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1.
Chin J Traumatol ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39242245

RESUMEN

PURPOSE: Autologous osteoperiosteal transplantation (AOPT) is one of the most feasible and effective techniques for cystic osteochondral lesions of the talus (OLT). However, few reports have been reported about the process of graft-host bone healing and bone articular surface reconstruction, which help us to further understand the actual situation of bone healing and modify surgical methods. METHODS: We retrospectively evaluated 33 osteochondral lesions in 30 patients undertaking AOPT for OLT with subchondral cysts from December 2016 to October 2021. According to CT observation, we used 4 variables to describe the bony articular repair, including the integration of the articular surface, the height of the bone filling, the status of bone union, and the appearance of bone resorption or cystic change. We also analyzed the demographic data and clinical function. Descriptive statistics were used for demographic and clinical variables. Normally distributed data were presented as mean ± SD, and non-normally distributed data were presented as median (Q1, Q3). Associations between these variables and the primary clinical outcomes were examined using t-test or one-way ANOVA test for continuous variables. RESULTS: The patients' mean age was (41.7 ± 14.0) years old and the mean follow-up time was (29.6 ± 17.8) months. The chondral lesion size was (14.3 ± 4.1) mm. The cyst depth was (10.9 ± 3.7) mm. Significant improvements were observed in functional outcomes (according to the numeric rating scale for pain when walking and the American orthopedic foot and ankle society score) between the preoperative and latest follow-up evaluations, from 4.2 ± 2.1 to 2.2 ± 2.0 (p < 0.001), and from 66.8 ± 12.9 to 83.2 ± 10.4, respectively (p < 0.001). The overall satisfaction reached 8.3 of 10 points. All patients returned to sports and their median daily steps reached 8000 steps with 27 (81.8%) patients walking over 6000 steps daily. According to CT observation, "discontinuous bony articular surface and gap > 1 mm" was found in 27 grafts (81.8%), and "below the level of the adjacent articular surface, ≤ 1 mm" in a third of the grafts. Abnormal height of bone filling affected numeric rating scale score (p = 0.049) and American Orthopedic Foot and Ankle Society score (p = 0.027). Of note, bone resorption or cystic changes appeared in up to 13 autografts (39.4%). CONCLUSIONS: AOPT is an effective and acceptable technique for cystic OLT. Bone reconstruction is essential for large cystic OLT. How to get better bony articular reconstruction and avoid cyst recurrence should still be paid more attention.

2.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2930-2939, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-39041152

RESUMEN

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.


Asunto(s)
Alcaloides , Medicamentos Herbarios Chinos , Fritillaria , Fritillaria/química , Alcaloides/análisis , Alcaloides/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Análisis de Componente Principal , Desecación/métodos
3.
Rev Cardiovasc Med ; 24(9): 267, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39076388

RESUMEN

Background: Hypertrophic obstructive cardiomyopathy (HOCM) patients are reported to have a potential risk of sudden cardiac death (SCD); however, HCM with left ventricular outflow tract (LVOT) obstruction, which is regarded as a risk indicator of SCD, is doubtful since the LVOT gradient is dynamic and may be confounded by various environmental factors and routine activities. The purpose of this study was to explore the clinical prognosis of HOCM through a multicenter cohort study with data-driven propensity score matching (PSM) analysis. Methods: The cohort included 2268 patients with HCM from 1996 to 2021 in 13 tertiary hospitals. In the present study, we excluded 458 patients who underwent alcohol septal ablation (ASA) and septal myectomy (SM) surgery so 1810 HCM patients were eventually included. We developed a data-driven propensity score using 24 demographic and clinical variables to create 1:1 propensity-matched cohorts. A Cox proportional hazard regression model was constructed to assess the effect of HOCM on mortality. Results: After logit-matching, there were no significant differences in all-cause mortality (log-rank χ 2 = 1.509, p = 0.22), cardiovascular mortality/cardiac transplantation (log-rank χ 2 = 0.020, p = 0.89) or SCD (log-rank χ 2 = 0.503, p = 0.48) between patients with HOCM and hypertrophic nonobstructive cardiomyopathy (HNCM), and according to the Cox proportional hazard regression model, LVOT obstruction was not a risk predictor in patients with HCM. Conclusions: In both matched and unmatched cohorts, there were no significant differences in clinical prognosis between HOCM and HNCM patients, and LVOT obstruction was not an independent risk predictor of prognosis in patients with HCM. Clinical Trial Registration: ChiCTR1800017330.

