A key event that follows pathogen recognition by a resistance(R)protein containing an NB-ARC(nucleotide-binding adaptor shared by Apaf-1,R proteins,and Ced-4)domain is hypersensitive response(HR)-type cell death accom...A key event that follows pathogen recognition by a resistance(R)protein containing an NB-ARC(nucleotide-binding adaptor shared by Apaf-1,R proteins,and Ced-4)domain is hypersensitive response(HR)-type cell death accompanied by accumulation of reactive oxygen species and nitric oxide.However,the integral mechanisms that underlie this process remain relatively opaque.Here,we show that a gain-offunction mutation in the NB-ARC protein RLS1(Rapid Leaf Senescence 1)triggers high-light-dependent HR-like cell death in rice.The RLS1-mediated defense response is largely independent of salicylic acid accumulation,NPR1(Nonexpressor of Pathogenesis-Related Gene 1)activity,and RAR1(Required for Mla12 Resistance 1)function.A screen for suppressors of RLS1 activation identified RMC(Root Meander Curling)as essential for the RLS1-activated defense response.RMC encodes a cysteine-rich receptor-like secreted protein(CRRSP)and functions as an RLS1-binding partner.Intriguingly,their co-expression resulted in a change in the pattern of subcellular localization and was sufficient to trigger cell death accompanied by a decrease in the activity of the antioxidant enzyme APX1.Collectively,our findings reveal an NBARC-CRRSP signaling module that modulates oxidative state,the cell death process,and associated immunity responses in rice.展开更多
利用基于OPLS-AA(optimized potentials for liquid simulations all atom)力场的分子动力学(molecular dynamics,MD)方法研究大豆中富含半胱氨酸蛋白的疏水性质以及蛋白与溶剂间的弱相互作用,并从热力学和动力学方面研究该蛋白在不同...利用基于OPLS-AA(optimized potentials for liquid simulations all atom)力场的分子动力学(molecular dynamics,MD)方法研究大豆中富含半胱氨酸蛋白的疏水性质以及蛋白与溶剂间的弱相互作用,并从热力学和动力学方面研究该蛋白在不同λ下的自由能变化规律.结果表明,半胱氨酸对蛋白的性质具有决定性影响,溶剂主要影响蛋白的构象.展开更多
Objective: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61(Cyr61), is important in its pathophysiology. Long-term clinical ...Objective: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61(Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula(SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod(IMQ)-induced psoriasis.Methods: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index(PASI) score,hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ(IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1(ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.Results: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples(78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin(18.66 ± 2.51 vs4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score(10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05),and pathological features compared with those in IMQ model group;SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the lev展开更多
A number of plant pathogenic species of Phytophthora are known to produce different classes of secretory proteins during interactions with their hosts.Although several small cysteine-rich(SCR)secretory proteins,conser...A number of plant pathogenic species of Phytophthora are known to produce different classes of secretory proteins during interactions with their hosts.Although several small cysteine-rich(SCR)secretory proteins,conserved in oomycete pathogens,have been identified in Phytophthora,their specific involvement in these interactions remains unknown.In this study,an SCR effector encoded by Pn SCR82 in P.nicotianae was identified and shown to have similarities to P.cactorum phytotoxic protein,Pc F(Phytophthora cactorum Fragaria).Agroinfection with potato virus X vector,Pn SCR82,was capable of inducing plant hypersensitive cell death in Nicotiana benthamiana and Solanum lycopersicum.Real-time PCR results indicated that transiently expressed Pn SCR82 in N.benthamiana leaves activated the jasmonate,salicylic acid and ethylene signaling pathways.Transient expression of Pn SCR82 enhanced plant resisitance to P.capsici.In summary,our results demonstrated that P.nicotianae Pn SCR82 elicits defensive responses in N.benthamiana and may potentially play a significant role in future crop protection programs.展开更多
Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted sperm...Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted spermatozoa and participates in gamete fusion through binding to egg complementary sites. Immunization of rats with DE inhibits fertility and sperm fusion ability, suggesting that DE represents a good epididymal contraceptive target. Recombinant DE fragments and synthetic peptides revealed that DE binds to the egg via a 12-amino acid region of an evolutionarily conserved motif, Signature 2 （S2）. The ability of other CRISP to bind to the rat egg was correlated with their S2 amino acid sequences. Although testicular protein Tpx- 1 （CRISP-2） was capable of binding to rodent eggs, human epididymal AEG-related protein （ARP） and helothermine （from lizard saliva） were not. The S2 region presented only two substitutions in Tpx-1 and four in ARP and helothermine, compared with the DE S2, suggesting that this amino acid sequence was relevant for egg interaction. Studies with Tpx- 1 and anti-Tpx- 1 revealed the participation of this protein in gamete fusion through binding to complementary sites in the egg. In competition studies, DE reduced binding of Tpx- 1 dose-dependently, indicating that both CRISP share the egg complementary sites. That anti-DE and anti-Tpx-1 inhibit sperm-egg fusion while recognizing only the corresponding proteins, suggests functional cooperation between these homologous CRISP to ensure fertilization success. These results increase our understanding of the molecular mechanisms of gamete fusion and contribute to the development of new and safer fertility regulating methods. （Asian J Androl 2007 July; 9： 528-532）展开更多
目的探讨甘精胰岛素联合格列美脲对2型糖尿病老年患者血糖控制效果及富含半胱氨酸的酸性分泌蛋白(SPARC)蛋白表达的影响.方法选取2016年1月~2018年1月在本院接受治疗的126例2型糖尿病患者为研究对象,依照随机数字表分为对照组和观察组,...目的探讨甘精胰岛素联合格列美脲对2型糖尿病老年患者血糖控制效果及富含半胱氨酸的酸性分泌蛋白(SPARC)蛋白表达的影响.方法选取2016年1月~2018年1月在本院接受治疗的126例2型糖尿病患者为研究对象,依照随机数字表分为对照组和观察组,每组63例,对照组给予甘精胰岛素治疗,观察组采用甘精胰岛素联合格列美脲治疗,比较两组患者治疗前和治疗3个月后空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HBA1C)及SPARC水平,对比两组患者治疗效果和不良反应发生情况.结果治疗后对照组有效率为79.4%,观察组有效率为90.5%,差异有统计学意义(P<0.05);治疗前两组患者FBG、2 h PG、HBA1C和SPARC水平的差异均无统计学意义(P>0.05),治疗后两组患者各指标均降低,且观察组FBG、2 hPG、HBA1c和SPARC水平均低于对照组,差异有统计学意义(P<0.05);对照组和观察组均未出现低血糖不良反应.结论甘精胰岛素联合格列美脲对2型糖尿病老年患者血糖控制效果良好,可降低糖尿病患者胰岛素抵抗,且安全性较高.展开更多
Cardiovascular disease, nervous system disorders, and cancer in association with other diseases such as diabetes mellitus result in greater than sixty percent of the global annual deaths. These noncommunicable disease...Cardiovascular disease, nervous system disorders, and cancer in association with other diseases such as diabetes mellitus result in greater than sixty percent of the global annual deaths. These noncommunicable diseases also affect at least one-third of the population in low and middle-income countries and lead to hypertension, elevated cholesterol, malignancy, and neurodegenerative disorders such as Alzheimer's disease and stroke. With the climbing lifespan of the world's population, increased prevalence of these disorders is expected requiring the development of new therapeutic strategies against these disabling disease entities. Targeting stem cellproliferation for cardiac disease, vascular disorders, cancer, and neurodegenerative disorders is receiving great enthusiasm, especially those that focus upon SIRT1, a mammalian homologue of the yeast silent information regulator-2. Modulation of the cellular activity of SIRT1 can involve oversight by nicotinamide/nicotinic acid mononucleotide adenylyltransferase, mammalian forkhead transcription factors, mechanistic of rapamycin pathways, and cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma over-expressed gene family members that can impact cytoprotective outcomes. Ultimately, the ability of SIRT1 to control the programmed cell death pathways of apoptosis and autophagy can determine not only cardiac, vascular, and neuronal stem cell development and longevity, but also the onset of tumorigenesis and the resistance against chemotherapy. SIRT1 therefore has a critical role and holds exciting prospects for new therapeutic strategies that can offer reparative processes for cardiac, vascular, and nervous system degenerative disorders as well as targeted control of aberrant cell growth during cancer.展开更多
基金supported by grants from the National Natural Science Foundation of China(grant numbers 31571248,31430063,and 31871586).
