1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon-Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently. 相似文献
AIMS: This study evaluates feasibility, safety, and efficacy of magnetic remote-controlled accessory pathway (AP) ablation. METHODS AND RESULTS: The novel magnetic navigation system (MNS) (Niobe, Stereotaxis) creates a steerable magnetic field (0.08 T) controlling the distal magnetic tip of an ablation catheter. In conjunction with a catheter advancer system (Cardiodrive, Stereotaxis) remote catheter ablation is enabled. Conventional electrophysiology study identified AP conduction in 59 patients (37 males, 36+/-14 years, 60 APs). First generation 1-magnet tip (1-M) (group I, n=18), second generation bipolar 3-magnet tip (3-M) (group II, n=27), and third generation quadripolar 3-magnet tip catheters (3-M quad.) (group III, n=14) were used for magnetic remote-controlled ablation. Successful AP ablation was achieved in 67% (group I), 85% (group II), and 92% (group III). A significant decrease of median [IQR: Q1-Q3] fluoroscopy time and dosage was observed: 21.2 [12.1-33.8] min, 1110 [395-3234] microGym2 (group I); 6.5 [4.4-15.4] min, 290 [129-489] microGym2 (group II), and 4.9 [3.4-8.0] min, 129 [74-270] microGym2 (group III). Mean procedure time (217+/-67 min; 182+/-68 min, and 172+/-90 min) significantly decreased in group III. Median number [Q1-Q3] of radiofrequency current applications in groups I, II, and III was 4 [2-9], 4 [2-6], and 2 [2-4], respectively. No complications occurred. CONCLUSION: Remote AP ablation is safe and feasible using the novel MNS. Introduction of the 3-magnet quadripolar ablation catheter significantly improved the efficacy of the procedure. 相似文献
Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP. 相似文献
The aim of this review article is to discuss the electrocardiographic presentation of the so called variants of pre‐excitation (“Mahaim fibers”) during sinus rhythm and tachycardia. 相似文献