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1.
Bioorg Chem ; 142: 106933, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890210

RESUMO

ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.


Assuntos
ATP Citrato (pro-S)-Liase , Neoplasias , Humanos , ATP Citrato (pro-S)-Liase/metabolismo , Neoplasias/metabolismo , Metabolismo dos Lipídeos
2.
Immunopharmacol Immunotoxicol ; 46(3): 319-329, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38466121

RESUMO

OBJECTIVE: Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury. METHODS: We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR. RESULTS: Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated. CONCLUSION: Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.


Assuntos
Injúria Renal Aguda , Anti-Inflamatórios , Cisplatino , Macrófagos , Quercetina , Animais , Quercetina/análogos & derivados , Quercetina/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/metabolismo , Camundongos , Cisplatino/farmacologia , Cisplatino/efeitos adversos , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Masculino , Camundongos Endogâmicos C57BL
3.
Inorg Chem ; 62(44): 18150-18156, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37870276

RESUMO

Two organic-inorganic hybrid zinc phosphites incorporating 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene (TIMB) molecules were synthesized under hydro(solvo)thermal methods and structurally characterized by single-crystal X-ray diffraction (SCXD). Interestingly, the solvent ratio of water to dimethylformamide induced the formation of a new compound of Zn2(TIMB)0.5(HPO3)2·3H2O (1) and our previously reported structure of Zn2(TIMB)0.5(HPO3)2·H2O (2). Additionally, their dehydrated crystals (1a and 2a) were prepared through heat treatment at 150 °C. SCXD and powder X-ray diffraction showed that all four compounds share the same framework formula of Zn2(TIMB)0.5(HPO3)2 but exhibit a huge difference in their inorganic components and final structures. In 1 and 1a, the inorganic units formed two-dimensional zincophosphite layers, while in 2 and 2a, they formed one-dimensional chains. The inorganic parts of 1 (1a) and 2 (2a) were bridged with TIMB linkers, resulting in 3D structures with rectangular and tubular windows, respectively. Furthermore, 1 was coated on the screen-printed carbon electron as a hybrid material, displaying excellent performance while having a linear relationship with an R2 value of 0.99 within the concentration range of 10-10 to 10-6 mol/L for detecting tryptamine (Try) molecules. Moreover, the results showed that 1 exhibits an ultralow limit of detection of 5.43 × 10-11 mol/L and high specificity toward Try over histamine, ascorbic acid, uric acid, and glucose. The synthesis, structural diversity, stability, and sensing ability are also discussed.

4.
BMC Psychiatry ; 23(1): 128, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849934

RESUMO

BACKGROUND: Previous studies have shown that depression was associated with HTR3B gene. The aim of this study was to investigate the relationship between polymorphisms of the HTR3B gene and depression and its executive dysfunction in Chinese Han population. METHODS: A total of 229 patients with depressive disorder and 202 healthy controls were enrolled. Six Single nucleotide polymorphism sites (SNPs) including rs10789970, rs4938056, rs12421126, rs1176744, rs2276305 and rs12795805 were genotyped by Snapshot. Clinical features were collected using a general demographic questionnaire. The 24-item Hamilton Depression Scale (HAMD) was used to assess the symptoms' severity of the patients. The patients' executive function was assessed using a series of cognitive tests including Maze Test, Symbolic Coding Test, Spatial Span Inverse Order Test, Linking Test, and Emotional Management Test. RESULTS: The genotypic and allelic distributions of rs1176744 in HTR3B gene were significantly different (χ2 = 11.129, P = 0.004, χ2 = 9.288, P = 0.002, respectively) between patients and controls. The A allele was positively correlated with depression. The proportion of A carriers was significantly higher and that of C carriers was lower in patients than those in controls. Patients had significantly lower scores of Spatial Span Inverse Order Test in carriers of A allele at locus rs1176744 and higher scores in carriers of C alleles at locus rs1176744 and rs12795805. CONCLUSIONS: The polymorphisms of HTR3B gene may be associated with depression in Chinese Han population. The A allele of rs1176744 may increase the risk of developing depression and executive dysfunction while C alleles of rs1176744 and rs12795805 may be the protective factors for executive dysfunction in patients with depression.


