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1.
J Clin Pharm Ther ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053745

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Focusing on the tolerance and pharmacokinetics of new drugs, phase I clinical drug trials are characterized by high risk, poor compliance and management difficulties. High-quality clinical drug trials ensure subjects' safety while extending new drug research and development. Many studies have examined micro-level concerns of trial design and implementation rather than macro-level factors. Accordingly, we evaluated the quality of phase I clinical drug trials (trial quality) and analysed the influence of organizational management factors from a macro-level perspective. METHODS: We surveyed staff at clinical trial institutions engaged in phase I clinical drug trials in China using convenience sampling. We employed a five-point Likert-scale questionnaire, comprising five items on phase I clinical drug trial quality and items on organizational management factors. Data from 604 questionnaires were analysed. We utilized a logistic regression model to estimate the influence of organizational management factors on trial quality, using individual demographic factors as controlling variables. RESULTS AND DISCUSSION: The trial quality score was 3.81, which indicates that substantial improvement is required. Government regulation, industry management and medical institution management had a positive effect on trial quality: ß = 0.842, 0.691 and 0.579, respectively; P < .01. Contract research organization management had a negative effect on trial quality: ß = -0.476; P = .013. Research team management had no effect on trial quality: ß = 0.325; P = .141. WHAT IS NEW AND CONCLUSION: This study is the first to model the influence of organizational management factors on the quality of phase I drug trials involving different organizations from a macro-perspective. Efforts are needed to help research teams take responsibility for trial quality and to correct the negative impact of contract research organizations on trial quality.

2.
J Am Chem Soc ; 142(5): 2532-2540, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31910340

RESUMO

Mitomycin C (MMC) has been using for the treatment of a variety of digestive tract cancers. However, its nonspecific DNA-alkylating ability usually causes severe side effects, thus largely limiting its clinical applications. The utilization of an efficient active targeted drug delivery technique would address this issue. Accordingly, we report the design and development of aptamer-mitomycin C conjugates that use different cross-linking chemistry. The targeted delivery ability and cytotoxicity of these conjugates were carefully studied. It is worth noting that a linker-dependent cytotoxicity effect was observed for these conjugates. The use of a reductant-sensitive disulfide bond cross-linking strategy resulted in significantly enhanced cytotoxicity of MMC against the target cancer cell lines. Importantly, this cytotoxicity enhancement was suited to different types of aptamers, demonstrating the success of our design. Mechanistic studies of the enhanced cytotoxicity effect indicated that the target recognition, specific binding, and receptor-mediated internalization of aptamer were also critical for the observed effect.

3.
Bioconjug Chem ; 31(1): 37-42, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31815437

RESUMO

Nucleic acid aptamers, also known as "chemical antibodies", have been widely employed in targeted cancer therapy and diagnosis. For example, aptamer-drug conjugates (ApDCs), through covalent conjugation of cytotoxic warheads to aptamers, have demonstrated anticancer efficacy both in vitro and in vivo. However, a general strategy to endow ApDCs with enhanced biostability, prolonged circulation half-life, and high drug loading content remained elusive. Herein, we present a polymeric approach to engineer ApDCs via conjugation of cell-targeting aptamers with water-soluble polyprodrugs containing a reductive environmentally sensitive prodrug and biocompatible brush-like backbone. The resultant high-drug loading Aptamer-PolyproDrug Conjugates (ApPDCs) exhibited high nuclease resistance, extended in vivo circulation time, specific recognition, and cellular uptake to target cells, reduction-triggered and fluorescent-reporting drug release, and effective cytotoxicity. We could also further expand this design principle toward combination therapy by using two kinds of therapeutic drugs with distinct pharmacological mechanisms.

4.
Cancer Med ; 8(14): 6250-6257, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31469256

RESUMO

BACKGROUND: To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal-type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Both fAIP and PDAC presented hyper-fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut-off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. CONCLUSIONS: The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC.

