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Background: Hypertensive intracerebral hemorrhage combined with cerebral hernia (HIH-CH) is a serious condition. Neuroendoscopy can effectively remove intracranial hematoma, but there is no relevant research support for its utility in patients with HIH-CH. The purpose of this study is to investigate the efficacy and safety of neuroendoscopy in patients with HIH-CH. Methods: Patients with HIH-CH who received craniotomy or neuroendoscopy treatment were included. The patients were divided into craniotomy (CHE) group and neuroendoscopy (NEHE) group. Clinical data and follow-up outcome of the two groups were collected. The primary outcome was hematoma clearance. Results: The hematoma clearance rate (%) of patients in NEHE group was 97.65 (92.75, 100.00), and that of patients in CHE group was 95.00 (90.00, 100.00), p > 0.05. The operation time and intraoperative bleeding volume of patients in NEHE group were significantly less than those in CHE group (p < 0.05). There was no significant difference in the volume of residual hematoma and the incidence of rebleeding between the two groups (p > 0.05). The length of stay in ICU in NEHE group was significantly shorter than that in CHE group (p < 0.05). Conclusion: Neuroendoscopy can safely and effectively remove the intracranial hematoma in patients with hypertensive intracerebral hemorrhage and cerebral hernia, significantly shorten the operation time, reduce the amount of intraoperative hemorrhage, shorten the ICU stay.
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Surgical clipping of pericallosal artery aneurysm is technically challenging since it is fragile and tends to rupture accidentally during the operation. This study was aimed to evaluate the efficacy and safety of MRI-neuronavigation-assisted microsurgery for pericallosal artery aneurysm clipping. Forty patients diagnosed with pericallosal artery aneurysms who underwent craniotomy clipping were enrolled. Among these patients, 18 cases accepted routine surgical approaches, while another 22 cases accepted MRI-neuronavigation-assisted microsurgery. Design of craniotomy, operation pathway, operation duration, intraoperative cerebral protection and superior drainage vein protection were analyzed retrospectively. All the 40 cases underwent aneurysm clipping by pre-coronal inter-hemispheric approach, and all aneurysms were clipped completely confirmed by postoperative CTA or DSA. During the operations, MRI-neuronavigation provided precise spatial configuration of pericallosal artery aneurysms, and allowed accurate and real-time identification for the adjacent arteries and brain structures, and no aneurysms ruptured accidentally during the operations. Functional cortex and draining veins were protected well. Compared with routine surgical approaches, the MRI-neuronavigation-assisted microsurgery showed less operation duration, few adverse events induced by accurate location for aneurysm and less invasion to draining veins. Therefore, MRI-neuronavigation-assisted microsurgery could precisely locate the pericallosal artery aneurysm, optimize surgical approaches, and help to cerebral protection. It is expected to reduce the surgical risk and improve the precision and security, can be regarded as an effective technology in the clipping of pericallosal artery aneurysms.
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Objective: The environment influences the sow's health and physiology during gestation. This study was conducted to evaluate indoor environmental parameters and physiological responses of early-gestation sows and investigate the possible methods for assessing the thermal environment in commercial houses. Methods: A total of 20 early-gestation sows (commercial purebred Yorkshire) with an average body weight of 193.20 ± 3.62 kg were used for this study in winter, spring, summer, and autumn. The indoor environment parameters comprising dry-bulb temperature (Tdb), relative humidity (RH), and carbon dioxide (CO2) were recorded in 30-min intervals. Physiological parameters including heart rate (HR) and respiration rate (RR) of sows were also measured every 30 min. Wet-bulb temperature (Twb) was calculated using Tdb, RH and atmospheric pressure was recorded at a nearby weather station. Results: The average indoor Tdb and RH were 12.98 ± 2.03°C and 80.4 ± 6.4% in winter, 18.98 ± 2.68°C and 74.4 ± 9.0% in spring, 27.49 ± 2.05°C and 90.6 ± 6.4% in summer, and 17.10 ± 2.72°C and 64.5 ± 10.9% in autumn. A higher average concentration of CO2 was observed in winter (1,493 ± 578 mg/m3) than in spring (1,299 ± 489 mg/m3), autumn (1,269 ± 229 mg/m3), and summer (702 ± 128 mg/m3). Compared with the HR and RR in the optimum environment, high RH in the house led to a significant decrease in both HR and RR (P < 0.05). In addition, a significant decline in HR was also obtained at high temperatures (P < 0.05). A temperature humidity index (THI), THI = 0.82 × Tdb + 0.18 × Twb, was determined for early-gestation sows, and the THI thresholds were 25.6 for HR. The variation in THI in summer showed that heat stress still occurred under the pad-fan cooling system. Conclusion: This study demonstrated the critical significance of considering physiological responses of early-gestation sows in commercial houses and THI thresholds. We recommend that much more cooling measures should be taken for early-gestation sows in summer.
