During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membra...During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.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
试验旨在研制具有高抗原活性的猪链球菌2型(Streptococcus suis type 2,SS2)疫苗培养基。研究以SS2 CVCC60615株为试验对象,通过单因素试验、Plackett-Burman试验、最陡爬坡试验和响应面分析得到SS2疫苗培养基。培养基发酵验证结果显示,...试验旨在研制具有高抗原活性的猪链球菌2型(Streptococcus suis type 2,SS2)疫苗培养基。研究以SS2 CVCC60615株为试验对象,通过单因素试验、Plackett-Burman试验、最陡爬坡试验和响应面分析得到SS2疫苗培养基。培养基发酵验证结果显示,SS2疫苗培养基菌液最大活菌数为1.09×10^(9) CFU/mL,是TSB培养基最大活菌数的2.41倍。测定SS2不同时间点的抗原活性发现,在SS2发酵培养过程中当活菌数达到最大值后的1~3 h内细菌的抗原活性最高。小鼠感染试验表明,SS2抗原活性最高时制备的灭活疫苗与商品化灭活疫苗相比具有更高的免疫球蛋白G(IgG)抗体效价和疫苗保护率。研究表明,采用研制得到的高抗原活性SS2疫苗培养基制备的灭活疫苗具有IgG抗体效价高、免疫保护力强的优点。展开更多
Hydrate-based CO_(2) sequestration is an effective method for reducing the greenhouse effect,and the presence of porous media and NaCl can impact the formation characteristics of hydrates.This study uses the constant ...Hydrate-based CO_(2) sequestration is an effective method for reducing the greenhouse effect,and the presence of porous media and NaCl can impact the formation characteristics of hydrates.This study uses the constant volume temperature search method to investigate the effects of quartz sand particle size(0.006‒0.03 mm),water saturation(30%–90%),and NaCl concentration(1%‒9%)on the phase equilibrium and kinetics of CO_(2) hydrates within a temperature range of 273‒285 K and pressure range of 1.0‒3.5 MPa.The results indicate that a decrease in quartz sand particle size or an increase in NaCl concentration shifts the hydrate phase equilibrium curve towards lower temperatures and higher pressures,making hydrate generation conditions more demanding.In different particle size systems,there are no significant changes in the rate of CO_(2) hydrate formation or conversion rate.The highest hydrate conversion rate of 71.1%is observed in a 0.015 mm particle size system.With increasing water saturation,both the generation rate and conversion rate of CO_(2) hydrates show a trend of first increasing and then decreasing.Meanwhile,low concentrations of NaCl(1%–3%)are found to enhance the formation and conversion rates of CO_(2) hydrates.However,as NaCl concentration increases,the rate of CO_(2) hydrate formation and conversion rate decrease.展开更多
Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medi...Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P <0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.展开更多
AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning...AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential(120 k Vp) protocol with 350 mg I/m L contrast medium and filtered back projection,and a low tube potential(80 k Vp) protocol with 270 mg I/m L contrast medium with iterative reconstruction.Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor.Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated.RESULTS:A 38% reduction in contrast medium dose(360.1 ± 13.3 mg I/kg vs 583.5 ± 21.5 mg I/kg,P < 0.001) and a 73% decrease in radiation dose(1898.5 m Gy·cm vs 6951.8 m Gy·cm) were observed.Interestingly,there was a strong positive correlation in hepatic arterial perfusion(r = 0.907,P < 0.001;r = 0.879,P < 0.001),hepatic portal perfusion(r = 0.819,P = 0.002;r = 0.831,P = 0.002),and hepatic blood flow(r = 0.945,P < 0.001;r = 0.930,P < 0.001) as well as a moderate correlation in hepatic perfusion index(r = 0.736,P = 0.01;r = 0.636,P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor.These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumorto-liver CNR during arterial and portal venous phases(5.63 ± 2.38 vs 6.16 ± 2.60,P = 0.814;4.60 ± 1.27 vs 5.11 ± 1.74,P = 0.587).CONCLUSION:Compared with the conventional protocol,low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.展开更多
基金supported by University of Florence RICATEN 2023 to EC.Grant/Award Numbers 58514_InternazionalizzazioneUniversity of Florence,to EC.Parkinson’s UK,Grant/Award Number:H-0902 to AJGWellcome Trust,Grant/Award Number:0926/Z/10/Z to AJG。
文摘During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.
