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1.
Bull Entomol Res ; 114(2): 302-307, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38557482

RESUMEN

Mosquito-borne diseases have emerged in North Borneo in Malaysia due to rapid changes in the forest landscape, and mosquito surveillance is key to understanding disease transmission. However, surveillance programmes involving sampling and taxonomic identification require well-trained personnel, are time-consuming and labour-intensive. In this study, we aim to use a deep leaning model (DL) to develop an application capable of automatically detecting mosquito vectors collected from urban and suburban areas in North Borneo, Malaysia. Specifically, a DL model called MobileNetV2 was developed using a total of 4880 images of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus mosquitoes, which are widely distributed in Malaysia. More importantly, the model was deployed as an application that can be used in the field. The model was fine-tuned with hyperparameters of learning rate 0.0001, 0.0005, 0.001, 0.01 and the performance of the model was tested for accuracy, precision, recall and F1 score. Inference time was also considered during development to assess the feasibility of the model as an app in the real world. The model showed an accuracy of at least 97%, a precision of 96% and a recall of 97% on the test set. When used as an app in the field to detect mosquitoes with the elements of different background environments, the model was able to achieve an accuracy of 76% with an inference time of 47.33 ms. Our result demonstrates the practicality of computer vision and DL in the real world of vector and pest surveillance programmes. In the future, more image data and robust DL architecture can be explored to improve the prediction result.


Asunto(s)
Aedes , Aprendizaje Profundo , Mosquitos Vectores , Animales , Malasia , Mosquitos Vectores/fisiología , Mosquitos Vectores/clasificación , Aedes/fisiología , Aedes/clasificación , Culex/clasificación , Culex/fisiología , Culicidae/clasificación , Culicidae/fisiología
2.
J Environ Manage ; 359: 120962, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677229

RESUMEN

Low-water-level regulation has been effectively implemented in the restoration of urban river sediments in Guangzhou City, China. Further investigation is needed to understand the microbial mechanisms involved in pollutant degradation in low-water-level environments. This study examined sediment samples from nine rivers, including low-water-level rivers (LW), tidal waterways (TW), and enclosed rivers (ER). Metagenomic high-throughput sequencing and the Diting pipeline were utilized to investigate the microbial mechanisms involved in sediment C/N/S geochemical cycling during low-water-level regulation. The results reveal that the degree of pollution in LW sediment is lower compared to TW and ER sediment. LW sediment exhibits a higher capacity for pollutant degradation and elimination of black, odorous substances due to its stronger microbial methane oxidation, nitrification, denitrification, anammox, and oxidation of sulfide, sulfite, and thiosulfate. Conversely, TW and ER sediment showcase greater microbial methanogenesis, anaerobic fermentation, and sulfide generation abilities, leading to the persistence of black, odorous substances. Factors such as grit and silt content, nitrate, and ammonia concentrations impacted microbial metabolic pathways. Low-water-level regulation improved the micro-environment for functional microbes, facilitating pollutant removal and preventing black odorous substance accumulation. These findings provide insights into the microbial mechanisms underlying low-water-level regulation technology for sediment restoration in urban rivers.


Asunto(s)
Sedimentos Geológicos , Ríos , Sedimentos Geológicos/microbiología , Nitrógeno/análisis , Carbono , China
3.
Hepatobiliary Pancreat Dis Int ; 22(1): 14-21, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36328894

RESUMEN

BACKGROUND: Liver transplantation (LT) is an effective treatment option for end-stage liver disease. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, are widely used post LT. DATA SOURCES: In this review, we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT. The literature available on PubMed for the period of January 1999-September 2022 was reviewed. The key words were rapamycin, sirolimus, liver transplantation, hepatocellular carcinoma, diabetes, and lipid metabolism disorder. RESULTS: Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens. It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma (HCC) recurrence post LT. Rapamycin is closely related to two long-term complications after LT, diabetes and lipid metabolism disorders. CONCLUSIONS: Rapamycin prevents HCC recurrence post LT in some patients, but it also induces metabolic disorders. Reasonable use of rapamycin benefits the liver recipients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Sirolimus/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico
4.
Pestic Biochem Physiol ; 188: 105261, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36464366

