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2.
Bioorg Chem ; 91: 103148, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376784

RESUMO

A series of new peptidomimetics targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was identified based on the potent and selective pentapeptide Plk1 PBD inhibitor PLHSpT. Unnatural amino acid residues were introduced to the newly designed compound and the N-terminal substituent of the peptidomimetic was investigated. The optimized compound 9 inhibited the Plk1 PBD with IC50 of 0.267 µM and showed almost no inhibition to Plk2 PBD or Plk3 PBD at 100 µM. Biolayer interferometry studies demonstrated that compound 9 showed potent binding affinity to Plk1 with a Kd value of 0.164 µM, while no Kd were detected against Plk2 and Plk3. Compound 9 showed improved stability in rat plasma compared to PLHSpT. Binding mode analysis was performed and in agreement with the observed experimental results. There are only two natural amino acids remained in the chemical structure of 9. This study may provide new information for further research on Plk1 PBD inhibitors.

3.
Drug Des Devel Ther ; 13: 2081-2096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417240

RESUMO

Purpose: To investigate the mitochondria-related mechanism of Gynura segetum (GS)-induced apoptosis and the protective effect of phosphocreatine (PCr), a mitochondrial respiration regulator. Methods: First, the mechanism was explored in human hepatocyte cell line. The mitochondrial oxidative stress was determined by fluorescence assay. The level of sirtuin 3 (SIRT3), acetylated superoxide dismutase 2 (Ac-SOD2), SOD2, and apoptosis were detected by Western blotting. Mito-TEMPO and cell lines of viral vector-mediated overexpression of SIRT3 and SIRT3H248Y were used to further verify the mechanism of GS-induced apoptosis. GS-induced liver injury mice models were built by GS through intragastric administration and interfered by PCr through intraperitoneal injection. A total of 30 C57BL/6J mice were assigned to 5 groups and treated with either saline, PCr (100 mg/kg), GS (30 g/kg), or PCr (50 or 100 mg/kg)+GS (30 g/kg). Liver hematoxylin and eosin (HE) staining, immunohistochemical analysis, and blood biochemical evaluation were performed. Results: GS induced hepatocyte apoptosis and elevated levels of mitochondrial ROS in L-02 cells. The expression of SIRT3 was decreased. Downregulation of SIRT3 was associated with increased levels of Ac-SOD2, which is the inactivated enzymatic form of SOD2. Conversely, when overexpressing SIRT3 in GS-treated cells, SOD2 activity was restored, and mitochondrial ROS levels and hepatocyte apoptosis declined. Upon administration of PCr to GS-treated cells, they exhibited a significant upregulation of SIRT3 and were protected against apoptosis. In animal experiments, serum ALT level and mitochondrial ROS of the mice treated with GS and 50 mg/kg PCr were significantly attenuated compared with only GS treated. The changes in SIRT3 expression were also consistent with the in vitro results. In addition, immunohistochemical analysis of the mouse liver showed that Ac-SOD2 was decreased in the PCr and GS co-treated group compared with GS treated group. Conclusion: GS caused liver injury by dysregulating mitochondrial ROS generation via a SIRT3-SOD2 pathway. PCr is a potential agent to treat GS-induced liver injury by mitochondrial protection.

