Formation and prediction of heterocyclic amines and N-nitrosamines in smoked sausages using back propagation artificial neural network.

BACKGROUND: Heterocyclic amines (HAs) and N-nitrosamines (NAs) are formed easily during the thermal processing of food, and epidemiological studies have demonstrated that consuming HAs and NAs increases the risk of cancer. However, there are few studies on the application of back propagation artificial neural network (BP-ANN) models to simultaneously predict the content of HAs and NAs in sausages. This study aimed to investigate the effects of cooking time and temperature, smoking time and temperature, and fat-to-lean ratio on the formation of HAs and NAs in smoked sausages, and to predict their total content based on the BP-ANN model. RESULTS: With an increase in processing time, processing temperature and fat ratio, the content of HAs and NAs in smoked sausages increased significantly, while the content of HA precursors and nitrite residues decreased significantly. The optimal network topology of the BP-ANN model was 5-11-2, the correlation coefficient values for training, validation, testing and all datasets were 0.99228, 0.99785, 0.99520 and 0.99369, respectively, and the mean squared error value of the best validation performance was 0.11326. The bias factor and the accuracy factor were within acceptable limits, and the predicted values approximated the true values, indicating that the model has good predictive performance. CONCLUSION: The contents of HAs and NAs in smoked sausages were significantly influenced by the cooking conditions, smoking conditions and fat ratio. The BP-ANN model has high application value in predicting the contents of HAs and NAs in sausages, which provides a theoretical basis for the suppression of carcinogen formation. © 2024 Society of Chemical Industry.

Factors Affecting the Prognosis of Patients with Acute Cerebrovascular Occlusion with High National Institutes of Health Stroke Scale Scores Treated with SWIM Technology.

Objective: We aimed to explore the factors affecting the prognosis of patients with acute cerebrovascular occlusion with high National Institutes of Health Stroke Scale (NIHSS) scores treated with the SWIM (Solitaire™ stent retriever-assisted thrombectomy with immediate mechanical aspiration) technique using an intracranial support catheter. Methods: A retrospective analysis was conducted in 72 patients with acute cerebrovascular occlusion who underwent SWIM surgery in the Affiliated Hospital of Chengde Medical University in China between January 2020 and June 2022. The patients were divided into a good prognosis group (Modified Rankin Score [mRS] 0 to 2; n = 30) and a poor prognosis group (mRS score 3 to 6; n = 42) on their mRS scores 3 months after surgery. The THRIVE (TICI, hemorrhage, reocclusion, infarction, vessel, and embolism) score at different time points before and after the SWIM procedure and the postoperative revascularization rate were compared in the 2 NIHSS score groups. Univariate and logistic regression analyses were performed to identify the risk factors that affected the prognosis of patients with acute cerebrovascular occlusion treated with the SWIM procedure. Results: The NIHSS score difference at various time points after SWIM surgery in patients with low to moderate NIHSS scores was significantly higher than in patients with high NIHSS scores (P < .05). The postoperative revascularization rate in patients with high NIHSS scores was 74.36%, which was not significantly different from that in patients with low to moderate scores (84.85%; P > .05). The poor prognosis in patients with acute cerebrovascular occlusion after SWIM surgery was related to age, hypertension, NIHSS score, Glasgow Coma Scale (GCS) score, Essen Stroke Risk Score (ESRS), onset-to-treatment time (OTT) and Alberta Collateral Grading Scale (ACGS) score (P < .05). Logistic regression analysis showed that age, admission NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure (P < .05). Conclusion: The prognosis in patients with acute cerebrovascular occlusion with high NIHSS scores after SWIM surgery was poor. Advanced age, high NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure. Overall, incorporating these findings into clinical practice promotes personalized approaches, interdisciplinary collaboration and timely interventions to optimize outcomes in patients undergoing the SWIM procedure for acute cerebrovascular occlusion.

In Vitro Assessment of CYP-Mediated Drug Interactions for Kinsenoside, an Antihyperlipidemic Candidate.

Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the potential for kinsenoside-drug interactions. Kinsenoside was tested at different concentrations of 0.1, 0.3, 1, 3, 10, 30, and 100 µM in human liver microsomes. The c Cktail probe assay based on liquid chromatography-tandem mass spectrometry was conducted to measure the CYP inhibitory effect of kinsenoside. Subsequently, the metabolism profiles of amlodipine and lovastatin in human liver microsomes were analyzed following co-incubation with kinsenoside. The concentration levels of the parent drug and the major metabolites were compared with the kinsenoside-cotreated samples. The effect of kinsenoside was negligible on the enzyme activity of all the CYP isozymes tested even though CYP2A6 was slightly inhibited at higher concentrations. The drug-drug interaction assay also showed that the concomitant use of kinsenoside has a non-significant effect on the concentration of lovastatin or amlodipine, and their major metabolites. So, it was concluded that there is almost no risk of drug interaction between kinsenoside and CYP drug substrates via CYP inhibition.

Heterocyclic aromatic amines in roasted chicken: Formation and prediction based on heating temperature and time.

The effects of chicken roasting temperature and time on the production of heterocyclic aromatic amines (HAAs) were investigated and an HAA prediction model based on heating conditions was established. Generally, the HAA content was significantly affected by the heating conditions in the roast chicken. Transportation of precursors from meat to skin, exposure of skin to high temperatures, and fat oxidation in the skin may result in higher HAAs than meat. Principal component analysis (PCA) showed that the effect of relatively high temperatures and long roasting times on HAAs was stronger than that of lower temperatures and shorter roasting times. In the prediction of HAA production, all regression correlation coefficient (R) values were close to one. The errors of 15 samples of experimental and predictive data were close to zero. Based on the results, backpropagation-artificial neural network (BP-ANN) has a high potential for predicting the production of HAAs under heating conditions.

