Chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME) are, amongst others, characterized by exercise intolerance, pain, post exertional malaise and orthostatic intolerance. It has been shown in venous diseas...Chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME) are, amongst others, characterized by exercise intolerance, pain, post exertional malaise and orthostatic intolerance. It has been shown in venous disease and sport participation that compression stockings may improve exercise performance and reduce post exercise muscle soreness. Moreover, its use is advocated in orthostatic hypotension. Therefore, it was hypothesized that compression stockings may reduce symptomatology in CFS/ME patients. Methods: 100 patients used compression stockings class II for minimally 3 weeks and thereafter filled in a questionnaire, based on the Rand 36 physical activity questions (n = 9), whether compression stockings changed perceived symptoms or not. Moreover, 7 questions referring to prolonged standing and sitting, to recovery post exercise, muscle pain during or immediately post exercise, and to dizziness/light-headedness during or immediately post exercise, while standing and during prolonged sitting were added. Questions were scored as 1: able to perform activity much less while wearing the stockings, 2: perform activity somewhat less, 3: no perceived change in activity, 4: perform activity slightly better, 5: able to perform activity much better while wearing the stockings. Results: In patients able to answer the question, all mean scores per activity were significantly higher than 3, being no perceived change in activity while wearing the stockings. Subgroup analysis showed that patients with orthostatic intolerance reported higher effects than patients without orthostatic intolerance. Conclusion: This pilot study suggests that compression stockings may be useful to reduce symptomatology of physical activities in CFS/ME patients, especially in patients with orthostatic intolerance. Larger prospective studies with hard endpoints are warranted.展开更多
It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this toleran...It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this tolerance induction remains unknown. In this study, the response and differentiation of ovalbumin (OVA)-specific CD4+ Th cells upon exposure to tolerogenic PEG conjugate of OVA (PEG-OVA) were studied. Na?ve OVA-specific Th cells from OT-II mice were labeled with carboxyfluorescein succinimidyl ester (CFSE), transferred into histocompatible C57BL/6 mice, and then subsequently stimulated with either tolerogenic PEG-OVA or with OVA. Upon stimulation with tolerogenic PEG-OVA in vivo, these cells showed a robust proliferative response comparable to that observed by stimulation with OVA. Nevertheless, upon prolonged exposure to PEG-OVA, OVA-specific Th cells became anergic, showing a markedly reduced capacity to respond, and to produce IL-2 and other cytokines when stimulated with antigenic OVA323-339 peptide in vitro. There was also a significant reduction of the frequency of clonotypic TCR Vα2+CD4+ T cells in the spleens of OT-II mice treated with PEG-OVA. These features of response of na?ve OVA-specific Th cells upon sustained exposure to PEG-OVA were quite analogous to those reported for the same cells transferred into mice with systemic expression of the transgenic OVA gene. The highly enhanced stability in the circulation that was observed for PEG-OVA was likely the basis of its tolerogenic capacity.展开更多
The conjugation of SUMO （small ubiquitin-like modifier） to protein substrates is a reversible process （SUMOylation/deSUMOylation） that regulates plant devel- opment and stress responses. The essential metal copper...The conjugation of SUMO （small ubiquitin-like modifier） to protein substrates is a reversible process （SUMOylation/deSUMOylation） that regulates plant devel- opment and stress responses. The essential metal copper （Cu） is required for normal plant growth, but excess amounts are toxic. The SUMO E3 ligase, SIZI, and SIZ1- mediated SUMOylation function in plant tolerance to excess Cu. It is unknown whether deSUMOylation also contributes to Cu tolerance in plants. Here, we report that OTSI, a protease that cleaves SUMO from its substrate proteins, participates in Cu tolerance in Arabidopsis thaliana （Arabi- dopsis）. OTS1 loss-of-function mutants （otsl-2 and otsl-3） displayed increased sensitivity to excess Cu. Redox homeostasis and the balance between SUMOylation and deSUMOylation were disrupted in the otsl-3 mutant under excess Cu conditions, The otsl-3 mutant accumulated higher levels of Cu in both shoots and roots compared to wild type. Specific Cu-related metal transporter genes were upregu- lated due to the loss-of-function of OTS% which might explain the high Cu levels in otsl-3. These results suggest that the SUMOylation/deSUMOylation machinery is acti- vated in response to excess Cu, and modulates Cu homeostasis and tolerance by regulating both Cu uptake and detoxification. Together, our findings provide insight into the biological function and regulatory role of SUMOylation/deSUMOylation in plant tolerance to Cu.展开更多
文摘Chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME) are, amongst others, characterized by exercise intolerance, pain, post exertional malaise and orthostatic intolerance. It has been shown in venous disease and sport participation that compression stockings may improve exercise performance and reduce post exercise muscle soreness. Moreover, its use is advocated in orthostatic hypotension. Therefore, it was hypothesized that compression stockings may reduce symptomatology in CFS/ME patients. Methods: 100 patients used compression stockings class II for minimally 3 weeks and thereafter filled in a questionnaire, based on the Rand 36 physical activity questions (n = 9), whether compression stockings changed perceived symptoms or not. Moreover, 7 questions referring to prolonged standing and sitting, to recovery post exercise, muscle pain during or immediately post exercise, and to dizziness/light-headedness during or immediately post exercise, while standing and during prolonged sitting were added. Questions were scored as 1: able to perform activity much less while wearing the stockings, 2: perform activity somewhat less, 3: no perceived change in activity, 4: perform activity slightly better, 5: able to perform activity much better while wearing the stockings. Results: In patients able to answer the question, all mean scores per activity were significantly higher than 3, being no perceived change in activity while wearing the stockings. Subgroup analysis showed that patients with orthostatic intolerance reported higher effects than patients without orthostatic intolerance. Conclusion: This pilot study suggests that compression stockings may be useful to reduce symptomatology of physical activities in CFS/ME patients, especially in patients with orthostatic intolerance. Larger prospective studies with hard endpoints are warranted.
