Cerium Oxide Nanoparticles Synthesis Using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects.

INTRODUCTION: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. METHOD: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. RESULTS: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. CONCLUSION: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.

Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells.

BACKGROUND: Drug resistance is one of the most critical problems in gastric cancer therapy. This study was performed to investigate the valproic acid effects on the proliferation of sensitive and resistant cell lines of human gastric cancer, and to explore the mechanism of the agent on multi drug resistance and apoptosis genes. METHODS: The cytotoxicity effect of valproic acid on the EPG85.257 and EPG85.257RDB cells was assessed by the MTT assay, and the IC50 concentration was evaluated. Apoptosis, genotoxicity, and drug resistance pump activity were evaluated using comet assay, Real-time PCR, and flow cytometry, respectively. Cell proliferation was assayed using a scratch test. RESULTS: Dose-dependent toxicity was recorded after treatment of cells with valproic acid. Valproic acid represented a significant growth inhibition on EPG85.257 cells with IC50 values of 5.84 µM and 4.78 µM after 48 h and 72 h treatment, respectively. In contrast, the drug-resistant counterpart represented 8.7 µM and 7.02 µM IC50 values after the same treatment time. Valproic acid induced PTEN, Bcl2, P53, Bax, P21, and caspase3 expression in EPG85.257 cells, whereas p21, p53, PTEN, and ABCB1 were overexpressed in EPG5.257RDB. Valproic acid hindered cell migration in both cell lines (P < 0.01). Valproate genotoxicity was significantly higher in the parent cells than in their resistant EPG85.257RDB counterparts. Valproate led to a 62% reduction in the daunorubicin efflux of the MDR1 pump activity. CONCLUSIONS: Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression.

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine.

The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP-binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug-metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds.

Epigenetic disruption of histone deacetylase-2 accelerated apoptotic signaling and retarded malignancy in gastric cells.

Background: The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. Methods: HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. Results: Cell proliferation, colony formation, wound healing and transwell invasion were inhibited in ΔHDAC2:EPG85.257 cells. Quantitative analyses revealed a significant downregulation of MMP1, p53, Bax, MAPK1, MAPK3, pro-Caspase3, ERK1/2, p-ERK1/2, AKT1/2/3, p-AKT1/2/3, p-NF-κB (p65), Twist, Snail and p-FAK transcripts/proteins, while SIRT1, PTEN, p21 and Caspase3 were upregulated in ΔHDAC2:EPG85.257 cells. Conclusion: These results indicated that HDAC2 enhanced migration, colony formation and transmigration ability. HDAC2 inhibition may improve gastric cancer chemotherapy pathways.

DNA changes are the main causes of cancer. Therefore, finding easy ways to manipulate and correct DNA changes has been the biggest medical concern in cancer treatment. Researchers have introduced CRISPR/Cas9 as the newest technology for gene editing that precisely and easily changes the genome of any cell. In our study, histone deacetylase-2 was disrupted in gastric cancer cells using CRISPR technology. This modification reduced growth kinetics and invasion of cancer cells. On the other hand, cell death (also called apoptosis) was induced. Sensitization of the cancer cells to chemotherapeutic agents is noticeable in this research. This study needs to uncover more signaling pathways in vitro and in vivo.

A comprehensive review of cancer therapies mediated by conjugated gold nanoparticles with nucleic acid.

Nucleic acids provide a promising therapeutic platform by targeting various cell signaling pathways involved in cancer and genetic disorders. However, maintaining optimal stability during delivery limits their utility. Nucleic acid delivery vehicles are generally categorized into biological and synthetic carriers. Regardless of the efficiency of biological vectors, such as viral vectors, issues related to their immunogenicity and carcinogenesis are very important and vital for clinical applications. On the other hand, synthetic vectors such as lipids or polymers, have been widely used for nucleic acid delivery. Despite their transfection efficiency, low storage stability, targeting inefficiency, and tracking limitations are among the limitations of the clinical application of these vectors. In the past decades, gold nanoparticles with unique properties have been shown to be highly efficient mineral vectors for overcoming these obstacles. In this review, we focus on gold nanoparticle-nucleic acid combinations and highlight their use in the treatment of various types of cancers. Furthermore, by stating the biological applications of these structures, we will discuss their clinical applications.

