Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype "combination therapy" targeting multiple mechanisms of stroke injury with a single agent. However, its role in the pathological process after WMLs has not been clarified. The present study was to investigate the role of a potent sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on multiple elements in white matter of mice brain after chronic hypoperfusion. Adult male C57BL/6 mice were subjected to bilateral carotid artery stenosis (BCAS) to induce WMLs. Administration of TPPU significantly inhibited microglia activation and inflammatory response, increased M2 polarization of microglial cells, enhanced oligodendrogenesis and differentiation of oligodendrocytes, promoted white matter integrity and remyelination following chronic hypoperfusion. Moreover, these cellular changes were translated into a remarkable functional restoration. The results suggest that sEH inhibition could exert multi-target protective effects and alleviate cognitive impairment after chronic hypoperfusion induced WMLs in mice.
Background: It has not been solved what kind of needle sensation might influence outcomes of acupuncture treatment. Effects of personality factors on the therapeutic effect of acupuncture have not been investigated. This study aimed to find the effects of the traits of personality on the objective outcome when different acupuncture techniques were used in treating patients with Bell's palsy. Methods: We performed a secondary analysis of a prospective multicenter randomized controlled trial of acupuncture for Bell's palsy. Patients were randomly assigned to the de qi and control groups, respectively. The primary outcome was facial nerve function at month 6. The intensity of each needle sensation was rated by a visual analog scale. Psychosocial factors were assessed by the pretreatment mediator questionnaire; 16 Personality Factor Questionnaire (16PF) was used for assessing personality factors and digit cancellation test for assessing attention. Results: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR]: 4.16, 95% confidence interval [CI]: 2.23–7.78). Path analysis showed that intensity of needle sensation of fullness had direct effect on House-Brackmann (HB) score at month 6. In de qi group, the low HB score on day 1 (OR: 0.13, 95% CI: 0.03–0.45) and the low Social Boldness score (OR: 0.63, 95% CI: 0.41–0.97) in 16PF were associated with better facial function. In control group, low HB score on day 1 (OR: 0.25, 95% CI: 0.13–0.50), low Vigilance score (OR: 0.66, 95% CI: 0.50–0.88), and high Tension score (OR: 1.41, 95% CI: 1.12–1.77) in 16PF were related to better facial function. Conclusions: The needle sensation of fullness could predict better facial function and personality traits might influence outcomes of acupuncture treatment. Both of them should be considered seriously in acupuncture treatment and research.
A Co-catalyzed reaction for the construction of 1,4-dicarbonyls has been reported in which cascade organocobalt addition/trapping/Kornblum-DeLaMare rearrangement were involved. In view of the easy availability of starting materials, wide substrate scope, high functionality tolerance, and operational simplicity, this protocol constituted a simple, practical, and powerful alternative compared with previous approaches.
A new radical-polar crossover reaction has been developed involving the combination of a tandem radical reaction and KornblumDeLaMare rearrangement in a one-pot process. This simple methodology allows for the construction of polyfunctionalized carbonyl compounds via the oxidative coupling of 1,3-dioxolanes with electron-deficient alkenes and vinylarenes in the presence of Co(salen) and TBHP under mild conditions. This reaction also exhibited high functional group tolerance, wide substrate scope, and operational simplicity.
Background: The traditional Chinese theory of acupuncture emphasizes that the intensity of acupuncture must reach a threshold to generate de qi, which is necessary to achieve the best therapeutic effect. De qi is an internal compound sensation of soreness, tingling, fullness, aching, cool, warmth and heaviness, and a radiating sensation at and around the acupoints. However, the notion that de qi must be achieved for maximum benefit has not been confirmed by modern scientific evidence.Methods: We performed a prospective multi-centre randomized controlled trial involving patients with Bell palsy. Patients were randomly assigned to the de qi (n = 167) or control (n = 171) group. Both groups received acupuncture: in the de qi group, the needles were manipulated manually until de qi was reached, whereas in the control group, the needles were inserted without any manipulation. All patients received prednisone as a basic treatment. The primary outcome was facial nerve function at month 6. We also assessed disability and quality of life 6 months after randomization.Results: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [ OR] 4.16, 95% confidence interval [ CI] 2.23-7.78), better disability assessment (differences of least squares means 9.80, 95% CI 6.29-13.30) and better quality of life (differences of least squares means 29.86, 95% CI 22.33-37.38). Logistic regression analysis showed a positive effect of the de qi score on facial-nerve function (adjusted OR 1.07, 95% CI 1.04-1.09).Interpretation: Among patients with Bell palsy, acupuncture with strong stimulation that elicited de qi had a greater therapeutic effect, and stronger intensity of de qi was associated with the better therapeutic effects. Trial registration: Clinicaltrials.gov no. NCT00685789.
