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基于血清和唾液弓形虫的虫体诱导炎症的机制和靶向治疗的计算机研究

In silico study to explore the mechanism of Toxoplasma-induced inflammation and target therapy based on sero and salivary Toxoplasma.

机构信息

Department of Microbiology & Immunology, Faculty of Dentistry, Pharos University in Alexandria, Alexandria, Egypt.

Department of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria, Egypt.

出版信息

Sci Rep. 2024 Jun 13;14(1):13600. doi: 10.1038/s41598-024-63735-z.

DOI:10.1038/s41598-024-63735-z
PMID:38866852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169245/
Abstract

We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.

摘要

我们旨在评估高危人群的唾液和血清弓形虫免疫球蛋白流行率,并评估针对 TgERP 的药物对接。这是一项在亚历山大大学医院门诊进行的横断面研究。2022 年 9 月至 2023 年 11 月期间共纳入 192 名参与者。通过 ELISA 法在血清和唾液中测定抗弓形虫 IgG 和 IgM。一项计算机模拟研究检查了 TgERP 与促炎细胞因子受体、抗炎细胞因子、细胞周期进展调节蛋白、增殖标志物和核膜完整性相关蛋白 lamin B1 的蛋白-蛋白相互作用(PPIs)。我们的研究结果表明,血清(66.1%)和唾液(54.7%)中均检测到抗 T. gondii IgG,两种样本中均有 2.1%的 IgM 呈阳性。唾液 IgG 的灵敏度为 75.59%,特异性为 86.15%,PPV 为 91.40%,NPV 为 64.40%,准确性为 79.17%,与血清 IgG 有良好的一致性。另一方面,检测唾液 IgM 的灵敏度、特异性、PPV、NPV 和准确性分别为 75.0%、99.47%、75.0%、99.47%和 98.96%。AUC 为 0.859,表明具有良好的鉴别力。所研究的合成药物和天然产物可以针对 TgERP 与 LB1 和 Ki67 相同结合界面上的特定氨基酸残基,从而阻止它们的相互作用。因此,唾液样本可能是一种很有前途的诊断方法。研究药物可以对抗 TgERP 的促炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/5379995bfede/41598_2024_63735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/f37afad0b81b/41598_2024_63735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/fcb3f12e63f2/41598_2024_63735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/4a1844210482/41598_2024_63735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/5379995bfede/41598_2024_63735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/f37afad0b81b/41598_2024_63735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/fcb3f12e63f2/41598_2024_63735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/4a1844210482/41598_2024_63735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b84/11169245/5379995bfede/41598_2024_63735_Fig4_HTML.jpg

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