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1.
Plant J ; 117(5): 1377-1391, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38017590

RESUMO

Plant NAC transcription factors play a crucial role in enhancing cold stress tolerance, yet the precise molecular mechanisms underlying cold stress remain elusive. In this study, we identified and characterized CaNAC035, an NAC transcription factor isolated from pepper (Capsicum annuum) leaves. We observed that the expression of the CaNAC035 gene is induced by both cold and abscisic acid (ABA) treatments, and we elucidated its positive regulatory role in cold stress tolerance. Overexpression of CaNAC035 resulted in enhanced cold stress tolerance, while knockdown of CaNAC035 significantly reduced resistance to cold stress. Additionally, we discovered that CaSnRK2.4, a SnRK2 protein, plays an essential role in cold tolerance. In this study, we demonstrated that CaSnRK2.4 physically interacts with and phosphorylates CaNAC035 both in vitro and in vivo. Moreover, the expression of two ABA biosynthesis-related genes, CaAAO3 and CaNCED3, was significantly upregulated in the CaNAC035-overexpressing transgenic pepper lines. Yeast one-hybrid, Dual Luciferase, and electrophoretic mobility shift assays provided evidence that CaNAC035 binds to the promoter regions of both CaAAO3 and CaNCED3 in vivo and in vitro. Notably, treatment of transgenic pepper with 50 µm Fluridone (Flu) enhanced cold tolerance, while the exogenous application of ABA at a concentration of 10 µm noticeably reduced cold tolerance in the virus-induced gene silencing line. Overall, our findings highlight the involvement of CaNAC035 in the cold response of pepper and provide valuable insights into the molecular mechanisms underlying cold tolerance. These results offer promising prospects for molecular breeding strategies aimed at improving cold tolerance in pepper and other crops.


Assuntos
Ácido Abscísico , Capsicum , Ácido Abscísico/metabolismo , Resposta ao Choque Frio , Capsicum/fisiologia , Estresse Fisiológico/genética , Fosforilação , Folhas de Planta/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
2.
Angew Chem Int Ed Engl ; 63(10): e202318372, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38205971

RESUMO

The site-specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor-targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a "drug factory" that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene-caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.


Assuntos
Compostos Heterocíclicos , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/uso terapêutico , Lipossomos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doxorrubicina/uso terapêutico
3.
BMC Bioinformatics ; 24(1): 43, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759776

RESUMO

BACKGROUND: It remains an important challenge to predict the functional consequences or clinical impacts of genetic variants in human diseases, such as cancer. An increasing number of genetic variants in cancer have been discovered and documented in public databases such as COSMIC, but the vast majority of them have no functional or clinical annotations. Some databases, such as CiVIC are available with manual annotation of functional mutations, but the size of the database is small due to the use of human annotation. Since the unlabeled data (millions of variants) typically outnumber labeled data (thousands of variants), computational tools that take advantage of unlabeled data may improve prediction accuracy. RESULT: To leverage unlabeled data to predict functional importance of genetic variants, we introduced a method using semi-supervised generative adversarial networks (SGAN), incorporating features from both labeled and unlabeled data. Our SGAN model incorporated features from clinical guidelines and predictive scores from other computational tools. We also performed comparative analysis to study factors that influence prediction accuracy, such as using different algorithms, types of features, and training sample size, to provide more insights into variant prioritization. We found that SGAN can achieve competitive performances with small labeled training samples by incorporating unlabeled samples, which is a unique advantage compared to traditional machine learning methods. We also found that manually curated samples can achieve a more stable predictive performance than publicly available datasets. CONCLUSIONS: By incorporating much larger samples of unlabeled data, the SGAN method can improve the ability to detect novel oncogenic variants, compared to other machine-learning algorithms that use only labeled datasets. SGAN can be potentially used to predict the pathogenicity of more complex variants such as structural variants or non-coding variants, with the availability of more training samples and informative features.


