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1.
Artículo en Inglés | MEDLINE | ID: mdl-37632973

RESUMEN

Objective: To assess the effect of a regional collaborative network on the treatment of ST-elevation myocardial infarction (STEMI) patients first admitted to non- percutaneous coronary intervention (PCI) hospitals. Methods: Using data from Kunshan Hospital of Traditional Chinese Medicine's chest pain center database, patients were grouped based on the establishment of the regional collaborative rescue network. Key timepoints and in-hospital complications were analyzed. Results: A total of 152 ST-elevation myocardial infarction patients were included in the study. Compared to control group, symptom-to-balloon time (S-B), time of first medical contact to balloon and inter-hospital referral time in observation group were significantly shorter [(314.03 ± 209.26) min vs (451.27 ± 290.44) min, P = .001], [(115.32 ± 54.73) min vs (191.67 ± 130.30) min, P = .001], [(55.09 ± 37.23) min vs (112.67 ± 95.90) min, P = .001], but time of symptom to first medical contact were not statistically significant[(210.27±217.07) min vs (239.61 ± 200.92) min, P = .136].The incidence of heart failure and total complications during hospitalization decreased [7 (8.14%) vs 13 (19.70%), P = .037] and [14 (16.28%) vs 24 (36.36%), P = .004]. However no statistically significant difference were observed in rate of death during hospitalization [2 (2.33%) vs 3 (4.55%), P = .450], ventricular fibrillation [2 (2.33%) vs 3 (4.55%), P = .450], left ventricular thrombosis [2 (2.33%) vs 4 (6.06%), P = .244] and recurrent myocardial infarction[1 (1.16%) vs 1 (1.52%), P = .851]. Conclusions: The regional cooperative rescue network notably reduces ischemic and referral times for STEMI patients, lowering the incidence of heart failure during their hospital stay.

2.
Altern Ther Health Med ; 29(6): 418-420, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37318891

RESUMEN

Kidney damage is one of the most common complications of diabetes, and inflammation caused by macrophage infiltration plays an important role. Folic acid (FA), a water-soluble vitamin, was previously found to affect inflammation by regulating macrophage polarization. In our study, we aimed to investigate the effect of FA on renal injury in mice with diabetic nephropathy (DN). We found that FA treatment ameliorated diabetic metabolic parameters in mice with DN, including reducing 24-hour food consumption, 24-hour urine volume and 24-hour water intake and increasing body weight and serum insulin. Of note, FA treatment improved renal functional and structural damage in mice with DN. In addition, FA treatment significantly reduced the number of renal infiltrating M1 macrophages, inflammatory cytokine FA stimulation significantly reduced the increase in F4/80+CD86+ cell ratio, inflammatory factor content and p-p65/p65 protein expression induced by high glucose exposure in RAW264.7 cells. All in all, our results indicated that FA protects against kidney damage in mice with DN by inhibiting M1 macrophage polarization, and its mechanism may be related to the inhibition of nuclear factor-k-gene binding (NF-kB) signaling pathway.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Animales , Ratones , Nefropatías Diabéticas/tratamiento farmacológico , Ácido Fólico/farmacología , Ácido Fólico/uso terapéutico , Riñón , Macrófagos , Inflamación
4.
Front Genet ; 13: 858882, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35464837

RESUMEN

Background: Glioblastoma (GBM) is widely known as a classical kind of malignant tumor originating in the brain with high morbidity and mortality. Targeted therapy has shown great promise in treating glioblastoma, but more promising targets, including effective therapeutic targets, remain to be identified. 18A (KIF18A) is a microtubule-based motor protein that is dysregulated and involved in the progression of multiple human cancers. However, the possible effects of KIF18A on GBM progression are still unclear. Methods: We performed DEG analysis, medical data analysis, and network analysis to identify critical genes affecting glioma progression. We also performed immunohistochemical analysis of the KIF18A levels in 94 patients with glioblastoma and the associated surrounding tissues. Patients were divided into two groups according to the high and low expression. Using a clinical analysis, we showed the potential associations between KIF18A expression and clinical characteristics of 94 GBM patients. We then investigated the effects of KIF18A on GBM cell proliferation by colony establishment, MTT, and immune blogging. The possible effect of KIF18A on GBM tumor growth was determined in mice. Results: We identified KIF18A as a potential gene affecting GBM progression. We further demonstrated that GBM tissues expressed KIF18A much higher, and its presentation was associated with recurrence in glioblastoma patients. We believe KIF18A promotes GBM cell proliferation. Conclusion: We demonstrated that KIF18A could be a promising target in treating GBM.

