Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Arch Toxicol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292235

RESUMEN

Reproductive toxicity is one of the important issues in chemical safety. Traditional laboratory testing methods are costly and time-consuming with raised ethical issues. Only a few in silico models have been reported to predict human reproductive toxicity, but none of them make full use of the topological information of compounds. In addition, most existing atom-based graph neural network methods focus on attributing model predictions to individual nodes or edges rather than chemically meaningful fragments or substructures. In current studies, we develop a novel fragment-based graph transformer network (FGTN) approach to generate the QSAR model of human reproductive toxicity by considering internal topological structure information of compounds. In the FGTN model, the compound is represented by a graph architecture using fragments to be nodes and bonds linking two fragments to be edges. A super molecule-level node is further proposed to connect all fragment nodes by undirected edges, obtaining global molecular features from fragment embeddings. The FGTN model achieved an accuracy (ACC) of 0.861 and an area under the receiver operating characteristic curve (AUC) value of 0.914 on nonredundant blind tests, outperforming traditional fingerprint-based machine learning models and atom-based GCN model. The FGTN model can attribute toxic predictions to fragments, generating specific structural alerts for the positive compound. Moreover, FGTN may also have the capability to distinguish various chemical isomers. We believe that FGTN can be used as a reliable and effective tool for human reproductive toxicity prediction in contribution to the advancement of chemical safety assessment.

2.
Front Pharmacol ; 15: 1441587, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234116

RESUMEN

Background: Chemicals may lead to acute liver injuries, posing a serious threat to human health. Achieving the precise safety profile of a compound is challenging due to the complex and expensive testing procedures. In silico approaches will aid in identifying the potential risk of drug candidates in the initial stage of drug development and thus mitigating the developmental cost. Methods: In current studies, QSAR models were developed for hepatotoxicity predictions using the ensemble strategy to integrate machine learning (ML) and deep learning (DL) algorithms using various molecular features. A large dataset of 2588 chemicals and drugs was randomly divided into training (80%) and test (20%) sets, followed by the training of individual base models using diverse machine learning or deep learning based on three different kinds of descriptors and fingerprints. Feature selection approaches were employed to proceed with model optimizations based on the model performance. Hybrid ensemble approaches were further utilized to determine the method with the best performance. Results: The voting ensemble classifier emerged as the optimal model, achieving an excellent prediction accuracy of 80.26%, AUC of 82.84%, and recall of over 93% followed by bagging and stacking ensemble classifiers method. The model was further verified by an external test set, internal 10-fold cross-validation, and rigorous benchmark training, exhibiting much better reliability than the published models. Conclusion: The proposed ensemble model offers a dependable assessment with a good performance for the prediction regarding the risk of chemicals and drugs to induce liver damage.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 835-839, 2024 Aug 15.
Artículo en Chino | MEDLINE | ID: mdl-39148388

RESUMEN

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.


Asunto(s)
Complemento C1q , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Complemento C1q/inmunología , Nefritis Lúpica/inmunología , Nefritis Lúpica/sangre , Femenino , Niño , Masculino , Lupus Eritematoso Sistémico/inmunología , Estudios Retrospectivos , Adolescente , Autoanticuerpos/sangre , Preescolar , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología
4.
Comput Biol Med ; 171: 108037, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38377716

RESUMEN

The development of deep learning models for predicting toxicological endpoints has shown great promise, but one of the challenges in the field is the accuracy and interpretability of these models. The bioactive conformation of a compound plays a critical role for it to bind in the target. It is a big issue to figure out the bioactive conformation in deep learning without the co-crystal structure or highly precise molecular simulations. In this study, we developed a deep learning framework of Multi-Conformation Point Network (MCPNET) to construct classification and regression models, respectively, based on electrostatic potential distributions on vdW surfaces around multiple conformations of the compound using a dataset of compounds with developmental toxicity in zebrafish embryo. MCPNET applied 3D multi-conformational surface point cloud to extract the molecular features for model training, which may be critical for capturing the structural diversity of compounds. The models achieved an accuracy of 85 % on the classification task and R2 of 0.66 on the regression task, outperforming traditional machine learning models and other deep learning models. The key feature of our model is its interpretability with the component visualization to identify the factors contributing to the prediction and to understand the compound action mechanism. MCPNET may predict the conformation quietly close to the bioactive conformation of a compound by attention-based multi-conformation pooling mechanism. Our results demonstrated the potential of deep learning based on 3D molecular representations in accurately predicting developmental toxicity. The source code is publicly available at https://github.com/Superlit-CC/MCPNET.