Assuntos
Disfunção Cognitiva , Depressão , Humanos , Estudos de Casos e Controles , Depressão/genética , Polimorfismo de Nucleotídeo Único , Genótipo , Receptores 5-HT3 de Serotonina/genética
5.
Sensors (Basel) ; 23(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36850441

RESUMO

Several methods for the measurement of tactile acuity have been devised previously, but unexpected nonspatial cues and intensive manual skill requirements compromise measurement accuracy. Therefore, we must urgently develop an automated, accurate, and noninvasive method for assessing tactile acuity. The present study develops a novel method applying a robotic tactile stimulator to automatically measure tactile acuity that comprises eye-opened, eye-closed training, and testing sessions. Healthy participants judge the orientation of a rotating grating ball presented on their index fingerpads in a two-alternative forced-choice task. A variable rotation speed of 5, 10, 40, or 160 mm/s was used for the tactile measurement at a variety of difficulties. All participants met the passing criteria for the training experiment. Performance in orientation identification, quantified by the proportion of trials with correct answers, differed across scanning directions, with the highest rotation speed (160 mm/s) having the worst performance. Accuracy did not differ between vertical and horizontal orientations. Our results demonstrated the utility of the pre-test training protocol and the functionality of the developed procedure for tactile acuity assessment. The novel protocol performed well when applied to the participants. Future studies will be conducted to apply this method to patients with impairment of light touch.


Assuntos
Sinais (Psicologia) , Robótica , Humanos , Voluntários Saudáveis , Rotação
6.
Entropy (Basel) ; 25(3)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36981409

RESUMO

Many datasets in statistical analyses contain missing values. As omitting observations containing missing entries may lead to information loss or greatly reduce the sample size, imputation is usually preferable. However, imputation can also introduce bias and impact the quality and validity of subsequent analysis. Focusing on binary classification problems, we analyzed how missing value imputation under MCAR as well as MAR missingness with different missing patterns affects the predictive performance of subsequent classification. To this end, we compared imputation methods such as several MICE variants, missForest, Hot Deck as well as mean imputation with regard to the classification performance achieved with commonly used classifiers such as Random Forest, Extreme Gradient Boosting, Support Vector Machine and regularized logistic regression. Our simulation results showed that Random Forest based imputation (i.e., MICE Random Forest and missForest) performed particularly well in most scenarios studied. In addition to these two methods, simple mean imputation also proved to be useful, especially when many features (covariates) contained missing values.

7.
Acta Cardiol Sin ; 39(6): 879-887, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38022424

RESUMO

Background: The 10-year atherosclerotic cardiovascular disease (ASCVD) risk - as assessed using the Framingham general cardiovascular risk score (FRS-CVD) or pooled cohort equations (PCE) - is commonly used in Western cohorts for the primary prevention of cardiovascular disease (CVD). However, the FRS-CVD and PCE have not been validated in Taiwanese cohorts. Objectives: We aimed to validate the FRS-CVD and PCE for assessing the 10-year ASCVD risk using a Taiwanese community-based population. Methods: We extracted patient data from the Landseed Integrated Outreaching Neighborhood Screening registry, a community-based prospective cohort study established in 2006. Cardiovascular events from 2006 to 2017 were determined from electronic medical records. The discriminative power and calibration of the FRS-CVD and PCE were evaluated. Results: Overall, 5,139 subjects were analyzed; the 10-year follow-up rate was 99.6%. The mean age at baseline was 52.8 ± 13.1 years, and 44.6% of the subjects were male. In total, 430 of 4,631 (9.3%) and 227 of 4,022 (5.6%) of the FRS-CVD- and PCE-like cohorts, respectively, had ASCVD events. The calibration χ2 of the FRS-CVD was 7.0267 (p = 0.6343) in males and 7.8845 (p = 0.5458) in females; the χ2 of PCE was 13.007 (p = 0.1623) in males and 38.785 (p < 0.001) in females. The area under the receiver operating characteristic curve (AUROC) of the FRS-CVD was 0.76 (0.72-0.79) in males and 0.71 (0.67-0.74) in females; the AUROC of PCE was 0.68 (0.62-0.73) in males and 0.61 (0.56-0.67) in females. Conclusions: Except for PCE in females, the FRS-CVD and PCE provided good calibration and modest discrimination in statin-naïve Taiwanese individuals without prior CVD.