4.
J Oral Rehabil ; 2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31378989

RESUMO

BACKGROUND: Orofacial function is usually impaired by temporomandibular disorders (TMDs). Several studies on TMDs have used the Jaw Functional Limitation Scale (JFLS) to assess mandibular dysfunction. However, it was originally created in English and hence needs to be validated for use among Chinese people. OBJECTIVE: To develop a Chinese version of the JFLS for Chinese TMD patients and to investigate the validity and reliability of the scale. METHODS: Content validity and temporal stability were evaluated at two different occasions. The reliability and validity of the JFLS were tested in 483 TMD patients. Cronbach's alpha coefficient and split-half reliability were used to assess internal consistency, while the validity was evaluated by factor analysis. RESULTS: Three factors were extracted during exploratory factor analysis, accounting for 62.39% of the variance. The three-factor model was then measured using confirmatory factor analysis (Chi-square/df = 3.6, root mean square error of approximation = 0.091, comparative fit index =0.896). Internal (coefficient alpha values of 0.906 for all items and Guttman split-half reliability of 0.756) and test-retest (intra-class correlation coefficient =0.851-0.897, 95% confidence interval =0.656-0.950) reliabilities were excellent. CONCLUSION: The Chinese version of the JFLS is reliable and valid for use in Chinese TMD patients. This article is protected by copyright. All rights reserved.

6.
Food Chem ; 300: 125209, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344629

RESUMO

Turbot can induce allergy in susceptible individuals due to the presence of parvalbumin (PV), a major fish allergen. This study aimed at evaluating the digestibility and the ability of PV to elicit the release of cellular degranulation, following treatment with tyrosinase (PV-Tyr), caffeic acid (PV-CA) and in combination (PV-Tyr/CA), using in vitro digestion and RBL-2H3 (passive rat basophil leukemia) cell line. The digestion assay products revealed that the stability of PV in simulated gastric fluid (SGF) was stronger, while in simulated intestinal fluid (SIF) was rather weak. Western blot analysis revealed that the IgG-binding abilities of the cross-linked PV were markedly reduced. Moreover, crosslinking hampered the release of cellular degranulation process in RBL-2H3 cell lines. PV-Tyr/CA showed highly significant reduction in the release rate of ß-hexosaminidase (66.02%), histamine (35.01%), tryptase (29.25%), cysteinyl leukotrienes (29.72%), prostaglandin D2 (34.96%), IL-4 (43.99%) and IL-13 (38.93%) and shown potential in developing hypoallergenic fish products.

7.
BMC Genomics ; 20(1): 585, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311503

RESUMO

BACKGROUND: Ganoderma lucidum, one of the best-known medicinal mushrooms in the world, produces more than 400 different bioactive compounds. However, the regulation of these bioactive compounds biosynthesis is still unclear. Lysine succinylation is a critical post-translational modification and has many important functions in all aspects of eukaryotic and prokaryotic cells. Although it has been studied for a long time, its function is still unclear in G. lucidum. In this study, a global investigation was carried out on the succinylome in G. lucidum. RESULTS: In total, 382 modified proteins which contain 742 lysine succinylated sites were obtained. The proteomics data are available through ProteomeXchange with the dataset accession number PXD013954. Bioinformatics analysis revealed that the succinylated proteins were distributed in various cellular biological processes and participated in a great variety of metabolic pathways including carbon metabolism and biosynthesis of secondary metabolites. Notably, a total of 47 enzymes associated with biosynthesis of triterpenoids and polysaccharides were found to be succinylated. Furthermore, two succinylated sites K90 and K106 were found in the conserved Fve region of immunomodulatory protein LZ8. These observations show that lysine succinylation plays an indispensable role in metabolic regulation of bioactive compounds in G. lucidum. CONCLUSIONS: These findings indicate that lysine succinylation is related to many metabolic pathways, especially pharmacologically bioactive compounds metabolism. This study provides the first global investigation of lysine succinylation in G. lucidum and the succinylome dataset provided in this study serves as a resource to further explore the physiological roles of these modifications in secondary metabolism.

