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1.
Mar Drugs ; 17(8)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398788

RESUMO

Angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from natural products have shown a blood pressure lowering effect with no side effects. In this study, two novel ACE inhibitory peptides (His-Leu-His-Thr, HLHT and Gly-Trp-Ala, GWA) were purified from pearl oyster (Pinctada fucata martensii) meat protein hydrolysate with alkaline protease by ultrafiltration, polyethylene glycol methyl ether modified immobilized metal ion affinity medium, and reverse-phase high performance liquid chromatography. Both peptides exhibited high ACE inhibitory activity with IC50 values of 458.06 ± 3.24 µM and 109.25 ± 1.45 µM, respectively. Based on the results of a Lineweaver-Burk plot, HLHT and GWA were found to be non-competitive inhibitor and competitive inhibitor respectively, which were confirmed by molecular docking. Furthermore, the pearl oyster meat protein hydrolysate exhibited an effective antihypertensive effect on SD rats. These results conclude that pearl oyster meat protein is a potential resource of ACE inhibitory peptides and the purified peptides, HLHT and GWA, can be exploited as functional food ingredients against hypertension.

2.
Org Biomol Chem ; 17(33): 7760-7771, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31389463

RESUMO

Recently, oxyntomodulin (OXM) has emerged as a treatment option for type 2 diabetes mellitus and obesity. In order to develop more promising novel OXM derivatives combining glycemic effects of glucagon-like peptide-1 (GLP-1) and lipolytic properties of glucagon, six 12-mer GLP-1 receptor agonists (PP01-PP06) were screened using a phage display method and then fused to OXM (3-37) to generate hybrid OXM derivatives (PP07-PP12). PP11, as a selected starting point, was further site-specifically modified with three lengths of fatty acid chains to provide long-acting conjugates PP13-PP24, among which PP18 was found not only to retain almost the entire balanced activation potency of PP11 in GLP-1/glucagon receptors but also to enhance plasma stability and prolong hypoglycemic activity. PP18 was further confirmed as an insulin secretagogue and glycemic agent in gene knockout mice. The protracted antidiabetic effects and in vivo half-life of PP18 were further proved by hypoglycemic efficacies in diet-induced obesity (DIO) mice and pharmacokinetics tests in Sprague Dawley (SD) rats, respectively. Nevertheless, administration of PP18 once per day normalized food intake, body weight, blood biochemical indexes, insulin resistance and islet function of DIO mice. These preclinical results suggested that PP18, as a novel OXM-based dual GLP-1 and glucagon receptor agonist, may serve as a novel therapeutic approach to treat T2DM and obesity.

3.
J Cell Biochem ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452254

RESUMO

The aim is to investigate the mechanism of miR-499a-5p on the damage of cardiomyocyte induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase (LDH), apoptosis rate and the expression of miR-499a-5p and cluster of differentiation 38 (CD38) in hypoxia-reoxygenation model cells were detected by LDH Cytotoxicity Assay Kit, flow cytometry, real-time polymerase chain reaction, and Western blot analysis, respectively. Apoptosis, the activity of LDH was detected after overexpression of miR-499a-5p or silencing of CD38 in H9c2 cells. The target relationship between miR-499a-5p and CD38 was verified by Targetscan online prediction and dual-luciferase assay. Apoptosis, the activity of LDH was detected after overexpression of miR-499a-5p and CD38. Apoptosis, the activity of LDH and the expression of CD38 were increased (P < .05) while expression of miR-499a-5p was decreased (P < .05) in hypoxia/reoxygenation model cells. Apoptosis and the activity of LDH in H9c2 cells after overexpression of miR-499a-5p or silence of CD38 were decreased (P < .05). The results of Targetscan online prediction and dual-luciferase assay indicated that CD38 was a potential target gene of miR-499a-5p. Overexpression of CD38 could reverse the inhibition of miR-499a-5p on LDH activity and apoptosis in H9c2 cells. miR-499a-5p could relief the injury of cardiomyocytes induced by hypoxia/reoxygenation via targeting CD38.