8.
Zhonghua Nan Ke Xue ; 28(2): 140-143, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-37462486

RESUMO

OBJECTIVE: To evaluate the influence of epididymitis history on the results of microsurgical vasoepididymostomy and spontaneous pregnancy in patients with epididymal obstruction. METHODS: Totally 205 patients with epididymal obstruction underwent microsurgical two-suture longitudinal intussusception vasoepididymostomy from January 2014 to December 2016. After surgery, we evaluated the semen quality of the patients every 3 months till conception and compared the rates of patency and spontaneous pregnancy between the patients with and those without an epididymitis history. RESULTS: The patients ranged in age from 22 to 46 (mean 31) years, 37 (22.2%) with and 126 (77.8%) without an epididymitis history among the 163 patients for whom a 25.4-month follow-up (from 7 to 42 months) was completed. No statistically significant differences were observed postoperatively between the patients with and those without an epididymitis history in the patency rate (73.0% vs 81.7%, P = 0.243), sperm concentration (18 ï¼»1.3-33.6ï¼½ vs 15.2 ï¼»0.8-33.4ï¼½ ×106/ml, P = 0.710), percentage of progressively motile sperm (27.5 ï¼»0-46.1ï¼½% vs 19.3 ï¼»0-41ï¼½% (P = 0.592) or rate of spontaneous pregnancy (24.3% vs 38.9%, P = 0.104). CONCLUSION: Microsurgical vasoepididymostomy is an effective method for the treatment of epididymal obstruction, and epididymitis history does not affect the results of the strategy.


Assuntos
Epididimo , Epididimite , Gravidez , Feminino , Humanos , Masculino , Adulto , Epididimo/cirurgia , Epididimite/complicações , Epididimite/cirurgia , Análise do Sêmen , Resultado do Tratamento , Microcirurgia/métodos , Sêmen , Ducto Deferente/cirurgia
9.
Bioorg Med Chem ; 45: 116331, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364224

RESUMO

As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR + ) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Neoplasias da Próstata/tratamento farmacológico , Proteólise/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Modelos Moleculares , Estrutura Molecular , Neoplasias da Próstata/metabolismo , Relação Estrutura-Atividade
10.
Sensors (Basel) ; 21(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803265

RESUMO

Diverse computer-aided diagnosis systems based on convolutional neural networks were applied to automate the detection of myocardial infarction (MI) found in electrocardiogram (ECG) for early diagnosis and prevention. However, issues, particularly overfitting and underfitting, were not being taken into account. In other words, it is unclear whether the network structure is too simple or complex. Toward this end, the proposed models were developed by starting with the simplest structure: a multi-lead features-concatenate narrow network (N-Net) in which only two convolutional layers were included in each lead branch. Additionally, multi-scale features-concatenate networks (MSN-Net) were also implemented where larger features were being extracted through pooling the signals. The best structure was obtained via tuning both the number of filters in the convolutional layers and the number of inputting signal scales. As a result, the N-Net reached a 95.76% accuracy in the MI detection task, whereas the MSN-Net reached an accuracy of 61.82% in the MI locating task. Both networks give a higher average accuracy and a significant difference of p < 0.001 evaluated by the U test compared with the state-of-the-art. The models are also smaller in size thus are suitable to fit in wearable devices for offline monitoring. In conclusion, testing throughout the simple and complex network structure is indispensable. However, the way of dealing with the class imbalance problem and the quality of the extracted features are yet to be discussed.


Assuntos
Algoritmos , Infarto do Miocárdio , Diagnóstico por Computador , Eletrocardiografia , Humanos , Infarto do Miocárdio/diagnóstico , Redes Neurais de Computação
11.
Sensors (Basel) ; 19(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554304

RESUMO

A mobile system that can detect viruses in real time is urgently needed, due to the combination of virus emergence and evolution with increasing global travel and transport. A biosensor called PAMONO (for Plasmon Assisted Microscopy of Nano-sized Objects) represents a viable technology for mobile real-time detection of viruses and virus-like particles. It could be used for fast and reliable diagnoses in hospitals, airports, the open air, or other settings. For analysis of the images provided by the sensor, state-of-the-art methods based on convolutional neural networks (CNNs) can achieve high accuracy. However, such computationally intensive methods may not be suitable on most mobile systems. In this work, we propose nanoparticle classification approaches based on frequency domain analysis, which are less resource-intensive. We observe that on average the classification takes 29 µ s per image for the Fourier features and 17 µ s for the Haar wavelet features. Although the CNN-based method scores 1-2.5 percentage points higher in classification accuracy, it takes 3370 µ s per image on the same platform. With these results, we identify and explore the trade-off between resource efficiency and classification performance for nanoparticle classification of images provided by the PAMONO sensor.