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This work presents a strategy for independent control of the amplitude and phase of transmissive circular-polarization (CP) waves. The designed meta-atom consists of an elliptical-polarization receiver and a CP transmitter. By changing the axial ratio (AR) and polarization of the receiver, amplitude modulation can be realized based on polarization mismatching theory, with negligible cumbrous components. While by rotating the element, a full phase coverage enabled by the geometric phase is achieved. Subsequently, a CP transmitarray antenna (TA) with high gain and low side-lobe level (SLL) is implemented to experimentally validate our strategy, and the tested results match well with the simulated ones. During the operating band from 9.6 to 10.4 GHz, the proposed TA obtains an average SLL of -24.5 dB, a lowest SLL of -27.7 dB at 9.9 GHz, and a maximum gain of 19 dBi at 10.3 GHz, with the measured AR lower than 1 dB, which mainly benefits from high polarization purity (HPP) of the proposed elements. The proposed strategy for full amplitude-phase manipulation of CP waves together with HPP paves a way for complicated field manipulations and indicates a promising candidate in antenna applications, such as anti-jamming systems and wireless communications.
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DNA sequence accounts for the majority of disease heritability, including cancer. Yet, not all familial cancer cases can be explained by genetic factors. It is becoming clear that environmentally induced epigenetic inheritance occurs and that the progeny's traits can be shaped by parental environmental experiences. In humans, epidemiological studies have implicated environmental toxicants, such as the pesticide DDT, in intergenerational cancer development, including breast and childhood tumors. Here, we show that the female progeny of males exposed to DDT in the pre-conception period have higher susceptibility to developing aggressive tumors in mouse models of breast cancer. Sperm of DDT-exposed males exhibited distinct patterns of small non-coding RNAs, with an increase in miRNAs and a specific surge in miRNA-10b levels. Remarkably, embryonic injection of the entire sperm RNA load of DDT-exposed males, or synthetic miRNA-10b, recapitulated the tumor phenotypes observed in DDT offspring. Mechanistically, miR-10b injection altered the transcriptional profile in early embryos with enrichment of genes associated with cell differentiation, tissue and immune system development. In adult DDT-derived progeny, transcriptional and protein analysis of mammary tumors revealed alterations in stromal and in immune system compartments. Our findings reveal a causal role for sperm RNAs in environmentally induced inheritance of cancer predisposition and, if confirmed in humans, this could help partially explain some of the "missing heritability" of breast, and other, malignancies.
