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1.
J Chem Phys ; 150(18): 184903, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31091923

RESUMEN

We present a systematic investigation on the effect of adding nanoparticles on the dynamics of polymer chains by using coarse-grained molecular dynamics simulation. The dynamics is characterized by three aspects: molecular motion, relaxation at different length scales, and dynamical heterogeneity. It is found that the motion of polymer chains slows down and the deviation from Gaussian distribution becomes more pronounced with increasing nanoparticle volume fractions. For polymer nanocomposites with R ≤ Rg, the relaxation at the wave vector q = 7.0 displays multistep decay, consistent with the previous reports in strongly interacting polymer nanocomposites. Moreover, a qualitatively universal law is established that dynamic heterogeneity at whole chain's scale follows a nonmonotonic increase with increasing nanoparticle loadings, where the volume fraction of the maximum dynamic heterogeneity corresponds to the particle loading when the average distance between nanoparticles is equal to the Kuhn length of polymer chains. We show that the decoupling between whole chain's dynamics and segment dynamics is responsible for the nonmonotonic behavior of dynamic heterogeneity of whole chains.

2.
Bioorg Med Chem Lett ; 28(4): 547-551, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29422390

RESUMEN

α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evaluated the vasodilatory activities of these compounds. Among them, we found that compounds 2, 7, 12, which contain 2-OCH3, 2-CH3 or 2, 5-CH3, respectively, exhibited potent α1-blocking activity similar to protype drug naftopidil (1). The antagonistic effects of 2, 7, and 12 on the (-)-noradrenaline-induced contractile response of isolated rat prostatic vas deferens (α1A), spleen (α1B) and thoracic aorta (α1D) were further characterized to assess the sub receptor selectivity. Compared with naftopidil (1) and terazosin, compound 12 showed the most desirable α1D/1A subtype selectivity, especially improved α1A subtype selectivity, and the ratios pA2 (α1D)/pA2 (α1B) and pA2 (α1A)/pA2 (α1B) were 17.0- and 19.5-fold, respectively, indicating less cardiovascular side effects when used to treat LUTS/BPH. Finally, we investigated the chiral pharmacology of 12. We found, however, that the activity of enantiomers (R)-12 and (S)-12 are not significantly different from that of rac-12.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Naftalenos/farmacología , Fenilacetatos/farmacología , Piperazinas/farmacología , Vasodilatadores/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/síntesis química , Antagonistas de Receptores Adrenérgicos alfa 1/química , Animales , Aorta/efectos de los fármacos , Masculino , Contracción Muscular/efectos de los fármacos , Naftalenos/síntesis química , Naftalenos/química , Fenilacetatos/síntesis química , Fenilacetatos/química , Piperazinas/síntesis química , Piperazinas/química , Prazosina/análogos & derivados , Prazosina/farmacología , Conejos , Ratas Sprague-Dawley , Bazo/efectos de los fármacos , Estereoisomerismo , Conducto Deferente/efectos de los fármacos , Vasodilatadores/síntesis química , Vasodilatadores/química
3.
J Inflamm Res ; 17: 2383-2397, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660574

RESUMEN

Objective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics. Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues. Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group. Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.

4.
Zhonghua Nan Ke Xue ; 18(6): 487-92, 2012 Jun.
Artículo en Zh | MEDLINE | ID: mdl-22774600

RESUMEN

OBJECTIVE: To analyze the expression of inducible nitric oxide synthase (iNOS) in the testis tissues of Fmr1 (fragile X mental retardation 1) knockout and wild-type male mice in different developmental stages, and provide background information for researches on fragile X syndrome. METHODS: This study included 4, 6, 8 and 10 weeks old Fmr1 knockout and wild-type male mice, 6 in each age group. We identified the genotype of the mice by PCR, and detected and compared the expression of iNOS in the testis tissues of the Fmr1 knockout and wild-type mice by immunohistochemistry. RESULTS: The iNOS expression was weakly positive in the Leydig cells of the 4-week-old mice, moderately positive in the 6-week-old ones, and strongly positive in 8- and 10-week-old ones, significantly weaker in the Fmr1 knockout than in the wild-type ones. CONCLUSION: The expression of iNOS significantly decreases in the testis of Fmr1 knockout mice, suggesting that iNOS may be involved in the pathogenesis of fragile X syndrome.


Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Testículo/metabolismo , Animales , Síndrome del Cromosoma X Frágil/genética , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Ratones Noqueados
5.
Zhong Yao Cai ; 35(10): 1557-61, 2012 Oct.
Artículo en Zh | MEDLINE | ID: mdl-23627117

RESUMEN

OBJECTIVE: To explore the relation between the quality of the Herb-Paris and their cultivation of soil nutritional status. METHODS: The soil nutrient status (0 - 30 cm) of Paris polyphylla var. yunnanensis, artificially cultivated areas were determined in 2009 and their rhizome qualities harvested in 2010 were evaluated respectively. Determination of 0 - 30cm depth soil ingredients status with soil conventional five nutritional analysis method of 29 artificial cultivation area, 9 Prefectures of Yunnan Province. RESULTS: Soil nutrient has effect on quality of Herb-Paris medicinal ingredients. CONCLUSION: The multiple linear stepwise regression analysis reveals that among a certain range, the steroidal saponin VII content is positively correlated with the content of soil organic matter and pH. Steroidal saponin H content is positively correlated with the content of soil organic matter, available P and pH. Steroidal saponin I is positively correlated with the content of available K, but negatively correlated with the content of available Herb-Paris, and steroidal saponin II is positively correlated with the content of soil organic matter and available K.


Asunto(s)
Liliaceae/química , Nitrógeno , Rizoma/química , Saponinas/análisis , Suelo/análisis , Agricultura/métodos , China , Cromatografía Líquida de Alta Presión , Fertilizantes , Concentración de Iones de Hidrógeno , Liliaceae/crecimiento & desarrollo , Fósforo , Potasio , Control de Calidad , Análisis de Regresión , Rizoma/crecimiento & desarrollo , Suelo/química
6.
J Food Biochem ; 46(3): e13932, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34528276

RESUMEN

The purpose of this study was to explore the hypouricemic effect in hyperuricemia mice of triterpenoid acids from Inonotus obliquus (TAIO), and decipher of the underlying xanthine oxidase inhibitory mechanism. Measurement of xanthine oxidase (XO) inhibitory activity was assayed. Organ indexes and serum biochemical indicators were measured in potassium oxonate-induced hyperuricemia mice. Studies showed that TAIO had the strong inhibitory effect on XO activity, and its inhibition type was mixed and reversible. In vivo, TAIO decreased efficiently uric acid level, hepatic XO, serum blood urea nitrogen activities in hyperuricemia mice. Indicating that TAIO may ameliorate kidney damage and relieve inflammation in hyperuricemic mice, and had the inhibitory effect on XO activity. Furthermore, eight triterpenoids were identified by Ultra performance liquid chromatography electrospray quadrupole time of flight mass spectrometry. These findings proved that triterpenoids from Inonotus obliquus would have potential biological characteristics and effect on controlling hyperuricemia and gout as an active supplement. PRACTICAL APPLICATIONS: There are a large amount of evidence indicating that hyperuricemia and gout are related to the hypertension and obesity. And gout and hyperuricemia are also possible connection with cardiovascular disease and metabolic syndrome. Currently, xanthine oxidase is the target of many kinds of chemical drugs at present, but the therapeutic drugs used in clinical medicine will produce more or less side effects. Therefore, the aim of this study was to explore the material basis of effective substances for reducing uric acid in Inonotus obliquus and to evaluate its effect. This study can provide a promising application of Inonotus obliquus in the fields of functional foods or medicines for gout and hyperuricemia.


Asunto(s)
Agaricales , Gota , Hiperuricemia , Triterpenos , Animales , Gota/tratamiento farmacológico , Hiperuricemia/inducido químicamente , Hiperuricemia/tratamiento farmacológico , Inflamación , Inonotus , Ratones , Triterpenos/farmacología , Triterpenos/uso terapéutico , Ácido Úrico , Xantina Oxidasa/metabolismo , Xantina Oxidasa/uso terapéutico
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 361-366, 2022 Apr.
Artículo en Zh | MEDLINE | ID: mdl-35395964

RESUMEN

OBJECTIVE: To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia. METHODS: A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared. RESULTS: After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P<0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P<0.001, ALL: P<0.001, CML: P<0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P<0.05). CONCLUSION: Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.


Asunto(s)
Hemostáticos , Leucemia Mieloide Aguda , Enfermedad Aguda , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Hemorragia , Humanos , Leucaféresis/métodos , Leucemia Mieloide Aguda/terapia
8.
J Chin Med Assoc ; 83(5): 471-477, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32217993

RESUMEN

BACKGROUND: Prostate cancer (PCa) is the most common malignancy seen in men and the second leading cause of cancer-related death in males. The incidence and mortality associated with PCa has been rapidly increasing in China recently. METHODS: Multiple diagnostic models of human PCa were developed based on Taylor database by combining the artificial neural networks (ANNs) to enhance the ability of PCa diagnosis. Genetic algorithm (GA) is used to select feature genes as numerical encoded parameters that reflect cancer, metastatic, or normal samples. Back propagation (BP) neural network and learning vector quantization (LVQ) neural network were used to build different Cancer/Normal, Primary/Metastatic, and Gleason Grade diagnostic models. RESULTS: The performance of these modeling approaches was evaluated by predictive accuracy (ACC) and area under the receiver operating characteristic curve (AUC). By observing the statistically significant parameters of the three training sets, our Cancer/Normal, Primary/Metastatic, and Gleason Grade models' with ACC and AUC can be drawn (97.33%, 0.9832), (99.17%, 0.9952), and (90.48%, 0.8742), respectively. CONCLUSION: These results indicated that our diagnostic models of human PCa based on Taylor database combining the feature gene expression profiling data and artificial intelligence algorithms might act as a powerful tool for diagnosing PCa. Gleason Grade diagnostic models were used as novel prognostic diagnosis models for biochemical recurrence-free survival and overall survival, which might be helpful in the prognostic diagnosis of PCa in patients.


Asunto(s)
Redes Neurales de la Computación , Neoplasias de la Próstata/diagnóstico , Anciano , Bases de Datos Factuales , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología
9.
Eur J Pharmacol ; 870: 172817, 2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-31756334

RESUMEN

Benign prostatic hyperplasia (BPH) is a common disorder of the urinary system in aging men. 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide (HJZ-3), which is derived from naftopidil, exhibited 97.7- and 64.6-fold greater inhibitory effects for a1D adrenoceptor than for a1B- and a1A-adrenoceptors in vitro, respectively. To investigate the therapeutic potential for treating BPH, we evaluated the pharmacological activity of HJZ-3. Specifically, we evaluated through estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo. HJZ-3 effectively prevented the progression of rat prostatic hyperplasia by suppressing the increase in prostate index and reducing the quantitative analysis of the relative acinus volume, relative stroma, epithelial volume and epithelial thickness and expression of proliferating cell nuclear antigen and α-smooth muscle actin. HJZ-3 decreased α1A- and α1D-adrenoceptor protein expressions in prostate tissue. HJZ-3 is a good alternative for α1A- and α1D-adrenoceptor blocker. It may relax smooth muscle tone and relieve symptoms of BPH.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/química , Indoles/química , Naftalenos/química , Piperazinas/química , Hiperplasia Prostática/tratamiento farmacológico , Receptores Adrenérgicos alfa 1/metabolismo , Actinas/genética , Actinas/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Andrógenos/metabolismo , Animales , Modelos Animales de Enfermedad , Estrógenos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Indoles/farmacología , Masculino , Naftalenos/farmacología , Piperazinas/farmacología , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/efectos de los fármacos , Ratas Sprague-Dawley
10.
Pathol Res Pract ; 216(1): 152732, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31780055