Assuntos
Algoritmos , Neoplasias , Humanos , Aprendizado de Máquina , Neoplasias/genética , Bases de Dados Factuais , Aprendizado de Máquina Supervisionado
4.
Mol Divers ; 26(4): 2103-2120, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34661800

RESUMO

A new series of ocotillol-derived lactone derivatives were designed and synthesized to consider their antibacterial activity, structure-activity relationships (SARs), antibacterial mechanism and in vivo antibacterial efficacy. Compound 6d, which exhibited broad antibacterial spectrum, was found to be the most active with minimum inhibitory concentrations (MICs) of 1-2 µg/mL against Gram-positive bacteria and 8-16 µg/mL against Gram-negative bacteria. The subsequent synergistic antibacterial tests displayed that 6d had the ability to improve the susceptibility of MRSA USA300, B. subtilis 168, and E. coli DH5α to kanamycin and chloramphenicol. This active molecule 6d also induced bacterial resistance more slowly than norfloxacin and kanamycin. Furthermore, compound 6d was membrane active and low toxic against mammalian cells, and it could rapidly inhibit the growth of MRSA and E. coli and did not obviously trigger bacterial resistance. Compound 6d also displayed strong in vivo antibacterial activity against S. aureus RN4220 in murine corneal infection models. Additionally, absorption, distribution, metabolism, and excretion properties of this type of compounds have shown drug-likeness with good oral absorption and moderate blood-brain barrier permeability. The obtained results demonstrated that ocotillol-derived compounds are a promising class of antibacterial agents worthy of further study.


Assuntos
Escherichia coli , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Ginsenosídeos , Canamicina , Lactonas/farmacologia , Mamíferos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
5.
BMC Med Inform Decis Mak ; 22(Suppl 2): 147, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35655307

RESUMO

BACKGROUND: Knowledges graphs (KGs) serve as a convenient framework for structuring knowledge. A number of computational methods have been developed to generate KGs from biomedical literature and use them for downstream tasks such as link prediction and question answering. However, there is a lack of computational tools or web frameworks to support the exploration and visualization of the KG themselves, which would facilitate interactive knowledge discovery and formulation of novel biological hypotheses. METHOD: We developed a web framework for Knowledge Graph Exploration and Visualization (KGEV), to construct and visualize KGs in five stages: triple extraction, triple filtration, metadata preparation, knowledge integration, and graph database preparation. The application has convenient user interface tools, such as node and edge search and filtering, data source filtering, neighborhood retrieval, and shortest path calculation, that work by querying a backend graph database. Unlike other KGs, our framework allows fast retrieval of relevant texts supporting the relationships in the KG, thus allowing human reviewers to judge the reliability of the knowledge extracted. RESULTS: We demonstrated a case study of using the KGEV framework to perform research on COVID-19. The COVID-19 pandemic resulted in an explosion of relevant literature, making it challenging to make full use of the vast and heterogenous sources of information. We generated a COVID-19 KG with heterogenous information, including literature information from the CORD-19 dataset, as well as other existing knowledge from eight data sources. We showed the utility of KGEV in three intuitive case studies to explore and query knowledge on COVID-19. A demo of this web application can be accessed at http://covid19nlp.wglab.org . Finally, we also demonstrated a turn-key adaption of the KGEV framework to study clinical phenotypic presentation of human diseases by Human Phenotype Ontology (HPO), illustrating the versatility of the framework. CONCLUSION: In an era of literature explosion, the KGEV framework can be applied to many emerging diseases to support structured navigation of the vast amount of newly published biomedical literature and other existing biological knowledge in various databases. It can be also used as a general-purpose tool to explore and query gene-phenotype-disease-drug relationships interactively.


