Toxicological assessments based on intestine 3D organoids reveal environmental low-dose nanosized microplastics (NPs) exposure aggravates radiation-induced intestine injury.

Background: Intestinal organoid has emerged as an energetic tool for modeling intestine physiology and relevant diseases in vitro. Here, we reported that development of intestinal organoids could be used to explore the toxicology mechanism for combination effects of low dose nanoplastic (NPs) chronic exposure and acute radiation on intestine injury, the two classical chemical and physical substances.

Methods: Integrated acute radiation-induced intestine injury model in vivo and mice intestinal organoids in vitro were conducted in this study.

Establishment and Application of a New Radiation Biodosimetric Method Based on the Quantitative RPA-SHERLOCK Amplification Technology.

Biodosimetry is a key diagnostic tool for radiation exposure, risk assessment and treatment planning of acute radiation sickness. To effectively respond to a large-scale radiological incident, there is a need for the development of biodosimetric methods with fast, portable, and convenient operating advantages. We employed the recombinase polymerase amplification specific high-sensitivity enzymatic reporter unlocking (RPA-SHERLOCK) technology to establish a method for fast radiation dose assessment by measuring the expression level of radiation-inducible genes.

Low-dose radiation promotes high-fat diet-induced atherosclerosis by activating cGAS signal pathway.

Background: Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis.

GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.

Background: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood.

Exposure to polystyrene nanoplastics induces abnormal activation of innate immunity via the cGAS-STING pathway.

Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted.

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment.

Radiation-targeted immunotherapy: A new perspective in cancer radiotherapy.

In contemporary oncology, radiation therapy and immunotherapy stand as critical treatments, each with distinct mechanisms and outcomes. Radiation therapy, a key player in cancer management, targets cancer cells by damaging their DNA with ionizing radiation. Its effectiveness is heightened when used alongside other treatments like surgery and chemotherapy.

Diverse applications and development of aptamer detection technology.

Aptamers have received extensive attention in recent years because of their advantages of high specificity, high sensitivity and low immunogenicity. Aptamers can perform almost all functions of antibodies through the combination of spatial structure and target, which are called "chemical antibodies". At present, aptamers have been widely used in cell imaging, new drug development, disease treatment, microbial detection and other fields.

PARP1 modulates METTL3 promoter chromatin accessibility and associated LPAR5 RNA mA methylation to control cancer cell radiosensitivity.

Chromatin remodeling and N-methyladenosine (mA) modification are two critical layers in controlling gene expression and DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent mA methylation of poly(A) RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription.

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice.

Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study.

LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway.

Background: Epithelial-to-mesenchymal transition (EMT) is a critical event contributing to more aggressive phenotypes in cancer cells. EMT is frequently activated in radiation-targeted cells during the course of radiotherapy, which often endows cancers with acquired radioresistance. However, the upstream molecules driving the signaling pathways of radiation-induced EMT have not been fully delineated.

Low dose radiation therapy attenuates ACE2 depression and inflammatory cytokines induction by COVID-19 viral spike protein in human bronchial epithelial cells.

Low-dose radiation therapy (LDRT) is an evidence-based anti-inflammatory treatment. In anti-COVID-19, our study suggests that low to moderate dose radiation of < 1.5 Gy can inhibit the induction of inflammatory cytokine and attenuate the ACE2 depression induced by spike protein in human bronchial epithelial cells in COVID-19 infection.

ZGRF1 promotes end resection of DNA homologous recombination via forming complex with BRCA1/EXO1.

To maintain genomic stability, the mammalian cells has evolved a coordinated response to DNA damage, including activation of DNA repair and cell cycle checkpoint processes. Exonuclease 1 (EXO1)-dependent excision of DNA ends is important for the initiation of homologous recombination (HR) repair of DNA breaks, which is thought to play a key role in activating the ATR-CHK1 pathway to induce G2/M cell cycle arrest. But the mechanism is still not fully understood.

DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a member of the phosphatidylinositol 3-kinase related kinase family, which can phosphorylate more than 700 substrates. As the core enzyme, DNA-PKcs forms the active DNA-PK holoenzyme with the Ku80/Ku70 heterodimer to play crucial roles in cellular DNA damage response (DDR). Once DNA double strand breaks (DSBs) occur in the cells, DNA-PKcs is promptly recruited into damage sites and activated.

A Biomarker Panel of Radiation-Upregulated miRNA as Signature for Ionizing Radiation Exposure.

