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Scopoletin is a coumarin synthesized by diverse medicinal and edible plants, which plays a vital role as a therapeutic and chemopreventive agent in the treatment of a variety of diseases. In this review, an overview of the pharmacology, pharmacokinetics, and toxicity of scopoletin is provided. In addition, the prospects and outlook for future studies are appraised. Scopoletin is indicated to have antimicrobial, anticancer, anti-inflammation, anti-angiogenesis, anti-oxidation, antidiabetic, antihypertensive, hepatoprotective, and neuroprotective properties and immunomodulatory effects in both in vitro and in vivo experimental trials. In addition, it is an inhibitor of various enzymes, including choline acetyltransferase, acetylcholinesterase, and monoamine oxidase. Pharmacokinetic studies have demonstrated the low bioavailability, rapid absorption, and extensive metabolism of scopoletin. These properties may be associated with its poor solubility in aqueous media. In addition, toxicity research indicates the non-toxicity of scopoletin to most cell types tested to date, suggesting that scopoletin will neither induce treatment-associated mortality nor abnormal performance with the test dose. Considering its favorable pharmacological activities, scopoletin has the potential to act as a drug candidate in the treatment of cancer, liver disease, diabetes, neurodegenerative disease, and mental disorders. In view of its merits and limitations, scopoletin is a suitable lead compound for the development of new, efficient, and low-toxicity derivatives. Additional studies are needed to explore its molecular mechanisms and targets, verify its toxicity, and promote its oral bioavailability.
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Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis. And then, biochemical assays and in vivo electrophysiological examination were performed on older AF patients, aging mice, and senescent atrial fibroblasts. The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac-p53)/p21, Smad3/p-Smads, and fibrosis-related factors. (2) p300 inhibitor curcumin and p300 knockdown treated aging mouse and senescence human atrial fibroblasts reduced the senescence ratio of atrial fibroblasts, ameliorated the atrial fibrosis, and decreased the AF inducibility. In contrast, over-expression of p300 can lead to the senescence of atrial fibroblasts and atrial fibrosis. (3) p53 knockdown decreased the expression of aging and fibrosis-related proteins. (4) Co-immunoprecipitation and immunofluorescence showed that p53 forms a complex with smad3 and directly regulates the expression of smad3 in atrial fibroblasts. Our findings suggest that the mechanism of atrial fibrosis induced by aging is, at least, partially dependent on the regulation of p300, which provides new sights into the AF treatment, especially for the elderly.
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Fibrilação Atrial , Proteína Supressora de Tumor p53 , Humanos , Animais , Camundongos , Idoso , Proteína Supressora de Tumor p53/metabolismo , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Acetiltransferases/metabolismo , Fibrose , Fibroblastos/metabolismo , Senescência Celular/fisiologia , Proteína Smad3/metabolismoRESUMO
Ginsenoside Re is a protopanaxatriol-type saponin extracted from the berry, leaf, stem, flower bud, and root of Panax ginseng. In recent years, ginsenoside Re (Re) has been attracting attention as a dietary phytochemical. In this review, studies on Re were compiled by searching a combination of keywords, namely "pharmacology," "pharmacokinetics," and "toxicology," in the Google Scholar, NCBI, PubMed, and Web of Science databases. The aim of this review was to provide an exhaustive overview of the pharmacological activities, pharmacokinetics, and toxicity of Re, focusing on clinical evidence that has shown effectiveness in specific diseases, such as diabetes mellitus, nervous system diseases, inflammation, cardiovascular disease, and cancer. Re is also known to eliminate virus, enhance the immune response, improve osteoporosis, improve skin barrier function, enhance intracellular anti-oxidant actions, regulate cholesterol metabolism, alleviate allergic responses, increase sperm motility, reduce erectile dysfunction, promote cyclic growth of hair follicles, and reduce gastrointestinal motility dysfunction. Furthermore, this review provides data on pharmacokinetic parameters and toxicological factors to examine the safety profile of Re. Such data will provide a theoretical basis and reference for Re-related studies and future applications.
