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1.
J Magn Reson Imaging ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675170

RESUMO

BACKGROUND: The diagnostic efficacy of contrast-enhanced magnetic resonance imaging (CEMRI) in diagnosing residual or recurrent hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) is currently not completely clear. PURPOSE: To investigate the diagnostic efficacy of CEMRI in detecting residual or recurrent HCCs after TACE by meta-analysis. STUDY TYPE: Systematic review and meta-analysis. POPULATION: A systematic literature search was performed in PubMed, Embase, Web of Science, Ovid, and the Cochrane Library database up to June 2019 to find original studies on diagnosing patients suspected of residual or recurrent HCCs after TACE with CEMRI. Thirteen studies comprising 721 nodules were finally included. FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T, CEMRI. ASSESSMENT: Quality assessment of the included studies was performed by applying the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATISTICAL TESTS: Sensitivity and specificity were pooled with a bivariate random-effects model. Heterogeneity was assessed by the chi-square test. The potential sources of heterogeneity were explored by subgroup and publication bias analyses. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic (ROC) curve (AUC) of CEMRI in diagnosing residual or recurrent HCCs after TACE were 91% (95% confidence interval [CI]: 87%-96%), 93% (95% CI: 85%-97%), 12.22 (95% CI: 5.62-26.57), 0.09 (95% CI: 0.05-0.18), 126.99 (95% CI: 34.76-436.99) and 0.97 (95% CI: 0.95-0.98), respectively. Subgroup analysis revealed that CEMRI performed significantly better in prospective studies than in retrospective studies: 0.99 (95% CI: 0.96-1.00) vs. 0.95 (95% CI: 0.92-0.96) with P < 0.05. DATA CONCLUSION: Our meta-analysis suggested that CEMRI had high diagnostic efficacy in detecting residual or recurrent HCCs after TACE and may serve as an alternative method for further evaluation after TACE. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2.

2.
BMC Pregnancy Childbirth ; 19(1): 393, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666022

RESUMO

BACKGROUND: This study aims to investigate the influencing factors of pregnancy after laparoscopic oviduct anastomosis. METHODS: The data of 156 cases of laparoscopic oviduct anastomosis in our hospital were analyzed. RESULTS: The pregnancy rate decreased with age (P < 0.005). The pregnancy rate after six years of anastomosis was higher in those with ligation (P < 0.005). The postoperative pregnancy rate significantly increased in subjects with oviduct lengths of > 7 cm (P < 0.01). The pregnancy rate of isthmus end-to-end anastomosis was higher (P < 0.005). The pregnancy rate after bilateral tubal recanalization was higher than that after unilateral tubal recanalization (P < 0.005). The pregnancy rate after laparoscopic tubal ligation and laparoscopic anastomosis was higher than that of open tubal ligation and laparoscopic anastomosis (P < 0.005). CONCLUSION: The pregnancy rate after laparoscopic oviduct anastomosis is higher in subjects below 35 years old, with a ligation duration of < 6 years, and a length of oviduct of > 7 cm, and those who underwent isthmus anastomosis and laparoscopic oviduct ligation and recanalization.

3.
Chem Biol Interact ; : 108871, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669218

RESUMO

Clopidogrel, a clinically used antiplatelet agent, can be readily hydrolyzed by human carboxylesterase 1A (CES1A) to release an inactive metabolite clopidogrel carboxylic acid (CCA). In this study, clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals (such as mouse, rat, rabbit, beagle dog, minipig and cynomolgus monkey). The results demonstrated that clopidogrel could be hydrolyzed into CCA by all tested hepatic microsomes from human or other mammals, but the hydrolytic rates greatly varied among species. Inhibition assays demonstrated that BNPP (an inactivator of mammalian CES) strongly inactivated clopidogrel hydrolytic activity in all tested hepatic microsomes, suggested that mammalian CES were major contributor(s) responsible for clopidogrel hydrolysis in hepatic preparations from all above-mentioned species. By contrast, the response of a reversible inhibitor of human CES1A on clopidogrel hydrolysis in these liver preparations varied significantly among different species. Moreover, the enzymatic kinetics and the apparent kinetic parameters of clopidogrel hydrolysis in hepatic microsomes from various animal species were evaluated and compared to each other. These findings provide crucial information for deeply understanding the differences in catalytic behaviors of mammalian CES, which will be very helpful for choosing suitable laboratory animal(s) for whole tests of CES1A substrate-drugs.