5.
Talanta ; 204: 238-247, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357288

RESUMO

In this article, an ambient mass spectrometric method with molecularly imprinted polymer (MIP)-coated wooden tips was developed for sensitive analysis of trace macrolide antibiotics in complex food samples. A novel solid-phase microextraction (SPME) probe was prepared, via the modification of a layer MIP coating (with roxithromycin as template molecule) on the surface of wooden tips. The obtained MIP-coated wooden-tip SPME probe can be applied directly to enrich trace macrolide antibiotics from complex food samples, with enrichment factors of 244-1604, 72-370, and 12-82 folds for analysis of five investigated macrolide antibiotics in drinking water, honey, and milk samples, respectively. After extraction, a high voltage and some spray solvent were applied on the loaded SPME probe to desorb and ionize analytes enriched on the probe surface for electrospray ionization mass spectrometric (ESI-MS) analysis under ambient and open-air conditions. The method showed good linearity, with correlation coefficient values (r2) no less than 0.9904, and the calibration function was verified via Mandel's fitting test (p > 0.063). The limits of detection were in the range of 0.003-0.05, 1.1-5.1, and 1.9-15.8 ng/g for analysis of drinking water, honey, and milk samples, respectively. Recoveries of the five targeted macrolide antibiotics in honey and milk samples ranged from 73.4% to 98.1%, with the standard deviations no higher than 8.6%. As a result, MIP-coated wooden-tip ESI-MS method could be feasibly used as a sensitive method for determination of trace macrolide antibiotics in complex food samples.


Assuntos
Antibacterianos/análise , Contaminação de Alimentos/análise , Macrolídeos/análise , Impressão Molecular , Ácidos Polimetacrílicos/química , Madeira/química , Animais , Antibacterianos/química , Água Potável/análise , Reutilização de Equipamento , Mel/análise , Limite de Detecção , Macrolídeos/química , Metacrilatos/química , Leite/química , Reprodutibilidade dos Testes , Microextração em Fase Sólida/instrumentação , Microextração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos
6.
J Environ Manage ; 246: 730-736, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220733

RESUMO

The trapping of sediments within permeable pavements during infiltration is an important process that contributes to their water quality treatment performance. However, this process also leads to clogging, which decreases the infiltration capacity of the pavement. With different rainfall intensities and durations, this study investigates the amount and size of sediment passing through a porous paver, as well as through the gravel-filled gaps that separate adjacent pavers. One of the major challenges in this study was to design an experiment where the characteristics of the sediment particles that are trapped while passing through these two different infiltration pathways are assessed. This was overcome by developing a new type of rainfall application device in combination with a two-tiered sediment capturing system. A better understanding of the infiltration pathways of sediment and the associated clogging processes should help designers improve the effective life of permeable pavements. Overall, it was found that while the porosity of porous pavers serves a useful function in terms of removing excess surface water during and after a rainfall event, it serves little purpose in removing sediment from stormwater.


Assuntos
Movimentos da Água , Purificação da Água , Porosidade , Chuva , Água , Qualidade da Água
7.
Org Lett ; 21(13): 5111-5115, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31199659

RESUMO

A mild amination protocol of N-heteroaryl alkyl ethers with various amines is described. This transformation is achieved by utilizing simple and readily available base as promoter via C-O bond cleavage, offering a new amination strategy to access several anticancer-active compounds. This work is highlighted by the excellent functional group compatibility, scalability, wide substrate scope, and easy derivatization of a variety of drugs.

8.
Oncol Lett ; 17(6): 5030-5038, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186714

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortalities worldwide. The role of ornithine transcarbamylase (OTC) in HCC remains unclear. In the present study, the expression of OTC in HCC was analyzed based on datasets from the Gene Expression Omnibus database of the National Center for Biotechnology Information and further confirmed by immunohistochemistry, western blotting analysis and reverse transcription-quantitative polymerase chain reaction assays on clinical samples and cell lines. Furthermore, the associations between OTC expression and clinicopathological parameters as well as clinical outcome, including the overall and disease-free survival rates were analyzed. Finally, the effect of OTC on HCC cells was measured using proliferation, bromodeoxyuridine and colony-formation assays. Lower OTC expression was observed in HCC cells and tissues compared with primary human hepatocytes. Further investigation demonstrated that low expression of OTC in HCC was associated with larger tumor size and advanced grade. A Kaplan-Meier analysis revealed that patients with lower levels of OTC exhibited shorter overall and disease-free survival times. Notably, OTC silencing with RNA interference facilitated cell proliferation in HCC SK-Hep-1 and Huh-7 cells. However, overexpression of OTC led to inhibition of cell proliferation. In conclusion, the present study identified a novel role of OTC in HCC development, providing a potential novel therapeutic target for this disease.

9.
J Am Chem Soc ; 141(16): 6458-6461, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30942594

RESUMO

Inspired by this elegant system of cellular adaptivity, we herein report the rational design of a dynamic artificial adaptive system able to sense and respond to environmental stresses in a unique sense-and-respond mode. Utilizing DNA nanotechnology, we constructed an artificial signal feedback network and anchored it to the surface membrane of a model giant membrane vesicle (GMV) protocell. Such a system would need to both senses incoming stimuli and emit a feedback response to eliminate the stimuli. To accomplish this mechanistically, our DNA-based artificial signal system, hereinafter termed DASsys, was equipped with a DNA trigger-induced DNA polymer formation and dissociation machinery. Thus, through a sequential cascade of stimulus-induced DNA strand displacement, DASsys could effectively sense and respond to incoming stimuli. Then, by eliminating the stimulus, the membrane surface would return to its initial state, realizing the formation of a cyclical feedback mechanism. Overall, our strategy opens up a route to the construction of artificial signaling system capable of maintaining homeostasis in the cellular micromilieu, and addresses important emerging challenges in bioinspired engineering.

10.
Cancer Lett ; 452: 90-102, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-30914208

RESUMO

Invasion and metastasis are the predominant causes of lethal outcomes in patients with hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the invasive or metastatic process are still insufficiently understood. Here, we first integrated several public databases and identified a novel protein kinase, PDZ-binding kinase (PBK) that was frequently upregulated and correlated with poor prognosis in patients with HCC. Gain- or loss-of-function analysis revealed that PBK promoted migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, PBK enhanced uPAR expression by activating its promoter activity. Chromatin immunoprecipitation (ChIP) assay showed that ETV4 directly bound to the core region of uPAR promoter while PBK could enhance the binding of ETV4 to uPAR promoter. In orthotopic mouse model, PBK knockdown markedly inhibited the lung metastasis of HCC cells, while this effect was significantly restored by uPAR overexpression. Finally, there was a positive correlation between PBK and uPAR, ETV4 and uPAR in HCC clinical samples. Collectively, these findings revealed that PBK acted as a crucial kinase by promoting invasion and migration via the ETV4-uPAR signaling pathway, and it therefore could be a promising diagnostic biomarker and therapeutic target for HCC metastasis.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Lectinas de Ligação a Manose/genética , Glicoproteínas de Membrana/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Receptores de Superfície Celular/genética , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células Hep G2 , Humanos , Fígado/citologia , Fígado/patologia , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/biossíntese , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais/genética
11.
Cancer Lett ; 451: 156-167, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30867140

