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1.
Hum Cell ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571148

RESUMO

It has been reported that lncRNA NBR2 regulates cancer metabolism. We investigated the role of NBR2 in colorectal cancer. We found that NBR2 was downregulated in colorectal cancer tissues than in adjacent healthy tissues. Decreased expression levels of NBR2 in tumor tissues were observed with the increase of clinical stages. MiRNA-21 was upregulated in colorectal cancer tissues than in adjacent healthy tissues, and was significantly and inversely correlated with NBR2. NBR2 overexpression downregulated miRNA-21 in colorectal cancer cells, while miRNA-21 overexpression failed to significantly affect NBR2 expression. NBR2 overexpression suppressed migration and invasion of colorectal cancer cells. MiRNA-21 overexpression played an opposite role and attenuated the effects of NBR2 overexpression. NBR2 overexpression did not significantly alter cancer cell proliferation. Therefore, lncRNA NBR2 inhibited colorectal cancer cell migration and invasion possibly by downregulating miRNA-21.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31571344

RESUMO

Ring-opening metathesis polymerization (ROMP) has become one of the most important living polymerizations. Despite being the most strained cyclic olefin, cyclopropenes (CPEs) remain underexplored for ROMP. We discovered that the simple swap of 1-methyl to 1-phenyl on 1-(benzoyloxymethyl)-CPEs elicited strikingly different modes of reactivity, switching from living polymerization to selective single addition and living alternating ROMP, respectively, to yield well-controlled polymers in both cases. This pronounced difference in reactivity stemmed from differences in steric repulsions at the Ru alkylidene after CPE ring-opening. Possible olefin or oxygen chelation from ring-opened CPE substituents was also observed to significantly affect the rate of propagation. These results demonstrate the versatility of CPEs as a new class of monomers for ROMP, provide mechanistic insights for designing new monomers with rare single addition reactivity, and generate a new functionalizable alternating copolymer scaffold with controlled molecular weight and low dispersity.

3.
Drug Des Devel Ther ; 13: 3217-3228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571825

RESUMO

Purpose: Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of ubenimex in GH3 and MMQ cells. Materials and methods: In this study, we investigated the anticancer effects of ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting. Results: The results revealed that treatment with ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate ubenimex-induced apoptosis and autophagy. Conclusion: Our studies revealed that ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.

4.
Chin Med Sci J ; 34(3): 226-229, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601306

RESUMO

A 22-year-old man suffered from acute pulmonary hemorrhage and deteriorated renal function occurred within 3 days after traumatic brain injury. Mechanical ventilation cannot correct his severe hypoxemia, therefore, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support was initiated and finally resolved his hypoxemia. Concomitantly, continuous renal replacement therapy was performed to improve his kidney function. Although no anti-glomerular basement membrane (anti-GBM) antibody was detected in serum, Goodpasture's syndrome was considered. After treated with methylprednisolone pulse therapy and plasmapheresis, his renal function was significantly improved. ECMO was eventually discontinued after 60 hours of treatment and extubated on day 10. He was discharged home with normal pulmonary and renal functions.

5.
World J Gastroenterol ; 25(37): 5655-5666, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31602165

RESUMO

BACKGROUND: The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma (GBC) after curative resection remain unclear. AIM: To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy. METHODS: Patients with curatively resected advanced gallbladder adenocarcinoma (T3 and T4) were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. A survival prediction model based on Bayesian network (BN) was constructed using the tree-augmented naïve Bayes algorithm, and composite importance measures were applied to rank the influence of factors on survival. The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3. The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy. RESULTS: A total of 818 patients met the inclusion criteria. The median survival time was 9.0 mo. The accuracy of BN model was 69.67%, and the area under the curve value for the testing dataset was 77.72%. Adjuvant radiation, adjuvant chemotherapy (CTx), T stage, scope of regional lymph node surgery, and radiation sequence were ranked as the top five prognostic factors. A survival prediction table was established based on T stage, N stage, adjuvant radiotherapy (XRT), and CTx. The distribution of the survival time (>9.0 mo) was affected by different treatments with the order of adjuvant chemoradiotherapy (cXRT) > adjuvant radiation > adjuvant chemotherapy > surgery alone. For patients with node-positive disease, the larger benefit predicted by the model is adjuvant chemoradiotherapy. The survival analysis showed that there was a significant difference among the different adjuvant therapy groups (log rank, surgery alone vs CTx, P < 0.001; surgery alone vs XRT, P = 0.014; surgery alone vs cXRT, P < 0.001). CONCLUSION: The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients. Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

6.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3582-3587, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602926

