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High concentrations of antioxidants in cancer cells are huge obstacle in cancer radiotherapy. Erastin was first discovered as an inducer of iron-dependent cell death called ferroptosis accompanied by antioxidant depletion caused by cystine glutamate antiporter inhibition. Therefore, treatment with erastin is expected to potentially enhance cellular radiosensitivity. In this study, we investigated the influence of treatment with erastin on the radiation efficiency against cancers. The clonogenic ability, glutathione peroxidase 4 (GPX4) expression, and glutathione concentration were evaluated using HeLa and NCI-H1975 adenocarcinoma cell lines treated with erastin and/or X-ray irradiation. For in vivo studies, NCI-H1975 cells were transplanted in the left shoulder of nude mice, and then radiosensitizing effect of erastin and glutathione concentration in the cancer were evaluated. Treatment with erastin induced ferroptosis and decreased the concentration of glutathione and GPX4 protein expression levels in the two tumor cell lines. Moreover, erastin enhanced X-ray irradiation-induced cell death in both human tumor cell lines. Furthermore, erastin treatment of a tumor-transplanted mouse model similarly demonstrated the radiosensitizing effect and decrease in intratumoral glutathione concentration in the in vitro study. In conclusion, our study demonstrated the radiosensitizing effect of erastin on two adenocarcinoma cell lines and the tumor xenograft model accompanied by glutathione depletion, indicating that ferroptosis inducers that reduce glutathione concentration could be applied as a novel cancer therapy in combination with radiotherapy.

The sodium-independent cystine-glutamate antiporter plays an important role in extracellular cystine uptake. It comprises the transmembrane protein, xCT and its chaperone, CD98. Because glutathione is only weakly cell membrane permeable, cellular uptake of its precursor, cystine, is known to be a key step in glutathione synthesis. Moreover, it has been reported that xCT expression affects the progression of tumors and their resistance to therapy. Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential. Here, we describe a radio-sensitizing effect of sulfasalazine using a B16F10 melanoma model. Sulfasalazine decreased glutathione concentrations and resistance to H2O2 in B16F10 melanoma cells, but not in mouse embryonic fibroblasts. It synergistically enhanced the cyto-killing effect of X-irradiation in B16F10 cells. It inhibited cellular DNA damage repair and prolonged cell cycle arrest after X-irradiation. Furthermore, in an in vivo transplanted melanoma model, sulfasalazine decreased intratumoral glutathione content, leading to enhanced susceptibility to radiation therapy. These results suggest the possibility of using SAS to augment the treatment of radio-resistant cancers.

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

Background Thyroid hormone (T3) is critical for development in all vertebrates. The mechanism underlying T3 effect has been difficult to study due to the uterus-enclosed nature of mammalian embryos. Anuran metamorphosis, which is dependent on T3 but independent of maternal influence, is an excellent model to study the roles of T3 and its receptors (TRs) during vertebrate development. We and others have reported various effects of TR knockout ( TRα and TRβ ) during Xenopus tropicalis development. However, these studies were largely focused on external morphology. Results We have generated TRβ knockout animals containing an out-frame-mutation of 5 base deletion by using the CRISPR/Cas9 system and observed that TRβ knockout does not affect premetamorphic tadpole development. We have found that the basal expression of direct T3-inducible genes is increased but their upregulation by T3 is reduced in the intestine of premetamorphic homozygous TRβ knockout animals, accompanied by reduced target binding by TR. More importantly, we have observed reduced adult stem cell proliferation and larval epithelial apoptosis in the intestine during T3-induced metamorphosis. Conclusions Our data suggest that TRβ plays a critical role in intestinal remodeling during metamorphosis.

. This study examined sex differences in passing performance using match data from the 2022 FIFA Men’s World Cup and the 2023 FIFA Women’s World Cup. A total of 128 team observations per tournament were analyzed using StatsBomb event data. . Passing performance was assessed using pass frequency, pass completion rate, mean pass distance, pass length categories (short, medium, and long), and pitch zones (defensive, middle, and attacking thirds). . Men showed significantly higher values for number of passes, pass completion rate, and mean pass distance than women. Women exhibited a higher proportion of short passes and a lower proportion of medium passes, whereas no clear difference was observed in long-pass proportion. Although pass distribution across pitch zones was similar between sexes, women attempted fewer passes in the defensive and middle thirds. Significant interactions between sex, pass length, and pitch zone were observed for all variables (all p < 0.05), indicating that sex differences depended on tactical context. . These findings suggest that sex differences in football passing performance are context-dependent rather than uniform. Integrating pass length and spatial context provides a more comprehensive understanding of performance differences between men’s and women’s football and may inform coaching and performance analysis in elite football.