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Molecular-level analyses of breast carcinogenesis benefit from vivo disease models. Estrogen receptor 1 (Esr1) and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) overexpression targeted to mammary epithelial cells in genetically engineered mouse models induces largely similar rates of proliferative mammary disease in prereproductive senescent mice. Herein, with natural reproductive senescence, Esr1 overexpression compared with CYP19A1 overexpression resulted in significantly higher rates of preneoplasia and cancer. Before reproductive senescence, Esr1, but not CYP19A1, overexpressing mice are tamoxifen resistant. However, during reproductive senescence, Esr1 mice exhibited responsiveness. Both Esr1 and CYP19A1 are responsive to letrozole before and after reproductive senescence. Gene Set Enrichment Analyses of RNA-sequencing data sets showed that higher disease rates in Esr1 mice were accompanied by significantly higher expression of cell proliferation genes, including members of prognostic platforms for women with early-stage hormone receptor-positive disease. Tamoxifen and letrozole exposure induced down-regulation of these genes and resolved differences between the two models. Both Esr1 and CYP19A1 overexpression induced abnormal developmental patterns of pregnancy-like gene expression. This resolved with progression through reproductive senescence in CYP19A1 mice, but was more persistent in Esr1 mice, resolving only with tamoxifen and letrozole exposure. In summary, genetically engineered mouse models of Esr1 and CYP19A1 overexpression revealed a diversion of disease processes resulting from the two distinct molecular pathophysiological mammary gland-targeted intrusions into estrogen signaling during reproductive senescence.
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Aromatasa , Células Epiteliales , Receptor alfa de Estrógeno , Glándulas Mamarias Animales , Animales , Femenino , Ratones , Embarazo , Células Epiteliales/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Estrógenos , Letrozol , Tamoxifeno/farmacología , Expresión Génica , Glándulas Mamarias Animales/metabolismo , Aromatasa/genética , Aromatasa/metabolismoRESUMEN
Age is a risk factor for human estrogen receptor-positive breast cancer, with highest prevalence following menopause. While transcriptome risk profiling is available for human breast cancers, it is not yet developed for prognostication for primary or secondary breast cancer development utilizing at-risk breast tissue. Both estrogen receptor α (ER) and aromatase overexpression have been linked to human breast cancer. Herein, conditional genetically engineered mouse models of estrogen receptor 1 (Esr1) and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) were used to show that induction of Esr1 overexpression just before or with reproductive senescence and maintained through age 30 months resulted in significantly higher prevalence of estrogen receptor-positive adenocarcinomas than CYP19A1 overexpression. All adenocarcinomas tested showed high percentages of ER+ cells. Mammary cancer development was preceded by a persistent proliferative transcriptome risk signature initiated within 1 week of transgene induction that showed parallels to the Prosigna/Prediction Analysis of Microarray 50 human prognostic signature for early-stage human ER+ breast cancer. CYP19A1 mice also developed ER+ mammary cancers, but histology was more divided between adenocarcinoma and adenosquamous, with one ER- adenocarcinoma. Results demonstrate that, like humans, generation of ER+ adenocarcinoma in mice was facilitated by aging mice past the age of reproductive senescence. Esr1 overexpression was associated with a proliferative estrogen pathway-linked signature that preceded appearance of ER+ mammary adenocarcinomas.
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Adenocarcinoma , Neoplasias de la Mama , Glándulas Mamarias Animales , Animales , Femenino , Ratones , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Envejecimiento/genética , Envejecimiento/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Expresión Génica , Aromatasa/genética , Aromatasa/metabolismo , Reproducción/genética , Reproducción/fisiologíaRESUMEN
In this paper, a novel broadband circularly polarized transmitarray antenna (CPTA) enabled by axial-ratio-improved receiver-transmitter metasurface loaded with parasitic patches is proposed. Split-ring-shaped parasitic patch is utilized to generate an additional resonant mode and significantly broaden the 3-dB axial ratio (AR) bandwidth of proposed receiver/transmitter patches from 6.64% to 15.61%. By cascading the receiver and transmitter with the same polarization and then rotating the cell, Pancharatnam-Berry phase can be exploited for providing a 2π phase shift. As verification, a CPTA prototype integrated with a self-made circularly polarized patch antenna is designed, fabricated, and measured. Experimental results show that the proposed CPTA obtains a 3-dB AR bandwidth of 27.1% from 12.1 to 15.9 GHz and an impedance bandwidth of 20.6% from 12.5 to 15.2 GHz. Additionally, it has a flat gain with a 3-dB gain bandwidth of 18.8% from 12.5 to 15.1 GHz, and a maximum gain of 25.6 dBi at 13.1 GHz is achieved. With the advantages of simple design, wide AR bandwidth, and flat gain performance, the proposed CPTA presents great potential applications in wireless systems.