4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 311-316, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631595

RESUMO

Objective: To investigate the anti-tumor effect of bortezomib on extranodal natural killer/T cell lymphoma, nasal type (ENKTL). Methods: SNK-6 cells were treated with different mass concentrations of bortezomib (0, 1, 2, 4, 5, 6 ng/mL) for 24, 48, 72 h, and different concentrations of nuclear factor-kappa B (NF-κB) signaling pathway inhibitor BAY11-7082 (0, 1, 2, 2.5, 5, 10, 20 µmol/L) for 24 h respectively, then the cell viability was measured by CCK8 kit and the half inhibitory concentration (IC 50) was calculated. SNK-6 cells were treated with 30µmol/L Z-VAD-FMK (Pan-caspase inhibitor)+3ng/mL bortezomib, and 5, 10 µmol/L BAY11-7082+3 ng/mL bortezomib for 24 h respectively, then the cell viability was measured by CCK8 kit. After treatment of SNK-6 cells with different mass concentrations of bortezomib for 24 h, apoptosis was detected by AnnexinⅤ/PI flow cytometry; the expression of apoptosis-related protein Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl-2 and NF-κB signaling pathway key proteins P65 and P100/P52 were detected by Western blot. Results: Bortezomib inhibited the proliferation of SNK-6 cells in a dose-dependent manner ( P<0.05), and IC 50( (2.87±0.06) ng/mL) at 24 h was lower than that at 48 h and 72 h ( P<0.05). BAY11-7082 also inhibited the proliferation of SNK-6 cells with an IC 50= (9.73±0.36) µmol/L at 24 h. The combination treatment indicated that Z-VAD-FMK could attenuate the inhibitory effect of bortezomib on the proliferation of SNK-6 cells ( P<0.05), while BAY11-7082 could enhance the inhibitory effect of bortezomib on the proliferation of SNK-6 cells ( P<0.05). After treatment of SNK-6 cells with bortezomib for 24 h, apoptosis-related protein Caspase-3 cleavage, PARP activation, and Bcl-2 cleavage; NF-κB signaling pathway-related protein P65 phosphorylation level decreased, and P52 decreased. Conclusion: Bortezomib inhibits ENKTL cells proliferation by inhibiting NF-κB signaling pathway and induces apoptosis of ENKTL cells via mitochondria-mediated caspase pathway.

5.
Br J Nutr ; : 1-23, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31623699

RESUMO

This study was conducted to evaluate the effects of glucose, soy oil, or glutamine on jejunal morphology, protein metabolism, and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isocaloric diets formulated with glucose, soy oil, or glutamine for 28 days. On day 14 or 28, the proteins in crypt enterocytes were analyzed with isobaric tags for relative and absolute quantification, and proteins involved in mTORC1 signaling pathway in villus or crypt compartment cells were determined by western blotting. Our results showed no significant differences (P > 0.05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function, and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of 4EBP1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soy oil. On day 28, higher protein expression of p-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soy oil. In conclusion, the isocaloric glucose, soy oil, or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared to soy oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.

6.
World J Pediatr ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612427

RESUMO

BACKGROUND: Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. METHODS: A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. RESULTS: 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P < 0.05), but no difference in alanine aminotransferase, ferritin, and ratio of ferritin/erythrocyte sedimentation rate (ESR) at onset of MAS when compared to pre-MAS stages of the disease. In addition, ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage. Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD. Receiver-operating characteristic analysis showed that 12,217.5 µg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity (80.0% and 90.5%) and specificity (88.2% and 86.7%), respectively, for predicting full-blown SJIA-MAS. The majority of the patients received corticosteroids (79/80), while biologic agents were used in 12.5% (10/80) of cases. Tocilizumab was the most commonly selected biologic agent. The overall mortality rate was 7.5%. CONCLUSIONS: About half of MAS occurred when the underlying autoimmune diseases (SJIA, KD, and CTD) were first diagnosed. Hypotension could be an important manifestation before MAS diagnosis. Decreased albumin and increased AST, LDH, ferritin, and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

