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1.
Adv Healthc Mater ; 9(1): e1901187, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31800164

RESUMO

Highly efficient and stimulus-responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid-triggered charge-reversible graphene-based all-in-one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co-transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR-21 (miR-21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted as GPCP/miR-21i/ICG) effectively protects miR-21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR-21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid-triggered charge reversal effect. Typically, the released miR-21i downregulate the endogenous miR-21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA-MB-231 triple-negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR-21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene-photo combined treatment of cancer, especially for intractable TNBC.

2.
Front Mol Biosci ; 6: 121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737645

RESUMO

Macromolecular complexes are essential to intracellular signal transduction by creating signaling niches and enabling a chain of reactions that transmit external signals into various cellular responses. Analysis of SMYD3 interactome indicates this protein lysine methyltransferase might be involved in calcium dependent signaling pathways through forming complexes with the phospholipase PLCB3, calcium/calmodulin dependent kinase CAMK2B, or calcineurin inhibitor RCAN3. SMYD3 is well-known as a histone H3K4 methyltransferase involved in epigenetic transcriptional regulation; however, any roles SMYD3 may play in signaling transduction remain unknown. KEGG pathway enrichment analysis reveals the SMYD3 interacting proteins are overrepresented in several signaling pathways such as estrogen signaling pathway, NOD-like receptor signaling pathway, and WNT signaling pathway. Sequence motif scanning reveals a significant enrichment of PXLXP motif in SMYD3 interacting proteins. The MYND domain of SMYD3 is known to bind to the PXLXP motif. The enrichment of the PXLXP motif suggests that the MYND domain is likely to be a key interaction module that mediates formation of some SMYD3 complexes. The presence of the PXLXP motifs in PLCB3 and CAMK2B indicates the potential role of the MYND domain in mediating complex formation in signaling. The structural basis of SMYD3 MYND domain-mediated interactions is unknown. The only available MYND-peptide complex structure suggests the MYND domain-mediated interaction is likely transient and dynamic. The transient nature will make this domain well-suited to mediate signaling transduction processes where it may allow rapid responses to cellular perturbations and changes in environment.

3.
Medicine (Baltimore) ; 98(46): e17996, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725666

RESUMO

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.


Assuntos
Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/fisiopatologia , Asma/epidemiologia , Asma/fisiopatologia , Índice de Massa Corporal , Bronquite Crônica/epidemiologia , Bronquite Crônica/fisiopatologia , Fumar Cigarros/epidemiologia , Progressão da Doença , Dispneia/epidemiologia , Humanos , Estudos Observacionais como Assunto , Fenótipo , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória
4.
Medicine (Baltimore) ; 98(22): e15776, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145299

RESUMO

OBJECTIVE: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD). METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis. RESULTS: Six studies (combined n = 415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P < .001, I = 69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P < .001, I = 15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P < .01, I = 0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P < .001, I = 0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P < .001, I = 0]; 6-minute walk test (6MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P < .001, I = 32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P < .05, I = 72%]. CONCLUSION: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6MWT distance, and SGRQ score.


Assuntos
Ansiedade/terapia , Depressão/terapia , Doença Pulmonar Obstrutiva Crônica/psicologia , Qigong/métodos , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/diagnóstico , Depressão/etiologia , Autoavaliação Diagnóstica , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória , Inquéritos e Questionários , Resultado do Tratamento , Teste de Caminhada
5.
Biomaterials ; 205: 106-119, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30913486

RESUMO

Currently, photoimmunotherapy based on a theranostic nanoplatform emerges as a promising modality in advanced cancer therapy. In this study, a new type of versatile nanoassemblies (denoted as PC@GCpD(Gd)) was rationally designed by integrating the polydopamine stabilized graphene quantum dots (GQD)-photosensitizer nanocomposites (denoted as GCpD), immunostimulatory polycationic polymer/CpG oligodeoxynucleotide (CpG ODN) nanoparticles (denoted as PC) and Gd3+/Cy3 imaging probes for dual magnetic resonance/fluorescence imaging-guided photoimmunotherapy. PC@GCpD(Gd) effectively killed the tumor cells through the amplified photothermal and photodynamic effects mediated by GCpD, and contemporaneously delivered CpG ODN to the targeted endosomal Toll-like receptor 9 (TLR9) to continuously stimulate the secretion of proinflammatory cytokines and the maturation of dendritic cells, thereby resulting in the activation and infiltration of T lymphocytes. As a result, PC@GCpD(Gd) achieved robust inhibition efficiency to almost completely suppress the EMT6 murine mammary cancer model under laser irradiation, implying the superior synergy of combined photoimmunotherapy. Moreover, the in vivo delivery and biodistribution of PC@GCpD(Gd) could be tracked using the high-quality bimodal magnetic resonance imaging/fluorescence imaging. This study highlighted the potent prospect of hybrid PC@GCpD(Gd) nanoassemblies for precise cancer photoimmunotherapy with a cascading effect.

6.
BMC Ophthalmol ; 18(1): 170, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30005593

RESUMO

BACKGROUND: Fungal keratitis (FK) is a sight-threatening disease, accounting for a significant portion with its complex presentation, suboptimal efficacy of the existing therapies and uncontrollable excessive innate inflammation. Phospholipase C-γ2 (PLCγ2) is a non-receptor tyrosine kinase that plays an important role at the early period of innate immunity. This study aimed to identify the role of PLCγ2 in Dectin-1-mediated Ca2+ Flux and its effect on the expression of proinflammatory mediators at the exposure to Aspergillus fumigatus (A. fumigatus) hyphae antigens in human corneal epithelial cells (HCECs). METHODS: The HCECs were preincubated with or without different inhibitors respectively before A. fumigatus hyphae stimulation. Intracellular calcium flux in HCECs and levels of PLCγ2 and spleen-tyrosine kinase (Syk) were detected by fluorescence imaging and Western Blotting. The expression of proinflammatory mediators was determined by reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: We demonstrated that an intracellular Ca2+ flux in HCECs was triggered by A. fumigatus hyphae and could be reduced by pre-treatment with PLCγ2-inhibitor U73122. A. fumigatus hyphae induced PLCγ2 phosphorylation was regulated by Dectin-1 via Syk. Furthermore, PLCγ2-deficient HCECs showed a drastic impairment in the Ca2+ signaling and the secretion of IL-6, CXCL1 and TNF-α. CONCLUSIONS: PLCγ2 plays a critical role for Ca2+ Flux in HCECs stimulated by A. fumigatus hyphae. Syk acts upstream of PLCγ2 in the Dectin-1 signaling pathway. The expressions of proinflammatory mediators induced by A. fumigatus are regulated by the activation of Dectin-1-mediated PLCγ2 signaling pathway in HCECs.


Assuntos
Aspergillus fumigatus/imunologia , Cálcio/metabolismo , Citocinas/biossíntese , Epitélio Anterior/metabolismo , Regulação da Expressão Gênica , Imunidade Inata/genética , Fosfolipase C gama/genética , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Epitélio Anterior/patologia , Infecções Oculares Fúngicas/genética , Infecções Oculares Fúngicas/imunologia , Infecções Oculares Fúngicas/metabolismo , Humanos , Fosfolipase C gama/biossíntese , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
7.
PLoS One ; 13(1): e0191371, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29346419

RESUMO

The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through directly binding to farnesylated Ras. It recruits farnesylated Ras to the non-lipid-raft membrane for interaction with downstream effectors. However, the cytosolic domain of NgBR itself is only partially folded. The lack of several conserved secondary structural elements makes this domain unlikely to form a complete farnesyl binding pocket. We find that inclusion of the extracellular and transmembrane domains that contain additional conserved residues to the cytosolic region results in a well folded protein with a similar size and shape to the E.coli cis-isoprenyl transferase (UPPs). Small Angle X-ray Scattering (SAXS) analysis reveals the radius of gyration (Rg) of our NgBR construct to be 18.2 Å with a maximum particle dimension (Dmax) of 61.0 Å. Ab initio shape modeling returns a globular molecular envelope with an estimated molecular weight of 23.0 kD closely correlated with the calculated molecular weight. Both Kratky plot and pair distribution function of NgBR scattering reveal a bell shaped peak which is characteristic of a single globularly folded protein. In addition, circular dichroism (CD) analysis reveals that our construct has the secondary structure contents similar to the UPPs. However, this result does not agree with the currently accepted topological orientation of NgBR which might partition this construct into three separate domains. This discrepancy suggests another possible NgBR topology and lends insight into a potential molecular basis of how NgBR facilitates farnesylated Ras recruitment.


Assuntos
Receptores de Superfície Celular/química , Sequência de Aminoácidos , Sítios de Ligação , Membrana Celular/metabolismo , Dicroísmo Circular , Citosol/metabolismo , Peso Molecular , Estrutura Secundária de Proteína , Receptores de Superfície Celular/metabolismo , Espalhamento a Baixo Ângulo , Homologia de Sequência de Aminoácidos , Solubilidade , Difração de Raios X
8.
AIMS Biophys ; 4(4): 557-575, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29051919

RESUMO

To date, X-ray crystallography remains the gold standard for the determination of macromolecular structure and protein substrate interactions. However, the unpredictability of obtaining a protein crystal remains the limiting factor and continues to be the bottleneck in determining protein structures. A vast amount of research has been conducted in order to circumvent this issue with limited success. No single method has proven to guarantee the crystallization of all proteins. However, techniques using antibody fragments, lipids, carrier proteins, and even mutagenesis of crystal contacts have been implemented to increase the odds of obtaining a crystal with adequate diffraction. In addition, we review a new technique using the scaffolding ability of PDZ domains to facilitate nucleation and crystal lattice formation. Although in its infancy, such technology may be a valuable asset and another method in the crystallography toolbox to further the chances of crystallizing problematic proteins.

9.
Oncol Lett ; 14(1): 977-980, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693261

RESUMO

Leiomyosarcomas (LMSs) originating from the wall of blood vessels are aggressive and rare neoplasms. The current study describes a case of a 52-year-old man who presented with intermittent abdominal pain without weight loss or diarrhea. Computed tomography of the abdomen identified a 4-cm, solid, heterogeneous tumor in the tail of the pancreas, while a hypodense lesion was also noted in the right hepatic lobe. The patient subsequently underwent splenic pedicle tumor resection, splenectomy and liver tumor resection. Notably, immunohistochemical and histological analyses identified LMS, which had originated from the smooth muscle of the splenic vein. Currently available information regarding LMSs of the splenic vein and their management is also discussed, with the aim of improving diagnostic accuracy.

10.
Angew Chem Int Ed Engl ; 56(35): 10462-10466, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28677259

RESUMO

Structural colors have profound implications in the fields of pigments, displays and sensors, but none of the current non-iridescent photonic materials can restore their functions after mechanical damage. Herein, we report the first self-healable organogel nanocomposites with angle-independent structural colors. The organogel nanocomposites were prepared through the co-assembly of oleophilic silica nanoparticles, silicone-based supramolecular gels, and carbon black. The organogel system enables amorphous aggregation of silica nanoparticles and the angle-independent structural colors in the nanocomposites. Moreover, the hydrogen bonding in the supramolecular gel provides self-healing ability to the system, and the structural colored films obtained could heal themselves in tens of seconds to restore storage modulus, structural color, and surface slipperiness from mechanical cuts or shear failure repeatedly.