4.
Biomed Chromatogr ; 37(1): e5524, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36241188

RESUMEN

In this study, we aimed to demonstrate the therapeutic effect of Ligustri Lucidi Fructus on chemotherapy-induced myelosuppression and elucidate its mechanism. A pharmacological study was conducted to investigate the mechanism of the inhibiting effects of Ligustri Lucidi Fructus on cyclophosphamide-induced bone marrow suppression in mice. HPLC was used to measure the chemical components. We demonstrated that medium and high doses of Ligustri Lucidi Fructus increased the amount of white blood cells and bone marrow nucleated cells (p < 0.05) in the cyclophosphamian-induced mouse model, and at the same time reduced granulocyte-macrophage-colony stimulating factor and thrombopoietin in the serum of myelosuppression mice (p < 0.01). Medium and high doses of Ligustri Lucidi Fructus can also adjust the thymus index and spleen index(p < 0.05). Ligustri Lucidi Fructus regulates the balance of bcl-2/bax, inhibits the expression of Caspase-3 and meanwhile stimulates the expression of mitogen-activated protein (MEK) and phospho extracellular regulated protein kinases (p-ERK) on the MAPK pathway. Five chemical constituents of Ligustri Lucidi Fructus, which may be related to myelosuppression, were analyzed. The content of specnuezhenide was 0.281%, that of ligustroflavone was 0.004%, that of salidroside was 0.094%, that of hydroxytyrosol was 0.060% and that of tyrosol was 0.069%. The effect of Ligustri Lucidi Fructus on myelosuppression after chemotherapy may be related to its multicomponent and multitarget nature. Ligustri Lucidi Fructus may be a promising potential drug for treatment after chemotherapy.


Asunto(s)
Medicamentos Herbarios Chinos , Ligustrum , Ratones , Animales , Ligustrum/química , Ciclofosfamida/efectos adversos , Ciclofosfamida/análisis , Medicamentos Herbarios Chinos/análisis , Frutas/química , Cromatografía Líquida de Alta Presión
5.
Knee Surg Sports Traumatol Arthrosc ; 31(6): 2174-2182, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36515734

RESUMEN

PURPOSE: To compare the clinical outcomes of the lasso-loop and simple suture techniques in arthroscopic anterior talofibular ligament (ATFL) repair for the treatment of chronic lateral ankle instability (CLAI). METHODS: From 2018 to 2020, patients with CLAI who underwent arthroscopic ATFL repair using the lasso-loop or simple suture technique were matched 1:1 (arthroscopic lasso-loop [AL] group, n = 29; simple arthroscopic suture [AS] group, n = 29) based on age, sex, affected side, body mass index, and follow-up duration using propensity score matching and retrospectively evaluated. Karlsson score, visual analogue scale (VAS) score, Tegner score, anterior drawer test (ADT) results, complications, patient-reported satisfaction, and magnetic resonance (MR) re-evaluation findings of ATFL quality were used to describe the outcomes. RESULTS: The patient characteristics or follow-up durations did not significantly differ between the two groups. The Karlsson score, VAS score, and Tegner score improved significantly in both groups after a mean follow-up duration of 29.6 ± 2.8 months. The postoperative clinical scores, ADT results, satisfaction rates, complication rates and MR re-evaluation findings were not significantly different between the two groups at the latest follow-up. CONCLUSION: The lasso-loop technique was equivalent to the simple suture technique in arthroscopic ATFL repair for the treatment of CLAI after a minimum follow-up of 2 years, suggesting that the simple suture technique is sufficient for arthroscopic ATFL repair in most patients without the need to add a lasso loop. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Humanos , Articulación del Tobillo/cirugía , Estudios Retrospectivos , Artroscopía/métodos , Ligamentos Laterales del Tobillo/cirugía , Inestabilidad de la Articulación/cirugía , Técnicas de Sutura
6.
Cancer Sci ; 113(8): 2616-2626, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35639349