RESUMO

Terpenoids are main bioactive components in Tripterygium wilfordii,but the contents of some terpenoids are relatively low. In order to provide scientific evidence for the regulation of terpenoids in T. wilfordii,this research explored the effect of GR24 on accumulations of four diterpenoids( triptolide,tripterifordin,triptophenolide,and triptinin B) in T. wilfordii suspension cells by biological technology and UPLC-QQQ-MS/MS. The results indicated that 100 µmol·L-1 GR24 inhibited the accumulations of triptolide,tripterifordin,triptophenolide,and triptinin B to different degrees. Compared with the control group,the contents of 4 diterpenoids( in the induced group) were down to 96.59%,63.80%,61.02% and 33.59% in 240 h,respectively. Among them,the accumulation of triptinin B iswas significantly inhibited. In addition,the key time point of inhibitory effect was 120 h after induction with GR24 in some diterpenoids. This is the first systematic study focusing on the effect of GR24 on the accumulations of diterpenoids in T. wilfordii suspension cells. The dynamic accumulation ruleregularity of four diterpenoids after induced by GR24 was summarized,which laid a foundation for further study on the chemical response mechanism of terpenoids to GR24.

7.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3601-3607, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602929

RESUMO

Magnoliae Officinalis Cortex( MOC),the stem bark of Magnolia officinalis( MO) and M. officinalis var. biloba( MOB),is a main ingredient in more than 200 types of Chinese formulae commonly used in clinics. MO and MOB are widely distributed in China,from Sichuan of the west to Zhejiang province of the east and from Shannxi province in the north to Guangxi province in the south. This review summarizes new findings on geo-heralism of MOC concerning textual research,plants taxonomy,genetic study,chemical study,and pharmacological activity,resulting in the following views. ①The original plants of MOC are suggested to be divided into three geographic clans according to the form of leave and the result of genetic research; ②Concentrations of magnolol,honokiol,magnoloside A,magnoloside B,magnoflorine,and ß-eudesmol in samples collected from different geographic areas are varied;③Samples of MOC produced in Hubei and Sichuan were traditionally regarded as Dao-di herbs,which were called Chuanpo,and the pure haplotype of MOC produced in Hubei may become a genetic index.

8.
Pathol Res Pract ; : 152677, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31591052

RESUMO

Sanguinarine (SAG), a benzophenanthridine alkaloid extracted from Sanguinaria canadensis, exerts antioxidant, anti-inflammatory and antiproliferative activities in a variety of malignancies. However, the underlying mechanisms by which SAG affects the tumorigenesis of gastric cancer (GC) are unclear. The common targets of SAG and GC were identified by network pharmacology, and the association of thymocyte selection-associated high mobility group box (TOX) with the clinicopathological characteristics and prognosis of patients with GC was analyzed by using datasets from The Cancer Genome Atlas (TCGA). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays, colony formation assays, flow cytometry analysis, and a xenograft tumor model were conducted to assess the effects of SAG on the growth of GC cells, and Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the effects of SAG on the TOX/DNA-PKcs/KU70/80 signaling pathway. We identified 9 collective targets of SAG and GC, of which TOX expression levels were dramatically downregulated in GC tissues compared with adjacent normal tissues, and a low expression of TOX served as an independent prognostic factor of poor survival in patients with GC. SAG suppressed cell viability, colony formation and in vivo tumorigenesis and induced cell apoptosis and cell cycle arrest. Furthermore, SAG increased the expression levels of TOX but decreased those of DNA-PKcs and KU70/80 in GC cells. Our findings indicate that SAG inhibits the tumorigenesis of GC cells by regulating TOX/DNA-PKcs/KU70/80 signaling and may provide therapeutic strategies for the treatment of GC.

9.
Adv Exp Med Biol ; 1164: 161-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576548

RESUMO

PTHrP was first discovered as the most common mediator of malignancy-associated hypercalcemia. Subsequently, the discovery of its ubiquitous expression in normal tissues unraveled its role as a physiological autocrine/paracrine regulator. The significance of PTHrP in cancer is not confined to malignancy-associated hypercalcemia, and sufficient evidence now also supports its role in skeletal metastasis through its modulation of bone turnover. Furthermore, our own studies have recently shown the critical role of PTHrP in breast cancer initiation, growth, and metastasis. More recently, we have provided new evidence that overexpression of PTHrP is associated with higher incidence of brain metastasis and decreased overall survival in triple-negative breast cancer patients. Further mechanistic studies in human and mouse model are necessary to fully understand the role of PTHrP in tumor progression and metastasis.