RESUMEN

BACKGROUND: FK506 binding protein 9 (FKBP9) has been reported and identified for a long time, but its relationship with cancer is rarely studied. For example, the role of FK506 binding protein 9 in prostate cancer (PCa) is still unclear. Therefore, we decided to detect the expression level of FKBP9 in PCa and explore its clinical significance. METHODS: The expression level of FKBP9 protein was detected by immunohistochemistry. In addition, it was demonstrated by high-throughput sequencing of mRNA levels in the TCGA (cancer genome atlas) dataset of 499 patients. Kaplan-meier analysis and Cox proportional hazard regression model were used to evaluate the relationship between FKBP9 expression and survival in prostate cancer patients. RESULTS: The expression of FKBP9 was localized in the cytoplasm, which in normal prostate tissues was obviously lower than that in PCa tissues (P = 0.001). High expression of FKBP9 was related with lymph node metastasis (P = 0.022) and distant metastasis (P = 0.028). Kaplan-Meier survival analysis revealed that the BCR-free survival of PCa patients with high FKBP9 level was significantly shortened (P=0.041). CONCLUSIONS: FKBP9 may be a cancer promoter that enhances PCa progression, and the level of FKBP9 may be used as an independent precursor of PCa patients.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas de Unión a Tacrolimus/metabolismo , Anciano , Progresión de la Enfermedad , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1678-1681, 2019 Oct.
Artículo en Zh | MEDLINE | ID: mdl-31607331

RESUMEN

OBJECTIVE: To analyze the diagnostic value of (1, 3) -ß-D-glucan and galactomannan (GM) tests in the patients with acute leukemia complicated by invasive fungal disease, and explore the application of serological detection (G/GM) and lung CT for early diagnosis of invasive fungal disease (IFD). METHODS: A total of 493 patients with acute leukemia complicated by high risk invasive fungal infection, also receival G and GM tests, in Department of hematology of our hospital from June 2016 to December 2016 were selected and were divided into IFD-confirmed group (62 cases) including confirmed and clinical diagnesed IFD, and IFD-unconfirmed group (431 cases) including suspected IFD and non-IFD according to the diagnostic criteria of IFD. The results of G and GM tests in patients of 2 groups were analyzed, then the diagnostic efficacy of G and GM done and combination evaluated. In addition, 26 patients whose lung CT negative at hospitalization, moreover, presentation of changes in lung by CT during hospitalization and serological G and GM test positive were selected, and the difference of time between serological that postive and presentation of changes in lung by CT were compared for the estimation of early diagnotic value. RESULTS: The positive rate of (1, 3) -ß-D-glucan in IFD-confirmed group and IFD-unconfirmed group was 56.5% and 10.4%, respectively. Meanwhile, that of galactomannan test was 41.9% and 9.0%, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of (1, 3) -ß-D-glucan was 56%, 90%, 44% and 92%, and that of galactomannan was 42%、91%、40% and 93%, respectively. Moreover, the combination of (1, 3) -ß-D-glucan and galactomannan could raise the sensitivity to 69% and specificity to 98%. The positive results of serological detection (G/GM) come earlier about five days than CT changes. CONCLUSION: Both (1, 3) -ß-D-glucan and galactomannan test have high sensitivity and specificity, and the combination of them can improve the diagnostic efficacy, and make the clinical antifungal therapy more precisely. In the early clinical diagnosis of IFD, the positive results of serological detection coming earlier than lung CT.


Asunto(s)
Infecciones Fúngicas Invasoras , Leucemia Mieloide Aguda , Galactosa/análogos & derivados , Humanos , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/etiología , Leucemia Mieloide Aguda/complicaciones , Mananos
12.
Asian Pac J Cancer Prev ; 19(7): 1761-1766, 2018 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-30049184

