Involvement of GSTP1 in low dose radiation-induced apoptosis in GM12878 cells.

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.

PURPOSE: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND METHODS: In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND CONCLUSIONS: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

One-step quaternization and macromolecular reconstruction to prepare micro-/nano-porous cellulose beads from homogeneous solution for low-concentration amoxicillin removal.

Designing advanced functional cellulose-based materials by one-step homogeneous preparation technology is a great challenge since cellulose is insoluble in common solvents or difficult to regenerate and shape. Quaternized cellulose beads (QCB) were prepared from a homogeneous solution by one-step cellulose quaternization homogeneous modification and macromolecules' reconstruction technology. Morphological and structural characterizations of QCB were conducted by SEM, FTIR and XPS, etc. The adsorption behavior of QCB was studied using amoxicillin (AMX) as a model molecule. The adsorption of QCB for AMX was multilayer adsorption controlled by both physical adsorption and chemical adsorption. The removal efficiency for 60 mg L-1 AMX reached 98.60 % through electrostatic interaction, and the adsorption capacity reached 30.23 mg g-1. AMX adsorption was almost reversible without loss of binding efficiency after three cycles. This facile and green method may offer a promising strategy for the development of functional cellulose materials.

Gut microbiota and ionizing radiation-induced damage: Is there a link?

According to observational findings, ionizing radiation (IR) triggers dysbiosis of the intestinal microbiota, affecting the structural composition, function, and species of the gut microbiome and its metabolites. These modifications can further exacerbate IR-induced damage and amplify proinflammatory immune responses. Conversely, commensal bacteria and favorable metabolites can remodel the IR-disturbed gut microbial structure, promote a balance between anti-inflammatory and proinflammatory mechanisms in the body, and mitigate IR toxicity. The discovery of effective and safe remedies to prevent and treat radiation-induced injuries is vitally needed because of the proliferation of radiation toxicity threats produced by recent radiological public health disasters and increasing medical exposures. This review examines how the gut microbiota and its metabolites are linked to the processes of IR-induced harm. We highlight protective measures based on interventions with gut microbes to optimize the distress caused by IR damage to human health. We offer prospects for research in emerging and promising areas targeting the prevention and treatment of IR-induced damage.

Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments.

Sometimes, people can be exposed to moderate or high doses of radiation accidentally or through the environment. Radiation can cause great harm to several systems within organisms, especially the hematopoietic system. Several types of drugs protect the hematopoietic system against radiation damage in different ways. They can be classified as "synthetic drugs" and "natural compounds." Their cellular mechanisms to protect organisms from radiation damage include free radical-scavenging, anti-oxidation, reducing genotoxicity and apoptosis, and alleviating suppression of the bone marrow. These topics have been reviewed to provide new ideas for the development and research of drugs alleviating radiation-induced damage to the hematopoietic system.

Metabolomics as a valid analytical technique in environmental exposure research: application and progress.

BACKGROUND: In recent years, studies have shown that exposure to environmental pollutants (e.g., radiation, heavy metal substances, air pollutants, organic pollutants) is a leading cause of human non-communicable diseases. The key to disease prevention is to clarify the harmful mechanisms and toxic effects of environmental pollutants on the body. Metabolomics is a high-sensitivity, high-throughput omics technology that can obtain detailed metabolite information of an organism. It is a crucial tool for gaining a comprehensive understanding of the pathway network regulation mechanism of the organism. Its application is widespread in many research fields such as environmental exposure assessment, medicine, systems biology, and biomarker discovery. AIM OF REVIEW: Recent findings show that metabolomics can be used to obtain molecular snapshots of organisms after environmental exposure, to help understand the interaction between environmental exposure and organisms, and to identify potential biomarkers and biological mechanisms. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review focuses on the application of metabolomics to understand the biological effects of radiation, heavy metals, air pollution, and persistent organic pollutants exposure, and examines some potential biomarkers and toxicity mechanisms.

MicroRNA: a novel implication for damage and protection against ionizing radiation.

Ionizing radiation (IR) is a form of high energy. It poses a serious threat to organisms, but radiotherapy is a key therapeutic strategy for various cancers. It is significant to reduce radiation injury but maximize the effect of radiotherapy. MicroRNAs (miRNAs) are posttranscriptionally regulatory factors involved in cellular radioresponse. In this review, we show how miRNAs regulate important genes on cellular response to IR-induced damage and how miRNAs participate in IR-induced carcinogenesis. Additionally, we summarize the experimental and clinical evidence for miRNA involvement in radiotherapy and discuss their potential for improvement of radiotherapy. Finally, we highlight the role that miRNAs play in accident exposure to IR or radiotherapy as predictive biomarker. miRNA therapeutics have shown great perspective in radiobiology; miRNA may become a novel strategy for damage and protection against IR.

pH-Responsive Cellulose-Based Microspheres Designed as an Effective Oral Delivery System for Insulin.

Functional modified cellulose microsphere (CMs) materials exhibit great application potential in drug various fields. Here, we designed pH-responsive carboxylated cellulose microspheres (CCMs) by the citric/hydrochloric acid hydrolysis method to enhance oral bioavailability of insulin by a green route. The CMs were high purity cellulose that dissolved and regenerated from a green solvent by the green sol-gel method. The prepared microspheres were characterized by spectroscopic techniques, such as field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectrum (FT-IR), X-ray diffraction (XPS), etc. The spherical porous structure and carboxylation of cellulose were confirmed by FESEM and FT-IR, respectively. Insulin was loaded into the CCMs by electrostatic interactions, and the insulin release was controlled through ionization of carboxyl groups and proton balance. In vitro insulin release profiles demonstrated the suppression of insulin release in artificial gastric fluid (AGF), while a significant increase at artificial intestinal fluid (AIF) was observed. The insulin release profile was fitted in Korsmeyer-Peppas kinetic model, and insulin release was governed by the Fickian diffusion mechanism. The stability of the secondary structure of insulin was studied by dichroism circular. Excellent biocompatibility and no cytotoxicity of designed CCMs cast them as a potential oral insulin carrier.

Functionalized phosphorylated cellulose microspheres: Design, characterization and ciprofloxacin loading and releasing properties.

In this work, functionalized phosphorylated cellulose microspheres (CMP) were designed as a carrier for the ciprofloxacin (CIP) drug delivery system. The CMP has been developed from cellulose microspheres (CM) and phosphoric acid via an esterification reaction. CIP, an antibiotic drug as a model, was loaded onto CIP via hydrogen bonds and electrostatic interactions. A series of test results showed that the CIP was successfully incorporated and released from the prepared CMP without the loss of structural integrity or changing its functionality. The release kinetics and mechanism suggest that CIP release follows first-order kinetics and non-Fickian diffusion mechanism. The cytotoxicity behavior of CMP enables the material as a suitable vehicle for the safe release of CIP. The CIP loaded microspheres exhibited a significant antibacterial effect due to the CIP release and diffusion from the microspheres. This study provides insight into the design of suitable cellulose microspheres for CIP delivery.

iTRAQ-Based Proteomic Profiling of Potential Biomarkers in Rat Serum for Uranium Tailing Suspension Intratracheal Instillation.

Protection against low-dose ionizing radiation is of great significance. Uranium tailings are formed as a byproduct of uranium mining and a potential risk to organisms. In this study, we identified potential biomarkers associated with exposure to low-dose radiation from uranium tailings. We established a Wistar rat model of low dose rate irradiation by intratracheal instillation of a uranium tailing suspension. We observed pathological changes in the liver, lung, and kidney tissues of the rats. Using isobaric tags for relative and absolute quantification, we screened 17 common differentially expressed proteins in three dose groups. We chose alpha-1 antiproteinase (Serpina1), keratin 17 (Krt17), and aldehyde dehydrogenase (Aldh3a1) for further investigation. Our data showed that expression of Serpina1, Krt17, and Aldh3a1 had changed after the intratracheal instillation in rats, which may be potential biomarkers for uranium tailing low-dose irradiation. However, the underlying mechanisms require further investigation.