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1.
Langmuir ; 39(41): 14811-14821, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37791913

RESUMO

The self-healable polymers that can repair physical damage autonomously to extend their lifetime and reduce maintenance costs are promising intelligent materials. However, utilizing shape memory to facilitate self-repair is unusual at present. In this work, a series of poly(acrylic acid)-polytetrahydrofuran-poly(acrylic acid) polymers (PAA-PTMG-PAA, diPAA-PTMG) are synthesized as a switching phase and healing accelerator to blend into poly(vinyl alcohol) (PVA). The water swelling rate of the blend is up to 400.0% at 1/1 molecular weight ratio of PTMG/PAA and 20.0 wt % blend ratio of diPAA-PTMG to PVA, and its crystallization is changed significantly under wet conditions. The blend membrane exhibits not only a good hydrothermal-response shape memory effect but also a favorable self-healing behavior. The tensile strength and elongation at break are 12.4 MPa and 320.0% after healing at 25 °C, respectively. In particular, the wound membrane can achieve a better self-healing effect with the assistance of shape memory at 37 °C, and the elongation at the break increased to 515.9% after healing. The membrane is not cytotoxic, so it will be a promising biomedical material.

2.
Chemotherapy ; 67(4): 223-233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35649347

RESUMO

BACKGROUND: Research suggests that circRNAs play important roles in non-small cell lung cancer (NSCLC). The function of hsa_circ_0068252 in NSCLC, especially in cisplatin (DDP) resistance and the mechanisms, was explored in this study. METHODS: NSCLC patient samples and two NSCLC cell lines along with corresponding DDP-resistant cell lines were used. Expression levels of circ_0068252 were detected. SiRNA for circ_0068252 and inhibitor for miRNA were used in all functional analyses. A co-culture system of NSCLC cells with CD8+ T cells was used. The cellular location of circ_0068252 was detected and its target miRNA was predicted and verified. Finally, the mechanism responsible for circ_0068252 function on PD-L1 was analyzed using luciferase reporter assay in the two DDP-resistant cell lines, as well as in the co-culture system. The cytotoxicity of T cells was detected by lactate dehydrogenase assay. RESULTS: Our findings revealed that a high level of circ_0068252 was correlated with poor prognosis of NSCLC and DDP resistance. Knockdown of circ_0068252 could promote the sensitivity of DDP-resistant NSCLC cells to DDP. Moreover, knockdown of circ_0068252 could regulate the immune microenvironment which was mediated via CD8+ T cells. Finally, circ_0068252 could up-regulate PD-L1 expression by adsorbing miR-1304-5p. CONCLUSION: The circ_0068252/miR-1304-5p/PD-L1 signal axis participates in the regulation of DDP resistance and immune escape of NSCLC cells. Our results suggest that circ_0068252 may be a potential diagnostic marker and therapeutic target for DDP-resistant NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , RNA Circular/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Antígeno B7-H1/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/uso terapêutico , Imunidade , Proliferação de Células , Microambiente Tumoral
3.
Int J Mol Sci ; 23(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897765

