Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we expl...Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks of Broussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1(Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase(JAK) 2, signal transducer and activator of transcription(STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.展开更多
The extraordinary optical and electronic properties of anisotropic two-dimensional materials,such as black phosphorus,ReS2,and GeSe,enable them a promising component of polarization-sensitive photodetectors.However,th...The extraordinary optical and electronic properties of anisotropic two-dimensional materials,such as black phosphorus,ReS2,and GeSe,enable them a promising component of polarization-sensitive photodetectors.However,these applications are significantly limited by the challenges of air-stability,response time,and linearly dichroic ratio.Interestingly,palladium diselenide(PdSe2)with high air stability is an emerging material that has robust in-plane anisotropy induced by its asymmetric pentagonal lattice structure.We have successfully prepared a few-layer PdSe2 using micromechanical exfoliation,and here we demonstrate the strong linear dichroism behavior of PdSe2 by polarization-resolved absorption spectra measurements.Such unique linear dichroism,endows the PdSe2 photodetector powerful ability to detect polarized light.The photodetector based on 5L PdSe2,as tested with polarization-dependent photocurrent mapping,exhibited competitive capability to detect polarized light,achieving a significant photocurrent on/off ratio(>10^2),the quite fast response time(<11 ms)and robust linearly dichroic ratios(/max//min≈1.9 at 532 nm).These results are essential advance in the development of polarization-sensitive photodetector,a crucial step towards opening up a new avenue for the application of 2D optoelectronic devices.展开更多
Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains un...Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.展开更多
背景:周围神经是人体最脆弱的结构,很容易因创伤而受损,巨噬细胞作为周围神经中最主要的免疫细胞,在周围神经损伤修复再生中发挥了极为重要的作用。随着对巨噬细胞各亚型功能及诱导机制研究越来越清楚,可以通过分子生物学方法诱导巨噬...背景:周围神经是人体最脆弱的结构,很容易因创伤而受损,巨噬细胞作为周围神经中最主要的免疫细胞,在周围神经损伤修复再生中发挥了极为重要的作用。随着对巨噬细胞各亚型功能及诱导机制研究越来越清楚,可以通过分子生物学方法诱导巨噬细胞成相应修复表型,并期许其成为周围神经损伤新的治疗靶点。目的:总结周围神经系统中巨噬细胞的起源、分类、巨噬细胞极化、极化调控以及在周围神经损伤修复再生中的应用。方法:通过检索CNKI、万方数据库、PubMed及Web of Science数据库相关文章。以“巨噬细胞极化,神经”为中文检索词,以“macrophage polarization,nerve”为英文检索词。然后根据纳入与排除标准对文章进行初筛,保留相关性和参考价值较高的73篇文章进行综述。结果与结论:巨噬细胞极化在周围神经损伤后的修复中发挥重要作用,有望成为治疗周围神经损伤的治疗靶点,但是控制这一过程的机制仍需要进一步深入研究,促进巨噬细胞M2极化的最佳方法也存在不确定性。因此,需要进一步研究巨噬细胞向M2极化的调控机制以及M2巨噬细胞如何调节神经功能恢复,为周围神经损伤的治疗奠定基础。展开更多
Astrocytes play multifaceted and vital roles in maintaining neurophysiological function of the central nervous system by regulating homeostasis, increasing synaptic plasticity, and sustaining neuroprotective effects. ...Astrocytes play multifaceted and vital roles in maintaining neurophysiological function of the central nervous system by regulating homeostasis, increasing synaptic plasticity, and sustaining neuroprotective effects. Astrocytes become activated as a result of inflammatory responses during the progression of pathological changes associated with neurodegenerative disorders. Reactive astrocytes(neurotoxic A1 and neuroprotective A2) are triggered during disease progression and pathogenesis due to neuroinflammation and ischemia. However, only a limited body of literature describes morphological and functional changes of astrocytes during the progression of neurodegenerative diseases. The present review investigated the detrimental and beneficial roles of astrocytes in neurodegenerative diseases reported in recent studies, as these cells have promising therapeutic potential and offer new approaches for treatment of neurodegenerative diseases.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81703530 and 81773995)the Natural Science Foundation of Jiangsu Province(Nos.BK20160032 and BK20170859)+2 种基金the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University(Traditional Chinese Pharmacology)Zhejiang Chinese Medical University(No.ZYAOX2018001)the Six Talent Peaks Project of Jiangsu Province(PANG Tao)
文摘Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks of Broussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1(Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase(JAK) 2, signal transducer and activator of transcription(STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.
基金This work was supported by the National Natural Science Foundation of China(No.61775241)Youth Innovation Team(No.2019012)+3 种基金of CSU,Hunan province key research and development project(No.2019GK2233)the Science and Technology Innovation Basic Research Project of Shenzhen(No.JCYJ20180307151237242)the Project of State Key Laboratory of High-Performance Complex Manufacturing,Central South University(No.ZZYJKT2020-12)Z.W.L.acknowledges the funding support from the Australian Research Council(ARC Discovery Projects,DP180102976).
文摘The extraordinary optical and electronic properties of anisotropic two-dimensional materials,such as black phosphorus,ReS2,and GeSe,enable them a promising component of polarization-sensitive photodetectors.However,these applications are significantly limited by the challenges of air-stability,response time,and linearly dichroic ratio.Interestingly,palladium diselenide(PdSe2)with high air stability is an emerging material that has robust in-plane anisotropy induced by its asymmetric pentagonal lattice structure.We have successfully prepared a few-layer PdSe2 using micromechanical exfoliation,and here we demonstrate the strong linear dichroism behavior of PdSe2 by polarization-resolved absorption spectra measurements.Such unique linear dichroism,endows the PdSe2 photodetector powerful ability to detect polarized light.The photodetector based on 5L PdSe2,as tested with polarization-dependent photocurrent mapping,exhibited competitive capability to detect polarized light,achieving a significant photocurrent on/off ratio(>10^2),the quite fast response time(<11 ms)and robust linearly dichroic ratios(/max//min≈1.9 at 532 nm).These results are essential advance in the development of polarization-sensitive photodetector,a crucial step towards opening up a new avenue for the application of 2D optoelectronic devices.
基金supported by the Shenyang Science and Technology Project,No.20-205-4-092(to AHX)。
文摘Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.
文摘背景:周围神经是人体最脆弱的结构,很容易因创伤而受损,巨噬细胞作为周围神经中最主要的免疫细胞,在周围神经损伤修复再生中发挥了极为重要的作用。随着对巨噬细胞各亚型功能及诱导机制研究越来越清楚,可以通过分子生物学方法诱导巨噬细胞成相应修复表型,并期许其成为周围神经损伤新的治疗靶点。目的:总结周围神经系统中巨噬细胞的起源、分类、巨噬细胞极化、极化调控以及在周围神经损伤修复再生中的应用。方法:通过检索CNKI、万方数据库、PubMed及Web of Science数据库相关文章。以“巨噬细胞极化,神经”为中文检索词,以“macrophage polarization,nerve”为英文检索词。然后根据纳入与排除标准对文章进行初筛,保留相关性和参考价值较高的73篇文章进行综述。结果与结论:巨噬细胞极化在周围神经损伤后的修复中发挥重要作用,有望成为治疗周围神经损伤的治疗靶点,但是控制这一过程的机制仍需要进一步深入研究,促进巨噬细胞M2极化的最佳方法也存在不确定性。因此,需要进一步研究巨噬细胞向M2极化的调控机制以及M2巨噬细胞如何调节神经功能恢复,为周围神经损伤的治疗奠定基础。
基金supported partially by the National Natural Science Foundation of China,No.81473577(to CGM)a grant from the Department of Science and Technology of Shanxi Province,China,No.201803D421073(to YQY)and No.201805D111009(to CGM)+2 种基金a grant from Shanxi Applied Basic Research Project,No.201901D211538(to LJS)Datong Bureau of Science and Technology of China,No.2019198(to CGM)Research Project Funds from Shanxi Scholarship Council of China,No.2014-7(to CGM)。
文摘Astrocytes play multifaceted and vital roles in maintaining neurophysiological function of the central nervous system by regulating homeostasis, increasing synaptic plasticity, and sustaining neuroprotective effects. Astrocytes become activated as a result of inflammatory responses during the progression of pathological changes associated with neurodegenerative disorders. Reactive astrocytes(neurotoxic A1 and neuroprotective A2) are triggered during disease progression and pathogenesis due to neuroinflammation and ischemia. However, only a limited body of literature describes morphological and functional changes of astrocytes during the progression of neurodegenerative diseases. The present review investigated the detrimental and beneficial roles of astrocytes in neurodegenerative diseases reported in recent studies, as these cells have promising therapeutic potential and offer new approaches for treatment of neurodegenerative diseases.