RESUMEN

Based on the previous finding that a substitution at 5-position of the benzene ring is favorable to enhance the degradation rates of sulfonylurea herbicides, a total of 16 novel 2,5-disubsituted sulfonylurea compounds were chemically synthesized and fully characterized by means of 1H NMR, 13C NMR, HRMS and X-ray diffraction. By using HPLC analysis, the degradation behavior of M03, a compound belonging to this family, was studied and confirmed that chlorsulfuron itself is not a degraded product of the 2,5-disubstituted sulfonylureas. Inhibition constants against plant acetohydroxyacid synthase (AHAS) were determined for selected compounds, among which SU3 showed seven times stronger activity against the mutant W574L enzyme than chlorsulfuron. Molecular docking suggested that the substituted group at 5-position of benzene ring is likely to interact with the surrounding residues Met200 and Asp376 of AtAHAS. From the greenhouse herbicidal assay and crop safety test, SU5 and SU6 are considered as herbicide candidates to control dicotyledon weeds in corn, while SU3 is likely to be a promising candidate to control dicotyledon weed species and barnyard grass in wheat. The present research has therefore provided some new insights to understand the structure-activity relationships of herbicidal sulfonylureas with di-substitutions at benzene ring.


Asunto(s)
Benceno , Herbicidas , Simulación del Acoplamiento Molecular , Compuestos de Sulfonilurea/farmacología , Sulfonamidas , Herbicidas/farmacología
5.
Plant Dis ; 2022 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-35306837

RESUMEN

Peanut (Arachis hypogaea L.), one of the most important oilseed crops in tropical and subtropical regions of the world (Kumar and Kirti 2011), is widely cultivated for its high protein and oil content in seeds. In August 2019, about 30% of A. hypogaea plants were found infected by leaf spot in the peanut-growing regions of Shandong Province, China. Disease symptoms appeared as the irregular and brown necrotic lesions on leaves that were 0.5 to 5.0 mm in diam. Twenty symptomatic plants were randomly sampled from peanut planting areas in Weihai and Yantai City. Small pieces (3 mm2) were cut from lesions, dipped in a 0.5% NaClO for 10 min, rinsed three times with sterilized distilled water, dried, placed onto potato-dextrose agar (PDA), and incubated in the dark at 25°C for 10 days. Three typical Cladosporium-like strains were isolated from diseased leaves of peanut. The colonies were grey to olivaceous green, reverse olivaceous black and woolly. The conidiophores were solitary, macronematous, unbranched or branched, straight or flexuous, cylindrical, slightly swollen at the apex, smooth. Conidiogenous cells were integrated, terminal and intercalary, with numerous loci on nodulose swelling. Ramoconidia were cylindrical, oblong, fusiform, 8.0 to 19.5×2.0 to 4.5 µm, aseptate or 1 septum, pale brown. Conidia were catenate, in densely branched chains, ellipsoid, ovoid, limoniform, aseptate, 4.0 to 11.5×2.5 to 5.5 µm, smooth, with conspicuous hila. The conidia easily break off from the chains. The morphological characteristics of these isolates matched the descriptions of Cladosporium tenuissimum (Bensch et al. 2010). For the molecular identification, the partial actin (act) and translation elongation factor 1-alpha (tef1) genes were amplified and sequenced using the respective primers ACT-512F/ACT-783R and EF1-728F/EF1-986R (Carbone and Kohn 1999). The representative sequences, deposited in GenBank (act: OL332701, OL332702 and OL332703; tef1: OL322090, OL322091 and OL322092), exhibited 99.6% and 100% identical to C. tenuissimum ex-type isolate CBS 125995 (HM148687 and HM148442). Phylogenetic analysis was done by Neighbor-Joining (NJ) analysis based on act+tef1 sequences. These three isolates were identified as C. tenuissimum by morphological and molecular characteristics. Pathogenicity of each C. tenuissimum isolate was tested on peanut in the greenhouse at 28°C with 75% relative humidity. Twenty plants of A. hypogaea were inoculated with the conidial suspension (1.0 × 105 conidia/ml) on the leaf surface. Ten plants were mock inoculated with sterile water as controls. Within 2 weeks, inoculated plants exhibited dark necrotic lesions on leaves which were similar to the symptoms observed in the field, while the mock inoculated plants remained symptomless. The fungal pathogen which was reisolated from inoculated rather than mock inoculated leaf tissues was identical to the original pathogen on the basis of morphological and molecular analysis, confirming Koch's postulates. To our knowledge, this is the first report of leaf spot caused by C. tenuissimum on peanut in China. The C. tenuissimum infection poses a serious threat by reducing the yield and quality of peanut in Shandong Province. This research is especially valuable to enhance epidemiological studies and implement effective control strategies.