RESUMO

The plant parasitic nematode, Aphelenchoides besseyi, is a serious pest causing severe damage to various crop plants and vegetables. The Bacillus thuringiensis (Bt) strains, GBAC46 and NMTD81, and the biological strain, FZB42, showed higher nematicidal activity against A. besseyi, by up to 88.80, 82.65, and 75.87%, respectively, in a 96-well plate experiment. We screened the whole genomes of the selected strains by protein-nucleic acid alignment. It was found that the Bt strain GBAC46 showed three novel crystal proteins, namely, Cry31Aa, Cry73Aa, and Cry40ORF, which likely provide for the safe control of nematodes. The Cry31Aa protein was composed of 802 amino acids with a molecular weight of 90.257 kDa and contained a conserved delta-endotoxin insecticidal domain. The Cry31Aa exhibited significant nematicidal activity against A. besseyi with a lethal concentration (LC50) value of 131.80 µg/mL. Furthermore, the results of in vitro experiments (i.e., rhodamine and propidium iodide (PI) experiments) revealed that the Cry31Aa protein was taken up by A. besseyi, which caused damage to the nematode's intestinal cell membrane, indicating that the Cry31Aa produced a pore-formation toxin. In pot experiments, the selected strains GBAC46, NMTD81, and FZB42 significantly reduced the lesions on leaves by up to 33.56%, 45.66, and 30.34% and also enhanced physiological growth parameters such as root length (65.10, 50.65, and 55.60%), shoot length (68.10, 55.60, and 59.45%), and plant fresh weight (60.71, 56.45, and 55.65%), respectively. The number of nematodes obtained from the plants treated with the selected strains (i.e., GBAC46, NMTD81, and FZB42) and A. besseyi was significantly reduced, with 0.56, 0.83., 1.11, and 5.04 seedling mL-1 nematodes were achieved, respectively. Moreover, the qRT-PCR analysis showed that the defense-related genes were upregulated, and the activity of hydrogen peroxide (H2O2) increased while malondialdehyde (MDA) decreased in rice leaves compared to the control. Therefore, it was concluded that the Bt strains GBAC46 and NMTD81 can promote rice growth, induce high expression of rice defense-related genes, and activate systemic resistance in rice. More importantly, the application of the novel Cry31Aa protein has high potential for the efficient and safe prevention and green control of plant parasitic nematodes.


Assuntos
Bacillus thuringiensis , Oryza , Rabditídios , Tylenchida , Animais , Antinematódeos/metabolismo , Antinematódeos/farmacologia , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/farmacologia , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Plantas/metabolismo , Rabditídios/metabolismo , Tylenchida/metabolismo
4.
Pharm Dev Technol ; 27(1): 1-8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34895029

RESUMO

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm2 and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections.


Assuntos
Antibacterianos , Microbolhas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Tigeciclina/farmacologia
5.
Environ Monit Assess ; 188(5): 266, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27048491

RESUMO

Nowadays, there is an urgent need for the investigation of the field dissipation and assessment of the preharvest interval for trichlorfon residues on rice. To protect consumers from potential health risks, this study can provide references for the safe application of trichlorfon in the rice fields. Results of the field dissipation study showed that the dissipation dynamic equations of trichlorfon were based on the first-order reaction dynamic equations and that the dissipation rates vary among rice plant, brown rice, rice bran, soil, and water. The 2-year field trials conducted in Yangzhou and Xiaogan suggested the interval of each application for trichlorfon on rice to be at least 7 days when 80 % trichlorfon SP was sprayed with a dose ranges between 80 and 160 a.i g/667 m(2). Additionally, the preharvest interval of the last application should be at least 15 days to ensure the amounts of residues below the maximum residue limits of trichlorfon on brown rice (0.1 mg/kg).


Assuntos
Monitoramento Ambiental , Inseticidas/análise , Modelos Químicos , Resíduos de Praguicidas/análise , Triclorfon/análise , Agricultura , Cinética , Oryza/química , Solo/química , Triclorfon/química
6.
J Org Chem ; 80(2): 1092-7, 2015 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-25495841

RESUMO

It was observed that the stable and commercially available N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, the so-called IDipp, catalyzes hydrogen/deuterium exchange reactions between pseudoacids and chloroform-d1, while the analogous saturated NHC 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene, the so-called SIMes, is inefficient for the same transformation. Experimental and computational DFT studies allowed these differences of reactivity to be attributed to the relative stability of the corresponding azolium­trichloromethyl anion ion pairs: in the former case, the complex evolves toward dissociation of the ions to produce an aromatic azolium cation and a basic trichloromethyl anion, while in the latter case, it evolves by ion recombination to give the product of formal carbene C­H insertion into the C­H bond of chloroform. These results provide a rationale for some early intuitions and observations of Wanzlick, Arduengo, and others on the reactivity of NHCs with chloroform as well as a simple organocatalytic method for the deuteration of pseudoacids (pKa,DMSO = 14­19) with chloroform-d1.

