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1.
BMC Neurol ; 24(1): 30, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233767

RESUMEN

OBJECTIVE: To explore the predictive value of interleukin-6 (IL-6) combined with human neutrophil lipocalin (HNL) of stroke-associated pneumonia (SAP) in patients who were diagnosed with acute ischemic stroke (AIS). METHODS: 108patients were divided into two groups: pneumonia group (52 cases) and non-pneumonia group (56 cases), according to whether the patients developed SAP within 7 days of admission. General information was compared between the two groups, like age, gender, history of hypertension, diabetes mellitus, cardiovascular disease, dysphagia, smoking and alcoholhistory. Clinical data were recorded and compared, including lipid profile, interleukin-6 (IL-6), homocysteine (Hcy), National Institutes of Health Stroke Scale (NIHSS) score, and HNL. Multivariate Logistic regression analysis was used to screen the risk factors of AIS-AP, and the predictive value of IL-6 and HNL alone and in combination was evaluated by receiver operating characteristic curve (ROC curve). RESULTS: Logistic regression analysis showed that dysphagia (OR,0.018; 95% CI, 0.001 ~ 0.427; P = 0.013), increased NIHSS scores(OR,0.012; 95% CI, 0.000 ~ 0.434; P = 0.016), and high levels of IL-6 (OR,0.014; 95% CI, 0.000 ~ 0.695; P = 0.032)and HNL (OR,0.006; 95% CI, 0.000 ~ 0.280; P = 0.009) were independent risk factors for SAP with significant difference (all P < 0.05). According to the ROC curve analysis of IL-6, the area under the curve (AUC) was 0.881 (95% CI: 0.820 ~ 0.942), and the optimal cutoff value was 6.89 pg/mL with the sensitivity of 73.1% and specificity of 85.7%. As for the ROC curve analysis of HNL, the AUC was 0.896 (95% CI: 0.839 ~ 0.954), and the best cutoff value was 99.66ng/mL with the sensitivity of 76.9% and specificity of 89.3%. The AUC of the combination of IL-6 and HNL increased to 0.952 (95% CI: 0.914 ~ 0.989), and the sensitivity and specificity increased to 80.8% and 92.9%, respectively. CONCLUSION: In this research, the levels of IL-6 ≥ 6.89 pg/mL and HNL ≥ 99.66ng/mL were considered as risk factors for AIS patients complicated with SAP. The combined detection had higher predictive value for patients with SAP, which may help to identify who were in highrisk.


Asunto(s)
Trastornos de Deglución , Accidente Cerebrovascular Isquémico , Neumonía , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Interleucina-6 , Citocinas , Neutrófilos , Pronóstico , Curva ROC , Neumonía/etiología , Estudios Retrospectivos
2.
Appl Opt ; 61(35): 10507-10518, 2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36607113

RESUMEN

This paper proposes a pattern recognition method for φ-OTDR based on self-reference features, where machine learning is applied to classify the vibration monitored. The φ-OTDR collects the light amplitude-time-space sequence, establishes a reference position in the spatial dimension, and combines the two dimensions of the vibration and reference positions to form self-reference features, which are then used as machine learning features. These self-reference features can effectively improve the pattern recognition accuracy. This paper selects a low sampling frequency for data collection, analyzes the influence of sample definition methods of different time lengths on the pattern recognition accuracy, and determines that the optimal sample length is 10 data points. The contribution of different feature parameters to pattern recognition is analyzed, and eight eigenvalues such as average, maximum, and minimum are finally determined to form self-reference features that are used as the input of the machine learning algorithm. The recognition accuracies of five machine learning algorithms including kNN, Decision Tree, Random Forest, LightGBM, and CatBoost are analyzed and compared, and the CatBoost algorithm in the integrated learning algorithm is finally determined as the optimal algorithm. On this basis, this paper proposes a filtering algorithm to deal with abnormal signals, which can effectively compensate for abnormal data and further improve the accuracy of pattern recognition. Finally, this paper conducts the pattern recognition study on four common events of tapping, bending, trampling, and blowing, and obtains the average recognition rate of 98%. In addition, this paper innovatively carried out pattern recognition research on five types of mining equipment, including ball mills, vibrating screens, conveyor belts, filters, and industrial pumps, and obtained the average recognition rate of 93.5%.