6.
Langmuir ; 37(43): 12529-12538, 2021 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-34689549

RESUMEN

Thermal stability is the key issue in the industrial application of supported metal nanocatalysts. A combination method of density functional theory calculations, machine learning, and molecular dynamics simulation is adopted to study the sintering behavior of supported platinum (Pt) nanoparticles on graphene or TiO2 nanosheet, and analyze sintering mechanisms under different temperatures, particle sizes, and metal support interactions (MSIs). The results show that the agglomeration of supported nanoparticles is mainly based on the mechanism of small particle migration and growth. Small-sized particles with high surface energy determine the sintering rate. In addition, the increase of temperature is conducive to the agglomeration of particles, especially for systems with strong MSI. Based on the analysis of the sintering process, a sintering kinetic model of supported Pt nanoparticles related to particle size, temperature, and MSI is established, which provides theoretical guidance for the design of supported metal catalysts with high thermal stability.

7.
Proc Natl Acad Sci U S A ; 115(41): E9649-E9658, 2018 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-30249642

RESUMEN

The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for antifungal drug discovery. First, we show that several AHAS inhibitors developed as commercial herbicides are powerful accumulative inhibitors of Candida albicans AHAS (Ki values as low as 800 pM) and have determined high-resolution crystal structures of this enzyme in complex with several of these herbicides. In addition, we have demonstrated that chlorimuron ethyl (CE), a member of the sulfonylurea herbicide family, has potent antifungal activity against five different Candida species and Cryptococcus neoformans (with minimum inhibitory concentration, 50% values as low as 7 nM). Furthermore, in these assays, we have shown CE and itraconazole (a P450 inhibitor) can act synergistically to further improve potency. Finally, we show in Candida albicans-infected mice that CE is highly effective in clearing pathogenic fungal burden in the lungs, liver, and spleen, thus reducing overall mortality rates. Therefore, in view of their low toxicity to human cells, AHAS inhibitors represent a new class of antifungal drug candidates.


Asunto(s)
Acetolactato Sintasa , Antifúngicos , Candida albicans/enzimología , Candidiasis , Criptococosis , Cryptococcus neoformans/enzimología , Proteínas Fúngicas , Acetolactato Sintasa/antagonistas & inhibidores , Acetolactato Sintasa/química , Acetolactato Sintasa/metabolismo , Animales , Antifúngicos/química , Antifúngicos/farmacología , Candidiasis/tratamiento farmacológico , Candidiasis/enzimología , Criptococosis/tratamiento farmacológico , Criptococosis/enzimología , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/química , Herbicidas/química , Herbicidas/farmacología , Humanos , Ratones
8.
Langmuir ; 35(19): 6393-6402, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31023009

RESUMEN

The structural and electronic properties of the interface are critical for the morphology of supported metal nanoparticles and thus the performance in catalysis, photonics, biomedical research, and other areas. To reveal the intrinsic mechanism of the formation of various morphologies, a multiscale simulation strategy is adopted to bridge the macroscopic structures by experimental observations and microscopic properties by theoretical calculations. This strategy incorporates the density functional theory (DFT) for the interaction energy calculation, the molecular dynamics (MD) simulation for the structure evolution, and theoretical model for the correlation with contact angles. The interaction energies between Pt atoms (four-atom clusters) and substrates are applied for the force field parametrization in the following MD simulation. Simulation results show the binding energies and structural properties such as radial distribution function and coordination number for supported metal nanoparticles with various sizes in detail. Notably, the contact angles of supported nanoparticles are well correlated by the strength of metal-support interactions. This work yields guidelines on the structure modulation of supported metal nanoparticles via interfacial control.