5.
Front Neurol ; 12: 673703, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34566833

RESUMEN

Objectives: Thousands of designated COVID-19 hospitals have been set up in China to fight the ongoing COVID-19 pandemic. Anecdotal reports indicate a falling rate of acute stroke diagnoses in these hospitals during the COVID-19 period. We conducted an exploratory single-center analysis to estimate the change in acute stroke presentation at the designated COVID-19 hospitals. Methods: This retrospective observational study included all patients admitted to Yongchuan Hospital Affiliated to Chongqing Medical University with acute stroke between January 24 and March 10, 2020. Patient demographics, characteristics of the stroke, treatment details, and clinical outcomes were compared with those of patients admitted in the corresponding period in the year before (2019, "the pre-COVID-19 period"). Subgroup analysis was performed in the ischemic and hemorrhagic stroke groups. Results: A total of 110 patients presented with acute stroke symptoms during the COVID-19 pandemic, compared with 173 patients in the pre-COVID-19 period. A higher proportion of stroke patients presented to the hospital via emergency medical services during the pandemic (48.2 vs. 31.8%, p = 0.006). There was a lower proportion of ischemic stroke patients (50.9 vs. 65.3%, p = 0.016) than in the preceding year. There were significantly fewer patients with 90-day modified Rankin Scale score ≥3 in the COVID-19 period compared with the pre-COVID-19 period (17.3 vs. 30.6%, p = 0.012). Among patients with ischemic stroke, the mean time from patient arrival to vessel puncture for emergency endovascular therapy in the COVID-19 period was shorter than that in the pre-COVID-19 period (109.18 ± 71.39 vs. 270.50 ± 161.51 min, p = 0.002). Among patients with hemorrhagic stroke, the rate of emergency surgical operation in the COVID-19 period was higher than that in the pre-COVID-19 period (48.1 vs. 30.0%, p = 0.047). The mean time from patient arrival to emergency surgical operation (15.31 ± 22.89 vs. 51.72 ± 40.47 min, p = 0.002) was shorter in the COVID-19 period than in the pre-COVID-19 period. Conclusions: Although fewer acute stroke patients sought medical care in this designated COVID-19 hospital during the COVID-19 pandemic, this type of hospital was more efficient for timely treatment of acute stroke. Recognizing how acute strokes presented in designated COVID-19 hospitals will contribute to appropriate adjustments in strategy for dealing with acute stroke during COVID-19 and future pandemics.

6.
Front Neurol ; 12: 655800, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025559

RESUMEN

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH. Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score. Results: This study included 76 patients (23.3%) with hematoma expansion and 61 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes. Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.

7.
Lipids Health Dis ; 19(1): 160, 2020 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-32622367

RESUMEN

BACKGROUND: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population. METHODS: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated. RESULTS: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P < 0.05) were significantly associated with ICAS but not with extracranial atherosclerotic stenosis after adjustment for confounding factors. Receiver operating characteristic (ROC) curves analysis revealed that the apo B/apo A-I ratio had the largest area under the ROC curve (AUC) among lipid levels alone and for lipid ratios (AUC = 0.588). Lipid ratios had higher AUC values than those for lipid levels alone for the identification of ICAS. CONCLUSION: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.


Asunto(s)
Arteriosclerosis Intracraneal/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Lípidos/sangre , Anciano , Apolipoproteína A-I/sangre , Apolipoproteína B-100/sangre , Pueblo Asiatico , Biomarcadores/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Constricción Patológica , Estudios Transversales , Femenino , Humanos , Arteriosclerosis Intracraneal/etiología , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Curva ROC
8.
Cancer Biother Radiopharm ; 34(9): 581-588, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31697592