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Lightweight design of leaf springs is conducive to reducing fuel consumption and improving vehicle comfort. The weight of leaf spring can be reduced obviously by using composite material. Stiffness and damping are the key factors that affect the properties of the leaf spring. The influence of the glass fiber laying angle and volume content on the stiffness and damping of the composite leaf spring was analyzed through experiment and simulation. The results show that the stiffness and damping properties of the leaf springs are related to the fiber laying angle and the fiber volume content. When the volume content and the number of layers are constant, the stiffness shows a nonlinear decreasing relationship with the laying angle, and the damping coefficient increases linearly with the laying angle. When the laying angle and the number of layers are constant, the stiffness increases linearly with the fiber volume content; the damping coefficient has a nonlinear decreasing relationship with the fiber volume content. The type of research can provide theoretical basis and reference for the design, analysis and optimization of composite leaf spring.
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Hojas de la Planta , Simulación por ComputadorRESUMEN
The problem of fault propagation which exists in the deeply integrated GNSS (Global Navigation Satellite System)/INS (Inertial Navigation System) system makes it difficult to identify faults. Once a fault occurs, system performance will be degraded due to the inability to identify and isolate the fault accurately. After analyzing the causes of fault propagation and the difficulty of fault identification, maintaining correct navigation solution is found to be the key to prevent fault propagation from occurring. In order to solve the problem, a novel robust algorithm based on convolutional neural network (CNN) is proposed. The optimal expansion factor of the robust algorithm is obtained adaptively by utilizing CNN, thus the adverse effect of fault on navigation solution can be reduced as much as possible. At last, the fault identification ability is verified by two types of experiments: artificial fault injection and outdoor occlusion. Experiment results show that the proposed robust algorithm which can successfully suppress the fault propagation is an effective solution. The accuracy of fault identification is increased by more than 20% compared with that before improvement, and the robustness of deep GNSS/INS integration is also improved.
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In this paper, a novel electrochemiluminescence (ECL) sensor of sol-gel@graphene luminescent composite film modified electrode for hyperin determination was prepared using graphene (G) as solid-phase microextraction (SPME) material, based on selective preconcentration of target onto an electrode and followed by luminol ECL detection. Hyperin was firstly extracted from aqueous solution through the modified GCE. Hydrogel, electrogenerated chemiluminescence reagents, pH of working solution, extraction time and temperature and scan rate were discussed. Under the optimum conditions, the change of ECL intensity was in proportion to the concentration of hyperin in the range of 0.02-0.24µg/mL with a detection limit of 0.01µg/mL. This method showed good performance in stability, reproducibility and precision for the determination of hyperin.
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Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel. Here we have investigated the effects of depletion of TNFAIP8 on the mRNA, microRNA and protein expression profiles in prostate and breast cancers and melanoma. Depending on the tumor cell type, knockdown of TNFAIP8 was found to be associated with increased mRNA expression of several antiproliferative and apoptotic genes (e.g., IL-24, FAT3, LPHN2, EPHA3) and fatty acid oxidation gene ACADL, and decreased mRNA levels of oncogenes (e.g., NFAT5, MALAT1, MET, FOXA1, KRAS, S100P, OSTF1) and glutamate transporter gene SLC1A1. TNFAIP8 knockdown cells also exhibited decreased expression of multiple onco-proteins (e.g., PIK3CA, SRC, EGFR, IL5, ABL1, GAP43), and increased expression of the orphan nuclear receptor NR4A1 and alpha 1 adaptin subunit of the adaptor-related protein complex 2 AP2 critical to clathrin-mediated endocytosis. TNFAIP8-centric molecules were found to be predominately implicated in the hypoxia-inducible factor-1α (HIF-1α) signaling pathway, and cancer and development signaling networks. Thus TNFAIP8 seems to regulate the cell survival and cancer progression processes in a multifaceted manner. Future validation of the molecules identified in this study is likely to lead to new subset of molecules and functional determinants of cancer cell survival and progression.