9.
Phys Chem Chem Phys ; 21(24): 12895-12904, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31157340

RESUMEN

Brittle porous materials offer a wide variety of promising applications due to their high surface-area-to-volume ratios and controllable porous structures. Getting comprehensive knowledge of the structural stability is of great significance for avoiding the irreversible destruction of these materials. Based on interpenetrating bicontinuous structures, we innovatively adopted a sequential mesoscopic simulation strategy to show the pore size effect on the mechanical stability, which involves structural evolution by the mesoscale dynamic density functional method and mechanical behavior by the highly efficient lattice spring model. Simulation results show that specific surface areas, Young's moduli and fracture strains decrease with the increase of pore widths on the premise of the same porosity. More uniform stress/strain distributions are observed in structures with smaller pore sizes or more uniform defect distributions. From the local stress distribution analysis, the effective stress transfer occurs in the solid phase, which runs through the simulation box along the tensile direction, and the mechanical disparity among systems with different pore sizes is due to different volume fractions and microstructures of the solid phase. Larger pore sizes result in lower Weibull moduli due to the increased heterogeneity and a less predictable failure behavior, and the concentrated defects usually result in mechanical anisotropy.

10.
Angew Chem Int Ed Engl ; 58(24): 8187-8191, 2019 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-30990948

RESUMEN

The regioselective hydroboration of aliphatic internal alkenes remains a great challenge. Reported herein is an iridium-catalyzed hydroboration of aliphatic internal alkenes, providing distal-borylated products in good to excellent yields with high regioselectivity (up to 99:1). We also demonstrate that the C-B bond of the distal-borylated product can be readily converted into other functional groups. DFT calculations indicate that the reaction proceeds through an unexpected IrIII /IrV cycle.

11.
J Biol Chem ; 291(3): 1115-22, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26511317

RESUMEN

Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxrα in mice with hepatocyte-specific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxrα produced equivalent, non-additive effects on the lipogenic genes. Thus, insulin was unable to induce the lipogenic genes in the absence of Lxrα, and LXRα was unable to induce the lipogenic genes in the absence of insulin. However, insulin was not required for LXRα to modulate the phospholipid profile, or to suppress genes in the ER stress or inflammation pathways. These data show that insulin is required specifically for the lipogenic effects of LXRα and that manipulation of the insulin signaling pathway could dissociate the beneficial effects of LXR on cholesterol efflux, inflammation, and ER stress from the negative effects on lipogenesis.


Asunto(s)
Estrés del Retículo Endoplásmico , Regulación de la Expresión Génica , Hepatitis/metabolismo , Insulina/metabolismo , Lipogénesis , Hígado/metabolismo , Receptores Nucleares Huérfanos/agonistas , Animales , Cruzamientos Genéticos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Hepatitis/complicaciones , Hepatitis/enzimología , Hepatitis/inmunología , Resistencia a la Insulina , Hígado/enzimología , Hígado/inmunología , Receptores X del Hígado , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores Nucleares Huérfanos/antagonistas & inhibidores , Receptores Nucleares Huérfanos/genética , Receptores Nucleares Huérfanos/metabolismo , Fosfolípidos/metabolismo , Receptor de Insulina/agonistas , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transducción de Señal
12.
J Chem Phys ; 145(22): 224306, 2016 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-27984876

RESUMEN

The method of time-dependent quantum wave packet dynamics has been successfully extended to study the charge transfer/exchange process in low energy two-body heavy particle collisions. The collision process is described by coupled-channel equations with diabatic potentials and (radial and rotational) couplings. The time-dependent coupled equations are propagated with the multiconfiguration time-dependent Hartree method and the modulo squares of S-matrix is extracted from the wave packet by the flux operator with complex absorbing potential (FCAP) method. The calculations of the charge transfer process 12Σ+ H-(1s2)+Li(1s22s)→22Σ+/32Σ+/12Π H(1s)+Li-(1s22s2l)(l=s,p) at the incident energy of about [0.3, 1.3] eV are illustrated as an example. It shows that the calculated reaction probabilities by the present FCAP reproduce that of quantum-mechanical molecular-orbital close-coupling very well, including the peak structures contributed by the resonances. Since time-dependent external interactions can be directly included in the present FCAP calculations, the successful implementation of FCAP provides us a powerful potential tool to study the quantum control of heavy particle collisions by lasers in the near future.

