The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of ...The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of an open pit slope.For this purpose,spatially conditioned DFN models were developed for the pit walls at Tasiast mine using comprehensive structural data from the mine.Using Sequential Gaussian Simulation(SGS),volumetric fracture intensities(P32)were modeled across the entire mine site in the form of 3D block models.The simulated P32 block models were used as the input constraints for conditional DFN fracture generation,where the DFN grid dimension is the same as the SGS 3D blocks.The spatially constrained DFN models were further calibrated using aerial fracture intensities(P21)data from the pit walls,obtained by a survey of the pit walls using an unmanned aerial vehicle(UAV)and measured traces of joints from 3D point cloud data.The final DFN model is expected to honor the fracture intensities gathered through different means with optimal model accuracy.Finally,bench-scale and interramp scale rock wedge slope stability analyses were conducted using the calibrated conditional DFN models.This work proves the significance of conditioned DFN models in rock wedge stability analysis.Such models provide detailed information regarding rock wedge stability so that site monitoring and prevention plans can be conducted with higher efficiency.展开更多
Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery...Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.展开更多
BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to r...BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to reduce this signaling.Autologous conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms.This systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal pathologies.AIM To evaluate the use of ACS as a conservative management option for spinal path-ology.METHODS A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal pathology.RESULTS Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS injections.Patients had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(DDD)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(SD)follow-up was 21.7(4.8)weeks from first ACS injection.All studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to baseline.ACS achieved comparable or su-perior results to lumbar epidural steroid injections.Adverse events were reported in 21 patients(3.1%),with no serious adverse events.CONCLUSION ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.展开更多
Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, a...Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.展开更多
Microseismic event location is one of the core parameters in microseismic monitoring,and the accuracy of localization will directly affect the effectiveness of engineering applications.However,limited by spatial facto...Microseismic event location is one of the core parameters in microseismic monitoring,and the accuracy of localization will directly affect the effectiveness of engineering applications.However,limited by spatial factors,the geometry of the sensor installation will be close to linear,which makes the localization equation suffer from the pathological problem,and the localization accuracy is greatly reduced.To address this problem,the reasons for the pathological problem are analyzed from the perspective of the objective function residuals and coefficient matrix.The pathological problem is caused by the combined effect of the poorer sensor array and data errors,and its residual isosurface shows a conical distribution,and as the residual value decreases,the apex of the isosurface gradually extends to the far side,and the localization results do not converge.For this reason,an improved regularized Newton downhill localization algorithm is proposed.In this method,firstly,the Newtonian downhill method is improved so that the magnitudes of the seismic source parameters are the same,and the condition number of the coefficient matrix is reduced;then,the L-curve method is used to calculate the regularization factor for the pathological equations,and the coefficient matrix is improved;finally,the pathological equations are regularized,and the seismic source coordinates are obtained by the improved Newtonian downhill method.The results of engineering applications show that compared with the traditional algorithm based on automatic of P-arrival picking,the number of effective microseismic events calculated by the proposed localization algorithm is increased by 194.7%,and the localization accuracy is substantially improved.The proposed algorithm reduces the problem of low accuracy of S-arrival picking and allows localization using only P-wave arrival.The method reduces the quality requirements of the data and significantly improves the utilization of microseismic events and positioning accuracy.展开更多
The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned sti...The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned stimulus （CS）. In the experiment, 36 participants were trained in differential DEC with a soft tone （60 dB） or a loud tone （85 dB） as the CS, paired with a corneal air-puff as the unconditioned stimulus （US）. After conditioning, awareness of the relationship between assessed with a 17-item the CS and the US was true/false questionnaire. Interestingly, during differential DEC with a soft-tone CS, a higher proportion of differential conditioned responses （CRs） was evident in participants who were aware than those who were unaware. In contrast, when a loud tone was used as the CS, the proportion of differential CRs of the aware participants did not differ significantly from those who were unaware over any of the blocks of 20 trials. In unaware participants, the percentage of differential CRs with a loud-tone CS was significantly higher than that with a soft-tone CS; however in participants classified as aware, the percentage of differential CRs with a loud-tone CS did not differ significantly from that with a soft-tone CS. The present findings suggest that awareness is critical for differential DEC when the delay task is rendered more difficult.展开更多
Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of ...Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).展开更多
This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are glob...This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are globally convergent for general convex functions.展开更多
Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain la...Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.展开更多
The discrete element method (DEM) was used to simulate the flow characteristic and strength characteristic of the conditioned sands in the earth pressure balance (EPB) tunneling. In the laboratory the conditioned sand...The discrete element method (DEM) was used to simulate the flow characteristic and strength characteristic of the conditioned sands in the earth pressure balance (EPB) tunneling. In the laboratory the conditioned sands were reproduced and the slump test and the direct shear test of the conditioned sands were implemented. A DEM equivalent model that can simulate the macro mechanical characteristic of the conditioned sands was proposed,and the corresponding numerical models of the slump test and the shear test were established. By selecting proper DEM model parameters,the errors of the slump values between the simulation results and the test results are in the range of 10.3%-14.3%,and the error of the curves between the shear displacement and the shear stress calculated with the DEM simulation is 4.68%-16.5% compared with that of the laboratory direct shear test. This illustrates that the proposed DEM equivalent model can approximately simulate the mechanical characteristics of the conditioned sands,which provides the basis for further simulation of the interaction between the conditioned soil and the chamber pressure system of the EPB machine.展开更多
Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progeni...Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments. After primary culture of bone marrow-derived macrophages, lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype. These cells were then treated with endothelial progenitor cell-conditioned medium or control medium. Polymerase chain reaction was used to determine mR NA expression levels of related inflammatory factors. Afterwards, primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2and either endothelial progenitor cell-conditioned medium or control medium. Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis. Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis. Compared with control medium, endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site, suppressed apoptosis, and promoted angiogenesis. Next, we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo. The rats were randomly administered intraperitoneal injection of PBS, control medium or endothelial progenitor cell-conditioned medium, once a day, for 6 consecutive weeks. Immunohistochemistry was used to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter. The Basso, Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury. Compared with the other two groups, the number of axons was increased, cavities in the spinal cord were decreased, the proportion of apoptotic neurons in the gray matter was reduced, and the Basso, Beattie and Bresnahan score was higher in the endothelial progenitor cell-conditioned medium group. Taken together, the in vivo and in vitro results suggest that endothelial progenitor cell-conditioned medium suppresses inflammation, promotes angiogenesis, provides neuroprotection, and promotes functional recovery after spinal cord injury.展开更多
A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fi...A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fibroblastlike cells to maintain culture homeostasis by producing TGF-β and insulin-like growth factor-lI （IGF-Ⅱ） in response to basic fibroblast growth factor （bFGF）. Although the importance of TGF-β family members in the maintenance of pluripotency of hESCs is widely established, very little is known about the role of IGF-Ⅱ. In order to ease hESC cul- ture conditions and to reduce xenogenic components, we sought （i） to determine whether hESCs can be maintained stable and pluripotent using CM from human foreskin fibroblasts （HFFs） and human mesenchymal stem cells （hM- SCs） rather than MEF-CM, and （ii） to analyze whether the cooperation of bFGF with TGF-β and IGF-Ⅱ to maintain hESCs in MEF-CM may be extrapolated to hESCs maintained in allogeneic mesenchymal stem cell （MSC）-CM and HFF-CM. We found that MSCs and HFFs express all FGF receptors （FGFR1-4） and specifically produce TGF-β in response to bFGF. However, HFFs but not MSCs secrete IGF-Ⅱ. Despite the absence of IGF-Ⅱ in MSC-CM, hESC pluripotency and culture homeostasis were successfully maintained in MSC-CM for over 37 passages. Human ESCs derived on MSCs and hESCs maintained in MSC-CM retained hESC morphology, euploidy, expression of surface markers and transcription factors linked to pluripotency and displayed in vitro and in vivo multilineage developmental potential, suggesting that IGF-Ⅱ may be dispensable for hESC pluripotency. In fact, IGF-Ⅱ blocking had no effect on the homeostasis of hESC cultures maintained either on HFF-CM or on MSC-CM. These data indicate that hESCs are successfully maintained feeder-free with IGF-Ⅱ-lacking MSC-CM, and that the previously proposed paracrine mechanism by which bFGF cooperates with TGF-β and IGF-Ⅱ in the maintenance of hESCs in MEF-CM may not be fully extrapolated to hESCs maintained in CM from human MSCs.展开更多