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Corosolic acid (CA) is the main active component of Lagetstroemia speciosa and has been known to serve as several different pharmacological effects, such as antidiabetic, anti-oxidant, and anticancer effects. In this study, effects of CA on the hepatic lipid accumulation were examined using HepG2 cells and tyloxapol (TY)-induced hyperlipidemia ICR mice. CA significantly inhibited hepatic lipid accumulation via inhibition of SREBPs, and its target genes FAS, SCD1, and HMGCR transcription in HepG2 cells. These effects were mediated through activation of AMPK, and these effects were all abolished in the presence of compound C (CC, an AMPK inhibitor). In addition, CA clearly alleviated serum ALT, AST, TG, TC, low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) levels, and obviously attenuated TY-induced liver steatosis and inflammation. Moreover, CA significantly upregulated AMPK, ACC, LKB1 phosphorylation, and significantly inhibited lipin1, SREBPs, TNF-α, F4/80, caspase-1 expression, NF-κB translocation, and MAPK activation in TY-induced hyperlipidemia mice. Our results suggest that CA is a potent antihyperlipidemia and antihepatic steatosis agent and the mechanism involved both lipogenesis and cholesterol synthesis and inflammation response inhibition via AMPK/SREBPs and NF-κB/MAPK signaling pathways.
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Hiperlipidemias/tratamento farmacológico , Hipolipemiantes , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Fitoterapia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Células Hep G2 , Humanos , Inflamação , Lagerstroemia/química , Camundongos Endogâmicos ICR , Estearoil-CoA Dessaturase/metabolismo , Receptor fas/metabolismoRESUMO
OBJECTIVE: The study aimed to evaluate the association between microbes in the lower respiratory tract (LRT) and the srisk for severe bronchopulmonary dysplasia (sBPD) in premature infants. METHODS: We conducted a retrospective, single-center study of preterm infants who were admitted to the neonatal intensive care unit (NICU) of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, China, between January 2015 and December 2017. The microbes in the LRT were screened by using tracheobronchial aspirate fluid (TAF) culture. RESULTS: One hundred and fifty-five infants were included in the analysis. Among 155 infants, 41 were diagnosed with sBPD, and 114 were diagnosed without sBPD. There were significant differences between infants with and without sBPD in regard to birth weight (BW), gestational age (GA), the duration of endotracheal ventilation and supplemental oxygen. The incidence of retinopathy (ROP) and sepsis was higher in the sBPD infants than in the infants without sBPD. There was a difference in the detection rate of Gram-negative bacteria (GNB) between the two groups. Stenotrophomonas maltophilia and Klebsiella pneumoniae were mainly detected in TAF. CONCLUSIONS: The LRT microbes were different between infants with and without sBPD, and GNB is more frequently detected in sBPD infants.
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Brônquios/microbiologia , Displasia Broncopulmonar/etiologia , Bactérias Gram-Negativas/isolamento & purificação , Traqueia/microbiologia , Displasia Broncopulmonar/microbiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: Patients with T1N0M0 stage ESCC (n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3-5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases]. RESULTS: Among the per-protocol population, the SSI+EUS group (n = 81) was superior to the EUS-only group (n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6-99.1) vs. 65.9% (95% CI, 55.8-76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1-100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001]. CONCLUSIONS: SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER.
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Detecção Precoce de Câncer/métodos , Endoscopia do Sistema Digestório/métodos , Endossonografia/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Cloreto de Sódio/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Feminino , Humanos , Mucosa Intestinal , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Adulto JovemRESUMO
PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. METHODS: MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. RESULTS: The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC50 values of 6.75±0.29 µM and 5.29±0.13 µM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing ß-catenin and increasing GSK-3ß expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial-mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. CONCLUSION: This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.