RESUMEN

Background: Glioblastoma is one of the most malignant tumors in the brain with high mortality. In recent years, immunotherapy and targeted therapy show great prospects in the treatments for glioblastoma, whereas more effective therapeutic targets are still urgently needed to be developed. Nucleobindin-2 (NUCB2) is the precursor protein of nesfatin-1, which have a variety of metabolic functions, such as food intake and temperature regulation. In recent years, the potential link between NUCB2 and the development of multiple cancer was gradually revealed; however, the effects of NUCB2 on the progression of glioblastoma are still unclear. Methods: Immunohistochemical assays were performed to explore the NUCB2 expression levels in 94 samples of glioblastoma and corresponding nontumor tissues; patients were divided into NUCB2 high expression group and low expression group. Clinical analysis related to the clinical features, the potential link between NUCB2 expression levels, and clinical features were analyzed; the effects of NUCB2 on cell proliferation and invasion of glioblastoma were detected through colony formation and MTT assay, and transwell assay respectively. The possible effects of NUCB2 on tumor growth and metastasis were measured in mice. Results: In this study, we demonstrated that NUCB2 over-expression was correlated with the high degree of recurrence of patients with glioblastoma. Further, we also revealed that NUCB2 promoted cell proliferation and invasion of glioblastoma in vitro and promoted the growth and metastasis of glioblastoma in mice. Conclusion: This study provided evidence that NUCB2 might be a novel therapeutic target of glioblastoma.


Asunto(s)
Glioblastoma/patología , Nucleobindinas/metabolismo , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Técnicas de Silenciamiento del Gen , Glioblastoma/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Nucleobindinas/genética , Pronóstico
9.
Mol Med Rep ; 20(1): 719-727, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31115556

RESUMEN

Puerarin, a major bioactive constituent of the Radix puerariae, can ameliorate myocardial ischemia/reperfusion (I/R) injury. Emerging evidence supports that microRNA (miR)­21 functions as a protective factor against I/R and/or hypoxia­reperfusion (H/R)­induced myocardial injury. However, the role of miR­21 in the cardioprotective effect of puerarin remains unclear. Therefore, the purpose of the present study was to demonstrate the involvement of miR­21 in the cardioprotective mechanisms of puerarin using a cell model of I/R injury, generated by culturing rat H9c2 cardiomyocytes under H/R conditions. The results demonstrated that pre­treatment with puerarin significantly increased cell viability, decreased lactate dehydrogenase activity and upregulated miR­21 expression in H/R­treated H9c2 cells. Transfection of an miR­21 inhibitor led to an increase in H/R­induced cytotoxicity and reversed the protective effects of puerarin. Additionally, miR­21 inhibition attenuated the puerarin­induced decrease in the rate of apoptosis, caspase­3 activity and the expression of apoptosis regulator Bax, and increased apoptosis regulator Bcl­2 expression, under H/R conditions. Furthermore, puerarin mitigated H/R­induced oxidative stress as evidenced by the decrease in endogenous reactive oxygen species production, malondialdehyde content and NADPH oxidase 2 expression, and enhanced the antioxidative defense system as illustrated by the increase in superoxide dismutase activity, catalase and glutathione peroxidase levels. These effects were all eliminated by miR­21 inhibitor transfection. Furthermore, the miR­21 inhibitor exacerbated the H/R­induced oxidative stress and attenuated the antioxidative defense system in H/R­treated H9c2 cells. Taken together, the results suggested that miR­21 mediated the cardioprotective effects of puerarin against myocardial H/R injury by inhibiting apoptosis and oxidative stress.


Asunto(s)
Isoflavonas/farmacología , MicroARNs/genética , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Cardiotónicos/farmacología , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología
10.
Neurocrit Care ; 28(3): 314-321, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29139015

RESUMEN

BACKGROUND: Midline shift (MLS) has been associated with unfavorable outcome in patients with intracerebral hemorrhage (ICH). However, the optimal criteria to define the MLS measurements that indicate future outcome in ICH patients are absent, and the quantitative threshold of MLS that differentiates favorable and poor clinical outcome should be further explored. METHODS: We enrolled patients with ICH who underwent admission computed tomography (CT) within 6 h after onset of symptoms. We assessed MLS at several locations, including the pineal gland, septum pellucidum, and cerebral falx. MLS(max) was defined as the maximum midline shift among these locations. Functional outcomes were assessed with the Modified Rankin Scale (mRS) at 3 months. We performed multivariate logistic regression analysis to investigate the MLS locations for predicting poor outcome. ROC curve analysis was used to establish whether MLS values were predictive of 90-day poor outcome. RESULTS: In 199 patients with ICH, 78 (39.2%) patients had poor functional outcome at 3-month follow-up. Pineal gland shift, septum pellucidum shift, cerebral falx shift, and MLS(max) all showed a significant difference between poor outcome and favorable outcome (p < 0.001). After adjustment for age, baseline Glasgow Coma Scale score, ICH location, time to initial CT, baseline ICH volume, and intraventricular hemorrhage, the MLS(max) was independently associated with poor outcome (p = 0.032). MLS(max) > 4 mm (our proposed optimal threshold) was more likely to have poorer outcomes than those without (p < 0.001). CONCLUSIONS: MLS(max) can be a good independent predictor of clinical outcome, and MLS(max) > 4 mm is an optimal threshold associated with poor outcome in patients with ICH.


