VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor.

Vascular endothelial growth factor (VEGF) is closely related to angiogenesis. Anticancer therapy by inhibiting VEGF signaling is well established. However, the role of VEGF in cell-cell communication during the response to ionizing radiation is not well understood.

-Derived Proline:Arginine Poly-Dipeptides Modulate Cytoskeleton and Mechanical Stress Response.

Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR poly-dipeptides affect cytoskeletal organization and focal adhesion (FA) formation. Here, we show that changes to the cytoskeleton and FA by PR poly-dipeptides result in the alteration of cell stiffness and mechanical stress response.

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R).

27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.

The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown.

Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways.

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU is thought to inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis and has been found to induce single- and double-strand DNA breaks. ATR Ser/Thr kinase (ATR) is a principal kinase in the DNA damage response and is activated in response to UV- and chemotherapeutic drug-induced DNA replication stress, but its role in cellular responses to 5-FU is unclear.

Brainstem Organoids From Human Pluripotent Stem Cells.

The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders.

Early and Delayed Induction of DSBs by Nontargeted Effects in ICR Mouse Lymphocytes after In Vivo X Irradiation.

The goal of this study was to determine whether in vivo X irradiation induces nontargeted effects, such as delayed effects and bystander effects in ICR mouse lymphocytes. We first examined the generation of DNA double-strand breaks (DSBs) in lymphocytes, isolated from ICR mice exposed to 1 Gy X irradiation, by enumeration of p53 binding protein 1 (53BP1) foci, and observed that the number of 53BP1 foci reached their maximum 3 days postirradiation and decreased to background level 30 days postirradiation. However, the number of 53BP1 foci was significantly increased in lymphocytes isolated from ICR mice 90-365 days postirradiation.

Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent Repair for DNA Double-strand Breaks.

Background/aim: Gemcitabine (GEM) is used in clinical chemo-radiotherapy; however, the mechanism that contributes to enhanced radiosensitivity by GEM is not fully-understood. We evaluated the effect of GEM on radiosensitization in pancreatic cancer cell lines.

Materials And Methods: Pancreatic cell lines PK-59 and PK-45p were used.

Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells.

Ionizing radiation-induced cellular senescence is thought to be caused by nuclear DNA damage that cannot be repaired. However, here we found that radiation induces delayed increase of intracellular oxidative stress after irradiation. We investigated whether the relief of delayed oxidative stress by ascorbic acid would suppress the radiation-induced cellular senescence in Syrian golden hamster embryo (SHE) cells.

Ionizing radiation-induced cell death is partly caused by increase of mitochondrial reactive oxygen species in normal human fibroblast cells.

Radiation-induced cell death is thought to be caused by nuclear DNA damage that cannot be repaired. However, in this study we found that a delayed increase of mitochondrial reactive oxygen species (ROS) is responsible for some of the radiation-induced cell death in normal human fibroblast cells. We have previously reported that there is a delayed increase of mitochondrial (·)O2(-), measured using MitoSOX™ Red reagent, due to gamma irradiation.

Comparison of the biological effects of (18)F at different intracellular levels.

We herein examined the biological effects of cells treated with (18)F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of (18)F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of (18)F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF).

Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells.

Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation.

Epigenetic gene silencing is a novel mechanism involved in delayed manifestation of radiation-induced genomic instability in mammalian cells.

We examined mechanisms involved in delayed mutagenesis in CHO-LacZeo cells harboring the fusion gene between the bacterial LacZ and the Zeocin-resistance genes. After X irradiation, Zeocin-resistant primary colonies were isolated, and the primary clones were subjected to the secondary colony formation in the absence of Zeocin. We found that the surviving primary clones showed a significantly higher delayed mutation frequency compared with those derived from nonirradiated CHO-LacZeo cells.