Objective: MCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line. Materials and methods: MCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining. Results: The percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05). Conclusion: Metformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.

In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1 and Tp53, and apoptosis in primary breast cancer cells (PBCCs). PBCCs were treated with two doses of metformin (0 mM, 25 mM). Proliferation was determined by BrdU assay. Real-time PCR was used to assess AMPK-alpha, cyclin D1, and Tp53 gene expressions; apoptotic indexes of PBCCs were analyzed using flow cytometry. 24 hour-incubation with 25 mM metformin reduced the proliferation of PBCCs. AMPK-alpha gene expression in PBCCs was not affected by 25 mM metformin treatment compared with the control group. PBCCs treated with 25 mM metformin had lower cyclin D1 expression compared with non-treated cells, however, the difference was not statistically significant. 25mM dose of metformin increased p53 expression significantly compared with the non-treated group. The high concentration of metformin elevated the number of Annexin V positive apoptotic cells, and the increase in the apoptotic index was statistically significant. Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction.

Neurodegenerative diseases, specifically Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are defined by progressively increased neuronal loss that lacks curative therapies. Increasing evidence supports that non-canonical regulated cell death pathways including ferroptosis, necroptosis, pyroptosis, and parthanatos, are implicated in pathological mechanisms of neuroinflammation, and oxidative stress, and mitochondrial dysfunction, likely impacting neurodegenerative pathologies. In this review, we summarize the existing literature on the molecular pathways and potential pathogenic implications of these cell death pathways in neurodegenerative diseases, highlighting their upstream triggers, regulatory proteins, and downstream effectors. We also briefly describe representative pharmacological agents, including ferrostatin-1, necrostatin-1, MCC950 and PARP-inhibitors, that have shown neuroprotective effects in experimental studies. Experimental studies provide valuable information, but translation to clinical treatments presents barriers including overlapping regulated cell death mechanisms, constraints of bloodbrain barrier penetrance and concern for safety. Future development may come through concepts such as biomarker-based patient stratification strategies, multivalent interventions, and improved translational models. Identifying these new regulated cell death pathways may eventually provide new avenues to slow the progression of neurodegeneration and develop more targeted therapies.

Objective: Alzheimer’s disease is a neurodegenerative sickness and increasing with age throughout the world. A substantial body of evidence suggests the role of exosomal noncoding ribonucleic acids in the development of Alzheimer’s disease, but the regulatory mechanisms mediated by these noncoding ribonucleic acids remain extensively unknown. Using plasma samples from Alzheimer’s disease patients, this study explored the exosomal circular ribonucleic acid–microribonucleic acid profiles. Materials and Methods: The ArrayExpress platform was used to convey data from 3 samples from each group (healthy, mild cognitive impairment, and Alzheimer’s disease). Using plasma exosomes, differentially expressed microribonucleic acids and differentially expressed circular ribonucleic acids were compared between the Alzheimer’s disease and mild cognitive impairment groups. Afterward, to define pathways, gene ontologies, and networks, differentially expressed microribonucleic acids and differentially expressed circular ribonucleic acids common to both mild cognitive impairment and Alzheimer’s disease groups were analyzed. Eventually, the selection of hub genes and protein–protein interaction network was analyzed. Results: A total of common 19 (7 upregulated and 12 downregulated) differentially expressed microribonucleic acids and 24 differentially expressed circular ribonucleic acids were recognized. A total of 4559 target genes were predicted for upregulated differentially expressed microribonucleic acids, while 6504 target genes were identified for downregulated differentially expressed microribonucleic acids, and most of the target genes involved in the phosphoinositide 3-kinases-Akt pathway and that were mostly regulated by hsa-mir-374a-3p, mir-196a-5p, let-205-5p, mir-185-3p, mir-374a-5p, mir-615-3p, let-7c-5p, mir-185-5p. Additionally, 9 hub genes (HSP90AA, ACTB, MAPK1, GSK3B, CCNE2, CDK6, AKT1, IGF1R, CCND1) were revealed as the genes considerably related to Alzheimer’s disease by a protein–protein interaction network using the cytohubba in Cytoscape software. Conclusion: Our findings provide a new perspective on how microribonucleic acids could connect with circular ribonucleic acids in the pathogenesis of Alzheimer’s disease. Cite this article as: Besli N, Sarikamis B, Kalkan Cakmak R, Kilic U. Exosomal circular ribonucleic acid–microribonucleic acid expression profile from plasma in Alzheimer’s disease patients by bioinformatics and integrative analysis. Eurasian J Med., 2023;55(3):218-227.