文摘A key event that follows pathogen recognition by a resistance(R)protein containing an NB-ARC(nucleotide-binding adaptor shared by Apaf-1,R proteins,and Ced-4)domain is hypersensitive response(HR)-type cell death accompanied by accumulation of reactive oxygen species and nitric oxide.However,the integral mechanisms that underlie this process remain relatively opaque.Here,we show that a gain-offunction mutation in the NB-ARC protein RLS1(Rapid Leaf Senescence 1)triggers high-light-dependent HR-like cell death in rice.The RLS1-mediated defense response is largely independent of salicylic acid accumulation,NPR1(Nonexpressor of Pathogenesis-Related Gene 1)activity,and RAR1(Required for Mla12 Resistance 1)function.A screen for suppressors of RLS1 activation identified RMC(Root Meander Curling)as essential for the RLS1-activated defense response.RMC encodes a cysteine-rich receptor-like secreted protein(CRRSP)and functions as an RLS1-binding partner.Intriguingly,their co-expression resulted in a change in the pattern of subcellular localization and was sufficient to trigger cell death accompanied by a decrease in the activity of the antioxidant enzyme APX1.Collectively,our findings reveal an NBARC-CRRSP signaling module that modulates oxidative state,the cell death process,and associated immunity responses in rice.
文摘利用基于OPLS-AA(optimized potentials for liquid simulations all atom)力场的分子动力学(molecular dynamics,MD)方法研究大豆中富含半胱氨酸蛋白的疏水性质以及蛋白与溶剂间的弱相互作用,并从热力学和动力学方面研究该蛋白在不同λ下的自由能变化规律.结果表明,半胱氨酸对蛋白的性质具有决定性影响,溶剂主要影响蛋白的构象.
基金supported by National Natural Science Foundation of China (No. 81803982, 82004366, and 82074428)Clinical Research Plan of Shanghai Shenkang Hospital Development Center(No. SHDC2020CR4041)+3 种基金Shanghai Municipal Commission of Science and Technology (No. 20XD1423600, 20DZ2301900)Sailing Program of Shanghai Rising-Star Program (No. 22YF1449700)the Project of Shanghai University of Traditional Chinese Medicine(No. Y2020064, Y2021019)Shanghai Municipal Commission of Economy and Information Technology,Shanghai Artificial Intelligence Innovation and Development Project-Intelligent Dermatology Clinic Based on Modern TCM Diagnostic Technology (No. 2020-RGZN-02038)。
文摘Objective: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61(Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula(SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod(IMQ)-induced psoriasis.Methods: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index(PASI) score,hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ(IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1(ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.Results: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples(78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin(18.66 ± 2.51 vs4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score(10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05),and pathological features compared with those in IMQ model group;SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the lev
基金supported by the National Natural Science Foundation of China(31972218,31501590,and 31601615)the Program for Talents in Qingdao Agricultural University,China(6631114307)the Independent Innovation of Agricultural Sciences in Jiangsu Province,China(CX(18)3012)。
文摘A number of plant pathogenic species of Phytophthora are known to produce different classes of secretory proteins during interactions with their hosts.Although several small cysteine-rich(SCR)secretory proteins,conserved in oomycete pathogens,have been identified in Phytophthora,their specific involvement in these interactions remains unknown.In this study,an SCR effector encoded by Pn SCR82 in P.nicotianae was identified and shown to have similarities to P.cactorum phytotoxic protein,Pc F(Phytophthora cactorum Fragaria).Agroinfection with potato virus X vector,Pn SCR82,was capable of inducing plant hypersensitive cell death in Nicotiana benthamiana and Solanum lycopersicum.Real-time PCR results indicated that transiently expressed Pn SCR82 in N.benthamiana leaves activated the jasmonate,salicylic acid and ethylene signaling pathways.Transient expression of Pn SCR82 enhanced plant resisitance to P.capsici.In summary,our results demonstrated that P.nicotianae Pn SCR82 elicits defensive responses in N.benthamiana and may potentially play a significant role in future crop protection programs.