4.
Aging Clin Exp Res ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352587

RESUMO

BACKGROUND AND AIMS: This study aimed to investigate the association between cumulative C-reactive protein (cumCPR) and arterial stiffness. METHODS: The cross-sectional study included 15,432 participants from the Kailuan Cohort. The participants were divided into four groups according to cumCRP quartiles. The average brachial-ankle pulse wave velocity (baPWV) and detective rate of increased arterial stiffness were compared between exposure groups. Statistical analysis was performed with multiple logistic regression analysis to estimate the association between cumCRP and arterial stiffness by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). The several sensitivity analyses were performed to test the robustness of our findings. RESULTS: The average baPWV increased from 1425.70 cm/s of Q1 group to 1626.48 cm/s of Q4 group. And the detective rate of arterial stiffness increased from 44.7 to 70.1% (P < 0.001). Multiple logistic regression analysis showed that after adjusting the confounding factors, compared to the Q1 group, the Q4 group had 42% (adjusted OR 1.42; 95% CI 1.24-1.63) higher arterial stiffness risk. In addition, 10% (adjusted OR 1.10; 95% CI 1.02-1.18) arterial stiffness risk was increased per 1 standard deviation (SD) of cumCRP after a fully adjusted regression model. CONCLUSION: Higher cumCRP exposure is associated with increased arterial stiffness.

5.
J Photochem Photobiol B ; 197: 111539, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31301638

RESUMO

Treatment of burn injury is clinically challenging one, therefore several steps and noteworthy approaches have been taken to improve wound mechanisms. Citrus pectin plays a stabilizing agent to synthesis of ZnO nanoparticles (ZnO NPs). The present study is focused on ZnO loaded collagen/chitosan nanofibrous were synthesized by electrospinning method using ZnO NPs. The chemical structure, phase purity and morphological observation were investigated under spectroscopic and mircoscopic techniques and demonstrated their suitable properties as a wound healing material. In addition, that prepared nanoparticles loaded biopolymeric fibrous nanomaterial showed suitable antibacterial activity against S. aureus and E. coli bacterial pathogens and also in vitro studies was confirmed the enhanced proliferation, cell viability and biocompatibility. In vitro evaluations have been exhibited acceptable cell proliferation is observed throughout the ZnO loaded Coll/CS nanofibrous within 3 days, which was comparable to the control material. In vivo wound healing ability was monitored on the rat wound experimental model. From the in vivo observations, revealed that the loaded of ZnO NPs with Coll/CS nanofibrous can effectively quicken wound healing mechanism, expressed in the initial stage healing process. These results suggest that ZnO loaded collagen/chitosan nanofibrous is a potential candidate for wound healing applications with enhanced biological properties.


Assuntos
Queimaduras/patologia , Quitosana/química , Colágeno/química , Nanopartículas Metálicas/química , Nanofibras/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Queimaduras/veterinária , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Nanofibras/uso terapêutico , Nanofibras/toxicidade , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Óxido de Zinco/química
6.
Theranostics ; 9(9): 2555-2571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131053

RESUMO

Cancer invasion and metastasis depend on accurate and rapid modulation of both chemical and mechanical activities. The S-nitrosylation (SNO) of membrane cytoskeletal cross-linker protein ezrin may regulate the malignant process in a tension-dependent manner. Methods: The level of nitrosylated ezrin in non-small cell lung cancer (NSCLC) tissues and A549 cell line were evaluated by biotin-switch assay. A few cysteine mutated plasmids of ezrin were used to identify active site for SNO. Newly designed ezrin or mutated-ezrin tension probes based on Förster resonance energy transfer (FRET) theory were applied to visually observe real-time tension changes. Cytoskeleton depolymerizing and motor molecular inhibiting experiments were performed to reveal the alternation of the mechanical property of ezrin after SNO. Transwell assays and xenograft mouse model were used to assess aggressiveness of A549 cells in different groups. Fluorescent staining was also applied to examine cellular location and structures. Results: High inducible nitric oxide synthase (iNOS) levels were observed to induce ezrin-SNO, and then promote malignant behaviors of NSCLC cells both in vitro and in vivo. Cys117 was identified as the only active site for ezrin-SNO. Meanwhile, an increased level of ezrin tension was observed after iNOS-induced SNO. Enhanced ezrin tension was positively correlated with aggressiveness of NSCLC. Moreover, Microfilament (MF) forces instead of microtubule (MT) forces played dominant roles in modulating ezrin tension, especially after ezrin nitrosylation. Conclusion: This study revealed a SNO-associated mechanism underlying the mechanical tension of ezrin. Ezrin-SNO promotes NSCLC cells invasion and metastasis through facilitating mechanical transduction from the cytoskeleton to the membrane. These studies implicate the therapeutic potential by targeting ezrin in the inhibition NSCLC invasion and metastasis.

