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- Inhalation and dermal exposure to atmospheric polycyclic aromatic hydrocarbons and associated carcinogenic risks in a relatively small city. [JOURNAL ARTICLE]
- Ecotoxicol Environ Saf 2014 Jul 18.:106-113.
The aim of this study was to conduct a carcinogenic risk assessment for exposure to polycyclic aromatic hydrocarbons (PAHs) via routes of inhalation and dermal contact. Concentrations of 19 PAH species were determined during a heating period at a site in the city of Balikesir, Turkey. Two questionnaires were administered to a sample of inhabitants to determine time-activity budgets and demographic information. The assessment was conducted for each participant and Balikesir population by deterministic and probabilistic approaches, respectively. Monte Carlo simulation was implemented to determine the population exposure-risk probability distributions. The estimates were based on benzo[a]pyrene equivalent (BaPeq) total PAH concentrations calculated using toxic equivalency factors. The mean and median BaPeq concentrations of gaseous and particulate phases were 3.25 and 1.34, and 38.5 and 34.0ng/m(3), respectively. Carcinogenic risk for inhalation exposure route was estimated by using two different slope factor values (3.9 and 304.5(mg/kg-day)(-1)), recommended by two different organizations, resulting in two (order(s) of magnitude apart) population risk ranges: 1.32×10(-7)-2.23×10(-4), and 1.61×10(-5)-7.95×10(-3), respectively. The population risks associated with dermal exposure were lower compared to those of inhalation, ranging from 6.58×10(-9) to 2.57×10(-6). The proportion of the population with risks higher than the general acceptable level (1.0×10(-6)) was estimated as >99 percent, for inhalation, and as 28 percent for dermal exposure route.
- Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Jul 18.
Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation.Here we have investigated the comparative pharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment.The comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats was studied by liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug-metabolizing genes after SHXXT treatment was investigated by microarray analysis and real-time polymerase chain reaction (RT-PCR).A validated LC-MS/MS method was applied to investigate the comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats. The pharmacokinetic results demonstrate that the loperamide-induced constipation reduced the absorption of rhein. The Cmax significantly reduced by 2.5-fold, the AUC decreased by 27.8%; however, the elimination half-life (t1/2) was prolonged by 1.6-fold. The Tmax and mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold, respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of microarray analysis on gene expression indicate that five drug-metabolizing genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the SHXXT (0.5g/kg) treatment.The loperamide-induced constipation reduced the absorption of rhein. Since among the 25, 338 genes analyzed, there were five genes significantly altered by SHXXT treatment. Thus, information on minor drug-metabolizing genes altered by SHXXT treatment indicates that SHXXT is relatively safe for clinical application.
- A Novel Feature Extraction Scheme with Ensemble Coding for Protein-Protein Interaction Prediction. [JOURNAL ARTICLE]
- Int J Mol Sci 2014; 15(7):12731-12749.
Protein-protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of the development of high-throughput technologies and computational methods, many problems are still far from being solved. In this study, a novel predictor was designed by using the Random Forest (RF) algorithm with the ensemble coding (EC) method. To reduce computational time, a feature selection method (DX) was adopted to rank the features and search the optimal feature combination. The DXEC method integrates many features and physicochemical/biochemical properties to predict PPIs. On the Gold Yeast dataset, the DXEC method achieves 67.2% overall precision, 80.74% recall, and 70.67% accuracy. On the Silver Yeast dataset, the DXEC method achieves 76.93% precision, 77.98% recall, and 77.27% accuracy. On the human dataset, the prediction accuracy reaches 80% for the DXEC-RF method. We extended the experiment to a bigger and more realistic dataset that maintains 50% recall on the Yeast All dataset and 80% recall on the Human All dataset. These results show that the DXEC method is suitable for performing PPI prediction. The prediction service of the DXEC-RF classifier is available at http://ailab.ahu.edu.cn:8087/ DXECPPI/index.jsp.
- The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool. [JOURNAL ARTICLE]
- J Vis Exp 2014; (88)
Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient's home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.
- Second trimester amniotic fluid glucose, uric acid, phosphate, potassium, and sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight centiles. [JOURNAL ARTICLE]
- J Matern Fetal Neonatal Med 2014 Jul 21.:1-6.
Abstract Objective: To study the evolution profile of amniotic fluid (AF) glucose, uric acid, phosphate, potassium, and sodium, in the second trimester of pregnancy, and explore the possible relations between the concentration of these components and maternal, as well as neonatal characteristics. Methods: AF of 52 pregnant women was analyzed using an automatic multichannel analyzer. Maternal age, pre-pregnancy Body Mass Index (BMI), inter-pregnancy intervals, and smoking status were derived from questionnaires. Information on pregnancy and delivery was collected from medical records. Results: Uric acid increased (r = 0.423, p < 0.01), while phosphate and glucose concentrations decreased during the period of 16-26th week of pregnancy (r = -0.590, p < 0.001 and r = -0.314, p < 0.05, respectively). Maternal pre-pregnancy BMI was significantly correlated with AF uric acid concentration (r = 0.460, p < 0.01) and marginally with AF glucose (r = 0.274, p = 0.052) and sodium (r = 0.254, p = 0.070) levels. Multiple linear regression indicated that mid-trimester AF uric acid and phosphate levels were significantly related to birth weight centiles (R(2)( )= 0.345, p < 0.05). Conclusions: Our results suggest that: (a) AF phosphate levels reflect gestational age to a satisfactory extent, (b) maternal pre-pregnancy BMI is significantly correlated with AF uric acid concentration, and (c) in appropriate for gestational age infants, AF phosphate and uric acid levels may serve as potential biomarkers of birth weight centiles. Further studies on AF composition may help to unravel the biochemical pathways underlying fetal development and could offer insight on the potential impact of maternal nutritional management on fetal growth regulation.