Asunto(s)
Aprendizaje Profundo , Animales , Pez Cebra , Aprendizaje Automático , Conformación Molecular , Programas Informáticos
5.
J Org Chem ; 88(15): 10448-10459, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37458429

RESUMEN

An efficient radical cascade cyclization of unactivated alkenes toward the synthesis of a series of ring-fused quinazolinones has been developed in moderate to excellent yields using commercially available ethers, alkanes, and alcohols, respectively, under a base-free condition in a short time without a transition metal as catalyst. Notably, the transformations can be carried out with the advantages of a broad substrate scope and high atomic economy. Density functional theory calculations and wavefunction analyses were performed to elucidate the radical reaction mechanism.

6.
Comput Biol Med ; 146: 105573, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35533460

RESUMEN

Chromosome aberration (CA) is a serious genotoxicity of a compound, leading to carcinogenicity and developmental side effects. In the present manuscript, we developed a QSAR model for CA prediction using artificial intelligence methodologies. The reliable QSAR model was constructed based on an enlarged data set of 3208 compounds by optimizing machine learning and deep learning algorithms based on hyperparametric iterations and using multiple descriptors of molecular fingerprint in combination with drug-like molecular properties (MP) screened by entropy weight methodology on the open-source Python platform. Furthermore, molecular similarity for returning search and molecular connection index for additional descriptor were additionally introduced to differentiate the compounds with high similarity for correct CA prediction for QSAR model generation. The final generated CA-(Q)SAR model exhibited good prediction accuracy of 80.6%. The bias of the final model is about 0.9793. On the basis of generated QSAR model, data analyses were further performed to analyze the typical structure features in numerical intervals (MPI) of molecular properties MW, XlogP, and TPSA, respectively, for potential CA or non-CA toxicity with a normalized occurrence probability (NOP) more than 70%, which may provide useful clues for drug design of leads or candidate devoid of CA genotoxicity.


Asunto(s)
Inteligencia Artificial , Relación Estructura-Actividad Cuantitativa , Algoritmos , Aberraciones Cromosómicas , Entropía , Humanos
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 607-612, 2022 Apr.
Artículo en Chino | MEDLINE | ID: mdl-35396004

RESUMEN

OBJECTIVE: To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity. METHODS: Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively. RESULTS: Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001). CONCLUSION: DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.


Asunto(s)
ADN Metiltransferasa 3A , Células Madre Hematopoyéticas , Hidroquinonas , Apoptosis , Proliferación Celular , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Hidroquinonas/toxicidad , Poli(ADP-Ribosa) Polimerasa-1 , ARN Mensajero/metabolismo
8.
Adv Manuf ; 9(1): 130-135, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33425459

RESUMEN

The World Health Organization emphasized the importance of goggles and face shields for protection of medical personnel at the outbreak of the COVID-19 pandemic. Unsurprisingly, almost all countries suffered from a critical supply shortage of goggles and face shields, as well as many other types of personal protective equipment (PPE), for a long period, owing to the lack of key medical material supplies and the inefficiency of existing fabrication methods arising from the need to avoid crowds during the outbreak of COVID-19. In this paper, we propose a novel combined shield design for eye and face protection that can be rapidly fabricated using three-dimensional printing technology. The designed prototype eye-face shield is accessible to the general public, offering more possibilities for yield improvement in PPE during emergent infectious disease events such as COVID-19.

9.
Nutr Cancer ; 73(11-12): 2832-2841, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33356605

RESUMEN

The Geriatric Nutritional Risk Index (GNRI) is widely applied as a prognostic factor in different cancers. We aimed to analyze the prognostic value of the GNRI in 257 patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Patients with GNRI >98, 92-98, and <92 were grouped into normal, low risk and moderate/high risk groups, respectively. There were 45.1% patients at risk for malnutrition. Kaplan-Meier survival curves indicated that patients with lower GNRI scores had a poorer overall survival (OS). Two-year OS for normal, low risk and moderate/high risk groups were 57.4%, 42.3% and 15.8%, respectively. In multivariate survival analysis, GNRI (<92), body mass index (BMI, ≥24 kg/m2), combined therapy, hemoglobin and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS. Stratifying by age groups, GNRI (<92), hemoglobin and NLR were independent prognostic factors of OS in patients aged <65 years. GNRI (<92), smoking, BMI (≥24 kg/m2) and platelet-to-lymphocyte ratio were independent prognostic factors of OS in patients aged ≥65 years. In conclusion, GNRI was a significant prognostic factor in advanced NSCLC patients regardless of age. A decreased GNRI may be considered as a clinical trigger for nutritional support in advanced NSCLC patients, though additional studies are still required to confirm the best cut-point.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Desnutrición , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Evaluación Nutricional , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
10.
Mikrochim Acta ; 187(7): 418, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32613273

