Background: Recently, nanomaterials have moved into biological and medicinal implementations like cancer therapy. Therefore, before clinical trials, their binding to plasma proteins like human serum albumin (HSA) and their cytotoxic effects against normal and cancer cell lines should be addressed. Methods: Herein, the interaction of magnesium oxide nanoparticles (MgO NPs) with HSA was studied by means of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and docking studies. Afterwards, the cytotoxic impacts of MgO NPs on human leukemia cell line (K562) and peripheral blood mononucleated cells (PBMCs) were evaluated by MTT and flow cytometry assays to quantify reactive oxygen species (ROS) generation and apoptosis. Results: It was demonstrated that MgO NPs spontaneously form a static complex with HSA molecules through hydrophobic interactions. Docking study based on the size of NPs demonstrated that different linkages can be established between MgO NPs and HSA. The CD investigation explored that MgO NPs did not alter the secondary structure of HSA. Cellular studies revealed that MgO NPs induced cytotoxicity against K562 cell lines, whereas no adverse effects were detected on PBMCs up to optimum applied concentration of MgO NPs. It was exhibited that ROS production mediated by IC50 concentrations of MgO NPs caused apoptosis-associated cell death. The pre-incubation of K562 with ROS scavenger (curcumin) inhibited the impact of MgO NPs -based apoptosis on cell fate, revealing the upstream effect of ROS in our system. Conclusion: In summary, MgO NPs may exhibit strong plasma distribution and mediate apoptosis by ROS induction in the cancer cell lines. These data demonstrate a safe aspect of MgO NPs on the proteins and normal cells and their application as a distinctive therapeutic approach in the cancer treatment.

Aim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. Methods: Herein, the interaction of as-synthesized Co₃O₄ NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co₃O₄ NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co₃O₄ NPs against three pathogenic bacteria were disclosed by antibacterial assays. Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co₃O₄ NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of − 33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co₃O₄ NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co₃O₄ NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co₃O₄ NPs can stimulate a promising antibacterial effect against pathogenic bacteria. Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.

Aim: It has been indicated that NPs may change the amyloidogenic steps of proteins and relevant cytotoxicity. Therefore, this report assigned to explore the impact of ZVFe NPs on the amyloidogenicity and cytotoxicity of α-synuclein as one of the many known amyloid proteins. Methods: The characterization of α-synuclein at amyloidogenic condition either alone or with ZVFe NPs was carried out by fluorescence, CD, UV-visible spectroscopic methods, TEM study, docking, and molecular modeling. The cytotoxicity assay of α-synuclein amyloid in the absence and presence of ZVFe NPs was also done by MTT, LDH, and flow cytometry analysis. Results: ThT fluorescence spectroscopy revealed that ZVFe NPs shorten the lag phase and accelerate the fibrillation rate of α-synuclein. Nile red and intrinsic fluorescence spectroscopy, CD, Congo red adsorption, and TEM studies indicated that ZVFe NP increased the propensity of α-synuclein into the amyloid fibrillation. Molecular docking study revealed that hydrophilic residues, such as Ser-9 and Lys-12 provide proper sites for hydrogen bonding and electrostatic interactions with adsorbed water molecules on ZVFe NPs, respectively. Molecular dynamics study determined that the interacted protein shifted from a natively discorded conformation toward a more packed structure. Cellular assay displayed that the cytotoxicity of α-synuclein amyloid against SH-SY5Y cells in the presence of ZVFe NPs is greater than the results obtained without ZVFe NPs. Conclusion: In conclusion, the existence of ZVFe NPs promotes α-synuclein fibrillation at amyloidogenic conditions by forming a potential template for nucleation, the growth of α-synuclein fibrillation and induced cytotoxicity.

Alzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets.