Chemoprophylatic strategies against development of multifactorial diseases utilize compounds to block the multistep events in chronic inflammation and carcinogenesis. The successful chemopreventative ...candidate must therefore selectively inhibit growth of transformed cells and be administered frequently to confer maximal protection with minimal side effects. In addition to synthetic and exogenous natural compounds, endogenous metabolites represent another class of compounds that exhibit anticarcinogenic and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the endogenous metabolites—phenyl acetate, ursodeoxycholate, and tauroursodeoxycholate—to determine the role of p53-induced cytotoxicity, with p53 mutant and deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays, and macroscopic colony counts were used to quantify cell survival. The results demonstrate that the bile acids, ursodeoxycholate and tauroursodeoxycholate, exhibit selective cytotoxicity toward nonfunctional p53 cell lines suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, the tauroursodeoxycholate demonstrates high significance suggesting it might have practical uses in vivo.
Chemoprevention strategies employ the use of compounds to inhibit the initiation, promotion, and progression phases of carcinogenesis. The successful chemopreventative candidate must therefore (1) ...selectively inhibit growth of transformed cells and (2) be administered on a frequent basis to confer maximal protection. Phytochemicals are a subclass of bioactive plant secondary metabolites that exhibit antioxidative, anticarcinogenic, and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the phytochemicals—curcumin, andrographolide, and d-limonene—to determine the role of p53-induced cytotoxicity, with p53-mutant and p53-deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays and macroscopic colony counts were used to quantify cell survival. The results demonstrate that each phytochemical exhibits selective cytotoxicity toward nonfunctional p53 cell lines, suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, only the d-limonene demonstrates considerable chemoprotection, suggesting it might have practical implications in vivo.
This short review explores the utility and applications of CRISPR/Cas9 systems in radiobiology. Specifically, in the context of experimentally simulating genotoxic effects of Ionizing Radiation (IR) ...to determine the contributions from DNA targets and ‘Complex Double-Stranded Breaks' (complex DSBs) to the IR response. To elucidate this objective, this review considers applications of CRISPR/Cas9 on nuclear DNA targets to recognize the respective ‘nucleocentric’ response. The article also highlights contributions from mitochondrial DNA (mtDNA) - an often under-recognized target in radiobiology. This objective requires accurate experimental simulation of IR-like effects and parameters with the CRISPR/Cas9 systems. Therefore, the role of anti-CRISPR proteins in modulating enzyme activity to simulate dose rate - an important factor in radiobiology experiments is an important topic of this review. The applications of auxiliary domains on the Cas9 nuclease to simulate oxidative base damage and multiple stressor experiments are also topics of discussion. Ultimately, incorporation of CRISPR/Cas9 experiments into computational parameters in radiobiology models of IR damage and shortcomings to the technology are discussed as well. Altogether, the simulation of IR parameters and lack of damage to non-DNA targets in the CRISPR/Cas9 system lends this rapidly emerging tool as an effective model of IR induced DNA damage. Therefore, this literature review ultimately considers the relevance of complex DSBs to radiobiology with respect to using the CRISPR/Cas9 system as an effective experimental tool in models of IR induced effects.
This short review explores the utility and applications of CRISPR/Cas9 systems in radiobiology. Specifically, in the context of experimentally simulating genotoxic effects of Ionizing Radiation (IR) ...to determine the contributions from DNA targets and ‘Complex Double-Stranded Breaks' (complex DSBs) to the IR response. To elucidate this objective, this review considers applications of CRISPR/Cas9 on nuclear DNA targets to recognize the respective ‘nucleocentric’ response. The article also highlights contributions from mitochondrial DNA (mtDNA) - an often under-recognized target in radiobiology. This objective requires accurate experimental simulation of IR-like effects and parameters with the CRISPR/Cas9 systems. Therefore, the role of anti-CRISPR proteins in modulating enzyme activity to simulate dose rate - an important factor in radiobiology experiments is an important topic of this review. The applications of auxiliary domains on the Cas9 nuclease to simulate oxidative base damage and multiple stressor experiments are also topics of discussion. Ultimately, incorporation of CRISPR/Cas9 experiments into computational parameters in radiobiology models of IR damage and shortcomings to the technology are discussed as well. Altogether, the simulation of IR parameters and lack of damage to non-DNA targets in the CRISPR/Cas9 system lends this rapidly emerging tool as an effective model of IR induced DNA damage. Therefore, this literature review ultimately considers the relevance of complex DSBs to radiobiology with respect to using the CRISPR/Cas9 system as an effective experimental tool in models of IR induced effects.
The main goal of the research was to determine whether commercially available common dietary phytochemical supplements (curcumin, andrographolide, and d-limonene) have radiomodulatory effects on ...p53-competent human colonic epithelial cells.
Clonogenic survival assays were used to characterize effects of the phytochemicals on cultured colonic epithelial cells (HCT116 p53
+/+
) in direct irradiation or upon receipt of irradiated-cell conditioned media (for bystander effects). In direct irradiation, feeding regimen experiments included compound administration pre- and post-irradiation, which was used as a basis to define effects as radioprotective and radiomitigative, respectively. In the bystander effect experiments, either donor or recipient cell cultures were fed with the phytochemicals and bystander-induced clonogenic cell death was quantitatively evaluated. Dose challenge was in the range of 0.5 − 5 Gy using the gamma source (Cs-137).