3.
Gynecol Oncol ; 151(2): 345-355, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30201235

RESUMEN

PURPOSE: This investigation was aimed at extrapolating whether and how lncRNA GAS5, miR-196a-5p and HOXA5 altered progression of ovarian cancer (OA). METHOD: Totally 195 pairs of OA tissues and adjacent normal tissues were collected. Also si-GAS5, pcDNA-GAS5, miR-196a-5p mimic, miR-196a-5p inhibitor and negative control (NC) were, respectively, transfected into OA cells. Besides, dual-luciferase reporter gene assay was performed to validate the targeted relationships between GAS5 and miR-196a-5p, as well as between miR-196a-5p and HOXA5. The impacts of GAS5, miR-196a-5p and HOXA5 on viability, proliferation and apoptosis of OA cells were appraised via conduction of colony formation assay, MTT assay and flow cytometry assay. RESULT: Lower GAS5 expression and higher miR-196a-5p expression were associated with larger tumor size (≥5 cm) and more advanced FIGO stage (III-IV) of OA patients (P < 0.05). Transfection of si-GAS5, miR-196a-5p mimic or si-HOXA5 conferred OA cells with stronger viability, faster proliferation and smaller percentage of apoptosis (P < 0.05). After injecting mice models with si-GAS5, miR-196a-5p mimic or si-HOXA5, a larger tumor size was also observed within the rats (P < 0.05). GAS5 was indicated to directly target miR-196a-5p and modify its expression, and the targeted relationship also seemed to exist between miR-196a-5p and HOXA5 (P < 0.05). The HOXA5 was found to reverse the effects imposed by miR-196a-5p on viability, proliferation and apoptosis of OA cells (P < 0.05). CONCLUSION: LncRNA GAS5 depressed OA development by targeting miR-196a-5p and thereby down-regulating HOXA5 expression, providing substance for developing lncRNA-based strategies to treat OA.


Asunto(s)
Proteínas de Homeodominio/biosíntesis , MicroARNs/biosíntesis , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , ARN Largo no Codificante/biosíntesis , Animales , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
4.
Chemphyschem ; 17(19): 2992-2997, 2016 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-27324212

RESUMEN

Using density functional theory and a hybrid exchange-correlation functional, a systematic study of the stability and electronic structure of neutral and multiply charged organic molecules, Bn C6-n X6 (n=0, 1, 2; X=H, F, CN) and Bn C5-n X5 (n=0, 1; X=H, F, CN) is performed. The results show that in addition to the aromaticity of the molecules, substituents play an important role in stabilizing the organic dianion complexes. In particular, it is demonstrated that CN groups are responsible for the stability of organic dianions as it has recently been found to be the case in B-cage compounds such as B12 (CN)122- and CB11 (CN)122- . It is also shown that the stable organic dianions B2 C4 (CN)62- and BC4 (CN)52- might be halogen-free electrolytes in Li-ion batteries.

5.
Chemphyschem ; 17(1): 184-9, 2016 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-26467557

RESUMEN

Benzene, the classic organic molecule obeying Hückel's rule of aromaticity, has negative electron affinity (EA), namely -1.15 eV. By using density functional theory with hybrid functional for exchange and correlation potential, we show that a series of organic molecules created by changing either the benzene core or the ligands, or both, result in species with EAs that range from 2.15 to 5.37 eV. This shows that ligand substitution is more effective than aromaticity in increasing the EA of organic molecules. The ability to create highly electronegative organic molecules by functionalizing benzene may provide new opportunities for synthesizing organic oxidizing agents with potential new applications.