Eight highly connected metal-organic frameworks (MOFs) based on flexible tricarboxylate ligands, namely, Na[Zn-5(L)(2)(mu(3)-OH)(5)] (1), (HTEA)[Zn-3(L)(2)(mu(3)-OH)]center dot 0.25H(2)O (2), [Zn-3(L)(2)(BIME)(H2O)(2)] (3), [Cd-3(L)(2)(BIME)(H2O)(2)] (4), [Pb-7(L)(4)(mu(3)-OH)(2)(H2O)(2)]center dot 8H(2)O (5), [Zn-4(L)(2)(BET)(mu(4)-O)] (6), [Zn-2(HL)(2)(PBIB)]center dot 2H(2)O (7), and [Zn-3(L)(2)(PBIB)(2)]center dot 4H(2)O (8) (H3L = (3,5-dicarboxylphenyl)-(4-(2'-carboxylphenyl) benzyl) ether, TEA = triethylamine, BIME = 1,2-bis(imidazol-1-yl)ethane, BET = 1,2-bis(1,2,4-triazole-1-yl) ethane, and PBIB = 1,4-bis(imidazol-1-ylmethyl)benzene) have been synthesized under hydrothermal conditions. Compound 1 exhibits a three-dimensional (3D) (3,12)-connected framework based on decanuclear [Zn-10(mu(3)-OH)(10)(COO)(12)] units. Compound 2 displays a 3D (3,6)-connected framework based on trinuclear [Zn-3(mu(3)-OH)(CO2)(6)] units. Compounds 3 and 4 display unusual 2-fold interpenetrated 3D (3,6)-connected frameworks with the same (4(2).6)(2)(4(4).6(2).8(8).10) topology. Compound 5 features a 3D tetranodal (3,3,4,8)-connected framework based on pentanuclear [Pb-5(COO)(8)(mu(3)-OH)(2)(H2O)(2)] units. Compound 6 exhibits an unprecedented 2D (3,8)-connected network with (3.4(2))(4(6).5(7).6(8).7(3).8) topology based on tetranuclear [Zn-4(mu(4)-O)(COO)(6)] units. Compound 7 reveals a wavy 2D sheet with (4(4).6(2)) topology. Further, each sheet is interdigitated by two others in a parallel fashion to yield an unusual 2D -> 3D interdigitated framework. Compound 8 displays a 3D rare trinodal (3,4,6)-connected framework with (3.4.5)(2)(3(2).10(3).11)(3(2).4(2).5(2).10(3).11(4).12.13) topology. These compounds have been characterized by IR spectra, UV-vis spectra, TGA, and powder XRD patterns. The optical band gaps and photoluminescent behaviors of 1-8 have been investigated in detail. In addition, surface photovoltage spectroscopies of compounds 1-4 indicate that these compounds possess positive surface photovoltage (SPV) responses in the range of 300-600 nm.
BACKGROUND Curcumin, an active ingredient of turmeric with antioxidant and anti-inflammatory properties has recently been reported to have anticonvulsant effects in several animal models of epilepsy. This study aimed to investigate the effects of curcumin on the pilocarpine rat model of status epilepticus. METHODS The effect of intraperitoneal administration of curcumin (30, 100, and 300 mg/kg) on pilocarpine-induced seizures in rats was tested. The correlation between seizure activity and hippocampal levels of nitric oxide synthase and free radicals was quantified. Whether curcumin treatment modulated these parameters was also investigated. RESULTS Curcumin significantly increased seizure threshold at doses of 100 and 300 mg/kg. Rats with pilocarpine- induced seizures showed significantly elevated levels of malonaldehyde, nitric oxide synthase, and lactate dehydrogenase, but decreased levels of superoxide dismutase and glutathione compared with normal control rats. At doses of 100 and 300 mg/kg, curcumin reversed the effects of pilocarpine-induced seizures on nitric oxide synthase, lactate dehydrogenase, glutathione, and superoxide dismutase. However, curcumin did not restore the elevated malonaldehyde levels. CONCLUSION Curcumin has anticonvulsant activity in the pilocarpine rat model of seizures, and that modulation of free radicals and nitric oxide synthase may be involved in this effect.
Kainate receptors, a subtype of ionotropic glutamate receptors, perform important functions in the spinal cord. This study aimed to examine the expression pattern of various kainate receptor subunits in the spinal cord over different stages of development. The regional distribution and levels of Grik1–5 mRNAs, which encode kainate receptor subunits, were examined in the spinal cord of embryonic, perinatal, and adult mice using in-situ hybridization and real-time PCR. At different developmental stages, the expression of Grik1–5 genes showed different regional distributions in the spinal cord. At E16.5, Grik2 and Grik3 were mainly expressed in the dorsal horns whereas Grik5 was expressed in the entire spinal cord. At P0 and P7, Grik2 expression accumulated at laminae II–IV, whereas Grik1 accumulated at the superficial laminae of the dorsal horns. At P30 and P60, the expression of Grik1–5 was concentrated in the superficial laminae of the dorsal horns. Development-related changes were observed in the expression pattern of Grik1–5. Grik5 was expressed in the entire spinal cord up to the perinatal period, whereas from P7 to adult stages, Grik5 expression was almost exclusively restricted to the dorsal horns. Similar observations were present with Grik1, Grik2, and Grik3. Consistently, quantitative determination of the expression levels of Grik1–5 was in accordance with the in-situ hybridization results. This age-related dynamic expression of kainate receptors may act as one driving force for the development of the anatomofunctional pattern and the maturation of the somatosensory circuitry in the spinal cord.