RESUMO

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme which is associated with poor prognosis in human breast, colon, lung and liver cancers. However, the molecular mechanisms underlying the pro-tumorigenic function of NQO1 remains unclear. This study investigated the function of NQO1 in the context of hepatocellular carcinoma (HCC) development. We found that NQO1 was frequently up-regulated in human liver cancer, and its high expression level was correlated with the tumor stage and low survival rate of HCC patients. Loss-of-function of NQO1 inhibited growth in HCC cells with increased apoptosis in vitro, and suppressed orthotopic tumorigenicity in vivo. Mechanistically, high level of NQO1 in HCC cells enhanced protein stability of X-linked inhibitor of apoptosis protein (XIAP) by increasing its phosphorylation at Ser 87. Reintroduction of wile type XIAP and the phospho-mimic mutants XIAPS87D significantly reversed NQO1 knock-down/out induced growth inhibition and apoptosis. In mouse model with orthotopically implanted hepatocarcinoma, NQO1 suppression and NQO1 inhibitor suppressed tumor growth and induced apoptosis. NQO1 plays an important role in sustaining HCC cell proliferation and may thus act as a potential therapeutic target in HCC treatment.


Assuntos
Apoptose , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Transformada , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NAD(P)H Desidrogenase (Quinona)/genética , Fosforilação
12.
Micromachines (Basel) ; 9(6)2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30424192

RESUMO

Swallowable capsule robots which travel in body cavities to implement drug delivery, minimally invasive surgery, and diagnosis have provided great potential for medical applications. However, the space constraints of the internal environment and the size limitations of the robots are great challenges to practical application. To address the fundamental challenges of narrow body cavities, a different-frequency driven approach for multiple capsule robots with screw structure manipulated by external electromagnetic field is proposed in this paper. The multiple capsule robots are composed of driven permanent magnets, joint permanent magnets, and a screw body. The screw body generates a propulsive force in a fluidic environment. Moreover, robots can form new constructions via mutual docking and release. To provide manipulation guidelines for active locomotion, a dynamic model of axial propulsion and circumferential torque is established. The multiple start and step-out frequencies for multiple robots are defined theoretically. Moreover, the different-frequency driven approach based on geometrical parameters of screw structure and the overlap angles of magnetic polarities is proposed to drive multiple robots in an identical electromagnetic field. Finally, two capsule robots were prototyped and experiments in a narrow pipe were conducted to verify the different motions such as docking, release, and cooperative locomotion. The experimental results demonstrated the validity of the driven approach for multiple capsule robots in narrow body cavities.

13.
Cancer Manag Res ; 10: 2499-2507, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122999

RESUMO

Background: Skeletal muscle depletion is a prognostic factor in patients with cancer. Here, we evaluated the association between the skeletal muscle index (SMI) and local and systemic responses in patients with colon cancer. Patients and methods: We analyzed the relationships of the SMI with neutrophil, lymphocyte, monocyte, and platelet counts; the neutrophil-to-lymphocyte ratio; albumin levels; and C-reactive protein levels in a cohort of 561 patients, and with the circulating levels of 39 cytokines in a cohort of 125 patients. We also studied the association between the SMI and tumor local inflammatory response and the effect of SMI on survival. Results: The median SMIs for male and female subjects were 44.1 and 34.2 cm2/m2, respectively. We observed positive correlations of the SMI with neutrophil (p=0.022), lymphocyte (p=0.001), and monocyte counts (p=0.003). A low SMI correlated significantly with an increased platelet count (p=0.017), decreased albumin level (p=0.006), neutrophil-to-lymphocyte ratio >3 (p=0.021), and an increased interferon γ-induced protein 10 level (IP-10, r = -0.276, p=0.002). The SMI did not correlate significantly with local inflammatory reactions or the C-reactive protein level. Finally, the SMI was a significant prognosticator in patients with stage III colon cancer (3-year disease-free survival rates: 35.1% for the low SMI arms versus 46.0% in the high SMI arms; HR =2.036; p=0.034). Conclusion: This study highlights the association of a low SMI with a high systematic inflammatory response and IP-10 levels. Furthermore, low SMI is a predictor of poor disease-free survival in patients with stage III colon cancer.

