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1.
Biosci Rep ; 39(9)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31427481

RESUMO

Preeclampsia (PE) is the main cause of maternal death in primipara, and commonly results in severe maternal and neonatal complications such as multiple organ dysfunction syndrome. However, the exact pathogenesis of this disease remains unclear. Circular RNAs (circRNAs) are noncoding RNAs that have been shown to be extensively involved in numerous physiological processes, but there is limited knowledge of their functions and mechanisms in PE. In the present study, we found the expression of a circRNA, hsa_circ_0088227 (circRNA of pregnancy-associated plasma protein A, circPAPPA), was down-regulated in both placenta and plasma samples from subjects with PE. Knockdown of circPAPPA led to decreased proliferation and invasion in HTR8-S/Vneo trophoblast cells. miR-384 was identified as a direct target of circPAPPA, and the gene encoding signal transducer and activator of transcription 3 (STAT3) was targeted by miR-384. We found that miR-384 was unregulated in PE, and overexpression of miR-384 could inhibit cell proliferation and invasion. In addition, we showed that the expression of STAT3 was decreased with knockdown of circPAPPA or the overexpression of miR-384 in trophoblast cells, but this decrease was partially reversed when co-transfection was performed with mimics of miR-384 inhibitor and si-circPAPPA. Together, these results suggest that down-regulation of circPAPPA facilitates the onset and development of PE by suppressing trophoblast cells, with involvement of the miR-384/STAT3 signaling pathway. Our study significantly increases the understanding of the occurrence and development of PE, and also provides a molecular target for the treatment of this disorder.

2.
Curr Top Med Chem ; 19(16): 1464-1483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264549

RESUMO

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.


Assuntos
Imunoterapia , Terapia de Alvo Molecular , Neoplasias/metabolismo , Neoplasias/terapia , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/metabolismo , Humanos , Receptores Acoplados a Proteínas-G/metabolismo , Bibliotecas de Moléculas Pequenas/química
3.
Oncol Rep ; 42(1): 115-130, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180554

RESUMO

Borax is a boron compound that is becoming widely recognized for its biological effects, including lipid peroxidation, cytotoxicity, genotoxicity, antioxidant activity and potential therapeutic benefits. However, it remains unknown whether exposure of human liver cancer (HepG2) cells to borax affects the gene expression of these cells. HepG2 cells were treated with 4 mM borax for either 2 or 24 h. Gene expression analysis was performed using Affymetrix GeneChip Human Gene 2.0 ST Arrays, which was followed by gene ontology analysis and pathway analysis. The clustering result was validated using reverse transcription­quantitative polymerase chain reaction. A cell proliferation assay was performed using Celigo Image Cytometer Instrumentation. Following this, 2­ or 24­h exposure to borax significantly altered the expression level of a number of genes in HepG2 cells, specifically 530 genes (384 upregulated and 146 downregulated) or 1,763 genes (1,044 upregulated and 719 downregulated) compared with the control group, respectively (≥2­fold; P<0.05). Twenty downregulated genes were abundantly expressed in HepG2 cells under normal conditions. Furthermore, the growth of HepG2 cells was inhibited through the downregulation of PRUNE1, NBPF1, PPcaspase­1, UPF2 and MBTPS1 (≥1.5­fold, P<0.05). The dysregulated genes potentially serve important roles in various biological processes, including the inflammation response, stress response, cellular growth, proliferation, apoptosis and tumorigenesis/oncolysis.

4.
Chemosphere ; 232: 345-355, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31158629

RESUMO

The semi-pilot scale bioleaching of electroplating sludge by the moderately thermophilic acidophilic consortium was carried out for the first time. During the microbial cultivation, Leptospirillum ferriphilum CS13, Acidithiobacillus caldus S2, and Sulfobacillus acidophilus CS5 could grow rapidly in a 300 L aeration packed reactor, in which the total suspended cell concentration could fluctuate around 3 × 108 cells/mL and the community structure remained relatively stable. During the bioleaching process, the microbial stock solution could effectively leach heavy metals from electroplating sludge in a stirred reactor within a few hours. Meanwhile, the effects of pH, temperature, the quantity of active culture, and liquid-solid ratio on the bioleaching behavior were also investigated. The optimal conditions for electroplating sludge bioleaching were pH 1.5, temperature 45 °C, bacterial liquid ratio 40%, liquid-solid ratio 4:1 L kg-1, and leaching time 5 h. The total removal rate of various heavy metals in electroplating sludge was over 99%. The bioleaching residue was successfully passed the TCLP test, and the total contents of heavy metals in the residue were also well below the regulatory criteria. In addition, the XRD analysis of the bioleaching residue was also confirmed that the moderately thermophilic consortium bioleaching provided a cleaner process than chemical leaching on the removal of the residual fraction metals, which was feasible and attractive for industrial treatment of electroplating sludge.


