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1.
Transl Stroke Res ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31485869

RESUMO

Early neurological deterioration (END) after thrombolysis occurs in 10% acute ischemic stroke (AIS) patients, and its mechanism remains unclear in majority of cases, named as unexplained END. We tested the hypothesis that penumbra/infarct growth beyond the initial penumbra might be the cause of unexplained END. We reviewed the database of AIS patients who received reperfusion therapy. Unexplained END was defined as ≥ 2-point increase of NIHSS from baseline to 24 h, without straightforward causes. For each unexplained END patient, we extracted 2 matched controls based on 4 clinical and radiological characteristics which were strongly associated with unexplained END. We defined extra-penumbra and extra-infarct as penumbra and infarct growth at 24 h beyond baseline penumbral tissue and then investigated the relationship between extra-penumbra and extra-infarct and the presence of unexplained END. Finally, 44 unexplained END patients and 88 matched controls were included. The volume of both extra-infarct (OR, 1.032 per 1-mL increase; p = 0.018) and extra-penumbra (OR, 1.070 per 1-mL increase; p < 0.001) were associated with the presence of unexplained END, while the absence of recanalization was associated with the presence of either extra-infarct or extra-penumbra (OR, 3.291; p = 0.001). Moreover, 51.4% cases with extra-penumbra at 24 h finally progressed to infarct at 7 days, and they underwent higher increase of NIHSS from 24 h to 7 days than those that did not progress to infarct at 7 days (4.0 vs 1.0; p = 0.017). Penumbra/infarct growth beyond the initial penumbra is involved in the unexplained END in AIS patients receiving reperfusion therapy.

2.
Nat Prod Rep ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490501

RESUMO

Covering: up to 2019Humanity is in dire need for novel medicinal compounds with biological activities ranging from antibiotic to anticancer and anti-dementia effects. Recent developments in genome sequencing and mining have revealed an unappreciated potential for bioactive molecule production in marine Proteobacteria. Also, novel bioactive compounds have been discovered through molecular manipulations of either the original marine host bacteria or in heterologous hosts. Nevertheless, in contrast to the large repertoire of such molecules as predicted by in silico analysis, few marine bioactive compounds have been reported. This review summarizes the recent advances in the study of natural products from marine Proteobacteria. Here we present successful examples on genetic engineering of biosynthetic gene clusters of natural products from marine Proteobacteria. We also discuss the future prospects of discovering novel bioactive molecules via both heterologous production methodology and the development of marine Proteobacteria as new cell factories.

3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1077-1082, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512446

RESUMO

Objective: To investigate the effectiveness of arthroscopic anterior cruciate ligament (ACL) reconstruction via transtibial (TT) and transportal (TP) techniques after 10 years follow-up. Methods: A clinical data of 103 patients who underwent arthroscopic ACL reconstruction with a single bundle of autologous hamstring tendon between March 2006 and March 2009 was retrospectively analyzed, among which 57 patients were reconstructed with TT technique (TT group) and 46 patients were reconstructed with TP technique (TP group). There was no significant difference in gender, age, cause of injury, interval between injury and operation, preoperative pivot shift test, preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, and KT-2000 side-to-side difference (SSD) between the two groups ( P>0.05). At 10 years after operation, Lachman test was used to evaluate the forward joint stability and pivot shift test to evaluate the rotational stability of the knee; KT-2000 SSD was used to measure tibial anterior displacement; IKDC score and Lysholm score were used to evaluate knee function; MRI examination was performed to observe graft healing and measure coronal inclination angles of the tibia and femoral tunnels. The rate of return to sports was also calculated. Results: The incisions healed by first intention in the two groups, and no early complication occurred after operation. All patients were followed up 10-13 years, with an average of 11.5 years. During the follow-up period, there was no limitation of knee extension and flexion, no discomfort of donor site or graft failure in either group. MRI examination showed that the graft healed well. The IKDC score, Lysholm score, and KT-2000 SSD in the two groups were significantly improved after 10 years ( P<0.05), and there was no significant difference between the two groups at 10 years after operation ( P>0.05). There were significant differences in coronal inclination angles of femoral tunnel and tibial tunnel between the two groups ( P<0.05). There was no significant difference in Lachman test and pivot shift test between the two groups ( P>0.05). The rate of return to sports of patients was 61.40% (35/57) in TT group and 63.04% (29/46) in TP group, showing no significant difference between the two groups ( χ 2=0.29, P=0.87). Conclusion: TT and TP techniques can both achieve good effectiveness in ACL reconstruction.