RESUMEN

Backgrounds: Targeted therapy for lung cancer depends on the genetic testing. Liquid biopsy provides a valuable source for the genetic testing. However, direct evidence was lacking for whether liquid biopsy could guide the targeted therapy. Methods: In this retrospective study, the admitted patients from Jan 2015 to Feb 2016 were screened through a pre-established database. Patients with metastatic, pathologically-confirmed, and treatment naïve non-small cell lung cancer who were prescribed with epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) from the guidance of liquid biopsy were enrolled (Liquid group). The mutation status in tumors was not mandatory. During the same period, patients medicated with TKI based on tumor samples were included in the Control group. They were enrolled in an age-, gender-, performance-, smoking-, and histology-matched manner. Results: We screened 536 patients and enrolled 26 patients in the Liquid group. Another 26 patients were enrolled in a 1:1 ratio in the Control group. In the Liquid group, a high consistence (84.6%) in EGFR mutation status between liquid and tumor was observed. The best response was partial response in 19 patients (73.1 %), and followed by stable disease in 6 patients (23.1 %). The median progression-free survival was 10.0 months (95%CI: 4.2-15.8 months). In the Control group, a similar disease control rate (88.4%, P=0.603) and comparable PFS (8.6 months, 95% CI: 7.6-10.4 months, P=0.714, HR=0.657, 95% CI: 0.309-1.396) was found. In the Liquid group, 3 of 4 patients with discordant results between tumor and liquid biopsy showed treatment responses favoring the liquid biopsy. Conclusion: This study provided direct evidence supporting the liquid biopsy for guiding the targeted therapy for lung cancer.


Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/diagnóstico , Terapia Molecular Dirigida , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Biopsia Líquida , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
13.
Oncol Lett ; 13(2): 847-850, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28356968

RESUMEN

Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.

14.
Reprod Toxicol ; 21(3): 301-6, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16257174

RESUMEN

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a reproductive and developmental toxicant that can alter endocrine status, leading to decreased fertility and altered embryonic development; however, there are limited reports on TCDD toxicity during early pregnancy. In the present study, pregnant and pseudopregnant NIH mice were exposed to TCDD orally (2, 50 and 100 ng/kg body weight) during early gestation (days 1-8), pre-implantation stages (days 1-3), and peri-implantation to early post-implantation stages (days 4-8). TCDD concentration in uterus, liver, kidney, brain and fat on day 9 of pregnancy was monitored by an aryl hydrocarbon receptor (Ah receptor, AhR)-mediated LacZ reporter system in yeast. Results showed that the number of implanted embryos was significantly reduced on day 9 of gestation by 50 and 100 ng/kg TCDD exposure. The number of implantation sites was lower for animals exposed to TCDD on days 1-3 versus those exposed during days 4-8. Decidualization in pseudopregnant mice was also inhibited by TCDD exposure. TCDD concentrations as low as 2 ng/kg significantly decreased serum progesterone levels but had no effect on serum estradiol. TCDD level in the uterus was equal to levels in the liver, but lower than the fat tissue. These results suggest that TCDD sensitivity might be attributed its local accumulation in the uterus.


Asunto(s)
Implantación del Embrión/efectos de los fármacos , Pérdida del Embrión/inducido químicamente , Contaminantes Ambientales/toxicidad , Dibenzodioxinas Policloradas/toxicidad , Útero/metabolismo , Animales , Decidua/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Femenino , Edad Gestacional , Ratones , Tamaño de los Órganos/efectos de los fármacos , Dibenzodioxinas Policloradas/farmacocinética , Embarazo , Progesterona/sangre , Seudoembarazo , Factores de Tiempo , Útero/efectos de los fármacos , Útero/patología
15.
Cell Biochem Biophys ; 73(3): 643-7, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27259306

RESUMEN

Conventionally, serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) are used as primary methods to diagnose and monitor multiple myeloma (MM). Recently, serum-free light chain (FLC) assay has been incorporated into hematological screening programs for myeloma. The purpose of this study is to compare the performance of the three methods in monitoring MM patients after autologous stem cell transplantation (ASCT). SPE, serum IFE and serum FLC assay were performed on 38 MM patients who underwent ASCT. In total, four patients had unexpected protein bands (UPBs) and 13 patients had relapsed after ASCT. Our results indicate that IFE is more sensitive than SPE and FLC assay in detection of UPBs and relapse. The results of IFE may provide useful information in advance of patient relapse.


