Activation of the Notch signaling pathway disturbs the CD4+/CD8+, Th17/Treg balance in rats with experimental autoimmune uveitis

Objective and design

The present study aimed to investigate the relationship between the disturbed balance of CD4⁺/CD8⁺, Th17/Treg and the activation of the Notch signaling pathway in experimental autoimmune uveitis (EAU).

Methods

An EAU rat model was induced in Lewis rats, and pathology analysis was performed by hematoxylin and eosin (H&E) staining. CD4⁺, CD8⁺, Th17, and Treg levels in spleen, lymph nodes and eye tissues were determined by flow cytometry. Meanwhile, the expression of Notch1, DLL4, IL-10, and IL-17 was determined by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the inhibitory effect of N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT) on Th17 differentiation by Notch signaling in vitro was further investigated using T lymphocytes from EAU rats on day 12 post-immunization by flow cytometry.

Results

The pathological results showed that inflammatory cell infiltration occurred in ocular tissues in EAU rats. The CD4⁺/CD8⁺ and Th17/Treg ratios in EAU rats were apparently higher than those in normal control individuals. Q-PCR and ELISA analyses indicated the expression of Notch1, DLL4, IL-10, and IL-17 in EAU rats gradually increased on day 6 after immunization, peaked on day 12, and then gradually decreased. The dynamic trends in Notch1 and DLL4 expression in EAU rats were identical to those of CD4⁺/CD8⁺ and Th17/Treg levels. DAPT can significantly inhibit the activation of Notch signaling, decrease Th17 cell differentiation, and attenuate the level of the Th17 cell lineage, contributing to the balance of the Th17/Treg ratio.

Conclusion

The activation of the Notch signaling pathway can regulate Th17 and Treg cell differentiation, disrupt the CD4⁺/CD8⁺ and Th17/Treg balance, and aggravate the severity of EAU; inactivation of the Notch signaling pathway contributes to the CD4⁺/CD8⁺ and Th17/Treg balance in EAU rats. Our findings highlighted that the dynamic change in the CD4⁺/CD8⁺ and Th17/Treg ratio was consistent with the expression trend of Notch signaling in EAU rats, suggesting that Notch signaling may be a potentially important therapeutic target in clinical practice.

     

直接冠状动脉内支架植入术的可行性研究

目的 :评价直接冠状动脉 (冠脉 )内支架植入术的安全性和可行性。方法 :对 1999年 12月～ 2 0 0 0年 6月接受冠脉内支架植入术的 171例患者中 ,孤立性、狭窄程度≤ 90 %、参考直径≥ 2 .5mm、长度≤ 18mm ;无明显的钙化、扭曲和成角 ,非完全闭塞和分叉处病变者 5 6例行直接冠脉内支架植入术。观察住院期和术后 3个月随访期内不良心脏事件的发生率。结果 :5 6例的 6 0处病变成功 5 5处 (91.7% ) ;1处因支架未能通过狭窄处而改行球囊预扩张后的支架植入术 ,1处在支架植入后因远端血管发生撕裂而需再植入 1个支架 ,3例因支架植入后冠脉造影显示支架扩张不满意而再用高压球囊扩张。住院期和术后随访期内无心源性死亡、心肌梗死、急诊冠脉旁路术发生 ;9例行冠脉造影复查 ,其中 2例因显示再狭窄而行再次经皮腔内冠脉成形术治疗。与经球囊导管预扩张后行冠脉内支架植入术相比 ,直接冠脉内支架植入术费用降低 2 9% ,造影剂用量减少 2 7% ,手术操作和X线照射时间缩短 2 6 %和 2 5 %。结论 :直接冠脉内支架植入术在经选择的病变中安全可行 ,并可降低手术费用 ,减少X线照射。     

参麦合剂对兔干眼症模型泪液分泌及眼表结构的影响

目的：探索参麦合剂对兔干眼症模型泪液分泌及眼表结构的影响。方法：将30只健康新西兰大白兔随机分为空白对照组、实验对照组、药物治疗组。制作干眼动物模型后,各组给予相应治疗。治疗前和治疗后第7、14、21、28 d分别测定Schirmer试验值,BUT值、眼表荧光素染色（FL）、结膜印记细胞学检查（CIC）,观察眼表泪膜状态和细胞学变化。治疗28 d后,每组随机选取5只动物,处死后剪下角结膜组织,行角结膜石蜡切片光镜观察。结果：药物治疗组用药14 d后,Schirmer值及BUT值均较其他两组明显增加（P〈0.01）;结膜细胞印迹学检查发现药物治疗组结膜杯状细胞数量较其他两组明显增多;光镜检查发现药物治疗组与其他两组相比,部分结膜上皮层数增多、杯状细胞增多。结论：参麦合剂能明显增加兔干眼症模型泪液分泌、改善泪膜稳定性和眼表细胞结构。     

Retraction: Enhanced adsorption of ionizable aromatic compounds on humic acid-coated carbonaceous adsorbents

Retraction of ‘Enhanced adsorption of ionizable aromatic compounds on humic acid-coated carbonaceous adsorbents’ by Yubing Sun et al., RSC Adv., 2012, 2, 10359–10364, DOI: 10.1039/C2RA21713A.