Asunto(s)
Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Evaluación de Resultado en la Atención de Salud/métodos , Índice de Severidad de la Enfermedad , Adulto , Anciano , Hemorragia Cerebral/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
11.
Stroke ; 48(11): 3019-3025, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29018128

RESUMEN

BACKGROUND AND PURPOSE: The aim of the study was to investigate the usefulness of the computed tomography (CT) island sign for predicting early hematoma growth and poor functional outcome. METHODS: We included patients with spontaneous intracerebral hemorrhage (ICH) who had undergone baseline CT within 6 hours after ICH symptom onset in our hospital between July 2011 and September 2016. Two readers independently assessed the presence of the island sign on the admission noncontrast CT scan. Multivariable logistic regression analysis was used to analyze the association between the presence of the island sign on noncontrast admission CT and early hematoma growth and functional outcome. RESULTS: A total of 252 patients who met the inclusion criteria were analyzed. Among them, 41 (16.3%) patients had the island sign on baseline noncontrast CT scans. In addition, the island sign was observed in 38 of 85 patients (44.7%) with hematoma growth. Multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and the presence of the island sign on baseline CT scan independently predicted early hematoma growth. The sensitivity of the island sign for predicting hematoma expansion was 44.7%, specificity 98.2%, positive predictive value 92.7%, and negative predictive value 77.7%. After adjusting for the patients' age, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, presence of subarachnoid hemorrhage, admission systolic blood pressure, baseline ICH volume, and infratentorial location, the presence of the island sign (odds ratio, 3.51; 95% confidence interval, 1.26-9.81; P=0.017) remained an independent predictor of poor outcome in patients with ICH. CONCLUSIONS: The island sign is a reliable CT imaging marker that independently predicts hematoma expansion and poor outcome in patients with ICH. The noncontrast CT island sign may serve as a potential marker for therapeutic intervention.


Asunto(s)
Presión Sanguínea , Hematoma Intracraneal Subdural , Tomografía Computarizada por Rayos X , Anciano , Biomarcadores , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/fisiopatología , Femenino , Estudios de Seguimiento , Hematoma Intracraneal Subdural/diagnóstico por imagen , Hematoma Intracraneal Subdural/mortalidad , Hematoma Intracraneal Subdural/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos
13.
World J Gastroenterol ; 22(10): 3031-7, 2016 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-26973399

RESUMEN

AIM: To determine if efficacy of chemotherapy on liver metastasis of gastrointestinal tract cancer can be predicted by apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). METHODS: In total, 86 patients with liver metastasis of gastrointestinal tract cancer (156 metastatic lesions) diagnosed in our hospital were included in this study. The maximum diameters of these tumors were compared with each other before treatment, 2 wk after treatment, and 12 wk after treatment. Selected patients were classified as the effective group and the ineffective group, depending on the maximum diameter of the tumor after 12 wk of treatment; and the ADC values at different treatment times between the two groups were compared. Spearman rank correlation was used to analyze the relationship between ADC value and tumor diameter. Receiver operating characteristic curve (ROC curve) was used to analyze the ADC values before treatment to predict the patient's sensitivity and specificity degree of efficacy to the chemotherapy. RESULTS: There was no difference in age between the two groups and in maximum tumor diameter before treatment and 2 wk after treatment. However, after 12 wk of treatment, maximum tumor diameter in the effective group was significantly lower than that in the ineffective group (P < 0.05). Before treatment, ADC values in the ineffective group were significantly higher than those in the effective group (P < 0.05). There was no difference in ADC values between the effective and ineffective groups after 2 and 12 wk of treatment. However, ADC values were significantly higher after 2 and 12 wk of treatment compared to before treatment in the effective group (P < 0.05). Spearman rank correlation analysis showed that ADC value before treatment and the reduced percentage of the maximum tumor diameter after 12 wk of treatment were negatively correlated, while the increase in the percentage of the ADC value 12 wk after treatment and the decrease in the percentage of the maximum tumor diameter were significantly positively correlated. The results of the ROC curve showed that ADC value with a chemotherapy ineffective threshold value of 1.14 × 10(-3) mm(2)/s before treatment had a sensitivity and specificity of 94.3% and 76.7%, respectively. CONCLUSION: DWI ADC values can be used to predict the response of patients with liver metastasis of gastrointestinal tract cancer to chemotherapy with high sensitivity and relatively high specificity.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias Gastrointestinales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Adulto , Anciano , Antineoplásicos/uso terapéutico , Área Bajo la Curva , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
14.
Drug Des Devel Ther ; 10: 745-55, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26937175