Assuntos
Galvanoplastia , Eliminação de Resíduos/métodos , Acidithiobacillus , Bactérias , Reatores Biológicos , Concentração de Íons de Hidrogênio , Metais Pesados/análise , Projetos Piloto , Temperatura Ambiente
5.
J Immunol ; 202(4): 1219-1228, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30642981

RESUMO

The appropriate inflammatory response is essential for normal wound repair, and skin commensal Staphylococcus epidermidis has been shown to regulate TLR3-mediated inflammatory response to maintain skin homeostasis after injury. However, the underlying mechanism by which S. epidermidis regulates wound-induced inflammation remains largely unexplored. In this study we identified a previously unknown lipopeptide 78 (LP78) from S. epidermidis and showed that LP78 inhibited TLR3-mediated skin inflammation to promote wound healing. Skin injury activated TLR3/NF-κB to promote the interaction of p65 and PPARγ in nuclei and then initiated the inflammatory response in keratinocytes. LP78 activated TLR2-SRC to induce ß-catenin phosphorylation at Tyr654 The phospho-ß-catenin translocated into nuclei to bind to PPARγ, thus disrupting the interaction between p65 and PPARγ. The disassociation between p65 and PPARγ reduced the expression of TLR3-induced inflammatory cytokines in skin wounds of normal and diabetic mice, which correlated with accelerated wound healing. Our data demonstrate that S. epidermidis-derived LP78 inhibits skin inflammation to promote wound healing and suggest that LP78 might be a potential compound for the treatment of delayed or unhealed wounds.


Assuntos
Inflamação/tratamento farmacológico , Lipopeptídeos/farmacologia , Pele/efeitos dos fármacos , Staphylococcus epidermidis/química , beta Catenina/metabolismo , Animais , Células Cultivadas , Humanos , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Pele/metabolismo , Cicatrização/efeitos dos fármacos
6.
Lab Chip ; 19(6): 974-983, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30694285

RESUMO

In melanoma surgery, it is difficult to identify residual scattered tumor cells at the surgical margin because of invasive growth. Mohs surgery, widely applied to increase the cure rate and decrease the recurrence rate of melanoma, involves examination of the tissue for tumor cells after tissue removal. Here, we established a liquid biopsy platform for rapid (<5 h), sensitive examination of residual tumor cells at the margin after Mohs surgery using clinical samples from patients with pigment nevus for a demonstration. The design involved highly sensitive, selective rare target cell separation from surgical margin lavage fluid (SMLF) through micropore-arrayed filtration. High recovery rates (86.7% ± 16.3% and 72.7% ± 46.7%, respectively) for separation of spiked 5 A375s (cultured human melanoma cells) and 1 A375 from 1 mL PBS were achieved for this platform. Detection of SMLF samples from patients with pigment nevus was performed, and many (66-7420) Melan-A-positive target cells were successfully recovered and identified, demonstrating the application performance of this rapid liquid biopsy for Mohs surgery in clinical practice. Moreover, a high-selectivity separation of larger target A375 cells from smaller background Jurkat cells was achieved with a high enrichment factor (4.2 ± 1.1). In clinical practice, high selectivity contributes to effective depletion of red blood cells (RBCs), thus ensuring verification of target cells from samples with severe RBC contamination. Furthermore, target cells were obtained with high purity (2.7-35.2%). The capability of this method for rare-cell separation with a high recovery rate and good selectivity may facilitate improvement of performance of Mohs surgery for real clinical practice, including shortening examination time and increasing detection sensitivity.