RESUMEN

More than 90% of ovarian cancer deaths are due to relapse following development of chemoresistance. Our main objective is to better understand the molecular mechanism underlying paclitaxel resistance (taxol resistance, Txr) in ovarian cancer. Here, we observed that the linker histone H1.0 is upregulated in paclitaxel-resistant ovarian cancer cells. Knockdown of H1.0 significantly downregulates the androgen receptor (AR) and sensitizes paclitaxel-resistant SKOV3/Txr and 2774/Txr cell lines to paclitaxel. Conversely, ectopic expression of H1.0 upregulates AR and increases Txr in parental SKOV3 and MDAH2774 cells. Notably, H1.0 upregulation is associated with disease recurrence and poor survival in a subset of ovarian cancer subjects. Inhibition of PI3K significantly reduces H1.0 mRNA and protein levels in paclitaxel-resistant cells, suggesting the involvement of the PI3K/AKT signaling pathway. Knockdown of H1.0 and AR also downregulates the Txr genes ABCB1 and ABCG2 in paclitaxel-resistant cells. Our data show that H1.0 induces GCN5 expression and histone acetylation, thereby enhancing Txr gene transactivation. These findings suggest that Txr in ovarian cancer involves the PI3K/AKT pathway and leads to upregulation of histone H1.0, recruitment of GCN5 and AR, followed by upregulation of a subgroup of Txr genes that include ABCB1 and ABCG2. This study is the first report describing the relationship between histone H1.0 and GCN5 that cooperate to induce AR-dependent Txr in ovarian cancer cells.


Asunto(s)
Resistencia a Antineoplásicos , Neoplasias Ováricas , Paclitaxel , Receptores Androgénicos , Factores de Transcripción p300-CBP , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Humanos , Recurrencia Local de Neoplasia/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Factores de Transcripción p300-CBP/genética , Factores de Transcripción p300-CBP/metabolismo
7.
Biomed Microdevices ; 24(4): 41, 2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36399220

RESUMEN

Lung cancer is the leading cause of cancer death in the United States. It has the lowest 5-year survival rate among the most common cancers and therefore, early diagnosis is critical to improve the survival rate. In this paper, a new handheld electronic device is proposed to detect nine lung cancer biomarkers in the exhaled breath. An electrochemical gas sensor was produced through deposition of a thin layer of graphene and Prussian blue on a chromium-modified silicon substrate. Selective binding of the analyte was formed by molecular imprinting polymer (MIP). Subsequent polymerization and removal of the analyte yielded a layer of a conductive polymer on top of the sensor containing molecularly imprinted cavities selective for the target molecule. The sensors were tested over 1-20 parts per trillion (ppt) level of concentration while the sensor resistance has been monitored as the sensors react to the analyte by resistance change. Pentane sensor was also tested for selectivity. A printed circuit board was designed to measure the resistance of each sensor and send the data to a developed application in smartphone through Bluetooth. This handheld device has the potential to be used as a diagnostic method in the near future.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Pulmonares , Humanos , Polímeros/química , Neoplasias Pulmonares/diagnóstico , Pulmón , Electrónica
8.
IEEE J Solid-State Circuits ; 57(11): 3324-3335, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36467393

RESUMEN

This paper presents a fully integrated RF energy harvester (EH) with 30% end-to-end power harvesting efficiency (PHE) and supports high output voltage operation, up to 9.3V, with a 1.07 GHz input and under the electrode model for neural applications. The EH is composed of a novel 10-stage self-biased gate (SBG) rectifier with an on-chip matching network. The SBG topology elevates the gate-bias of transistors in a non-linear manner to enable higher conductivity. The design also achieves >20% PHE range of 12-dB. The design was fabricated in 65 nm CMOS technology and occupies an area of 0.0732-mm2 with on-chip matching network. In addition to standalone EH characterization measurement results, animal tissue stimulation test was performed to evaluate its performance in a realistic neural implant application.

