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1.
Int J Mol Sci ; 24(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37833969

RESUMO

Pore-forming toxins (PFTs) exert physiological effects by rearrangement of the host cell cytoskeleton. Staphylococcus aureus-secreted PFTs play an important role in bovine mastitis. In the study, we examined the effects of recombinant Panton-Valentine leukocidin (rPVL) on cytoskeleton rearrangement, and identified the signaling pathways involved in regulating the process in bovine mammary epithelial cells (BMECs) in vitro. Meanwhile, the underlying regulatory mechanism of baicalin for this process was investigated. The results showed that S. aureus induced cytoskeleton rearrangement in BMECs mainly through PVL. S. aureus and rPVL caused alterations in the cell morphology and layer integrity due to microfilament and microtubule rearrangement and focal contact inability. rPVL strongly induced the phosphorylation of cofilin at Ser3 mediating by the activation of the RhoA/ROCK/LIMK pathway, and resulted in the activation of loss of actin stress fibers, or the hyperphosphorylation of Tau at Ser396 inducing by the inhibition of the PI3K/AKT/GSK-3ß pathways, and decreased the microtubule assembly. Baicalin significantly attenuated rPVL-stimulated cytoskeleton rearrangement in BMECs. Baicalin inhibited cofilin phosphorylation or Tau hyperphosphorylation via regulating the activation of RhoA/ROCK/LIMK and PI3K/AKT/GSK-3ß signaling pathways. These findings provide new insights into the pathogenesis and potential treatment in S. aureus causing bovine mastitis.


Assuntos
Mastite Bovina , Proteínas Proto-Oncogênicas c-akt , Feminino , Animais , Bovinos , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Staphylococcus aureus/metabolismo , Citoesqueleto/metabolismo , Fosforilação , Microtúbulos/metabolismo , Células Epiteliais/metabolismo , Fatores de Despolimerização de Actina/metabolismo
2.
Front Pharmacol ; 14: 1170240, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351504

RESUMO

Necroptosis is a programmed form of necrotic cell death that serves as a host gatekeeper for defense against invasion by certain pathogens. Previous studies have uncovered the essential role of necroptosis in tumor progression and implied the potential for novel therapies targeting necroptosis. However, no comprehensive analysis of multi-omics data has been conducted to better understand the relationship between necroptosis and tumor. We developed the necroptosis index (NI) to uncover the effect of necroptosis in most cancers. NI not only correlated with clinical characteristics of multiple tumors, but also could influence drug sensitivity in glioma. Based on necroptosis-related differentially expressed genes, the consensus clustering was used to classify glioma patients into two NI subgroups. Then, we revealed NI subgroup I were more sensitive to immunotherapy, particularly anti-PD1 therapy. This new NI-based classification may have prospective predictive factors for prognosis and guide physicians in prioritizing immunotherapy for potential responders.

3.
Aging (Albany NY) ; 15(5): 1628-1651, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36917093

RESUMO

BACKGROUND: Pyroptosis, also known as inflammatory necrosis, is a programmed cell death that manifests itself as a continuous swelling of cells until the cell membrane breaks, leading to the liberation of cellular contents, which triggers an intense inflammatory response. Pyroptosis might be a panacea for a variety of cancers, which include immunotherapy and chemotherapy-insensitive tumors such as glioma. Several findings have observed that long non-coding RNAs (lncRNAs) modulate the bio-behavior of tumor cells by binding to RNA, DNA and protein. Nevertheless, there are few studies reporting the effect of lncRNAs in pyroptosis processes in glioma. METHODS: The principal goal of this study was to identify pyroptosis-related lncRNAs (PRLs) utilizing bioinformatic algorithm and to apply PCR techniques for validation in human glioma tissues. The second goal was to establish a prognostic model for predicting the overall survival patients with glioma. Predict algorithm was used to construct prognosis model with good diagnostic precision for potential clinical translation. RESULTS: Noticeably, molecular subtypes categorized by the PRLs were not distinct from any previously published subtypes of glioma. The immune and mutation landscapes were obviously different from previous subtypes of glioma. Analysis of the sensitivity (IC50) of patients to 30 chemotherapeutic agents identified 22 agents as potential therapeutic agents for patients with low riskscores. CONCLUSIONS: We established an exact prognostic model according to the expression profile of PRLs, which may facilitate the assessment of patient prognosis and treatment patterns and could be further applied to clinical.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , Piroptose/genética , RNA Longo não Codificante/genética , Glioma/genética , Apoptose , Algoritmos , Prognóstico
4.
Sci Rep ; 13(1): 2606, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788275