Assuntos
Separação Celular/métodos , Biópsia Líquida , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Linhagem Celular Tumoral , Humanos , Margens de Excisão , Melanoma/patologia , Microfluídica , Cirurgia de Mohs , Pele/patologia , Neoplasias Cutâneas/patologia
7.
Exp Biol Med (Maywood) ; : 1535370218813525, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458645

RESUMO

IMPACT STATEMENT: The abnormal expression of many regulatory factors may be involved in the development of PE. circRNAs are proved to have a series of important biological functions; however, reports about circRNA and PE are rare. In this work, we evaluated the profile analysis of circRNAs in human placenta of PE by RNA-seq and found some newly differentially expressed circRNAs which might be involved in PE. Combined with bioinformatics analysis, their possible functions were preliminarily discussed.

8.
Acta Pharmacol Sin ; 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30315252

RESUMO

Tamoxifen (TMX) is an antiestrogen drug that is used in the treatment and prevention of all stages of estrogen-dependent breast cancer. Adverse effects of TMX include hepatotoxicity. In this study, we investigated the therapeutic effects of osthole, isolated from medicinal plants especially Fructus Cnidii, on TMX-induced acute liver injury in mice. Mice were injected with osthole (100 mg/kg, ip) or vehicle, followed by TMX (90 mg/kg, ip) 24 h later. We showed that a single injection of TMX-induced liver injury and oxidative stress. Pretreatment with osthole attenuated TMX-induced liver injury evidenced by dose-dependent reduction of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Pretreatment with osthole also blunted TMX-induced oxidative stress, evidenced by significant increase of reduced glutathione (GSH) as well as reduction of malondialdehyde (MDA) and hydrogen peroxide (H2O2). Consistently, osthole significantly enhanced the expressions of antioxidant genes (GPX1, SOD2, GCL-c, and G6pdh), but suppressed those of pro-oxidant genes (NOX2 and ACOX). Furthermore, osthole inhibited the production of inflammatory cytokines, reduced the metabolic activation of TMX, and promoted its clearance. We further revealed that osthole elevated hepatic cAMP and cGMP levels, but inhibition of PKA or PKG failed to abolish the hepatoprotective effect of osthole. Meanwhile, prominent phosphorylation of p38 was observed in liver in response to TMX, which was significantly inhibited by osthole. Pretreatment with SB203580, a p38 inhibitor, significantly attenuated TMX-induced increase of ALT and AST activities, reduced oxidative stress, and reversed the alterations of gene expression caused by TMX. Moreover, pretreatment with L-buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, partly reversed the effect of osthole on TMX-induced liver injury. Consistently, pretreatment with N-acetyl-L-cysteine (NAC) significantly attenuated TMX-induced increase in ALT and AST activities. Notably, both BSO and NAC had no detectable effect on the phosphorylation levels of p38. Collectively, our results suggest that osthole prevents TMX hepatotoxicity by suppressing p38 activation and subsequently reducing TMX-induced oxidative damage.

9.
Sci Adv ; 4(3): eaar3979, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29740603

RESUMO

Ultrasonic imaging has been implemented as a powerful tool for noninvasive subsurface inspections of both structural and biological media. Current ultrasound probes are rigid and bulky and cannot readily image through nonplanar three-dimensional (3D) surfaces. However, imaging through these complicated surfaces is vital because stress concentrations at geometrical discontinuities render these surfaces highly prone to defects. This study reports a stretchable ultrasound probe that can conform to and detect nonplanar complex surfaces. The probe consists of a 10 × 10 array of piezoelectric transducers that exploit an "island-bridge" layout with multilayer electrodes, encapsulated by thin and compliant silicone elastomers. The stretchable probe shows excellent electromechanical coupling, minimal cross-talk, and more than 50% stretchability. Its performance is demonstrated by reconstructing defects in 3D space with high spatial resolution through flat, concave, and convex surfaces. The results hold great implications for applications of ultrasound that require imaging through complex surfaces.