Investigation of the therapeutic role of native plant compounds against colorectal cancer based on system biology and virtual screening.

This study investigated the anticancer effects of compounds extracted from native plants on colon cancer following drug-target-network analysis and molecular docking. Based on the ChEBI database, compounds were identified in medicinal plants and weeds in the Chaharmahal and Bakhtiari provinces of Iran. A drug-target network was constructed based on candidate colon cancer protein targets and selective compounds. Network pharmacology analysis was conducted against the identified compounds and subjected to molecular docking studies. Based on molecular dynamics simulations, the most efficient compounds were evaluated for their anticancer effects. Our study suggests that TREM1, MAPK1, MAPK8, CTSB, MIF, and DPP4 proteins may be targeted by compounds in medicinal plants for their anti-cancer effects. Multiorthoquinone, Liquiritin, Isoliquiritin, Hispaglabridin A, Gibberellin A98, Cyclomulberrin, Cyclomorusin A, and Cudraflavone B are effective anticancer compounds found in targeted medicinal plants and play an important role in the regulation of important pathways in colon cancer. Compounds that inhibit MIF, CTSB, and MAPK8-16 appear to be more effective. Additional in vitro and in vivo experiments will be helpful in validating and optimizing the findings of this study.

The important role of miR-770 as a novel potential diagnostic and therapeutic target for human cancer and other diseases.

MicroRNA-770 (miR-770) is an RNA gene, located on chromosome 14q32.2. It has important effects on the pathobiology of cancers and other human diseases. It is known to be a tumor suppressor in breast cancer, ovarian cancer, gastric cancer, non-small cell lung cancer, prostate cancer, and glioblastoma. In colorectal adenocarcinoma and oral squamous cell carcinoma, miR-770 is regarded as an oncogenic miRNA. In several disorders, miR-770 dysregulation has been recognized as a potential biomarker for disease diagnosis and prognosis. Dysregulation of miR-770 has also been demonstrated in non-malignant human disorders, including Alzheimer's disease, dilated cardiomyopathy, diabetic nephropathy, Hirschsprung's disease, osteoarthritis, silicosis, and type 2 diabetes mellitus. In the current review, we have obtained the miR-770 target genes, ontology, and related pathways. We have also provided a comprehensive review of miR-770 in both malignant and non-malignant disorders and explained its possible therapeutic implications.

Long non-coding RNAs and gastric cancer: An update of potential biomarkers and therapeutic applications.

The frequent metastasis of gastric cancer (GC) complicates the cure and therefore the development of effective diagnostic and therapeutic approaches is urgently necessary. In recent years, lncRNA has emerged as a drug target in the treatment of GC, particularly in the areas of cancer immunity, cancer metabolism, and cancer metastasis. This has led to the demonstration of the importance of these RNAs as prognostic, diagnostic and therapeutic agents. In this review, we provide an overview of the biological activities of lncRNAs in GC development and update the latest pathological activities, prognostic and diagnostic strategies, and therapeutic options for GC-related lncRNAs.

CRISPR/Cas9 as precision and high-throughput genetic engineering tools in gastrointestinal cancer research and therapy.

