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1.
Analyst ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475698

RESUMO

A novel dual-shell magnetic nanoparticle coated with a cationic covalent organic framework, containing ethidium bromide, is easily prepared, characterized and applied as an adsorbent for fast, simple and highly selective capture of nine hydroxylated polycyclic aromatic hydrocarbons in urine samples of non-smokers and smokers who smoked cigarettes with different tar yields. This is the first time that a cationic crystalline framework with high thermal and chemical stability was used for magnetic solid phase extraction. Multiple probes and quantum chemistry theory calculations were conducted to describe the versatile adsorption property directly and quantifiably. A method using high-performance liquid chromatography with a fluorescence detector based on the prepared magnetic adsorbent was established and used to investigate differences in the exposure levels of OH-PAHs in non-smokers and smokers smoking cigarettes with different tar yields. All the OH-PAH analyses present good linearities in the range of 0.1-100 ng mL-1, with R2 > 0.9965. The LOD for the 9 OH-PAHs ranged from 0.0030 to 0.0096 ng mL-1 and the LOQ ranged from 0.096 to 0.030 ng mL-1. The recoveries of the 9 OH-PAHs ranged from 93.3 to 121.3% with the RSD ranging from 0.47 to 3.53%. These results imply that the versatile EB-DS MNPs as adsorbents have great potential in the analysis of trace targets in samples with complex matrices.

2.
Mikrochim Acta ; 186(9): 662, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473812

RESUMO

An electrochemical aptamer-based assay is described for the determination of CFP-10 which is an early secretary biomarker of Mycobacterium tuberculosis. CFP-10 is specifically captured by its aptamer and then induces a DNA cross-linking click reaction, the release of CFP-10, and an amplification cycle of repeated CFP-10 release. This mechanism (with dual amplification via DNA click and target release cycle) causes more and more CFP-10 Apt strands on the electrode surface to expose their 5' overhang and to hybridize with the DNA complexes linked to the gold nanoparticles (AuNPs). Consequently, large amounts of AuNPs, each loaded with a number of quadruplex DNA motifs, can be bound on the electrode surface and remarkably enhance the signal. Under optimal conditions, the method has a detection limit as low as 10 pg.mL-1 of CFP-10. The method was successfully applied to the diagnosis of M. tuberculosis in sputum. Graphical abstract Schematic representation of an electrochemical CFP-10 (10-kDa culture filtrate protein) assay using click DNA cycling in combination with gold nanoparticles loaded with quadruplex DNA motifs. Click chemistry reaction between Dibenzocyclooctyne (DBCO)-DNA and azido-DNA can liberate the CFP-10 antigen for the next cycle, which can be viewed as the first amplification step. G-quadruplex-based DNAzyme is formed due to the guanine-rich sequences of DNA S1, which can be viewed as the second amplification step.

3.
Bioelectrochemistry ; 130: 107341, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31400568

RESUMO

Telomerase is considered a pivotal biomarker for early cancer diagnosis and a valuable therapeutic target. However, the current methods to detect telomerase activity have some limitations. Herein, we propose a homogeneous electrochemical strategy to develop a simple, rapid, and highly sensitive assay to detect human telomerase activity from crude cancer cell extracts. Our strategy is based on magnetic bead separation and exonuclease III-aided target recycling amplification. The complementary probes can hybridize with the extended telomeric repeats, which allows exonuclease III to recognize and digest the latter once the hybrid product is separated with magnetic beads. The released complementary probes can hybridize with and open multiple methylene blue (MB)-labeled hairpin (HP) DNA probes, allowing exonuclease III to digest the duplex. Then, the opened hairpin couples with the captured mononucleotides on the surface of the gold electrode. By taking advantage of the exonuclease III-aided target recycling strategy, the present assay enables the detection of telomerase activity at a single-cell level. Furthermore, the assay is carried out in a homogeneous solution achieved by magnetic purification, which removes the interferents present in crude lysates and avoids false negatives, thus, providing a powerful platform to detect telomerase activity in samples of early-stage cancer.

