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OBJECTIVE: Tissue fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc), and an increasing number of promising molecular targets for antifibrotic therapies have been described recently. Transforming growth factor beta (TGFbeta) is well known to be the principal factor that leads to tissue fibrosis. The present study was undertaken to investigate the ability of HSc025, a novel small compound that antagonizes TGFbeta/Smad signaling through the activation of nuclear translocation of Y-box binding protein 1, to prevent tissue fibrosis in vitro or in mouse models of SSc. METHODS: Human dermal fibroblasts were exposed to HSc025 at various concentrations in the presence of TGFbeta, and levels of collagen or fibronectin expression were determined. HSc025 (15 mg/kg/day for 14 days) was administered orally to tight skin mice and to mice with bleomycin-induced pulmonary fibrosis. Improvement of tissue fibrosis was evaluated by histologic or biochemical examination in each model. RESULTS: Pretreatment with HSc025 prevented Smad-dependent promoter activation, in a dose-dependent manner; however, HSc025 had no effect on TGFbeta-induced phosphorylation of Smad3. The inhibitory effects of HSc025 on TGFbeta-induced collagen or fibronectin expression were also confirmed in vitro. Orally administered HSc025 significantly reduced hypodermal thickness and hydroxyproline content in tight skin mice, and markedly decreased the histologic score and hydroxyproline content in the lungs of bleomycin-treated mice. CONCLUSION: These results demonstrate that HSc025 is a novel inhibitor of TGFbeta/Smad signaling, resulting in the improvement of skin and pulmonary fibrosis. Orally available HSc025 might therefore be useful in the treatment of SSc. [ABSTRACT FROM AUTHOR]

Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, includingl-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressingl-selectin, ICAM-1 or their ligands were examined in mice lackingl-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss ofl-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss ofl-selectin or combined loss ofl-selectin and ICAM-1. In both situations, the combined loss ofl-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-γ and tumour necrosis factor (TNF)-α but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1,l-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate thatl-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response.

The aim of this study was to determine trapezius muscle hardness in 9 healthy volunteers before and after word processing tasks with a video display terminal (VDT) at three different heights. When using a desktop personal computer (PC), no change was observed in muscle hardness even after a 30-min task if a subject was in the reference posture with a declination angle formed by the Reid's line directed toward the upper edge of the PC screen and the horizontal plane within 5-10 degrees. However, an increase in muscle hardness was observed after a 15-min task in a posture of looking up at the screen (angle of elevation: 15-20 degrees) and after a 30-min task in a posture of looking down at the screen (angle of declination: 15-20 degrees). When the same tasks were performed with a notebook PC, muscle hardness increased after 15 min. Fifteen minutes of relaxation exercise reduced the muscle hardness caused by VDT work. [ABSTRACT FROM AUTHOR]

To narrow down the candidates of the alloying element powders for Ti-5Al-1Fe products manufactured with BE/PM, two master alloy powders, atomized spherical 5Al-1Fe and crushed-andground polyhedron 5Al-1Fe-4Ti ternary powders, were investigated with emphasizing on homogeneity of alloying elements, Al and Fe, in sintered Ti-5Al-1Fe. Intense Al segregation is recognized in the sintered specimen manufactured using 5Al-1Fe atomized powders, while strong segregation is not observed in the specimen manufactured using 5Al-1Fe-4Ti crushed-and-ground powders. Density of sintered specimen manufactured using 5Al-1Fe atomized powders is lower than that manufactured using 5Al-1Fe-4Ti crushed-and-ground powders. Al segregation and lower sintered density are probably caused by lower density of the powder substance, high flowability of spherical powders and phase constitutions some of which have low melting points. Those factors have to be taken into account to manufacture sintered titanium alloys with high homogeneity by BE/PM.

To challenge the significant reduction of manufacturing cost of Ti thin sheet or foil in the future, manufacturing of Ti foil by electrodeposition route was studied with emphasizing on factors affecting quality of the foil and separability from Mo cathode. Current density was one of the strong factors affecting soundness of deposited Ti foil and its separability from the cathode. Electrolyte bath temperature also affected soundness and separability of deposited Ti foil. Separability was closely related to interdiffusion distance of Ti and Mo, that is, shorter diffusion distance, which was brought by low temperature and low current density, led to good separability as well as good surface quality. By reflecting above knowledge, post card size Ti foil of around 0.1 mm in thickness was successfully obtained. It had good quality and could be separated from the cathode by hand. O and Fe contents were drastically decreased by this process.