RESUMEN

An organic-inorganic hybrid monolithic column doped with gold nanorods (AuNRs) was prepared and evaluated for solid phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs). Excellent dispersibility of AuNRs in binary green porogen system consisting of 1-hexyl-3-methylimidazolium tetrafluoroborate and deep eutectic solvents (DESs) was confirmed by energy dispersive spectrometry (EDS). The particle size of the resulting AuNRs (70-90 nm) was thoroughly examined by a transmission electron microscopy (TEM). The redox system including ammonium persulfate (APS) and tetramethylethylenediamine (TEMED) was used to initiate in situ polymerization at 4 °C to prepare the hybrid monolith. The mesoporous structure of the AuNR hybrid monoliths was confirmed by scanning electron microscopy (SEM) and nitrogen adsorption. With enrichment factors (EFs) of 150- to 292-fold, the developed method was successfully applied to the determination of 10 PAHs in wastewater samples. The recoveries at a spiked level were in the range 84.9 to 99.5% with limit of detections (LODs) and relative standard deviations (RSDs) ranging from 0.02 to 0.10 µg L-1 and 1.5 to 4.2%, respectively. The correlation coefficients (R2) for the calibration function obtained were better 0.9991 for the target compounds. Compared to the AuNR-free monolith, the extraction efficiency of the AuNR-incorporated monolith is more than two times higher. The results indicated that the doping of AuNRs is an effective approach to obtain the hybrid monolithic column with good separation ability for PAHs. Graphical abstract.

11.
Environ Health Prev Med ; 25(1): 25, 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32590951

RESUMEN

BACKGROUND: Emerging evidence implicates excess weight as a potential risk factor for hearing loss. However, this association remained inconclusive. Therefore, we aimed to systematically and quantitatively review the published observational study on the association between body mass index (BMI) or waist circumference (WC) and hearing loss. METHODS: The odds ratios (ORs) or relative risks (RRs) with their 95% confidence intervals (CIs) were pooled under a random-effects model. Fourteen observational studies were eligible for the inclusion in the final analysis. RESULTS: In the meta-analysis of cross-sectional studies, the ORs for prevalent hearing loss were 1.10 (95% CI 0.88, 1.38) underweight, 1.14 (95% CI 0.99, 1.32) for overweight, OR 1.40 (95% CI 1.14, 1.72) for obesity, 1.14 (95% CI 1.04, 1.24) for each 5 kg/m2 increase in BMI, and 1.22 (95% CO 0.88. 1.68) for higher WC. In the meta-analysis of longitudinal studies, the RRs were 0.96 (95% CI 0.52, 1.79) for underweight, 1.15 (95% CI 1.04, 1.27) for overweight, 1.38 (95% CI 1.07, 1.79) for obesity, 1.15 (95% CI 1.01, 1.30) for each 5 kg/m2 increase in BMI, and 1.11 (95% CI 1.01, 1.22) for higher WC. CONCLUSIONS: In summary, our findings add weight to the evidence that elevated BMI and higher WC may be positively associated with the risk of hearing loss.


Asunto(s)
Adiposidad , Índice de Masa Corporal , Pérdida Auditiva/epidemiología , Circunferencia de la Cintura , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Pérdida Auditiva/etiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Adulto Joven
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 365-370, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-32319364