Objectives Endoscopic transpapillary gallbladder stenting (EGBS) has demonstrated high technical and clinical success rates in endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis. The effectiveness of a 5‐Fr endoscopic naso‐gallbladder drainage (ENGBD) tube for flushing and the internal fistula technique after tube cutting has also been reported. We developed an alternative one‐step semi‐deployed flushing and stenting technique for EGBS using a 7‐Fr pigtail stent that avoids tube resection and evaluated its effectiveness and safety compared with that of endoscopic nasogastric gallbladder drainage. Methods We retrospectively evaluated 30 patients who underwent ETGBD for acute cholecystitis between April 2023 and November 2024. Results The technical and clinical success rates of the one‐step semi‐deployment flushing and stenting techniques were 95.2% (20/21) and 100% (20/20), respectively. No adverse events were reported. The procedure time did not differ significantly from that of ENGBD. Conclusions EGBS using one‐step semi‐deployment flushing and stenting is a simple and effective treatment for acute cholecystitis in patients with ETGBD.

Purpose Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3- 18 F-fluoropropyl)-2-nitroimidazole ( 18 F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. Methods Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with  18 F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, 18 F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. Results Eribulin significantly reduced  18 F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in 18 F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with 18 F-DiFA accumulation. Conclusion These results demonstrated that 18 F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.

Thyroid hormone (T3) regulates adult intestine development through T3 receptors (TRs). It is difficult to study TR function during postembryonic intestinal maturation in mammals due to maternal influence. We chose intestinal remodeling during Xenopus tropicalis metamorphosis as a model to study TR function in adult organ development. By using ChIP (chromatin immunoprecipitation)-Seq, we identified over 3000 TR-bound genes in the intestine of premetamorphic wild type or TRα (the major TR expressed during premetamorphosis)-knockout tadpoles. Surprisingly, cell cycle-related GO (gene ontology) terms and biological pathways were highly enriched among TR target genes even though the first major event during intestinal metamorphosis is larval epithelial cell death, and TRα knockout drastically reduced this enrichment. More importantly, treatment of tadpoles with cell cycle inhibitors blocked T3-induced intestinal remodeling, especially larval epithelial cell death, suggesting that TRα-dependent activation of cell cycle is important for T3-induced apoptosis during intestinal remodeling. Tanizaki et al use ChIP-Seq to identify over 3000 Thyroid hormone (T3) receptor (TR)-bound genes in the intestine of premetamorphic wild type Xenopus tropicalis tadpoles and in TRα-knockouts. They show that treatment of tadpoles with cell cycle inhibitors blocked T3-induced intestinal remodeling, suggesting that TRα-dependent activation of the cell cycle is important for T3-induced apoptosis during intestinal remodelling.

Objectives Appropriate sedative and analgesic selection is essential to reduce patient discomfort and body movement to safely conduct endoscopic ultrasonography (EUS). However, few cases have examined sedation with propofol in EUS, and few studies the need for combined analgesia. In this study, we retrospectively evaluated the usefulness and safety of propofol without analgesics for sedation in biliopancreatic observational EUS. Methods This single‐center retrospective study included 516 observational biliopancreatic EUS procedures using propofol alone performed between April 2021 and March 2023. The primary and secondary endpoints were the observational biliopancreatic EUS results obtained with propofol alone and adverse event occurrence, respectively. Results The median examination time and total propofol dose were 22 (range: 10–67) min and 186.5 (range: 50–501) mg, respectively. The median starting Richmond Agitation‐Sedation Scale and Visual Analog Scale scores were −5 (range: −5–1) and 0 (range: 0–10), respectively. The median recovery time was 22 (range: 5–80) min. Adverse events occurred in 60 (11.6%) patients. Trainee‐performed examination (odds ratio [OR] 3.52, 95% confidence interval [CI]: 1.63–7.60, p = 0.0014) and examination length (>22 min; OR 1.67, 95% CI: 0.95–2.92, p = 0.07) were risk factors for adverse events. High body mass index (OR 1.87, 95% CI: 1.10–3.16, p = 0.02) and extended examination time (OR 4.23, 95% CI: 2.08–8. 57, p < 0.001) were risk factors for delayed recovery. Conclusions During observational biliopancreatic EUS, propofol is useful as a single sedative and offers high patient satisfaction and relative safety.

Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.