4.
Int J Biol Macromol ; 139: 1018-1027, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31401283

RESUMO

To explore the variation and phylogenetic utility of mitogenomes among lineages of the diverse hemipteran superfamily Membracoidea, we sequenced four new mitogenomes of four treehopper species of the subfamily Centrotinae (Membracidae): Hypsauchenia hardwichii, Leptocentrus albolineatus, Maurya qinlingensis, and Tricentrus brunneus. The mitogenomes are 15,508 to 16,467 bp in size, and comprise the typical set of 37 mitochondrial genes and a large non-coding region (AT-rich region). Gene organization, nucleotide composition and codon usage of protein-coding genes (PCGs) are similar to those of most other sequenced Membracidae mitogenomes. All PCGs start with a typical ATN or TTG and end with TAA/G or the incomplete stop codon (a single T). All transfer RNA genes can be folded into typical clover-leaf secondary structures, except for trnS1. The location, length and AT content of the rrnS and rrnL genes are highly conserved in the Membracidae mitogenomes. In contrast, the AT-rich control region is highly variable in length and in numbers of tandem repeats present. Phylogenetic analyses based on the nucleotide and amino acid sequence data of 13 PCGs from 59 species of Membracoidea and four outgroups (Cercopoidea and Cicadoidea species) recovered Membracoidea as monophyletic with strong support, and Cicadellidae as paraphyletic with respect to Aetalionidae + Membracidae, in agreement with previous analyses. Relationships among membracoid subfamilies were also in general agreement with results from prior studies. The monophyly of Centrotinae is strongly supported, with relationships among tribes recovered as ((Centrotini+ (Tricentrini + Antialcidini)) + ((Leptobelini + Hypsauchenini) + Leptocentrini).

5.
Molecules ; 24(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398934

RESUMO

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

6.
Food Res Int ; 123: 559-566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31285005

RESUMO

The dynamic changes of wine ester production during mixed fermentation with Hanseniaspora uvarum Yun268 and Saccharomyces cerevisiae F5 was investigated at different levels and timings of nitrogen nutrient addition. Nitrogen additions were performed by supplementing yeast assimilable nitrogen (YAN) into a synthetic grape must with defined composition. Ester precursors and extracellular metabolites involved in ester synthesis were analyzed throughout the fermentation. Results showed that nitrogen additions covering 50-200 mg/L YAN at the point of yeast inoculation slightly affected yeast competition and ester profiles. Interestingly, when YAN was supplemented in the mid-stage, the survival of H. uvarum Yun268 was enhanced, resulting in more than a 2-fold increase in the levels of higher alcohol acetates compared to that at the initial stage. Furthermore, carbon fluxes may be redistributed in the central pathway, which contributed to the production of medium-chain fatty acids and eventually triggered a 1.2-fold elevation in corresponding ethyl ester levels.

7.
Eur J Obstet Gynecol Reprod Biol ; 240: 261-266, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31344665

RESUMO

Kisspeptins are a family of neuropeptides that are critical for the puberty initiation and female fertility. Plasma or serum kisspeptin is mainly derived from the placenta during pregnancy and plasma kisspeptin levels significantly increase across pregnancy. Plasma kisspeptin levels could be used as a potential biomarker for the detection of miscarriage, pre-eclampsia, gestational trophoblastic neoplasia (GTN), and fetal development. Kisspeptin may also be involved in the process of parturition by stimulating oxytocin secretion during term pregnancy. This review discussed the potential use of kisspeptin as a marker across pregnancy and highlighted the unresolved problems in this area. Tweetable abstract: Plasma kisspeptin levels could be used as a potential biomarker across pregnancy.

8.
Neuroimmunomodulation ; 26(3): 139-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31340205

RESUMO

OBJECTIVE: Alzheimer's disease (AD) is an age-related devastating neurodegenerative disorder. The hippocampus and cerebral cortex are the most closely related brain regions of cognitive function and neurogenesis. The present study investigated the role of C-terminal-binding protein 1 (CTBP1) in AD. METHODS: AD rat models were established through intracerebroventricular injection of ß-amyloid polypeptide Aß(25-35) and intragastric administration of aluminum chloride solution, and the expression pattern that CTBP1 showed in the hippocampus and cerebral cortex was determined. The learning and memory abilities of AD rats after CTBP1 overexpression were assessed. Hippocampal and cortical neurons were transfected with siRNA against CTBP1 or CTBP1-overexpressing plasmids in order to study the effects of CTBP1 elevation or depletion on neuron morphological changes, apoptosis, and viability. The expression of CTBP1, proapoptotic factor (B-cell lymphoma 2; Bcl-2), and antiapoptotic factors (Bcl-2-associated X protein [Bax] and caspase-3) was subsequently evaluated. RESULTS: CTBP1 was poorly expressed in the hippocampus and cerebral cortex. AD rats displayed enhanced learning and memory abilities following CTBP1 overexpression. Furthermore, overexpression of CTBP1 improved morphological changes of hippocampal and cortical neurons, increased neuron activity, and inhibited neuron apoptosis in AD rats. Moreover, the expression of Bax and caspase-3 decreased, yet Bcl-2 increased. CONCLUSION: Collectively, CTBP1 plays a protective role in the degeneration of hippocampal and cortical neurons whereby overexpressed CTBP1 attenuated the hippocampal and cortical neuron apoptosis and enhanced neuron activity, highlighting the potential of CTBP1 as a target for AD treatment.