7.
Environ Monit Assess ; 187(1): 4205, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25504193

RESUMO

The farmland weed Youngia erythrocarpa has been found to have the basic characteristics of a cadmium (Cd) hyperaccumulator. This study carried out preliminary and further Cd concentration gradient experiments and field experiment using Y. erythrocarpa to confirm this fact. The results showed that the biomass and resistance coefficient of Y. erythrocarpa decreased, but the root/shoot ratio and the Cd content in roots and shoots increased with the increase in soil Cd concentration. The Cd content in shoots of Y. erythrocarpa exceeded 100 mg/kg when the soil Cd concentration was 25 mg/kg in the two concentration gradient experiments, up to the maxima of 293.25 and 317.87 mg/kg at 100 mg/kg soil Cd. Both the bioconcentration factor of the shoots and the translocation factor exceeded 1 in all Cd treatments. In the field experiment, the total Cd extraction by shoots was 0.934-0.996 mg/m(2) at soil Cd levels of 2.04-2.89 mg/kg. Therefore, Y. erythrocarpa is a Cd hyperaccumulator that could be used to remediate Cd-contaminated farmland soil efficiently.


Assuntos
Cádmio/análise , Raízes de Plantas/metabolismo , Poluentes do Solo/análise , Biodegradação Ambiental , Biomassa , Cádmio/metabolismo , Monitoramento Ambiental , Raízes de Plantas/química , Solo , Poluentes do Solo/metabolismo
8.
Zhong Yao Cai ; 38(1): 119-22, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-26214880

RESUMO

OBJECTIVE: To establish an enzyme linked immunosorbent assay(ELISA) for mangiferin (MRn), artificial antigen of MRn was synthesized. METHODS: Oxidation method using sodium iodide was used to synthesize immunogenic antigen (MRn-BSA) and coating antigen(MRn-OVA) of MRn. The characterization of the synthesis was examined by UV spectrometry. BALB/c mice were immunized with the prepared MRn-BSA immunogenic antigen. The titer of the anti-serum was detected by ELISA, in the meanwhile the immunogenicity of MRn-BSA was confirmed by indirect competitive ELISA (icELISA). RESULTS: UV spectroscopy showed that MRn was successfully conjugated with OVA and BSA,so the new compound of MRn-BSA was synthesized, the coupling ratio was 6: 1. After immuned MRn-BSA, the mice could produce anti-MRn antibodies specifically, of which titer was up to 1: 4 000, and the general range was 1 - 100 µg/mL. CONCLUSION: Anti-MRn antibodies are discovered in the serum of mice, which indicates that artificial antigen of MRn is successfully synthesized,for the purpose of preparing monoclonal antibodies, as well as the establishment of appropriate immune methods.


Assuntos
Antígenos/química , Ensaio de Imunoadsorção Enzimática , Xantonas/imunologia , Animais , Anticorpos/sangue , Camundongos , Camundongos Endogâmicos BALB C
9.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2295-9, 2014 Jun.
Artigo em Zh | MEDLINE | ID: mdl-25244762

RESUMO

The establishment of high specificity and sensitivity method of small molecule monoclonal antibody-based immunoassay has a great importance in the study of small molecule compounds in Chinese medicine, wherein synthesis of small molecule artificial antigen is a critical step in the preparation of small molecule antibodies. Oxidation method using sodium iodide was used to synthesize immunogenic antigen (FRn-BSA) and coating antigen (FRn-OVA) of forsythin. UV spectroscopy and thin layer chromatography showed that forsythin was successfully conjugated with BSA and OVA. After immuned FRn-BSA, the mice could specifically produce anti-forsythin antibodies with titer up to 1:8 000, and the linear range was from 1 mg x L(-1) to 100 mg x L(-1). In this paper, the artificial antigen of forsythin was successfully synthesized, which can be applied for preparation of monoclonal antibodies and establishment of appropriate immune method.