10.
PLoS One ; 12(12): e0190160, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29272304

RESUMO

Exercise has been recommended to improve motor function in Parkinson patients, but its value in altering progression of disease is unknown. In this study, we examined the neuroprotective effects of running wheel exercise in mice. In adult wild-type mice, one week of running wheel activity led to significantly increased DJ-1 protein concentrations in muscle and plasma. In DJ-1 knockout mice, running wheel performance was much slower and Rotarod performance was reduced, suggesting that DJ-1 protein is required for normal motor activity. To see if exercise can prevent abnormal protein deposition and behavioral decline in transgenic animals expressing a mutant human form of α-synuclein in all neurons, we set up running wheels in the cages of pre-symptomatic animals at 12 months old. Activity was monitored for a 3-month period. After 3 months, motor and cognitive performance on the Rotarod and Morris Water Maze were significantly better in running animals compared to control transgenic animals with locked running wheels. Biochemical analysis revealed that running mice had significantly higher DJ-1, Hsp70 and BDNF concentrations and had significantly less α-synuclein aggregation in brain compared to control mice. By contrast, plasma concentrations of α-synuclein were significantly higher in exercising mice compared to control mice. Our results suggest that exercise may slow the progression of Parkinson's disease by preventing abnormal protein aggregation in brain.


Assuntos
Cognição , Modelos Animais de Doenças , Atividade Motora , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Condicionamento Físico Animal , alfa-Sinucleína/metabolismo , Animais , Comportamento Animal , Encéfalo , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/sangue , Proteínas de Choque Térmico HSP70/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Proteína Desglicase DJ-1/sangue , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismo , alfa-Sinucleína/genética
11.
Exp Ther Med ; 13(6): 3529-3534, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28587437

RESUMO

Rapid growth of residual tumors can occur as a result of their recurrence and progression. The present study aimed to investigate the expression of hypoxia inducible factor-2 subunit α (HIF-2α), vascular endothelial growth factor A (VEGFA), erythropoietin-producing hepatocellular A2 (EphA2) and angiogenesis in residual hepatocellular carcinoma (HCC), following treatment with high-intensity focused ultrasound (HIFU) ablation, in order to investigate the association between protein expression and tumor recurrence and growth. Athymic BALB/c (nu/nu) mice were subcutaneously inoculated with the HCC cell line HepG2, in order to create xenograft tumors. Approximately 30 days post-inoculation, eight mice were treated with HIFU, whereas eight mice received no treatment and acted as the control group. Residual tumor tissues were obtained from the experimental groups after one month. Levels of HIF-2α, VEGFA, EphA2 and cluster of differentiation 31 (CD31) expression was measured by immunohistochemical staining. CD31-positive vascular endothelial cells were counted to calculate microvascular density (MVD), and western blot analysis was performed to determine levels of HIF-2α, VEGFA, and EphA2 protein. It was found that the expression levels of HIF-2α, VEGFA, EphA2, and MVD proteins in residual HCC tissues were significantly higher than in the control group tissues (P<0.05). Tumor MVD was strongly correlated with VEGFA (R=0.957, P<0.01) and EphA2 (R=0.993, P<0.01) protein expression levels. Furthermore, there was a significant positive correlation between HIF-2α and EphA2 expression (R=0.991, P<0.01). The correlation between VEGFA and EphA2 expression was also positive (R=0.985, P<0.01). These data suggest that overexpression of HIF-2α, VEGFA and EphA2 is related to angiogenesis in residual HCC following HIFU ablation, potentially via their association with key mediators of recurrence.

12.
Phys Chem Chem Phys ; 19(20): 12749-12758, 2017 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-28484752

RESUMO

Nanothermites offer high energy density and high burn rates, but are mechanistically only now being understood. One question of interest is how initiation occurs and how the ignition temperature is related to microscopic controlling parameters. In this study, we explored the potential role of oxygen ion transport in Bi2O3 as a controlling mechanism for condensed phase ignition reaction. Seven different doped δ-Bi2O3 were synthesized by aerosol spray pyrolysis. The ignition temperatures of Al/doped Bi2O3, C/doped Bi2O3 and Ta/doped Bi2O3 were measured by temperature-jump/time-of-flight mass spectrometer coupled with a high-speed camera respectively. These results were then correlated to the corresponding oxygen ion conductivity (directly proportional to ion diffusivity) for these doped Bi2O3 measured by impedance spectroscopy. We find that ignition of thermite with doped Bi2O3 as oxidizer occurs at a critical oxygen ion conductivity (∼0.06 S cm-1) of doped Bi2O3 in the condensed-phase so long as the aluminum is in a molten state. These results suggest that oxygen ion transport limits the condensed state Bi2O3 oxidized thermite ignition. We also find that the larger oxygen vacancy concentration and the smaller metal-oxide bond energy in doped Bi2O3, the lower the ignition temperature. The latter suggests that we can consider the possibility of manipulating microscopic properties within a crystal, to tune the resultant energetic properties.