RESUMO

Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Apoptosis and necrosis caused by the interaction between the host and the pathogen, as well as the host's inflammatory response, play an important role in the pathogenesis of TB. Dual-specificity phosphatase 1 (DUSP1) plays a vital role in regulating the host immune responses. However, the role of DUSP1 in the regulation of THP-1 macrophage apoptosis induced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection remains unclear. In the present study, we report that infection with BCG significantly induces macrophage apoptosis and induces the production of DUSP1, TNF-α and IL-1ß. DUSP1 knockdown significantly inhibited BCG-induced macrophage apoptosis and activation of MAPKs/NF-κB signaling pathway. In addition, DUSP1 knockdown suppressed BCG-induced inflammation in vivo. Taken together, this study demonstrates that DUSP1, as a regulator of MAPKs/NF-κB signaling pathway, plays a novel role in BCG-induced macrophage apoptosis and inflammatory response.


Assuntos
Mycobacterium bovis , Tuberculose , Humanos , NF-kappa B/metabolismo , Vacina BCG , Células THP-1 , Transdução de Sinais , Tuberculose/metabolismo , Apoptose , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo
5.
Br J Neurosurg ; 37(2): 148-157, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34553657

RESUMO

PURPOSE: The preferred surgical method for treating adults with moyamoya disease (MMD) remains controversial. The purpose of this study was to compare the efficacy of different surgical methods in the treatment of adults with ischaemic-type MMD. METHODS: We retrospectively analyzed the data of patients with ischaemic-type MMD who underwent indirect bypass (IB), direct bypass (DB), or combined bypass (CB) at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2019. Postoperative complications, improvements in neurological function, haemodynamics, recurrent stroke and neovascularization were compared. RESULTS: A total of 310 adults (371 hemispheres) with ischaemic-type MMD were included in our study. Ninety, 127, and 154 hemispheres underwent IB, DB and CB, respectively. A total of 24 (6.5%) ischaemic events and 8 (2.8%) symptomatic hyperperfusion events occurred after the operations. There was no significant difference in postoperative complications among the three types of surgery (p = 0.300). During the follow-up period, there were 21 cases (5.7%) of recurrent ischaemia and 12 cases (3.2%) of recurrent haemorrhage. Kaplan-Meier survival analysis showed that the ischaemia-free survival of the CB group was significantly longer than that of the IB group (p = 0.047), but there was no significant difference in haemorrhage-free survival among the three groups (p = 0.660). Six months after the operation, DB and CB were superior to IB in improving cerebral blood flow and neovascularization (p = 0.002), but there was no significant difference in the improvement of neurological function among the three groups at the last follow-up (p = 0.784). CONCLUSION: The three surgical methods achieved satisfactory results in the treatment of ischaemic-type MMD. DB and CB can significantly improve haemodynamics and reduce recurrent stroke. In terms of improving neurological function, the curative effect of the three surgical methods remains to be further explored.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Humanos , Adulto , Seguimentos , Estudos Retrospectivos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Revascularização Cerebral/métodos , Infarto Cerebral , Complicações Pós-Operatórias/epidemiologia , Neovascularização Patológica , Resultado do Tratamento
6.
Chemosphere ; 308(Pt 2): 136000, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35973501

RESUMO

Tibetan sheep (Ovis aries) are the most numerous livestock in Tibet Plateau pasture ecosystem and have strong ecological adaptability. In the natural grazing system, soil as a natural nutrient carrier and involuntarily or intentionally ingested by Tibetan sheep contribute as an important feed approach. However, quantifying the dosages of soil ingestion for the Tibetan sheep still needs to be clarified. This study aims to characterize nutrient digestibility and rumen bacterial communities by Tibetan sheep in response to different levels of soil ingestion. Thirty sheep were selected and divided into five treatments with soil ingestion (0%, 5%, 10%, 15%, and 20%). The conclusion demonstrated that soil ingestion improved the dry matter digestibility (59.3-62.97%), ether extract (59.79-67.87%) and crude protein (59.81-66.47%) digestibility, particularly 10% soil ingestion has highest nutrient digestibility. The rumen fermentation environment adjusted after soil ingestion by improvement of pH, ammonia nitrogen and volatile fatty acids. Appropriate soil ingestion reduced the bacterial diversity ranged from 946 to 1000 OUTs as compared control (1012), and the rumen bacterial community dominant by typical fiber digestion associated Firmicutes (47.48-53.56%), Bacteroidetes (34.93-40.02%) and Fibrobacteres (4.36-9.27%). Especially, the highest digestible feed capacity and stronger environment adaptability present in 10% soil ingestion Tibetan sheep. Overall, soil ingestion stimulates rumen metabolism by creating a favorable environment for microbial fermentation, improved bacterial community abundance associated with cellulose and saccharide degradation, contribute nutrient digestibility and growth performance of Tibetan sheep.