文摘It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this tolerance induction remains unknown. In this study, the response and differentiation of ovalbumin (OVA)-specific CD4+ Th cells upon exposure to tolerogenic PEG conjugate of OVA (PEG-OVA) were studied. Na?ve OVA-specific Th cells from OT-II mice were labeled with carboxyfluorescein succinimidyl ester (CFSE), transferred into histocompatible C57BL/6 mice, and then subsequently stimulated with either tolerogenic PEG-OVA or with OVA. Upon stimulation with tolerogenic PEG-OVA in vivo, these cells showed a robust proliferative response comparable to that observed by stimulation with OVA. Nevertheless, upon prolonged exposure to PEG-OVA, OVA-specific Th cells became anergic, showing a markedly reduced capacity to respond, and to produce IL-2 and other cytokines when stimulated with antigenic OVA323-339 peptide in vitro. There was also a significant reduction of the frequency of clonotypic TCR Vα2+CD4+ T cells in the spleens of OT-II mice treated with PEG-OVA. These features of response of na?ve OVA-specific Th cells upon sustained exposure to PEG-OVA were quite analogous to those reported for the same cells transferred into mice with systemic expression of the transgenic OVA gene. The highly enhanced stability in the circulation that was observed for PEG-OVA was likely the basis of its tolerogenic capacity.
基金supported by the National Transgenic Major Project of China (2016ZX08009-003-002 to H.L.)the National Natural Science Foundation of China (31600201 to H.Z+1 种基金 31470342 and 31670235 to H.L.)the National Basic Research Program of China (2015CB150100 to H.L)
文摘The conjugation of SUMO （small ubiquitin-like modifier） to protein substrates is a reversible process （SUMOylation/deSUMOylation） that regulates plant devel- opment and stress responses. The essential metal copper （Cu） is required for normal plant growth, but excess amounts are toxic. The SUMO E3 ligase, SIZI, and SIZ1- mediated SUMOylation function in plant tolerance to excess Cu. It is unknown whether deSUMOylation also contributes to Cu tolerance in plants. Here, we report that OTSI, a protease that cleaves SUMO from its substrate proteins, participates in Cu tolerance in Arabidopsis thaliana （Arabi- dopsis）. OTS1 loss-of-function mutants （otsl-2 and otsl-3） displayed increased sensitivity to excess Cu. Redox homeostasis and the balance between SUMOylation and deSUMOylation were disrupted in the otsl-3 mutant under excess Cu conditions, The otsl-3 mutant accumulated higher levels of Cu in both shoots and roots compared to wild type. Specific Cu-related metal transporter genes were upregu- lated due to the loss-of-function of OTS% which might explain the high Cu levels in otsl-3. These results suggest that the SUMOylation/deSUMOylation machinery is acti- vated in response to excess Cu, and modulates Cu homeostasis and tolerance by regulating both Cu uptake and detoxification. Together, our findings provide insight into the biological function and regulatory role of SUMOylation/deSUMOylation in plant tolerance to Cu.
文摘目的研究15 d-6°头低位卧床(HDBR)对女性立位耐力的影响。方法 15名女性青年志愿者经历15 d-6°HDBR,于卧床前1天及卧床后第1天分别接受70°被动立位测试,记录测试全程的心血管血液动力学指标,同时观察血浆肾素活性(PRA)、血管紧张素Ⅱ(ATⅡ)和去甲肾上腺素(NE)含量变化。结果经过15 d头低位卧床后,女性立位耐力不良的发生率为8/15(53.3%)。其中,晕厥前症状中止者为6/15(40.0%),立位后心动过速(POTS)中止者为2/15(13.3%)。立位刺激可引起舒张压、心率和血管总外周阻力明显增加(P<0.05),每博量和心输出量显著降低(P<0.05)。同时,15 d HDBR可显著增加安静平卧位时的舒张压和心率,并减少每博量,但对血管总外周阻力和心输出量的影响并不明显(P>0.05)。立位耐力正常和不良者的差异主要表现为心率(HR)在立位刺激后有明显的增加,组间差异明显。血液生化指标结果显示两组间NE基础水平有显著差异,但在立位刺激下的NE含量的变化幅度未有明显差别(P>0.05)。立位刺激可导致血浆中ATⅡ含量的明显升高,而15 d HDBR则可导致血浆PRA的明显减少(P<0.01)。结论经过15 d头低位卧床后,女性立位耐力不良发生率较高,且存在着不同的表现类型。