13.
Biochem Biophys Res Commun ; 482(4): 1207-1212, 2017 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-27923653

RESUMO

Tyrosylprotein sulfotransferases (TPSTs) are Golgi-resident enzymes that catalyze the transfer of a sulfuryl group to the side chain hydroxyl of tyrosine residues. Sulfotyrosine residues are involved in protein-protein interactions in the extracellular space. These interactions are important for chemokines to bind cognate receptor, for cell adhesion and trafficking, and for pathogen entry into cells. To better understand the role of TPSTs in cellular processes and disease states, we are interested in identifying small molecules to modulate TPST activity in experimental systems. Towards that end, we developed a fluorescent peptide assay for TPST2 activity. Here, we demonstrate that this assay can be used to screen the 1280 compound LOPAC library in a 384-well format and in a high-throughput manner. We identified 19 primary hits for a hit rate of 1.5%. Three of the primary hits were verified by dose-response assay and confirmed as inhibitors by a secondary mass spectrometry assay for TPST activity. One hit, suramin, possessed inhibitory properties consistent with a competitive inhibitor of substrate binding and molecular docking revealed a good fit into the TPST2 substrate-binding pocket. This assay can be used to screen larger libraries to identify small molecules that inhibit TPST sulfotransferase activity.


Assuntos
Sulfotransferases/antagonistas & inibidores , Sulfotransferases/química , Suramina/química , Baculoviridae , Cromatografia Líquida , Técnicas de Química Combinatória , Relação Dose-Resposta a Droga , Fluorescência , Humanos , Concentração Inibidora 50 , Isoenzimas/química , Cinética , Simulação de Acoplamento Molecular , Peptídeos/química , Especificidade por Substrato , Espectrometria de Massas em Tandem
14.
Sci Rep ; 6: 33434, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27633259

RESUMO

Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and migration assays of human umbilical vein endothelial cells (HUVECs) in vitro. A structure-activity relationship (SAR) study was carried out and optimization toward this series of compounds resulted in the discovery of N-(3-methoxyphenyl)-4-methyl-2-(2-propyl-4-pyridinyl)thiazole-5-carboxamide (3k). The results indicated that compound 3k showed similar or better effects compared to Vandetanib in suppressing HUVECs colony formation and migration as well as VEGF-induced angiogenesis in the aortic ring spreading model and chick embryo chorioallantoic membrane (CAM) model. More importantly, compound 3k also strongly blocked tumor growth with the dosage of 30 mg/kg/day, and subsequent mechanism exploration suggested that this series of compounds took effect mainly through angiogenesis signaling pathways. Together, these results suggested compound 3k may serve as a lead for a novel class of angiogenesis inhibitors for cancer treatments.


Assuntos
Descoberta de Drogas , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Transdução de Sinais , Tiazóis/uso terapêutico , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Embrião de Galinha , Ensaio de Unidades Formadoras de Colônias , Desenho de Drogas , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Nus , Neoplasias/patologia , Neovascularização Patológica/patologia , Fosforilação/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Ratos Sprague-Dawley , Fibras de Estresse/efeitos dos fármacos , Fibras de Estresse/metabolismo , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia , Cicatrização/efeitos dos fármacos
15.
PLoS One ; 11(8): e0160847, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27512998

