Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

注射用肉毒毒素制剂及其研发进展

肉毒毒素(Botulinum Toxin,BoNT)已成为现代医学最具多用途的治疗药物之一。通过将肉毒毒素注射到特定过度活动的肌肉中,可以阻断神经和肌肉之间的信号传导,引起肌肉的松弛性麻痹,从而达到治疗的功效。从业者应熟悉各类产品的特性,以实现安全有效地使用。除了已经上市的众多肉毒毒素产品外,目前还在开发其他新型制剂,这些产品将会进一步扩大肉毒毒素的适用范围,以及给患者提供更多的选择。     

基于网络药理学的济脉通片降压机制研究

目的 采用网络药理学阐明济脉通片多成分-多靶点-多途径的作用理念，为进一步研究济脉通片降压药效物质基础和机制提供一定理论参考。方法 通过TCMSP数据库，结合口服利用度（≥ 30%）和类药性分析（≥ 0.18）参数，筛选济脉通片的活性成分；通过Drugbank和TCMSP数据库进行靶点预测分析；通过GENCARD数据库筛选出高血压疾病相关基因；结合DAVID和KEGG数据库进行GO分析和通路分析；使用Cystoscope软件构建"化合物-靶点-作用通路"网络图。结果 经筛选后得到济脉通片的33个化合物，148个潜在靶基因并映射到了223条信号通路，其中31条信号通路与高血压的发生发展密切相关，其中AGE-RAGE signaling pathway in diabetic complications、PI3K-Akt signaling pathway、TNFsignaling pathway、Adrenergic signaling in cardiomyocytes和Focal adhesion为重要的通路枢纽。结论 济脉通片主要通过多成分、多靶点、多通路调节血管内皮功能、炎症反应、钙钠离子转运、糖脂代谢等参与血管舒张、改善炎症、调节机体代谢、调节离子转运等而产生降压作用。     

膝痹宁对膝骨关节炎模型大鼠滑膜纤维化的影响

目的观察膝痹宁对膝骨关节炎(KOA)模型大鼠滑膜纤维化的影响。方法大鼠分为空白组、KOA组、膝痹宁组;KOA组、膝痹宁组造模。分别在膝痹宁灌胃治疗的第1、14、28、42、56天测量各组大鼠的膝关节横径;第56天处死大鼠提取滑膜组织,解剖学观察滑膜组织形态;天狼星红染色评估滑膜组织胶原沉积情况;WB和PCR检测纤维化标记物生长转化因子-β(TGF-β)、Ⅰ型胶原α1链(COL1α1)、金属蛋白酶抑制剂1(TIMP1)的蛋白和基因表达。结果膝痹宁用药14天,28天时,膝关节横径变化并不显著,但膝痹宁用药42天,56天时,膝关节横径则较KOA模型明显减小,差异具有统计学意义(P<0.05);用药56天后对大鼠进行膝关节解剖学观察,KOA大鼠滑膜组织较正常大鼠有一定程度的增厚、充血、欠规则;而上述表现在膝痹宁大鼠有所减轻;天狼星红染色显示膝痹宁用药大鼠滑膜组织胶原沉积较少;纤维化标记指标物TGF-β、COL1α1、TIMP1的基因和蛋白表达在膝痹宁组均较KOA组降低,差异具有统计学意义(P<0.05)。结论膝痹宁对能有效减轻KOA滑膜纤维化,以“温经活血”立法的中药复方对组织纤维化具有良性干预效应。     

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.     

Effect of group reminiscence therapy on depression and perceived meaning of life of veterans diagnosed with dementia at veteran homes

ABSTRACT

Most senior veterans who live in veteran homes in Taiwan have few interpersonal relationships. Aging is often accompanied by solitude and illness, which causes senior veterans to doubt the meaning of life and to lose confidence in the value of life. This study tested the effectiveness of a group reminiscence therapy protocol on the depression and meaning of life among elderly institutionalized veterans. A quasi-experimental design was applied. A convenience sample of older adults was drawn from two veteran homes in southern Taiwan. Participants were assigned to intervention or control groups based on the veterans' homes they attended. The participants in the intervention group carried out group reminiscence therapy for 8 weeks in addition to their daily activities. The participants in the comparison group maintained their daily activities. Both groups were evaluated using the GDS-SF and MLS scale including two aspects of depression mood and meaning of life in weeks 1 and 8. The overall life satisfaction increased significantly over time for the intervention group compared to the comparison group from week 1 to week 8. The group reminiscence therapy programs showed promising effects in improving the depression and meaning of life of older veterans living in veteran homes.