RESUMEN

OBJECTIVE: To investigate the biological effects and mechanism of WNK1 on K562 cells through regulating MAPK7. METHODS: Cells were routinely cultured in vitro, the expression of WNK1 and MAPK7 in different blood tumor cell lines was analyzed by RT-qPCR and Western blot analysis.K562 cells were transfected with siRNA-WNK1 lentivirus.The effect of WNK1 on K562 cell proliferation was analyzed by using CCK-8 reagent.And K562 cell apoptosis was analyzed by using flow cytometry. The expression level of phosphorylated MAPK7 protein and total MAPK7 protein in K562 cells was analyzed by Western blot. RESULTS: The mRNA and protein of WNK1 were highly expressed in HL60, THP-1, U266 and K562 cells, however, the expressions were the highest in K562 cells (P<0.05), while the changes of mRNA and protein expressions of MAPK7 were not significantly in HL60, THP-1, U266 and K562 cells (P>0.05), but the phosphorylated MAPK7 expression was the highest in K562 cells (P<0.05). Proliferation of K562 cells transfected by WNK siRNA was significantly suppressed, and apoptosis was obviously increased (P<0.05). And the pMAPK7 protein expression in K562 cells transfected by WNK1 siRNA significantly decreased (P<0.05), however, the total MAPK7 protein expression in K562 cells showed no obvious change (P>0.05). CONCLUSION: WNK1 is highly expressed in K562 cells, which can promote the proliferation of K562 cells and reduce apoptosis probably by promoting phosphorylation of its downstream MAPK7.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Apoptosis , Proliferación Celular , Humanos , Células K562 , Proteína Quinasa 7 Activada por Mitógenos , Fosforilación , ARN Interferente Pequeño , Proteína Quinasa Deficiente en Lisina WNK 1
13.
Br J Nutr ; 123(9): 1013-1023, 2020 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-31964442

RESUMEN

The association between milk consumption and the metabolic syndrome remains inconclusive, and data from Chinese populations are scarce. We conducted a cross-sectional study to investigate the association between milk consumption and the metabolic syndrome and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 5149 participants were included in the final analysis. A logistic regression model was applied to estimate the OR and 95 % CI for the prevalence of the metabolic syndrome and its components according to milk consumption. In addition, the results of our study were further meta-analysed with other published observational studies to quantify the association between the highest v. lowest categories of milk consumption and the metabolic syndrome and its components. There was no significant difference in the odds of having the metabolic syndrome between milk consumers and non-milk consumers (OR 0·86, 95 % CI 0·73, 1·01). However, milk consumers had lower odds of having elevated waist circumference (OR 0·78, 95 % CI 0·67, 0·92), elevated TAG (OR 0·83, 95 % CI 0·70, 0·99) and elevated blood pressure (OR 0·85, 95 % CI 0·73, 0·99). When the results were pooled together with other published studies, higher milk consumption was inversely associated with the risk of the metabolic syndrome (relative risk 0·80, 95 % CI 0·72, 0·88) and its components (except elevated fasting blood glucose); however, these results should be treated with caution as high heterogeneity was observed. In summary, the currently available evidence from observational studies suggests that higher milk consumption may be inversely associated with the metabolic syndrome.


Asunto(s)
Dieta/efectos adversos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etiología , Leche , Adulto , Animales , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad
14.
Onco Targets Ther ; 12: 5947-5953, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413592

RESUMEN

PURPOSE: Non-small-cell lung cancer (NSCLC) is the most diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze whether fasting blood glucose (FBG) levels could provide prognostic information in Chinese patients with NSCLC, using the Suzhou Lung Cancer Survival study. PATIENTS AND METHODS: A prospective cohort study of adult patients with primary NSCLC was performed. The patients who were hospitalized between January 2016 and April 2018 in two hospitals affiliated with Soochow University were recruited. Patient information, including lifestyle habits and clinical and laboratory data, were collected through face-to-face interviews and evaluation of medical records. Follow-up was initiated from the date of patient enrollment until May 8, 2018 or until patient death. The long-term survival of patients was assessed every 6 months. Patient vital status was confirmed by using hospital records, telephone interview, or local death registration system. Cox proportional hazards regression was used to estimate hazard ratio and 95% confidence interval (CI) for death, with adjustment for cancer stage, medical treatments, smoking, and other potential confounders. RESULTS: A total of 387 patients were included in the analysis, and the numbers (percentages) of patients with stages I, II, III, and IV NSCLC were 53 (13.7%), 41 (10.6%), 64 (16.5%), and 215 (55.6%), respectively. The median duration of follow-up was 19.1 months. Compared with patients in the second tertile of FBG, the HRs for mortality were 2.16 (95% CI: 1.26-3.73) and 1.87 (95% CI: 1.03-3.42) for those in the lowest one and diabetic group, respectively. Subgroup analysis according to various patient characteristics confirmed these associations. CONCLUSION: Diabetes and low FBG could be important predictors of death in patients with NSCLC. Maintaining appropriate blood glucose levels may improve prognosis in patients with NSCLC.