RESUMO

Parkinson's disease is characterized by the death of dopaminergic neurons in the substantia nigra. To understand the molecular mechanisms of the disease, an in vitro model is important. In the 1990s, we used the SV40 large T antigen to immortalize dopaminergic neurons derived from Embryonic Day 14 rat mesencephalon. We selected a clone for its high expression of dopaminergic neuron markers such as tyrosine hydroxylase (TH), and we named it 1RB3AN27 (N27). Because the original N27 cell line has been passaged many times, the line has become a mixture of cell types with highly variable expression of TH. In the current study, we have performed multiple rounds of clonal cultures and have identified a dopaminergic cell clone expressing high levels of TH and the dopamine transporter (DAT). We have named this new clone N27-A. Nearly 100% of N27-A cells express TH, DAT and Tuj1. Western blots have confirmed that N27-A cells have three to four times the levels of TH and DAT compared to the previous mixed population in N27. Further analysis has shown that the new clone expresses the dopamine neuron transcription factors Nurr1, En1, FoxA2 and Pitx3. The N27-A cells express the vesicular monoamine transporter (VMAT2), but do not express dopamine-beta-hydroxylase (DßH), the enzyme responsible for converting dopamine to norepinephrine. Functional analysis has shown that N27-A cells are more sensitive than N27 cells to neurotoxins taken up by the dopamine transporter such as 6-hydroxydopamine and 1-methyl-4-phenylpyridine (MPP+). The DAT inhibitor nomifensine can block MPP+ induced toxicity. The non-selective toxic effects of hydrogen peroxide were similar in both cell lines. The N27-A cells show dopamine release under basal and depolarization conditions. We conclude that the new N27-A clone of the immortalized rat dopaminergic cell line N27 should provide an improved in vitro model for Parkinson's disease research.


Assuntos
Linhagem Celular , Clonagem Molecular , Doença de Parkinson/patologia , Animais , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Fator 3-beta Nuclear de Hepatócito/metabolismo , Proteínas de Homeodomínio/metabolismo , Mesencéfalo/citologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Ratos , Fatores de Transcrição/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo
16.
Nat Commun ; 7: 12332, 2016 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-27515900

RESUMO

Nanoparticles hosted in conductive matrices are ubiquitous in electrochemical energy storage, catalysis and energetic devices. However, agglomeration and surface oxidation remain as two major challenges towards their ultimate utility, especially for highly reactive materials. Here we report uniformly distributed nanoparticles with diameters around 10 nm can be self-assembled within a reduced graphene oxide matrix in 10 ms. Microsized particles in reduced graphene oxide are Joule heated to high temperature (∼1,700 K) and rapidly quenched to preserve the resultant nano-architecture. A possible formation mechanism is that microsized particles melt under high temperature, are separated by defects in reduced graphene oxide and self-assemble into nanoparticles on cooling. The ultra-fast manufacturing approach can be applied to a wide range of materials, including aluminium, silicon, tin and so on. One unique application of this technique is the stabilization of aluminium nanoparticles in reduced graphene oxide film, which we demonstrate to have excellent performance as a switchable energetic material.

17.
Thromb Res ; 144: 165-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27352239

RESUMO

INTRODUCTION: Information about the incidence and risk factors of venous thromboembolism (VTE) after thyroid operation is limited. This study aimed to analyze the incidence and risk factors of postoperative VTE in patients who had undergone thyroid surgery. MATERIALS AND METHODS: A prospective, multi-center cohort study was performed from June 2013 to June 2015 in 3 hospitals throughout South Central China. We analyzed 5029 patients who had undergone thyroid operation and received no VTE prophylaxis postoperatively. For the diagnosis of deep vein thrombosis (DVT), bilateral whole-leg ultrasound was conducted in patients with a high pretest probability of DVT. Lung ventilation/perfusion scintigraphy, pulmonary angiography, or helical computed tomography was implemented in patients suspected to have pulmonary embolism (PE). RESULTS: DVT was diagnosed in 18 patients (0.36%). No patient was diagnosed with PE. Binomial logistic regression analysis revealed that age and left lower limb intraoperative venous access (IVA) were significant risk factors for DVT. The incidence of DVT increased as the number of risk factors increased. CONCLUSIONS: VTE is uncommon in patients who have undergone thyroid surgery. The left lower limb was not an appropriate insertion site IVA. Pharmacologic thromboprophylaxis was not mandatory, particularly in those patients without risk factors.