RESUMEN

INTRODUCTION: mTOR and MDM2 signaling pathways are frequently deregulated in cancer development, and inhibition of mTOR or MDM2 independently enhances carcinoma-cell apoptosis. However, responses to mTOR and MDM2 antagonists in renal cell carcinoma (RCC) remain unknown. MATERIALS AND METHODS: A498 cells treated with MDM2 antagonist MI-319 and/or mTOR inhibitor rapamycin were employed in the present study. Cell apoptosis and Western blot analysis were performed. RESULTS AND CONCLUSION: We found that the MDM2 inhibitor MI-319 induced RCC cell apoptosis mainly dependent on p53 overexpression, while the mTOR antagonist rapamycin promoted RCC cell apoptosis primarily through upregulation of HIF1α expression. Importantly, strong synergistic effects of MI-319 and rapamycin combinations at relatively low concentrations on RCC cell apoptosis were observed. Depletion of p53 or HIF1α impaired both antagonist-elicited apoptoses to differential extents, corresponding to their expression changes responding to chemical treatments, and double knockdown of p53 and HIF1α remarkably hindered MI-319- or rapamycin-induced apoptosis, suggesting that both p53 and HIF1α are involved in MDM2 or mTOR antagonist-induced apoptosis. Collectively, we propose that concurrent activation of p53 and HIF1α may effectively result in cancer-cell apoptosis, and that combined MDM2 antagonists and mTOR inhibitors may be useful in RCC therapy.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Renales/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Renales/patología , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/metabolismo , Antineoplásicos/química , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Indoles/química , Indoles/farmacología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Relación Estructura-Actividad , Serina-Treonina Quinasas TOR/metabolismo , Proteína p53 Supresora de Tumor/genética
15.
Tumour Biol ; 36(5): 3417-22, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25527159

RESUMEN

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phospho(tyr421)-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.


Asunto(s)
Carcinoma de Células Renales/patología , Cortactina/fisiología , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quinasa de Cadena Ligera de Miosina/metabolismo , Metástasis de la Neoplasia
16.
Metab Brain Dis ; 27(1): 91-100, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22109853

RESUMEN

It has been suggested that pancreatic cancer is associated with a greater prevalence of depression than many other cancers, but the mechanism accounting for this potential association has not yet been illustrated. In the present study, conditioned media (CM) from three pancreatic cancer cell lines and primary pancreatic cancer cells from two patients were added to culture system of differentiated pheochromocytoma cell line PC12. The release of dopamine (DA) and norepinephrine (NE) by PC12 was significantly inhibited after CM treatment (P < 0.05), similar to what happened after recombinant interleukin 6(IL-6) treatment. Furthermore, pretreatment with anti-IL-6 antibody significantly blocked the inhibitory effects of pancreatic cancer CM on DA and NE production (P < 0.05). We also demonstrated that tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of catecholamine, was reduced after exposure to IL-6, which was accompanied by JAK-STAT3 pathway activation. Our results demonstrated that IL-6 in CM from pancreatic cancer down-regulated the production of DA and NE by PC12 cell. The possible underlying mechanisms might be decreasing TH production via activation of JAK-STAT3 signal transduction pathway. The present study might help to better understand the close relationship between pancreatic cancer and depression.