- Pulmonary hypertension associated with chronic obstructive lung disease and idiopathic pulmonary fibrosis. [JOURNAL ARTICLE]
- Curr Opin Pulm Med 2014 Jul 18.
Severe pulmonary hypertension worsens the prognosis of patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). With the aim of better understanding the pathogenesis of this event and identifying the possible targets for therapeutic intervention, a great deal of clinical and translational research is now focused on this relevant field of medicine.Some studies that were published last year have helped to better define the clinical and physiological profiles of patients with COPD or IPF and severe pulmonary hypertension. The importance of pulmonary rehabilitation was confirmed, particularly in patients with pulmonary hypertension associated with IPF. Information on the use of drugs approved for the treatment of pulmonary arterial hypertension is still very limited, because of some limitations and selection biases in the studies' design. New strategies (i.e. the use of fasudil or sepiapterin in pulmonary hypertension associated with IPF) have been evaluated in animal models.Pulmonary hypertension in COPD or IPF may range from mild to severe. When pulmonary hypertension is more advanced, it can drive a poor outcome. Therefore, future studies should focus on this subset.
- Purification, characterization and immunoreactivity of β'-component, a major allergen from the roe of large yellow croaker (Pseudosciaena crocea). [JOURNAL ARTICLE]
- Food Chem Toxicol 2014 Jul 18.
Fish roe, a nutritious food, is favored by consumers, but has also been confirmed to be allergenic in salmonid fish. However, little information is available in other fish species. To determine the allergen in the roe of large yellow croaker (Pseudosciaena crocea), crude extracts were incubated with sera of allergic patients. The major allergen was purified by column chromatography methods, revealing a single band with 16 kDa and was confirmed as β'-component (β'-c) by mass spectrometry. The results of physicochemical characterization showed that β'-c was a glycoprotein and was relatively stable following thermal or acid/alkali treatment. Furthermore, β'-c was easily degraded by pepsin, but was resistant to trypsin and α-chymotrypsin. After treatment with different processing methods, including Maillard reaction (MR), ultraviolet radiation (UVR), ultrasound-heat (UH), and retorting (RT), the IgG-binding activity of β'-c decreased obviously by MR, but decreased slightly by UVR and UH. Cross-immunoreactivity results of the allergens in the roes of different species revealed that β'-c was a specific allergen in teleostean, and the cross-immunoreactivity between the roe of large yellow croaker and other kinds of fish roe was relatively strong.
- Dynactin 3D structure: Implications for assembly and dynein binding. [JOURNAL ARTICLE]
- J Mol Biol 2014 Jul 18.
The multisubunit protein complex, dynactin, is an essential component of the cytoplasmic dynein motor. High resolution structural work on dynactin and the dynein/dynactin supercomplex has been limited to small subunits and recombinant fragments that do not report fully on either≈1 MDa assembly. In the present study, we used negative stain electron microscopy and image analysis based on random conical tilt reconstruction to obtain a three-dimensional structure of native vertebrate dynactin. The 35nm long dynactin molecule has a V-shaped shoulder at one end and a flattened tip at the other, both offset relative to the long axis of the actin-related protein (Arp) backbone. The shoulder projects dramatically away from the Arp filament core in a way that cannot be appreciated in 2D images, which has implications for the mechanism of dynein binding. The 3D structure allows the helical parameters of the entire Arp filament core, which includes the actin capping protein, CP, to be determined for the first time. This structure exhibits near identity to F-actin and can be well fitted into the dynactin envelope. Molecular fitting of modeled CP-Arp polymers into the envelope shows that the filament contains between 7 and 9 Arp protomers and is capped at both ends. In the 7-Arp model, which agrees best with measured Arp stoichiometry and other structural information, actin capping protein (CP) is not present at the distal tip of the structure, unlike what is seen in the other models. The 3D structure suggests a mechanism for dynactin assembly and length specification.
- A Comprehensive Protocol for Manual Segmentation of the Medial Temporal Lobe Structures. [JOURNAL ARTICLE]
- J Vis Exp 2014; (89)
The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, hippocampus, and the associated parahippocampal regions (perirhinal, entorhinal, and parahippocampal proper). Unlike most other tracing protocols available, typically focusing on certain MTL areas (e.g., amygdala and/or hippocampus), the integrative perspective adopted by the present tracing guidelines allows for clear localization of all MTL subregions. By integrating information from a variety of sources, including extant tracing protocols separately targeting various MTL structures, histological reports, and brain atlases, and with the complement of illustrative visual materials, the present protocol provides an accurate, intuitive, and convenient guide for understanding the MTL anatomy. The need for such tracing guidelines is also emphasized by illustrating possible differences between automatic and manual segmentation protocols. This knowledge can be applied toward research involving not only structural MRI investigations but also structural-functional colocalization and fMRI signal extraction from anatomically defined ROIs, in healthy and clinical groups alike.
- Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. [JOURNAL ARTICLE]
- J Recept Signal Transduct Res 2014 Jul 21.:1-14.
Abstract Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.