Assuntos
Digestão , Rúmen , Amônia/metabolismo , Ração Animal/análise , Animais , Bactérias/metabolismo , Celulose/metabolismo , Dieta/veterinária , Ingestão de Alimentos , Ecossistema , Éteres , Ácidos Graxos Voláteis/metabolismo , Fermentação , Nitrogênio/análise , Nutrientes , Extratos Vegetais/farmacologia , Rúmen/microbiologia , Ovinos , Solo , Tibet
7.
Nanomaterials (Basel) ; 12(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35457969

RESUMO

Exchange-coupled magnets are promising candidates for a new generation of permanent magnets. Here, we investigated the effect of soft magnetic shell thickness and the aspect ratio of the hard magnetic core on the magnetic properties for isolated core/shell cylinder exchange-coupled magnets, as well as the packing effect of the cylindrical array via a micromagnetic simulation method. It was found that the shape anisotropy contributions to the magnetic properties in the cylindrical core/shell exchange-coupled magnets are closely related to the thickness of the soft magnetic shell. When the soft magnetic shell is thin, the magnetic properties are dominated by the hard-soft exchange coupling effects, and the contributions of shape anisotropy are quite limited. When the soft magnetic shell is relatively thick, utilizing shape anisotropy would be an effective method to improve the magnetic performance of hard-soft exchange-coupled magnets. The present work provides an in-depth fundamental understanding of the underlying magnetization reversal mechanism. This work could be useful for designing high-performance permanent magnets and avoiding pitfalls.

8.
Infect Genet Evol ; 97: 105158, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34826624

RESUMO

Alveolar macrophage apoptosis induced by Mycobacterium tuberculosis (Mtb) plays a significant role in mediating the pathogenesis of tuberculosis. There is growing evidence that guanylate-binding proteins (GBPs) are associated with different pathological processes such as microbial infection. However, it remains unclear whether GBPs can regulate the apoptosis of macrophages induced by Mtb. In this study, we investigated the potential effect of GBP1 on RAW 264.7 cell apoptosis during Bacillus Calmette-Guerin (BCG) infection. The results demonstrated that BCG could induce macrophage apoptosis and GBP1 upregulation. In addition, we explored the role of GBP1 in regulating BCG-induced RAW 264.7 cell apoptosis using small interfering RNAs targeting GBP1. The results showed that knockdown of GBP1 could attenuate BCG-induced apoptosis in RAW 264.7 cells. Moreover, we found that GBP1 knockdown decreased the levels of cleaved-Caspase 3 and cleaved-PARP-1, while decreased those of cleaved-Caspase 9, BAX, Cytochrome C and APAF1. These findings imply that GBP1 knockdown can prevent BCG-induced apoptosis through an endogenous apoptosis pathway. In addition, the mitochondrial membrane potential of macrophages was significantly increased after BCG infection, and GBP1 knockdown could alleviate this phenomenon. Furthermore, downregulation of GBP1 also attenuated BCG-induced accumulation of reactive oxygen species in macrophages. Mechanistically, GBP1 suppressed the phosphorylation of the target molecules in p38/JNK pathway, thus regulating the apoptosis of BGC-infected macrophages. Collectively, these findings reveal a significant role of GBP1 in mediating cell apoptosis in macrophages infected with BCG, and the molecular mechanism underlying its suppressive effect on BCG-induced apoptosis.