11.
Colloids Surf B Biointerfaces ; 154: 383-390, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28384617

RESUMO

Enhancing the affinity of scaffolds for endothelial cell (EC) is a crucial procedure for promoting angiogenesis in tissue engineering. In this work, to achieve stronger binding affinity with ECs, the peptide sequence REDV was conjugated onto gold nanoparticles (AuNPs) to construct a multivalent ligand (cREDV). Then, the EC adhesion and proliferation were studied to determine ligand affinity for ECs in vitro. The results show that the cREDV-modified alginate (cREDV-ALG) surface exhibited a selective adhesion to human umbilical vein endothelial cells (HUVECs) compared with NIH 3T3 cells. The average area of individual HUVEC that adhered to cREDV-ALG was approximately 2.27-fold higher than that adhered to the monovalent REDV-modified alginate (REDV-ALG) surface. Additionally, a superior ability to promote the proliferation of HUVECs compared to the REDV-ALG surface was demonstrated. In vivo angiogenic assays were also carried out to assess the effect of multivalent strategy on the vascularization of scaffolds. The results illustrated that cREDV-ALG could stimulate new vessel formation in the scaffold, and the blood vessel density was at least 20% higher than that observed with monovalent REDV-ALG with a similar degree of ligand substitution. These results demonstrated that a multivalent ligand strategy was beneficial for the vascularization of engineered tissues.


Assuntos
Alginatos/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Tecidos Suporte , Adsorção , Alginatos/química , Animais , Proliferação de Células/efeitos dos fármacos , Feminino , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ouro/química , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis , Ligantes , Nanopartículas Metálicas/química , Camundongos , Células NIH 3T3 , Oligopeptídeos/química , Ratos , Ratos Wistar , Engenharia Tecidual
12.
Cardiovasc Res ; 113(6): 620-632, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453729

RESUMO

Aims: To resolve the controversy as to whether periostin plays a role in myocardial regeneration after myocardial infarction (MI), we created a neonatal mouse model of MI to investigate the influence of periostin ablation on myocardial regeneration and clarify the underlying mechanisms. Methods and results: Neonatal periostin-knockout mice and their wildtype littermates were subjected to MI or sham surgery. In the wildtype mice after MI, fibrosis was detectable at 3 days and fibrotic tissue was completely replaced by regenerated myocardium at 21 days. In contrast, in the knockout mice, significant fibrosis in the infarcted area was present at even 3 weeks after MI. Levels of phosphorylated-histone 3 and aurora B in the myocardium, detected by immunofluorescence and western blotting, were significantly lower in knockout than in wildtype mice at 7 days after MI. Similarly, angiogenesis was decreased in the knockout mice after MI. Expression of both the endothelial marker CD-31 and α-smooth muscle actin was markedly lower in the knockout than in wildtype mice at 7 days after MI. The knockout MI group had elevated levels of glycogen synthase kinase (GSK) 3ß and decreased phosphatidylinositol 3-kinase (PI3K), phosphorylated serine/threonine protein kinase B (p-Akt), and cyclin D1, compared with the wildtype MI group. Similar effects were observed in experiments using cultured cardiomyocytes from neonatal wildtype or periostin knockout mice. Administration of SB216763, a GSK3ß inhibitor, to knockout neonatal mice decreased myocardial fibrosis and increased angiogenesis in the infarcted area after MI. Conclusion: Ablation of periostin suppresses post-infarction myocardial regeneration by inhibiting the PI3K/GSK3ß/cyclin D1 signalling pathway, indicating that periostin is essential for myocardial regeneration.


Assuntos
Moléculas de Adesão Celular/deficiência , Ciclina D1/metabolismo , Infarto do Miocárdio/enzimologia , Miocárdio/enzimologia , Fosfatidilinositol 3-Quinase/metabolismo , Regeneração , Proteínas Repressoras/metabolismo , Transdução de Sinais , Animais , Animais Recém-Nascidos , Moléculas de Adesão Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Neovascularização Fisiológica , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regeneração/efeitos dos fármacos , Proteínas Repressoras/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
13.
Biochem Biophys Res Commun ; 485(2): 529-534, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28179147

RESUMO

The CXC chemokine receptor 2 (CXCR2) is a G protein coupled receptor mediating interleukin-8 chemotactic signaling and plays an important role in neutrophil mobility and tumor migration. However, efficient CXCR2 signaling requires PDZ domain-mediated scaffolding of signaling complexes at the plasma membrane and functional coupling of the signaling to specific downstream signaling pathways, in which only one PDZ protein has been characterized to interact with CXCR2. Here, we identified five novel CXCR2-binding PDZ-containing proteins, among which PDZ-RhoGEF is of particular interest because this PDZ and RGS-containing guanine nucleotide exchange factor (GEF) is also involved in cell signaling and mobility. To reveal the molecular basis of the interaction, we solved the crystal structure of PDZ-RhoGEF PDZ domain in complex with the CXCR2 C-terminal PDZ binding motif. The structure reveals that the PDZ-CXCR2 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four CXCR2 residues contributing to specific interactions. Structural comparison of CXCR2-binding PDZ domains and PDZ-RhoGEF PDZ bound with different ligands reveals PDZ- and ligand-specific interactions that may underlie the ability of promiscuous CXCR2 binding by different PDZ domains and PDZ binding promiscuity. The structure also reveals an unexpected asymmetric disulfide bond-linked PDZ dimer that allows simultaneous parallel binding of CXCR2 to two PDZ domains. This study provides not only the structural basis for PDZ-mediated CXCR2-PDZ-RhoGEF interaction, but also a new mode of PDZ dimerization, which both could prove valuable in understanding signaling complex scaffolding in CXCR2 signaling and coupling to specific signaling pathways.


Assuntos
Domínios PDZ , Multimerização Proteica , Receptores de Interleucina-8B/química , Fatores de Troca de Nucleotídeo Guanina Rho/química , Sequência de Aminoácidos , Sítios de Ligação/genética , Cristalografia por Raios X , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Modelos Moleculares , Ligação Proteica , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Homologia de Sequência de Aminoácidos
14.
Sci Total Environ ; 574: 1000-1011, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27668852

RESUMO

Road networks affect the spatial structure of urban landscapes, and with continuous expansion, it will also exert more widespread influences on the regional ecological environment. With the support of geographic information system (GIS) technology, based on the application of various spatial analysis methods, this study analyzed the spatiotemporal changes of road networks and landscape ecological risk in the research area of Beijing to explore the impacts of road network expansion on ecological risk in the urban landscape. The results showed the following: 1) In the dynamic processes of change in the overall landscape pattern, the changing differences in landscape indices of various landscape types were obvious and were primarily related to land-use type. 2) For the changes in a time series, the expansion of the road kernel area was consistent with the extension of the sub-low-risk area in the urban center, but some differences were observed during different stages of development. 3) For the spatial position, the expanding changes in the road kernel area were consistent with the grade changes of the urban central ecological risk, primarily because both had a certain spatial correlation with the expressways. 4) The influence of road network expansion on the ecological risk in the study area had obvious spatial differences, which may be closely associated with the distribution of ecosystem types.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Transportes , Pequim , Cidades , Ecologia , Sistemas de Informação Geográfica , Medição de Risco
15.
Front Plant Sci ; 7: 1394, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27708655

RESUMO

Seed aging is a process that results in a delayed germination, a decreased germination percentage, and finally a total loss of seed viability. However, the mechanism of seed aging is poorly understood. In the present study, Yliangyou 2 hybrid rice (Oryza sativa L.) seeds were artificially aged at 100% relative humidity and 40°C, and the effect of artificial aging on germination, germination time course and the change in protein profiles of embryo and endosperm was studied to understand the molecular mechanism behind seed aging. With an increasing duration of artificial aging, the germination percentage and germination rate of hybrid rice seeds decreased. By comparing the protein profiles from the seeds aged for 0, 10 and 25 days, a total of 91 and 100 protein spots were found to show a significant change of more than 2-fold (P < 0.05) in abundance, and 71 and 79 protein spots were identified, in embryos and endosperms, respectively. The great majority of these proteins increased in abundance in embryos (95%) and decreased in abundance in endosperms (99%). In embryos, most of the identified proteins were associated with energy (30%), with cell defense and rescue (28%), and with storage protein (18%). In endosperms, most of the identified proteins were involved in metabolism (37%), in energy (27%), and in protein synthesis and destination (11%). The most marked change was the increased abundance of many glycolytic enzymes together with the two fermentation enzymes pyruvate decarboxylase and alcohol dehydrogenase in the embryos during aging. We hypothesize that the decreased viability of hybrid rice seeds during artificial aging is caused by the development of hypoxic conditions in the embryos followed by ethanol accumulation.

