Radiation is a form of energy derived from a source that is propagated through material in space. It consists of ionizing radiation or nonionizing radiation. Ionizing radiation is a feature of the environment and an important tool in medical treatment, but it can cause serious damage to organisms. A number of protective measures and standards of protection have been proposed to protect against radiation. There is also a need for biomarkers to rapidly assess individual doses of radiation, which can not only estimate the dose of radiation but also determine its effects on health. Proteomics, genomics, metabolomics, and lipidomics have been widely used in the search for such biomarkers. These topics are discussed in depth in this review.
Breast cancer (BC) is one of the most common malignancies affecting women. BC is a heterogeneous disease that involves multiple oncogenic pathways and/or genetic alterations. MicroRNAs (miRNAs or miRs) are a type of small endogenous single-stranded RNA that pairs with the 3'untranslated region of target mRNAs to negatively regulate the gene expression of specific mRNA targets. miRNAs are thus involved in various cellular processes, including proliferation, differentiation, apoptosis, migration, metabolism and the stress response. Over the past decade, a number of studies have demonstrated that the expression levels of miRNAs are dysregulated in a number of types of cancer, including BC.In the present review, recent research on miRNAs involved in the occurrence and development of BC, as well as the current findings on miRNAs as potential biomarkers for BC are summarized. In addition, the association between miRNA dysregulation and BC development, and the current status of BC treatment and prognosis are discussed. Finally, several signaling pathways involved in the development of BC and the potential roles of miRNAs in these pathways are reviewed. The present review aims to provide insight into the roles of miRNAs in BC. Contents1. Introduction 2. Potential biomarkers in BC 3. miRNA dysregulation in BC 4. miRNAs as therapeutic targets of BC 5. miRNAs and various signaling pathways, and therapeutic targets involved in BC 6. Summary and future perspectives
The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received <50, 50–500, and 500–1000 μGy/h of 137Cs radiation for 180 d. We found that the pathological changes in liver tissues were more obvious as the irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.
Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL‐60 cell differentiation involves down‐regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS‐induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein‐α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL‐60 cells resulted in down‐regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL‐60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS‐mediated down‐regulation of CRT and up‐regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG‐rich element in the 3′ untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS‐induced leukaemic cell differentiation.
Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.
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