Assuntos
Apoptose , Proteínas de Ligação ao GTP/genética , Sistema de Sinalização das MAP Quinases , Mycobacterium bovis/fisiologia , Animais , Proteínas de Ligação ao GTP/deficiência , Técnicas de Silenciamento de Genes , Camundongos , Células RAW 264.7
9.
Front Oncol ; 11: 748586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707993

RESUMO

PURPOSE: The purpose was to explore the correlation between hematological parameters and the progression of WHO grade II meningioma, and establish a clinical prognostic model based on hematological parameters and clinical prognostic factors to predict the progression-free survival (PFS) of patients. METHODS: A total of 274 patients with WHO grade II meningiomas were included. Patients were randomly divided into a training cohort (192, 70%) and a test cohort (82, 30%). In the training cohort, the least absolute shrinkage and selection operator Cox regression analysis were used to screen for hematological parameters with prognostic value, and the hematological risk model (HRM) was constructed based on these parameters; univariate and multivariate Cox regression analyses were utilized to screen for clinical prognostic factors, and a clinical prognostic model was constructed based on clinical prognostic factors and HRM. The prognostic stability and accuracy of the HRM and clinical prognostic model were verified in the test cohort. Subgroup analysis was performed according to the patients' different clinical characteristics. RESULTS: Preoperative neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, albumin-to-globulin ratio, D-dimer, fibrinogen, and lactate dehydrogenase were associated with the PFS of patients. The areas under curve of the HRM were 0.773 (95% confidence interval [CI] 0.707-0.839) and 0.745 (95% CI 0.637-0.852) in the training cohort and test cohort, respectively. The progression risk was higher in the high-risk group than that in the low-risk group categorized by the optimal cutoff value (2.05) of hematological risk scores. The HRM, age, tumor location, tumor size, peritumoral edema, extent of resection, Ki-67 index, and postoperative radiotherapy were the prognostic factors for the progression of meningiomas. The corrected C-index of the clinical prognosis model was 0.79 in the training cohort. Clinical decision analysis showed that the clinical prognostic model could be used to obtain favorable clinical benefits. In the subgroup analysis, the HRM displayed excellent prognostic stability and general applicability in different subgroups. CONCLUSIONS: Preoperative hematological parameters are associated with the postoperative progression of WHO grade II meningiomas. The clinical prognosis model constructed based on hematological parameters and clinical prognostic factors has favorable predictive accuracy and clinical benefits.

10.
ACS Appl Mater Interfaces ; 13(11): 13548-13555, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33703872

RESUMO

Specially designed SmCo5/Co magnetic nanocomposites have been fabricated by a "bottom up" process. SmCo5 nanochips were first prepared by solution-phase chemical synthesis combined with reductive annealing and then coated by chemical deposition of Co nanorods. Both the SmCo5 nanochips and Co nanorods are anisotropic and could be simultaneously aligned under the external magnetic field. Magnetic measurements applied on these "bi-anisotropic" SmCo5/Co composites show high magnetic performance with the Co phase content in a wide range from 10 to 80 wt %. For the first time ever, the applicable exchange-coupled nanocomposites with a rare-earth content lower than 7 wt % was realized, which exhibits the coercivity close to 10 kOe and remanence 31% larger than that of single phase SmCo5. 3-D micromagnetic simulations were performed to reveal that the reversal mechanism in the Co phase was transferred from the incoherent mode to the coherent mode under a tip interface exchange-coupling with a SmCo5 surface.

11.
Eur J Pharmacol ; 895: 173865, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460616

RESUMO

Diabetes, a chronic non-communicable disease, has become one of the most serious and critical public health problems with increasing incidence trends. Chronic vascular complications are the major causes of disability and death in diabetic patients with endothelial dysfunction. Diabetes is intimately associated with endothelial mitochondrial dysfunction, indicated by increased oxidative stress, decreased biogenesis, increased DNA damage, and weakened autophagy in mitochondria. All these morphological and functional changes of mitochondria play important roles in diabetic endothelial dysfunction. Herein, we reviewed the roles and mechanisms of endothelial mitochondrial dysfunction, particularly mitochondrial dynamics in the vascular complications of diabetes and summarized the potential mitochondria-targeted therapies in diabetic vascular complications.


Assuntos
Angiopatias Diabéticas/patologia , Células Endoteliais/patologia , Mitocôndrias/patologia , Dinâmica Mitocondrial , Animais , Dano ao DNA , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Humanos , Cinética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitofagia , Estresse Oxidativo
12.
Environ Geochem Health ; 43(3): 1091-1107, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32839956

