Farahani Narges Nodeh, Kalani Behrooz Sadeghi, Monavari Seyed Hamidreza, Mirkalantari Shiva, Montazer Fatemeh, Sholeh Mohammad, Javanmard Zahra, Irajian Gholamreza
Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Iran J Microbiol. 2021 Jun;13(3):360-371. doi: 10.18502/ijm.v13i3.6399.
causes several gastrointestinal diseases, including asymptomatic gastritis, chronic peptic ulcer, duodenal ulcer, lymphoma of the mucosa-associated lymphoid tissue (MALT), and gastric adenocarcinoma. In recent years, failure to eradicate infections has become an alarming problem for physicians. It is now clear that the current treatment strategies may become ineffective, necessitating the development of innovative antimicrobial compounds as alternative treatments.
In this experimental study, a cell-penetrating peptide-conjugated peptide nucleic acid (CPP-PNA) was used to target the expression. expression was evaluated using RT-qPCR assay after treatment by the CPPPNA in cell culture and animal model. Additionally, immunogenicity and toxicity of the CPP-PNA were assessed in both cell culture and animal models.
Our analysis showed that mRNA levels reduced in -infected HT29 cells after treatment with CPPPNA in a dose-dependent manner. Also, expression in bacterial RNA extracted from stomach tissue of mice treated with PNA was reduced compared to that of untreated mice. The expression of inflammatory cytokines also decreased in cells and tissue of -infected mice after PNA treatment. The tested CPP-PNA showed no significant adverse effects on cell proliferation of cultured cells and no detectable toxicity and immunogenicity were observed in mice.
These results suggest the effectiveness of CPP-PNA in targeting CagA for various research and therapeutic purposes, offering a potential antisense therapy against infections.
引发多种胃肠道疾病,包括无症状性胃炎、慢性消化性溃疡、十二指肠溃疡、黏膜相关淋巴组织淋巴瘤(MALT)以及胃腺癌。近年来,根除感染失败已成为医生们面临的一个令人担忧的问题。目前很明显,当前的治疗策略可能会失效,因此需要开发新型抗菌化合物作为替代治疗方法。
在这项实验研究中,一种细胞穿透肽偶联的肽核酸(CPP-PNA)被用于靶向表达。在细胞培养和动物模型中用CPPPNA处理后,使用RT-qPCR测定法评估表达情况。此外,在细胞培养和动物模型中评估了CPP-PNA的免疫原性和毒性。
我们的分析表明,用CPPPNA处理后,感染幽门螺杆菌的HT29细胞中的mRNA水平呈剂量依赖性降低。而且,与未处理的小鼠相比,用PNA处理的小鼠胃组织中提取的细菌RNA中的表达降低。PNA处理后,感染幽门螺杆菌的小鼠的细胞和组织中炎性细胞因子的表达也降低。所测试的CPP-PNA对培养细胞的细胞增殖没有显著不良影响,并且在小鼠中未观察到可检测到的毒性和免疫原性。
这些结果表明CPP-PNA在针对各种研究和治疗目的靶向CagA方面是有效的,为抗幽门螺杆菌感染提供了一种潜在的反义疗法。