Curcumin, andrographolide, and d-limonene appeared to not exhibit radioprotective and radiomitigative properties in HCT116 p53
+/+
cells. D-limonene was found to induce radiosensitization in post-irradiation administration. All three compounds appeared not to modulate the radiation-induced bystander signal production and response in HCT116 p53
+/+
cells.
Curcumin, andrographolide, and d-limonene are known to have many chemoprotective benefits. This work shows that they, however, did not protect colonic epithelial HCT116 p53
+/+
cells from radiation killing. As HCT116 p53
+/+
cells are tumourigenic in nature, this finding implies that these three dietary compounds would not reduce the killing efficacy of radiation in gastrointestinal tumorigenesis. The post-irradiation radiosensitizing effect of d-limonene was an intriguing observation worth further investigation.
Purpose: To determine the level of awareness, beliefs and experience of healthcare professionals (HCPs) regarding mobile applications for self-management of type 2 diabetes mellitus.
Methods: This ...review was done by searching the literature using three databases viz: PubMed, Web of Science and Scopus. Assessment of quality of studies was carried out using the scale of the Agency for Healthcare Research and Quality. The results were presented in accordance with the PRISMA 2020 guidelines.
Results: The search strategy identified 725 unique research papers, 4 of which were included. A survey among pharmacists showed that 56 % of participants were aware of the existence of mobile health applications, and that 60 % of those who were aware recommended their use. In the multi-HCPs setting, depending on the study, apps recommendation rate varied from 45.5 to 62 %. Most of the participants (88 %) agreed that a mobile app would help strengthen their treatment recommendations to the patients (88 %), and 84 % also agreed that it would help patients manage diabetes better.
Conclusion: Not much research has been done on this topic. Available data suggest that the awareness of HCPs regarding mobile applications is unsatisfactory, and that those familiar with these apps find them useful and are ready to recommend them to patients. There is need for further research and measures to increase awareness and knowledge of HCPs about available mobile applications, in order to ensure adequate support to patients with diabetes.
Abstract The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with ...unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile. The results show that membrane related functions of calcium and 5HT are critical for true bystander effect expression. Our original inter-animal experiments used fish species whole body irradiated with low doses of X-rays, which prevented us from addressing the abscopal effect question. Data which are much more relevant in radiotherapy are now available for rats which received high dose local irradiation to the implanted right brain glioma. The data were generated using quasi-parallel microbeams at the biomedical beamline at the European Synchrotron Radiation Facility in Grenoble France. This means we can directly compare abscopal and “true” bystander effects in a rodent tumour model. Analysis of right brain hemisphere, left brain and urinary bladder in the directly irradiated animals and their unirradiated partners strongly suggests that bystander effects (in partner animals) are not the same as abscopal effects (in the irradiated animal). Furthermore, the presence of a tumour in the right brain alters the magnitude of both abscopal and bystander effects in the tissues from the directly irradiated animal and in the unirradiated partners which did not contain tumours, meaning the type of signal was different.
This thesis examines select natural dietary compounds for their radioprotective properties in vitro. These compounds were selected on the basis of their use in the treatment of CFIDS (Chronic Fatigue ...Immune Dysfunction Syndrome). CFIDS in humans encompasses symptoms similar to those in ionizing radiation (IR) exposures. Therefore, compounds that address CFIDS symptoms might also have utility in dietary chemical radioprotection. Specifically, this thesis examines the radioprotective effects of plant metabolites –curcumin, andrographolide, d-limonene – and endogenous metabolites – phenylacetate, ursodeoxycholate, tauroursodeoxycholate – in clonogenic in vitro experiments. Compounds were examined for their radioprotective effects in p53 variant human colon carcinoma cells which share similar features to radiosensitive stem cells of the gastrointestinal tract. Experiments examined compounds on the basis of their chemoprotective, bystander inhibitory, radioprotective and radiomitigative properties. The d-limonene demonstrated notable chemoprotective properties as noted by the preferential toxicity to p53 defective cell lines. There were no compounds that exhibited bystander inhibitory effects. In acute high dose experiments, the phenylacetate demonstrated significant radioprotective effects up to 2 Gy with minor radioprotective effects from tauroursodeoxycholate at 0.5 Gy exposures. There were no compounds that demonstrated radiomitigative effects. Ultimately, this thesis demonstrates that natural consumer products in the treatment of IR-like syndromes provide an attractive basis on which to screen compounds the fields of radioprotection.
Thesis
Doctor of Philosophy (PhD)
The valence band electronic structure of isolated silver iodide nanoparticles (AgI NP) was investigated by vacuum-ultraviolet aerosol photoelectron spectroscopy using the velocity map imaging ...technique (VUV VMI-PES). The VUV VMI-PES results were obtained for polydisperse aerosol produced by aggregation of hydrocolloid of silver iodide particles 8 - 15 nm in size. The ionization energy of the AgI particles was found to be 6.0 ± 0.1 eV with respect to the vacuum level. The DFT calculations showed that the main contribution to the density of AgI electronic states in the valence region originates from I 5p orbitals. The dependence of the asymmetry parameter on the electron energy showed that the value of the characteristic energy loss of excited photoelectrons was 2.7 eV, which coincided with the band gap of the nanomaterial.
PDF