Assuntos
Extremidade Inferior/irrigação sanguínea , Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tromboembolia Venosa/etiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Estudos Prospectivos , Fatores de Risco
18.
Int J Mol Med ; 37(6): 1465-74, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27082928

RESUMO

FcγRIIIa (CD16) is a low-affinity Fc receptor of IgG. As the idio-binding receptor of IgG Fc, it plays an important role in the antibody-dependent cellular cytotoxicity of natural killer cells. The aim of the present study was to investigate the distribution of Kupffer cells (KCs) and the expression of their surface receptor FcγRIIIa in hepatocellular carcinoma. Furthermore, we also aimed to observe the functional mechanism of FcγRIIIa. Immunohistochemical analysis was employed to study KCs and FcγRIIIa. In order to explore the role of FcγRIIIa in the growth of cancer cells, KCs and H22 tumor cells were co-cultured in different serum. The mRNA expression levels of tumor necrosis factor (TNF)-α and FcγRIIIa were analyzed by RT-qPCR; the TNF-α and FcγRIIIa protein expression levels were examined by enzyme­linked immunosorbent assay and western blot analysis, respectively. Our results showed that the number of Kuppfer cells in cancerous tissues (21.6±7.8) was lower than those in para-cancerous (68.8±9.1) tissues and adjacent normal hepatic tissues (62.0±1.9) (P<0.01); this decreased with the reduction in the differentiation degree of cancer (P<0.05). FcγRIIIa-positive cells were similar in morphology to KCs, and their distributive tendency was coincident (P<0.05). The increase in CD16a mRNA levels in the group treated with immune serum was 3.9-, 4.9- and 3.9-fold greater than that in the ordinary serum group at different time points, and CD16a protein expression also markedly increased (P<0.05). However, these effects were inhibited by the addition of anti-IgG Fc serum (P<0.05). The results of the present study suggested that FcγRIIIa resided in KCs, and it contributed to the inhibition of the growth of liver tumor cells.


Assuntos
Carcinoma Hepatocelular/imunologia , Hepatócitos/imunologia , Macrófagos do Fígado/imunologia , Neoplasias Hepáticas/imunologia , RNA Mensageiro/imunologia , Receptores de IgG/imunologia , Animais , Anticorpos Anti-Idiotípicos/farmacologia , Ascite/genética , Ascite/imunologia , Ascite/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Comunicação Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Soros Imunes/farmacologia , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Cultura Primária de Células , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , Receptores de IgG/antagonistas & inibidores , Receptores de IgG/genética , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
Am J Respir Cell Mol Biol ; 55(3): 439-49, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27093578

RESUMO

Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.


Assuntos
Células Epiteliais Alveolares/metabolismo , Citoproteção , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Desglicase DJ-1/metabolismo , Fumar/efeitos adversos , Adenoviridae/metabolismo , Aldeídos/metabolismo , Células Epiteliais Alveolares/patologia , Apoptose/genética , Separação Celular , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteína Desglicase DJ-1/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Mol Med Rep ; 13(4): 3213-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26935255

RESUMO

Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell­cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death­inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV­TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans­retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in­vitro and in­vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. The gene expression of HSV­TK transfected by ultrasound wave irradiation in the HepG2 cells was quantified using reverse transcription­quantitative polymerase chain reaction analysis. The effects on cell death were assessed using an MTT assay. The protein expression levels of Cx32 in ATRA­untreated or ATRA­treated tissues were quantified by immunohistochemical analysis and Western blot assays. The HSV­TK gene was successfully transfected into the HepG2 cell using ultrasound wave irradiation, and was stably expressed. Compared with the other groups, the HSV­TK gene group treated with ATRA exhibited an increased number of apoptotic cells (P<0.05) and improved tumor suppression (P<0.05). ATRA significantly increased the expression of Cx32 in the hepatoma tissues (P<0.01). The present study demonstrated that ATRA elevated the protein expression of Cx32 and enhanced the bystander effect of the HSV­TK/GCV suicide gene therapy system, which may provide a potential strategy for hepatocellular carcinoma treatment.


Assuntos
Apoptose/efeitos dos fármacos , Conexinas/metabolismo , Tretinoína/farmacologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Western Blotting , Efeito Espectador , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Conexinas/genética , Ganciclovir , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simplexvirus/genética , Timidina Quinase/genética , Transfecção , Transplante Heterólogo , Tretinoína/uso terapêutico
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