Asunto(s)
Depresión/metabolismo , Dopamina/metabolismo , Interleucina-6/farmacología , Norepinefrina/metabolismo , Neoplasias Pancreáticas/metabolismo , Animales , Anticuerpos Monoclonales , Línea Celular Tumoral , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Depresión/etiología , Humanos , Células PC12 , Neoplasias Pancreáticas/complicaciones , Fosforilación , Ratas , Factor de Transcripción STAT3/metabolismo , Transducción de Señal
17.
Zhongguo Gu Shang ; 25(8): 627-31, 2012 Aug.
Artículo en Chino | MEDLINE | ID: mdl-25058949

RESUMEN

OBJECTIVE: To analyze micromovement of distal tihiofihular joints in different motion range of ankle joint ,and define the micromovement characteristic and range of distal tibiofihular joints. METHODS: Twelve normal Chinese were chosen. There were 9 males and 3 females, aged from 19 to 37 years old with an average (26.5 +/- 0.5) years. Detection terminals of laser photographic scanner were installed near the highest point between medial malleolus and lateral malleolos, the change of detection terminals on the position of dorsiflex, extension, introversion and eversion of ankle joint were scanned by 3D-laser scanner. The displacement of two detection terminals on the X ,Y and Z-axis (X-axis stands for the vertical-axis between coronal plane and Z-axis Y-axis stands for the vertical-axis between sagittal plane and Z-axis Z-axis stands for macroaxis of tibia). RESULTS: Along with increased range of motion on the position of dorsiflex ,extension, introversion and eversion of ankle joint, the range of micromovement of distal tibiofibolar joints increased too. The max-displacement of X, Y and Z were respectively (1.04 +/- 0.12) mm, (1.70 +/- 0.16) mm and--(0.87 +/- 0.10) mm. CONCLUSION: 3D-laser scanner can be used to determine the detailed displacement of distal tibiofibolar joint on the X , Y and Z, and measure the motion of distal tibiofibular joint. The method can be used to study the pathologic change of distal tibiofibular joint ,and provide basic biomechnics data for internal fixtor fitting for the characteristic of distal tibiofibular joint.


Asunto(s)
Articulación del Tobillo/fisiología , Pueblo Asiatico , Peroné , Movimiento , Tibia , Adulto , Femenino , Humanos , Masculino , Rango del Movimiento Articular , Adulto Joven
18.
Artículo en Chino | MEDLINE | ID: mdl-22096847

RESUMEN

OBJECTIVE: To investigate the association between the polymorphisms of metabolic genes and telomere length of genomic DNA in peripheral blood of workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One hundred and forty five coke-oven workers exposed to PAHs and sixty eight non-exposed medical staffs were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) served as the internal exposure dose of PAHs for all subjects. Relative telomere length (RTL) of genomic DNA in peripheral blood was used as telomere length and measured by real-time PCR. Polymorphisms of metabolic genes were detected by PCR-based methods. RESULTS: Compared with control group, the exposure group shown a decreased RTL (1.10 +/- 0.75 vs 1.43 +/- 1.06, P < 0.05). In the coke-oven workers, after adjusting the sex, age, cigarettes per day and urinary 1-OHP, RTL (1.25 +/- 0.93) of workers with CT genotype at the CYP1A1 3801 T > C was significantly longer than that (0.93 +/- 0.51) of workers with TT genotype (P < 0.05). RTL (0.90 +/- 0.58) of individuals with the Tyr/His genotype at mEH Tyr113His was significantly shorter than that (1.24 +/- 0.90) of individuals with the Tyr/Tyr genotype (P < 0.05). RTL (1.02 +/- 0.64) of individuals with the CT genotype at AHR rs10250822 was significantly shorter than that (1.36 +/- 1.14) of individuals with the CC genotype (P < 0.05). RTL (0.93 +/- 0.54) of individuals with the AT genotype at AHR rs10247158 was significantly shorter than that (1.19 +/- 0.84) of individuals with the AA genotype (P < 0.05). CONCLUSION: The results of present study suggested that PAHs exposure could induce the shorted RTL, CYP1A1, mEH, AHR polymorphisms might influence the change of telomere length of genomic DNA in peripheral blood of workers exposed to PAHs.


Asunto(s)
Exposición Profesional , Hidrocarburos Policíclicos Aromáticos/toxicidad , Polimorfismo de Nucleótido Simple , Telómero/genética , Adulto , Estudios de Casos y Controles , Citocromo P-450 CYP1A1/genética , ADN/genética , Daño del ADN , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Artículo en Chino | MEDLINE | ID: mdl-22096852

RESUMEN

OBJECTIVE: To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. METHODS: In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. RESULTS: The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). CONCLUSION: The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure.


Asunto(s)
Hexanos/efectos adversos , Proteína Básica de Mielina/sangre , Exposición Profesional , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Adulto Joven
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