Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells.

Cancer, the leading cause of death worldwide, has witnessed significant advancements in treatment through targeted therapies. Among the proto-oncogenes prevalent in human cancers, KRAS stands out, and recent research has focused on long noncoding RNAs (lncRNAs) as regulators of miRNAs targeting the KRAS oncogene. This study specifically explores lncRNAs involved in the KRAS pathway in colorectal cancer (CRC). To investigate this, researchers employed iron oxide nanoparticles coated with glucose and conjugated with Oleuropein (Fe3O4@Glu-Oleuropein NPs) to evaluate their impact on candidate lncRNAs associated with KRAS pathway deregulation. The study utilized TCGA data to identify genes affected by KRAS mutation and lncRNAs linked to KRAS in CRC. Enrichr and MsigDB databases helped identify relevant pathways. Genes with a correlation coefficient above 0.5 and a P-value less than 0.01 with candidate lncRNAs were selected. MTT and flow cytometry assays determined the anti-proliferative and apoptotic effects of Fe3O4@Glu-Oleuropein NPs on CRC cells (SW480) and normal cells (HEK293). The findings showed that increased expression of FEZF1-AS1, GAS6-AS1, and LINC00920 correlated with mutated KRAS, and co-expressed genes were significantly involved in hypoxia, KRAS signaling, DNA repair, and IL-2/STAT5 signaling pathways. Fe3O4@Glu-Oleuropein NPs exhibited higher toxicity toward cancer cells, with IC50 values of 92 µg/ml for SW480 and 281 µg/ml for HEK293. Flow cytometry analysis revealed a substantial increase in necrotic and apoptotic cells when treated with Fe3O4@Glu-Oleuropein, along with down-regulation of GAS6-AS1, LINC00920, and FEZF1-AS1 lncRNAs in treated cells. In conclusion, this study highlights the therapeutic potential of Fe3O4@Glu-Oleuropein on colon cancer cells in vitro. The identification of lncRNAs involved in the KRAS pathway provides insights into the underlying mechanisms and offers avenues for further research in targeted cancer therapies.

Synthesis of Novel Magnetic Quercetin-Neuropeptide Nanocomposite as a Smart Nano-Drug Shuttle System: Investigation of Its Effect on Behavior, Histopathological Characteristics, and Expression of MAPT and APP Genes in Alzheimer's Disease Rats.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia. The drugs introduced for this disease have many side effects and limitations in use, so the production of a suitable herbal medicine to cure AD patients is essential. OBJECTIVE: The aim of this research is to make a magnetic neuropeptide nano shuttle as a targeted carrier for the transfer of quercetin to the brains of AD model rats. METHODS: In this work, a magnetic quercetin-neuropeptide nanocomposite (MQNPN) was fabricated and administered to the rat's brain by the shuttle drug of the Margatoxin scorpion venom neuropeptide, and will be a prospect for targeted drug delivery in AD. The MQNPN has been characterized by FTIR, spectroscopy, FE-SEM, XRD, and VSM. Investigations into the efficacy of MQNPN, MTT, and real Time PCR for MAPT and APP genes expression were performed. After 7 days treatment with Fe3O4 (Ctr) and MQNPN treatment in AD rat, superoxide dismutase activity and quercetin in blood serum and brain was detected. Hematoxylin-Eosin staining was applied for histopathological analysis. RESULTS: Analysis of data showed that MQNPN increased the activity of superoxide dismutase. The histopathology results of the hippocampal region of AD rats also confirmed their improvement after treatment with MQNPN. MQNPN treatment caused a significant decrease in the relative expression of MAPT and APP genes. CONCLUSION: MQNPN is a suitable carrier for the transfer of quercetin to the rat hippocampus, and has a significant effect in reducing AD symptoms in terms of histopathology, behavioral testing, and changing the expression of AD-related genes.

Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research.

OBJECTIVES: Breast cancer (BC) is one of the most common cancers with a high mortality rate in women worldwide. The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient's life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using "R" software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method. RESULTS: This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.

Circular RNAs as novel biomarkers in triple-negative breast cancer: a systematic review.

More effective prognostic and diagnostic tools are urgently required for early detecting and treating triple-negative breast cancer, which is the most acute type of breast cancer because of its lower survival rate, aggressiveness, and non-response to various common treatments. So, it remains the most harmful malignancy for women worldwide. Recently, circular RNAs, as a group of non-coding RNAs, with covalently closed loop and high stability have been discovered, which can modulate gene expression through competing with endogenous microRNA sponges. This finding provided further insight into novel approaches for controlling genes affected in many disorders and malignancies. This review concentrates on the dysregulated expression of circRNAs like their diagnostic and prognostic values in TNBC. This review aims to focus on the abnormal expression of circRNAs and their diagnostic and prognostic values in TNBC. We used PubMed, Embase, and Web of Science databases and ClinicalTrials.gov to systematically search for all relevant clinical studies. This review is based on articles published in databases up to April 2022 with the following keywords: "Circular RNA", "CircRNA", "Triple-Negative Breast Cancer" and "TNBC". We conducted a review of published CircRNA profiled-research articles to identify candidate CircRNA biomarkers for TNBC. The review is registered on JBI at https://jbi.global/systematic-review-register . Accumulating evidence has shown that several circRNAs are downregulated and some are upregulated in TNBC. The results of these studies confirm that circRNAs might be potential biomarkers with the diagnostic, prognostic, and therapeutic target value for TNBC. We also consider the connection between circRNAs and TNBC cell proliferation, apoptosis, metastasis, and chemotherapy resistance and sensitivity.

