in HepG2 and HCT116 cells, with Zn-Q showing the highest potential for inducing apoptosis via the caspase pathway. Tracking intracellular zinc complex absorption using zinc fluorescent probes revealed zinc (II) localization around the cell nucleus. Interestingly, there was a proportional increase in intracellular quercetin absorption in conjunction with zinc (II) uptake. Our research highlights the advantages of quercetin complexation with zinc (II): enhanced anticancer efficacy compared to the parent compound and improved bioavailability of both quercetin and zinc (II). Notably, our findings, which include enhanced intracellular uptake of both quercetin and zinc (II) upon complex formation and its implications in apoptosis, contribute significantly to the understanding of metal-polyphenol complexes. Moving forward, comprehensive functional assessments and insights into its mechanism of action, supported by animal studies, are anticipated.


Assuntos
Complexos de Coordenação , Zinco , Humanos , Animais , Zinco/química , Quercetina/farmacologia , Quercetina/química , Células HCT116 , Espectroscopia de Infravermelho com Transformada de Fourier , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Apoptose
5.
iScience ; 26(11): 108306, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38026209

RESUMO

Human pluripotent stem cell (hPSC)-derived neurons have shown promise in treating spinal cord injury (SCI). We previously showed that hPSC-derived dorsal spinal γ-aminobutyric acid (GABA) neurons can alleviate spasticity and promote locomotion in rats with SCI, but their long-term safety remains elusive. Here, we characterized the long-term fate and safety of human dorsal spinal GABA neural progenitor cells (NPCs) in naive rats over one year. All grafted NPCs had undergone differentiation, yielding mainly neurons and astrocytes. Fully mature human neurons grew many axons and formed numerous synapses with rat neural circuits, together with mature human astrocytes that structurally integrated into the rat spinal cord. The sensorimotor function of rats was not impaired by intraspinal transplantation, even when human neurons were activated or inhibited by designer receptors exclusively activated by designer drugs (DREADDs). These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

6.
Gut Microbes ; 15(1): 2238959, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37505920

RESUMO

Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , LDL-Colesterol , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos
7.
Saudi Pharm J ; 30(8): 1079-1087, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36164567

RESUMO

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

8.
J Cancer Prev ; 27(1): 58-67, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35419303

RESUMO

6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is an active ingredient present in Wasabi, which is a popular pungent spice used in Japanese cuisine. Our previous studies suggested that the primary antioxidant activity of 6-MSITC may link to other biological activity. This study aimed to clarify how the antioxidant activity of 6-MSITC contributes to preventing overloaded lipid stress in hepatic cell model. HepG2 cells were treated with 6-MSITC at defined concentrations and times in normal medium or in combined fatty acids (CFA) medium, and the targeted proteins were detected by Western blotting. The kinetic data revealed that 6-MSITC activated AMP-activated protein kinase α (AMPKα) and nuclear factor (erythroid-derived 2) like 2 (Nrf2), and then enhanced the protein expression of Forkhead box protein O1 (FOXO1) and Sirtuin1 as well as that of the Nrf2 target proteins, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). Furthermore, lipid metabolic stress was mimicked in HepG2 cells by overloading CFA. 6-MSITC significantly alleviated CFA-induced formation of thiobarbituric acid reactive substances and fat accumulation. Signaling analysis data revealed that 6-MSITC enhanced phosphorylation of AMPKα, upregulated the expression of Nrf2, NQO1, heme oxygenase 1, FOXO1, and Siruin1, and downregulated the expression of PPARα. Taken together, our results suggested that the AMPKα/Nrf2-mediated signaling pathways might be involved in the cytoprotective effects of Wasabi 6-MSITC against metabolic lipid stress.

9.
Oxid Med Cell Longev ; 2021: 6631929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545298

RESUMO

Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin may possess potent anti-inflammatory properties; however, the underlying molecular mechanism is not fully elucidated. In the present study, the regulatory effect of crocetin on redox balance was systematically investigated in lipopolysaccharide- (LPS-) stimulated RAW264.7 cells. The results showed that crocetin dose-dependently inhibited LPS-induced nitric oxide production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells. Molecular data revealed that crocetin exerted its anti-inflammatory property by inhibiting the MEK1/JNK/NF-κB/iNOS pathway and activating the Nrf2/HO-1 pathway. The shRNA-knockdown (KD) of MEK1 and ERK1 confirmed that the activation of MEK1 and inhibition of JNK mediated the anti-inflammatory effect of crocetin. Moreover, the pull-down assay and computational molecule docking showed that crocetin could directly bind to MEK1 and JNK1/2. It is noticed that both KD and knockout (KO) of HO-1 gene blocked this action. More detailed data have shown that HO-1-KO blocked the inhibition of p-IκB-α by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-κB/iNOS pathway and the Nrf2/HO-1 pathway, highlighting HO-1 as a major player. Therefore, the present study reveals that crocetin can act as a potential candidate for redox-balancing modulation in charge of its anti-inflammatory and chemopreventive effect, which strengthens its potency in the subsequent clinic application in the near future.