Assuntos
Antígenos/imunologia , Compostos Bicíclicos Heterocíclicos com Pontes/imunologia , Medicamentos de Ervas Chinesas/química , Furanos/imunologia , Animais , Anticorpos/imunologia , Antígenos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Furanos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C
10.
Front Oncol ; 14: 1346124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559563

RESUMO

Objective: To develop a contrast-enhanced computed tomography (CECT) based radiomics model using machine learning method and assess its ability of preoperative prediction for the early recurrence of hepatocellular carcinoma (HCC). Methods: A total of 297 patients confirmed with HCC were assigned to the training dataset and test dataset based on the 8:2 ratio, and the follow-up period of the patients was from May 2012 to July 2017. The lesion sites were manually segmented using ITK-SNAP, and the pyradiomics platform was applied to extract radiomic features. We established the machine learning model to predict the early recurrence of HCC. The accuracy, AUC, standard deviation, specificity, and sensitivity were applied to evaluate the model performance. Results: 1,688 features were extracted from the arterial phase and venous phase images, respectively. When arterial phase and venous phase images were employed correlated with clinical factors to train a prediction model, it achieved the best performance (AUC with 95% CI 0.8300(0.7560-0.9040), sensitivity 89.45%, specificity 79.07%, accuracy 82.67%, p value 0.0064). Conclusion: The CECT-based radiomics may be helpful to non-invasively reveal the potential connection between CECT images and early recurrence of HCC. The combination of radiomics and clinical factors could boost model performance.

11.
Biomed Res Int ; 2023: 4343350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36760475

RESUMO

Objective: ETS1 and ETS2, the main ETS family of transcription factors, have been found to act as downstream effectors of the RAS/MAPK pathway. This study explores the expression and prognostic values of ETS1 and ETS2 across cancers. We also aimed to explore the significance of ETS1 and ETS2 expression in normal immune cells with relation to tumorigenesis. Methods: The expression of ETS1 and ETS2 was examined in the HPA and GEPIA2 databases. The KM plotter was applied to examine prognostic value of ETS1 and ETS2. Correlation between ETS1/ETS2 and infiltrating immune cells and immune checkpoints was assessed using TIMER2.0. The mutation landscape of ETS1/ETS2 was explored using the cBioPortal. STRING and GEPIA2 were used to screen ETS1/ETS2 binding and correlated genes. Enrichr was applied to perform GO and KEGG enrichment analyses. Results: ETS1 showed enhanced expression in lymphoid tissue, while ETS2 showed low tissue specificity. ETS1 was increased in 12 and decreased in 6 cancers, while ETS2 was increased in 4 and decreased in 13 cancers. Both ETS1 and ETS2 were favorable prognostic markers in LIHC and KIRC, while they showed different prognostic roles in more cancers. ETS1 showed stronger correlation with several infiltrating immune cells and immune checkpoints compared with ETS2. Both ETS1 and ETS2 harbored low mutation ratio. ETS1 interacting and correlated genes were enriched in GO terms in response to cadmium ion and response to oxidative stress, while those of ETS2 were enriched in transcription regulation. Conclusion: ETS1 and ETS2 showed different patterns in expression, prognostic values, correlation with immune infiltrating, and immune checkpoints. ETS1 and ETS2 play distinct roles across cancer.


Assuntos
Proteína Proto-Oncogênica c-ets-1 , Proteína Proto-Oncogênica c-ets-2 , Humanos , Carcinogênese , Prognóstico , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-2/genética , Proteína Proto-Oncogênica c-ets-2/metabolismo , Fatores de Transcrição/metabolismo
12.
Medicine (Baltimore) ; 102(8): e32976, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36827067

RESUMO

S100 family members (S100s) are small molecular EF hand calcium binding proteins and widely expressed in many tissues and organs. S100s are shown to be biomarkers of disease progression and prognosis in various types of cancers. Nevertheless, the expression patterns, function, and prognostic values of S100s and its association with tumor-infiltrating immune cells in pancreatic adenocarcinoma (PAAD) patients have not been systematically clarified. We explored the expression and roles of the entire 20 S100s in PAAD patients by using the following public databases: Oncomine, gene expression profiling interactive analysis, cBioPortal, Metascape, search tool for recurring instances of neighboring genes, Tumor IMmune Estimation Resource, and GeneMANIA. The S100A2/A3/A4/A6/A8/A9/A10/A11/A13/A14/A16/B/P mRNA expressions were significantly upregulated in PAAD patients. The mRNA expression of S100A3/A4/A5/A6/A10/A11/A14/A16/Z were significantly negatively related with the tumor stage in PAAD patients. We found that the S100A2/A3/A5/A10/A11/A14/A16 were significantly correlated with poor overall survival, whereas the increased levels of S100A1/B/G/Z were strongly associated with good overall survival. We found significant correlations among S100s and tumor-infiltrating immune cells. Cox proportional risk models revealed that B cells, Dendritic cells and S100A1/A5/A6/A8/A9/A13/A14 were significantly related with outcomes in PAAD patients. These results suggest that S100A2/A3/A10/A11/A14/A16 may serve as new diagnostic and prognostic biomarkers for PAAD patients and provide new clues for immunotherapy in PAAD patients.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Recidiva Local de Neoplasia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais , Neoplasias Pancreáticas
13.
J Extra Corpor Technol ; 44(2): 66-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22893985

