Objective:To observe the effects of p38 mitogen activated protein kinase(MAPK) inhibitor SB203580 by intra-thecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer p...Objective:To observe the effects of p38 mitogen activated protein kinase(MAPK) inhibitor SB203580 by intra-thecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods:Eleven rats were used to establish the models of bone cancer pain,six rats were treated by intrathecal SB203580 injection,and the other 5 were as the controls. The paw withdrawal latency(PWL),histology and the spinal levels of IL-1β and TNF-α were detected. Results:All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However,following intrathecal injection of SB203580,the left PWLs(12.12 ± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days) were significant higher than that of controls(9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days),P < 0.05. Meanwhile,intrathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion:Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity,which might result from inhibiting intracellular p38 MAPK signaling transduction,and thereby reducing the release of the proinflammatory cytokines.展开更多
Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)cells.However,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17...Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)cells.However,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in MS.Here,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse models.Conditional knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE mice.Furthermore,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE progression.In conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.展开更多
In this paper, a cost-benefit analysis based optimal planning model of battery energy storage system(BESS) in active distribution system(ADS) is established considering a new BESS operation strategy. Reliability impro...In this paper, a cost-benefit analysis based optimal planning model of battery energy storage system(BESS) in active distribution system(ADS) is established considering a new BESS operation strategy. Reliability improvement benefit of BESS is considered and a numerical calculation method based on expectation is proposed for simple and convenient calculation of system reliability improvement with BESS in planning phase. Decision variables include both configuration variables and operation strategy control variables. In order to prevent the interaction between two types of variables and enhance global search ability, intelligent single particle optimizer(ISPO) is adopted to optimize this model. Case studies on a modified IEEE benchmark system verified the performance of the proposed operation strategy and optimal planning model of BESS.展开更多
基金a grant from the National Nature Sciences Foundation of China (No. 30672426).
文摘Objective:To observe the effects of p38 mitogen activated protein kinase(MAPK) inhibitor SB203580 by intra-thecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods:Eleven rats were used to establish the models of bone cancer pain,six rats were treated by intrathecal SB203580 injection,and the other 5 were as the controls. The paw withdrawal latency(PWL),histology and the spinal levels of IL-1β and TNF-α were detected. Results:All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However,following intrathecal injection of SB203580,the left PWLs(12.12 ± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days) were significant higher than that of controls(9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days),P < 0.05. Meanwhile,intrathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion:Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity,which might result from inhibiting intracellular p38 MAPK signaling transduction,and thereby reducing the release of the proinflammatory cytokines.
基金supported by grants from the National Natural Science Foundation of China(82072062,82270016,and 82102249)the National Science and Technology Key Projects for Major Infectious Diseases(2017ZX10302301-002)+2 种基金the Natural Science Foundation of Guangdong Province(2023A1515030065)the Open Research Funds from the Sixth Affliated Hospital of Guangzhou Medical University,Qingyuan People's Hospital(202301-102)the Development Project of Foshan Fourth People's Hospital(FSSYKF-2020003).
文摘Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)cells.However,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in MS.Here,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse models.Conditional knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE mice.Furthermore,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE progression.In conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.
文摘In this paper, a cost-benefit analysis based optimal planning model of battery energy storage system(BESS) in active distribution system(ADS) is established considering a new BESS operation strategy. Reliability improvement benefit of BESS is considered and a numerical calculation method based on expectation is proposed for simple and convenient calculation of system reliability improvement with BESS in planning phase. Decision variables include both configuration variables and operation strategy control variables. In order to prevent the interaction between two types of variables and enhance global search ability, intelligent single particle optimizer(ISPO) is adopted to optimize this model. Case studies on a modified IEEE benchmark system verified the performance of the proposed operation strategy and optimal planning model of BESS.