Assuntos
Anti-Inflamatórios/farmacologia , Carotenoides/farmacologia , Transdução de Sinais/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Sítios de Ligação , Carotenoides/química , Carotenoides/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 1/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa/antagonistas & inibidores , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Vitamina A/química , Vitamina A/metabolismo , Vitamina A/farmacologia
10.
J Biomed Nanotechnol ; 17(7): 1364-1370, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446139

RESUMO

Researchers have conducted in-depth research on DNA methylation mechanism, which is related to various diseases such as deficiency of imprinted gene and occurrence of tumors. This study provides a novel rapid quantitative detection assay and real-time fluorescence recombinase-aided amplification assay (RAA) for DNA methylation. Firstly, specific sequence of methylation genes was chosen and primers and fluorogenic probe for RAA experiment were designed and synthesized. Lastly, these amplification products were proven by sequencing and analysis. Results showed that the amplification efficiency and template concentration of RAA had linear dependent (R² > 95%) when the concentration range was 4.64×108 copies/µL˜4.64×104 copies/µL. The test assay can also detect positive samples when the template concentration is below 4.64×104 copies/µL. Remarkably, the entire experiment process only takes 15-20 minutes, so it is beneficial for rapid bedside simple screening of some special DNA methylation sites, such as detection of resistance genes. In a word, this method has very great potential for diseases with DNA methylation in clinical settings, especially if methylation analysis needs to be done quickly and easily.


Assuntos
Metilação de DNA , Recombinases , Primers do DNA , Técnicas de Amplificação de Ácido Nucleico , Recombinases/genética , Recombinases/metabolismo , Sensibilidade e Especificidade
11.
J Anim Sci Biotechnol ; 11: 92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944233

RESUMO

BACKGROUND: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid (PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong (Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide (LPS). METHODS: Thirty-six piglets (Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet (CTL), a diet added 50 mg/kg of aureomycin (AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS (10 µg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals (n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16S rRNA gene sequencing. RESULTS: Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances (TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α (P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio (P < 0.05). Spearman's correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group (P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio (P < 0.05), whereas AUR had no significant effect on these bacteria. CONCLUSIONS: These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.

12.
Cell Prolif ; 53(7): e12822, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32530560

RESUMO

Breast cancer has seriously been threatening physical and mental health of women in the world, and its morbidity and mortality also show clearly upward trend in China over time. Through inquiry, we find that survival rate of patients with early-stage breast cancer is significantly higher than those with middle- and late-stage breast cancer, hence, it is essential to conduct research to quickly diagnose breast cancer. Until now, many methods for diagnosing breast cancer have been developed, mainly based on imaging and molecular biotechnology examination. These methods have great contributions in screening and confirmation of breast cancer. In this review article, we introduce and elaborate the advances of these methods, and then conclude some gold standard diagnostic methods for certain breast cancer patients. We lastly discuss how to choose the most suitable diagnostic methods for breast cancer patients. In general, this article not only summarizes application and development of these diagnostic methods, but also provides the guidance for researchers who work on diagnosis of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 231: 118109, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062512

RESUMO

Puerariae Radix (PR) is a natural herb whose active ingredient is mainly flavonoids. To explore the interaction between PR flavonoids and DNA not only has important biological implications for understanding the mechanism of action, but also helps develop PR products for the design of appropriate dietary interventions to aid cancer treatment. In this work, we comprehensively studied the interaction between six kinds of PR flavonoids and DNA from four different and progressive levels, including molecular docking, multi-spectral analysis, and functional analysis in vitro and in cell. Results show that the DNA binding affinity of six flavonoids is in an order of quercetin > formononetin > daidzein > puerarin > 4'-methoxy puerarin > puerarin 6″-O-xyloside (POS), in which quercetin can significantly inhibit DNA amplification owing to its strongest binding affinity. The binding between quercetin and DNA is further revealed to be intercalated binding, which can cause conformational changes in DNA, thereby exhibiting an activity of cell cycle arrest and anti-proliferative. This property of quercetin can be utilized for the further development of flavonoids with anticancer activity. In addition to the potential application, this work also provides a platform for the comprehensive study of the interaction between micromolecules and DNA.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , DNA/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Pueraria/química , Células A549 , Animais , Bovinos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA/química , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
14.
Ear Hear ; 41(3): 669-677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31567561