6.
Angew Chem Int Ed Engl ; 55(11): 3704-8, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26880349

RESUMEN

Multiply charged negative ions are seldom stable in the gas phase. Electrostatic repulsion leads either to autodetachment of electrons or fragmentation of the parent ion. With a binding energy of the second electron at 0.9 eV, B12 H12 (2-) is a classic example of a stable dianion. It is shown here that ligand substitution can lead to unusually stable multiply charged anions. For example, dodecacyanododecaborate, B12 (CN)12 (2-) , created by substituting H by CN is found to be highly stable with the second electron bound by 5.3 eV, which is six times larger than that in the B12 H12 (2-) . Equally important is the observation that CB11 (CN)12 (2-) , which contains one electron more than needed to satisfy the Wade-Mingos rule, is also stable with its second electron bound by 1.1 eV, while CB11 H12 (2-) is unstable. The ability to stabilize multiply charged anions in the gas phase by ligand manipulation opens a new door for multiply charged species with potential applications as halogen-free electrolytes in ion batteries.

7.
Tumour Biol ; 36(9): 6867-73, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25846738

RESUMEN

MicroRNAs play critical roles in regulating tumor occurrence and drug sensitivity in ovarian cancers. This study aimed to investigate the key members of MicroRNAs (miRNAs) involved in modulating tumor initiation and drug resistance in primary ovarian cancer cells. An in vitro assay based on tumor clonal formation was established to evaluate tumorigenicity and cisplatin sensitivity. By performing real-time polymerase chain reaction, we examined the expression of nine microRNAs associated with the pathology of ovarian cancers in primary ovarian tumor cells, which were surgically resected from 46 patients with distinct sensitivity to platinum-based chemotherapy. MiR-9, miR-145, and miR-429 were expressed significantly higher in drug-sensitive patients (n = 26) than in drug-resistant ones (n = 20), while higher miR-26a expression was found in resistant patients (p < 0.05). In addition, tumor cells from drug sensitive patients were more tumorigenic than those of drug resistance (p = 0.0013). Cisplatin treatment led to a sharp decrease of clonal formation of drug-sensitive cells but showed slight effects on drug resistant cells. Specific anti-miRs were then employed to downregulate the expression of microRNAs in primary tumor cells. Inhibition of miR-9 resulted in decreased clonal formation and sensitivity to cisplatin, while the knockdown of other three microRNAs did not show any influence in tumorigenesis and drug sensitivity. In conclusion, this study showed that in primary ovarian tumor cells, high expression of miR-9 was associated with enhanced tumorigenesis and increased sensitivity of the tumor cells to cisplatin treatment.


Asunto(s)
Cisplatino/administración & dosificación , MicroARNs/genética , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Adulto , Apoptosis/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/biosíntesis , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología
8.
Clin Neurol Neurosurg ; 244: 108406, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38968812

RESUMEN

OBJECTIVE: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke. METHODS: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment. RESULTS: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively. CONCLUSION: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS.

9.
Plants (Basel) ; 12(15)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37570960

RESUMEN

Apple leaf diseases are one of the most important factors that reduce apple quality and yield. The object detection technology based on deep learning can detect diseases in a timely manner and help automate disease control, thereby reducing economic losses. In the natural environment, tiny apple leaf disease targets (a resolution is less than 32 × 32 pixel2) are easily overlooked. To address the problems of complex background interference, difficult detection of tiny targets and biased detection of prediction boxes that exist in standard detectors, in this paper, we constructed a tiny target dataset TTALDD-4 containing four types of diseases, which include Alternaria leaf spot, Frogeye leaf spot, Grey spot and Rust, and proposed the HSSNet detector based on the YOLOv7-tiny benchmark for professional detection of apple leaf disease tiny targets. Firstly, the H-SimAM attention mechanism is proposed to focus on the foreground lesions in the complex background of the image. Secondly, SP-BiFormer Block is proposed to enhance the ability of the model to perceive tiny targets of leaf diseases. Finally, we use the SIOU loss to improve the case of prediction box bias. The experimental results show that HSSNet achieves 85.04% mAP (mean average precision), 67.53% AR (average recall), and 83 FPS (frames per second). Compared with other standard detectors, HSSNet maintains high real-time detection speed with higher detection accuracy. This provides a reference for the automated control of apple leaf diseases.