12.
J Org Chem ; 83(19): 12184-12191, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30153730

RESUMO

The highly enantioselective conjugate addition of a variety of arylboronic acids to ß-nitroacrylates is reported to provide optically active α-aryl ß-nitropropionates in up to 70% yields and >99.5% ee's, which are useful building blocks for preparing chiral ß2-amino acids. The applicability of this transformation is demonstrated by converting 3aa into the ß2-amino acid 5 and transforming 3ap to ß-amino ester 7 via reduction and reductive N-alkylation. The latter compound is a precursor for preparing ent-ipatasertib.

13.
Bioorg Med Chem ; 26(17): 4761-4773, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30143365

RESUMO

Two series of derivatives with 1,2,3-triazole as heterocyclic moiety of Jiyuan Oridonin A, a new ent-kaurene diterpenoid which was isolated from genus Isodon rubescens, were synthesized and biologically evaluated. All the derivatives possessed good anti-proliferative activities. Among them, compound 8g was found to significantly induce cell apoptosis and cell cycle arrest in MGC-803 via a series of signals activated by the increased intracellular ROS levels.


Assuntos
Triazóis/química , Triazóis/farmacologia , Acetilcisteína/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química
14.
J Am Chem Soc ; 139(4): 1545-1553, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28045511

RESUMO

A series of 2-methyl-1,3-propenylene-bridged (η5-diarylphosphinocyclopentadienyl)(phosphine)manganese(I) dicarbonyl complexes 2 have been developed as a new class of phosphine-olefin ligands based on a planar-chiral transition-metal scaffold, which show better robustness as well as higher enantioselectivity over phosphine-olefin ligands 1 with a planar-chiral (η6-arene)chromium(0) framework. The practical enantiospecific and scalable synthesis of 2 has been established. Phosphine-olefin ligands 2 enable construction of an effective chiral environment around a transition-metal center upon coordination, and thus their rhodium(I) complexes exhibit excellent catalytic performance in the various asymmetric addition reactions of arylboron nucleophiles. Complex 2b, which has a bis(3,5-dimethylphenyl)phosphino group on the cyclopentadienyl ring, is found to be a superior chiral ligand in the rhodium-catalyzed asymmetric 1,4-addition reactions of arylboronic acids to various cyclic/acyclic enones giving the corresponding arylation products in over 99% ee. On the other hand, 2c and 2d, which have bis[3,5-bis(trifluoromethyl)phenyl]phosphino and bis(3,5-di-tert-buthyl-4-methoxyphenyl)phosphino groups, respectively, are highly efficient chiral ligands in the rhodium-catalyzed asymmetric 1,2-addition reactions of the arylboron nucleophiles to imines or aldehydes showing up to 99.9% ee. The X-ray crystallographic studies of (R)-2b and [RhCl((S*)-2b)]2 reveal the absolute configuration of 2b and its phosphine-olefin bidentate coordination to a rhodium(I) cation. Structural comparison with [RhCl((R*)-1b)]2 postulates the origins of the higher enantioselectivity of newly developed phosphine-olefin ligands 2.

15.
Biochim Biophys Acta Biomembr ; 1859(5): 917-923, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28143758

RESUMO

Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding. Dynamic light scattering (DLS) and leakage assay results further indicated that neither membrane pores nor membrane fragmentations were observed in the presence of HaTx. To clarify the binding details, Langmuir trough experiments were performed with phospholipid monolayers by mimicking the external leaflet of membrane bilayers, indicating the involvement of acyl chains in such interactions between HaTx and phospholipids. Our current study thus describes the interaction pattern of HaTx with vesicle membranes, defining a membrane-partitioning mechanism for peptide insertion involving the membrane hydrocarbon core without pore formation.


