Beheshtizadeh Nima, Salimi Alireza, Golmohammadi Mahsa, Ansari Javad Mohajer, Azami Mahmoud
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
BMC Chem. 2023 Jun 8;17(1):52. doi: 10.1186/s13065-023-00969-4.
One of the most notable required features of wound healing is the enhancement of angiogenesis, which aids in the acceleration of regeneration. Poor angiogenesis during diabetic wound healing is linked to a shortage of pro-angiogenic or an increase in anti-angiogenic factors. As a result, a potential treatment method is to increase angiogenesis promoters and decrease suppressors. Incorporating microRNAs (miRNAs) and small interfering RNAs (siRNAs), two forms of quite small RNA molecules, is one way to make use of RNA interference. Several different types of antagomirs and siRNAs are now in the works to counteract the negative effects of miRNAs. The purpose of this research is to locate novel antagonists for miRNAs and siRNAs that target multiple genes to promote angiogenesis and wound healing in diabetic ulcers.In this context, we used gene ontology analysis by exploring across several datasets. Following data analysis, it was processed using a systems biology approach. The feasibility of incorporating the proposed siRNAs and miRNA antagomirs into polymeric bioresponsive nanocarriers for wound delivery was further investigated by means of a molecular dynamics (MD) simulation study. Among the three nanocarriers tested (Poly (lactic-co-glycolic acid) (PLGA), Polyethylenimine (PEI), and Chitosan (CTS), MD simulations show that the integration of PLGA/hsa-mir-422a is the most stable (total energy = -1202.62 KJ/mol, Gyration radius = 2.154 nm, and solvent-accessible surface area = 408.416 nm). With values of -25.437 KJ/mol, 0.047 nm for the Gyration radius, and 204.563 nm for the SASA, the integration of the second siRNA/ Chitosan took the last place. The results of the systems biology and MD simulations show that the suggested RNA may be delivered through bioresponsive nanocarriers to speed up wound healing by boosting angiogenesis.
伤口愈合最显著的必要特征之一是血管生成的增强，这有助于加速再生。糖尿病伤口愈合过程中血管生成不良与促血管生成因子短缺或抗血管生成因子增加有关。因此，一种潜在的治疗方法是增加血管生成促进剂并减少抑制剂。引入微小RNA（miRNA）和小干扰RNA（siRNA）这两种相当小的RNA分子形式，是利用RNA干扰的一种方式。目前有几种不同类型的抗miRNA寡核苷酸和siRNA正在研发中，以对抗miRNA的负面影响。本研究的目的是寻找针对多个基因的新型miRNA和siRNA拮抗剂，以促进糖尿病溃疡中的血管生成和伤口愈合。在这种情况下，我们通过探索多个数据集进行基因本体分析。数据分析后，采用系统生物学方法进行处理。通过分子动力学（MD）模拟研究，进一步研究了将所提出的siRNA和miRNA拮抗剂整合到用于伤口递送的聚合物生物响应纳米载体中的可行性。在测试的三种纳米载体（聚乳酸-乙醇酸共聚物（PLGA）、聚乙烯亚胺（PEI）和壳聚糖（CTS））中，MD模拟表明PLGA/hsa-mir-422a的整合最稳定（总能量=-1202.62 KJ/mol，回转半径=2.154 nm，溶剂可及表面积=408.416 nm）。第二个siRNA/壳聚糖的整合以-25.437 KJ/mol的值、0.047 nm的回转半径和204.563 nm的溶剂可及表面积排在最后。系统生物学和MD模拟的结果表明，所建议的RNA可以通过生物响应纳米载体递送，以通过促进血管生成来加速伤口愈合。