4.
J Vasc Access ; : 1129729819872881, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31495268

RESUMO

INTRODUCTION: Over one billion intravascular devices are used worldwide, annually. Due to the associated complications with these devices, the development of a reliable yet cost-effective securement technique is extremely important. The purpose of this study is to demonstrate the strength of a novel catheter securement cyanoacrylate for securing peripheral venous catheters, central venous catheters, peripherally inserted central catheters, and all other intravascular catheter types. MATERIALS AND METHODS: An unprecedented in vitro method was performed to quantify and compare the strength of a novel cyanoacrylate product when securing intravascular catheters inserted into prepared porcine skin. In vivo, canine subjects were used to implant various types of catheters. These catheters were secured with a novel catheter securement cyanoacrylate to test the strength and durability while undergoing simulated clinical stresses. RESULTS: In vitro, the catheter securement cyanoacrylate demonstrated superior strength over conventional catheter securement methods as well as other known cyanoacrylates. The catheter securement cyanoacrylate demonstrated the ability to maintain superior strength for up to 7 days. In vivo, the catheter securement cyanoacrylate demonstrated the ability to withstand five weight tugs per hour for a 3-h duration, alone, while securing three types of catheters in canine subjects. CONCLUSION: This is one of the first studies to provide quantitative data to support the use of cyanoacrylate for intravascular catheter securement. The results from this research suggest that the novel catheter securement cyanoacrylate can be a simple and cost-effective catheter securement device that can improve the current health care protocol for intravascular catheterization.

5.
J Affect Disord ; 258: 25-32, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382101

RESUMO

BACKGROUND: There were differences in the characteristics and prevalence rates between individuals with a history of one suicide attempt and those with multiple suicide attempts. This large-scale study was conducted to test, among Chinese adolescents, the associations of emotional and behavioral problems with single and multiple suicide attempts and whether these associations vary with adolescents' academic performance. METHODS: Data were drawn from the 2019 School-based Chinese Adolescents Health Survey (n = 20,702). Information about emotional and behavioral problems, suicide attempts, suicidal ideation, academic performance, and sleep duration was gathered. Multinomial logistic regression models using Firth penalized likelihood approach and appropriate sampling weights were performed. RESULTS: Compared with no suicide attempt, peer problems, emotional problems, conduct problems, and hyperactivity were associated with an elevated risk of both a single suicide attempt and multiple suicide attempts, respectively (P < 0.05); the magnitudes of these associations in multiple suicide attempters were higher than those in single suicide attempters. Further stratification analyses by academic performance showed a greater association of the four difficulties with multiple suicide attempts in adolescents reporting poor academic performance than in those with good or average academic performance. LIMITATIONS: The school-based study sample only included students, and causal inference could not be delineated due to the cross-sectional design. CONCLUSIONS: Emotional and behavioral problems are associated with an elevated risk of single and multiple suicide attempts with differences between multiple suicide attempters and single suicide attempters. Adolescent academic performance plays a modulating role in these associations for multiple suicide attempts.

6.
J Affect Disord ; 258: 89-95, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400628

RESUMO

BACKGROUND: There is a lack of literature about the joint effects of PM2.5 exposure and sleep disturbance on suicide attempts. This study aimed to estimate the association of PM2.5 exposure or sleep disturbance with suicide attempts among Chinese adolescents and to test their interaction effects on both additive and multiplicative scales. METHODS: Data was drawn from a subsample of the School-based Chinese Adolescents Health Survey (SCAHS) during 2014-2015 in Guangdong province, including 21,780 eligible participants. The 3-year (2011-2013) annual average concentration of PM2.5 was estimated using satellite data. Multi-level logistic regression models with weights were fitted, and both multiplicative and additive interactions for PM2.5 and sleep disturbance were tested. RESULTS: A total of 608 students (2.8%) reported having suicide attempts. After adjusting for significant demographics and depressive symptoms, PM2.5 exposure (Adjusted odds ratio [AOR] = 1.25, 95% CI = 1.03-1.56) and sleep disturbance (AOR = 1.69, 95% CI = 1.41-2.02) were positively associated with suicide attempts, respectively. The adjusted additive interaction effect of PM2.5 and sleep disturbance was 2.42 (95% CI = 1.80-3.26) with a synergistic index of 1.31. The multivariable multi-level logistic regression models did not find any significant multiplicative interaction item (P > 0.05). LIMITATION: The school-based cross-sectional study design CONCLUSION: Long-term exposure to PM2.5 may elevate the risks of suicide attempts among Chinese adolescents. Moreover, the significant interaction effects of PM2.5 exposure and sleep disturbance on suicide attempts were found in the additive model, suggesting decreasing long-term exposure to a higher level of PM2.5 may be helpful to reduce the risk of suicide attempts among adolescents with sleep disturbance.