7.
J Chem Inf Model ; 59(3): 973-982, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30807141

RESUMO

Endocrine disruption (ED) has become a serious public health issue and also poses a significant threat to the ecosystem. Due to complex mechanisms of ED, traditional in silico models focusing on only one mechanism are insufficient for detection of endocrine disrupting chemicals (EDCs), let alone offering an overview of possible action mechanisms for a known EDC. To remove these limitations, in this study both single-label and multilabel models were constructed across six ED targets, namely, AR (androgen receptor), ER (estrogen receptor alpha), TR (thyroid receptor), GR (glucocorticoid receptor), PPARg (peroxisome proliferator-activated receptor gamma), and aromatase. Two machine learning methods were used to build the single-label models, with multiple random under-sampling combining voting classification to overcome the challenge of data imbalance. Four methods were explored to construct the multilabel models that can predict the interaction of one EDC against multiple targets simultaneously. The single-label models of all the six targets have achieved reasonable performance with balanced accuracy (BA) values from 0.742 to 0.816. Each top single-label model was then joined to predict the multilabel test set with BA values from 0.586 to 0.711. The multilabel models could offer a significant boost over the single-label baselines with BA values for the multilabel test set from 0.659 to 0.832. Therefore, we concluded that single-label models could be employed for identification of potential EDCs, while multilabel ones are preferable for prediction of possible mechanisms of known EDCs.

8.
Medicine (Baltimore) ; 98(2): e14032, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633196

RESUMO

RATIONALE: Chronic active Epstein-Barr virus infection (CAEBV) is a common infectious disease that often affects multiple organs or systems. However, it is liable to be neglected and misdiagnosed owing to its insidious onset, lack of specific findings in the early phase, and a general lack of awareness among clinicians. PATIENT CONCERNS:: a 27-year-old woman case has been described who was initially misdiagnosed as drug-induced liver injury due to onset presentation of mild splenomegaly, recurrent liver dysfunction, and disputable pathological evidence of liver biopsy. DIAGNOSES: CAEBV complicated with natural killer (NK) cell lymphoma and hemophagocytic lymphohistiocytosis (HLH) was diagnosed by in situ hybridization of liver tissue section with EBV-encoded RNA -1 probe and flow cytometry of bone marrow. INTERVENTIONS: After admission, the patient received symptomatic treatment and antiviral therapy (combination of acyclovir and foscarnet sodium) as well as adjuvant treatment (thymosin alpha 1 and methylprednisolone); later, the patient received etoposide and dexamethasone for diagnosis of EBV associated HLH. Subsequently, the disease progressed to NK cell lymphoma and the patient received the revised EPOCH chemotherapy regimen [etoposide (100 mg/d, d1-5), dexamethasone (7.5 mg/d, d1-5; 5 mg/d, d6-14), cyclophosphamide (0.8 g/d, d1-2), and pegaspargase (3750 u/d, tid, d1-2)]. OUTCOMES: Although the patient received a series of therapies and other comprehensive measures, finally she died of gastrointestinal hemorrhage and multiple organ failure. LESSONS: Liver is one of the main target organs of EBV infection. In the clinical setting of unexplained fever and liver injury, it is necessary to be aware of CAEBV, as well as its fatal complication such as EBV associated NK cell lymphoma and HLH.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Linfoma/complicações , Adulto , Doença Crônica , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/patologia , Evolução Fatal , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/patologia , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/patologia
9.
J Agric Food Chem ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30511571

RESUMO

Angiotensin converting enzyme (ACE) inhibitory peptides derived from food protein exhibited antihypertensive effects by inhibiting ACE activity. In this work, the interaction between ACE inhibitory peptide GMKCAF (GF-6) and ACE was studied by isothermal titration calorimetry, molecular docking, UV absorption spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. Experimental results revealed that the binding of GF-6 to ACE was a spontaneous exothermic process driven by both enthalpy and entropy. The interaction occurred via a static quenching mechanism and involved the alteration of the conformation of ACE. In addition, ITC and molecular docking results indicated binding of GF-6 to ACE via multiple binding sites on the protein surface. This study could be deemed helpful for the better understanding of the inhibitory mechanism of ACE inhibitory peptides.

