Helicobacter pylori infection in human is one of the most common infections worldwide. However, the origin and transmission of this bacterium has not been clearly explained. One of the suggested theories is transmission via water. This study was conducted to determine the prevalence rate of H. pylori in tap water, dental units' water, and bottled mineral water in Iran. In the present study, totally 200 water samples were collected in Isfahan province and tested for H. pylori by cultural method and polymerase chain reaction (PCR) by the detection of the ureC (glmM) gene. Using cultural method totally 5 cultures were positive. Two out of 50 tap water samples (4%), 2 out of 35 dental units' water (5.8%) samples, and 1 out of 40 (2.5% ) from water cooler in public places were found to be contaminated with H. pylori. H. pylori ureC gene was detected in 14 (7%) of water samples including 5 tap water (10%), 4 dental units' water (11.4%), 1 refrigerated water with filtration, and 4 (10%) water cooler in public places samples. This may be due to the coccoid form of bacteria which is detected by PCR method.
A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.
Background
Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs.
Materials and methods
Herein, we designed a novel DDS based on magnetic mesoporous silica core–shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors.
Results
Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects.
Conclusion
These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy.
Graphic abstract
Although surgery with or without (neo)adjuvant chemo/radiotherapy, as the standard treatments, can be suitable therapeutic strategies for gastric cancer, side effects and drug resistance are two main treatment obstacles. It has been discovered that pomegranate and its natural derivatives, especially ellagic acid (EA), offer significant anti-cancer effects while causing trivial side effects. In this study, we aimed to explore the anti-cancer effects of EA on a human gastric adenocarcinoma cell line (AGS) as well as in immunocompromised mice bearing human gastric tumors, for the first time. HPLC was used for determining EA in samples. MTT assay, apoptosis and scratch assay, gelatin zymography, and quantitative RT-PCR were used to determine the anti-cancer properties of different concentrations of pomegranate fruit juice, pomegranate peel extract, and EA. Furthermore, the effects of these compounds were investigated on immunosuppressed C57BL/6 mice carrying human gastric cancer tumors. EA could inhibit the proliferation and migration of gastric cancer cells. It also had significant effects on reducing both expression and activity of MMP-2 and MMP-9. Further, it was demonstrated that with alterations in the expression of genes involved in apoptosis and inflammation including P53, BAX, APAF1, BCL2, iNOS, NF-κB, IL-8, and TNF-α, EA treatment led to increased cancer cell death and reduced inflammation. Furthermore, its use in mice bearing gastric tumors resulted in a significant reduction in tumor volume without any obvious side effects. Ellagic acid exhibited anti-cancer effects on gastric adenocarcinoma, and can be considered as a safe anti-cancer agent for further preclinical studies on this cancer.
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