10.
J Colloid Interface Sci ; 553: 494-502, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31229868

RESUMO

We prepared ionic liquids (ILs) modified magnetic alginate nanoparticles and used these as supports for lipase immobilization. The novel supports were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1HNMR), vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and water contact angle (WCA) measurements. The immobilized lipase (PPL-IL-MSA) exhibited high activity, 2.1-fold higher than that compared to free lipase and 1.59-fold higher compared to immobilized lipase without IL (PPL-MSA). In addition, the pH and temperature application range of PPL-IL-MSA were both found to be broader than that of free lipase and PPL-MSA. The thermal stability, denaturation stability, and reusing stability of PPL-IL-MSA were also higher than those of other samples. After 10 times of reuse, the residual activity of PPL-IL-MSA was 89.7% higher than that of PPL-MSA (84.4%). Furthermore, the kinetic constant Km of PPL-IL-MSA was 13.7 mg/mL lower than that of free lipase (21.2 mg/mL) and PPL-MSA (18.4 mg/mL). Circular dichroism (CD) was used to study the secondary structure of enzymes in order to explain the mechanism of the performance improvement of PPL-IL-MSA. This work involving the development of a new supports for enzyme immobilization may serve as a reference for further studies in this field.

11.
Cell Cycle ; 18(16): 1938-1947, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234753

RESUMO

Acidic microenvironment is an important feature of solid tumors that contributes to malignant transformation. Low extracellular pH could promote epithelial-mesenchymal transition (EMT) thereby endowing tumor cells with higher invasive capability. However, the relation between EMT and tumor cell proliferation under long-term acidic condition is still not fully understood. Here, we show that tumor cells have undergone a phenotypic transition from EMT to mesenchymal-epithelial transition (MET) during adaptation to acidosis, and is closely related with cell proliferative state. Under early stage of acidic stress, tumor cells entered a non-cycling quiescent state with mesenchymal phenotype and expressed high level of stemness genes. Whereas, after long-term acid culture (2 months), acid-adapted cells resumed proliferating but lost mesenchymal phenotype. Further, our results show that the acid-adapted cells have distinct proliferative mechanism from non-acid cells, as the G1-S transcriptional factor E2F1 protein was not recovered in the adapted cells. Meanwhile, mini-chromosome maintenance 7 (MCM7) is shown to regulate the EMT to MET phenotypic transition, and is required for proliferation of the adapted cells under acidic condition. MCM7 Knockdown promoted mesenchymal phenotype and inhibited proliferation of the acid-adapted cells. While, MCM7 overexpression inhibited acid-induced EMT and supported tumor cell proliferation under acidic condition. Thus, our study provides evidence that tumor cells display phenotypic plasticity that allows them to survive acid stress.

12.
Food Chem ; 297: 124972, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253320

RESUMO

The aim of the present study was to evaluate Paralichthys olivaceus parvalbumin (PV) following treatment by laccase (LAC) in the presence of propyl gallate (PG) on the structure and potential allergenicity. The structure of LAC + PG treated PV was analyzed through SDS-PAGE, CD, fluorescence, and allergenicity was analyzed by immunological and cell model. Our results showed that LAC + PG treatment can induce structural changes through PV cross-linking. Western blotting and indirect ELISA analysis revealed the decrease in IgG binding capacity of PV, corresponding with the structural changes. The results of in vitro digestion illustrate that LAC + PG treated PV showed more resistance to gastrointestinal digestion compared to untreated PV. The release rate of ß-hexosaminidase and histamine decreased by 35.6% and 66.9%, respectively, with LAC + PG treatment by RBL-2H3 cell assay. Considering the wide utilization of LAC in food industry, our treatment reveals its potential for creation of hypoallergenic fish products under mild reaction conditions.


Assuntos
Alérgenos/imunologia , Proteínas de Peixes/imunologia , Linguados/imunologia , Lacase/metabolismo , Parvalbuminas/imunologia , Galato de Propila/química , Animais , Catálise , Reagentes para Ligações Cruzadas/química , Digestão , Ensaio de Imunoadsorção Enzimática , Proteínas de Peixes/química , Indústria Alimentícia , Histamina/metabolismo , Parvalbuminas/química , beta-N-Acetil-Hexosaminidases/metabolismo
13.
Nat Commun ; 10(1): 2500, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175298