Gastrointestinal cancer (GI) is one of the most serious and health-threatening diseases worldwide. Many countries have encountered an escalating prevalence of shock. Therefore, there is a pressing need to clarify the molecular pathogenesis of these cancers. The use of high-throughput technologies that allow the precise and simultaneous investigation of thousands of genes, proteins, and metabolites is a critical step in disease diagnosis and cure. Recent innovations have provided easy and reliable methods for genome investigation, including TALENs, ZFNs, and the CRISPR/Cas9 (clustered regularly interspaced palindromic repeats system). Among these, CRISPR/Cas9 has been revolutionary tool in genetic research. Recent years were prosperous years for CRISPR by the discovery of novel Cas enzymes, the Nobel Prize, and the development of critical clinical trials. This technology utilizes comprehensive information on genes associated with tumor development, provides high-throughput libraries for tumor therapy by developing screening platforms, and generates rapid tools for cancer therapy. This review discusses the various applications of CRISPR/Cas9 in genome editing, with a particular focus on genome manipulation, including infection-related genes, RNAi targets, pooled library screening for identification of unknown driver mutations, and molecular targets for gastrointestinal cancer modeling. Finally, it provides an overview of CRISPR/Cas9 clinical trials, as well as the challenges associated with its use.

Designed miR-19a/b sponge induces apoptosis in lung cancer cells through the PI3K-PTEN-Akt pathway regulation.

BACKGROUND: MicroRNAs (miRNAs) are one of the main factors in cancer development and can alter the activity of proto-oncogenic or tumor suppressor genes. The miR-17-92 cluster, which comprises miR-17, miR-18a, miR-19a/b, miR-20a, and miR-92a, has been identified as a biomarker in a variety of cancer types. Among them, miR-19a/b exerts an oncogenic effect by suppressing tumor suppressor genes, including PTEN and TP53INP1in numerous types of cancers, including NSCLC. An miRNA sponge is an mRNA with multiple repetitive sequences that prevents miRNAs from interacting with their targets, thereby inhibiting their action. METHODS AND RESULTS: In this study, we designed an miR-19a/b sponge plasmid and transfected it into A549 lung cancer cell lines and analyzed its effects on PTEN and TP53INP1 gene expression as the main miR-19a/b target and apoptosis rate in these cell lines. CONCLUSIONS: The findings revealed that miR-19a/b sponge significantly increased PTEN and TP53INP1 mRNA expression. The effect of the sponge on TP53INP1 was much greater than that on PTEN. This is because TP53INP1 is directly (sponge effect) and indirectly (AKT pathway is affected by the P53 gene) affected by this sponge. In addition, compared with the control group, the percentage of primary and secondary apoptosis increased significantly (P value < 0.0001).

Butylcycloheptylprodigiosin and undecylprodigiosin are potential photosensitizer candidates for photodynamic cancer therapy.

BACKGROUND: Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments. METHODS AND RESULTS: Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3 Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5 Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05). CONCLUSIONS: In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Detection of SENV Virus in Healthy, Hepatitis B- and Hepatitis C-Infected Individuals in Yazd Province, Iran.

BACKGROUND: SEN virus (SENV) is the latest virus proposed as a cause of unknown hepatitis cases. Among nine detected genotypes of the virus, genotypes D and H are more frequent in hepatitis cases of unknown origin. The aim of this study was to determine the frequency of SENV-D and SENV-H genotypes in the sera of healthy individuals and hepatitis B and C patients. METHODS: Totally, 200 serum samples from healthy individuals as well as 50 hepatitis B and 50 hepatitis C patients were collected. Anti-HCV (hepatitis C virus), anti-human immunodeficiency virus, hepatitis B surface antigen and anti-HBV (hepatitis B virus) core antigen were detected, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Viral DNA was subjected to nested PCR. Fisher's exact and unpaired ANOVA tests were used for statistical analyses. RESULTS: SENV was detected in 90%, 66%, and 46% of the healthy individuals HBV and HCV-positive individuals, respectively. The frequency of SENV and its two genotypes were significantly lower in hepatitis B and hepatitis C patients (P<0.01). Also, the frequency of SENV-H was higher than SENV-D in all studied groups. In SENV-positive HBV patients, the level of ALT and AST enzymes were significantly less than SENV-negative patients (P<0.05). It was the same for SENV-H-negative and -positive cases. CONCLUSIONS: The levels of liver enzymes were significantly lower in HBV patients co-infected with SENV compared to HBV patients (P<0.05), indicating a positive impact of the virus in liver pathology by decreasing liver damage and thus decreasing the liver enzymes.