Assuntos
Neoplasias Ósseas , Hipercalcemia , Proteína Relacionada ao Hormônio Paratireóideo , Animais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/genética , Neoplasias Ósseas/fisiopatologia , Neoplasias da Mama , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Hipercalcemia/etiologia , Hipercalcemia/genética , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo
10.
Org Biomol Chem ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599296

RESUMO

The condensation of carboxylic acids and amines mediated by silane derivatives provided a straightforward and sustainable method for amide bond formation with minimal waste. However, the detailed mechanism and structure-activity relationship of substrates, the topics that are of interest for both academic and industrial applications, were not clear. Herein, a systematic computational study was conducted to solve the two questions. We found that the two previously proposed mechanisms involving intramolecular acyl transfer or silanolate were less likely because the associated silanone intermediate and zwitterion adducts were too unstable with higher overall energy barriers. By comparison, the mechanism involving deprotonation of carboxylic acids, addition of carboxylates on silane reagents, dihydrogen formation to afford an acyloxysilane intermediate, carboxylic-acid-assisted addition of amines, and concerted proton transfer/amide formation, was found to be more favorable with overall energy barriers varying between 24 and 28 kcal mol-1 for the different calculated cases. Meanwhile, the dihydrogen formation and amide formation processes are both potential rate-determining steps. Energy composition, atomic charge, and distortion-interaction analyses indicated that the steric effect of silane reagents was more important than the electronic effect, making less bulky silane reagents more reactive. On the other hand, the dihydrogen formation process was mainly controlled by the electronic effect of the substituents of carboxylic acids and amines while the amide formation process was mainly influenced by their steric effect. As a result, less bulky, less acidic alkyl carboxylic acids are more reactive than unsaturated carboxylic acids, and less bulky, medium basic primary alkyl amines are more reactive than secondary alkyl amines and primary aryl amines. The related results provided deeper mechanistic insights into the amide bond formation mediated by silane derivatives and can act as a reference for further experimental design.

11.
Chemistry ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585022

RESUMO

Chiral α,α-difluoromethyl carbinols are recurring structural motifs in many therapeutic agents. Despite the indubitable interest in the catalytic asymmetric synthesis of such compounds, this research field still remains largely underexplored. Herein, an efficient approach to a range of chiral homopropargylic α,α-difluoromethyl carbinols has been developed, via a Cu-catalyzed enantioselective propargylation of α,α-difluoroketones with (pinacolato)allenylboron. In the presence of an cuprous complex, generated in-situ from CuCl and a spiroketal-based diphosphine (SKP) ligand, a variety of aryl-, heteroaryl-, alkyl-, alkynyl, alkenyl or benzyloxycarbonyl-substituted α,α-difluoromethyl carbinols were obtained in 75-99% yields with 84-98% ee values. The catalytic system was further investigated using a combined dynamic NMR spectroscopic, X-ray crystallographic, and non-linear effect studies. The origin of the enantioselection was rationalized based on DFT calculations. Finally, several efficient transformations were showcased to highlight the utilities of the protocol in synthesis of complex compounds bearing a α,α-difluoromethyl carbinol moiety.

12.
Int J Mol Sci ; 20(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575039

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin α family member Karyopherin-α1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.

13.
Health Informatics J ; : 1460458219867231, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566452

RESUMO

Many patients with mental disorders take dietary supplement, but their use patterns remain unclear. In this study, we developed a method to detect signals of associations between dietary supplement intake and mental disorder in Twitter data. We developed an annotated dataset and trained a convolutional neural network classifier that can identify language use pattern of dietary supplement intake with an F1-score of 0.899, a precision of 0.900, and a recall of 0.900. Using the classifier, we discovered that melatonin and vitamin D were the most commonly used supplements among Twitter users who self-diagnosed mental disorders. Sentiment analysis using Linguistic Inquiry and Word Count has shown that among Twitter users who posted mental disorder self-diagnosis, users who indicated supplement intake are more active and express more negative emotions and fewer positive emotions than those who have not mentioned supplement intake.

14.
J Cell Physiol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566716

RESUMO

Non-small-cell lung cancer (NSCLC) is a kind of lung cancer with high incidence and poor outcomes all over the world. Studies have validated that the upregulation of long noncoding RNA LINC00657 is related to several cancers. Nevertheless, the underlying regulatory mechanism of LINC00657 in NSCLC has not been well elucidated. In the present study, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) revealed that LINC00657 level was apparently elevated in NSCLC cells. Loss-of function assays demonstrated that LINC00657 silence retarded cell proliferation and migration in NSCLC cells. Moreover, the chromatin immunoprecipitation result identified the transcription factor SP1 could bind with LINC00657 promoter, and RT-qPCR proved SP1 positively regulated LINC00657 expression in NSCLC cells. In addition, the mechanistic investigations unveiled that LINC00657 was an endogenous sponge of miR-26b-5p and therefore boosted the expression of copper metabolism MURR1 domain-containing 8 (COMMD8), one of the targets of miR-26b-5p. Besides, miR-26b-5p could negatively regulate LINC00657 or COMMD8 in NSCLC cells. With the application of rescue assays, we uncovered that overexpression of COMMD8 partly mitigated the impairment of LINC00657 repression on NSCLC cell proliferation and migration. Together, our study illustrated that SP1-stimulated LINC00657 promoted NSCLC progression through targeting miR-26b-5p/COMMD8 axis, offering a novel potential therapeutic target for NSCLC.