14.
Anal Chem ; 90(11): 6936-6944, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29707954

RESUMO

Lipidomics is a significant way to understand the structural and functional roles that lipids play in biological systems. Although many mass spectrometry (MS)-based lipidomics strategies have recently achieve remarkable results, in vivo, in situ, and microscale lipidomics for small biological organisms and cells have not yet been obtained. In this article, we report a novel lipidomics methodology for in vivo, in situ, and microscale investigation of small biological organisms and cells using biocompatible surface-coated probe nanoelectrospray ionization mass spectrometry (BSCP-nanoESI-MS). A novel biocompatible surface-coated solid-phase microextration (SPME) probe is prepared, which possesses a probe-end diameter of less than 5 µm and shows excellent enrichment capacity toward lipid species. In vivo extraction of living biological organisms (e.g., zebrafishes), in situ sampling a precise position of small organisms (e.g., Daphnia magna), and even microscale analysis of single eukaryotic cells (e.g., HepG2) are easily achieved by the SPME probe. After extraction, the loaded SPME probe is directly applied for nanoESI-MS analysis, and a high-resolution mass spectrometer is employed for recording spectra and identifying lipid species. Compared with the conventional direct infusion shotgun MS lipidomics, our proposed methodology shows a similar result of lipid profiles but with simpler sample pretreatment, less sample consumption, and shorter analytical times. Lipidomics of zebrafish, Daphnia magna, and HepG2 cell populations were investigated by our proposed BSCP-nanoESI-MS methodology, and abundant lipid compositions were detected and identified and biomarkers were obtained via multivariate statistical analysis.


Assuntos
Materiais Revestidos Biocompatíveis/química , Lipídeos/análise , Animais , Daphnia , Células Hep G2 , Humanos , Espectrometria de Massas , Análise Multivariada , Propriedades de Superfície , Peixe-Zebra
15.
Eur Radiol ; 28(10): 4362-4369, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29651766

RESUMO

OBJECTIVES: To explore the relationship between osteosclerotic changes and chemotherapy response in non-small-cell lung cancer (NSCLC) patients with bone metastases (BM). METHODS: Fifty-two NSCLC patients with BM were enrolled from 1 January 2010-31 June 2015 and divided into two groups based on their CT features: an osteosclerotic change (OC) group and a no-osteosclerotic change (NOC) group. The disease control rate (DCR) was evaluated, and progression-free survival (PFS) was analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse the factors that could affect PFS. RESULTS: Osteosclerotic changes were observed in 35/52 patients. The median interval when osteosclerotic changes occurred was 2 months (range 1-3 months) after chemotherapy. The OC group had a significantly higher 3-month DCR than the NOC group (p < 0.001). The OC group had a higher 1-year PFS rate than the NOC group (1-year PFS: 74.9% vs. 30.2%, p < 0.001). Univariate Cox regression analysis indicated that pathological subtype (HR = 4.419; 95% CI = 1.635-11.941, p = 0.003) and osteosclerotic changes (HR = 0.199; 95% CI = 0.083-0.477, p < 0.001) were significant predictors of PFS. CONCLUSION: Early osteosclerotic changes predict chemotherapy response in NSCLC patients with BM. KEY POINTS: • Osteosclerotic changes were prevalent CT features after chemotherapy in NSCLC patients. • Osteosclerotic changes were positively related to increased 3-month DCR. • Osteosclerotic changes were positively related to increased 1-year PFS rate.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Osteosclerose/diagnóstico por imagem , Adulto , Idoso , Neoplasias Ósseas/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
Hepatology ; 68(4): 1260-1276, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29624717

RESUMO

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA), which serves as a template for HBV RNA transcription, is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified silent mating type information regulation 2 homolog 3 (SIRT3) as a host factor restricting HBV transcription and replication by screening seven members of the sirtuin family, which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA, as well as replicative intermediate DNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. A mechanistic study found that nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9. Importantly, occupancy of SIRT3 on cccDNA could increase the recruitment of histone methyltransferase suppressor of variegation 3-9 homolog 1 to cccDNA and decrease recruitment of SET domain containing 1A, leading to a marked increase of trimethyl-histone H3 (Lys9) and a decrease of trimethyl-histone H3 (Lys4) on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor Yin Yang 1 to cccDNA. Finally, hepatitis B viral X protein could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. CONCLUSION: SIRT3 is a host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase; these data provide a rationale for the use of SIRT3 activators in the prevention or treatment of HBV infection. (Hepatology 2018).


