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Background@#The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. @*Methods@#Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain.The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. @*Results@#Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. @*Conclusions@#Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.
ABSTRACT
Background@#The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. @*Methods@#Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain.The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. @*Results@#Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. @*Conclusions@#Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.
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Objective To investigate the effects of curcumin on the growth and apoptosis of human hepatoma HCC-LM3 cells and explore the molecular mechanisms.Methods The human hepatoma HCC-LM3 cells were treated with different concentrations of curcumin and the cell growth inhibition rate was detected by CCK-8.The effect of curcumin on human hepatoma HCC-LM3 cells was observed.Refer to the relevant literature,the human hepatoma HCC-LM3 cells were treated with the concentration of 2.5,5.0,10.0,15.0,20.0,40.0,60.0 μmol/L of curcumin for 48 hours,taking the 0 μmol/L curcumin as control group,and the cell growth inhibition rate was detected by CCK-8.According to the results of CCK-8,selecting the concentration of 0 μmol/L as control group and the concentration of 10.0,20.0,40.0 μmol/L as experimental groups,which has significant difference on growth inhibition rates.Cell cloning assay was used to detect cell cloning ability,Flow cytometry was used to detect apoptosis,and Western blotting to detect the protein expression levels of Mcl-1,Bax,Bcl-2 and Bcl-xL.The measurement data were expressed in ((x) ± s),and the single factor analysis of variance was used for comparison between groups.Results CCK-8 assay showed that with treated by the concentration of 2.5,5.0,10.0,15.0,20.0,40.0,60.0 μmol/L,the growth inhibition rates were(6.71 ± 3.45)％,(12.33 ± 5.02)％,(20.07 ± 5.60)％,(57.80 ±7.34)％,(78.37 ±6.53)％,(91.73 ±6.14)％ and (96.18 ±3.45)％,suggesting that curcumin could inhibit the growth of human hepatoma HCC-LM3 cells in a dose-dependent manner.Cell clone formation experiment showed that curcumin could inhibit the clone of the human hepatoma HCC-LM3 cells,and the clone of the cells was inhibited significantly when the concentration of the curcumin was over 20.0μmol/L.The result of Annexin V-FITC/PI double staining analysis showed that the apoptotic rates of experimental groups and control groups were (5.20 ± 1.44) ％,(9.90 ± 3.31) ％,(55.67 ± 5.29) ％,(79.63 ±4.71)％,with all the apoptotic rates of experimental group over the control groups (P ＜0.05),suggesting curcumin could induce the apoptosis of human hepatoma HCC-LM3 cells.The Westen blotting showed that curcumin increased the expression of Bax protein while decreasing expression of Mcl-1 protein significantly in concentration-dependent manner (P ＜ 0.05),but have no effect on the expression of Bcl-2 and Bcl-xL proteins.Conclusion Curcumin could inhibit the proliferation and clone of human hepatoma HCC-LM3 cells,and induce apoptosis in a dose dependent manner.
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Objective To assess the value of cardiac magnetic resonance (CMR) imaging in left ventricular structure and function in patients with end stage renal disease (ESRD).Methods Twenty-five patients with ESRD and 10 healthy subjects underwent CMR.Left ventricular end diastolic volume(EDV),end-diastolic diameter(EDD),end-systolic volume(ESV),end-systolic diameter(ESD),stroke volume(SV),ejection fraction(EF),LVM and interventricular septum (IVS) thickness were measured and compared.The parameters from CMR and 2DTTE were compared.Results The EF in patients with ESRD was significantly lower than that in controls (P＜0.001),while ESV,ESD,IVS and LVM were respectively higher than these in controls (P＜0.05).There was no significant difference (P＞0.05) in ESV between CMR and 2DTTE,but EF of CMR was significantly higher than this of 2DTTE (P＜0.05).There was no significant difference (P =0.296) in left ventricular systolic functional category.Bland-Altman plots showed a good agreement between the two methods.Conclusion CMR is a helpful tool to assess left ventricular structure and function in patients with ESRD.
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ObjectiveTo investigate the pathogenesy and operation method in patients with ossification of thoracic ligamentum flavum.MethodsThe imaging and clinical data of 56 patients who underwent laminectomy combined with posterolateral fusion were studied retrospectively.The method of laminectomy included enbloc laminectomy and decomposed laminectomy.Postoperative outcomes were evaluated according to a recovery scale in terms of JOA score.ResultsThe patients were followed up for 18-70 (25.00 ± 11.56) months.There were a total of 237 ossified segments in this series,57.4％(136/237)located in lower thoracic segments.According to the configuration of ossification on CT scans,lateral type occurred in 6 patients,diffuse type in 17 patients and thickened nodular type in 33 patients.All patients with lateral type and majority of patients with diffuse type were treated with enbloc laminectomy,and the rate of fineness of postoperative outcome was 83.3％ (5/6),82.4％ ( 14/17 ) respectively.Most of the patients with thickened nodular type were treated with decomposed laminectomy,and the rate of fineness of postoperative outcome was 78.8％ (26/33).Four patients withthickened nodular type were performed with enbloc laminectomy,2 of them resulted in deteriorated myelopathy.Twenty-nine patients with thickened nodular type were performed with decomposed laminectomy,however,only 2 of them resulted in worse outcomes.ConclusionsThe pathogenesis of ossification of thoracic ligamentum flavum is mainly due to the localizedmechanical stress.Laminectomy combining with lateral fusion may be the ideal method for the treatment ofthis condition.Furthermore,enbloc laminectomy is suitable for the patients in lateral type and diffuse type according to the configuration of ossifications.For the thickened nodular type,decomposed laminectomy is favorable.
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Objective To investigate the effect of propofol and isoflurane anesthesia on serum heat shock protein 70 ( HSP70 ) of perioperative patients with brain injury and compare the anesthetic effect of the two narcotic drugs. Methods 30 patients with medium or severe traumatic brain injury,treated by hematoma evacuation operation,were randomly divided into propofol ( n = 15 ) and isoflurane group ( n = 15 ). After anesthesia induction,propofol (target effect concentration of 3 ～ 4 μg/ml ) was intravenously injected and 1.2% isoflurane was inhalated into the patients of the 2 groups,respectively. In addition,vecuronium and fentany were intermittent intravenously injected into patients to maintain the depth of anesthesia. HSP70 in blood of patients were detected before anesthesia induction, 1 h after the dura was opened and 24 h after the operation by ELISA method. Recovery and tracheal extubation time of patients were recorded. Results HSP70 levels in blood of patients in the 2 groups were significantly increased compared with the former time point(P＜0.05 ). HSP70 content in propofol group was significantlyhigher at 1 h after the dura was opened( ( 2.00 ± 0. 24 ) ng/ml, ( 2.19 ± 0.26 ) ng/ml, t = 2. 080, P = 0.047 ) and 24 h after the operation( t=2.086, P=0.046) ,and recovery and tracheal extubation time was shorter compared with the isoflurane group(P＜0. 05). Conclusion Perioperative moderate stress,and early postoperative recovery and extubation can be maintained in patients with traumatic brain injury with profol anesthesia.