Assuntos
Bicamadas Lipídicas/química , Peptídeos/química , Fosfolipídeos/química , 1,2-Dipalmitoilfosfatidilcolina/química , Luz , Espalhamento de Radiação
16.
Chemistry ; 23(8): 1830-1838, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-27797164

RESUMO

An enantioselective RhI -catalyzed conjugate addition reaction of α-substituted ß-nitroacrylates with various arylboronic acids by using chiral RhI diene catalysts is described for the first time. The addition reaction proceeds under mild conditions in a range of common organic solvents and additives, and it affords the corresponding quaternary-carbon-containing α,α-disubstituted ß-nitropropionate products in up to 63 % yield and 99 % ee. Reaction of either (E)- or (Z)-ß-nitroacrylates provided the same enantiomer of the product, and a range of esters and aryl groups were tolerated. To demonstrate the utility of the method, ethyl (R)-1,1-methyl-1-phenyl-3-nitropropionate, prepared herein, was converted to the non-proteinogenic ß2,2 -amino acid, (R)-2-(aminomethyl)-2-phenylpropanoic acid, and to the ß2,2 -lactam, (R)-3-methyl-3-phenylazetidin-2-one. In addition, a tripeptide, which comprised l-phenylalanine, l-alanine, and ß2,2 -amino acid 7, was also synthesized.

17.
J Comput Neurosci ; 38(3): 483-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25761744

RESUMO

Granger causality (GC) analysis has emerged as a powerful analytical method for estimating the causal relationship among various types of neural activity data. However, two problems remain not very clear and further researches are needed: (1) The GC measure is designed to be nonnegative in its original form, lacking of the trait for differentiating the effects of excitations and inhibitions between neurons. (2) How is the estimated causality related to the underlying synaptic weights? Based on the GC, we propose a computational algorithm under a best linear predictor assumption for analyzing neuronal networks by estimating the synaptic weights among them. Under this assumption, the GC analysis can be extended to measure both excitatory and inhibitory effects between neurons. The method was examined by three sorts of simulated networks: those with linear, almost linear, and nonlinear network structures. The method was also illustrated to analyze real spike train data from the anterior cingulate cortex (ACC) and the striatum (STR). The results showed, under the quinpirole administration, the significant existence of excitatory effects inside the ACC, excitatory effects from the ACC to the STR, and inhibitory effects inside the STR.


Assuntos
Redes Neurais de Computação , Sinapses/fisiologia , Potenciais de Ação , Algoritmos , Causalidade , Simulação por Computador , Corpo Estriado/citologia , Corpo Estriado/fisiologia , Fenômenos Eletrofisiológicos , Giro do Cíngulo/citologia , Giro do Cíngulo/fisiologia , Humanos , Modelos Lineares , Modelos Neurológicos , Dinâmica não Linear
18.
Int J Mol Sci ; 16(10): 24983-5001, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26492243

RESUMO

The purpose of this experiment was to determine the antidiabetic and lipid-lowering effects of (-)-epicatechin-3-O-ß-D-allopyranoside (BB) from the roots and stems of Davallia formosana in mice. Animal treatment was induced by high-fat diet (HFD) or low-fat diet (control diet, CD). After eight weeks of HFD or CD exposure, the HFD mice were treating with BB or rosiglitazone (Rosi) or fenofibrate (Feno) or water through gavage for another four weeks. However, at 12 weeks, the HFD-fed group had enhanced blood levels of glucose, triglyceride (TG), and insulin. BB treatment significantly decreased blood glucose, TG, and insulin levels. Moreover, visceral fat weights were enhanced in HFD-fed mice, accompanied by increased blood leptin concentrations and decreased adiponectin levels, which were reversed by treatment with BB. Muscular membrane protein levels of glucose transporter 4 (GLUT4) were reduced in HFD-fed mice and significantly enhanced upon administration of BB, Rosi, and Feno. Moreover, BB treatment markedly increased hepatic and skeletal muscular expression levels of phosphorylation of AMP-activated (adenosine monophosphate) protein kinase (phospho-AMPK). BB also decreased hepatic mRNA levels of phosphenolpyruvate carboxykinase (PEPCK), which are associated with a decrease in hepatic glucose production. BB-exerted hypotriglyceridemic activity may be partly associated with increased mRNA levels of peroxisome proliferator activated receptor α (PPARα), and with reduced hepatic glycerol-3-phosphate acyltransferase (GPAT) mRNA levels in the liver, which decreased triacylglycerol synthesis. Nevertheless, we demonstrated BB was a useful approach for the management of type 2 diabetes and dyslipidemia in this animal model.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Hiperlipidemias/prevenção & controle , Hipoglicemiantes/uso terapêutico , Plantas Medicinais/química , Proteínas Quinases Ativadas por AMP/genética , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fenofibrato/uso terapêutico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Rosiglitazona , Tiazolidinedionas/uso terapêutico
19.
Eur J Neurosci ; 40(5): 2811-21, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24964034