BACKGROUND:Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats.METHODS:With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses.RESULTS:Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds).CONCLUSION:Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.
Objective To investigate the effect of curcumin on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptor-mediated calcium influx in cultured rat hippocampal neurons. Methods The hippocampal neurons from SD rat embryos (17 days old) were cultured for 9 days, and fluorescent calcium chelator and confocal microscopy calcium imaging were used to observe the changes in intracellular free calcium in the neurons following stimulation with 100 μmol/L KA. The effect of curcumin pretreatment at different concentrations (10, 30, 50, 100, 200 and 300 μmol/L) for 30 min on 100 μmol/L KA-induced intracellular calcium changes in the neurons were evaluated, and the effect of 15 μmol/L curcumin on intracellular calcium in the neurons stimulated with 10, 30, 50, 100, 200 and 300 μmol/L KA were also assessed. Cobalt staining was used to examine the expression of calcium permeable AMPA/KA channel in the hippocampal neurons treated with 30 and 100 μmol/L KA. Results Curcumin pretreatment at different concentrations for 30 min significantly relieved the elevation of flee calcium concentration induced by 100 or 30 μmol/L KA (P<0.05), and the effect was especially obvious with 15 μmol/L KA curcumin. Both 30 and 100 μmol/L KA increased the ratio of cobalt staining-positive hippocampal neurons, and curcumin pretreatment at 15 μmol/L, but not at 5 or 30 μmol/L, significantly reduced the ratio of the positive neurons (P<0.05). Conclusion Curcumin at appropriate concentrations can modulate calcium influx mediated by AMPA and KA in cultured rat hippocampal neurons, which might be one of the anti-epileptic mechanisms of curcumin
Objective To explore the effects of curcumin on the synaptic transmission of the cultured hippocampal neurons of rats.Methods Hippocampal neurons were obtained from 18-day-old fetal SD rats,cultured for 9 days,and then divided into 2 groups:curcumin group,with curcumln of the final concentration of 10 μmol/L added into the culture fluid for 24 h,and control group with DMSO added into the cultured fluid.Simultaneous excitatory postsynaptic current(sEPSC)and miniature excitatory postsynaptic current(mEPSC)of the rat hippocampal neurons in these two groups were observed usmg the method of patch clamp,whole cell recording,and gap free mode. Results (1)The frequency of sEPSC in the neurons treated with curcumin was 1.4 Hz±0.5 Hz,significantly higher than that of the control group (0.8 Hz±0.4 Hz,P<0.01).The amplitude of sEPSC of the neurons treated with curcumin was 1834 pA±244 pA,not significantly different from that of the control group(1721 pA±391 pA,P=0.115).(2)The frequency of mEPSC in the neurons treated with curcumin was 6.4 Hz±0.8 Hz,significantly higher than that of the control group(5.1 Hz±0.9 Hz,P<0.001).The amplitude of mEPSC in the neurons treated with curcumin was 34 pA±10 pA.Not significantly different from that in the neurons treated with DMSO(30 pA±9 pA,P=0.057).Conclusion Curcumin modulates or enhances the synaptic transmission,which possibly contributes to the cognition enhancing effect of curcumin in rats suffering from cerebral ischemia.
The full-solution method has been developed as a low-cost process for making YBa2Cu3O7-x (YBCO) coated conductors. In this study, highly biaxially textured CeO2 buffer layers have been fabricated on yttria-stabilized zirconia (YSZ) single-crystal substrates by the sol-gel method using inorganic cerium nitrate as the starting precursor material. High-quality superconducting YBCO film has also been fabricated on CeO2-buffered YSZ substrate by the trifluoroacetate metal-organic deposition (TFA-MOD) method. For YBCO superconducting film, only (001) diffraction peaks can be detected by x-ray diffraction (XRD) analysis. Also from the XRD analysis, the YBCO films show sharp in-plane and out-of-plane texture for all samples, which indicates that the YBCO film is epitaxially grown on the CeO2 buffer layer. From scanning electron microscope (SEM) observations, the YBCO film shows a uniform surface structure. A critical transition temperature, T-c0, of 91 K and a critical current density of 3 MA cm(-2) (77 K, self-field) were obtained for a 0.2 mu m thick YBCO film on CeO2-buffered YSZ substrate.