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Sinomenine hydrochloride loaded thermosensitive liposomes combined with microwave hyperthermia for the treatment of rheumatoid arthritis.

盐酸青藤碱热敏脂质体联合微波热疗治疗类风湿关节炎

  • 影响因子:4.35
  • DOI:10.1016/j.ijpharm.2019.119001
  • 作者列表:"Shen Q","Zhang X","Qi J","Shu G","Du Y","Ying X
  • 发表时间:2020-02-25
Abstract

:The conventional medications are still facing a huge challenge for the treatment of rheumatoid arthritis (RA). Thus, looking for an effective therapy of RA has became an urgent issue nowadays. In this study, a novel thermosensitive liposome loaded with sinomenine hydrochloride (SIN-TSL) was developed by a pH gradient method. The SIN-TSL had a mean particle size of around 100 nm, and an high entrapment efficiency and drug loading capacity. The results also suggested that SIN-TSL had a thermosensitive drug release behaviour, with the drug release rate at 43 °C was much faster than the one at 37 °C. The SIN-TSL could be effectively taken up by lipopolysaccharide-activated HUVECs, without any cytotoxicity was observed. In addition, both in vitro and in vivo studies indicated that the SIN-TSL combined with microwave hyperthermia exhibited superior anti-rheumatoid arthritis effect. Overall, these results suggest that SIN-loaded thermosensitive liposomes combined with microwave hyperthermia could provide an optional strategy for alleviating the clinical symptoms of RA.

摘要

传统的药物治疗类风湿关节炎 (RA) 仍然面临着巨大的挑战。因此,寻找一种有效的 RA 治疗方法已成为当今迫切需要解决的问题。本研究采用 pH 梯度法研制了一种新型载盐酸青藤碱温敏脂质体 (SIN-TSL)。SIN-TSL 的平均粒径约为 100 nm,包封率和载药量均较高。结果还表明,SIN-TSL 具有温敏释药行为,43 ℃ 时的释药速率比 37 ℃ 时快得多。SIN-TSL 可被脂多糖激活的 HUVECs 有效摄取,无任何细胞毒性。此外,体外和体内研究均表明,SIN-TSL 联合微波热疗显示出优越的抗类风湿关节炎作用。总之,这些结果表明,负载 SIN 的热敏脂质体联合微波热疗可以为缓解 RA 的临床症状提供一种可选的策略。

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发表时间:2020-01-29
来源期刊:Autoimmunity
DOI:10.1080/08916934.2019.1710831
作者列表:["Gomes da Silva IIF","Lima CAD","Monteiro MLA","Barboza DASP","Rushansky E","Mariano MHQA","Sandrin-Garcia P","de Souza PRE","Maia MMD"]

METHODS:Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in and genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92;  = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index ( = .021) and rs2430561 with DAS28 ( = .029) and CDAI ( = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index  < .001) and ESR ( = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ ( = 5.497;  < .001) and ESR ( = 2.727;  = .032)). Our analysis indicated that in the studied population +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.

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影响因子:1.64
发表时间:2020-01-29
DOI:10.1080/13813455.2020.1716810
作者列表:["Fattah SA","Abdel Fattah MA","Mesbah NM","Saleh SM","Abo-Elmatty DM","Mehanna ET"]

METHODS:ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

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影响因子:9.18
发表时间:2020-01-29
DOI:10.1136/annrheumdis-2019-216539
作者列表:["Emery P","Horton S","Dumitru RB","Naraghi K","van der Heijde D","Wakefield RJ","Hensor EMA","Buch MH"]

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