Asunto(s)
Electroforesis de las Proteínas Sanguíneas/métodos , Proteínas Sanguíneas/análisis , Pruebas Hematológicas/métodos , Mieloma Múltiple/sangre , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo/efectos adversos , Humanos , Inmunoensayo/métodos , Mieloma Múltiple/cirugía , Mieloma Múltiple/terapia , Sensibilidad y Especificidad
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(6): 1597-601, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24370055

RESUMEN

This study was aimed to explore the method for induction and expansion of EB virus specific cytotoxic T lymphocytes (EBV-CTL) in vitro, and to detect their killing effect. Peripheral blood mononuclear cells (PBMNC) were collected from 6 EBV seropositive healthy donors, and EBV-transformed B lymphoblastoid cells (BLCL)were used as the antigen-presenting cells and antigen stimulant which was irradiated by 40 Gy (60)Co irradiator. The autologous PBMNC and irradiated BLCL were cultured to induce and expand the EBV-CTL, and the immunophenotype was identified by the flow cytometry. The killing effect of the EBV-CTL against the autologous BLCL (autoBLCL), the autologous PHA cultured B lymphoblastoid cells( PHA-BLCL), the allogeneic BLCL (alloBLCL) and the K562 cells were measured with LDH release assay under different effector-to-target ratio. The results showed that the 6 cell lines of EBV-CTL were induced and expanded from the EBV seropositive healthy donors, the overall increase in cell numbers varied from 18.6 to 55.0 times. After 10 stimulations, the specific killing efficiency of the EBV-CTL for the autoBLCL were 59.4%, 43.2% and 29.0% under the effector-to-target ratio of 20: 1, 10: 1 and 5: 1. The nonspecific killing efficiency for the PHA-blast, alloBLCL and K562 cells were 7.1%, 9.4% and 10.3% (P < 0.05) under the 20: 1 ratio; 6.6%, 8.3% and 8.1% (P < 0.05) under 10: 1; 5.4%, 7.3% and 6.3% (P < 0.05) under 5: 1, respectively. It is concluded that the EBV-CTL can be successfully induced and expanded ex vivo for specific killing of HLA matched BLCL and may become a potential treatment for EBV related post-transplant lymphoproliferative disorders.


Asunto(s)
Linfocitos B/inmunología , Herpesvirus Humano 4/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/virología , Línea Celular Transformada , Humanos , Células K562 , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Linfocitos T Citotóxicos/citología
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(2): 436-40, 2013 Apr.
Artículo en Zh | MEDLINE | ID: mdl-23628049

RESUMEN

This study was aimed to establish a model for detecting the donor chimerism rate following the multi-donor hematopoietic stem cell transplantations, and simplify its calculation method. Patients with hematologic disease receiving allogeneic hematopoietic stem cell transplantation including single-donor and multi-donor were selected in this study and the donor cell chimerism rates were detected, using STR-PCR combined with capillary electrophoresis. The results indicated that the peaks of the sister alleles coming from the same individual were confirmed to have the approximate areas and can be replaced each other in the situation of mixed chimerism. In the calculation model, the value between reference chimerism and approximate chimerism have no significant difference using the hypothetical peak areas, and the result was confirmed to be accepted basing on typical measurement error between sister alleles (5% - 20%). It is concluded that the areas of share peaks can be replaced by non-share peaks and this conclusion can be used to calculate the double-donor CHM (DD-CHM)(%). Compared to the D alleles, R alleles show more strategic importance because it can lead to more accurate result and allowed simplifying the arithmetic calculations for DD-CHM(%).