Assuntos
COVID-19 , Humanos , Pandemias , Reconhecimento Automatizado de Padrão , Fenótipo , Reprodutibilidade dos Testes
6.
Angew Chem Int Ed Engl ; 60(7): 3672-3678, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33119201

RESUMO

Although ultra-large optical asymmetry appears in crystalline materials, distractions from the mesoscopic ordering often causes inauthenticity in chiropticity. In amorphous materials, however, it remains challenging and elusive to achieve large chiropticity. Herein, we report the quantitative control of chiral amplification, on amorphous supramolecular structures of cholesteryl-linked bis(dipyrrinato)zinc(II), to an exceptionally high level. A proper chiral packing of the building block at several molecular scale considerably contributes to the absorptive dissymmetry factor gabs , although the system is overall disordered. The intense and tunable aggregation strength renders a variable gabs value up to +0.10 and +0.31 in the solution and in film state. On this basis, a superior ON-OFF switching of chiropticity is realized under external stimuli. This work establishes a general design principle to control over ultra-large optical asymmetry on a wider scope of chiral materials.

7.
BMC Med Inform Decis Mak ; 20(Suppl 11): 322, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33380331

RESUMO

BACKGROUND: Natural language processing (NLP) tools can facilitate the extraction of biomedical concepts from unstructured free texts, such as research articles or clinical notes. The NLP software tools CLAMP, cTAKES, and MetaMap are among the most widely used tools to extract biomedical concept entities. However, their performance in extracting disease-specific terminology from literature has not been compared extensively, especially for complex neuropsychiatric disorders with a diverse set of phenotypic and clinical manifestations. METHODS: We comparatively evaluated these NLP tools using autism spectrum disorder (ASD) as a case study. We collected 827 ASD-related terms based on previous literature as the benchmark list for performance evaluation. Then, we applied CLAMP, cTAKES, and MetaMap on 544 full-text articles and 20,408 abstracts from PubMed to extract ASD-related terms. We evaluated the predictive performance using precision, recall, and F1 score. RESULTS: We found that CLAMP has the best performance in terms of F1 score followed by cTAKES and then MetaMap. Our results show that CLAMP has much higher precision than cTAKES and MetaMap, while cTAKES and MetaMap have higher recall than CLAMP. CONCLUSION: The analysis protocols used in this study can be applied to other neuropsychiatric or neurodevelopmental disorders that lack well-defined terminology sets to describe their phenotypic presentations.


Assuntos
Transtorno do Espectro Autista , Processamento de Linguagem Natural , Benchmarking , Humanos , PubMed , Software
8.
Genetica ; 147(3-4): 327-335, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31342301

RESUMO

The Sichuan snub-nosed monkey (Rhinopithecus roxellana) is an endangered species endemic to China, where the smallest population resides in Shennongjia National Park, Hubei Province. In this study, the genetic diversity of the Sichuan snub-nosed monkeys from two areas, Qianjiaping (QJP) and Dalongtan (DLT) in Shennongjia National Park was evaluated using single nucleotide polymorphisms (SNPs) data derived from restriction site-associated DNA sequencing (RAD-seq). A total of 41,260 SNP loci were found in 29 Sichuan snub-nosed monkey individuals. The genome-wide nucleotide diversity (π) of the Shennongjia population was 0.001842. The genetic differentiation (FST) between the QJP and DLT subpopulations was 0.034. The heterozygosity of individuals from QJP was 0.3475 ± 0.03696 and 0.3148 ± 0.03501 for individuals from DLT. Although the DLT and QJP subpopulations did not show significant genetic differences, genetic differentiation between the two subpopulations was confirmed using Bayesian cluster analysis, neighbor-joining trees and principal component analysis. These results suggest that the Shennongjia population of Sichuan snub-nosed monkey has relatively low genetic diversity at the genomic level. The little genetic differentiation noted between the DLT and QJP subpopulations likely due to natural and anthropogenic barriers which may exacerbate loss of genetic diversity of this endangered subpopulation.