7.
Nat Chem Biol ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406373

RESUMO

The flagellar hook protein FlgE from spirochaete bacteria self-catalyzes the formation of an unusual inter-subunit lysinoalanine (Lal) crosslink that is critical for cell motility. Unlike other known examples of Lal biosynthesis, conserved cysteine and lysine residues in FlgE spontaneously react to form Lal without the involvement of additional enzymes. Oligomerization of FlgE via its D0 and Dc domains drives assembly of the crosslinking site at the D1-D2 domain interface. Structures of the FlgED2 domain, dehydroalanine (DHA) intermediate and Lal crosslinked FlgE subunits reveal successive snapshots of the reaction. Cys178 flips from a buried configuration to release hydrogen sulfide (H2S/HS-) and produce DHA. Interface residues provide hydrogen bonds to anchor the active site, facilitate ß-elimination of Cys178 and polarize the peptide backbone to activate DHA for reaction with Lys165. Cysteine-reactive molecules accelerate DHA formation, whereas nucleophiles can intercept the DHA intermediate, thereby indicating a potential for Lal crosslink inhibitors to combat spirochaetal diseases.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31420667

RESUMO

BACKGROUND: Individuals with cocaine addiction are characterized by under-responsiveness to natural reinforcers. As part of the dopaminergic pathways the hypothalamus supports motivated behaviors. Rodent studies suggested inter-related roles of the hypothalamus in regulating drug and food intake. However, few studies have investigated hypothalamic responses to drugs and food or related cues in humans. METHODS: We examined regional responses in 20 cocaine dependent (CD) and 24 healthy control (HC) participants exposed to cocaine/food (CD) and food (HC) vs. neutral cues during fMRI. We examined the relationship between imaging findings and clinical variables, and performed mediation analyses to examine the inter-relationships between cue-related activations, tonic cocaine craving, and recent cocaine use. RESULTS: At a corrected threshold, CD demonstrated higher activation to cocaine as compared to food cues in the hypothalamus, inferior parietal cortex, and visual cortex. CD as compared to HC also demonstrated higher hypothalamic activation to food cues. Further, the extent of these cue-induced hypothalamic activations was correlated with tonic craving, as assessed by the Cocaine Craving Questionnaire (CCQ) and days of cocaine use in the prior month. In mediation analyses hypothalamic activation to cocaine and food cues both completely mediated the relationship between the CCQ score and days of cocaine use in the past month. CONCLUSIONS: The results were consistent with the proposition that the mechanisms of feeding and drug addiction are inter-linked in the hypothalamus and altered in cocaine addiction. The findings provide new evidence in support of hypothalamic dysfunction in cocaine addiction.

9.
Int Immunopharmacol ; 75: 105793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401379

RESUMO

BACKGROUND: T helper (Th17) cells play an important role in many autoimmune diseases. In this meta-analysis, we aimed to specify the proportion of Th17 cells and the levels of Th17-related cytokines in neuromyelitis optica spectrum disorders (NMOSD) patients, we did this meta-analysis. METHODS: Using previously reported data from PubMed, EMBASE, and Web of Science and Cochrane, we explored the proportion of Th17 cells in CD4+ T cells in peripheral blood (PB) and the level of Th17-related cytokines, such as interleukin (IL)1ß, IL6, IL17, IL21, IL22, IL23 and transforming growth factor -beta (TGFß), in cerebrospinal fluid (CSF), plasma, and serum in NMOSD patients compared to control group and multiple sclerosis (MS) patients. RESULTS: In total, 38 trials were included for our analysis. Results showed that the proportion of Th17 cells was higher in NMOSD patients than in the control and MS groups. The levels of IL1ß, IL6, IL17 and IL21 in CSF and plasma, and IL6, IL21, IL22, and IL23 in the serum were higher in NMOSD patients than in the control group. The levels of IL6 in CSF and serum and IL17 in plasma and serum were higher in NMOSD patients than in MS patients. CONCLUSION: The proportion of Th17 cells and the levels of Th17-related cytokines was increased in NMOSD patients compared with the control group and MS patients. The results of this meta-analysis indicated that Th17 cells and Th17-associated cytokines may play an essential role in the pathogenesis of NMOSD. PROSPERO registration: CRD42019128785.