RESUMO

OBJECTIVES: The purpose of this study was to develop a deep-learning framework for the diagnosis of chronic otitis media (COM) based on temporal bone computed tomography (CT) scans. DESIGN: A total of 562 COM patients with 672 temporal bone CT scans of both ears were included. The final dataset consisted of 1147 ears, and each of them was assigned with a ground truth label from one of the 3 conditions: normal, chronic suppurative otitis media, and cholesteatoma. A random selection of 85% dataset (n = 975) was used for training and validation. The framework contained two deep-learning networks with distinct functions: a region proposal network for extracting regions of interest from 2-dimensional CT slices; and a classification network for diagnosis of COM based on the extracted regions. The performance of this framework was evaluated on the remaining 15% dataset (n = 172) and compared with that of 6 clinical experts who read the same CT images only. The panel included 2 otologists, 3 otolaryngologists, and 1 radiologist. RESULTS: The area under the receiver operating characteristic curve of the artificial intelligence model in classifying COM versus normal was 0.92, with sensitivity (83.3%) and specificity (91.4%) exceeding the averages of clinical experts (81.1% and 88.8%, respectively). In a 3-class classification task, this network had higher overall accuracy (76.7% versus 73.8%), higher recall rates in identifying chronic suppurative otitis media (75% versus 70%) and cholesteatoma (76% versus 53%) cases, and superior consistency in duplicated cases (100% versus 81%) compared with clinical experts. CONCLUSIONS: This article presented a deep-learning framework that automatically extracted the region of interest from two-dimensional temporal bone CT slices and made diagnosis of COM. The performance of this model was comparable and, in some cases, superior to that of clinical experts. These results implied a promising prospect for clinical application of artificial intelligence in the diagnosis of COM based on CT images.


Assuntos
Aprendizado Profundo , Otite Média , Inteligência Artificial , Humanos , Otite Média/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
Biosens Bioelectron ; 141: 111416, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31279179

RESUMO

Lung cancer is primary cancer threatening human life worldwide with the highest mortality rate. The early detection of lung cancer plays a critical role in the early diagnosis and subsequent treatment. However, the conventional methodologies limit the applications due to the low sensitivity, being expensive, and invasive procedure. Tumor markers as biochemical parameters can reflect cancer occurrence and progression, which show sensitivity, convenience, and low cost in developing biosensors, and act as good candidates for fabricating biosensors of detecting lung cancer. This review describes various biosensors (2013-2019) for detection of lung cancer biomarkers. Firstly, the various reported tumor markers of lung cancer are briefly described. Then, the advancements of designing biosensors for sensitive, stable, and selective identification of lung cancer biomarkers are systematically provided, with a specific focus on the main clinical biomarkers such as neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA 21-1). Finally, the recent challenges and further opportunities for developing effective biosensors for early diagnosis of lung cancer are discussed.


Assuntos
Técnicas Biossensoriais/métodos , Neoplasias Pulmonares/diagnóstico , Animais , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Técnicas Biossensoriais/instrumentação , Detecção Precoce de Câncer/instrumentação , Detecção Precoce de Câncer/métodos , Desenho de Equipamento , Humanos , Queratina-19/análise , Fosfopiruvato Hidratase/análise
16.
Anim Nutr ; 4(3): 288-293, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30175257

RESUMO

Blue honeysuckle is rich in polyphenols, and recently receiving attention because of its potential antioxidant and anti-inflammatory properties. Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease that develops hepatic inflammation and metabolic syndrome. The present study aims to study the effect of blue honeysuckle extract (BHE) on fat deposition and hepatic lipid peroxidation in a high-fat-diet (HFD)-induced mouse model. Mice were fed a normal diet (ND) or a HFD containing 0.5% or 1% of BHE or not for 45 d. Liver sections were stained by hematoxylin-eosin staining. Serum lipids were measured by a clinical analyzer. Insulin was examined by ELISA, and hepatic proteins were detected by Western blotting. Dietary supplementation of BHE dose-dependently suppressed HFD-induced obesity and hepatic fat deposition. Moreover, BHE improved glucose metabolism by increasing insulin sensitivity and attenuated oxidative stress potentially by up-regulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated pathway.

17.
J Nanosci Nanotechnol ; 16(3): 2474-81, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455657

RESUMO

Sizes of nanoscale contrast agents play an important role in targeting specific organs and distribution in organisms. lodinated oil nanoemulsions with uniform size distribution and containing indocyanine green (ICG) fluorescent dye (25 nm, 60 nm, 100 nm) were synthesized by stirring, combined with ultrasonic emulsification technique. Rats were intravenously injected with the iodinated oil nanoemulsions with different sizes, used as contrast agents, and investigated with enhanced computed tomography (CT) and fluorescence imaging. Through experiments, the distribution and metabolism of the contrast agents in rat's bodies were studied, and their influence on enhanced CT imaging of different organs was compared. The results demonstrated that target accumulating organs for the iodinated oil nanoemulsions were liver and spleen, with obvious dosage-dependence. Large sized nanoemulsion preferred to accumulate into spleen, and liver, and the phagocytosis was getting weaker with the decrease of the nanoemulsion size. The CT imaging of the inferior vena cava was rapidly enhanced and reached the highest point after administration of the nanoemulsion. The nanoemulsion gradually gathered and metabolized in the spleen and liver, resulting in rapidly decreased CT imaging, with weak rebound, of the inferior vena cava.


Assuntos
Emulsões , Iodo/metabolismo , Nanotecnologia , Óleos/metabolismo , Animais , Fígado/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Ratos , Ratos Sprague-Dawley , Baço/metabolismo , Distribuição Tecidual , Tomografia Computadorizada por Raios X
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