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Proteínas Reguladoras de la Apoptosis/genética , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Melanoma/genética , Neoplasias de la Próstata/genética , Proteómica/métodos , Secuencia de Aminoácidos , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia Celular , Progresión de la Enfermedad , Transportador 3 de Aminoácidos Excitadores/genética , Transportador 3 de Aminoácidos Excitadores/metabolismo , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de SeñalRESUMEN
UNLABELLED: Estrogen (E2) exerts a dual function on E2-deprived breast cancer cells, with both initial proliferation and subsequent induction of stress responses to cause apoptosis. However, the mechanism by which E2 integrally regulates cell growth or apoptosis-associated pathways remains to be elucidated. Here, E2 deprivation results in many alterations in stress-responsive pathways. For instance, E2-deprived breast cancer cells had higher basal levels of stress-activated protein kinase, c-Jun N-terminal kinase (JNK), compared with wild-type MCF-7 cells. E2 treatment further constitutively activated JNK after 24 hours. However, inhibition of JNK (SP600125) was unable to abolish E2- induced apoptosis, whereas SP600125 alone arrested cells at the G2 phase of the cell cycle and increased apoptosis. Further examination showed that inhibition of JNK increased gene expression of TNFα and did not effectively attenuate expression of apoptosis-related genes induced by E2. A notable finding was that E2 regulated both JNK and Akt as the downstream signals of insulin-like growth factor-1 receptor (IGFIR)/PI3K, but with distinctive modulation patterns: JNK was constitutively activated, whereas Akt and Akt-associated proteins, such as PTEN and mTOR, were selectively degraded. Endoplasmic reticulum-associated degradation (ERAD) was involved in the selective protein degradation. These findings highlight a novel IGFIR/PI3K/JNK axis that plays a proliferative role during the prelude to E2-induced apoptosis and that the endoplasmic reticulum is a key regulatory site to decide cell fate after E2 treatment. IMPLICATIONS: This study provides a new rationale for further exploration of E2-induced apoptosis to improve clinical benefit.
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Neoplasias de la Mama/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Estrógenos/farmacología , Receptor IGF Tipo 1/metabolismo , Antracenos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/fisiología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrógenos/deficiencia , Femenino , Humanos , MAP Quinasa Quinasa 4/antagonistas & inhibidores , MAP Quinasa Quinasa 4/metabolismo , Sistema de Señalización de MAP Quinasas , Células MCF-7 , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
OBJECTIVE: To evaluate the effects of 4-aminopyridine-3-methyl hydroxide (4-AP-3-MeOH) in rat's acute spinal cord injury. METHODS: A total of 12 adult male SD rats (250-300 g) were randomly divided into treatment (n = 6) and control (n = 6) groups. After compressing segment T11 of spinal cord for 30 min, the injured segment received 1 ml 4-AP-3-MeOH (100 µmol/ml) by topically application in treatment group while the control group received 1 ml saline.Somatosensory evoked potential (SSEP) was detected in both groups at pre-injury, 30 min post-injury and post-dosing. Then Luxol fast blue (LFB) staining of target spinal segment was performed. RESULTS: In treatment group, the values of SSEP at pre-injury, 30 min post-injury and post-dosing were 1.26 ± 0.35, 0.03 ± 0.05 and 0.45 ± 0.19 µv respectively. Comparing SSEP of 30 min post-injury with post-dosing, the difference was statistically significant (P < 0.01).While in control group, the values of SSEP at pre-injury, 30 min post-injury and post-dosing were 1.05 ± 0.39, 0.01 ± 0.02 and 0.02 ± 0.02 µv respectively. Comparing SSEP of 30 min post-injury with post-dosing, there was no statistical difference (P > 0.05). After 30 min injury, there were swelling and bleeding of spinal cord.LFB staining showed that both gray and white matter had swelling and bleeding and central canal was destroyed with varying degrees of demyelination. CONCLUSION: After 30 min of acute spinal cord injury, there are bleeding of gray and white matter with varying degrees of demyelination. Topical usage of K(+) blocker 4-AP-3-MeOH can effectively improve the conduction of SSEP after acute spinal cord injury in rats.