In vitro growth and maintenance of embryonic stem (ES) cell lines derived from ICM cells of various blastocysts of 129 strain mice, the sustenance of their pluripotency and normal karyotype depend on the feeder layer ...In vitro growth and maintenance of embryonic stem (ES) cell lines derived from ICM cells of various blastocysts of 129 strain mice, the sustenance of their pluripotency and normal karyotype depend on the feeder layer of mouse embryonic fibroblasts (MEF). Compared with the feeder layer of MEF cells, medium conditioned by Buffalo rat liver cells (BRL-CM) is able to maintain pluripotency and karyo-typic normality of ES cells only in short term cell propagation. Besides, ES cells grown in BRL-CM are also capable of aggregation with 8-cell embryos of Swiss strain and develop into germ line chimaeras. Modification to the method of aggregating ES cells with early embryos by making a hole in agar layer on the top of MEF feeder cells was shown to be more convenient and efficient than the conventional microdrop method.展开更多
Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place ...Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.展开更多
The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place p...The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for along time without affecting total CREB protein levels. The effect of F9204 was similar to morphine whicheffect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitiveN-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phos-phorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also thephosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterationsin the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence.NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.展开更多
Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord.One important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1)...Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord.One important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1)mutant-mediated mitochondrial toxicity,leading to apoptosis in neurons.This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1(G-Rg1)and conditioned medium(CM)on a mutational SOD1 cell model,and to explore the underlying mechanisms.We found that the contents of nerve growth factor,glial cell line-derived neurotrophic factor,and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells(hUCMSCs)were exposed to neuron differentiation reagents for seven days.CM or G-Rg1 decreased the apoptotic rate of SOD1^(G93A)-NSC34 cell to a certain extent,but their combination brought about the least apoptosis,compared with CM or G-Rg1 alone.Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups.Proteins associated with mitochondrial apoptotic pathways,such as Bax,caspase 9(Cas-9),and cytochrome c(Cyt c),were downregulated.Furthermore,CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B(NF-κB)signaling pathway by reducing the phosphorylation of p65 and IκBa.CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid(BetA),an agonist of the NF-κB signaling pathway.In summary,the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^(G93A)-NSC34 cells through suppresing the NF-κB/Bcl-2 sgaling pathway(Fig.1 is a graphcal representation of the abstract).展开更多
Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different ...Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm. Results: MRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice. Conclusion: Based on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.展开更多
In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curve...In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curves of conditioned rubber specimens under di?erent conditioned strains are obtained. Test results show di?erences between these curves. Based on an analysis of the classical constitutive models, a new modi?ed eight-chain model is proposed, which takes account of both the locking stretch of chains and the interaction e?ect in the network. Fitting test data shows that the modi?ed model well characterizes the incompressible hyperelastic mechanical behavior of conditioned rubbers under the moderate ?nite deformation as well as under the large deformation.展开更多
OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METH...OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METHODS:A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice.The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol.Concentrations of dopamine(DA),Glutamate(Glu),and?-aminobutyric acid(GABA)in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay.RESULTS:Although PG did not alter spontaneous activity in mice,it reduced the growth of spontaneous activity stimulated by ethanol.The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased.CONCLUSION:Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice.The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system.This suggests that PG might be useful for the prevention and treatment of alcohol addiction.展开更多
Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction ...Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.展开更多
基金Kinross Gold and MITACS for their financial support(Grant No.FR42880).