13.
J Chem Phys ; 144(5): 054306, 2016 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-26851920

RESUMEN

K-vacancy Auger states of N(q+) (q = 2-5) ions are studied by using the complex multireference single- and double-excitation configuration interaction (CMRD-CI) method. The calculated resonance parameters are in good agreement with the available experimental and theoretical data. It shows that the resonance positions and widths converge quickly with the increase of the atomic basis sets in the CMRD-CI calculations; the standard atomic basis set can be employed to describe the atomic K-vacancy Auger states well. The strong correlations between the valence and core electrons play important roles in accurately determining those resonance parameters, Rydberg electrons contribute negligibly in the calculations. Note that it is the first time that the complex scaling method has been successfully applied for the B-like nitrogen. CMRD-CI is readily extended to treat the resonance states of molecules in the near future.

14.
Sheng Li Xue Bao ; 68(6): 783-789, 2016 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-28004073

RESUMEN

The aim of this study is to investigate the effects of hypoxia inducible factor-2α (HIF-2α) and Notch3 on CoCl2-induced migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were exposed to normoxia (21% O2) or chemical hypoxia (21% O2 plus CoCl2). Short hairpin RNA (shRNA) was used to knock down HIF-2α and Notch3 in MCF-7 cells. The mRNA expression levels of HIF-2α, Notch3 and Hey1 were measured by RT-PCR. Western blot was performed to determine the protein expression levels of HIF-2α, Notch3, Hey1, Snail and E-cadherin. CoCl2 treatment resulted in higher protein expression levels of HIF-2α, Notch3, Hey1, Snail (P < 0.05) and lower levels of E-cadherin (P < 0.05), and promoted migration and invasion of MCF-7 cells (P < 0.05). shRNA-HIF-2α suppressed CoCl2-induced mRNA expression of Notch3 and Hey1. Notch3 knockdown down-regulated Snail and up-regulated E-cadherin at protein level under simulated hypoxia (P < 0.05), and inhibited CoCl2-induced migration and invasion of MCF-7 cells (P < 0.05). In conclusion, our data provide evidence that HIF-2α may promote the migration and invasion of MCF-7 cells under chemical hypoxic conditions by potentiating Notch3 pathway.


Asunto(s)
Neoplasias de la Mama , Movimiento Celular , Transducción de Señal , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Cadherinas , Hipoxia de la Célula , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Células MCF-7 , Invasividad Neoplásica , ARN Interferente Pequeño , Receptor Notch3 , Regulación hacia Arriba
15.
J Oral Maxillofac Surg ; 73(5): 985-93, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25883003

RESUMEN

PURPOSE: To evaluate the split patterns of the mandibular ramus in sagittal split ramus osteotomy (SSRO) using cone-beam computed tomography (CBCT) and examine the related anatomic features that may be associated with these split patterns. PATIENTS AND METHODS: The authors designed and implemented a retrospective cohort study and enrolled a sample composed of consecutive patients with different maxillofacial deformities who underwent an SSRO from July 2011 through October 2012 at the Department of Orthognathic Surgery at the Tianjin Stomatological Hospital of Nankai University. The split patterns, which were selected at random at 1 side per patient, were evaluated by CBCT as the outcome variable 1 month after the operation. The predictor variable was composed of a set of heterogeneous anatomic variables that could be associated with the split patterns. Type I split was defined as a split at the lingual side near the mylohyoid sulcus. Type II split was defined as a split at the posterior border of the mandibular ramus. Appropriate bivariate and regression statistics were computed, and the level of statistical significance was set at a P value less than .05. RESULTS: One hundred thirty patients with different maxillofacial deformities (62 male and 68 female; mean age, 23 yr) underwent an SSRO. Two types of split patterns of the mandibular ramus were observed in SSRO: a split at the lingual side near the mylohyoid sulcus, which occurred in 75.38% of patients, and split at the posterior border region of the mandibular ramus, which occurred in 24.62% of patients. No fracture lines were observed through the mandibular canal. The thickness of the lingual cortical bone between the mandibular canal and the posterior border of the ramus was significantly associated with the split patterns (P < .05). The thickness of the cortical bone in the posterior border of the ramus, the degree of the mandibular angle, and the shapes of the mandibular ramus in the axial plane also were found to influence these split patterns. There was no meaningful association between the split patterns and a patient's age and gender. CONCLUSION: The split patterns of the mandibular ramus during SSRO were influenced by some anatomic features of the mandibular ramus. Therefore, examining the anatomy of the mandible with CBCT before surgery may play an important role in predicting the split patterns of the mandibular ramus during SSRO.