Assuntos
DNA Viral/genética , Epigênese Genética/genética , Hepatite B/genética , Domínios PR-SET/genética , Sirtuína 3/genética , Replicação Viral/genética , DNA Complementar/genética , Hepatite B/fisiopatologia , Vírus da Hepatite B/genética , Histona Metiltransferases/metabolismo , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade
17.
Front Plant Sci ; 9: 11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29403521

RESUMO

Rapid and non-destructive diagnostic tools to accurately assess crop nitrogen nutrition index (NNI) are imperative for improving crop nitrogen (N) diagnosis and sustaining crop production. This study was aimed to develop the relationships among NNI, leaf N gradient, chlorophyll meter (CM) readings gradient, and positional differences chlorophyll meter index [PDCMI, the ratio of CM readings between different leaf layers (LLs) of crop canopy] and to validate the accuracy and stability of these relationships across the different LLs, years, sites, and cultivars. Six multi-N rates (0-320 kg ha-1) field experiments were conducted with four summer maize cultivars (Zhengdan958, Denghai605, Xundan20, and Denghai661) at two different sites located in China. Six summer maize plants per plot were harvested at each sampling stage to assess NNI, leaf N concentration and CM readings of different LLs during the vegetative growth period. The results showed that the leaf N gradient, CM readings gradient and PDCMI of different LLs decreased, while the NNI values increased with increasing N supply. The leaf N gradient and CM readings gradient increased gradually from top to bottom of the canopy and CM readings of the bottom LL were more sensitive to changes in plant N concentration. The significantly positive relationship between NNI and CM readings of different LLs (LL1 to LL3) was observed, yet these relationships varied across the years. In contrast, the relationships between NNI and PDCMI of different LLs (LL1 to LL3) were significantly negative. The strongest relationship between PDCMI and NNI which was stable across the cultivars and years was observed for PDCMI1-3 (NNI = -5.74 × PDCMI1-3+1.5, R2 = 0.76**). Additionally, the models developed in this study were validated with the data acquired from two independent experiments to assess their accuracy of prediction. The root mean square error value of 0.1 indicated that the most accurate and robust relationship was observed between PDCMI1-3 and NNI. The projected results would help to develop a simple, non-destructive and reliable approach to accurately assess the crop N status for precisely managing N application during the growth period of summer maize crop.

18.
BMC Biophys ; 10: 7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28919974

RESUMO

BACKGROUND: Proteins with low sequence identity but almost identical tertiary structure and function have been valuable to uncover the relationship between sequence, tertiary structure, folding mechanism and functions. Two homologous chemokines, CCL11 and CCL24, with low sequence identity but similar tertiary structure and function, provide an excellent model system for respective studies. RESULTS: The kinetics and thermodynamics of the two homologous chemokines were systematically characterized. Despite their similar tertiary structures, CCL11 and CCL24 show different thermodynamic stability in guanidine hydrochloride titration, with D50% = 2.20 M and 4.96 M, respectively. The kinetics curves clearly show two phases in the folding/unfolding processes of both CCL11 and CCL24, which suggests the existence of an intermediate state in their folding/unfolding processes. The folding pathway of both CCL11 and CCL24 could be well described using a folding model with an on-pathway folding intermediate. However, the folding kinetics and stability of the intermediate state of CCL11 and CCL24 are obviously different. CONCLUSION: Our results suggest homologous proteins with low sequence identity can display almost identical tertiary structure, but very different folding mechanisms, which applies to homologues in the chemokine protein family, extending the general applicability of the above observation.