文摘The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of an open pit slope.For this purpose,spatially conditioned DFN models were developed for the pit walls at Tasiast mine using comprehensive structural data from the mine.Using Sequential Gaussian Simulation(SGS),volumetric fracture intensities(P32)were modeled across the entire mine site in the form of 3D block models.The simulated P32 block models were used as the input constraints for conditional DFN fracture generation,where the DFN grid dimension is the same as the SGS 3D blocks.The spatially constrained DFN models were further calibrated using aerial fracture intensities(P21)data from the pit walls,obtained by a survey of the pit walls using an unmanned aerial vehicle(UAV)and measured traces of joints from 3D point cloud data.The final DFN model is expected to honor the fracture intensities gathered through different means with optimal model accuracy.Finally,bench-scale and interramp scale rock wedge slope stability analyses were conducted using the calibrated conditional DFN models.This work proves the significance of conditioned DFN models in rock wedge stability analysis.Such models provide detailed information regarding rock wedge stability so that site monitoring and prevention plans can be conducted with higher efficiency.
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
文摘BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to reduce this signaling.Autologous conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms.This systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal pathologies.AIM To evaluate the use of ACS as a conservative management option for spinal path-ology.METHODS A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal pathology.RESULTS Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS injections.Patients had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(DDD)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(SD)follow-up was 21.7(4.8)weeks from first ACS injection.All studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to baseline.ACS achieved comparable or su-perior results to lumbar epidural steroid injections.Adverse events were reported in 21 patients(3.1%),with no serious adverse events.CONCLUSION ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.
文摘Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.
基金the financial support from the National Natural Science Foundation of China(Grant no.42077263).
文摘Microseismic event location is one of the core parameters in microseismic monitoring,and the accuracy of localization will directly affect the effectiveness of engineering applications.However,limited by spatial factors,the geometry of the sensor installation will be close to linear,which makes the localization equation suffer from the pathological problem,and the localization accuracy is greatly reduced.To address this problem,the reasons for the pathological problem are analyzed from the perspective of the objective function residuals and coefficient matrix.The pathological problem is caused by the combined effect of the poorer sensor array and data errors,and its residual isosurface shows a conical distribution,and as the residual value decreases,the apex of the isosurface gradually extends to the far side,and the localization results do not converge.For this reason,an improved regularized Newton downhill localization algorithm is proposed.In this method,firstly,the Newtonian downhill method is improved so that the magnitudes of the seismic source parameters are the same,and the condition number of the coefficient matrix is reduced;then,the L-curve method is used to calculate the regularization factor for the pathological equations,and the coefficient matrix is improved;finally,the pathological equations are regularized,and the seismic source coordinates are obtained by the improved Newtonian downhill method.The results of engineering applications show that compared with the traditional algorithm based on automatic of P-arrival picking,the number of effective microseismic events calculated by the proposed localization algorithm is increased by 194.7%,and the localization accuracy is substantially improved.The proposed algorithm reduces the problem of low accuracy of S-arrival picking and allows localization using only P-wave arrival.The method reduces the quality requirements of the data and significantly improves the utilization of microseismic events and positioning accuracy.
基金supported by the National Natural Science Foundation of China (81171249)
文摘The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned stimulus （CS）. In the experiment, 36 participants were trained in differential DEC with a soft tone （60 dB） or a loud tone （85 dB） as the CS, paired with a corneal air-puff as the unconditioned stimulus （US）. After conditioning, awareness of the relationship between assessed with a 17-item the CS and the US was true/false questionnaire. Interestingly, during differential DEC with a soft-tone CS, a higher proportion of differential conditioned responses （CRs） was evident in participants who were aware than those who were unaware. In contrast, when a loud tone was used as the CS, the proportion of differential CRs of the aware participants did not differ significantly from those who were unaware over any of the blocks of 20 trials. In unaware participants, the percentage of differential CRs with a loud-tone CS was significantly higher than that with a soft-tone CS; however in participants classified as aware, the percentage of differential CRs with a loud-tone CS did not differ significantly from that with a soft-tone CS. The present findings suggest that awareness is critical for differential DEC when the delay task is rendered more difficult.
基金This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No.002p1503).
文摘Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).
文摘This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are globally convergent for general convex functions.