文摘Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted spermatozoa and participates in gamete fusion through binding to egg complementary sites. Immunization of rats with DE inhibits fertility and sperm fusion ability, suggesting that DE represents a good epididymal contraceptive target. Recombinant DE fragments and synthetic peptides revealed that DE binds to the egg via a 12-amino acid region of an evolutionarily conserved motif, Signature 2 （S2）. The ability of other CRISP to bind to the rat egg was correlated with their S2 amino acid sequences. Although testicular protein Tpx- 1 （CRISP-2） was capable of binding to rodent eggs, human epididymal AEG-related protein （ARP） and helothermine （from lizard saliva） were not. The S2 region presented only two substitutions in Tpx-1 and four in ARP and helothermine, compared with the DE S2, suggesting that this amino acid sequence was relevant for egg interaction. Studies with Tpx- 1 and anti-Tpx- 1 revealed the participation of this protein in gamete fusion through binding to complementary sites in the egg. In competition studies, DE reduced binding of Tpx- 1 dose-dependently, indicating that both CRISP share the egg complementary sites. That anti-DE and anti-Tpx-1 inhibit sperm-egg fusion while recognizing only the corresponding proteins, suggests functional cooperation between these homologous CRISP to ensure fertilization success. These results increase our understanding of the molecular mechanisms of gamete fusion and contribute to the development of new and safer fertility regulating methods. （Asian J Androl 2007 July; 9： 528-532）
文摘目的探讨甘精胰岛素联合格列美脲对2型糖尿病老年患者血糖控制效果及富含半胱氨酸的酸性分泌蛋白(SPARC)蛋白表达的影响.方法选取2016年1月~2018年1月在本院接受治疗的126例2型糖尿病患者为研究对象,依照随机数字表分为对照组和观察组,每组63例,对照组给予甘精胰岛素治疗,观察组采用甘精胰岛素联合格列美脲治疗,比较两组患者治疗前和治疗3个月后空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HBA1C)及SPARC水平,对比两组患者治疗效果和不良反应发生情况.结果治疗后对照组有效率为79.4%,观察组有效率为90.5%,差异有统计学意义(P<0.05);治疗前两组患者FBG、2 h PG、HBA1C和SPARC水平的差异均无统计学意义(P>0.05),治疗后两组患者各指标均降低,且观察组FBG、2 hPG、HBA1c和SPARC水平均低于对照组,差异有统计学意义(P<0.05);对照组和观察组均未出现低血糖不良反应.结论甘精胰岛素联合格列美脲对2型糖尿病老年患者血糖控制效果良好,可降低糖尿病患者胰岛素抵抗,且安全性较高.
基金American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSNIH ARRA
文摘Cardiovascular disease, nervous system disorders, and cancer in association with other diseases such as diabetes mellitus result in greater than sixty percent of the global annual deaths. These noncommunicable diseases also affect at least one-third of the population in low and middle-income countries and lead to hypertension, elevated cholesterol, malignancy, and neurodegenerative disorders such as Alzheimer's disease and stroke. With the climbing lifespan of the world's population, increased prevalence of these disorders is expected requiring the development of new therapeutic strategies against these disabling disease entities. Targeting stem cellproliferation for cardiac disease, vascular disorders, cancer, and neurodegenerative disorders is receiving great enthusiasm, especially those that focus upon SIRT1, a mammalian homologue of the yeast silent information regulator-2. Modulation of the cellular activity of SIRT1 can involve oversight by nicotinamide/nicotinic acid mononucleotide adenylyltransferase, mammalian forkhead transcription factors, mechanistic of rapamycin pathways, and cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma over-expressed gene family members that can impact cytoprotective outcomes. Ultimately, the ability of SIRT1 to control the programmed cell death pathways of apoptosis and autophagy can determine not only cardiac, vascular, and neuronal stem cell development and longevity, but also the onset of tumorigenesis and the resistance against chemotherapy. SIRT1 therefore has a critical role and holds exciting prospects for new therapeutic strategies that can offer reparative processes for cardiac, vascular, and nervous system degenerative disorders as well as targeted control of aberrant cell growth during cancer.