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Quimera por Trasplante/genética , Alelos , Electroforesis Capilar , Humanos , Reacción en Cadena de la Polimerasa , Periodo Posoperatorio , Donantes de Tejidos , Trasplante Homólogo
18.
J Toxicol Sci ; 36(6): 713-24, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22129735

RESUMEN

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs) and similar compounds are toxic to animals and humans. Based on a yeast reporter system, AhR-activating ligands similar in concentration to 2 ng/l of TCDD were detected in two canal waters in Guangzhou, China. In this study, a three-generation experiment was conducted to assess the reproductive and developmental risks associated with these waters in C57BL/6J female mice, including female reproduction, pup indices, reproductive hormone levels, and levels of AhR, ARNT, and CYP1A2 in the uterus. Similar reproductive toxic effects were produced in the offspring of mice that drank the canal water as would occur if they drank 2 ng/l/day TCDD. The major reproductive indices that were affected included mating time and gestation length over all the generations. A striking finding is the TCDD (2 ng/l) and the water samples significantly reduced Day 4 pup survival rates in the F2 and F3. Both TCDD exposure and drinking canal water decreased estradiol-17ß (E2) levels in the multiparous females and decreased follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 levels in the virgin females. Immunochemical staining revealed that the AhR and CYP1A2 positive signals were enhanced, and the ARNT positive signal was weakened in the uteri of mice drinking water with TCDD (2 ng/l) and the canal water samples. These results imply that the canal water contains AhR ligands that could induce similar toxic effects as do low levels of TCDD. Exposure to these contaminants can significantly impair the reproductive health of female mice. Considering this canals are open directly to Pearl River, whether these effects could be caused in human reproduction and development warrants further study.


Asunto(s)
Disruptores Endocrinos/toxicidad , Exposición Materna , Dibenzodioxinas Policloradas/toxicidad , Receptores de Hidrocarburo de Aril/metabolismo , Contaminantes Químicos del Agua/toxicidad , Animales , Proteínas Portadoras/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Drenaje de Agua , Estradiol/sangre , Femenino , Proteínas Fetales/metabolismo , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos , Dibenzodioxinas Policloradas/análogos & derivados , Embarazo , Reproducción/efectos de los fármacos , Útero/efectos de los fármacos , Útero/metabolismo
19.
Zhonghua Xue Ye Xue Za Zhi ; 30(11): 741-4, 2009 Nov.
Artículo en Zh | MEDLINE | ID: mdl-20137308

RESUMEN

OBJECTIVE: To explore the relationship between CMV reactivation and KIR haplotype or HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell transplantation (HSCT). METHODS: From January 2003 to December 2008 the HLA-Cw/KIR genotype of 48 patient-donor pairs were determined by polymerase chain reaction with sequence specific primers (PCR-SSP) and sequence specific nucleotide (PCR-SSOP). Posttransplant CMV reactivation was performed by immune histochemically assay. RESULTS: Of 48 patients, 15 were transplanted from unrelated donors with an antigen mismatch for HLA Cw and 33 patient-donor pairs were matched for HLA-Cw. The CMV reaction rate was 66.7% for HLA-Cw mismatch group and 48.5% for HLA-Cw match group (chi(2) = 1.39, P = 0.2375). Thirty-seven donor-patients pairs belonged to group C1 and 11 to group C2, and CMV reaction rate was 64.9% in group C1 and 18.2% in group C2 (chi(2) = 18.13, P < 0.0001). Twenty-six patients received graft from KIR haplotype A (group A donor) and 22 from KIR haplotype B donors (group B donor) and CMV reaction rate was 57.7% in group A donor and 50.0% in group B donor (chi(2) = 0.28, P = 0.5941). The number of donor activating KIRs (aKIRs) was less than that of recipient aKIRs in 34 patient-donor pairs in which the CMV reaction rate was 70.6%, and the number of donor aKIRs was more than that of recipient aKIRs in 14 patient-donor pairs in which the CMV reactivation was 14.3%. There was a significan difference between the two group (chi(2) = 12.44, P = 0.0004). CONCLUSION: KIR and HLA-Cw genotypes influence the rate of CMV reactivation following non-T cell deleted unrelated donor hematopoietic cell transplantation.


Asunto(s)
Haplotipos , Trasplante de Células Madre Hematopoyéticas , Genotipo , Antígenos HLA-C/genética , Humanos , Receptores KIR/genética
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