基金supported by grants from the National Natural Science Foundation of China (31671091 and 81771197)the Natural Science Foundation of Jiangsu Province, China (BK20171255)the Science and Technology Planning Project of Nantong Municipality, China (MS12017023-9)
文摘Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
基金Project (2007CB714006) supported by the National Basic Research Program of China
文摘The discrete element method (DEM) was used to simulate the flow characteristic and strength characteristic of the conditioned sands in the earth pressure balance (EPB) tunneling. In the laboratory the conditioned sands were reproduced and the slump test and the direct shear test of the conditioned sands were implemented. A DEM equivalent model that can simulate the macro mechanical characteristic of the conditioned sands was proposed,and the corresponding numerical models of the slump test and the shear test were established. By selecting proper DEM model parameters,the errors of the slump values between the simulation results and the test results are in the range of 10.3%-14.3%,and the error of the curves between the shear displacement and the shear stress calculated with the DEM simulation is 4.68%-16.5% compared with that of the laboratory direct shear test. This illustrates that the proposed DEM equivalent model can approximately simulate the mechanical characteristics of the conditioned sands,which provides the basis for further simulation of the interaction between the conditioned soil and the chamber pressure system of the EPB machine.
基金supported by the National Natural Science Foundation of China,No.81171173 and 81672161
文摘Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments. After primary culture of bone marrow-derived macrophages, lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype. These cells were then treated with endothelial progenitor cell-conditioned medium or control medium. Polymerase chain reaction was used to determine mR NA expression levels of related inflammatory factors. Afterwards, primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2and either endothelial progenitor cell-conditioned medium or control medium. Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis. Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis. Compared with control medium, endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site, suppressed apoptosis, and promoted angiogenesis. Next, we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo. The rats were randomly administered intraperitoneal injection of PBS, control medium or endothelial progenitor cell-conditioned medium, once a day, for 6 consecutive weeks. Immunohistochemistry was used to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter. The Basso, Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury. Compared with the other two groups, the number of axons was increased, cavities in the spinal cord were decreased, the proportion of apoptotic neurons in the gray matter was reduced, and the Basso, Beattie and Bresnahan score was higher in the endothelial progenitor cell-conditioned medium group. Taken together, the in vivo and in vitro results suggest that endothelial progenitor cell-conditioned medium suppresses inflammation, promotes angiogenesis, provides neuroprotection, and promotes functional recovery after spinal cord injury.
文摘A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fibroblastlike cells to maintain culture homeostasis by producing TGF-β and insulin-like growth factor-lI （IGF-Ⅱ） in response to basic fibroblast growth factor （bFGF）. Although the importance of TGF-β family members in the maintenance of pluripotency of hESCs is widely established, very little is known about the role of IGF-Ⅱ. In order to ease hESC cul- ture conditions and to reduce xenogenic components, we sought （i） to determine whether hESCs can be maintained stable and pluripotent using CM from human foreskin fibroblasts （HFFs） and human mesenchymal stem cells （hM- SCs） rather than MEF-CM, and （ii） to analyze whether the cooperation of bFGF with TGF-β and IGF-Ⅱ to maintain hESCs in MEF-CM may be extrapolated to hESCs maintained in allogeneic mesenchymal stem cell （MSC）-CM and HFF-CM. We found that MSCs and HFFs express all FGF receptors （FGFR1-4） and specifically produce TGF-β in response to bFGF. However, HFFs but not MSCs secrete IGF-Ⅱ. Despite the absence of IGF-Ⅱ in MSC-CM, hESC pluripotency and culture homeostasis were successfully maintained in MSC-CM for over 37 passages. Human ESCs derived on MSCs and hESCs maintained in MSC-CM retained hESC morphology, euploidy, expression of surface markers and transcription factors linked to pluripotency and displayed in vitro and in vivo multilineage developmental potential, suggesting that IGF-Ⅱ may be dispensable for hESC pluripotency. In fact, IGF-Ⅱ blocking had no effect on the homeostasis of hESC cultures maintained either on HFF-CM or on MSC-CM. These data indicate that hESCs are successfully maintained feeder-free with IGF-Ⅱ-lacking MSC-CM, and that the previously proposed paracrine mechanism by which bFGF cooperates with TGF-β and IGF-Ⅱ in the maintenance of hESCs in MEF-CM may not be fully extrapolated to hESCs maintained in CM from human MSCs.