9.
Scand J Clin Lab Invest ; 81(7): 564-572, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34570657

RESUMEN

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Catecolaminas/sangre , Dopamina/análogos & derivados , Metanefrina/sangre , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/sangre , Anticoagulantes/farmacología , Dopamina/sangre , Epinefrina/sangre , Hemoglobinas/análisis , Humanos , Metaboloma , Norepinefrina/sangre , Normetanefrina/sangre , Paraganglioma/sangre , Feocromocitoma/sangre , Triglicéridos/sangre
10.
Nano Lett ; 20(9): 6437-6443, 2020 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-32787165

RESUMEN

In this paper, we report all-optical manipulation of magnetization in ferromagnetic Co/Pt thin films enhanced by plasmonic resonances. By annealing a thin Au layer, we fabricate large-area Au nanoislands on top of the Co/Pt magnetic thin films, which show plasmonic resonances around the wavelength of 606 nm. Using a customized magneto-optical Kerr effect setup, we experimentally observe an 18.5% decrease in the minimum laser power required to manipulate the magnetization, comparing the on- and off-resonance conditions. The results are in very good agreement with numerical simulations. Our research findings demonstrate the possibility to achieve an all-optical magnetic recording with low energy consumption, low cost, and high areal density by integrating plasmonic nanostructures with magnetic media.

11.
J Cell Physiol ; 234(6): 8760-8775, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30317630

RESUMEN

We report here that the androgen receptor (AR) and ABCB1 are upregulated in a model of acquired taxol resistance (txr) in ovarian carcinoma cells. AR silencing sensitizes txr cells to taxol threefold, whereas ectopic AR expression in AR-null HEK293 cells induces resistance to taxol by 1.7-fold. AR activation using the agonist dihydrotestosterone (DHT) or sublethal taxol treatment upregulates ABCB1 expression in both txr cells and AR-expressing HEK293 cells. In contrast, AR inactivation using the antagonist bicalutamide downregulates ABCB1 expression and enhances cytotoxicity to taxol. A functional ABCB1 promoter containing five predicted androgen-response elements (AREs) is cloned. Deletion assays reveal a taxol-responsive promoter segment which harbors ARE4. Notably, DHT- or taxol-activated AR potentiates binding of the AR to ARE4 as revealed by the chromatin immunoprecipitation. On the other hand, txr cells display an increase in chromatin remodeling. AR/H3K9ac and AR/H3K14ac complexes bind specifically to ARE4 in response to taxol. Furthermore, acetyltransferase protein levels (p300 and GCN5) are upregulated in txr cells. Silencing of p300 or GCN5 reduces chromatin modification and enhances cytotoxicity in both parental and txr SKOV3 cells. While the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (AKT) pathway is significantly activated by taxol, taxol-induced ABCB1 expression, histone posttranslational modifications, and p300 binding to ARE4 are suppressed following inhibition of the PI3K/AKT cellular pathway. These results demonstrate that the AKT/p300/AR axis can be activated to target ABCB1 gene expression in response to taxol, thus revealing a new treatment target to counter taxol resistance.


