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评估纳米环孢素A在溃疡性结肠炎小鼠模型中的疗效:一项荟萃分析。

Evaluating the efficacy of nano-cyclosporine A in mice model of ulcerative colitis: a meta-analysis.

作者信息

Mehreen Aqsa, Batool Faiza, Awan Uzma Azeem, Shabnam Nadia, Haider Adnan, Aslam Shaista, Ghazanfar Madiha, Ud-Din Fakhar, Siddique Muhammad Irfan, Naeem Muhammad, Saeed Rida Fatima

机构信息

Department of Biological Sciences, National University of Medical Science, Rawalpindi, Punjab, Pakistan.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-E-Azam University, Islamabad, Pakistan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul;398(7):8813-8823. doi: 10.1007/s00210-025-03797-6. Epub 2025 Jan 28.

Abstract

Cyclosporine A is an immunosuppressive drug used in clinics to treat steroid-refractory ulcerative colitis (UC). However, due to its side effects, researchers are evaluating novel drug delivery-based treatment options. Nanoparticles-based cyclosporine (Nano-CSA) offers a promising option for the treatment of UC, and various in vivo studies on animals have been conducted. This meta-analysis was performed to clarify the effects of using Nano-CSA based formulations in the mouse UC model. A systemic literature search was conducted on five different electronic databases (ScienceDirect, PubMed, Embase, PMC, and Cochrane) to search studies conducted between the timeline of 2016 and 2024. The search terms include "nanoparticles," "ulcerative colitis," and "cyclosporine A." The primary outcomes include histological scores and colon length. The Nano-CSA effects on UC were assessed by analyzing the difference between the treatment and untreated control groups, through the use of standardized mean difference (SMD). A fixed effect model was used where heterogeneity was less than 50%, for higher heterogeneity random effect model was used. The total number of included studies for this systematic review was six, from which meta-analysis was performed on four studies. In all the studies, dextran sulfate sodium (DSS) was used to induce UC, except for one study that used TNBS (2,4,6-trinitrobenzene sulfonic acid) for UC induction. Four studies measured histological score and colon length, and two studies measured other secondary outcomes (IL-6, TNF-α, and MPO (myeloperoxidase activity)). Meta-analysis results have demonstrated that there is an increase in colon length with SMD of 6.879 and a decrease in histological score with SMD of 10.956 in the Nano-CSA treated group. There was also a decrease in the levels of pro-inflammatory cytokines including TNF-α and IL-6 in the Nano-CSA treated group and no significant difference in MPO activity of the two groups. Colon length, MPO activity, and TNF-α expression demonstrated heterogeneity values of 84.638, 86.113, and 51.567 respectively. The results of this meta-analysis have demonstrated the potential therapeutic efficiency of Nano-CSA for the treatment of UC in mice models. Further research is required in order to explore nano-based novel therapeutics options for UC treatment in other models as well as with human applications.

摘要

环孢素A是一种临床上用于治疗激素难治性溃疡性结肠炎(UC)的免疫抑制药物。然而,由于其副作用,研究人员正在评估基于新型药物递送的治疗方案。基于纳米颗粒的环孢素(Nano-CSA)为UC治疗提供了一个有前景的选择,并且已经在动物身上进行了各种体内研究。进行这项荟萃分析是为了阐明在小鼠UC模型中使用基于Nano-CSA的制剂的效果。对五个不同的电子数据库(ScienceDirect、PubMed、Embase、PMC和Cochrane)进行了系统的文献检索,以查找2016年至2024年期间进行的研究。检索词包括“纳米颗粒”、“溃疡性结肠炎”和“环孢素A”。主要结果包括组织学评分和结肠长度。通过使用标准化均值差(SMD)分析治疗组与未治疗对照组之间的差异,评估Nano-CSA对UC的影响。当异质性小于50%时使用固定效应模型,对于更高的异质性则使用随机效应模型。该系统评价纳入的研究总数为六项,从中对四项研究进行了荟萃分析。在所有研究中,除了一项使用三硝基苯磺酸(TNBS)诱导UC的研究外,均使用葡聚糖硫酸钠(DSS)诱导UC。四项研究测量了组织学评分和结肠长度,两项研究测量了其他次要结果(白细胞介素-6、肿瘤坏死因子-α和髓过氧化物酶(MPO)活性)。荟萃分析结果表明,Nano-CSA治疗组的结肠长度增加,SMD为6.879,组织学评分降低,SMD为10.956。Nano-CSA治疗组中促炎细胞因子包括肿瘤坏死因子-α和白细胞介素-6的水平也有所降低,两组的MPO活性无显著差异。结肠长度、MPO活性和肿瘤坏死因子-α表达的异质性值分别为84.638、86.113和51.567。这项荟萃分析的结果证明了Nano-CSA在小鼠模型中治疗UC的潜在治疗效果。需要进一步研究以探索在其他模型以及人类应用中基于纳米的UC治疗新方法。

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