文摘In vitro growth and maintenance of embryonic stem (ES) cell lines derived from ICM cells of various blastocysts of 129 strain mice, the sustenance of their pluripotency and normal karyotype depend on the feeder layer of mouse embryonic fibroblasts (MEF). Compared with the feeder layer of MEF cells, medium conditioned by Buffalo rat liver cells (BRL-CM) is able to maintain pluripotency and karyo-typic normality of ES cells only in short term cell propagation. Besides, ES cells grown in BRL-CM are also capable of aggregation with 8-cell embryos of Swiss strain and develop into germ line chimaeras. Modification to the method of aggregating ES cells with early embryos by making a hole in agar layer on the top of MEF feeder cells was shown to be more convenient and efficient than the conventional microdrop method.
文摘Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.
文摘The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for along time without affecting total CREB protein levels. The effect of F9204 was similar to morphine whicheffect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitiveN-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phos-phorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also thephosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterationsin the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence.NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.
基金supported by the Scientific Research Project of the Traditional Chinese Medicine Bureau of Guangdong Province(Nos.20203002,20211188,and 20222082)the Special Funding for TCM Science and Technology Reasearch of Guangdong Provincial Hospital of Chinese Medicine(No.CMR-2017022-1001).
文摘Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord.One important aspect of ALS pathogenesis is superoxide dismutase 1(SOD1)mutant-mediated mitochondrial toxicity,leading to apoptosis in neurons.This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1(G-Rg1)and conditioned medium(CM)on a mutational SOD1 cell model,and to explore the underlying mechanisms.We found that the contents of nerve growth factor,glial cell line-derived neurotrophic factor,and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells(hUCMSCs)were exposed to neuron differentiation reagents for seven days.CM or G-Rg1 decreased the apoptotic rate of SOD1^(G93A)-NSC34 cell to a certain extent,but their combination brought about the least apoptosis,compared with CM or G-Rg1 alone.Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups.Proteins associated with mitochondrial apoptotic pathways,such as Bax,caspase 9(Cas-9),and cytochrome c(Cyt c),were downregulated.Furthermore,CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B(NF-κB)signaling pathway by reducing the phosphorylation of p65 and IκBa.CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid(BetA),an agonist of the NF-κB signaling pathway.In summary,the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^(G93A)-NSC34 cells through suppresing the NF-κB/Bcl-2 sgaling pathway(Fig.1 is a graphcal representation of the abstract).
基金Project supported by the National Basic Research Program (973) of China (No. 2003CB515402), and the Science and Technology Coun-cil of Zhejiang Province (No. 2005C23G2010166), China
文摘Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm. Results: MRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice. Conclusion: Based on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.
文摘In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curves of conditioned rubber specimens under di?erent conditioned strains are obtained. Test results show di?erences between these curves. Based on an analysis of the classical constitutive models, a new modi?ed eight-chain model is proposed, which takes account of both the locking stretch of chains and the interaction e?ect in the network. Fitting test data shows that the modi?ed model well characterizes the incompressible hyperelastic mechanical behavior of conditioned rubbers under the moderate ?nite deformation as well as under the large deformation.
基金Supported by Grants from The Administration of Traditional Chinese Medicine Sichuan Province(Exploration of Molecular Mechanisms of Fuyangfang Which Based on the TCM Theory of Yang Deficiency Qi Qie about Alcohol Addiction about Alcohol Addiction Memory and Eliminate,No.2014-E-069)
文摘OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METHODS:A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice.The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol.Concentrations of dopamine(DA),Glutamate(Glu),and?-aminobutyric acid(GABA)in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay.RESULTS:Although PG did not alter spontaneous activity in mice,it reduced the growth of spontaneous activity stimulated by ethanol.The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased.CONCLUSION:Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice.The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system.This suggests that PG might be useful for the prevention and treatment of alcohol addiction.
基金supported by grants from the National Basic Research Development Program (973 Program) of China (2011CB707802,2011CB707800)the National Natural Science Foundation of China (81171302)
文摘Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.