RESUMO

Angiotensin converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, myocardial infarction, and congestive heart failure. They have a known adverse effect of unresponsiveness to vasoconstrictors resulting in hypotension for the patients undergoing cardiac surgery. We report a case of a 43-year-old female patient with preoperative lisinopril (2.5 mg per day for a week prior to cardiac surgery), who was diagnosed with severe mitral and tricuspid valve regurgitation. She underwent both a mitral and tricuspid valve replacement operation using cardiopulmonary bypass (CPB). To address her ACEI-associated hypotension on cardiopulmonary bypass, bypass flows were as high as cardiac index of greater than 3 (3.1 +/- .2) L/min/m2 to provide sufficient perfusion indicated by cerebral oxymetry monitoring and adequate urine on pump. In addition, due to unresponsiveness to regular concentration of neosynephrine (neo), boluses of higher concentrations up to 320 microg/mL of neo were administered to maintain the perfusion pressure on pump. The patient was weaned from CPB uneventfully and was discharged home on postoperative day 7. Additional therapeutic treatment to ACEI-associated hypotension and unresponsiveness to neo for the patients undergoing cardiac surgery using CPB is reviewed as well in this paper.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Ponte Cardiopulmonar , Lisinopril/efeitos adversos , Fenilefrina/administração & dosagem , Vasoconstritores/administração & dosagem , Adulto , Feminino , Humanos , Hipotensão/induzido quimicamente , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Tricúspide/cirurgia
14.
Int J Biol Macromol ; 217: 1037-1043, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35905767

RESUMO

Biodegradable shape-memory polymers (SMPs) which are functional materials with applicability for medicine devices are designed to acquire their therapeutically relevant shape and drug release after implantation. In the work, an amphiphilic polymer (PVAD) is synthesized by using polytetrahydrofuran (PTMG), vinyl acetate (VAc), acrylic acid (AA), tetramethyltetravinylcyclotetrasiloxane (D4vi) as raw materials. PVAD encapsulating hydrophilic drug as switching phase and poly(l-lactide) (PLLA) as fixing matrix construct an SM system with the characteristic of "reservoir-matrix" drug release. The shape recovery ratio (Rr) of medicated PVAD/PLLA reaches 99 % by heat-water stimulation. The effects of release temperature and SM on drug release are investigated. With the release temperature increasing, the medicated PVAD/PLLA accelerates drug release and shows burst release initially, while the drug release for the medicated PLLA changes slightly. The drug release rate goes up after 3 rounds of SM. The mechanism of SM system controlling drug release is put forward based on structural changes. The yield strength and elongation at break of medicated PVAD/PLLA are 29.8 MPa and 44.6 %, respectively. It opens up new perspectives for drug carrier matrices in Pharmaceutical Sciences.