10.
Int J Mol Med ; 51(2)2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36660951

RESUMEN

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the ß­actin control western blotting data featured in Fig. 3E were strikingly similar to data appearing in different form in another article by different authors. Upon asking the authors to explain this phenomenon, they were unable to provide the raw data for this experiment. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 847­856, 2019; DOI: 10.3892/ijmm.2019.4257].

11.
Anal Cell Pathol (Amst) ; 2022: 1732365, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35602576

RESUMEN

Ovarian cancer (OC) is the leading cause of death for women diagnosed with gynecological cancer. Studies have shown that dysregulated miRNA expression is related to various cancers, including OC. Here, we aimed to explore the biological function and mechanism of miR-585-3p in the occurrence and development of OC. The expression level of miR-585-3p was found to be low in OC tissues and cells. We analyzed the biological function of miR-585-3p in OC through in vitro cell experiments. The results indicated that overexpression of miR-585-3p inhibited the proliferation, invasion, and migration of SW626 cells, while low expression of miR-585-3p had the opposite effect in SKOV3 cells. We then screened the target genes of miR-585-3p through miRDB database and detected the expression of target genes in OC cells. FSCN1 was found to be most significantly upregulated in OC cells. Dual-luciferase reporter assays revealed FSCN1 as a potential target of miR-585-3p. Western blot analysis showed that miR-585-3p targeted FSCN1 to inhibit protein phosphorylation of ERK. In vivo animal experiments also confirmed that miR-585-3p targets FSCN1 to inhibit tumor growth and block the MAPK signaling pathway. In summary, miR-585-3p inhibits the proliferation, migration, and invasion of OC cells by targeting FSCN1, and its mechanism of action may be achieved by inhibiting the activation of the MAPK signaling pathway. miR-585-3p may serve as a potential biomarker and therapeutic target for OC.


Asunto(s)
MicroARNs , Neoplasias Ováricas , Animales , Carcinoma Epitelial de Ovario/genética , Proteínas Portadoras/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Neoplasias Ováricas/metabolismo , Transducción de Señal
12.
J Chem Phys ; 134(9): 094309, 2011 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-21384971

RESUMEN

The electronic structures of CuBO(2)(-), Cu(BO(2))(2)(-), Cu(2)(BO(2))(-), and Cu(2)(BO(2))(2)(-) clusters were investigated using photoelectron spectroscopy. The measured vertical and adiabatic detachment energies of these clusters revealed unusual properties of Cu(BO(2))(2) cluster. With an electron affinity of 5.07 eV which is larger than that of its BO(2) superhalogen (4.46 eV) building-block, Cu(BO(2))(2) can be classified as a hyperhalogen. Density functional theory based calculations were carried out to identify the ground state geometries and study the electronic structures of these clusters. Cu(BO(2)) and Cu(BO(2))(2) clusters were found to form chainlike structures in both neutral and anionic forms. Cu(2)(BO(2)) and Cu(2)(BO(2))(2) clusters, on the other hand, preferred a chainlike structure in the anionic form but a closed ringlike structure in the neutral form. Equally important, substantial differences between adiabatic detachment energies and electron affinities were found, demonstrating that correct interpretation of the experimental photoelectron spectroscopy data requires theoretical support not only in determining the ground state geometry of neutral and anionic clusters, but also in identifying their low lying isomers.