10.
ACS Appl Mater Interfaces ; 10(39): 33269-33275, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30199222

RESUMO

In the past years, considerable efforts have been devoted to the deliberate synthesis of nanosulfur in various hosts with sophisticated structures to improve the performance of lithium-sulfur batteries (LSBs) and reveal the structure-property relationship. It is taken for granted that these elaborate sulfur nanostructures are well maintained in the ultimate electrode after the traditional mixing and coating method. Herein, we, for the first time, reveal the unexpected sulfur structure deterioration in nanosulfur/graphene composites during the electrode preparation using the traditional method because of the long-term neglected dissolution-recrystallization effect of sulfur in solvents. Consequently, compared with binder-free three-dimensional graphene/sulfur electrodes, the milled graphene/sulfur electrodes exhibit much worse electrochemical performance. On the basis of this, we further propose a facile and universal graphene oxide-assisted assembly method to avoid the dissolution-recrystallization of sulfur, by which binder-free three-dimensional ethylenediamine-functionalized graphene/sulfur (3DEFGS) electrodes have been successfully prepared. The 3DEFGS electrodes with a high areal sulfur loading of ∼6 mg cm-2 exhibit an ultrahigh initial capacity of 1394 mA h g-1 at 0.1 C, an excellent rate performance with a capacity of 796 mA h g-1 at 4 C, and superior long-term cycling stability (885 mA h g-1 after 500 cycles at 1 C), which are among the best performances achieved by all reported LSB cathodes with high areal sulfur loadings.

11.
J Chem Inf Model ; 58(10): 2051-2056, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30251842

RESUMO

Drug-likeness, comprising absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, plays a significant role in early drug discovery. However, as for current strategies of lead optimization, in vitro potency is still the focus, which may cause "molecular obesity" (poor ADMET properties). Therefore, optimization of ADMET properties would be a preferable complement for drug discovery. In this paper, we present a web server, ADMETopt, that applies scaffold hopping and ADMET screening for lead optimization. More than 50 000 unique scaffolds were extracted by fragmenting chemicals deposited in the ChEMBL and Enamine databases. Up to 15 ADMET properties can be predicted to screen the potential molecules, including seven physicochemical properties and eight biological properties. All of the models were built in terms of our previous studies and are available in our web server admetSAR. For the plausibility measurement of the modified molecules, synthetic accessibility and quantitative evaluation of drug-likeness were then implemented. As a case study, a scaffold similarity network was constructed for compounds that have bioactivities on estrogen receptors. The results demonstrated that the feasibility and practicability of our web server are acceptable. The web server is publicly accessible at http://lmmd.ecust.edu.cn/admetsar2/admetopt/ .

12.
Pathol Res Pract ; 214(10): 1694-1699, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30196985

RESUMO

The aim of the study was to investigate whether microvessel density (MVD) could be associated with skeletal extramedullary disease relapse (skeletal-EMDR) in patients with multiple myeloma (MM) who have skeletal-EMD at diagnosis. Seventy-nine newly diagnosed MM patients who have skeletal-EMD were retrospectively enrolled in this study. The 4-year cumulative incidence of skeletal-EMDR was 35.0%±8.3%. The 4-year probability of overall survival (OS) was 54.0%±7.6%. Multivariate analysis showed that skeletal-EMDR (HR = 4.144; 95% CI: 1.608-10.685; P = 0.003) was independently associated with inferior OS for the MM patients who have skeletal-EMD at diagnosis. The factors associated with skeletal-EMDR were MVD (HR = 3.990, 95%CI:1.136-14.018; P = 0.031), white blood cell (WBC) (HR = 0.262, 95% CI:0.090-0.769; P = 0.015), and the EMD sites involved at onset (HR = 0.263, 95% CI: 0.074-0.937; P = 0.039). The MVD in patients with thoracic and lumbar vertebrae as the involved sites at diagnosis was significantly lower than those with other sites involved (41.59 ± 14.39 vs. 60.82 ± 35.14, P=0.001). Our data suggest that increased MVD could be used to predict skeletal-EMDR, which is associated with inferior survival in patients with MM who have skeletal-EMD at diagnosis.


Assuntos
Microvasos/patologia , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Neovascularização Patológica/patologia , Adulto , Idoso , Neoplasias Ósseas/patologia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos
13.
Bioinformatics ; 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30165565

RESUMO

Summary: admetSAR was developed as a comprehensive source and free tool for the prediction of chemical ADMET properties. Since its first release in 2012 containing 27 predictive models, admetSAR has been widely used in chemical and pharmaceutical fields. This update, admetSAR 2.0, focuses on extension and optimization of existing models with significant quantity and quality improvement on training data. Now 47 models are available for both drug discovery and environmental risk assessment. In addition, we added a new module named ADMETopt for lead optimization based on predicted ADMET properties. Availability: Free available on the web at http://lmmd.ecust.edu.cn/admetsar2/. Supplementary information: Supplementary data are available at Bioinformatics online.