Development of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the determination of kinsenoside, an antihyperlipidemic candidate, in rat plasma and its application to pharmacokinetic studies.

Kinsenoside is a major bioactive constituent isolated from Anoectochilus formosanus and is investigated as an antihyperlipidemic candidate. In this study, a rapid, sensitive, and reliable bioanalytical method was developed for the determination of kinsenoside in rat plasma using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The plasma sample was pretreated with 1% acetic acid, followed by protein precipitation with acetonitrile:methanol (70:30). Chromatographic separation was performed on a HILIC silica column (2.1mm×100mm, 3µm). The mobile phases consisted of 0.1% acetic acid in distilled water (solvent A) and 0.1% acetic acid in acetonitrile (solvent B). A gradient program was used at a flow rate of 0.2mL/min. For mass spectrometric detection, the multiple reaction monitoring mode was used; the MRM transitions were m/z 265.2→m/z 102.9 for kinsenoside and m/z 163.3→m/z 132.1 for the internal standard (IS) nicotine in the positive ionization mode. A calibration curve was constructed in the range of 2-500ng/mL. The intra- and interday precision and accuracy were within 5%. The HILIC-MS/MS method was specific, accurate, and reproducible and was successfully applied in a pharmacokinetic study of kinsenoside in rats.

NVP-BEZ235, a novel dual PI3K-mTOR inhibitor displays anti-glioma activity and reduces chemoresistance to temozolomide in human glioma cells.

Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. However, a considerable number of GBM cases are refractory to TMZ, the need for more effective therapeutic options is overwhelming. Mounting evidence shows that endogenous AKT (protein kinase B) activity can be activated in response to clinically relevant concentrations of TMZ. AKT activation correlated with the increased tumorigenicity, invasiveness and stemness and overexpression of an active form of AKT increases glioma cell resistance to TMZ. Previous studies also show that TMZ contributes to glioma cell apoptosis by inhibiting mTOR signaling. Thus, we hypothesized that the dual PI3K-mTOR inhibitor NVP-BEZ235 may act as antitumor agent against gliomas and potentiate the cytotoxicity of TMZ. In the present study, we found that NVP-BEZ235 treatment of glioma cell lines led to G1 cell cycle arrest, and induced apoptosis. Combination treatment with both TMZ and NVP-BEZ235 resulted in synergistically inhibited glioma cell growth and induced apoptosis (combination index CI<1) in a subset of glioma cell lines, as shown in the increased levels of Bax, and active Caspase-3, and decreased level of Bcl-2. Furthermore, NVP-BEZ235 treatment reversed p-AKT levels enhanced by TMZ. Inhibition of mTOR (p70S6K) signaling with the combination of TMZ and NVP-BEZ235 can be augmented beyond that achieved using each agent individually. In vivo xenograft models in mice, the combinatorial treatment with TMZ and NVP-BEZ235 significantly reduced tumor growth rates and prolonged median survival of tumor-bearing mice. These findings exhibit that TMZ in combination with NVP-BEZ235 act synergistically to inhibit proliferation of glioma cells by down-regulating of the PI3K-AKT-mTOR pathway, suggesting TMZ and NVP-BEZ235 combination therapy may be an option for GBM treatment.

Parallel acceleration for modeling of calcium dynamics in cardiac myocytes.

Spatial-temporal calcium dynamics due to calcium release, buffering, and re-uptaking plays a central role in studying excitation-contraction (E-C) coupling in both healthy and defected cardiac myocytes. In our previous work, partial differential equations (PDEs) had been used to simulate calcium dynamics with realistic geometries extracted from electron microscopic imaging data. However, the computational costs of such simulations are very high on a single processor. To alleviate this problem, we have accelerated the numerical simulations of calcium dynamics by using graphics processing units (GPUs). Computational performance and simulation accuracy are compared with those based on a single CPU and another popular parallel computing technique, OpenMP.

A localized meshless approach for modeling spatial-temporal calcium dynamics in ventricular myocytes.

Spatial­temporal calcium dynamics due to calcium release, buffering and re-uptaking plays a central role in studying excitation­contraction (E­C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ a meshless method, namely, the local radial basis function collocation method (LRBFCM), to model such calcium behaviors by solving a nonlinear system of reaction­diffusion partial differential equations. In particular, a simplified structural unit containing a single transverse tubule (T-tubule) and its surrounding half sarcomeres is investigated using the meshless method. Numerical results are compared with those generated by finite element methods, showing the capability and efficiency of the LRBFCM in modeling calcium dynamics in ventricular myocytes. The single T-tubule model is also extended to the whole-cell scale with T-tubules excluded to demonstrate the scalability of the proposed meshless method in handling very large domains. The experiments have shown that the LRBFCM is suitable to multiscale modeling of calcium dynamics in ventricular myocytes with high accuracy and efficiency.

Multiscale modeling of calcium dynamics in ventricular myocytes with realistic transverse tubules.

Spatial-temporal Ca(2+) dynamics due to Ca(2+) release, buffering, and reuptaking plays a central role in studying excitation-contraction (E-C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ two numerical methods, namely, the meshless method and the finite element method, to model such Ca(2+) behaviors by solving a nonlinear system of reaction-diffusion partial differential equations at two scales. In particular, a subcellular model containing several realistic transverse tubules (or t-tubules) is investigated and assumed to reside at different locations relative to the cell membrane. To this end, the Ca(2+) concentration calculated from the whole-cell modeling is adopted as part of the boundary constraint in the subcellular model. The preliminary simulations show that Ca(2+) concentration changes in ventricular myocytes are mainly influenced by calcium release from t-tubules.