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二乙基亚硝胺诱导雄性大鼠肝癌干细胞(CD、CD和CD)的评估及生物合成银纳米颗粒的治疗

Evaluation of hepatic cancer stem cells (CD, CD, and CD) induced by diethylnitrosamine in male rats and treatment with biologically synthesized silver nanoparticles.

作者信息

Pervez Amber, Khan Behramand, Khan Gul Nabi, Khattak Sumayya, Ali Mazhar, Mujeeb Komal, Nasib Bushra, Kim Hyung Goo, Qureshi Irfan Zia, Arshad Muhammad

机构信息

Department of Zoology, Islamia College University, Peshawar, Pakistan.

Department of Chemistry, Islamia College University, Peshawar, Pakistan.

出版信息

Mol Biol Rep. 2025 Apr 15;52(1):393. doi: 10.1007/s11033-025-10495-2.

Abstract

BACKGROUND

Cancer stem cells (CSCs) play a critical role in the initiation and heterogeneity of a variety of cancers due to their pluripotent nature and capacity for asymmetric cell division. Therefore, uncovering the carcinogens that increase the CSC population in target tissues is crucial for understanding the genesis of cancer. The therapeutic potential of Operculina turpethum (OT) derived silver nanoparticles (AgNPs) was assessed in diethylnitrosamine (DEN)-induced CSC populations; CD73+, CD44+, and CD90 + of hepatic tissues in male rats.

METHODS

Histopathology, fluorescence-activated cell sorting (FACS), and RT-qPCR were performed on the control, DEN, DEN + AgNPs, and AgNPs-treated groups. AgNPs were characterized by FTIR, EDX, XRD, and SEM.

RESULTS

AgNPs were confirmed by intense surface plasmon resonance at 425 nm. Antioxidants, the reducing sugars responsible for Ag reduction and subsequent conjugate formation with nanoparticles, were confirmed by vibrational spectra. The spherical morphology, composition, and conjugation of silver nanoparticles to phytoconstituents with partially crystalline, face-centered cubic structure were established through SEM, EDX spectrum, and XRD, respectively. Disrupted tissue architecture, cell enlargement, mild pleomorphism, and expanded central veins were observed in hepatic tissues of DEN-treated animals. However, a moderate inflammatory response was observed in the DEN + AgNPs-treated group. CSC populations were significantly increased in the DEN-treated group, but decreased with AgNPs-treatment. The mRNA expression levels of CD90, CD44, and CD73 genes were significantly up-regulated in the DEN-treated group compared to control group however, in DEN + AgNPs and AgNPs groups it were similar to control group.

CONCLUSION

All together, DEN-induced the hepatic CSC cell populations and the OT mediated AgNPs have therapeutic potential to attenuate the harmful effects of DEN. This study provides evidenced that OT-synthesised AgNPs may be considered as a therapeutic agent for liver related malignancies.

摘要

背景

癌症干细胞(CSCs)由于其多能性和不对称细胞分裂能力,在多种癌症的发生和异质性中起着关键作用。因此,揭示增加靶组织中癌症干细胞数量的致癌物对于理解癌症的发生至关重要。评估了旋花科植物盒果藤(OT)衍生的银纳米颗粒(AgNPs)对二乙基亚硝胺(DEN)诱导的雄性大鼠肝组织中癌症干细胞群体(CD73 +、CD44 +和CD90 +)的治疗潜力。

方法

对对照组、DEN组、DEN + AgNPs组和AgNPs处理组进行组织病理学、荧光激活细胞分选(FACS)和RT-qPCR检测。通过傅里叶变换红外光谱(FTIR)、能量散射X射线光谱(EDX)、X射线衍射(XRD)和扫描电子显微镜(SEM)对AgNPs进行表征。

结果

在425 nm处通过强烈的表面等离子体共振证实了AgNPs的存在。通过振动光谱证实了抗氧化剂,即负责还原银并随后与纳米颗粒形成共轭物的还原糖。分别通过扫描电子显微镜、能量散射X射线光谱和X射线衍射确定了银纳米颗粒的球形形态、组成以及与具有部分结晶面心立方结构的植物成分的共轭。在DEN处理动物的肝组织中观察到组织结构破坏、细胞肿大、轻度多形性和中央静脉扩张。然而,在DEN + AgNPs处理组中观察到中度炎症反应。在DEN处理组中癌症干细胞群体显著增加,但经AgNPs处理后减少。与对照组相比,DEN处理组中CD90、CD44和CD73基因的mRNA表达水平显著上调,然而,在DEN + AgNPs组和AgNPs组中,其与对照组相似。

结论

总之,DEN诱导了肝癌症干细胞群体,而OT介导的AgNPs具有减轻DEN有害影响的治疗潜力。本研究提供的证据表明,OT合成的AgNPs可被视为治疗肝脏相关恶性肿瘤的药物。

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