14.
Toxicol Res (Camb) ; 7(2): 211-220, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30090576

RESUMO

Genotoxicity tests can detect compounds that have an adverse effect on the process of heredity. The in vivo micronucleus assay, a genotoxicity test method, has been widely used to evaluate the presence and extent of chromosomal damage in human beings. Due to the high cost and laboriousness of experimental tests, computational approaches for predicting genotoxicity based on chemical structures and properties are recognized as an alternative. In this study, a dataset containing 641 diverse chemicals was collected and the molecules were represented by both fingerprints and molecular descriptors. Then classification models were constructed by six machine learning methods, including the support vector machine (SVM), naïve Bayes (NB), k-nearest neighbor (kNN), C4.5 decision tree (DT), random forest (RF) and artificial neural network (ANN). The performance of the models was estimated by five-fold cross-validation and an external validation set. The top ten models showed excellent performance for the external validation with accuracies ranging from 0.846 to 0.938, among which models Pubchem_SVM and MACCS_RF showed a more reliable predictive ability. The applicability domain was also defined to distinguish favorable predictions from unfavorable ones. Finally, ten structural fragments which can be used to assess the genotoxicity potential of a chemical were identified by using information gain and structural fragment frequency analysis. Our models might be helpful for the initial screening of potential genotoxic compounds.

15.
Eye Contact Lens ; 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30067519

RESUMO

PURPOSE: To compare the visual and refractive outcomes of transepithelial photorefractive keratectomy (Trans-PRK) and sub-Bowman femtosecond-assisted laser in situ keratomileusis (SBK). SETTING: University hospital. DESIGN: Retrospective, comparative study. METHODS: Two hundred forty patients with myopia and myopic astigmatism underwent SBK (n=157) or Trans-PRK (n=83). The main outcome measures included manifest spherical equivalent refraction (MRSE), logarithm of the minimum angle of resolution uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA), which were evaluated at 1 and 3 months postoperatively. RESULTS: The preoperative mean MRSE was -4.00±1.2 diopters (D) and -4.05±1.36 D (P=0.76) in Trans-PRK and SBK groups, respectively. There was a significant improvement in UCVA after Trans-PRK (1.29-0.00 at 1 month and -0.05 at 3 months; P<0.001 for both) and SBK (1.25 to -0.04 at 1 month and -0.05 at 3 months; P<0.001 for both). Both UCVA and BCVA were better after SBK compared with Trans-PRK at 1 month (-0.07 vs. -0.03; P<0.001) but not at 3 months (-0.08 vs. -0.07; P=0.223). The patients in Trans-PRK group were significantly more hyperopic compared with those in the SBK group at 1 month (0.11 vs. 0.04; P=0.034) and 3 months (0.11 vs. 0.04; P=0.011) postoperatively. Subgroup analysis showed that patients with myopia >3 diopters were more hyperopic at 1 month postoperatively as compared to patients with myopia of ≤3 diopters. CONCLUSIONS: Both Trans-PRK and SBK are effective procedures to correct mild to moderate myopia and myopic astigmatism. Patients undergoing SBK experience quick visual recovery. Both procedures had no difference in visual outcomes 3 months postoperatively.

16.
Front Pharmacol ; 9: 668, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997503

RESUMO

Traditional Chinese medicine (TCM) is typically prescribed as formula to treat certain symptoms. A TCM formula contains hundreds of chemical components, which makes it complicated to elucidate the molecular mechanisms of TCM. Here, we proposed a computational systems pharmacology approach consisting of network link prediction, statistical analysis, and bioinformatics tools to investigate the molecular mechanisms of TCM formulae. Taking formula Tian-Ma-Gou-Teng-Yin as an example, which shows pharmacological effects on Alzheimer's disease (AD) and its mechanism is unclear, we first identified 494 formula components together with corresponding 178 known targets, and then predicted 364 potential targets for these components with our balanced substructure-drug-target network-based inference method. With Fisher's exact test and statistical analysis we identified 12 compounds to be most significantly related to AD. The target genes of these compounds were further enriched onto pathways involved in AD, such as neuroactive ligand-receptor interaction, serotonergic synapse, inflammatory mediator regulation of transient receptor potential channel and calcium signaling pathway. By regulating key target genes, such as ACHE, HTR2A, NOS2, and TRPA1, the formula could have neuroprotective and anti-neuroinflammatory effects against the progression of AD. Our approach provided a holistic perspective to study the relevance between TCM formulae and diseases, and implied possible pharmacological effects of TCM components.

17.
J Agric Food Chem ; 66(27): 7015-7022, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29916239

RESUMO

Carapax Trionycis (the shell of the turtle Pelodiscus sinensis) was hydrolyzed by six different commercial proteases. The hydrolysate prepared from papain showed stronger inhibitory activity against angiotensin I-converting enzyme (ACE) than other extracts. Two noncompetitive ACE inhibitory peptides were purified successively by ultrafiltration, gel filtration chromatography, ion exchange column chromatography, and high-performance liquid chromatography (HPLC). The amino acid sequences of them were identified as KRER and LHMFK, with IC50 values of 324.1 and 75.6 µM, respectively, confirming that Carapax Trionycis is a potential source of active peptides possessing ACE inhibitory activities. Besides, both enzyme kinetics and isothermal titration calorimetry (ITC) assay showed that LHMFK could form more stable complex with ACE than KRER, which is in accordance with the better inhibitory activity of LHMFK.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Peptídeos/farmacologia , Tartarugas , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos/métodos , Hidrólise , Concentração Inibidora 50 , Peptídeo Hidrolases/metabolismo , Peptídeos/química , Peptídeos/isolamento & purificação , Hidrolisados de Proteína/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Relação Estrutura-Atividade
18.
Toxicol Sci ; 165(2): 396-407, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29893961

RESUMO

Avoidance of structural alerts (SAs) might reduce the risk of failure in drug discovery. However, there are still some marketed drugs containing SA, which indicates that SA should be analyzed carefully to avoid their excessive uses. Several detection systems, including automatic mining methods and expert systems, have been developed to identify SA. These methods only focus on toxic compounds that support the SA without consideration of nontoxic ones. Here, we proposed a frequency-based substructure detection protocol that learns from the nontoxic compounds containing SA to get nontoxic substructures (NTSs), whose appearance will reduce the probability of a compound becoming toxic. Kazius and Hansen's Ames mutagenicity dataset was used as an example to demonstrate the protocol. SARpy and ToxAlerts were first employed to obtain the potential SA. Then 2 kinds of NTS were exploited: reverse effect substructures (RESs) and conjugate effect substructures. Contribution and prediction performance of the substructures were evaluated via neural network and rule-based methods. We also compared substructure-based methods with the conventional machine learning-based methods. The results demonstrated that most substructures contributed as supposed and substructure-based methods performed better in the resistance of overfitting. This work indicated that the protocol could effectively reduce the false positive rate in prediction of chemical mutagenicity, and possibly extend to other endpoints.

19.
Medicine (Baltimore) ; 97(25): e11182, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924034

RESUMO

RATIONALE: Sporotrichosis is the most common subcutaneous mycosis. It is caused by the dimorphic fungus Sporothrix schenckii. Ocular sporotrichosis is uncommon and has been rarely reported. PATIENT CONCERNS: We describe a 34-year-old female who presented with a nodule increasing in size near the medial angle of the left eye. Originally, she was misdiagnosed with a dacryocyst space-occupying lesion, and the lesion was removed by surgery. DIAGNOSES: Findings of fungal structures in the histopathological examination contributed to the diagnosis of Sporothrix dacryocystitis. Further culture of conjunctival secretions and contact lens storage solution was positive for Sporothrix. INTERVENTIONS: She was treated with oral itraconazole, 200 mg by mouth twice daily. OUTCOMES: After 3 months of treatment with oral itraconazole, culture of the conjunctival secretions was negative. LESSONS: It is of paramount importance to clinically suspect mycosis, even in unusual locations or in the absence of the typical epidemiological history.


Assuntos
Dacriocistite/etiologia , Itraconazol/uso terapêutico , Sporothrix/isolamento & purificação , Esporotricose/complicações , Adulto , Antifúngicos/uso terapêutico , Lentes de Contato Hidrofílicas/microbiologia , Dacriocistite/tratamento farmacológico , Dacriocistite/patologia , Dacriocistite/cirurgia , Erros de Diagnóstico , Feminino , Humanos , Itraconazol/administração & dosagem , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/etiologia , Sporothrix/efeitos dos fármacos , Esporotricose/tratamento farmacológico , Esporotricose/patologia , Resultado do Tratamento
20.
Front Chem ; 6: 129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29688231

RESUMO

[This corrects the article on p. 30 in vol. 6, PMID: 29515993.].

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