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Antineoplásicos/farmacologia , Berberina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Berberina/química , Berberina/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
Objective: To assess the efficacy and safety of artemether emulsion in patients with papulopustular rosacea. Methods: A total of 130 (randomized 1:1) were externally administered either artemether emulsion (1%) or metronidazole emulsion (3%) twice daily for 4 weeks with an open-label 8-week follow-up. The primary endpoints included the proportion of patients who achieved clinical effective responses, as well as erythema and papule and pustule score at week 4. Results: Numerically more patients achieved an effective response at week 4 with artemether emulsion (87.1%) than metronidazole emulsion (80.0%) (p > .05). Patients with artemether emulsion had comparable baseline erythema score (2.45 ± 0.67 versus 2.42 ± 0.70, p = .809) and papule and pustule score (2.11 ± 0.96 versus 2.32 ± 0.83, p = .264), but significantly lower papule and pustule score (0.21 ± 0.52 versus 0.42 ± 0.83, p = .001) and comparable erythema score (0.53 ± 0.88 versus 0.62 ± 0.88, p = .999) compared to patients with metronidazole emulsion at week 4. There was a significantly higher proportion of patients with metronidazole emulsion relapse compared to metronidazole emulsion during the open-label 8-week follow-up period (21.6% versus 2.4%, p < .01). Conclusions: Artemether emulsion improved papulopustular rosacea in the metronidazole emulsion group as early as 4 weeks, but its beneficial effect was maintained through the 8-week follow-up period compared to metronidazole emulsion.
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Artemeter/uso terapêutico , Rosácea/tratamento farmacológico , Adulto , Artemeter/efeitos adversos , Artemeter/química , Esquema de Medicação , Emulsões/química , Feminino , Humanos , Masculino , Metronidazol/química , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Prurido/etiologia , Rosácea/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Enlarged retropharyngeal lymph nodes (RLNs) are very common in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The most suitable treatment option for enlarged RLNs depends on the pathological results. However, RLN sampling is difficult and imminent in the clinic setting. We recently developed a novel minimally invasive technique termed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for sampling RLN tissues sufficient for pathological or cytological diagnosis. METHODS: We enrolled 30 post-radiotherapy patients with NPC with suspected RLN metastasis detected via magnetic resonance imaging (MRI). The EUS probe was introduced into the nasopharynx via the nostrils, and EUS was then used to scan the retropharyngeal space and locate the RLN in the anterior carotid sheath. EUS-FNA was subsequently performed. The safety and efficacy of using EUS-FNA to sample the RLN tissues were assessed. RESULTS: Strips of tissue were successfully sampled from all patients using EUS-FNA. Of the 30 patients, 23 were confirmed to have cancer cells in the biopsied tissues via pathology or cytology examinations with 1 EUS-FNA biopsy session. The seven cases without confirmed cancer cells were subsequently reanalyzed by using another EUS-FNA biopsy session, and two more cases were confirmed possessing cancer cells. The other five patients without confirmed cancer cells were closely followed with MRI every month for 3 months. After follow-up for 3 months, three patients were still considered cancer-free due to the presence of RLNs with stable or shrinking diameters. The rest two patients who showed progressive disease underwent a third EUS-FNA biopsy procedure and were further confirmed to be cancer cell-positive. In the whole cohort reported here, the EUS-FNA procedure was not associated with any severe complications. CONCLUSION: EUS-FNA is a safe and effective diagnostic approach for sampling tissues from the RLNs in patients with suspected recurrent NPC.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Linfonodos/diagnóstico por imagem , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adulto , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In order to reveal the properties of polar metabolome in inflammatory cells, we selected LPS-induced RAW264.7 inflammatory cell models as the carrier for the research of metabolic fingerprint analysis. In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics protocol was optimized for the extraction of polar metabolites from RAW264.7 cell line. Then orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data, and finally, a total of 17 metabolites were selected and identified. The results showed that MeOH-CHCl3-H2O (8â¶1â¶1) was chosen as the optimal extraction solvent to achieve higher number of chromatographic peaks, with the best relative extraction efficiency and stability. Comparing with the normal cells, the inflammatory cells presented an abnormal metabolism in protein, carbohydrate, nucleotide and phospholipids. In this study, a UPLC-Q-TOF/MS-based metabolomics protocol for the polar metabolites from RAW264.7 cell line was developed, which may provide important information for the study of mechanism of inflammation and the anti-inflammatory drugs.