Asunto(s)
Cromatina/metabolismo , Genes MDR/genética , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacología , Receptores Androgénicos/metabolismo , Transcripción Genética/efectos de los fármacos , Subfamilia B de Transportador de Casetes de Unión a ATP , Antineoplásicos/farmacología , Línea Celular Tumoral , Cromatina/genética , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Receptores Androgénicos/genética
12.
Bioorg Med Chem ; 27(12): 2480-2486, 2019 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-30837167

RESUMEN

OBJECTIVE: To explore whether Arctigenin-Valine ester (ARG-V) can treat myelosuppression caused by chemotherapy. METHODS: The number of peripheral blood cells of the mice was measured by an automatic blood analyzer, and the hematopoietic progenitor colonies CFU-GM, CFU-E, BFU-E, and CFU-Meg were cultured in vitro. Hematopoietic progenitor colonies and BMNCs were counted under an inverted microscope. The expressions of cytokines GM-CSF, EPO and TPO were detected by ELISA. The cell cycle was measured by flow cytometry. The expressions of related proteins MEK and p-ERK were quantitated by western blots, and the thymus index and spleen index were quantitated. RESULTS: After taking ARG-V, the peripheral blood cells of the mice gradually returned to normal, the number of nucleated cells in the bone marrow increased, the thymus index increased, the spleen index decreased, the number of hematopoietic progenitor cells increased, and the hematopoietic cytokines decreased. And ARG-V promoted the transformation of myelosuppression cells from G0/G1 to S and from S to G2/M. ARG-V could up-regulate the expression of MEK and p-ERK, and low dose ARG-V is not as effective in all aspects as high dose ARG-V. CONCLUSION: ARG-V can effectively alleviate the myelosuppression that caused by intraperitoneal injection of CTX in 100mg/kg, and ARG-V can promote the proliferation and differentiation of hematopoietic progenitor cells and improve immunity, and the effect of high-dose Arctigenin-Valine ester is more significant to some extent.


Asunto(s)
Células de la Médula Ósea/metabolismo , Furanos/química , Lignanos/química , Valina/química , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Citocinas/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias/tratamiento farmacológico
13.
J Cell Physiol ; 233(3): 2489-2501, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28771725

RESUMEN

We report here that toll-like receptor 4 (TLR4) and ABCB1 are upregulated in SKOV3 ovarian carcinoma cells that acquired resistance to the anticancer drug taxol. Silencing of TLR4 using short-hairpin RNA sensitized taxol-resistant SKOV3 cells to taxol (4.6 fold), whereas ectopic expression of TLR4 in parental, taxol-sensitive SKOV3 cells or TLR4-null HEK293 cells induced taxol resistance (∼2 fold). A sub-lethal dose of taxol induced ABCB1 protein expression in taxol-resistant SKOV3 cells. Inactivation of TLR4 using chemical inhibitors (CLI-095 and AO-I) downregulated ABCB1 protein expression and enhanced the cytotoxic activity of taxol in taxol-resistant SKOV3 cells. While the sensitization effect of TLR4 inactivation was also detected in TOV21G ovarian cancer cells, which express moderate level of TLR4, ectopic expression of ABCB1 prevented the sensitization effect in these cells. Notably, the NFκB pathway was significantly activated by taxol, and inhibition of this pathway suppressed TLR4-regulated ABCB1 expression. Furthermore, taxol-induced NFκB signaling was reduced following TLR4 silencing in taxol-resistant SKOV3 cells. Consistent with these results, ectopic expression of TLR4 in taxol-sensitive SKOV3 cells enhanced ABCB1 expression and conferred resistance to taxol. The protective effect of exogenous TLR4 expression against taxol was reduced by treatment with NFκB inhibitor in these cells. These results demonstrate that taxol activates the TLR4-NFκB pathway which in turn induces ABCB1 gene expression. This cellular pathway thus represents a novel target to limit resistance to taxol in ovarian cancer cells.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma/tratamiento farmacológico , Resistencia a Antineoplásicos , FN-kappa B/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Sitios de Unión , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Concentración 50 Inhibidora , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Regiones Promotoras Genéticas , Interferencia de ARN , Sulfonamidas/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/genética , Transfección , Regulación hacia Arriba
14.
Br J Cancer ; 117(2): 233-244, 2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28588321