7.
Neurol Res ; 41(12): 1075-1082, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31591945

RESUMO

Objectives: To explore the role of mTOR signaling pathway in modulating epileptogenesis in an N-methyl-D-aspartic acid (NMDA)-induced infant spasm (IS) rat model. Methods: After inducing IS successfully, the phosphorylation status of PI3K, Akt, mTOR and S6K of brain and hippocampus tissues was assessed using western blot and immunochemistry analysis, respectively. The possible mechanism of mTOR signaling pathway was evaluated by the, inhibitors for mTOR and PI3K, rapamycin and wortmannin, respectively. The inhibitors were injected into the intraperitoneal space of the rats to examine the effects of PI3K and mTOR in IS rat model. Results: The phosphorylated levels of mTOR and PI3K in hippocampus increased significantly (P < 0.05) 7 days after IS induction in rats. After administration of wortmannin, the phosphorylated levels of PI3K and mTOR decreased. However, only the phosphorylated level of mTOR decreased obviously after rapamycin administration. No obvious neurogenesis was found after IS induction. Discussion: Results of the present study suggest that hippocampal PI3K may be another potential target for IS treatment.

8.
World J Pediatr ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31515696

RESUMO

BACKGROUND: Ultrasonography has become a useful tool in the clinical rheumatology settings in the last two decades, but its use has only recently been explored by pediatric rheumatologists. The aim of this article is to review the literature on the current status and recent advances on the use of ultrasound in pediatric rheumatic diseases. DATA SOURCES: We have retrieved and reviewed the relevant articles from MEDLINE/PubMed databases published so far, on the applications of ultrasound in juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, dermatomyositis, enthesitis, Sjogren's syndrome, and other rheumatic diseases. In addition, articles on novel ultrasound imaging technology of potential use in pediatric rheumatology are also reviewed. RESULTS: In JIA, ultrasound can be used to detect subclinical synovitis, to improve the classification of patients in JIA subtypes, to capture early articular damage, to monitor treatment response, and to guide intraarticular injections. Ultrasound is also considered useful in other rheumatic disorders for the evaluation of musculoskeletal symptoms, assessment of parotid gland pathology, and measurement of skin thickness and pathology. Novel ultrasound techniques developed to augment the functionality of ultrasonography may also be applicable in pediatric rheumatic disorders. CONCLUSIONS: Ultrasound shows great promise in the assessment and management of children with rheumatologic disorders. However, standardization and validation of ultrasound in healthy children and in patients with rheumatic diseases are still needed.

9.
JMIR Mhealth Uhealth ; 7(9): e11229, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31516128

RESUMO

BACKGROUND: The diagnosis of paroxysmal events in infants is often challenging. Reasons include the child's inability to express discomfort and the inability to record video electroencephalography at home. The prevalence of mobile phones, which can record videos, may be beneficial to these patients. In China, this advantage may be even more significant given the vast population and the uneven distribution of medical resources. OBJECTIVE: The aim of this study is to investigate the value of mobile phone videos in increasing the diagnostic accuracy and cost savings of paroxysmal events in infants. METHODS: Clinical data, including descriptions and home videos of episodes, from 12 patients with paroxysmal events were collected. The investigation was conducted in six centers during pediatric academic conferences. All 452 practitioners present were asked to make their diagnoses by just the descriptions of the events, and then remake their diagnoses after watching the corresponding home videos of the episodes. The doctor's information, including educational background, profession, working years, and working hospital level, was also recorded. The cost savings from accurate diagnoses were measured on the basis of using online consultation, which can also be done easily by mobile phone. All data were recorded in the form of questionnaires designed for this study. RESULTS: We collected 452 questionnaires, 301 of which met the criteria (66.6%) and were analyzed. The mean correct diagnoses with and without videos was 8.4 (SD 1.7) of 12 and 7.5 (SD 1.7) of 12, respectively. For epileptic seizures, mobile phone videos increased the mean accurate diagnoses by 3.9%; for nonepileptic events, it was 11.5% and both were statistically different (P=.006 for epileptic events; P<.001 for nonepileptic events). Pediatric neurologists with longer working years had higher diagnostic accuracy; whereas, their working hospital level and educational background made no difference. For patients with paroxysmal events, at least US $673.90 per capita and US $128 million nationwide could be saved annually, which is 12.02% of the total cost for correct diagnosis. CONCLUSIONS: Home videos made on mobile phones are a cost-effective tool for the diagnosis of paroxysmal events in infants. They can facilitate the diagnosis of paroxysmal events in infants and thereby save costs. The best choice for infants with paroxysmal events on their initial visit is to record their events first and then show the video to a neurologist with longer working years through online consultation.