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Macrófagos/metabolismo , Metabolômica , Animais , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Camundongos , Células RAW 264.7RESUMO
The arseniasis in Southwest Guizhou, China has been identified as a unique case of endemic arseniasis caused by exposure to indoor combustion of high As-content coal. Present investigation targeted the microdistribution and speciation of the element arsenic in human hair and environmental samples collected in one of the hyper-endemic villages of arseniasis in the area. Analyses were performed by micro-beam X-ray fluorescence (µ-XRF) and X-ray absorption fine structure (XAFS). The total As level in hair samples of diagnosed patients was detected at almost the same level as in their asymptomatic neighbors. Concentrations in the lateral cut of hair samples were high-low-high (from surface to center). XAFS revealed the coexistence of both the As+3 and As+5 states in hair samples. However, the samples from patients displayed a tendency of higher As+3 / As+5 ratio than the asymptomatic fellow villagers. The µ-XRF mapping of rice grains shows that arsenic penetrates the endosperm, the major edible part of the grain, when rice grains were stored over the open fire of high As-content coal. Synchrotron radiation techniques are suitable to determine arsenic species concentrations in different parts of hair and rice grain samples. As arsenic penetrates the endosperm, rinsing the rice grains with water will remain largely ineffective.
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Auranofin (AF) is used in clinic for the treatment of rheumatoid arthritis, repurposing of AF as an anticancer drug has just finished a phase I/II clinical trial, but the developmental toxicity of AF remains obscure. This study focused on its developmental toxicity by using zebrafish embryos. Zebrafish embryos were exposed to different concentrations (1, 2.5, 5, 10 µm) of AF from 2 h post-fertilization (hpf) to 72 hpf. At 72 hpf, two major developmental defects caused by AF were found, namely severe pericardial edema and hypopigmentation, when embryos were exposed to concentrations higher than 2.5 µm. Biochemical detection of oxidative stress enzyme combined with expressions of a series of genes related to oxidative stress, cardiac, metal stress and pigment formation were subsequently tested. The superoxide dismutase activity was decreased while malondialdehyde content was accumulated by AF treatment. The expression of oxidative stress-related genes (sod1, gpx1a, gst), pigment-related genes (mitfb, trp-1a) and one metal stress-related gene ctr1 were all decreased by AF exposure. The expressions of cardiac-related genes (amhc, vmhc) and one metal-related gene hsp70 were found to be significantly upregulated by AF exposure. These findings indicated the potential developmental toxicity of AF on zebrafish early development. Copyright © 2016 John Wiley & Sons, Ltd.
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Antirreumáticos/toxicidade , Auranofina/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Peixe-Zebra , Animais , Edema/induzido quimicamente , Edema/patologia , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Coração/efeitos dos fármacos , Hipopigmentação/induzido quimicamente , Hipopigmentação/genética , Hipopigmentação/patologia , Malondialdeído/metabolismo , Metais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , TeratogênicosRESUMO
Esophageal squamous cell carcinoma (ESCC) is known for its rapid progression and poor outcomes. China has the highest incidence and mortality in the world. Diagnoses made at early stages and accurate staging are associated with better outcomes, all of which can play a significant role in the selection of treatment protocols. ESCC is staged according to the widely accepted TNM system. Common imaging modalities used in staging ESCC before treatment include endoscopy, computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Endoscopic ultrasound is useful for staging tumor depth and nodal status. Narrow band imaging is valuable for early stage disease assessment. CT and PET provide additional valuable information regarding node and metastasis staging. The ability of MRI to delineate ESCC is continuously being improved and adds information regarding locoregional status to routine examinations.