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.
文摘试验旨在研制具有高抗原活性的猪链球菌2型(Streptococcus suis type 2,SS2)疫苗培养基。研究以SS2 CVCC60615株为试验对象,通过单因素试验、Plackett-Burman试验、最陡爬坡试验和响应面分析得到SS2疫苗培养基。培养基发酵验证结果显示,SS2疫苗培养基菌液最大活菌数为1.09×10^(9) CFU/mL,是TSB培养基最大活菌数的2.41倍。测定SS2不同时间点的抗原活性发现,在SS2发酵培养过程中当活菌数达到最大值后的1~3 h内细菌的抗原活性最高。小鼠感染试验表明,SS2抗原活性最高时制备的灭活疫苗与商品化灭活疫苗相比具有更高的免疫球蛋白G(IgG)抗体效价和疫苗保护率。研究表明,采用研制得到的高抗原活性SS2疫苗培养基制备的灭活疫苗具有IgG抗体效价高、免疫保护力强的优点。
基金the National Natural Science Foundation of China(NSFC 21676145)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD,China).
文摘Hydrate-based CO_(2) sequestration is an effective method for reducing the greenhouse effect,and the presence of porous media and NaCl can impact the formation characteristics of hydrates.This study uses the constant volume temperature search method to investigate the effects of quartz sand particle size(0.006‒0.03 mm),water saturation(30%–90%),and NaCl concentration(1%‒9%)on the phase equilibrium and kinetics of CO_(2) hydrates within a temperature range of 273‒285 K and pressure range of 1.0‒3.5 MPa.The results indicate that a decrease in quartz sand particle size or an increase in NaCl concentration shifts the hydrate phase equilibrium curve towards lower temperatures and higher pressures,making hydrate generation conditions more demanding.In different particle size systems,there are no significant changes in the rate of CO_(2) hydrate formation or conversion rate.The highest hydrate conversion rate of 71.1%is observed in a 0.015 mm particle size system.With increasing water saturation,both the generation rate and conversion rate of CO_(2) hydrates show a trend of first increasing and then decreasing.Meanwhile,low concentrations of NaCl(1%–3%)are found to enhance the formation and conversion rates of CO_(2) hydrates.However,as NaCl concentration increases,the rate of CO_(2) hydrate formation and conversion rate decrease.
基金supported by a grant from the ITI International Team for Implantology Foundation 1235_2017 to M.B.A
文摘Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P <0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.
基金National Natural Science Foundation of China,No.NSFC 81171389Key Program of Basic Research from Shanghai Municipal Science and Technology Commission,No.12JC1406500the Program of Shanghai Municipal Health Outstanding Discipline Leader,No.XBR 2013110
文摘AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential(120 k Vp) protocol with 350 mg I/m L contrast medium and filtered back projection,and a low tube potential(80 k Vp) protocol with 270 mg I/m L contrast medium with iterative reconstruction.Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor.Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated.RESULTS:A 38% reduction in contrast medium dose(360.1 ± 13.3 mg I/kg vs 583.5 ± 21.5 mg I/kg,P < 0.001) and a 73% decrease in radiation dose(1898.5 m Gy·cm vs 6951.8 m Gy·cm) were observed.Interestingly,there was a strong positive correlation in hepatic arterial perfusion(r = 0.907,P < 0.001;r = 0.879,P < 0.001),hepatic portal perfusion(r = 0.819,P = 0.002;r = 0.831,P = 0.002),and hepatic blood flow(r = 0.945,P < 0.001;r = 0.930,P < 0.001) as well as a moderate correlation in hepatic perfusion index(r = 0.736,P = 0.01;r = 0.636,P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor.These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumorto-liver CNR during arterial and portal venous phases(5.63 ± 2.38 vs 6.16 ± 2.60,P = 0.814;4.60 ± 1.27 vs 5.11 ± 1.74,P = 0.587).CONCLUSION:Compared with the conventional protocol,low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.