Ionizing radiation causes serious injury to the human body and has long-time impacts on health. It is important to find optimal biomarkers for the early quick screening of exposed individuals. A series of miRNAs signatures have been developed as the new biomarkers for diagnosis, survival, and prognostic prediction of cancers.

The p53/RMRP/miR122 signaling loop promotes epithelial-mesenchymal transition during the development of silica-induced lung fibrosis by activating the notch pathway.

Background: Understanding the roles of long noncoding RNAs (lncRNAs) in EMT would help with establishing novel avenues for further uncovering the mechanisms of lung fibrosis and identifying preventative and therapeutic targets. This study aimed to identify silica-induced specific lncRNAs and investigate the feedback loop regulation among their upstream and downstream genes.

Methods And Materials: A microarray assay, quantitative real-time polymerase chain reaction and Western blot analysis dual-luciferase reporter gene activity and chromatin immunoprecipitation assays were used.

MiRNA-155-5p inhibits epithelium-to-mesenchymal transition (EMT) by targeting GSK-3β during radiation-induced pulmonary fibrosis.

Radiation-induced pulmonary fibrosis (RIPF) is a major lung complication in using radiotherapy to treat thoracic diseases. MicroRNAs (miRNAs) are reported to be the therapeutic targets for many diseases. However, the miRNAs involved in the pathogenesis of RIPF are rarely studied as potential therapeutic targets.

HUWE1-dependent DNA-PKcs neddylation modulates its autophosphorylation in DNA damage response.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is the core component of DNA-PK complex in the non-homologous end-joining (NHEJ) repair of DNA double-strand breaks, and its activity is strictly controlled by DNA-PKcs phosphorylation. The ubiquitin-like protein, NEDD8 is involved in regulation of DNA damage response, but it remains mysterious whether and how NEDD8-related neddylation affects DNA-PKcs and the NHEJ process. Here, we show that DNA-PKcs is poly-neddylated at its kinase domain.

Self-Assembled Multivalent Aptamer Nanoparticles with Potential CAR-like Characteristics Could Activate T Cells and Inhibit Melanoma Growth.

In this study, the CAR-like multivalent aptamer nanoparticles (X-polymers) were assembled with the dimer of murine CD28 RNA aptamer (CD28Apt7), the tetramer of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) RNA aptamer (Del60), and a folic acid labeled ssDNA fragment in a stable nucleic acid three-way junction scaffold (3WJ). Results showed that the X-polymers could recognize both the mCD28 and mCTLA-4 molecules. Confocal imaging and flow cytometry assays showed that the X-polymers could target both T cells and B16 cells .

Identification of Functional mimotopes of human Vasorin Ectodomain by Biopanning.

Human vasorin (VASN) as a type I transmembrane protein, is a potential biomarker of hepatocellular carcinoma, which could expedite HepG2 cell proliferation and migration significantly . The ectodomain of VASN was proteolytically released to generate soluble VASN (sVASN), which was validated to be the active form. Among several monoclonal antibodies produced against sVASN, the clone V21 was found to bind with the recombinant human sVASN (rhsVASN) with the highest affinity and specificity, and also have inhibitory effects on proliferation and migration of HepG2 cells.

Aptamer selection and application in multivalent binding-based electrical impedance detection of inactivated H1N1 virus.

The type A influenza viruses are the most virulent and variable human pathogens with epidemic or even pandemic threat. The development of sensitive, specific and safe field testing methods is in particular need and quite challenging. We report here the selection and practical utilization of the inactivated influenza virus-specific aptamers.

An alternative microRNA-mediated post-transcriptional regulation of GADD45A by p53 in human non-small-cell lung cancer cells.

GADD45A (growth arrest and DNA damage inducible alpha), a stress response gene induced by genotoxic and nongenotoxic stresses, is implicated in various key processes, including the control of cell cycle checkpoints and DNA repair. The expression of GADD45A is directly regulated by numerous transcription factors, with p53 being the most representative. Moreover, post-transcriptional regulation also plays a role in GADD45A expression.

Species-specific mutual regulation of p53 and miR-138 between human, rat and mouse.

In recent years, p53 was identified to regulate the expression of many miRNAs and was also regulated by miRNAs. In this paper, we found that miR-138 showed a pronounced increase after p53 activation in human non-small cell lung cancer (NSCLC) cells, which is mediated by p53 binding sites in the promoter region of its host gene, but this did not happen with rat and mouse cells. More interestingly, we found that p53 could be also regulated by miR-138 in mouse and rat cells, but not in the human NSCLC cells.