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Aminopiridinas/uso terapéutico , Compresión de la Médula Espinal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Masculino , Conducción Nerviosa/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Médula Espinal/fisiopatología , Compresión de la Médula Espinal/fisiopatologíaRESUMEN
PURPOSE: Our publications demonstrate that physiological concentrations of oestrogen (E2) induce endoplasmic reticulum and oxidative stress which finally result in apoptosis in E2-deprived breast cancer cells, MCF-7:5C. c-Src is involved in the process of E2-induced stress. To mimic the clinical administration of c-Src inhibitors, we treated cells with either E2, a c-Src inhibitor PP2, or the combination for 8 weeks to further explore the apoptotic potential of the c-Src inhibitor and E2 on MCF-7:5C cells. METHODS: Protein levels of receptors and signalling pathways were examined by immunoblotting. Expression of mRNA was detected through real-time polymerase chain reaction (PCR). Cell cycles were analysed by flow cytometry. RESULTS: Long-term treatment with PP2 alone or E2 alone decreased cell growth. In contrast, a combination of PP2 and E2 blocked apoptosis and the resulting cell line (MCF-7:PF) was unique, as they grew vigorously in culture with physiological levels of E2, which could be blocked by the pure antioestrogen ICI182,780. One major change was that PP2 collaborated with E2 to increase the level of insulin-like growth factor-1 receptor beta (IGF-1Rß). Blockade of IGF-1Rß completely abolished E2-stimulated growth in MCF-7:PF cells. Furthermore, combination treatment up-regulated transcription factors, Twist1 and Snail, and repressed E-cadherin expression which made MCF-7:PF cells display a characteristic phenotype of epithelial-mesenchymal transition (EMT). CONCLUSIONS: These data illustrate the role of the c-Src inhibitor to block E2-induced apoptosis and enhance E2-stimulated growth. Caution must be exercised when considering c-Src inhibitors in clinical trials following the development of acquired resistance to aromatase inhibitors, especially in the presence of the patient's own oestrogen.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Estrógenos/farmacología , Familia-src Quinasas/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacología , Fulvestrant , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Immunoblotting , Células MCF-7 , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirimidinas/farmacología , Receptor IGF Tipo 1/antagonistas & inhibidores , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Proteína 1 Relacionada con Twist/metabolismo , Tirfostinos/farmacología , Familia-src Quinasas/antagonistas & inhibidoresRESUMEN
The emergence of anti-estrogen resistance in breast cancer is an important clinical phenomenon affecting long-term survival in this disease. Identifying factors that convey cell survival in this setting may guide improvements in treatment. Estrogen (E2) can induce apoptosis in breast cancer cells that have been selected for survival after E2 deprivation for long periods (MCF-7:5C cells), but the mechanisms underlying E2-induced stress in this setting have not been elucidated. Here, we report that the c-Src kinase functions as a key adapter protein for the estrogen receptor (ER, ESR1) in its activation of stress responses induced by E2 in MCF-7:5C cells. E2 elevated phosphorylation of c-Src, which was blocked by 4-hydroxytamoxifen (4-OHT), suggesting that E2 activated c-Src through the ER. We found that E2 activated the sensors of the unfolded protein response (UPR), IRE1α (ERN1) and PERK kinase (EIF2AK3), the latter of which phosphorylates eukaryotic translation initiation factor-2α (eIF2α). E2 also dramatically increased reactive oxygen species production and upregulated expression of heme oxygenase HO-1 (HMOX1), an indicator of oxidative stress, along with the central energy sensor kinase AMPK (PRKAA2). Pharmacologic or RNA interference-mediated inhibition of c-Src abolished the phosphorylation of eIF2α and AMPK, blocked E2-induced ROS production, and inhibited E2-induced apoptosis. Together, our results establish that c-Src kinase mediates stresses generated by E2 in long-term E2-deprived cells that trigger apoptosis. This work offers a mechanistic rationale for a new approach in the treatment of endocrine-resistant breast cancer.