10.
Pathol Oncol Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502038

RESUMO

Small nucleolar RNA host gene 16 (SNHG16) is reported to be involved in the tumorigenesis of various kinds of tumors. SNHG16 expression was reported to be upregulated in colon cancer, however, the underlying mechanism of how SNHG16 affects the colon cancer development remains poorly elucidated. In our study, with the aim to identify the role of SNHG16 on colon cell proliferation, SNHG16 was overexpressed or knocked down in vitro, respectively. SNHG16 overexpression accelerated colon cancer cell growth, while cell growth ability was impaired in SNHG16 silencing cells. Furthermore, the starBase database predicted that miR-302a-3p was the target gene of SNHG16, which was supported by dual luciferase assay. The effect of promoting cell proliferation ability induced by SNHG16 overexpression could be partly reversed by co-transfection of miR-302a-3p mimic. Application of the miRanda database indicated that AKT may be modulated by SNHG16, further evidenced by western blot and quantitative PCR assays. AKT overexpression could partly reverse the attenuated colon cancer cell growth caused by miR-302a-3p mimic transfection. Meanwhile, the combination of miR-302a-3p inhibitor and shAKT achieved the parallel result. In conclusion, our study revealed the SNHG16/miR-302a-3p/AKT axis might play a crucial role in colon cancer cell proliferation, thus participating in the process of colon cancer development.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 845-850, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506140

RESUMO

OBJECTIVE: To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms. METHODS: A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time. RESULTS: Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05). CONCLUSIONS: For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Espasmos Infantis , Anticonvulsivantes , Humanos , Lactente , Modelos de Riscos Proporcionais , Espasmo , Espasmos Infantis/tratamento farmacológico
12.
Nano Lett ; 19(9): 6569-6576, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31381357

RESUMO

Reports reveal that the piezoresistance coefficients of silicon carbide (SiC) nanowires (NWs) are 2 to 4 times smaller than those of their corresponding bulk counterparts. It is a challenge to eliminate contamination in adhering NWs onto substrates. In this study, a new setup was developed, in which NWs were manipulated and fixed by a goat hair and conductive silver epoxy in air, respectively, in the absence of any depositions. The goat hair was not consumed during manipulation of the NWs. The process took advantage of the stiffness and tapered tip of the goat hair, which is unlike the loss issue of beam sources in depositions. With the new fixing method, in situ transmission electron microscopy (TEM) electromechanical coupling measurements were performed on pristine SiC NWs. The piezoresistance coefficient and carrier mobility of SiC NW are -94.78 × 10-11 Pa-1 and 30.05 cm2 V-1 s-1, respectively, which are 82 and 527 times respectively greater than those of SiC NWs reported previously. We, for the first time, report that the piezoresistance coefficient of SiC NW is 17 times those of its bulk counterparts. These findings provide new insights to develop high performance SiC devices and to help avoid catastrophic failure when working in harsh environments.