15.
J Med Food ; 22(10): 1000-1008, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31460816

RESUMEN

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Colesterol/sangre , Lactoferrina/farmacología , Animales , Aorta/patología , Colesterol 7-alfa-Hidroxilasa/metabolismo , Colesterol en la Dieta/administración & dosificación , Dieta Alta en Grasa , Hígado Graso/fisiopatología , Homeostasis , Intestino Delgado/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Proteínas de Transporte de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE
16.
Sci Rep ; 9(1): 8143, 2019 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-31148582

RESUMEN

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80-3.04) and 2.64 (95% CI: 1.35-5.16) for patients in the second and the highest tertiles of CRP (P-trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29-0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15-7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.


Asunto(s)
Albúminas/análisis , Proteína C-Reactiva/análisis , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Anciano , Biomarcadores de Tumor/sangre , China , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Enfermedades Respiratorias/diagnóstico , Encuestas y Cuestionarios
17.
Anticancer Drugs ; 28(2): 197-205, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27775991

RESUMEN

Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine. T-cells isolated from the vaccinated mice showed cytotoxicity against the parental tumor cells in a dose-dependent manner. Meanwhile, sera from the mice vaccinated with LL/2-VEGF164 showed higher titers of antibodies against parental tumor cells compared with the nonvaccinated groups. Our results indicated that VEGF164-modified tumor vaccine could modulate host antitumor immune response and hold therapeutic potential for cancer.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Inmunoterapia Adoptiva/métodos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/genética , Relación Dosis-Respuesta Inmunológica , Femenino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/inmunología , Transfección , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/inmunología
18.
Int J Pharm ; 496(2): 822-33, 2015 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-26474963

RESUMEN

This paper reported the facile fabrication of drug delivery devices for zero-order sustained release by molecular crowding strategy of molecularly imprinting technology. Crowding-assisted molecularly imprinting polymers (MIPs) matrices were prepared by free-radical precipitation polymerization using aminoglutethimide (AG) as a model drug. The crowding effect was achieved by adding polystyrene as a macromolecular co-solute in pre-polymerization mixture. The MIP prepared under the non-MMC condition and the two corresponding non-imprinted particles were tested as controlled vehicles. The release profiles presented zero-order behaviors from two crowding-assisted polymers, the duration of approximately 18h for the crowding-assisted MIP and 10h for the crowding-assisted NIP, respectively while AG were all very rapid released from the other two controlled particles (85% occurring in the first hour). The BET surface area and pore volume of the crowding-assisted MIP were about ten times than those of the controlled MIP. The value of imprinting factor is 6.02 for the crowding-assisted MIP and 1.19 for the controlled MIP evaluated by the equilibrium adsorption experiment. Furthermore, the values of effective diffusivity (Deff) obtained from crowding-assisted MIP (10(-17)cm(2)/s) was about two orders of magnitude smaller than those from the controlled MIP, although the values of free drug diffusivity (D) were all found in the order of 10(-13)cm(2)/s. Compared with the commercial AG tablet, the MMC-assisted MIP gave a markedly high relative bioavailability of 266.3%, whereas the MMC-assisted NIP gave only 57.7%. The results indicated that the MMC condition can modulate the polymer networks approaciate to zero-order release of the drug and maintain the molecular memory pockets, even if under the poor polymerization conditions of MIPs preparation.


Asunto(s)
Sistemas de Liberación de Medicamentos/instrumentación , Impresión Molecular/métodos , Aminoglutetimida/química , Animales , Preparaciones de Acción Retardada , Matemática , Polimerizacion , Poliestirenos/química , Ratas , Ratas Wistar , Solubilidad
20.
Acta Haematol ; 129(2): 101-5, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23171959

RESUMEN

POEMS syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Bortezomib is an important component of the chemotherapy regimen associated with multiple myeloma, and has been previously applied to POEMS syndrome. We present a 56-year-old Chinese man who was given subcutaneous administration of bortezomib as part of the BDex (bortezomib-dexamethasone) regimen for his POEMS syndrome. The peripheral neuropathy and laboratory-test results of the patient improved dramatically with 4 cycles of treatment, resulting in a complete response. In addition, the treatment was well tolerated and adequate peripheral blood hematopoietic stem cells were collected for an ensuing autologous stem cell transplant.


Asunto(s)
Ácidos Borónicos/administración & dosificación , Terapia Neoadyuvante , Síndrome POEMS/tratamiento farmacológico , Pirazinas/administración & dosificación , Administración Oral , Bortezomib , Dexametasona/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Inducción de Remisión
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA