Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating ...Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.展开更多
A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates t...A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane”的研究论文,揭示了Rab27a及其效应分子SYTL1和SYTL4通过促进流感病毒膜蛋白转运从而有利于病毒粒子出芽的分子机制。展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secret...Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.展开更多
Tiller number represents a critical agronomic trait determining sugarcane yield.Strigolactones(SLs) are plant hormones regulating plant architecture.D27,an essential enzyme in the SL biosynthetic pathway,catalyzes a r...Tiller number represents a critical agronomic trait determining sugarcane yield.Strigolactones(SLs) are plant hormones regulating plant architecture.D27,an essential enzyme in the SL biosynthetic pathway,catalyzes a reversible isomerization reaction.ScD27.2,the D27 homolog in sugarcane,contains abiotic stress-responsive elements in its promoter,suggesting its potential importance in SL biosynthesis and stress tolerance.ScD27.2 potentially optimizes sugarcane agronomic traits,particularly tiller number and yield.Understanding its mechanisms will advance the development of high-yielding,stresstolerant sugarcane varieties.To investigate the role of D27 in sugarcane tillering,the key carotene isomerase gene ScD 27.2 was silenced(via RNAi) and overexpressed(OE) in sugarcane cultivar ‘XTT22' plantlets.ScD27-RNAi-2 sugarcane exhibited decreased ScD27.2 expression and increased tiller numbers compared to the wild type ‘XTT22'.Conversely,overexpression lines(ScD27-OE-1,ScD27-OE-5,and ScD27-OE-9) showed increased ScD27.2 expression and decreased tiller numbers.ScD27-OE-9 demonstrated notable lateral bud germination,while ScD27-RNAi-2 exhibited reduced drought tolerance.Under normal light and water management conditions,transgenic sugarcane plants showed significant differences in tiller number and plant height.During extended drought conditions,ScD27-RNAi-2 height was significantly reduced compared to wild type ‘XTT22' and ScD27-OE-9,manifesting a dwarf,multi-tiller phenotype.Additionally,ScD27-RNAi-2 showed significantly reduced SLs content.These findings demonstrate that ScD27.2 regulates tillering under drought stress,likely through SL biosynthesis,and that its drought response may be mediated by the transcription factor ScMYB44.展开更多
基金support for this work for ASH was from National Eye Institute R01 EY026546an NEI Center Core Grant EY014801.
文摘Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.
文摘A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane”的研究论文,揭示了Rab27a及其效应分子SYTL1和SYTL4通过促进流感病毒膜蛋白转运从而有利于病毒粒子出芽的分子机制。
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
基金funded by the Deutsche Forschungsgemeinschaft(DFG)grant number(KA2663/3-1)supported by the Ministry of Science,Research and Cultural Affairs of the State of Brandenburg.
文摘Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.
基金funded by the National Natural Science Foundation of China (31860405)the National Key Laboratory for Tropical Crop Breeding,China (NKLTCB-YAAS-2024-S05)+4 种基金the Yunnan Provincial Modern Agricultural Technology System,Chinathe Yunnan Provincial Science and Technology Innovation TalentProgram,China (202305AD160041)the Yunnan Provincial “Xingdian Talent Support Program”,Chinathe Yunnan Haizhi Station for Sugarcane Research Institute of Yunnan Academy of Agricultural Sciences,China (HHZ202201)the Yunnan Provincial Key Research and Development Program,China (202403AM140025)。
文摘Tiller number represents a critical agronomic trait determining sugarcane yield.Strigolactones(SLs) are plant hormones regulating plant architecture.D27,an essential enzyme in the SL biosynthetic pathway,catalyzes a reversible isomerization reaction.ScD27.2,the D27 homolog in sugarcane,contains abiotic stress-responsive elements in its promoter,suggesting its potential importance in SL biosynthesis and stress tolerance.ScD27.2 potentially optimizes sugarcane agronomic traits,particularly tiller number and yield.Understanding its mechanisms will advance the development of high-yielding,stresstolerant sugarcane varieties.To investigate the role of D27 in sugarcane tillering,the key carotene isomerase gene ScD 27.2 was silenced(via RNAi) and overexpressed(OE) in sugarcane cultivar ‘XTT22' plantlets.ScD27-RNAi-2 sugarcane exhibited decreased ScD27.2 expression and increased tiller numbers compared to the wild type ‘XTT22'.Conversely,overexpression lines(ScD27-OE-1,ScD27-OE-5,and ScD27-OE-9) showed increased ScD27.2 expression and decreased tiller numbers.ScD27-OE-9 demonstrated notable lateral bud germination,while ScD27-RNAi-2 exhibited reduced drought tolerance.Under normal light and water management conditions,transgenic sugarcane plants showed significant differences in tiller number and plant height.During extended drought conditions,ScD27-RNAi-2 height was significantly reduced compared to wild type ‘XTT22' and ScD27-OE-9,manifesting a dwarf,multi-tiller phenotype.Additionally,ScD27-RNAi-2 showed significantly reduced SLs content.These findings demonstrate that ScD27.2 regulates tillering under drought stress,likely through SL biosynthesis,and that its drought response may be mediated by the transcription factor ScMYB44.