15.
J Cell Mol Med ; 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31565850

RESUMO

Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)-induced colitis remain unclear. After DSS-induced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRT-PCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNF-α, IL-1ß and IL-6 in DSS-induced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokine-receptor signalling were predominantly enriched in TOE-treated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSS-induced colitis, where TOE also induced the enrichment of S24-7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSS-induced colitis by regulating fatty acid degradation and microbial dysbiosis.

16.
Sensors (Basel) ; 19(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597310

RESUMO

A simple hetero-core optical fiber (MMF-NCF-MMF) surface plasmon resonance (SPR) sensing structure was proposed. The SPR spectral sensitivity, full width of half peak (FWHM), valley depth (VD), and figure of merit (FOM) were defined to evaluate the sensing performance comprehensively. The effect of gold film thickness on the refractive index and temperature sensing performance was studied experimentally. The optimum gold film thickness was found. The maximum sensitivities for refractive index and temperature measurement were obtained to be 2933.25 nm/RIU and -0.91973 nm/°C, respectively. The experimental results are helpful to design the SPR structure with improved sensing performance. The proposed SPR sensing structure has the advantages of simple structure, easy implementation, and good robustness, which implies a broad application prospect.

17.
Org Lett ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580688

RESUMO

Two guaianolide sesquiterpenoid tetramers named ainsliatetramers A and B were separated from Ainsliaea fragrans. Through spectroscopic analyses, especially the band-selective CT-HSQC and CT-HMBC techniques, the complex skeleton was constructed from four sesquiterpene units via three different linkages. A biosynthetic pathway was proposed featuring a Michael addition and a regular and a hetero-Diels-Alder cycloaddition. Both exhibited potent cytotoxicity against human cancer cell lines with IC50 values ranging from 2 to 15 µM.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31580705

RESUMO

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.

19.
Waste Manag ; 101: 1-8, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585272

RESUMO

Co-pelletization of sewage sludge (SS) and conventional fuels for combustion is considered to be a feasible SS disposal method. Oxy-fuel combustion is recognized as a promising technology to reduce the emission of CO2. In practical applications, the combustion atmosphere in oxy-fuel boiler is O2/CO2/H2O, which is different from that in the conventional boiler (O2/N2). Therefore, the effects of gas composition on the combustion characteristics of boiler fuels should be both taken into consideration. In this work, the SS/pine sawdust (PS) and SS/bituminous coal (BC) blended fuel particles were prepared, and the single particle combustion experiments were conducted in O2/N2, O2/CO2 and O2/CO2/H2O atmospheres. The influences of SS blending proportion and gas composition on combustion characteristics of fuel particles were analyzed. The results reveal that increasing the blending proportion of SS from 20 to 40 wt% decreases the ignition delay time, burnout time and combustion temperature. The substitution of N2 by CO2 increases the ignition delay time and burnout time, while decreases the combustion temperature. Replacing CO2 by 10 vol%, 20 vol% and 30 vol% H2O decreases the ignition delay time and burnout time, while increases the combustion temperature.

20.
J Comput Neurosci ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506807

RESUMO

Acute hepatic encephalopathy (AHE) due to acute liver failure is a common form of delirium, a state of confusion, impaired attention, and decreased arousal. The electroencephalogram (EEG) in AHE often exhibits a striking abnormal pattern of brain activity, which epileptiform discharges repeat in a regular repeating pattern. This pattern is known as generalized periodic discharges, or triphasic-waves (TPWs). While much is known about the neurophysiological mechanisms underlying AHE, how these mechanisms relate to TPWs is poorly understood. In order to develop hypotheses how TPWs arise, our work builds a computational model of AHE (AHE-CM), based on three modifications of the well-studied Liley model which emulate mechanisms believed central to brain dysfunction in AHE: increased neuronal excitability, impaired synaptic transmission, and enhanced postsynaptic inhibition. To relate our AHE-CM to clinical EEG data from patients with AHE, we design a model parameter optimization method based on particle filtering (PF-POM). Based on results from 7 AHE patients, we find that the proposed AHE-CM not only performs well in reproducing important aspects of the EEG, namely the periodicity of triphasic waves (TPWs), but is also helpful in suggesting mechanisms underlying variation in EEG patterns seen in AHE. In particular, our model helps explain what conditions lead to increased frequency of TPWs. In this way, our model represents a starting point for exploring the underlying mechanisms of brain dynamics in delirium by relating microscopic mechanisms to EEG patterns.

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