9.
Adv Mater ; 31(36): e1903580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339207

RESUMO

2D planar structures of nonlayered wide-bandgap semiconductors enable distinguished electronic properties, desirable short wavelength emission, and facile construction of 2D heterojunction without lattice match. However, the growth of ultrathin 2D nonlayered materials is limited by their strong covalent bonded nature. Herein, the synthesis of ultrathin 2D nonlayered CuBr nanosheets with a thickness of about 0.91 nm and an edge size of 45 µm via a controllable self-confined chemical vapor deposition method is described. The enhanced spin-triplet exciton (Zf , 2.98 eV) luminescence and polarization-enhanced second-harmonic generation based on the 2D CuBr flakes demonstrate the potential of short-wavelength luminescent applications. Solar-blind and self-driven ultraviolet (UV) photodetectors based on the as-synthesized 2D CuBr flakes exhibit a high photoresponsivity of 3.17 A W-1 , an external quantum efficiency of 1126%, and a detectivity (D*) of 1.4 × 1011 Jones, accompanied by a fast rise time of 32 ms and a decay time of 48 ms. The unique nonlayered structure and novel optical properties of the 2D CuBr flakes, together with their controllable growth, make them a highly promising candidate for future applications in short-wavelength light-emitting devices, nonlinear optical devices, and UV photodetectors.

10.
Cancer Med ; 8(11): 5137-5147, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343111

RESUMO

In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R-CHOP-treated diffuse large B-cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three-year progression-free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax ), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan-Meier analysis, and log-rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P-value = 0.000, and 0.988, P-value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35-46.30, P = 0.002, and HR = 4.86, 95% CI 1.27-18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86-32.24, P = 0.005, and HR = 2.96, 95% CI 1.16-7.54, P = 0.023, respectively). After dichotomy, NCCN-IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0 , TLG0 and dichotomized NCCN-IPI, and the interim variables TMTV1 and %ΔSUVmax , presented independent prognostic value for PFS. In prognostic model 2 (TLG0  + %ΔSUVmax ), the group with TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31344800

RESUMO

The recycling of waterworks sludge has become a trending issue because it not only solves the problem of difficult disposal but also saves land resources. This paper aimed to provide a new idea for the utilization of waterworks sludge to form ceramsite and to purify sewage. The specific surface area, average pore size, and pore volume of the made ceramsite were 8.15 m2/g, 8.53 nm, and 1.88 cm2/g, respectively. The made ceramsite was applied in a vertical-flow constructed wetland, and the removal efficiency of nitrogen, phosphorus and organic matter in sewage were investigated under the conditions of different start-up periods, hydraulic retention times, matrix filling heights and water quality. The removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) in the constructed wetlands were stable at 70%, 60%, and 79%, respectively. This constructed wetland with a ceramic matrix has certain advantages in the total amount of denitrifying microorganisms, with a proportion of 14.92%. The results prove the feasibility of preparing ceramsite from waterworks sludge and applying it as a matrix in a constructed wetland to purify sewage.

12.
Ying Yong Sheng Tai Xue Bao ; 30(6): 1993-2001, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31257772

RESUMO

To understand the influence of roots of understory plant entering litter layer on litter decomposition in forest ecosystems, we examined the effects of different treatments of Lolium multiflorum root biomass on microorganisms and enzyme activities during leaf litter decomposition of Symplocos setchuensis, a dominant species in a mid-subtropical evergreen broad-leaved forest, through a litter bag simulation experiment. Results showed that diversity index of bacterial and fungal communities of leaf litter surface under three treatments, i.e. no root (N), less roots (L), more roots (M), in a 240-day decomposition process showed the following pattern: M > L > N. The effects of these different root biomass treatments on the composition and quantity of fungal community were more significant than those on bacterial community. The biomass of living roots growing in the litter bag gradually decreased at the end of the growing season of L. multiflorum. The impacts of root growth on the composition of the fungal community gradually decreased during decomposition. At the same decomposition stage, the activities of acid phosphatase, ß-glucosidase, polyphenol oxidase, and peroxidase on the litter surface were higher in the treatments with roots than that without roots. These results indicated that root growth could change the composition and quantity of microbial communities and increase the extracellular enzyme activities of microbes, and thus stimulating litter decomposition.