RESUMO

The clayey aquitard has the potential to release geogenic poisonous chemicals such as arsenic (As) to the adjacent aquifer owing to complex hydrologic or biogeochemical processes. However, it remains unclear whether the aquitard has effect on As enrichment in the underlying aquifer in regions without extensive groundwater pumping, and the related processes have been poorly known. Based on piezometer water chemistry, stable water isotopes, sediment chemistry and reactive-transport model, this study aims to reveal the impact process of the aquitard to As accumulation of underlying aquifer from central Yangtze River Basin, a As-affected area without extensive groundwater pumping. On the whole, As migrated from top to bottom of the aquitard (especially the depth over 10 m) and significantly influenced the As accumulation in the underlying aquifer. Nonetheless, the results of three topical boreholes showed two different hydrogeological conditions affected As release in the aquitard and enrichment in the underlying aquifer. Different hydrogeological conditions could result in the input of different species organic carbon and then impact As concentrations in the aquifer. When the aquitard was near surface water bodies, the reductive dissolution of iron oxides was the main driver for As release and the aquitard had a significant influence on the enrichment of arsenic in the aquifer. At areas without surface water bodies nearby, the desorption of As(V) from minerals was the main source of As and the concentrations of As in pore water were quite low; this pattern had little effect on the enrichment of arsenic in the aquifer.


Assuntos
Arsênio/análise , Água Subterrânea/química , Rios/química , Poluentes Químicos da Água/análise , China , Movimentos da Água
13.
Environ Pollut ; 266(Pt 1): 115212, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32698056

RESUMO

Nitrogen pollution of groundwater has created problems worldwide. Riparian zones form a connection hub for terrestrial and aquatic ecosystems. As a potential source of ammonium in groundwater, aquitards have an important effect on the environment of riparian zones. The spatial distribution and factors influencing the ammonium content in the riparian zone aquitard of a small watershed were analyzed through three geological boreholes with increasing distances from the river: boreholes A > B > C. The results show that the distribution of ammonium was closely related to the lithology of sediments. Under the influence of the river and floods, the average content of ion exchange form of ammonium of sediments in borehole A (stable sedimentary environment) was 94.31 mg kg-1, accounting for 21.2% of the transferable ammonium. The average proportions of ion exchange form of ammonium in the transferable ammonium of boreholes B and C (unstable sedimentary environment) were 19.1% and 17.4%, respectively. The carbonate and iron-manganese oxide forms of ammonium content of sediments in three boreholes were 0.96-15.28 mg kg-1 and 2.3-54.4 mg kg-1, respectively; this was mainly affected by the pH and Eh of the sedimentary environment. Organic sulfide, the form of transferable ammonium of sediments mainly exists in organic matter. The ammonium content in pore water generally increased with depth and was mainly derived from the mineralization of humic-like organic matter in borehole A. The ammonium in pore water in boreholes B and C mixed with ammonium from the mineralization of organic matter and the desorption of ion exchange form ammonium within sediments. The ammonium content in the pore water (up to 5.34 mg L-1) was much higher than the limit for drinking water of 0.5 mg L-1 in China. Therefore, the aquitard has a high risk of releasing ammonium and poses a certain threat to the quality of groundwater.


Assuntos
Compostos de Amônio/análise , Poluentes Químicos da Água/análise , China , Ecossistema , Sedimentos Geológicos , Rios , Água
14.
RSC Adv ; 8(40): 22429-22436, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35539748

RESUMO

Grain boundary plane distributions (GBPDs) are demonstrated to be spatially inhomogeneous in RCo5 permanent magnets. The potential effect of GBPDs on magnetic properties is proposed from major performance considerations, and approaches to exactly differentiate the boundary population are introduced. The crystallographic texture in permanent magnets should cover not only the texture of the crystals, but also the texture between crystals, which is helpful to advance the present understanding of the relationship between textures and properties in permanent magnets.

15.
Nat Commun ; 8: 14900, 2017 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-28447608

RESUMO

Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10-8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition.


Assuntos
Dismenorreia/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Povo Asiático/genética , China , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Hiperalgesia/genética , Fator de Crescimento Neural/genética , Dor/genética , Polimorfismo de Nucleotídeo Único , Adulto Jovem
16.
J Pharm Biomed Anal ; 126: 98-102, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27179187

RESUMO

In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of tivantinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 (2.1mm×50mm, 1.7µm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 1.0-100ng/mL (r(2)>0.9967) with a lower limit of quantification (1.0ng/mL). The extraction recovery was in the range of 79.4-84.2% for tivantinib and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.9% and accuracy was from -7.2% to 9.5%. No notable matrix effect and astaticism was observed for tivantinib. The method has been successfully applied to a pharmacokinetic study of tivantinib in rats for the first time, which provides the basis for the further development and application of tivantinib.