Functionalisation of Fe3O4 nanoparticles by 2-((pyrazol-4-yl) methylene) hydrazinecarbothioamide enhances the apoptosis of human breast cancer MCF-7 cells.

Cancer is a major cause of death. Thus, the incidence and mortality rate of cancer is globally important. Regarding vast problems caused by chemotherapy drugs, efforts have progressed to find new anti-cancer drugs. Pyrazole derivatives are known as components with anti-cancer properties. In here, Fe3O4 nanoparticles were first functionalized with (3-chloropropyl) trimethoxysilane, then 2-((pyrazol-4-yl) methylene) hydrazinecarbothioamide (P) was anchored on the surface of magnetic nanoparticles (PL). The synthesized nano-compounds were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, Zeta potential, dynamic light scattering, and energy-dispersive x-ray spectrometry analyses. The cytotoxicity effect was evaluated using MTT assay, apoptosis test by Flow cytometry, cell cycle analysis, Caspase-3 activity assay and Hoechst staining on MCF-7 cell line. The high toxicity for tumor cells and low toxicity on normal cells (MCF10A) was considered as an important feature (selectivity index, 10.9). Based on results, the IC50 for P and PL compounds were 157.80 and 131.84 µM/ml respectively. Moreover, apoptosis inducing, nuclear fragmentation, Caspase 3 activity and induction of cell rest in sub-G1 and S phases, were also observed. The inhibitory effect of PL was significantly higher than P, which could be due to the high penetrability of Fe3O4 nanoparticles.

Synthesis of Nano-Paramagnetic Oleuropein to Induce KRAS Over-Expression: A New Mechanism to Inhibit AGS Cancer Cells.

Background and objectives: Human gastric adenocarcinoma (AGS) is one of the most common malignant cancers worldwide. The present study aimed to transfer oleuropein into cancer cells using synthetic paramagnetic nanoparticles and study their effect on the AGS (ATCC® CRL1739™) cell line. Materials and Methods: Paramagnetic nano-oleuropein was synthesized using four-stage co-precipitation by developing NH-connected bridges and was evaluated by EDS, SEM and FTIR methods. Different concentrations of magnetic oleuropein (0, 0.15, 0.45, 1.37, 4.12, 12.35, 37.04, 111.11, 333.33, 1000 µg/mL) were used to treat the AGS cell line in a completely randomized design using a statistical framework with three replicates. The relative expression rate of miR-200 and KRAS oncogenes was evaluated using real-time PCR. The inhibition rate of the AGS cells was assessed using the MTT test at 24, 48 and 72 h intervals. Results: The results showed that there was a significant difference between the inhibition rates of magnetic nano-oleuropein at IC50-24h (23.6 µg/mL), IC50-48h (15.2 µg/mL) and IC50-72h (9.2 µg/mL). Real-time PCR indicated that the relative expression of KRAS and miR-200 genes was highest at IC50 at these intervals. Conclusions: Magnetic nano-oleuropein can be subjected to objective testing and clinical evaluations as a natural antioxidant to prevent and treat gastric adenocarcinoma.

Optimized quantities of GDNF overexpressed by engineered astrocytes are critical for protection of neuroblastoma cells against 6-OHDA toxicity.

Optimized levels of glial cell line-derived neurotrophic factor (GDNF) are critical for protection of dopaminergic neurons against parkinsonian cell death. Recombinant lentiviruses harboring GDNF coding sequence were constructed and used to infect astrocytoma cell line 1321N1. The infected astrocytes overexpressed GDNF mRNA and secreted an average of 2.2 ng/mL recombinant protein as tested in both 2 and 16 weeks post-infection. Serial dilutions of GDNF-enriched conditioned medium from infected astrocytes added to growing neuroblastoma cell line SK-N-MC resulted in commensurate resistance against 6-OHDA toxicity. SK-N-MC cell survival rate rose from 51% in control group to 84% in the cells grown with astro-CM containing 453 pg secreted GDNF, an increase that was highly significant (P < 0.0001). However, larger volumes of the GDNF-enriched conditioned medium failed to improve cell survival and addition of volumes that contained 1,600 pg or more GDNF further reduced survival rate to below 70%. Changes in cell survival paralleled to changes in the percent of apoptotic cell morphologies. These data demonstrate the feasibility of using astrocytes as minipumps to stably oversecrete neurotrophic factors and further indicate that GDNF can be applied to neuroprotection studies in PD pending the optimization of its concentrations.

Statistical approach to discovery of factors impacting on emergence of blood cancers in iran.

Cancer is now the main cause of increasing mortality throughout the world. Minor alterations in the cell cycle which are inherited and not removed by apoptosis are important risk factors. Blood cancers are asmong the types which most readily cause death. Here in this study, usual but important factors such as age, gender, Rh and ABO blood typing, weight, and platelet counts are analyzed for impact on blood cancers. Frequencies and distributions, correlations and chi-square test were utilized in order to clarify the perspective of important factors. Our statistical results show males and females to have same risk in blood cancer but A blood type (40%) along with positive Rh (73%) had the highest risk. Low platelet counts are related to more than 80% of cases. Obesity has a statistically ignorable role in blood cancer prevalence. The fact that blood cancer cases increase during the second decade of life (45.7%) which might be because of involvement of maturation processes.