10.
J Environ Manage ; 249: 109406, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450195

RESUMO

The quantitative study of urban-rural gradients for persistent organic pollutants (POPs) is extremely important to understand the behavior of POPs as well as for ecological risk assessment and management. In this study, a practical urban-rural gradient model (URGM) was developed using atmospheric point source diffusion combined with a fugacity approach to test potential mathematical relationships among urban and rural soils. The mean value of polycyclic aromatic hydrocarbons (PAHs) for urban soils (0-2-km sites) was 570.80 ng/g, and was approximately 3.5 times higher than rural soils (30-50 km sites). Significant linear correlations were found between the amounts of PAHs in the surface soil and the city population and between the soil concentration and artificial surface area. Urban-rural PAH concentrations were simulated by the URGM and calibrated by city population and land-cover data, with average relative errors of 12.84%. The results showed that the URGM was suitable for simulating urban-rural PAH concentrations at a regional scale. The combustion of fossil fuels, biomass, and coal was the main source of soil PAHs in the study area, and the characteristic ratios of PAHs indicated a transition trend from pyrogenic to petrogenic sources along the urban-rural transects. This study thus provides a combined method for quantifying urban-rural gradients of PAHs and can thereby promote quantitative research on coupling among land cover, socio-economic data, and POP concentrations.

11.
Mol Cancer Res ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444231

RESUMO

Drug resistance continues to be a major obstacle of effective therapy for colorectal cancer, leading to tumor relapse or treatment failure. Cancer stem cells (CSC) or tumor-initiating cells are a subpopulation of tumor cells which retain the capacity for self-renewal and are suggested to be implicated in drug resistance. LGR5 is highly expressed in colorectal cancer and marks CSCs that drive tumor growth and metastasis. LGR5(+) CSCs cells were shown to interconvert with more drug-resistant LGR5(-) cancer cells, and treatment with LGR5-targeted antibody-drug conjugates (ADC) eliminated LGR5(+) tumors, yet a fraction of LGR5(-) tumors eventually recurred. Therefore, it is important to identify mechanisms associated with CSC plasticity and drug resistance in order to develop curative therapies. Here, we show that loss of LGR5 in colon cancer cells enhanced resistance to irinotecan and 5-fluorouracil and increased expression of adhesion G-protein-coupled receptor, GPR56. GPR56 expression was significantly higher in primary colon tumors versus matched normal tissues and correlated with poor survival outcome. GPR56 enhanced drug resistance through upregulation of MDR1 levels via a RhoA-mediated signaling mechanism. Loss of GPR56 led to suppression of tumor growth and increased sensitivity of cancer cells to chemotherapy and monomethyl auristatin E-linked anti-LGR5 ADCs, by reducing MDR1 levels. These findings suggest that upregulation of GPR56 may be a mechanism associated with CSC plasticity by which LGR5(-) cancer cells acquire a more drug-resistant phenotype.Implications: Our findings suggest that targeting GPR56 may provide a new strategy for the treatment of colorectal cancer and combatting drug resistance.

12.
Soft Matter ; 15(33): 6615-6625, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31406972

RESUMO

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

13.
Gen Comp Endocrinol ; : 113237, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31374285

RESUMO

The molecular mechanism underlying myostatin (MSTN)-regulated metabolic cross-talk remains poorly understood. In this study, we performed comparative proteomic and phosphoproteomic analyses of gluteus muscle tissues from MSTN-/- transgenic cattle using a shotgun-based tandem mass tag (TMT) 6-plex labeling method to explore the signaling pathway of MSTN in metabolic cross-talk and cellular metabolism during muscle development. A total of 72 differentially expressed proteins (DEPs) and 36 differentially expressed phosphoproteins (DEPPs) were identified in MSTN-/- cattle compared to wild-type cattle. Bioinformatics analyses showed that MSTN knockout increased the activity of many key enzymes involved in fatty acid ß-oxidation and glycolysis processes in cattle. Furthermore, comprehensive pathway analyses and hypothesis-driven AMP-activated protein kinase (AMPK) activity assays suggested that MSTN knockout triggers the activation of AMPK signaling pathways to regulate glucose and lipid metabolism by increasing the AMP/ATP ratio. Our results shed new light on the potential regulatory mechanism of MSTN associated with metabolic cross-talk in muscle development, which can be used in animal breeding to improve meat production in livestock animals, and can also provide valuable insight into treatments for obesity and diabetes mellitus in humans.