RESUMEN

BACKGROUND: Accumulating evidence indicates that N-cadherin is a cell adhesion molecule that has critical roles in tumour progression. However, the role of N-cadherin in hepatocellular carcinoma (HCC) remains controversial. METHODS: This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC. RESULTS: The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. We identified that miR-199b-5p binds to the 3'-UTR of N-cadherin mRNA, thus decreasing N-cadherin expression in HCC cells. We also found the downregulation of miR-199b-5p in HCC specimens, which was inversely correlated with N-cadherin upregulation, predicted poor clinical outcomes in HCC patients. Next, we determined that miR-199b-5p overexpression promoted cell aggregation, suppressed cell migration and invasion in HCC cells, and inhibited xenografts tumour metastasis in nude mice. Moreover, we demonstrated that miR-199b-5p attenuated TGF-ß1 induced epithelial-mesenchymal transition (EMT) -associated traits, while its effects could be partially reversed by N-cadherin restoration. Finally, we examined that N-cadherin downregulation or miR-199b-5p overexpression suppressed TGF-ß1-induced Akt phosphorylation, and inhibition of PI3K/Akt pathway blocked TGF-ß1-induced N-cadherin overexpression in HCC cells. CONCLUSIONS: Our data demonstrate that N-Cadherin was markedly overexpressed and miR-199b-5p was significantly downregulated in HCC. MiR-199b-5p exerts inhibitory effects on EMT, and directly targets N-cadherin in HCC, supporting the potential utility of miR-199b-5p as a promising strategy to treat HCC. Also, a positive regulatory loop exists between N-cadherin and Akt signalling represents a novel mechanism of TGF-ß1-mediated EMT in HCC cells.


Asunto(s)
Cadherinas/biosíntesis , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Cadherinas/genética , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Ratones , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
15.
J Cell Physiol ; 229(3): 309-22, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23939952

RESUMEN

The oncogenic latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is involved in the pathogenesis of human nasopharyngeal carcinoma (NPC) and lymphoma. We and other authors have shown earlier that LMP1 induces apoptosis and inhibits xenograft tumor growth in mice, but the mechanism underlying these processes has not been investigated so far. In the present study, we show that knockdown of LMP1 renders the EBV-positive NPC cell line CG-1 resistant to various genotoxic drugs (cisplatin, etoposide, and adriamycin). LMP1 inhibits the expression of Cabin1, a Ca(2+) regulated protein shown earlier to inhibit calcineurin. Knockdown of calcineurin binding protein (Cabin1) with small hairpin RNA sensitizes CG-1 cells to genotoxic drugs. In contrast, LMP1 overexpression reduces Cabin1 level and renders both CG-1 cells and EBV-negative NPC cell lines sensitive to cisplatin. The c-Jun-N-terminal kinase (JNK) and ERK pathways are required for LMP1-induced suppression of Cabin1 at the transcriptional level. Chromatin immunoprecipitation assays further confirm that the JNK-activated transcription factor AP-1 mediates the LMP1-induced down-regulation of Cabin1 gene expression. LMP1 knockdown also increases the resistance of xenograph tumors to cisplatin in mice, therefore confirming the relevance of our findings in vivo. This study reveals the molecular mechanism underlying the pro-apoptotic activity of LMP1 during cisplatin-based NPC chemotherapy.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Proteínas de la Matriz Viral/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis/efectos de los fármacos , Sitios de Unión , Carcinoma , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Desnudos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Regiones Promotoras Genéticas , Interferencia de ARN , Factores de Tiempo , Factor de Transcripción AP-1/metabolismo , Transfección , Carga Tumoral , Proteínas de la Matriz Viral/genética , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Tumour Biol ; 35(2): 1057-63, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24061638