Assuntos
Variação Genética , Presbytini/genética , Animais , Teorema de Bayes , China , Espécies em Perigo de Extinção , Feminino , Masculino , Parques Recreativos , Filogenia , Polimorfismo de Nucleotídeo Único , População/genética , Análise de Sequência de DNA
9.
BMC Complement Altern Med ; 19(1): 304, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703679

RESUMO

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/metabolismo , Cucurbitaceae/química , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética
11.
Chemistry ; 24(41): 10306-10309, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-29701275

RESUMO

Conversion of multicolor luminescence is one of desirable goals in study and development of next-generation molecular emitters, whereas involving visible light into the control of the above-mentioned ability has been poorly addressed due to the need of a relatively complicate molecular design. In this work, we present a novel dyad with a linkage of 4-piperazinyl-1,8-naphthalimide and cyanostyryl-modified azulene moiety, upon which the luminescence signal can be orthogonally controlled by protonation and green light irradiation. The superior features of the protonation induced excited state energy alteration, followed by green light driven photoisomerization led to a progressive luminescent color conversion among blue, yellow and green at the single molecular level. This strategy may bring in novel insights for preparing advanced function-integrated optoelectronic materials.

12.
Nucleic Acids Res ; 44(4): 1718-31, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26819409

RESUMO

Ku70-binding protein 5 (Kub5)-Hera (K-H)/RPRD1B maintains genetic integrity by concomitantly minimizing persistent R-loops and promoting repair of DNA double strand breaks (DSBs). We used tandem affinity purification-mass spectrometry, co-immunoprecipitation and gel-filtration chromatography to define higher-order protein complexes containing K-H scaffolding protein to gain insight into its cellular functions. We confirmed known protein partners (Ku70, RNA Pol II, p15RS) and discovered several novel associated proteins that function in RNA metabolism (Topoisomerase 1 and RNA helicases), DNA repair/replication processes (PARP1, MSH2, Ku, DNA-PKcs, MCM proteins, PCNA and DNA Pol δ) and in protein metabolic processes, including translation. Notably, this approach directed us to investigate an unpredicted involvement of K-H in DNA mismatch repair (MMR) where K-H depletion led to concomitant MMR deficiency and compromised global microsatellite stability. Mechanistically, MMR deficiency in K-H-depleted cells was a consequence of reduced stability of the core MMR proteins (MLH1 and PMS2) caused by elevated basal caspase-dependent proteolysis. Pan-caspase inhibitor treatment restored MMR protein loss. These findings represent a novel mechanism to acquire MMR deficiency/microsatellite alterations. A significant proportion of colon, endometrial and ovarian cancers exhibit k-h expression/copy number loss and may have severe mutator phenotypes with enhanced malignancies that are currently overlooked based on sporadic MSI+ screening.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Reparo de Erro de Pareamento de DNA/genética , Instabilidade Genômica , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Antígenos Nucleares/genética , Proteínas de Ciclo Celular/genética , Quebras de DNA de Cadeia Dupla , DNA Topoisomerases Tipo I/genética , Proteínas de Ligação a DNA/genética , Células HeLa , Humanos , Autoantígeno Ku , Complexos Multiproteicos/genética , Proteínas de Neoplasias/genética , Neoplasias/metabolismo , RNA Helicases/genética , RNA Polimerase II/genética , Proteínas Repressoras/genética
13.
J Am Chem Soc ; 139(2): 785-791, 2017 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-28027639

RESUMO

In nanoscience, chirality has shown a significant ability to tune materials' electronic properties, whereas imposing macrochirality into the regulation of singlet-triplet features of organic optoelectronics remains a challenging research topic. Since the tuning for singlet and triplet excited-state properties in a single π-functional molecule connects to its multicolor luminescent application and potential improvement of internal quantum efficiency, we here report that supramolecular chirality can be employed to toggle the singlet and triplet emissions in a well-designed asterisk-shaped molecule. Employing a hexathiobenzene-based single luminophore as a prototype and functionalizing it with chiral α-lipoiate side groups, we find that helical nanoarchitectures can accordingly form in mixed DMF/H2O solution. On this basis, switching between fluorescence and phosphorescence of the material can be realized upon helical self-assembly and dissociation. Such a behavior can be attributed to a helical-conformation-dependent manipulation of the intersystem crossing. Furthermore, reversible mechanoluminescence of the corresponding solid sample was also observed to rely on an analogous molecular self-assembly alternation. These results can probably provide new visions for the development of next-generation supramolecular chiral functional materials.