Assuntos
Florestas , Microbiota , Raízes de Plantas/crescimento & desenvolvimento , Microbiologia do Solo , Bactérias , Biomassa , Ecossistema , Folhas de Planta
14.
Ann Emerg Med ; 74(1): e7-e8, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31248505
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 692-701, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204918

RESUMO

OBJECTIVE: To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment(CGA) in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people. METHODS: Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed. RESULTS: The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated. CONCLUSION: The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.


Assuntos
Leucemia Mieloide Aguda , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos
16.
Reprod Biomed Online ; 39(1): 161-167, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31230668

RESUMO

RESEARCH QUESTION: Can serum kisspeptin levels 14 and 21 days after frozen-thawed embryo transfer predict the early pregnancy outcome of patients? DESIGN: Prospective study, with 133 patients undergoing frozen-thawed embryo transfer. Patients were divided into non-pregnant group and pregnant group (including biochemical pregnancy, singleton pregnancy, miscarriage and twin groups). RESULTS: Serum kisspeptin levels on day 21 were significantly higher than day 14 in singleton pregnancy, miscarriage and twin groups (all P < 0.0001), but not in the biochemical pregnancy group. Similarly, serum human chorionic gonadotrophin (HCG) levels were higher on day 21 compared with day 14 except for the biochemical pregnancy group. Compared with the twin group (296.9 pg/ml), the other four groups showed significantly higher serum kisspeptin levels on day 14 (non-pregnant 548.9, biochemical pregnancy 440.4, miscarriage 434.9, singleton pregnancy group 420.9 pg/ml, P < 0.01, P = 0.016, P = 0.034, P = 0.036, respectively). The miscarriage (762.2 pg/ml), singleton pregnancy (730.8 pg/ml) and twin groups (826.3 pg/ml) had significantly higher kisspeptin levels than the biochemical pregnancy group (397.3 pg/ml) on day 21 (P < 0.001, P < 0.01, P < 0.001, respectively). Serum kisspeptin levels on day 14 were negatively correlated with embryo implantation rate (P = 0.035, R2 = -0.880). Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage compared with serum HCG levels (area under the curve = 0.53 and 0.78, respectively). CONCLUSIONS: Serum kisspeptin levels on day 14 are negatively correlated with embryo implantation rate. Serum kisspeptin levels on day 21 have a poor predictive value of miscarriage.

17.
Anal Bioanal Chem ; 411(22): 5721-5727, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31214754

RESUMO

Metastases are the leading causes of death in cancer patients. Due to intimate connection with metastasis, Smoothened (Smo) has become a therapeutic target for antimetastatic drugs and can provide early warning of metastasis in breast cancer. Thus, we have developed an electrochemical method in Smo analysis based on small-molecule drugs. Smo on the metastatic cell surface can be internalized after combination with the small-molecule drug. The surplus small-molecule drug and rolling circle amplification (RCA) primer are competitively binding with capture probe on the electrode surface through the click chemical reaction. After RCA reaction, methylene blue is used to label the RCA product. In this process, the more Smo on the metastatic cell surface, the more RCA primer is bound with peptide on the electrode. Therefore, the obtained signal response is positively correlated to Smo on the cancer cells. Moreover, the RCA provides sufficiently high sensitivity, enabling the limit of detection of Smo to be calculated as 0.1 pM (S/N = 3). Owing to its desirable sensitivity, excellent reproducibility, and high selectivity, the proposed method may hold great potential in clinical practice in the future. Graphical abstract.