Assuntos
Materiais Biocompatíveis , Polímeros , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Poliésteres/química , Polímeros/química
15.
Biochem J ; 417(3): 705-15, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-18795890

RESUMO

Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by PKC (protein kinase C) activation, and the K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In the present study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular N- and C-termini of Kv4.2 GST (glutathione transferase) tagged fusion protein revealed that the C-terminal of Kv4.2 was phosphorylated by PKC, whereas the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Ser447 and Ser537. A phospho-site-specific antibody showed that phosphorylation at the Ser537 site was increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that mutation to alanine of both Ser447 and Ser537 in order to block phosphorylation at both of the PKC sites increased surface expression compared with wild-type Kv4.2. Electrophysiological recordings of the wild-type and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 (Kv4 channel-interacting protein 3) revealed no significant difference in the half-activation or half-inactivation voltage of the channel. Interestingly, Ser537 lies within a possible ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Quinase C/metabolismo , Canais de Potássio Shal/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Animais , Sítios de Ligação , Células COS , Chlorocebus aethiops , Citoplasma/metabolismo , DNA Complementar/genética , DNA Complementar/metabolismo , Humanos , Proteínas Interatuantes com Canais de Kv/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Dados de Sequência Molecular , Oócitos/metabolismo , Fosforilação , Ratos , Proteínas Repressoras/metabolismo , Xenopus
16.
J Extra Corpor Technol ; 42(2): 103-13, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20648894

RESUMO

UNLABELLED: Platelets play a major role in the thromboembolic diseases and upon vascular injury, especially arterial vascular injury. These platelets rapidly adhere to the exposed subendothelial area, where they become activated by contacting with stimulants. Antiplatelet therapy remains extremely important in treatment and prophylaxis of arterial thromboembolic disorders such as coronary arterial diseases and stroke. The antiplatelet drugs (APDs) are among the most widely used in the world. Based on the molecular targets, APDs are classified as Thromboxane A2 pathway blockers, ADP receptor antagonists, GPIIa/IIIb antagonists, adenosine reuptake inhibitors, phosphodiesterase inhibitors, thrombin receptor inhibitors, and others. Coronary artery bypass graft (CABG) surgery is an important therapeutic approach to treat coronary artery disease. Long-term success after CABG depends on the patency of the bypass vessels. Since platelets play a crucial role in the pathogenesis of thrombosis in the blood vessels, APDs are broadly used to reduce serious cardiovascular events. Platelets also are an integral part of inflammation and APDs have demonstrated to reduce the inflammation mediators in the healthy volunteers and coronary artery disease patients; it will be an interesting topic to determine if platelet inhibition will attenuate CPB-induced systemic inflammatory response syndrome. Due to concerns of post-op bleeding with use of APDs, it is a common practice to withhold APDs prior to surgery; however, recent studies have demonstrated that continuation of APDs prior to surgery (even until the day of surgery) does not increase the risk of post-op bleeding. With extensive use of APDs in cardiovascular thromboembolic events, APD resistance becomes problematic in clinical antiplatelet therapy. Since there is no standardized or universal definition available to quantify APDs resistance, a clinically meaningful definition of APD resistance needs to be developed based on data linking laboratory tests to clinical outcomes in patients. KEYWORDS: antiplatelet drug, coronary artery diseases, cardiopulmonary bypass, clinical trials, drug resistance, platelet mapping.


Assuntos
Ponte Cardiopulmonar/métodos , Doença da Artéria Coronariana/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Terapia Combinada , Humanos
17.
J Neurochem ; 106(4): 1929-40, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18513371

RESUMO

Extracelluar signal-regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down-regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho-ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole-cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A-current, which could lead to altered intrinsic membrane excitability during SE.


Assuntos
Canais de Potássio Shal/metabolismo , Estado Epiléptico/metabolismo , Animais , Eletroencefalografia/métodos , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Canais de Potássio Shal/antagonistas & inibidores , Canais de Potássio Shal/biossíntese , Estado Epiléptico/fisiopatologia , Transmissão Sináptica/fisiologia , Sinaptossomos/metabolismo , Sinaptossomos/fisiologia , Regulação para Cima/fisiologia
18.
J Agric Food Chem ; 66(47): 12471-12478, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30403860

RESUMO

Spirotetramat is a pesticide with bidirectional systemicity and can effectively control pests by inhibiting the biosynthesis of fatty acids. In this study, adsorption and desorption behaviors of spirotetramat in six soils and its interaction mechanism were studied using the batch equilibrium method and infrared radiation. The results showed that the adsorption and desorption behaviors of spirotetramat conformed to the Freundlich isotherm model. The values of adsorption capacities KF-ads ranged from 2.11 to 12.40, and the values of desorption capacities KF-des varied from 2.97 to 32.90. From the hysteresis coefficient, spirotetramat was easily desorbed from the test soils. The adsorption capacity of the soil to spirotetramat enhanced with an increasing temperature. Moreover, the changes in pH values and exogenous addition of humic acid and surfactant could also affect soil adsorption capacity, but for desorption, there was no correlation.