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Apoptosis/fisiología , Neoplasias de la Mama/metabolismo , Estrógenos/deficiencia , Estrógenos/metabolismo , Estrés Oxidativo/fisiología , Familia-src Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Proteína Tirosina Quinasa CSK , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Endorribonucleasas/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Femenino , Hemo-Oxigenasa 1/metabolismo , Humanos , Células MCF-7 , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Estrógenos/metabolismo , Respuesta de Proteína Desplegada/fisiología , eIF-2 Quinasa/metabolismoRESUMEN
A new method that utilizes zincon-modified activated carbon (AC-ZCN) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III) and Pb(II) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES). The separation/preconcentration conditions of analytes were investigated, including effects of pH, the shaking time, the sample flow rate and volume, the elution condition and the interfering ions. At pH 4, the maximum adsorption capacity of Cr(III) and Pb(II) onto the AC-ZCN were 17.9 and 26.7 mg g(-1), respectively. The adsorbed metal ions were quantitatively eluted by 1 mL of 0.1 mol L(-1) HCl. Common coexisting ions did not interfere with the separation. According to the definition of IUPAC, the detection limits (3 sigma) of this method for Cr(III) and Pb(II) were 0.91 and 0.65 ng mL(-1), respectively. The relative standard deviation under optimum condition is less than 3.5% (n=8). The method has been applied for the determination of Cr(III) and Pb(II) in biological materials and water samples with satisfactory results.
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Compuestos Azo/química , Carbón Orgánico/química , Cromo/análisis , Contaminantes Ambientales/análisis , Plomo/análisis , Adsorción , Cromo/aislamiento & purificación , Contaminantes Ambientales/aislamiento & purificación , Formazáns , Concentración de Iones de Hidrógeno , Iones , Plomo/aislamiento & purificación , Extracción en Fase Sólida/métodosRESUMEN
A new method that utilizes ethylenediamine-modified activated carbon (AC-EDA) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES). The new sorbent was prepared by oxidative surface modification. Experimental conditions for effective adsorption of trace levels of Cr(III), Fe(III), Hg(II) and Pb(II) were optimized with respect to different experimental parameters using batch and column procedures in detail. The optimum pH value for the separation of metal ions simultaneously on the new sorbent was 4.0. Complete elution of absorbed metal ions from the sorbent surface was carried out using 3.0 mL of 2% (%w/w) thiourea and 0.5 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation and determination of target metal ions. The maximum static adsorption capacity of the sorbent at optimum conditions was found to be 39.4, 28.9, 60.5 and 49.9 mg g(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The time for 94% adsorption of target metal ions was less than 2 min. The detection limits of the method was found to be 0.28, 0.22, 0.09 and 0.17 ng mL(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The precision (R.S.D.) of the method was lower 4.0% (n=8). The prepared sorbent as solid-phase extractant was successfully applied for the preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) in natural and certified samples with satisfactory results.
Asunto(s)
Métodos Analíticos de la Preparación de la Muestra/métodos , Carbón Orgánico/química , Etilenodiaminas/química , Metales/aislamiento & purificación , Extracción en Fase Sólida/métodos , Adsorción , Animales , Ácidos Carboxílicos/química , Concentración de Iones de Hidrógeno , Hígado/química , Metales/análisis , Metales/química , Ácido Nítrico/química , Oxidación-Reducción , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Porcinos , Factores de TiempoRESUMEN
OBJECTIVE: Cantharidimide cause blister. The effect of blister on immunoregulation was investigated. METHODS: Cantharidimide was placed on the skin, 48h later, the blister was analyzed by flow cytometry. RESULTS: The blister contained 1 x 10(6) - 1 x 10(7) cells per ml, most of which were neutrophils, macrophages, dendritic cells (DC), and IL-12 secreted by Thl cells. CONCLUSION: There are high concent of DC in the blister, which is differential and induce the secretion of Th1, the activation of T cell. The blister modulate the biological response of patients and is helpful for treatment with infective disease.