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Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.
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Cellular heterogeneity is crucial for understanding tissue biology and disease pathophysiology.Phar-macological research is being advanced by single-cell metabolic analysis,which offers a technique to identify variations in RNA,proteins,metabolites,and drug molecules in cells.In this review,the recent advancement of single-cell metabolic analysis techniques and their applications in drug metabolism and drug response are summarized.High-precision and controlled single-cell isolation and manipulation are provided by microfluidics-based methods,such as droplet microfluidics,microchamber,open micro-fluidic probe,and digital microfluidics.They are used in tandem with variety of detection techniques,including optical imaging,Raman spectroscopy,electrochemical detection,RNA sequencing,and mass spectrometry,to evaluate single-cell metabolic changes in response to drug administration.The ad-vantages and disadvantages of different techniques are discussed along with the challenges and future directions for single-cell analysis.These techniques are employed in pharmaceutical analysis for studying drug response and resistance pathway,therapeutic targets discovery,and in vitro disease model evaluation.
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Researches on detection of human papillomavirus (HPV) high-risk samples were carried out by poly-merase chain reaction (PCR) coupled with microchip electrophoresis (MCE). Herein, we introduced a simple, rapid, automated method for detecting high-risk samples HPV16 and HPV18. In this research, general primers were initially selected to obtain sufficient detectable yield by PCR to verify feasibility of MCM method for HPV detection, then type-specific primers were further used to evaluate the specificity of MCE method. The results indicated MCE method was capable of specifically detecting high-risk HPV16 and HPV18, and also enabled simultaneous detection of multiplex samples. This MCE method described here has been successfully applied to HPV detection and displayed excellent reliability demonstrating by sequencing results. The inherent capability of MCE facilitated HPV detection conducted in a small chip with automated, high throughput, massive parallelized analysis. We envision that MCE method will definitely pave a way for clinical diagnosis, and even on-site screening of cervical cancer.
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The metastasis in which the cancer cells degrade the extracellular matrix (ECM) and invade to the sur-rounding and far tissues of the body is the leading cause of mortality in cancer patients. With a lot of advancement in the field, yet the biological cause of metastasis are poorly understood. The microfluidic system provides advanced technology to reconstruct a variety of in vivo-like environment for studying the interactions between tumor cells (TCs) and endothelial cells (ECs). This review gives a brief account of both two-dimensional models and three-dimensional microfluidic systems for the analysis of TCs-ECs co-culture as well as their applications to anti-cancer drug screening. Furthermore, the advanced methods for analyzing cell-to-cell interactions at single-cell level were also discussed.
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OBJECTIVE: To explore the effects of different doses of chest multislice spiral computed tomography( MSCT) in screening pneumoconiosis. METHODS: Forty workers exposed to coal dust and silica dust were selected by random sampling method,and scanned by conventional dose( 130 k V,25. 0-75. 0 m As) and low-dose of MSCT which included program 1( 110 k V,50. 0 m As),program 2( 110 k V,16. 0 m As) and program 3( 80 k V,16. 0 m As) respectively. Comparative analysis was given to the reconstructions of high-resolution 1. 5 mm thin-section,5. 0 mm of ordinary-section and the maximum intensity projection of 5. 0 mm coronary position respectively. RESULTS: Program 1 and program 2 exceeded program 3 in both image quality scores and low-dose MSCT image evaluation score( P < 0. 01). Both program 1 and 2 were able to show the p,q,s and t small shadows of 40 cases,and had no statistical significant difference in small shadow scores compared with those of conventional dose group( P > 0. 02),except the t small shadow scores of program 2;program 3 distinctly showed fewer images of the 4 kinds of small shadow and more false images,its images of p,q and t small shadow scores were lower than those of conventional dose group( P < 0. 01). We evaluated the radiation dose indexes including the CT dose index volume,CT dose index weighted,dose length product and the average effective dose,and all the results showed the following trend sequence from high to low: the conventional dose group > program 1 > program 2 >program 3 group( P < 0. 05). CONCLUSION: All low doses of MSCT schemes can meet the demands of pneumoconiosis screening. Using the program of 110 k V,16. 0 m As can not only achieve better quality image,but also effectively reduce the radiation doses that patients receive in screening.
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<p><b>OBJECTIVE</b>To assay and study the microwave leakage of 4 types of interphones.</p><p><b>METHODS</b>The radiation intensities of four types of 199 interphones were determined by the microwave leakage measure instrument of model ML-91 made in China.</p><p><b>RESULTS</b>The average intensities of microwave leakage at a distance of 5 cm from aerial part and other parts of interphones during launching [(1 316.0 +/- 144.3), (971.0 +/- 131.6) microW/cm(2) respectively] were significantly higher than during waiting [(14.4 +/- 5.3), (13.2 +/- 4.9) microW/cm(2) respectively] (P < 0.01). The average intensities of microwave leakage at a distance of 50 cm from different parts were (357.3 +/- 27.8) microW/cm(2). The daily average intensity of microwave leakage to which the head, chest and abdomen exposed was (945.5 +/- 447.1) microW.h/cm(2) in total, that exceeded the hygienic standard of microwave in China (400 microW.h/cm(2)), during the normal communication by interphones.</p><p><b>CONCLUSION</b>The microwave leakage was higher during launching than during waiting, and was the highest at the aerial part of the interphones. The microwave radiation of most interphones was higher than the current national standard. It may lead to potential effects on the owner of interphone, so protection against it should be made.</p>