RESUMEN

The purposes of the present work were to construct the shRNA plasmids for BAG-1 gene of human and test the expression of mRNA and protein of BAG-1. Recombinant plasmids containing green fluorescent protein reporter genes are constructed using gene cloning methods. The shRNA plasmids for the BAG-1 gene are constructed by RNA interference technology. We applied fluorescent plasmid-transfected target cells in the cell transfection experiments and monitored the transfection rate of plasmids by observing the fluorescence amount. We transfected three synthesized shRNA in target screening cell and adopted RT-PCR and Western test to identify the difference of target gene transfection and translation level in cells. The specific shRNA plasmid for the BAG-1 gene was successfully recombined, and stably transfected colon cancer Lo Vo cell lines were obtained. The results present that the constructed shRNA plasmids significantly inhibited the expression of mRNA and protein of Lo Vo cell BAG-1, and can maintain the effect for a long term. pGPH1/GFP/Neo-BAG-1-homo-825 was screened as the optimum sequence of interference so as to lay a solid foundation to explore into the research on the BAG-1 gene and the biological behavior of colon cancer cells. It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing.


Asunto(s)
Neoplasias del Colon/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica/genética , Interferencia de ARN , Factores de Transcripción/genética , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/patología , Proteínas de Unión al ADN/antagonistas & inhibidores , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Humanos , Plásmidos/genética , Factores de Transcripción/antagonistas & inhibidores , Transfección
17.
Environ Sci Technol ; 48(19): 11090-9, 2014 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-25211339

RESUMEN

Oil sands process-affected water (OSPW) is a toxic and poorly biodegradable mixture of sand, silt, heavy metals, and organics. In this study, qualitative and quantitative comparisons of naphthenic acids (NAs) were done using ultraperformance liquid chromatography time-of-flight mass spectrometry (UPLC TOF-MS), Fourier transform ion cyclotron resonance (FT-ICR) MS, and ion mobility spectrometry (IMS). The unique combination of these analyses allowed for the determination and correlation of NAs, oxidized NAs, and heteroatom (sulfur or nitrogen) NAs. Despite its lower resolution, UPLC-TOF MS was shown to offer a comparable level of reliability and precision as the high resolution FT-ICR MS. Additionally, the impacts of ozonation (35 mg/L utilized ozone dose) and subsequent NAs degradation on OSPW toxicity were assessed via a collection of organisms and toxicity end points using Vibrio fischeri (nonspecific), specific fish macrophage antimicrobial responses, and fish olfactory responses. Fish macrophages exposed to ozonated OSPW for 1 week showed higher production of reactive oxygen and nitrogen intermediates; however, after 12 weeks the responses were reduced significantly. Fish olfactory tests suggested that OSPW interfered with their perception of odorants. Current results indicate that the quantification of NAs species, using novel analytical methods, can be combined with various toxicity methods to assess the efficiency of OSPW treatment processes.


Asunto(s)
Bioensayo/métodos , Espectrometría de Masas/métodos , Yacimiento de Petróleo y Gas , Ozono/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Aliivibrio fischeri/efectos de los fármacos , Animales , Antibacterianos/farmacología , Ácidos Carboxílicos/análisis , Ácidos Carboxílicos/toxicidad , Exposición a Riesgos Ambientales/análisis , Iones , Macrófagos/efectos de los fármacos , Oncorhynchus mykiss , Estándares de Referencia , Reproducibilidad de los Resultados , Olfato/efectos de los fármacos , Pruebas de Toxicidad , Contaminantes Químicos del Agua/toxicidad
18.
Eur Arch Otorhinolaryngol ; 271(10): 2751-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24748412

RESUMEN

The purpose of the present study was to evaluate the associations between the findings of drug-induced sleep endoscopy (DISE) and upper airway computed tomography (UACT) in obstructive sleep apnea (OSA) patients. This study was a non-randomized, prospective, clinical trial. We used DISE to identify the obstruction pattern according to VOTE classification. All 62 study subjects (all men) showed velum-related obstruction; 47 (75.8%) had lateral oropharyngeal obstruction, 45 (72.6%) had tongue-base-related obstruction, and 6 (9.7%) had epiglottal obstruction. The following UACT measurements significantly differed between subjects with and without lateral oropharyngeal obstruction (P < 0.05): airway length, laryngopharynx length, mandibular plane to hyoid distance, minimum lateral dimension of the retroglossal airway, retropalatal anteroposterior/lateral dimension, and retroglossal anteroposterior/lateral dimension. None of the UACT measurements significantly differed between subjects with and without tongue-base-related or epiglottal obstruction. These results indicate that in OSA patients, obstruction related to the lateral oropharyngeal walls can be identified using these UACT measurements. Thus, UACT, which is performed during wakefulness, can partially replace DISE, which is both time consuming and costly.