13.
Cancer Med ; 8(13): 5995-6009, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31448575

RESUMO

BACKGROUND: A series of studies have investigated the vital role of microRNA-181 (miR-181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it might be associated with the prognosis of CRC. However, inconsistent findings have hindered its clinical application. METHODS: A comprehensive meta-analysis and an integrative bioinformatics analysis were carried out for concluding current available evidence, clarifying the preliminary prognostic value and unfolding the underlying biological function of miR-181 in CRC patients. RESULTS: The findings revealed that elevated expression levels of miR-181 were associated with significantly poorer overall survival rates (HR = 1.75, 95% CI: 1.26-2.43, P < .05). Meanwhile, the target genes of miR-181 were identified and enriched into several important gene ontology (GO) categories and signaling pathways including miRNAs in cancer, pathways in cancer, proteoglycans in cancer, colorectal cancer, FoxO signaling pathway, PI3K-Akt signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, mTOR signaling pathway, and cAMP signaling pathway, which were confirmed highly involved in the initiation and progression of CRC. In addition, the protein-protein interaction (PPI) networks were set up by miR-181 targets to screen hub nodes and significant modules, which were also considerably associated with the molecular pathogenesis of CRC. CONCLUSIONS: The present study demonstrated that miR-181 could be a promising biomarker with predictive value for prognosis for CRC patients. However, future studies comprising large cohorts from multicenter are warranted to further investigate the biomarker value of miR-181.

14.
Expert Rev Anticancer Ther ; 19(8): 731-738, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31424306

RESUMO

Introduction: The poor prognosis for patients with esophageal cancer (EC) requires evolving current treatment regimens. Immune checkpoint inhibitors show clinical efficacy and a great safety profile in multiple tumors. And the monoclonal antibodies that target programmed death receptor-1/programmed death receptor ligand-1 or the cytotoxic T lymphocyte antigen-4 pathway has shown potential curable effect of EC. Areas covered: This review article covers the prognostic significance of immune checkpoint expression, the accumulating current clinical studies of checkpoint inhibitors in esophageal cancer patients, and future directions. Expert opinion: Many clinical studies have reported favorable survival results with manageable toxicity of anti-programmed death receptor-1/programmed death receptor ligand-1 and anti-cytotoxic T lymphocyte antigen-4 treatment. More results are expected from future clinical studies. It is believed that combining chemoradiotherapy and immune checkpoint inhibitors can induce safe and efficient anti-tumor immune responses and can be a promising therapeutic strategy.

16.
Nanotoxicology ; 13(8): 1117-1132, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31272252

RESUMO

Engineered nanomaterials are of public health concern. Recently, there has been an increasing attention on the toxicity of nanoplastics and nanoZnO because of their increasing utilization and presence in the environment. However, knowledge of their toxicological behavior and metabolic interactions with the cellular machinery that determine their potential health effects are extremely limited. In this study, the cellular uptake, cytotoxic effects, and metabolic responses of bronchus epithelial (BEAS-2B) cells exposed to nanopolystyrene (nanoPS) and a widely used metallic nanoparticle, nanoZnO, were investigated using a tandem mass spectrometry-based metabolomics approach. The results revealed that even with low cytotoxicity, these nanoparticles (NPs) affected cell metabolism. NanoPS exposure showed autophagic- and endoplasmic reticulum (ER) stress-related metabolic changes such as increased in amino acids and tricarboxylic acid cycle (TCA) intermediate metabolites, a process known to play a critical role in regulating cell resistance to cytotoxic effects. Both metabolomics profiling and ER-stress pathway, together with quantitative real-time RT-polymerase chain reaction (qRT-PCR) analyses, demonstrated that autophagy was reciprocally regulated to couple metabolic and transcriptional reprograming. In contrast, nanoZnO-induced ROS-mediated cell death was associated with mitochondrial dysfunction and interference in regulating energy metabolism. Collectively, these two types of NPs were observed to cause perturbations albeit differential in cellular metabolism associated with their cytotoxic effects. Our findings provided an in depth understanding of metabolic changes influenced by two different types of NPs, with contrasting molecular mechanisms for the adverse effects observed.

17.
Biotechnol Bioeng ; 116(11): 3006-3015, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31282986

RESUMO

There has been growing interest in using microalgae as production hosts for a wide range of value-added compounds. However, microalgal genetic improvement is impeded by lack of genetic tools to concurrently control multiple genes. Here, we identified two novel strong promoters, designated Pt202 and Pt667, and delineated their potential role on simultaneously driving the expression of key lipogenic genes in Phaeodactylum tricornutum. In silico analyses of the identified promoter sequences predicted the presence of essential core cis elements such as TATA and CAAT boxes. Regulatory role of the promoters was preliminarily assessed by using GUS reporter which demonstrated strong GUS expression. Thereafter, two key lipogenic genes including malic enzyme (PtME) and 5-desaturase (PtD5b), were overexpressed by the two promoters Pt202 and Pt667, respectively, in P. tricornutum. Combinatorial gene overexpression did not impair general physiological performance, meanwhile neutral lipid content was remarkably increased by 2.4-fold. GC-MS analysis of fatty acid methyl esters revealed that eicosapentaenoic acid (EPA; C20:5) was increased significantly. The findings augment a crucial kit to microalgal genetic tools that could facilitate the multiple-gene expression driven by various promoters, and promote microalgae for industrial bioproduction.

18.
Fitoterapia ; 137: 104199, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175950

RESUMO

Human carboxylesterase 1 (CES1), primarily expressed in the liver and adipocytes, is responsible for the hydrolysis of endogenous esters (such as cholesteryl esters and triacylglycerols) and the metabolism of xenobiotic esters (such as clopidogrel and oseltamivir), thus participates in physiological and pathological processes. In this study, a series of natural pentacyclic triterpenoids were collected and their inhibitory effects against CES1 and CES2 were assayed using D-luciferin methyl ester (DME) and N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de] isoquinolin- 6-yl)- 2-chloroacetamide (NCEN) as specific optical substrate for CES1, and CES2, respectively. To this end, betulinic acid (BA) was found with strong inhibitory effect on CES1 (IC50, 15 nM) and relative high selectivity over CES2 (>2400-fold). Primary structure-activity relationships (SAR) analysis and docking simulations revealed that the carboxyl group at the C-28 site of BA is very essential for CES1 inhibition. The inhibition kinetic analyses demonstrated that BA was a potent competitive inhibitor against CES1-mediated DME hydrolysis. Further investigation on the inhibitory effect of BA in living cells (HepG2) based assays demonstrated that BA displayed potent inhibitory effects on intracellular CES1 activities, with the low IC50 value of 1.30 µM. These results demonstrated that BA is potent and highly selective CES1 inhibitor, which might be used as the promising tool for exploring the biological functions of CES1 in complex biological systems.


Assuntos
Hidrolases de Éster Carboxílico/antagonistas & inibidores , Triterpenos/farmacologia , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
19.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
20.
ACS Nano ; 13(7): 7483-7492, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31184133

RESUMO

Nanowires (NWs) have been envisioned as building blocks of nanotechnology and nanodevices. In this study, NWs were manipulated using a weasel hair and fixed by conductive silver epoxy, eliminating the contaminations and damages induced by conventional beam depositions. The fracture strength of the amorphous silicon carbide was found to be 8.8 GPa, which was measured by in situ transmission electron microscopy nanomechanical testing, approaching the theoretical fracture limit. Here, we report that self-healing of mismatched fractured amorphous surfaces of brittle NWs was discovered. The fracture strength was found to be 5.6 GPa on the mismatched fractured surfaces, recovering 63.6% of that of pristine NWs. This is an ultrahigh recovery, due to the limits of reconstruction of dangling bonds on the fractured amorphous surfaces and the mismatched areas. Simulation by molecular dynamics showed fracture strength recovery of 65.9% on the mismatched fractured amorphous surfaces, which is in good agreement with the experimental results. Healing on the mismatched fractured amorphous surfaces is by reorganization of Si-C bonds forming Si-C and Si-Si bonds. The potential energy increases 2.6 eV in the reorganized Si-C bonds and decreases by 3.2 and 1.9 eV, respectively, in the formed Si-C and Si-Si bonds. These findings provide insights for the reliability, design, and fabrication of high performance NW-based devices, to avoid catastrophic failure working in harsh and extreme environments.

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