13.
Int J Mol Med ; 44(3): 847-856, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31257467

RESUMEN

Oxidized low­density lipoprotein (ox­LDL)­mediated endothelial cell injury has an important role in the vascular complications of type 2 diabetes. Astragaloside IV (ASV) is an active component of Radix Astragali, which has been demonstrated to exert protective effects against endothelial damage. The present study explored whether microRNAs (miRNAs) are involved in mediating the protective effects of ASV on ox­LDL­induced damage in human umbilical vein endothelial cells (HUVECs). RNA sequencing and reverse transcription­quantitative PCR analyses revealed that ox­LDL treatment significantly downregulated miR­140­3p expression in HUVECs. miR­140­3p overexpression promoted cell proliferation and inhibited apoptosis in ox­LDL­induced HUVECs. However, inhibition of miR­140­3p expression could reverse the effects of ASV on ox­LDL­induced HUVECs and reactivate ASV­inhibited PI3K/Akt signaling in ox­LDL­induced HUVECs. In addition, Krüppel­like factor 4 (KLF4) was identified as a target of miR­140­3p in ox­LDL­treated HUVECs. Subsequent experiments revealed that KLF4 overexpression partially counteracted the protective effects of miR­140­3p or ASV treatment in ox­LDL­induced HUVECs. Taken together, the current findings demonstrated that the protective effects of ASV on HUVECs were dependent on miR­140­3p upregulation and subsequent inhibition of KLF4 expression, which in turn suppressed the PI3K/Akt signaling pathway. The present results shed light to the molecular mechanism by which ASV alleviated ox­LDL­induced endothelial cell damage.


Asunto(s)
Células Endoteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Lipoproteínas LDL/metabolismo , MicroARNs/genética , Saponinas/farmacología , Triterpenos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos
14.
Yonago Acta Med ; 59(2): 100-10, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27493480

RESUMEN

BACKGROUND: Gingerol, the generic term for pungent constituents in ginger, has been used for treating vomiting in China. We are going to investigate the mechanisms of inhibitive effect of gingerol on cisplatin-induced pica behaviour by studying on both peripheral and central levels, and the effects of gingerol on homeostasis of dopamine (DA) transmission: dopamine D2 receptor (D2R), dopamine transporter (DAT) and tyrosine hydroxylase (TH). METHODS: The antiemetic effect of gingerol was investigated on a vomiting model in rats induced by cisplatin 3 mg·kg(-1) intraperitoneal injection (i.p.). Rats were randomly divided into the normal control group (C), simple gingerol control group (CG), cisplatin control group (V), cisplatin + metoclopramide group (M), cisplatin + low-dose gingerol group (GL), cisplatin + middle-dose gingerol group (GM) and cisplatin + high-dose gingerol group (GH). In observation period, rats in Groups C and V were pretreated with sterile saline 3 mL i.g.; rats in Group CG were pretreated with gingerol 40 mg·kg(-1) i.g.; rats in Group M were pretreated with metoclopramide 2.5 mg·kg(-1) i.g.; rats in Groups GL, GM and GH were pretreated with gingerol 10, 20 and 40 mg·kg(-1) i.g. for 3 days, respectively. Cisplatin (3 mg·kg(-1), i.p.) was administered one time after each treatment with the antiemetic agent or its vehicle except the Groups C and CG. The distribution of D2R, DAT and TH in the area postrema and ileum were measured by immunohistochemistry and quantitated based on the image analysis, and the expression of DAT and TH in the area postrema and ileum were measured by RT-PCR. The weights of kaolin eaten of the remaining rats were observed in every 6 h continuously for 72 h. RESULTS: The weight of kaolin eaten in rats induced by cisplatin was significantly reduced by pretreatment with gingerol in a dose-dependent manner during the 0-24 h and 24-72 h periods (P < 0.05). Gingerol markedly improved gastric emptying induced by cisplatin in a dose-dependent manner (P < 0.05), and exhibited effective dose-dependent inhibition on the increase of expression levels of D2R and TH and the decrease of expression levels of DAT in both the ileum and area postrema (P < 0.05). CONCLUSION: Gingerol is effective on cisplatin-induced emesis in rats possibly by inhibiting central or peripheral increase of DA by inhibiting D2R, TH and accelerating DAT.