19.
Radiol Med ; 122(11): 837-849, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28721650

RESUMO

PURPOSE: To investigate the predictive clinical and imaging factors associated with pulmonary metastasis in pulmonary nodules (PNs) ≤10 mm in patients with primary extrapulmonary malignancy (PEPM) on initial CT as well as the inter-nodular imaging features in the non-solitary PNs patients, to make a more reliable diagnosis and appropriate management of the PNs at an earlier stage after detection. MATERIALS AND METHODS: 161 patients with PNs ≤10 mm were reviewed from April 2013 to December 2013. The nature of PNs were determined on the interval change in imaging features on serial CT images (158 patients) and histologically proven (three patients). Independent predictors of changed PNs on initial CT were examined by multivariate regression analysis. RESULTS: 36.6% of patients developed interval change in nodules size. The average interval of the first change was 65.0 days (29-144 days). Tumor staging of III (P = 0.011) and IV (P < 0.001), the nodules number of 2-4 (P = 0.016), 5-9 (P < 0.001) and 10-20 (P < 0.001), the nodules margin of being smooth (P = 0.001) and slight lobulated (P < 0.001), and nodules with no near short strips (P = 0.001) were significant predictors of changed PNs. For patients with non-solitary PNs, 40.2% had PNs with identical imaging features, the incidence rate of change of which (74.3%) was significantly higher compared with that of varied features (32.7%), P < 0.001; and 94.3% of patients had all nodules per patient showing consistent prognosis. CONCLUSIONS: For PNs ≤10 mm in patients with PEPM on baseline CT, the morphological characteristics and primary malignancies stage could differentiate the majority of the PNs. The interval for further CT evaluation of uncertain PNs should be early at 1-3 months after detection, and increased alert is needed for the possibility of pulmonary metastasis when an early interval change was detected.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/secundário , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Meios de Contraste , Feminino , Humanos , Iohexol , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
20.
J Vasc Interv Radiol ; 28(4): 481-489, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28111196

RESUMO

PURPOSE: To retrospectively evaluate risk factors related to incomplete computed tomography (CT)-guided radiofrequency (RF) ablation of metastatic and primary lung tumors. MATERIALS AND METHODS: This study included 93 patients with 147 tumors: 70 men, 23 women; median age 54 y (range, 19-81 y); 24 cases of primary lung tumors, 69 cases of metastases; average largest diameter of tumors, 1.8 cm ± 1.2 (range, 0.3-6.0 cm). Local efficacy was evaluated based on CT follow-up scans. Complete ablation rates (CARs) for tumors were calculated according to several variables; independent risk factors for local tumor progression (LTP) were examined by binary logistic regression analysis. RESULTS: CAR of tumors was 60.54% within first 6 months after lung RF ablation; median interval of LTP was 1.5 months (mean, 1.3 months ± 1.0; range, 0 days to 3 months). Compared with tumors > 3 cm, CAR of tumors ≤ 3 cm was significantly higher (68.55% vs 17.39%, P < .001). CAR of tumors with complete ablation margin (AM) was dramatically higher compared with tumors with incomplete AM (74.77% vs 16.67%, P < .001). Among tumors with complete AM, CAR of tumors with shortest distance between outer edge of tumor and AM (ablative margin D) ≥ 5 mm was compared with tumors with ablative margin D 1-4 mm (85.96% vs 62.96%, P = .005). Multivariate regression analysis showed that lobulation and/or spicules, contact with blood vessels, and ablative margin D < 5 mm were independent risk factors for incomplete lung RF ablation. LTP was likely to develop at the edge of ablated lesions and especially the site of incomplete AM or shortest AM. CONCLUSIONS: RF ablation for lung cancers should be individualized based on tumor size, morphology, and tumor type to obtain an adequate AM.


Assuntos
Ablação por Cateter/efeitos adversos , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/patologia , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Neoplasia Residual , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
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