EphA7 is one of the most important members of the Eph family .It is a key regulatory factor of cell adhesion and repulsion ,it also contributes to establish men ,maintain ance and tissue remodeling in cell mor-phology .In recent years ,its function in tumors has been revealed gradually .It plays a variety of roles in different tumors.The overexpression of EphA7 can be detected in acute leukemia ,glioblastomamultiforme,lung cancer and hepatic carcinoma ,which suggests EphA 7 may be involved in the development of these tumors .While in colon cancer,prostate cancer,follicular lymphoma and gastric cancer ,a significant reduction of EphA7 expression with promoter hypermethylation is discovered ,which suggests EphA 7 play a tumor suppressor role in these tumors .E-ven though the function of EphA 7 is still under exploration , EphA7 and tumor development are inextricably linked,it may have roles in the pathogenesis and development of these carcinomas .

A serumal metabonomics method based on UPLC/Q-TOF-MS was established to investigate the mechanism of Schisandra chinensis to treating diabetic nephropathy. The diabetic model was established by feeding with high-fat and high-sucrose chow and streptozotocin intraperitoneal injection. After intragastric administration for 12 weeks, the content of protein and creatinine in rat urine was detected. The results showed that Schisandra chinensis could reduce the content of protein in urine of diabetic rat ( p<0 . 05 ) and ameliorate the condition of diabetic nephropathy. The serum metabolic profiling was analysed by using UPLC/Q-TOF-MS and partial least squares-discriminated analysis ( PLS-DA) was used for data analysis. The score of PLS-DA showed that there was significant difference among the metabolic profile of control group, model group and Schisandra chinensis group ( WWZ ) . Potential biomarkers of Schisandra chinensis ameliorating diabetic nephropathy were selected by orthogonal partial least squares ( OPLS)-DA model. According to the results of OPLS-DA, the MS/MS data of each compound which provided greater contribution to separation of each group were searched from the HMDB databases. Seven endogenous metabolites were identified as potential biomarkers such as xanthurenic acid, palmitic amide, oleamide, uric acid, 5-hydroxyhexanoic acid, p-cresol sulfate, and p-cresol glucuronide. The results revealed that Schisandra chinensis mainly affected the pathways of tryptophan metabolism, gut microbiota metabolism, purine metabolism and fatty acid metabolism to treating type 2 diabetes mellitus. The gut microbiota metabolism and purine metabolism was an important pathway on diabetic nephropathy.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
Aconitine/pharmacology* ; Analgesics/pharmacology* ; Animals ; Pharmaceutical Preparations ; Rats ; Rats, Sprague-Dawley