14.
Chemistry ; 23(32): 7642-7647, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28370577

RESUMO

Although organic light-emitting molecules have received a growing attention and applicability in modern bioimaging science, the design and control of complex photoluminescent properties in unimolecularly selective imaging remains a challenging topic. Considering that tunable multipathway imaging can be advantagedly connected with treatment processes in therapy, the integration of an azulene and a cyanostyryl moiety into one skeleton is carried out for the generation of in situ stimuli-responsive luminescent materials, with the aim to achieve tunable and effective emissions in distinct channels through smart molecular design on a single-molecular platform. This strategy takes advantage of 1) the Z/E isomerization of the cyanostyryl unit that can vary the push-pull effect of the substitution on azulene, accompanied by altering absorption and emission of individual excited states, and 2) an optimized excited-state regulation for opening a near infrared emissive channel and making up for a controllable dual-pathway luminescent system together with the utilization of visible emission. As exemplified by a demonstration of manipulating the luminescence at the cell level, the materials exhibit a superior application potential for unimolecularly selective imaging, labeling and probing events.

15.
Anticancer Drugs ; 28(2): 161-169, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27754994

RESUMO

The Wnt/ß-catenin signaling pathway dominates numerous cellular processes including cell proliferation, differentiation, and epithelial-mesenchymal transition, which play a crucial role in human cancer malignancies. Regulator of G-protein signaling 3 (RGS3) is a pivotal molecule involved in the Wnt/ß-catenin signaling pathway, which is worthy of intensive research as a potential target in cancer treatment. In this study, we found that RGS3 is significantly upregulated in gastric cancer (GC) tumor samples compared with normal samples from the analysis of two independent GC mRNA microarray datasets in the NCBI public database. Further immunohistochemistry assay and western-blot experiments confirmed this finding on the basis of the results of our own 102 paired GC specimens and three GC cell lines. We found that a high expression of RGS3 is associated with advanced TNM stages and more aggressive malignant behaviors. In addition, the association of overexpression of RGS3 and poor overall survival and progression-free survival outcomes suggests that RGS3 has the potential to serve as a molecular therapy target for GC. Interestingly, our pathways analysis and the follow-up dual-luciferase reporter assay showed that there is a direct 3'-untranslated region binding site between RGS3 mRNA and microRNA-126, a GC inhibitor. On the basis of all the above evidences, our findings suggest that overexpressed RGS3 regulated by microRNA-126 through the post-transcriptional modulation is associated significantly with a poor prognosis of GC patients.


Assuntos
MicroRNAs/genética , Proteínas RGS/genética , Neoplasias Gástricas/genética , Humanos , Imuno-Histoquímica , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Proteínas RGS/biossíntese , Proteínas RGS/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima
16.
Chemistry ; 22(28): 9599-606, 2016 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-27245378

RESUMO

Considerable lithium-driven volume changes and loss of crystallinity on cycling have impeded the sustainable use of transition metal oxides (MOs) as attractive anode materials for advanced lithium-ion batteries that have almost six times the capacity of carbon per unit volume. Herein, Co3 O4 was used as a model MO in a facile process involving two pyrolysis steps for in situ encapsulation of nanosized MO in porous two-dimensional graphitic carbon nanosheets (2D-GCNs) with high surface areas and abundant active sites to overcome the above-mentioned problems. The proposed method is inexpensive, industrially scalable, and easy to operate with a high yield. TEM revealed that the encaged Co3 O4 is well separated and uniformly dispersed with surrounding onionlike graphitic layers. By taking advantage of the high electronic conductivity and confinement effect of the surrounding 2D-GCNs, a hierarchical GCNs-coated Co3 O4 (Co3 O4 @GCNs) anode with 43.5 wt % entrapped active nanoparticles delivered a remarkable initial specific capacity of 1816 mAh g(-1) at a current density of 100 mA g(-1) . After 50 cycles, the retained capacity is as high as 987 mAh g(-1) . When the current density was increased to 1000 mA g(-1) , the anode showed a capacity retention of 416 mAh g(-1) . Enhanced reversible rate capability and prolonged cycling stability were found for Co3 O4 @GCN compared to pure GCNs and Co3 O4 . The Co3 O4 @GCNs hybrid holds promise as an efficient candidate material for anodes due to its low cost, environmentally friendly nature, high capacity, and stability.