RESUMO

Precise control of interlayer spacing and functionality is crucial in two-dimensional material based membrane separation technology. Here we show anion intercalation in protonated graphite phase carbon nitride (GCN) that tunes the interlayer spacing and functions of GCN-based membranes for selective permeation in aqueous/organic solutions. Sulfate anion intercalation leads to a crystalline and amphipathic membrane with an accessible interlayer spacing at ~10.8 Å, which allows high solvent permeability and sieves out the solutes with sizes larger than the spacing. We further extend the concept and illustrate the example of GCN-based chiral membrane via incorporating (1R)-(-)-10-camphorsulfonic anion into protonated GCN layers. The membrane exhibits a molecular weight cutoff around 150 among various enantiomers and highly enantioselective permeation towards limonene racemate with an enantiomeric excess value of 89%. This work paves a feasible way to achieve water purification and chiral separation technologies using decorated laminated membranes.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31187660

RESUMO

Background: Accurate registration for surgical navigation of laparoscopic surgery is highly challenging due to vessel deformation. Here, we describe the design of a deformable model with improved matching accuracy by applying the finite element method (FEM). Material and methods: ANSYS software was used to simulate an FEM model of the vessel after pull-up based on laparoscopic gastrectomy requirements. The central line of the FEM model and the central line of the ground truth were drawn and compared. Based on the material and parameters determined from the animal experiment, a perigastric vessel FEM model of a gastric cancer patient was created, and its accuracy in a laparoscopic gastrectomy surgical scene was evaluated. Results: In the animal experiment, the FEM model created with Ogden foam material exhibited better results. The average distance between the two central lines was 6.5mm, and the average distance between their closest points was 3.8 mm. In the laparoscopic gastrectomy surgical scene, the FEM model and the true artery deformation demonstrated good coincidence. Conclusion: In this study, a deformable vessel model based on FEM was constructed using preoperative CT images to improve matching accuracy and to supply a reference for further research on deformation matching to facilitate laparoscopic gastrectomy navigation.

15.
BMC Pediatr ; 19(1): 200, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208399

RESUMO

BACKGROUND: Noma is a rare disease, which is characterized by rapid progression and a high rate of mortality; however, relatively few cases of noma infection accompanied by septic shock in children have been described. Further, most health care professionals have no knowledge of this disease or of its clinical significance. CASE PRESENTATION: Herein, we present a case report of a six-year-old male patient who was diagnosed with noma infection at a Chinese pediatric medical intensive care unit (PMICU), at which time, it was discovered that he had septic shock. Following treatment by continuous renal replacement therapy (CRRT) for septic shock arising from noma, the patient was in generally good condition, and the local wound was seen to be essentially healed five weeks post-admission. CONCLUSION: Noma is an opportunistic infectious disease condition. Treatment of the acute phase of noma predominantly focuses on controlling the infection and improving systemic conditions. In addition, CRRT could be considered as a treatment option for cases that present with noma accompanied by septic shock.

17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(3): 256-261, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31030720

RESUMO

Objective To investigate the effect of saikosaponin D (SSD) on the proliferation and transformation of human embryonic lung fibroblasts (HELFs) induced by transforming growth factor-beta 1 (TGF-ß1) and the regulation of signal pathway of TGF-ß1/Smads family. Methods HELFs were cultured in vitro and divided into 5 groups: a control group, 1 ng/mL TGF-ß1-induced group, 1 ng/mL TGF-ß1 combined with 0.5 µmol/L SSD treatment group, 1 ng/mL TGF-ß1 combined with 1 µmol/L SSD treatment group, and 1 ng/mL TGF-ß1 combined with 2 µmol/L SSD treatment group. Cell viability of HELFs was detected by CCK-8 assay. The expression of Smad2, Smad3 and Smad7 mRNA were detected by real-time fluorescence quantitative PCR. The protein levels of α-smooth muscle actin (α-SMA), type 1 collagen (Col1), Smad2, Smad3, phosphorylated Smad2 (p-smad2), p-smad3 and Smad7 were assessed by Western blot analysis. Results Compared with the control group, TGF-ß1-induced group showed the apparently increased proliferation ability, the increased protein levels of Col1 and α-SMA, the significantly increased mRNA and protein phosphorylation levels of Smad2 and Smad3, and the significantly decreased mRNA and protein expression of Smad7. Compared with the TGF-ß1-induced group, the cell proliferation of HELFs in different concentrations of SSD treatment groups was reduced, which could reverse the changes of the above indicators in a dose-dependent manner. Conclusion SSD plays an important role in anti-pulmonary fibrosis by regulating TGF-ß1/Smads signaling pathway.


