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- Gamasaee, Niusha Abbasi, et al.
(författare)
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The effects of nickel oxide nanoparticles on structural changes, heme degradation, aggregation of hemoglobin and expression of apoptotic genes in lymphocytes.
- 2020
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : Informa UK Limited. - 0739-1102 .- 1538-0254. ; 38:12, s. 3676-3686
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Tidskriftsartikel (refereegranskat)abstract
- Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24 hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.
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| 2. |
- Majid, Abbasi, et al.
(författare)
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miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells via Targeting CRKL
- 2020
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X .- 2296-889X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal expressions of microRNAs are involved in growth and progression of human cancers including hepatocellular carcinoma (HCC). An adaptor protein CRKL plays a pivotal role in HCC growth, whereas miR-124-3p downregulation is associated with clinical stage and the poor survival of patients. However, the relationship between miR-124-3p and CRKL and the molecular mechanisms through which they regulate HCC metastasis remains unclear. In the current work, we explored miR-124-3p and its correlation with CRKL expression in HCC patient tissues. We found that miR-124-3p deficiency is inversely co-related with CRKL overexpression in tumorous tissues of HCC patients, which was also consistent in HCCLM3 and Huh7 HCC cell lines. Target validation data shows that miR-124-3p directly targets CRKL. The overexpression of miR-124-3p reverses the CRKL expression at both mRNA and protein levels and inhibits the cell development, migration, and invasion. Mechanistic investigations showed that CRKL downregulation suppresses the ERK pathway and EMT process, and concomitant decrease in invasion and metastasis of HCC cells. The expressions of key molecules in the ERK pathway such as RAF, MEK, ERK1/2, and pERK1/2 and key promoters of EMT such as N-cadherin and vimentin were downregulated, whereas E-cadherin, a key suppression indicator of EMT, was upregulated. MiR-124-3p-mediated CRKL suppression led to BAX/BCL-2 increase and C-JUN downregulation, which inhibited the cell proliferation and promoted the apoptosis in HCC cells. Collectively, our data illustrates that miR-124-3p acts as an important tumor-suppressive miRNA to suppress HCC carcinogenesis through targeting CRKL. The miR-124-3p-CRKL axial regulated pathway may offer valuable indications for cancer research, diagnosis, and treatment.
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