15.
DNA Cell Biol ; 34(1): 55-62, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25211326

RESUMEN

Cisplatin is a most active drug for the treatment of ovarian cancer; however, acquired cisplatin resistance is easily seen in patients with ovarian cancer. The aim of this study is to clarify the molecular mechanism of cisplatin resistance and try to reverse cisplatin resistance in ovarian cancer lines in vitro and in vivo. First, we used ovarian cancer cell line A2780, and its cisplatin-resistant subline, A2780/DDP as cell model. Cell viability was determined by MTT assay and the IC50 values were observed to increase in a dose- and time-dependent manner. Next, the expression of ß-catenin was determined by western blotting analysis, and the results demonstrated that the expression level of ß-catenin in A2780/DDP cells was significantly higher than that in A2780 cells (p<0.01). Moreover, we detected the distribution of cytoplasmic and nuclear ß-catenin by western blot analysis, which showed that ß-catenin was mainly located in nucleus. Compared with A2780 cells, there was no obvious change as the increasing dose of cisplatin in A2780/DDP cells reveal that cisplatin resistance was related to the exrpession of ß-catenin. Furthermore, interference with the expression of ß-catenin could effectively reverse cisplatin resistance as IC50 was significantly decreased from 123.7 to 42.43 µM in A2780/DDP cells. Additionally, transient interference of ß-catenin by siRNA promoted the apoptosis of A2780/DDP cells, for increased apoptosis rates and cleaved caspase-3 levels were detected being treated with cisplatin. Finally, tumorigenicity experiments showed that tumor growth was significantly suppressed in ß-catenin shRNA group. The body weight was not significantly changed during the experimental days. In conclusion, all the results showed that cisplatin resistance was partly induced by Wnt/ß-catenin signaling pathway. Interfering the expression of ß-catenin could reverse cisplatin resistance in vitro and in vivo. Thus, ß-catenin could be a potential therapeutic target for the therapy of cisplatin-resistant ovarian cancer.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Resistencia a Antineoplásicos , Neoplasias Ováricas/metabolismo , beta Catenina/genética , Animales , Línea Celular Tumoral , Núcleo Celular/metabolismo , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Interferencia de ARN , ARN Interferente Pequeño/genética , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismo
16.
Eur J Endocrinol ; 166(1): 99-105, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22019891

RESUMEN

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance (IR). Berberine (BBR) is an isoquinoline derivative alkaloid extracted from Chinese medicinal herbs that has been used as an insulin sensitizer. BBR may have a potential therapeutic value for PCOS. The aim of this study was to evaluate the effects of BBR in comparison to metformin (MET) on the metabolic features of women with PCOS. DESIGN AND METHODS: Eighty-nine subjects with PCOS and IR subjects were randomized into one of three treatment groups: BBR+compound cyproterone acetate (CPA; n=31), MET+CPA (n=30), and placebo+CPA (n=28) for 3 months. Clinical characteristics of the women and metabolic and hormonal parameters were assessed before and after the period of treatment. RESULTS: Treatment with BBR in comparison to MET showed decrease in waist circumference and waist-to-hip ratio (WHR; P<0.01), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC; P<0.05) as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG; P<0.05). Similarly, treatment with BBR in comparison to placebo showed decrease in WHR, fasting plasma glucose, fasting insulin, homeostasis model assessment for IR, area under the curve of insulin, TC, LDLC, and TG (P<0.05) as well as increase in HDLC and SHBG (P<0.01). CONCLUSIONS: Intake of BBR improved some of the metabolic and hormonal derangements in a group of treated Chinese women with PCOS. Main effects could be related to the changes in body composition in obesity and dyslipidemia. Further controlled studies are needed for the assessment of the potential favorable metabolic effects of BBR in women with PCOS.


Asunto(s)
Berberina/uso terapéutico , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Femenino , Humanos , Resistencia a la Insulina/fisiología , Triglicéridos/metabolismo , Circunferencia de la Cintura/efectos de los fármacos , Relación Cintura-Cadera
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