RESUMO

Axon collateral projections to various lobules of the cerebellar cortex are thought to contribute to the coordination of neuronal activities among different parts of the cerebellum. Even though lobules I/II and IX/X of the cerebellar vermis are located at the opposite poles in the anterior-posterior axis, they have been shown to receive dense vestibular mossy fiber projections. For climbing fibers, there is also a mirror-image-like organisation in their axonal collaterals between the anterior and posterior cerebellar cortex. However, the detailed organisation of mossy and climbing fiber collateral afferents to lobules I/II and IX/X is still unclear. Here, we carried out a double-labeling study with two retrograde tracers (FluoroGold and MicroRuby) in lobules I/II and IX/X. We examined labeled cells in the vestibular nuclei and inferior olive. We found a low percentage of double-labeled neurons in the vestibular nuclei (2.1 ± 0.9% of tracer-labeled neurons in this brain region), and a higher percentage of double-labeled neurons in the inferior olive (6.5 ± 1.9%), especially in its four small nuclei (18.5 ± 8.0%; including the ß nucleus, dorsal cap of Kooy, ventrolateral outgrowth, and dorsomedial cell column), which are relevant for vestibular function. These results provide strong anatomical evidence for coordinated information processing in lobules I/II and IX/X for vestibular control.


Assuntos
Vermis Cerebelar/anatomia & histologia , Neurônios/citologia , Núcleo Olivar/anatomia & histologia , Núcleos Vestibulares/anatomia & histologia , Animais , Feminino , Vias Neurais/anatomia & histologia , Técnicas de Rastreamento Neuroanatômico , Fotomicrografia , Ratos Long-Evans
20.
Cerebellum ; 13(1): 97-108, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24057318

RESUMO

Neuronal oscillations have been shown to contribute to the function of the cerebral cortex by coordinating the neuronal activities of distant cortical regions via a temporal synchronization of neuronal discharge patterns. This can occur regardless whether these regions are linked by cortico-cortical pathways or not. Less is known concerning the role of neuronal oscillations in the cerebellum. Golgi cells and Purkinje cells are both principal cell types in the cerebellum. Purkinje cells are the sole output cells of the cerebellar cortex while Golgi cells contribute to information processing at the input stage of the cerebellar cortex. Both cell types have large cell bodies, as well as dendritic structures, that can generate large currents. The discharge patterns of both these cell types also exhibit oscillations. In view of the massive afferent information conveyed by the mossy fiber-granule cell system to different and distant areas of the cerebellar cortex, it is relevant to inquire the role of cerebellar neuronal oscillations in information processing. In this study, we compared the discharge patterns of Golgi cells and Purkinje cells in conscious rats and in rats anesthetized with urethane. We assessed neuronal oscillations by analyzing the regularity in the timing of individual spikes within a spike train by using autocorrelograms and fast-Fourier transform. We measured the differences in neuronal oscillations and the amount of information content in a spike train (defined by Shannon entropy processed per unit time) in rats under anesthesia and in conscious, awake rats. Our findings indicated that anesthesia caused more prominent neuronal oscillations in both Golgi cells and Purkinje cells accompanied by decreases in Shannon information entropy in their spike trains.


Assuntos
Cerebelo/fisiologia , Interneurônios/fisiologia , Células de Purkinje/fisiologia , Potenciais de Ação/efeitos dos fármacos , Anestesia , Anestésicos Intravenosos/farmacologia , Animais , Cerebelo/efeitos dos fármacos , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Feminino , Análise de Fourier , Teoria da Informação , Interneurônios/efeitos dos fármacos , Locomoção/fisiologia , Células de Purkinje/efeitos dos fármacos , Ratos , Ratos Long-Evans , Fatores de Tempo , Uretana/farmacologia
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