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Endossonografia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Humanos , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Treatment options and prognosis of esophageal squamous cell carcinoma (ESCC) depend on the primary tumor depth (T-staging) and regional lymph node status (N-staging). Endoscopic ultrasound (EUS) has emerged as a useful staging tool, but studies regarding its benefits have been variable. The objective of this study was to evaluate the diagnostic accuracy of EUS for detecting preoperative ESCC. METHODS: We included in our meta-analysis studies involving EUS-based staging of preoperative ESCC compared with pathological staging. Using a random-effects model, we performed a meta-analysis of the accuracy of EUS by calculating pooled estimates of sensitivity, specificity and the diagnostic odds ratio. In addition, we created a summary receiver operating characteristic (SROC) curve. RESULTS: Forty-four studies (n = 2880) met the inclusion criteria. The pooled sensitivity and specificity of T1 were 77% (95%CI: 73 to 80) and 95% (95%CI: 94 to 96). Among the T1 patients, EUS had a pooled sensitivity in differentiating T1a and T1b of 84% (95%CI: 80 to 88) and 83% (95%CI: 80 to 86), and a specificity of 91% (95%CI: 88 to 94) and 89% (95%CI: 86 to 92). To stage T4, EUS had a pooled sensitivity of 84% (95%CI: 79 to 89) and a specificity of 96% (95%CI: 95 to 97). The overall accuracy of EUS for T-staging was 79% (95%CI: 77 to 80), and for N-staging, 71% (95%CI: 69 to 73). CONCLUSIONS: EUS has good diagnostic accuracy for staging ESCC, which has better performance in T1 sub-staging (T1a and T1b) and advanced disease (T4).
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Carcinoma de Células Escamosas/diagnóstico por imagem , Endossonografia/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Período Pré-Operatório , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Linfonodos , Masculino , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Primary pulmonary synovial sarcoma is a rare lesion that occurs in 0.5% cases of lung malignancies. Chest computed tomography (CT) reveals a heterogeneously enhancing mass in the lobe or hilum of the lungs, frequently calcified and with pleural invasion. Involvement of the mediastinum in the course of primary pulmonary synovial sarcoma, in particular detection of a large mass in the mediastinum as the sole initial imaging manifestation, is extremely rare, which may contribute to a delayed diagnosis or misdiagnosis. The present case report describes an extremely rare case of a patient with primary pulmonary synovial sarcoma presenting with a large mass in the left upper mediastinum. A 59-year-old patient was admitted to the Department of Respiratory Medicine of Taizhou People's Hospital in May 2014, complaining of a persistent cough and blood sputum for 2 weeks. Following admission, a chest CT showed a large mass in the left upper mediastinum. Thoracoscopy was performed and revealed that the left pulmonary artery was engulfed by the mass, and thus surgical resection of the tumor was abandoned. The patient was definitively diagnosed with primary pulmonary synovial sarcoma following the histopathological and immunohistochemical analysis of biopsy specimens obtained via thoracoscopy. Following the final diagnosis, the patient was transferred to the Department of Oncology for chemotherapy treatments with ifosfamide and doxorubicin. Unfortunately, no partial regression was achieved after two rounds of chemotherapy, and the patient was lost to follow-up 3 months after the diagnosis was confirmed. The present case may promote the consideration of primary pulmonary synovial sarcoma in the differential diagnosis of patients who present with a large mass in the mediastinum.
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Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer ('IARC'), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer.
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Oxidized lowdensity lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cellmediated LDL oxidation remain to be elucidated. The present study investigated whether nativeLDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methylßcyclodextrin (MßCD), LDLstimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MßCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to labelfree quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following nativeLDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that nativeLDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.