Assuntos
Antineoplásicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Pirrolidinonas/sangue , Quinolinas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Antineoplásicos/análise , Limite de Detecção , Masculino , Pirrolidinonas/análise , Quinolinas/análise , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos
17.
J Thromb Thrombolysis ; 42(2): 205-11, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27116356

RESUMO

To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of rivaroxaban, apixaban and edoxaban in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm × 50 mm, 1.7 µm) using gradient elution with a mobile phase of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 436.1 â†’ 145.1 for rivaroxaban, m/z 460.0 â†’ 443.1 for apixaban, m/z 548.2 â†’ 366.1 for edoxaban and m/z 285.2 â†’ 193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 1.0-200 ng/mL for rivaroxaban, 1.0-100 ng/mL for apixaban and 1.0-500 ng/mL for edoxaban. Total time for each chromatograph was 3.5 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations <10.5 % and the accuracy values ranged from -9.9 to 11.3 %. The method was successfully applied to a pharmacokinetic study of rivaroxaban, apixaban and edoxaban in rats.


Assuntos
Inibidores do Fator Xa/sangue , Pirazóis/sangue , Piridinas/sangue , Piridonas/sangue , Rivaroxabana/sangue , Espectrometria de Massas em Tandem/métodos , Tiazóis/sangue , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Inibidores do Fator Xa/farmacocinética , Pirazóis/farmacocinética , Piridinas/farmacocinética , Piridonas/farmacocinética , Ratos , Padrões de Referência , Reprodutibilidade dos Testes , Rivaroxabana/farmacocinética , Espectrometria de Massas em Tandem/normas , Tiazóis/farmacocinética
18.
Pharmacology ; 97(1-2): 43-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26588583

RESUMO

The objective of this work was to investigate the effect of orally administered evodiamine on the pharmacokinetics of dapoxetine and its active metabolite desmethyl dapoxetine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 10 mg/kg dapoxetine alone) and the combination group (10 mg/kg dapoxetine orally co-administered with 100 mg/kg evodiamine). The plasma concentration of dapoxetine and desmethyl dapoxetine were estimated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and different pharmacokinetic parameters were calculated using the Drug and Statistics 2.0 software. Compared to the control group, the pharmacokinetic parameter of t1/2, AUC(0-∞) and Tmax of dapoxetine in combination group was significantly increased by 63.3% (p < 0.01), 44.8% (p < 0.01) and 50.4% (p < 0.01), respectively. Moreover, evodiamine had significantly decreased the pharmacokinetic parameter of t1/2 and AUC(0-∞) of desmethyl dapoxetine. This study demonstrated that evodiamine inhibits the metabolism of dapoxetine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing dapoxetine to the patients already taking evodiamine.


Assuntos
Benzilaminas/farmacocinética , Naftalenos/farmacocinética , Quinazolinas/farmacologia , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Meia-Vida , Masculino , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
20.
Biochem Biophys Res Commun ; 341(4): 964-72, 2006 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-16458253

RESUMO

Organ-specific metastasis is an important character of cancer cells. Cancer cells that can metastasize to a special organ were thought to have different proteins in cell membrane, which might have potential utility as diagnostic markers and therapeutic targets. In the present work, based on high liver-metastatic gastric cancer cells, XGC9811-L, a screening approach with phage displayed peptide library, was successfully used to isolate 8-mer peptide ligands binding to the target cells. The phage20 had the highest binding efficiency to XGC9811-L cells, which also displayed remarkable cell specificity. Peptide20 that was displayed on phage20 could suppress the motility and invasion of XGC9811-L significantly. The adhesive ability of XGC9811-L to collagen IV was also inhibited by peptide20. Furthermore, phage20 could significantly reduce the incidence of liver metastasis of gastric cancer transplanted into nude mice and was also beneficial for the reduction the number of metastatic nodules in the liver. In conclusion, the phage display is an effective method to screen for the new molecules associated with organ-specific metastasis. The selected peptide20 can reverse the liver metastasis behavior of the gastric cancer cells.


Assuntos
Neoplasias Hepáticas/secundário , Metástase Neoplásica/tratamento farmacológico , Biblioteca de Peptídeos , Peptídeos/uso terapêutico , Neoplasias Gástricas/patologia , Sequência de Aminoácidos , Animais , Bacteriófagos/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Camundongos , Invasividade Neoplásica/fisiopatologia
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