16.
Cardiovasc Diabetol ; 15(1): 136, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27659110

RESUMO

BACKGROUND: Left ventricular (LV) dysfunction is closely associated with LV hypertrophy or diabetes, as well as insufficient autophagic flux. Acute or chronic hyperglycemia is a prognostic factor for patients with myocardial infarction. However, the effect of acute hyperglycemia on LV dysfunction of the hypertrophic heart and the mechanisms involved are still unclear. This study aimed to confirm our hypothesis that either acute or chronic hyperglycemia suppresses LV diastolic function and autophagic flux. METHODS: The transverse aortic constriction (TAC) model and streptozocin-induced type 1 diabetic mellitus mice were used. LV function was evaluated with a Millar catheter. Autophagic levels and autophagic flux in the whole heart and cultured neonatal rat cardiomyocytes in response to hyperglycemia were examined by using western blotting of LC3B-II and P62. We also examined the effect of an autophagic inhibitor on LC3B-II and P62 protein expression and LC3 puncta. RESULTS: In mice with TAC, we detected diastolic dysfunction as early as 30 min after TAC. This dysfunction was indicated by a greater LV end-diastolic pressure and the exponential time constant of LV relaxation, as well as a smaller maximum descending rate of LV pressure in comparison with sham group. Similar results were also obtained in mice with TAC for 2 weeks, in addition to increased insulin resistance. Acute hyperglycemic stress suppressed diastolic function in mice with myocardial hypertrophy, as evaluated by invasive LV hemodynamic monitoring. Mice with chronic hyperglycemia induced by streptozocin showed myocardial fibrosis and diastolic dysfunction. In high glucose-treated cardiomyocytes and streptozocin-treated mice, peroxisome proliferator-activated receptor-γ coactivator 1α was downregulated, while P62 was upregulated. Autophagic flux was also significantly inhibited in response to high glucose exposure in angiotensin-II treated cardiomyocytes. CONCLUSIONS: Acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes.

17.
Fish Shellfish Immunol ; 58: 210-219, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27591045

RESUMO

White spot syndrome virus (WSSV) infects all shrimp species and is the greatest detriment to shrimp culture. To better understand the mechanism of molecular responses to WSSV infection in "Huanghai No. 2" Fenneropenaeus chinensis, a microarray technique was used. Microarray gene expression profiling of 59,137 unigenes identified Differentially Expressed Genes (DEGs) both in live and moribund shrimp at early, peak and late phases. In live shrimp, 1307, 1479 and 1539 DEGs were obtained in the early, peak and late phase, respectively. Meanwhile, 1536, 2181 and 1591 DEGs were obtained in moribund shrimp. Twenty known annotation genes are uniquely expressed in the late phase of live shrimp, including adhesion regulating molecule 1, arginine kinase, BUD31 homolog, and QM. Compared to WSSV-susceptible shrimp, 75 known annotation genes are uniquely expressed in WSSV-resistant shrimp, including arginine kinase, BUD31 homolog, clottable protein 2, caspase 2, cathepsin C, calnexin, HMGBb, Histone 3, and selenoprotein M. The gene expression patterns of the infected shrimp were altered by WSSV infection. To further confirm the expression of differentially expressed genes, real-time RT-PCR was performed to test six randomly selected genes. The data will provide valuable information to understand the immune mechanism of shrimp's response to WSSV.


Assuntos
Proteínas de Artrópodes/genética , Análise de Sequência com Séries de Oligonucleotídeos , Penaeidae/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/metabolismo , Regulação da Expressão Gênica/imunologia , Hepatopâncreas/imunologia , Penaeidae/imunologia , Penaeidae/virologia , Reação em Cadeia da Polimerase , Transcriptoma
18.
PLoS One ; 11(6): e0158514, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27355349