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Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Microdomínios da Membrana/metabolismo , Animais , Western Blotting , Proteínas de Choque Térmico/metabolismo , Humanos , Immunoblotting , Macrófagos/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos , Microscopia Confocal , Oxirredução/efeitos dos fármacos , Peroxidase/metabolismo , Proteoma/metabolismo , Proteômica , Células RAW 264.7 , Reprodutibilidade dos TestesRESUMO
The aim of the present study was to investigate the effect of the small interfering RNA (siRNA)-induced inhibition of the Trop2 gene on the proliferation and invasion of lung adenocarcinoma H460 cells. A recombinant adenovirus expression vector, which contained siRNA targeting open reading frames for Trop2 (rAd5-siTrop2), was transfected into lung adenocarcinoma H460 cells. Three groups were included in the study, namely the Ctrl (non-transfected control), rAd5-siCtrl (native control) and rAd5-siTrop2 (knockdown Trop2 gene) groups. The mRNA and protein expression levels of Trop2 were detected using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of cyclin Dl and phospho-extracellular signal regulated kinase (p-ERK)-1 were detected using western blot analysis. The effects of Trop2 inhibition on the proliferation and invasion of lung adenocarcinoma H460 cells were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay. Trop2-targeted siRNA recombinant plasmids were successfully constructed. The recombinant adenovirus vector, rAd5-siTrop2, significantly downregulated the mRNA and protein expression levels of Trop2 in the lung adenocarcinoma H460 cells, with cyclin D1 and p-ERK-1 expression downregulated simultaneously. In addition, following the silencing of Trop2, the proliferation and invasion rates of the lung adenocarcinoma H460 cells were reduced. Therefore, the results indicated that Trop2 serves a key function in the proliferation and invasion of lung adenocarcinoma H460 cells in vitro.
RESUMO
BACKGROUND: The preoperative detection of recurrent laryngeal nerve lymph node (RLN LN) metastasis provides important information for the treatment of esophageal cancer. We investigated the possibility of applying endobronchial ultrasonography (EBUS) with conventional preoperative endoscopic ultrasonography (EUS) and computerized tomography (CT) examination to evaluate RLN LN metastasis in patients with esophageal cancer. METHODS: A total of 115 patients with advanced thoracic esophageal cancer underwent EBUS examinations. Patients also underwent EUS and CT imaging as reference diagnostic methods. Positron emission tomography /computed tomography (PET/CT) was also introduced in partial patients as reference method. The preoperative evaluation of RLN LN metastasis was compared with the surgical and pathological staging in 94 patients who underwent radical surgery. RESULTS: The sensitivities of the preoperative evaluations of RLN LN metastasis by EBUS, EUS and CT were 67.6%, 32.4% and 29.4%, respectively. The sensitivity of EBUS was significantly different from that of EUS or CT, especially in the detection of right RLN LNs. In addition, according to the extra data from reference method, PET/CT was not superior to EBUS or EUS in detecting RLN LN metastasis. Among all 115 patients, 21 patients who were diagnosed with tracheal invasions by EUS or EBUS avoided radical surgery. Another 94 patients who were diagnosed as negative for tracheobronchial tree invasion by EUS and EBUS had no positive findings in radical surgery. CONCLUSIONS: EBUS can enhance the preoperative sensitivity of the detection of RLN LN metastasis in cases of thoracic esophageal cancer and is a useful complementary examination to conventional preoperative EUS and CT, which can alert thoracic surgeons to the possibility of a greater range of preoperative lymph node dissection. EBUS may also indicate tracheal invasion in cases of esophageal stricture.
Assuntos
Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Período Pré-Operatório , Nervo Laríngeo Recorrente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
The aim of the present study was to investigate the effects of baicalein on the protein expression of SATB1 in the MDA-MB-231 human breast cancer cell line. MDA-MB-231 cells were treated with various concentrations of baicalein (0, 10, 20, 40 µM). Following treatment, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and wound healing assay were used to detect the changes in cell proliferation and migration. In addition, western blot analysis was performed to detect the changes in the protein expression levels of SATB1 in the MDA-MB-231 cell line. With the prolongation of administration time and the increase in drug concentration, the inhibitory effect of baicalein on the proliferation and migration of MDA-MB-231 cells gradually increased in a time- and dose-dependent manner (P<0.05). In addition, baicalein was shown to markedly decrease the protein expression levels of SATB1 in the MDA-MB-231 cells. With increasing drug concentrations, the protein expression levels of SATB1 decreased gradually (P<0.05). Therefore, baicalein was demonstrated to inhibit the proliferation of MDA-MB-231 cells and downregulate the protein expression of SATB1, indicating that baicalein can significantly inhibit the proliferation, migration and invasiveness of MDA-MB-231 cells by downregulating the expression of SATB1.