17.
Anticancer Drugs ; 27(7): 651-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27187019

RESUMO

Ulinastatin (UTI) is a kind of urinary trypsin inhibitor regulating broad-spectrum proteases and is used widely in the treatment of inflammatory diseases. Some evidence has suggested that UTI has antitumor functions in human carcinomas, but its function in gastric cancer (GC) has not been discussed extensively. In this study, we investigated the effects of UTI on GC SGC-7901 cells in vitro by preincubating cells with the UTI. The expression of the related molecules, urokinase-type plasminogen activator (uPA), was investigated at both the mRNA and the protein stages. Activation of uPA was analyzed and the phosphorylation of ERK1/2 downstream uPA was detected. According to the results, UTI downregulated uPA expression and significantly suppressed the activation of uPA and the phosphorylation of ERK1/2. Furthermore, the SGC-7901 cells treated by UTI showed a significant decrease in cell proliferation and impairment of invasion and migration. However, no significant influence was observed on cell apoptosis. By ectopically expressing uPA in SGC-7901 cells, suppression effects of UTI were rescued. We suggest that UTI suppresses GC cell proliferation, motility, and at least partly conducted through uPA. Although the effects of UTI in GC cells need to be validated further, UTI represents a strong therapeutic strategy that is worth following up in GC treatment.


Assuntos
Glicoproteínas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Inibidores da Tripsina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
18.
Kidney Blood Press Res ; 41(6): 802-814, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27832647

RESUMO

BACKGROUND/AIMS: Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. METHODS: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW) and extracellular water (ECW), as well as cardiac index (CI) and total peripheral resistance index (TPRI). RESULTS: The ECW/TBW was 0.453 (0.05) pre-dialysis and 0.427 (0.04) post-dialysis in controls vs. 0.478 (0.03) and 0.461 (0.03) in IH patients (p=0.01 post-dialysis). The ECW/TBW change was -0.027 (0.03) in controls and -0.013 (0.02) in IH patients (p=0.1). In controls, pre- and post-dialysis TPRI were 3254 (994) and 2469 (529) dynes/sec/cm2/m2 vs. 2983 (747) and 3408 (980) dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis). There were between-group differences in TPRI change (0=0.0001), but not CI (p=0.09). CONCLUSIONS: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.


Assuntos
Líquido Extracelular/fisiologia , Hipertensão/fisiopatologia , Diálise Renal/efeitos adversos , Vasoconstrição , Adulto , Água Corporal/metabolismo , Estudos de Casos e Controles , Impedância Elétrica , Feminino , Deslocamentos de Líquidos Corporais/fisiologia , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva
20.
Phys Chem Chem Phys ; 17(48): 32251-6, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26580293

RESUMO

In this study we probe the electrocatalytic activity of Pt nanoparticles supported on ceria nanoparticles (NPs) and nanorods (NRs) in the ethanol oxidation reaction (EOR) in alkaline media. The goal of this study was to relate morphology, support structure and composition to the EOR catalytic activity by using in situ X-ray absorption fine structure (XAFS) studies. Cyclic voltammetry experiments showed that both ceria supported catalysts (NP vs. NR) had similar peak current densities at fast scan rates, however at slow scan rates, the ceria NR catalyst showed superior catalytic activity. In situ XAFS studies in KOH showed that both ceria supported catalysts had more electron density in their d-band (with the ceria NR having more electron density overall) than ceria - free Pt/Vulcan standard. However, in an ethanol solution the ceria NR catalyst had the least electron density. We propose that this change is due to the increased charge transfer efficiency between the ceria nanorod support and platinum. In the KOH solution, the increased electron density makes the platinum less electrophilic and hinders Pt-OH bond formation. In the EtOH solution, platinum's increased nucleophilicity facilitates the bond formation between Pt and the electron deficient carbon in ethanol which in turn withdraws the electron density from platinum and increases the white line intensity as observed in the XAS measurements.

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