RESUMO

High-mobility group box1 (HMGB1) exerts effects on inflammation by binding to receptor for advanced glycation end products (RAGE) or Toll-like receptor 4. Considering that inflammation is involved in pressure overload-induced cardiac hypertrophy, we herein attempted to investigate whether HMGB1 plays a role in myocardial hypertrophy in RAGE knockout mice as well as in the growth and apoptosis of cardiomyocytes. The myocardial expression of RAGE was not significantly changed while TLR4 mRNA was upregulated in response to transverse aortic constriction (TAC) for 1 week. The myocardial expression of HMGB1 protein was markedly increased in TAC group when compared to the sham group. Heart weight to body weight ratio (HW/BW) and lung weight to body weight ratio (LW/BW) were evaluated in RAGE knockout (KO) and wild-type (WT) mice 1 week after TAC. Significant larger HW/BW and LW/BW ratios were found in TAC groups than the corresponding sham groups, but no significant difference was found between KO and WT TAC mice. Similar results were also found when TAC duration was extended to 4 weeks. Cultured neonatal rat cardiomyocytes were treated with different concentrations of recombinant HMGB1, then cell viability was determined using MTT and CCK8 assays and cell apoptosis was determined by Hoechst staining and TUNEL assay. The results came out that HMGB1 exerted no influence on viability or apoptosis of cardiomyocytes. Besides, the protein expression levels of Bax and Bcl2 in response to different concentrations of HMGB1 were similar. These findings indicate that HMGB1 neither exerts influence on cardiac remodeling by binding to RAGE nor induces apoptosis of cardiomyocytes under physiological condition.


Assuntos
Cardiomegalia , Proteína HMGB1/metabolismo , Miocárdio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Aorta/patologia , Apoptose , Sobrevivência Celular , Células Cultivadas , Dano ao DNA , Homozigoto , Masculino , Camundongos , Camundongos Knockout , Miócitos Cardíacos/citologia , Tamanho do Órgão , Ratos , Receptor 4 Toll-Like/metabolismo
19.
Regul Toxicol Pharmacol ; 74: 117-22, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26619782

RESUMO

The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 µg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 µg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 µg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 µg/kg/day, which is approximately 250 times above the therapeutic dosage.


Assuntos
Compostos de Bifenilo/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Feto/efeitos dos fármacos , Lignanas/toxicidade , Fármacos Neuroprotetores/toxicidade , Animais , Compostos de Bifenilo/administração & dosagem , Relação Dose-Resposta a Droga , Embrião de Mamíferos/patologia , Emulsões , Feminino , Feto/patologia , Idade Gestacional , Injeções Intravenosas , Lignanas/administração & dosagem , Exposição Materna , Fármacos Neuroprotetores/administração & dosagem , Nível de Efeito Adverso não Observado , Gravidez , Ratos Sprague-Dawley , Medição de Risco
20.
Sci Rep ; 5: 15480, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26486652

RESUMO

Transgene insertions might have unintended side effects on the transgenic host, both crop and hybrids with wild relatives that harbor transgenes. We employed proteomic approaches to assess protein abundance changes in seeds from Bt-transgenic oilseed rape (Brassica napus) and its hybrids with wild mustard (B. juncea). A total of 24, 15 and 34 protein spots matching to 23, 13 and 31 unique genes were identified that changed at least 1.5 fold (p < 0.05, Student's t-test) in abundance between transgenic (tBN) and non-transgenic (BN) oilseed rape, between hybrids of B. juncea (BJ) × tBN (BJtBN) and BJ × BN (BJBN) and between BJBN and BJ, respectively. Eight proteins had higher abundance in tBN than in BN. None of these proteins was toxic or nutritionally harmful to human health, which is not surprising since the seeds are not known to produce toxic proteins. Protein spots varying in abundance between BJtBN and BJBN seeds were the same or homologous to those in the respective parents. None of the differentially-accumulated proteins between BJtBN and BJBN were identical to those between tBN and BN. Results indicated that unintended effects resulted from transgene flow fell within the range of natural variability of hybridization and those found in the native host proteomes.


Assuntos
Brassica napus/genética , Proteínas de Plantas/biossíntese , Plantas Geneticamente Modificadas/genética , Proteômica , Brassica napus/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fluxo Gênico , Hibridização Genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Transgenes
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