15.
Dalton Trans ; 48(33): 12466-12481, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31355396

RESUMO

Tuning the synthesis conditions and further regulating the magnetic dynamics of single-molecule magnets (SMMs) are crucial challenges for chemists. Some feasible approaches have been developed to understand magneto-structural correlations and regulate relaxation behaviors via rational design. Based on the solvent-induced effect or ligand ratio regulation, three new dysprosium(iii) coordination compounds, [Dy(L)(Dppd)]·solvent (1), [Dy(L)(Dppd)] (2) and [Dy(L)(Dppd)2]·solvent (3) (H2L = N,N'-bis(2-hydroxy-5-methyl-3-formylbenzyl)-N,N'-bis-(pyridin-2-ylmethyl)ethylenediamine, Dppd = dibenzoylmethane) have been successfully prepared. Compounds 1 and 2 are mononuclear structures. 3 is a dinuclear core in which the metal centers are bridged by two phenol-O atoms of one L2- ligand. Dy(iii) cations in compounds 1-3 present acta-coordination geometries. More interestingly, compounds 1 and 2 can be mutually transformed through the reversible single-crystal-to-single-crystal (SCSC) transformation under different solvent environments. The crystals of 1 and 2 underwent a dissolution-precipitation process and changed into 3, respectively. The distinct structures and magnetic properties were determined through combined structural, experimental and theoretical investigations.

16.
Environ Int ; 131: 104982, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299603

RESUMO

Although wastewater treatment plants (WWTPs) can purify wastewater, they also discharge numerous contaminants into the environment through effluent discharge and sludge disposal. The occurrence, emission flux, and risk assessment of traditional pollutants (e.g., heavy metals [HMs]), and emerging pollutants (e.g., perfluoroalkyl substances [PFASs] and pharmaceutical and personal care products [PPCPs]) in WWTP emissions are of important concern. The present study analyzed 17 PFASs, 25 PPCPs, and 8 HMs in influent, effluent, and excess sludge from six WWTPs along the Yanghe River, North China. Samples were collected during four sampling campaigns from November 2016 to July 2017. The mean concentrations of PFASs and PPCPs in influent were 46.4 ng L-1 and 6.57 µg L-1, respectively; while those in effluent were 38.5 ng L-1 and 2.14 µg L-1, respectively. The highest concentrations of HMs was detected of Zn in influent (2,866 µg L-1) and effluent (3,960 µg L-1). According to the concentration composition, short-chain PFASs, fluoroquinolones (FQs), and Zn were the predominant components in both influents and effluents. The mean PFAS and PPCP concentrations in excess sludge were 5.95 ng g-1 and 3.74 µg g-1 dry weight (dw). Zn was the most abundant HMs in excess sludge with the concentration range of 156-14,271 µg g-1 dw. The compositions of PFASs, PPCPs and HMs differed between wastewater and excess sludge. The estimated emission flux of these pollutants was ordered as HMs > PPCPs > PFASs through effluent discharge and sludge disposal. Sludge disposal discharged more PPCPs and HMs into the environment than effluent discharge, which was contrary for PFASs. Relative risk of each pollutant is calculated by comparing the mean effluent concentration with the median effective concentration. Algae and fish were selected as recipient organisms to calculate the relative risk of 23 selected pollutants towards aquatic organisms. The highest-risk pollutant was Zn on both algae and fish, while perfluorobutane sulfonate (PFBS) and atenolol (ATE) posed the lowest risk. In general, HMs (regarded as traditional pollutants) presented higher risks in effluent, followed by the emerging pollutants (PPCPs and PFASs). Therefore, control of traditional pollutants should be prioritized in WWTPs in this region. This study presents an overall assessment of the current status of traditional and emerging pollutants in WWTPs and provides useful information for upgrading wastewater treatment processes.

17.
Regul Toxicol Pharmacol ; 107: 104420, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295511

RESUMO

To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean Cmax of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high Cmax in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, Cmax, csf and AUCcsf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.