18.
Cell Death Dis ; 10(6): 422, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142732

RESUMO

The role of M1 macrophages (M1M)-derived exosomes in the progression of neointimal hyperplasia remains unclear now. Using a transwell co-culture system, we demonstrated that M1M contributed to functional change of vascular smooth muscle cell (VSMC). We further stimulated VSMCs with exosomes isolated from M1M. Our results demonstrated that these exosomes could be taken up by VSMCs through macropinocytosis. Using a microRNA array assay, we identified that miR-222 originated from M1M-derived exosomes triggered the functional changes of VSMCs. In addition, we confirmed that miR-222 played a key role in promoting VSMCs proliferation and migration by targeting Cyclin Dependent Kinase Inhibitor 1B (CDKN1B) and Cyclin Dependent Kinase Inhibitor 1C (CDKN1C) in vitro. In vivo, M1M-derived exosomes significantly aggravated neointima formation following carotid artery ligation injury and wire injury and these effects were partly abolished by miR-222 inhibitor 2'OMe-miR-222. Our findings thus suggest that exosomes derived from M1M could aggravate neointimal hyperplasia through delivering miR-222 into VSMCs. Future studies are warranted to validate if the post-injury vascular neointimal hyperplasia and restenosis could be attenuated by inhibiting miR-222.

19.
Clin Ther ; 41(6): 1151-1163, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079860

RESUMO

PURPOSE: The objective of this study was to characterize the population pharmacokinetics of voriconazole and to identify factors that significantly affect pharmacokinetic parameters and to further investigate optimal dosage regimens in Chinese adult patients with hematologic malignancies. METHODS: A prospective population pharmacokinetic analysis was performed on 186 concentration measurements obtained from 41 adult patients with hematologic malignancies. All enrolled patients were treated with voriconazole for diagnosed or suspected invasive fungal diseases. Oral voriconazole was routinely administered at a maintenance dose of 200 mg q12h. Serial blood samples were collected after steady-state of each patient. Monte Carlo simulation was applied to optimize dosage strategies. FINDINGS: A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.18 L/h, the volume of distribution was 88.9 L, and the absorption rate constant was 0.729 h-1. Clearance and steady-state exposure (AUC0-12) were found to be significantly associated with age and CYP2C19 phenotype. The average AUC0-12 of elderly patients (aged 60-90 years) was 2.1 times higher than that of relative younger patients (aged 18-59 years). The average AUC0-12 of poor metabolizers (PMs) was approximately 2.5 and 1.8 times higher than that of extensive and intermediate metabolizers (IMs), respectively. Considering both efficacy and tolerability, dosage regimens of 100 and 50 mg orally administered every 12 hours were recommended for elderly IMs and PMs, respectively. IMPLICATIONS: A population pharmacokinetic model for voriconazole in Chinese adult patients with hematologic malignancies was successfully developed and could well capture voriconazole's pharmacokinetic characteristics. Age and CYP2C19 phenotype were found to significantly influence voriconazole clearance and should be taken into consideration clinically for dose optimization. The optimal dosage strategies in specific clinical scenarios were proposed in this study based on model simulation. Because of the high incidence of mutant CYP2C19*2 and *3 alleles, genetic testing seems to be necessary for Asian elderly patients when voriconazole treatment is initiated.

20.
J Transl Med ; 17(1): 166, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109331

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease in terms of genetic basis, clinical, biological and prognostic, and is a malignant clonal disease of leukemia stem cells (LSCs). Nearly half of adult AML patients exhibit a cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of NCALD gene was associated with the prognosis of ovarian cancer and non-small cell lung cancer (NSCLC). The expression level of NCALD gene is still unclear in the prognosis of patients with AML. METHOD: We integrated 5 independent datasets totally 665 AML patients (497 CN-AML patients) to analyzed relation between NCALD gene expression and the clinical FAB classification, gene mutation, therapy, prognosis of CN-AML. We analyzed the NCALD gene expression with the prognosis and LSC of 165 AML patients from The Cancer Genome Atlas (TCGA) dataset and 78 AML patients from GEO dataset. RESULTS: High NCALD-expressing CN-AML patients were associated with poor event-free survival (EFS) and overall survival (OS) compared to low NCALD expression (EFS, P < 0.0001, OS, P < 0.0001). In AML patients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), high NCALD expression was associated with poor survival prognosis in EFS and OS (EFS, P < 0.0051, OS, P = 0.028). Post-chemotherapy in AML patients, high NCALD expression led a worse prognosis in EFS and OS (EFS, P = 0.011; OS, P = 0.0056). In multivariate analysis, high NCALD expression was an independent prognostic factor that predicts shorter EFS and OS (EFS, P = 3.84E-05, OS, P = 8.53E-05) of CN-AML. CONCLUSION: Our results indicate that high expression of NCALD gene is a poor prognostic factor for CN-AML. NCALD can be considered as independent predictors of CN-AML patients and can be used as a biomarker for the prognosis of CN-AML.

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