Assuntos
Transdução de Sinais , Proliferação de Células , Colágeno , Fibroblastos , Humanos , Proteína Smad2 , Proteína Smad3 , Fator de Crescimento Transformador beta1
18.
Medicine (Baltimore) ; 98(14): e14979, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946324

RESUMO

BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM. METHODS: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. RESULTS: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias. CONCLUSION: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Derrame Pleural/metabolismo , Biomarcadores Tumorais/metabolismo , Exsudatos e Transudatos/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Sensibilidade e Especificidade
19.
Brain Res ; 1717: 66-73, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30986407

RESUMO

Ischemic preconditioning (IPC) exerts protective effects against ischemic cerebral injury. In the present study, an in vitro model of cerebral ischemia (oxygen and glucose deprivation, OGD) was established to investigate the neuroprotective mechanism of IPC. We found that conditioned medium (C.M.) from astrocytes rather than neurons nor microglia cell line BV2 exerted neuroprotection. Moreover, exosomes derived from OGD preconditioned astrocytes can be taken up by neurons and attenuated OGD-induced neuron death and apoptosis. High-throughput microRNA (miRNA) sequencing revealed that miR-92b-3p levels in exosomes released from preconditioned astrocytes were increased. Overexpression of miR-92b-3p in neurons with miR-92b-3p mimic achieved the same protective effects as C.M. from astrocytes. Thus, we propose that the mechanism of IPC may associate with astrocytes, and that exosome-mediated miR-92b-3p shuttle from preconditioned astrocytes to neurons participate in these process.

20.
J Matern Fetal Neonatal Med ; : 1-5, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31018788

RESUMO

OBJECTIVE: To evaluate whether cell-free DNA (cfDNA) testing could replace an invasive procedure in pregnancies with isolated fetal omphalocele. STUDY DESIGN: This was a retrospective study of all pregnancies with sonographically detected fetal omphalocele at three tertiary referral centers between 2012 and 2016. Invasive diagnostic testing was performed for genetic investigations using conventional karyotyping or chromosomal microarray. cfDNA testing was assumed to be offered to patients with isolated fetal omphalocele for screening for common aneuploidies. RESULTS: Invasive genetic testing was performed in a total of 107 pregnancies with a fetal omphalocele. Abnormal karyotype was found in 66% (31/47) of nonisolated omphalocele cases and in 1.7% (1/60) of isolated omphalocele cases. No pathogenic copy number variations (CNVs) were detected in 59 cases with isolated omphalocele and normal karyotype. If cfDNA screening was used in cases with isolated omphalocele, the affected fetus with trisomy 18 would be detected, and no rare chromosomal aberrations or submicroscopic pathogenic CNVs would be missed. CONCLUSIONS: cfDNA testing could be recommended for prenatal genetic evaluation in pregnancies with isolated fetal omphalocele after thorough pretest counseling. Key Message: A very low percentage of aneuploidies and rare chromosomal/subchromosomal abnormalities are found in prenatal cases of isolated omphalocele. It seems that for pregnancies with isolated omphalocele, cfDNA testing represents an alternative for patients who choose to continue the pregnancies and are reluctant to undertake invasive diagnostic testing.

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