18.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1799-1807, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342705

RESUMO

Chalcone synthase( CHS) and chalcone isomerase( CHI) are key enzymes in the biosynthesis pathway of flavonoids. In this study,unigenes for CHS and CHI were screened from the transcriptome database of Arisaema heterophyllum. The open reading frame( ORFs) of chalcone synthase( Ah CHS) and chalcone isomerase( Ah CHI) were cloned from the plant by RT-PCR. The physicochemical properties,expression and structure characteristics of the encoded proteins Ah CHS and Ah CHI were analyzed. The ORFs of Ah CHS and Ah CHI were 1 176,630 bp in length and encoded 392,209 amino acids,respectively. Ah CHS functioned as a symmetric homodimer. The N-terminal helix of one monomer entwined with the corresponding helix of another monomer. Each CHS monomer consisted of two structural domains. In particular,four conserved residues define the active site. The tertiary structure of Ah CHI revealed a novel open-faced ß-sandwich fold. A large ß-sheet( ß4-ß11) and a layer of α-helices( α1-α7) comprised the core structure. The residues spanning ß4,ß5,α4,and α6 in the three-dimensional structure were conserved among CHIs from different species. Notably,these structural elements formed the active site on the protein surface,and the topology of the active-site cleft defined the stereochemistry of the cyclization reaction. The homology comparison showed that Ah CHS had the highest similarity to the CHS of Anthurium andraeanum,while Ah CHI had the highest similarity to the CHI of Paeonia delavayi. This study provided the basis for the functional study of Ah CHS and Ah CHI and the further study on plant flavonoid biosynthesis pathway.


Assuntos
Aciltransferases/genética , Arisaema/enzimologia , Liases Intramoleculares/genética , Proteínas de Plantas/genética , Aciltransferases/química , Arisaema/genética , Clonagem Molecular , Liases Intramoleculares/química , Proteínas de Plantas/química
19.
Mol Oncol ; 13(9): 1993-2009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294922

RESUMO

The cross-talk between hepatic stellate cells (HSCs) and hepatic carcinoma cells contributes to hepatocellular carcinoma (HCC) progression, but the underlying mechanism is largely unknown. We report here that activated HSCs induce upregulation of nicotinamide N-methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in HCC tissues were positively correlated with vascular invasion, increased serum HBV-DNA levels, and distant metastasis. In addition, functional assays showed that NNMT promoted HCC cell invasion and metastasis by altering the histone H3 methylation on 27 methylation pattern and transcriptionally activating cluster of differentiation 44 (CD44). NNMT-mediated N6-methyladenosine modification of CD44 mRNA resulted in the formation of a CD44v3 splice variant, while its product 1-methyl-nicotinamide stabilized CD44 protein by preventing ubiquitin-mediated degradation. Finally, NNMT was also shown to be a target of statins that inhibited metastasis of hepatoma cells. Taken together, our study shows for the first time that the NNMT/CD44v3 axis regulates HCC metastasis and presents NNMT as a promising prognostic biomarker and therapeutic target for HCC.

20.
Brain Behav ; 9(8): e01346, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31286688

RESUMO

INTRODUCTION: Connectome-based predictive modeling (CPM) is a recently developed machine-learning-based framework to predict individual differences in behavior from functional brain connectivity (FC). In these models, FC was operationalized as Pearson's correlation between brain regions' fMRI time courses. However, Pearson's correlation is limited since it only captures linear relationships. We developed a more generalized metric of FC based on information flow. This measure represents FC by abstracting the brain as a flow network of nodes that send bits of information to each other, where bits are quantified through an information theory statistic called transfer entropy. METHODS: With a sample of individuals performing a sustained attention task and resting during functional magnetic resonance imaging (fMRI) (n = 25), we use the CPM framework to build machine-learning models that predict attention from FC patterns measured with information flow. Models trained on n - 1 participants' task-based patterns were applied to an unseen individual's resting-state pattern to predict task performance. For further validation, we applied our model to two independent datasets that included resting-state fMRI data and a measure of attention (Attention Network Task performance [n = 41] and stop-signal task performance [n = 72]). RESULTS: Our model significantly predicted individual differences in attention task performance across three different datasets. CONCLUSIONS: Information flow may be a useful complement to Pearson's correlation as a measure of FC because of its advantages for nonlinear analysis and network structure characterization.

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