Asunto(s)
Mandíbula/cirugía , Anomalías Maxilofaciales/diagnóstico por imagen , Osteotomía Sagital de Rama Mandibular , Adulto , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Estudios Retrospectivos , Adulto Joven
16.
Sheng Li Xue Bao ; 67(6): 611-7, 2015 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-26701637

RESUMEN

The aim of this study was to investigate the effects of digoxin on the chemoresistance of human breast cancer cell line MCF-7/adriamycin (ADR) and its underlying mechanism. MCF-7 and MCF-7/ADR cells were designated as control and ADR groups, respectively. MCF-7/ADR cells in ADR + digoxin group received 48 h of digoxin (10 nmol/L) treatment; MCF-7/ADR cells transfected with pLKO.1-shHIF-1α and pLKO.1-shcontrol plasmids were named shHIF-1α and shcontrol groups, respectively. CCK-8 assay was employed to detect the cytotoxic effect of ADR on MCF-7/ADR cells, and IC50 value and resistance index were calculated according to CCK-8. RT-PCR was used to measure the mRNA levels of hypoxia inducible factor-1α (HIF-1α) and multidrug resistance-1 (MDR1). Western blot was used to analyze the protein levels of HIF-1α and MDR1. Flow cytometry was used to determine the apoptosis. The result showed that the resistance index of MCF-7/ADR cells was 115.6, and it was reduced to 47.2 under the action of digoxin (P < 0.05). In comparison with control group, ADR groups showed increased protein and mRNA levels of HIF-1α and MDR1 (P < 0.05). Digoxin reduced the protein levels of HIF-1α and MDR1, as well as the mRNA level of MDR1, but did not affect the mRNA level of HIF-1α. After HIF-1α gene was silenced, the protein levels of HIF-1α and MDR1 were down-regulated (P < 0.05), and the pro-apoptotic effect of ADR on MCF-7/ADR cells was enhanced. Although it was also observed that digoxin promoted cell apoptosis in both shcontrol and shHIF-1α groups, the difference between the two groups was not significant. In conclusion, the results suggest that digoxin may partially reverse the ADR resistance in human breast cancer cell line MCF-7/ADR by means of down-regulating the expression levels of HIF-1α and MDR1 and promoting apoptosis via HIF-1α-independent pathway.


Asunto(s)
Digoxina/farmacología , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células MCF-7/efectos de los fármacos , ARN Mensajero , Transfección
17.
Blood ; 120(3): 636-46, 2012 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-22661702

RESUMEN

Sickle cell disease (SCD) is associated with a complex vascular pathophysiology that includes activation of coagulation and inflammation. However, the crosstalk between these 2 systems in SCD has not been investigated. Here, we examined the role of tissue factor (TF) in the activation of coagulation and inflammation in 2 different mouse models of SCD (BERK and Townes). Leukocytes isolated from BERK mice expressed TF protein and had increased TF activity compared with control mice. We found that an inhibitory anti-TF antibody abrogated the activation of coagulation but had no effect on hemolysis or anemia. Importantly, inhibition of TF also attenuated inflammation and endothelial cell injury as demonstrated by reduced plasma levels of IL-6, serum amyloid P, and soluble vascular cell adhesion molecule-1. In addition, we found decreased levels of the chemokines MCP-1 and KC, as well as myeloperoxidase in the lungs of sickle cell mice treated with the anti-TF antibody. Finally, we found that endothelial cell-specific deletion of TF had no effect on coagulation but selectively attenuated plasma levels of IL-6. Our data indicate that different cellular sources of TF contribute to activation of coagulation, vascular inflammation, and endothelial cell injury. Furthermore, it appears that TF contributes to these processes without affecting intravascular hemolysis.


Asunto(s)
Anemia de Células Falciformes/inmunología , Coagulación Sanguínea/fisiología , Inflamación/inmunología , Tromboplastina/inmunología , Tromboplastina/metabolismo , Anemia de Células Falciformes/sangre , Animales , Quimiocina CCL2/sangre , Quimiocina CXCL1/sangre , Modelos Animales de Enfermedad , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Eritrocitos/citología , Eritrocitos/fisiología , Femenino , Hemólisis/fisiología , Inflamación/sangre , Interleucina-6/sangre , Leucocitos/inmunología , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Transgénicos , Neutrófilos/inmunología , Componente Amiloide P Sérico/metabolismo , Molécula 1 de Adhesión Celular Vascular/sangre
18.
Blood ; 119(23): 5543-52, 2012 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-22547577

RESUMEN

Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF Ab. Of the 2 TF-positive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.