Assuntos
Compostos Aza/química , Praguicidas/química , Solo/química , Compostos de Espiro/química , Adsorção , Substâncias Húmicas/análise , Concentração de Íons de Hidrogênio , Cinética , Poluentes do Solo/química
19.
J AOAC Int ; 101(3): 848-857, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28982415

RESUMO

With the purpose of guaranteeing the safe use of spirotetramat and preventing its potential health threats to consumers, a QuEChERS extraction method coupled with LC triple-quadrupole tandem MS was applied in this study to determine residual spirotetramat metabolites in different tissues of amaranth (Amaranthus tricolor) and in soil. The results indicate that the spirotetramat degraded into different types of metabolites that were located in different tissues of amaranth and in soil. B-keto, B-glu, and B-enol were the three most representative degradation products in the leaf of amaranth, and B-glu and B-enol were the two major degradation products found in the stem of amaranth; however, only B-enol was detected in the root of amaranth. B-keto and B-mono were the two products detected in the soil in which the amaranth grew. The cytotoxicity results demonstrate that spirotetramat and its metabolite B-enol inhibited cellular growth, and the toxicity of spirotetramat and its metabolite B-enol exceeded than that of the metabolites B-keto, B-mono, and B-glu. This investigation is of great significance to the safe use of spirotetramat in agriculture.


Assuntos
Compostos Aza/análise , Cromatografia Líquida/métodos , Inseticidas/análise , Compostos de Espiro/análise , Espectrometria de Massas em Tandem/métodos , Amaranthus/química , Amaranthus/metabolismo , Animais , Compostos Aza/isolamento & purificação , Compostos Aza/metabolismo , Compostos Aza/toxicidade , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Inseticidas/isolamento & purificação , Inseticidas/metabolismo , Inseticidas/toxicidade , Limite de Detecção , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Solo/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/metabolismo , Compostos de Espiro/toxicidade , Spodoptera/efeitos dos fármacos
20.
J Neurochem ; 103(4): 1381-95, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17727632

RESUMO

We evaluated a role for the nuclear factor-kappa B (NF-kappaB) pathway in the regulation of seizure susceptibility and transcriptional activation during prolonged, continuous seizures (status epilepticus). Using two functionally distinct NF-kappaB inhibitors we observed a decrease in latency to onset of kainate-induced seizures and status epilepticus. To assess NF-kappaB transcriptional activation, we evaluated inhibitor kappa B alpha (IkappaBalpha) and brain-derived neurotrophic factor (bdnf) gene targets. Inhibition of the NF-kappaB signaling pathway significantly attenuated the increases in IkappaBalpha and bdnf mRNA levels that occurred during prolonged seizure activity, suggesting that the NF-kappaB pathway was involved in the up-regulation of these transcripts during status epilepticus. DNA-binding studies and chromatin immunoprecipitation assays using hippocampal extracts from animals with status epilepticus revealed that NF-kappaB subunits were associated with the candidate kappaB-binding elements within promoter 1 of the bdnf gene. The pattern of association was different for the p50 and p65 subunits supporting complex NF-kappaB modifications within promoter 1. In summary, our findings provide additional insights into the role of NF-kappaB transcriptional regulation in hippocampus following status epilepticus and suggest that NF-kappaB pathway activation contributes to seizure susceptibility.


Assuntos
Convulsivantes/toxicidade , NF-kappa B/fisiologia , Convulsões/metabolismo , Transcrição Gênica/fisiologia , Animais , Ácido Caínico/toxicidade , Masculino , NF-kappa B/antagonistas & inibidores , NF-kappa B/biossíntese , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Gênica/efeitos dos fármacos
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