The Royal Society of Chemistry, with the agreement of the named authors, hereby wholly retracts this RSC Advances article due to concerns with the reliability of the data in the published article.Repeating fragments can be observed in the XRD spectrum for GONs in Fig. 1C, which indicates that it has been manipulated. In addition, there are unexpected similarities in the baseline of the XRD data presented for MWCNTs and AC (Fig. 1C) in the 32.5–40° and 45–57.5° regions.Given the significance of the concern about the validity of the data, the findings presented in this paper are no longer reliable.Signed: Yubing Sun, Dadong Shao, Guixia Zhao, Shubin Yang and Xiangke WangDate: 27^th March 2020Changlun Chen, Jiaxing Li and Xiaoli Tan were contacted but did not respond.Retraction endorsed by Laura Fisher, Executive Editor, RSC Advances     

Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats

Carbon monoxide (CO) poisoning is one of the leading causes of toxicity‐related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC‐1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and thioredoxin‐1 (Trx‐1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle‐dose or high‐dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.     

急性心肌梗死患者初期支架植入和rt-PA静脉溶栓加补救支架植入对比研究

目的比较急性心肌梗死(AMI)患者冠状动脉内初期支架植入和静脉rt-PA溶栓加补救支架植入治疗的临床疗效.方法 98例首次AMI患者随机给以冠状动脉内初期支架植入(初期支架组48例)和静脉rt-PA溶栓加补救支架植入(溶栓加支架组50例).所有患者行急诊冠状动脉造影以TIMI血流分级法判断梗死相关冠状动脉(IRA)开通情况.记录住院期心脏事件;出院前用二维超声心动图测定两组患者左心室舒张末期和收缩末期容量并推算左心室射血分数(LVEF).结果急诊冠状动脉造影显示支架组47例(97.91%)溶栓加支架组50例(100%)IRA血流TIMI 2-3级,但前者IRA前向血流TIMI 3级者明显增多(分别为93.8%和60.0%,P=0.0001).两组患者住院期死亡率和心脏事件相似,但出院前超声心动图显示支架组LVEF(62.01%±14.03%)高于溶栓加支架组(50.01%±132%),P=0.0001.结论与静脉rt-PA溶栓加补支架治疗相比,AMI初期支架植入可更好改善急性期心肌再灌注,并减少患者住院期心功能减退.     

主动脉球囊反搏术对急性心肌梗死并发心源性休克患者冠状动脉介入术后C反应蛋白水平的影响

目的:评价急性心肌梗死(AMI) 并发心源性休克患者行急诊介入治疗(PCI)时主动脉球囊反搏术(IABP)对术后C反应蛋白(CRP)水平的影响.方法:43例在IABP支持下行急诊PCI的并发心源性休克的AMI患者为IABP组,将同期行急诊PCI但没有行IABP支持的合并心源性休克的AMI患者48例设为对照组;入院后分别测定入院时以及第3天、第7天的CRP水平;比较2组PCI术后TnI峰值,术后2周、3个月的左室射血分数,随访患者术后3个月的病死率.结果:2组患者入院时的CRP水平无明显差异,而第3天、第7天的CRP水平IABP组明显低于对照组[(80.3±42.8):(98.9±31.6) mg/L , (70.6±34.3):(85.8±25.8 )mg/L;均P<0.05];IABP组患者术后TNI峰值明显低于对照组[(21.6±4.1):(23.7±4.6)ng/ml, P<0.05],术后2周、3个月的左室射血分数较对照组明显改善[(44.7±7.3)%:(40.5±6.2)%,( 45.1±6.6)%:(40.7±4.4)%;均P<0.05];而IABP组术后3个月内的病死率明显降低(P<0.05).结论:对并发心源性休克的AMI患者行急诊PCI术同时采用IABP支持治疗能明显降低术后CRP水平,并能有效地改善左室功能和降低术后3个月内病死率.     

急性颅脑损伤病人血浆脂质过氧化物含量及红细胞超氧化物歧化酶活性变化的初步观察

本文报道30例急性颅脑损伤病人伤后不同时间血浆 LPO 含量及红细胞 SOD 活性的变化,并初步探讨其机制。结果表明,脑损伤后14天内,机体自由基水平明显升高,且以伤后第3天为最高,伤后部分时间红细胞 SOD 活性明显低于正常。损伤程度与自由基含量及红细胞SOD 活性之间无明显相关。按目前常规使用的甘露醇及糖皮质激素的方法,尚不足以有效地清除脑损伤后产生的过多的自由基。