Asunto(s)
Coagulación Sanguínea , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/metabolismo , Tromboplastina/metabolismo , Trombosis de la Vena/complicaciones , Animales , Línea Celular Tumoral , Micropartículas Derivadas de Células/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Hemostasis , Humanos , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/genética , ARN Mensajero/genética , Tromboplastina/genética , Trombosis de la Vena/metabolismo
19.
Arterioscler Thromb Vasc Biol ; 33(8): 1829-36, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23723374

RESUMEN

OBJECTIVE: Individuals with elevated prothrombin, including those with the prothrombin G20210A mutation, have increased risk of venous thrombosis. Although these individuals do not have increased circulating prothrombotic biomarkers, their plasma demonstrates increased tissue factor-dependent thrombin generation in vitro. The objectives of this study were to determine the pathological role of elevated prothrombin in venous and arterial thrombosis in vivo, and distinguish thrombogenic mechanisms in these vessels. APPROACH AND RESULTS: Prothrombin was infused into mice to raise circulating levels. Venous thrombosis was induced by electrolytic stimulus to the femoral vein or inferior vena cava ligation. Arterial thrombosis was induced by electrolytic stimulus or ferric chloride application to the carotid artery. Mice infused with prothrombin demonstrated increased tissue factor-triggered thrombin generation measured ex vivo, but did not have increased circulating prothrombotic biomarkers in the absence of vessel injury. After venous injury, elevated prothrombin increased thrombin generation and the fibrin accumulation rate and total amount of fibrin ≈ 3-fold, producing extended thrombi with increased mass. However, elevated prothrombin did not accelerate platelet accumulation, increase the fibrin accumulation rate, or shorten the vessel occlusion time after arterial injury. CONCLUSIONS: These findings reconcile previously discordant findings on thrombin generation in hyperprothrombinemic individuals measured ex vivo and in vitro, and show elevated prothrombin promotes venous, but not arterial, thrombosis in vivo.


Asunto(s)
Coagulación Sanguínea/fisiología , Protrombina/metabolismo , Trombofilia/metabolismo , Trombosis de la Vena/metabolismo , Animales , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Arterias Carótidas/fisiología , Cloruros/farmacología , Modelos Animales de Enfermedad , Vena Femoral/fisiología , Compuestos Férricos/farmacología , Fibrina/metabolismo , Humanos , Ratones , Noxas/farmacología , Protrombina/farmacología , Factores de Riesgo , Trombofilia/inducido químicamente , Trombofilia/epidemiología , Vena Cava Inferior/fisiología , Trombosis de la Vena/inducido químicamente , Trombosis de la Vena/epidemiología
20.
Dent Traumatol ; 30(5): 385-390, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24735156

RESUMEN

BACKGROUND: Although traumatic dental injuries are most common during childhood and can cause significant health problems, the literature contains few reports of the prevalence of traumatic dental injuries in children in China. AIM: To study the prevalence of and factors related to traumatic dental injuries among 8- to 12-year-old schoolchildren in Pinggu District, Beijing during 2012. MATERIAL AND METHODS: An epidemiological survey of traumatic dental injuries was performed in all nine primary schools of Pinggu District, Beijing, China. Andreasen criteria as the diagnostic criteria were used in the study. A sample of 5165 students aged from 8 to 12 years old were examined, consisting of 2711 boys and 2454 girls. RESULTS: A total of 367 students (7.1%), 251 boys and 116 girls, were found to have traumatic dental injuries, and 442 permanent teeth were involved. Maxillary central incisors were the most affected by dental injuries (378, 85.5%). Among the 52 traumatized teeth (11.8%) that were treated, endodontic treatment (55.8%) was the most common method. CONCLUSIONS: The study showed a relatively low prevalence of dental injuries in Pinggu District. The treatment rate of traumatized teeth was relatively low. Schoolchildren need more medical assistance when they face accidents. Policymakers should develop a strategy for the prevention of traumatic dental injuries. Educational programs to increase the knowledge of traumatic dental injuries and prevent them should be initiated for teachers and schoolchildren.


Asunto(s)
Traumatismos de los Dientes/epidemiología , Niño , China/epidemiología , Femenino , Humanos , Masculino
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