Asunto(s)
Endoscopía/métodos , Hipnóticos y Sedantes/administración & dosificación , Laringe/diagnóstico por imagen , Apnea Obstructiva del Sueño/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Tráquea/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Apnea Obstructiva del Sueño/fisiopatología
19.
Water Sci Technol ; 70(5): 771-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25225922

RESUMEN

The interaction between organic fractions in oil sands process-affected water (OSPW) and three polymeric membranes with varying hydrophilicity (nylon, polyvinylidene fluoride and polytetrafluoroethylene) at different pHs was studied to evaluate the impact of filtration on the quantification of acid-extractable fraction (AEF) and naphthenic acids (NAs). Four functional groups predominated in OSPW (amine, phosphoryl, carboxyl and hydroxyl) as indicated by the linear programming method. The nylon membranes were the most hydrophilic and exhibited the lowest AEF removal at pH of 8.7. However, the adsorption of AEF on the membranes increased as the pH of OSPW decreased due to hydrophobic interactions between the membrane surfaces and the protonated molecules. The use of ultra pressure liquid chromatography-high resolution mass spectrometry (UPLC/HRMS) showed insignificant adsorption of NAs on the tested membranes at pH 8.7. However, 26±2.4% adsorption of NAs was observed at pH 5.3 following the protonation of NAs species. For the nylon membrane, excessive carboxylic acids in the commercial NAs caused the formation of negatively charged assisted hydrogen bonds, resulting in increased adsorption at pH 8.2 (25%) as compared to OSPW (0%). The use of membranes for filtration of soluble compounds from complex oily wastewaters before quantification analysis of AEF and NAs should be examined prior to application.


Asunto(s)
Ácidos Carboxílicos/análisis , Filtración/instrumentación , Membranas Artificiales , Contaminantes Químicos del Agua/análisis , Purificación del Agua/instrumentación , Adsorción , Cromatografía Líquida de Alta Presión , Yacimiento de Petróleo y Gas , Polímeros , Espectroscopía Infrarroja por Transformada de Fourier , Aguas Residuales
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(2): 293-9, 2014 Feb.
Artículo en Zh | MEDLINE | ID: mdl-24822388

RESUMEN

Based on the principle of spectral scanning filtering method, a new scanning filtering method for improving signal-to-noise ratio (SNR) of the chirped pulse by using the photorefractive effect was proposed and theoretically analyzed. For the scanning filtering implement of Fabry-Perot (F-P) etalon with a built-in photorefractive crystal, the transmittance spectral characteristics of the scanning filter were analyzed quantitatively. Furthermore, the effects of the reflectivity of the parallel-plates of Fabry-Perot etalon, the bandwidth of the transmittance spectral window, the variation of the controlling parameters of the applied field and the variation of the chirped rate to the photorefractive crystal on the SNR improvement and the overall transmittance were discussed in details. The results show that the higher the reflectivity of the F-P parallel-plates is, the transmittance spectral is sharper and the transmittance window is narrower, resulting in the better filtering effect. In order to ensure the efficient SNR improvement, the reflectivity of the F-P parallel-plates should be higher than 0. 99. The control of the applied field exhibits significant impact on the scanning filtering. In practical applications, the applied field and chirped rate should be controlled precisely in order to ensure the synchronous matching between the signal pulse and the filtering function. For the chirped signal pulse with the central wavelength 800 nm, the SNR improvement of about 3 orders of magnitude can be obtained via filtering out the amplified spontaneous emission (ASE) random noise and pre-pulse by the use of the spectral scanning filtering method proposed in this paper.

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