To respond to the requirements for porous Ti sheet with the balanced properties of high porosity and good mechanical properties, and to optimize the manufacturing conditions of the simple powder-filling plus sintering process, effects of sintering temperatures on density and bending strength in porous Ti sheet were investigated. The optimum sintering condition was 900-950 °C for 1h to obtain porous Ti sheet with the balanced density ratio (around 40%) and high bending strength. The polyhedron shape of HDH powders contributed to those balanced properties, in which localized sintering raised bending strength with keeping high porosity (low density). Using the optimum manufacturing conditions, large sized porous Ti sheet of 400 × 800 × 0.5 mm was successfully manufactured.

Abstract Background Bacteria release a wide variety of small molecules including cell-to-cell signaling compounds. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl-HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. QS plays a significant role in the pathogenesis of infectious diseases and in beneficial symbiosis by responding to acyl-HSLs in Pseudomonas aeruginosa. It is considered that the selection of bacterial languages is necessary to regulate gene expression and thus it leads to the regulation of virulence and provides a growth advantage in several environments. In this study, we hypothesized that RND-type efflux pump system MexAB-OprM of P. aeruginosa might function in the selection of acyl-HSLs, and we provide evidence to support this hypothesis. Results Loss of MexAB-OprM due to deletion of mexB caused increases in QS responses, as shown by the expression of gfp located downstream of the lasB promoter and LasB elastase activity, which is regulated by a LasR-3-oxo-C12-HSL complex. Either complementation with a plasmid containing wild-type mexB or the addition of a LasR-specific inhibitor, patulin, repressed these high responses to 3-oxo-acyl-HSLs. Furthermore, it was shown that the acyl-HSLs-dependent response of P. aeruginosa was affected by the inhibition of MexB transport activity and the mexB mutant. The P. aeruginosa MexAB-OprM deletion mutant showed a strong QS response to 3-oxo-C10-HSL produced by Vibrio anguillarum in a bacterial cross-talk experiment. Conclusion This work demonstrated that MexAB-OprM does not control the binding of LasR to 3-oxo-Cn-HSLs but rather accessibility of non-cognate acyl-HSLs to LasR in P. aeruginosa. MexAB-OprM not only influences multidrug resistance, but also selects acyl-HSLs and regulates QS in P. aeruginosa. The results demonstrate a new QS regulation mechanism via the efflux system MexAB-OprM in P. aeruginosa.

A single epithelial cell embedded in extracellular matrix (ECM) can proliferate to form an apical lumen-harboring cyst, whose formation is a fundamental step in epithelial organ development. At an early two-cell stage after cell division, the cell doublet typically displays "inverted" polarity, with apical and basolateral proteins being located to the ECM-facing and cell-cell-contacting plasma membranes, respectively. Correct cystogenesis requires polarity reorientation, a process containing apical protein endocytosis from the ECM-abutting periphery and subsequent apical vesicle delivery to a cell-cell contact site for lumen formation. Here, we show that downstream of the ECM-signal-transducer β1-integrin, Rac1, and its effector IQGAP1 promote apical protein endocytosis, contributing to polarity reorientation of mammalian epithelial Madin-Darby canine kidney (MDCK) cells at a later two-cell stage in three-dimensional culture. Rac1-GTP facilitates IQGAP1 interaction with the Rac-specific activator Tiam1, which also contributes to the endocytosis and enhances the effect of IQGAP1. These findings suggest that Tiam1 and IQGAP1 form a positive feedback loop to activate Rac1. With Rac1-GTP, IQGAP1 also binds to AP2α, an adaptor protein subunit for clathrin-mediated endocytosis; depletion of the AP2 complex impairs apical protein endocytosis in MDCK doublets. Thus, Rac1 likely participates in polarity reorientation at the two-cell stage via its interaction with IQGAP1., (© 2024 The Author(s). Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC)., Methods: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate., Results: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia., Conclusions: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC., (© 2024. The Author(s).)

Interleukin-10 (IL-10) is a highly pleiotropic cytokine that regulates immunological homeostasis through anti-inflammatory and/or immunostimulatory functions. Moreover, IL-10 is well known to exert diverse roles in tumor immunology and immunotherapy. The present study investigated the presence of circulating tumor antigen-specific IL-10-producing T cells in patients with head and neck squamous cell carcinoma (HNSCC), and determined factors that may influence the immunodynamics of IL-10-producing T cells. In vitro , peripheral blood mononuclear cells (PBMCs) stimulated with the tumor antigens p53 and MAGE-A4 were evaluated for interferon (IFN)-γ/IL-10 production using the IFN-γ/IL-10 double-color enzyme-linked immunosorbent spot assay. The proportion of T cells expressing immune checkpoint molecules in PBMCs was analyzed using flow cytometry. Of the 18 patients with HNSCC, 2 (11.1%) and 9 (50.0%) exhibited p53-specific IFN-γ and IL-10 production, respectively. Meanwhile, MAGE-A4-specific IFN-γ and IL-10 production was detected in 4 (28.6%) and 7 (50.0%) of 14 patients. In the p53-specific responses, IL-10-producing T cells were observed in significantly more patients than IFN-γ producing T cells (P=0.0275). In both CD4 + and CD8 + T cells, the proportion of T cells expressing lymphocyte activation gene-3 (Lag-3) was significantly lower in patients with p53-specific IL-10 production than in those without. In certain patients, Lag-3 blockade enhanced tumor antigen-specific IL-10. Taken together, the present study successfully demonstrated that tumor antigen-specific IL-10-producing T cells exist in the peripheral blood of patients with HNSCC and that Lag-3 + T cells may serve an important role in modulating IL-10-producing T cells. These findings provide novel insights into the roles of IL-10 and Lag-3 in mediating antitumor immune responses., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Horikawa et al.)

Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms., (© 2024. The Author(s).)

This study aimed to investigate whether quadriceps muscle thickness (QMT) is useful for nutritional assessment in patients with stroke. This was a retrospective cohort study. Nutritional risk was assessed using the Geriatric Nutritional Risk Index (GNRI), with GNRI < 92 indicating a risk of malnutrition and GNRI ≥ 92 indicating normal conditions. Muscle mass was assessed using QMT and calf circumference (CC). The outcome was Functional Independence Measure (FIM) effectiveness. The cutoff values of QMT and CC for discriminating between high and low GNRI were determined using the receiver operating characteristic curve. The accuracy of the nutritional risk discrimination model was evaluated using the Matthews correlation coefficient (MCC). Multiple regression analysis was performed to assess the relationship between nutritional risk, as defined by QMT and CC, and FIM effectiveness. A total of 113 patients were included in the analysis. The cutoff values of QMT and CC for determining nutritional risk were 49.630 mm and 32.0 cm for men (MCC: 0.576; 0.553) and 41.185 mm and 31.0 cm for women (MCC: 0.611; 0.530). Multiple regression analysis showed that only nutritional risk defined by QMT was associated with FIM effectiveness. These findings indicate that QMT is valid for assessing nutritional risk in patients with stroke.

Proper nutritional management is important for the growth and development of children with motor or intellectual disabilities; however, few studies have investigated the nutrient intake of children with disabilities. This study aimed to investigate the nutrient intake and food groups that are the main sources of nutrients for children with disabilities. This cross-sectional observational study included twenty-five children (mean age, 11⋅8 years) from five hospitals in Japan. Using a 3-d weighed dietary record, we estimated the daily nutrient intake and food and beverage sources that contributed to nutrient intake. The mean values of calcium, magnesium, iron, vitamin A, thiamine, riboflavin, and vitamin C intake were below the recommended dietary allowance, and those of dietary fiber and potassium were below the levels recommended by the Tentative Dietary Goal for Preventing Lifestyle-related Diseases (DG). In contrast, the mean intake values of fat, saturated fatty acids, and sodium were above the DG levels. Dairy products, meat, vegetables, and cereals were found to be the major contributors of nutrients. Increased intake of vegetables may help alleviate insufficient micronutrient intake in children with disabilities., (© The Author(s) 2023.)

This report describes a net C-H radiocyanation reaction for the transformation of electron rich (hetero)aromatic substrates into 11 CN-labeled products. Electrophilic C(sp 2 )-H iodination of the (hetero)arene with N -iodosuccinimide is followed by Cu-mediated radiocyanation with K 11 CN. This sequence is applied to a variety of substrates, including the nucleobases uracil and cytosine, the amino acids tyrosine and tryptophan, and the peptide LYRAGWRAFS, which undergoes selective C-H radiocyanation at the tryptophan (W) residue., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Objectives: Gene therapy using viral vectors and antibody-based therapies continue to expand within the pharmaceutical market. We evaluated whether Cellhesion ® VP, a chitin-based material, can be used as 3D culture platform for cell lines used for the production of antibodies and viral vectors., Results: The results of Cell Counting Kit-8 assay and LDH assay revealed that Cellhesion ® VP had no adverse effect to Human Embryonic Kidney (HEK) 293, A549 and Chinese hamster ovary (CHO) DG44-Interferon-β (IFN) cells. Cell growth analyses showed that Cellhesion ® VP supported the 3D culture of HEK293, A549 and CHO DG44- IFN-β cells with a spherical morphology. Importantly, subculture of these cell lines on Cellhesion ® VP was easily performed without trypsinization because cells readily transferred to newly added scaffold. Our data also suggest that CHO DG44-IFNβ, cultured on Cellhesion ® VP secreted IFNβ stably and continuously during the culture period., Conclusions: Cellhesion ® VP provides a simple and streamlined expansion culture system for the production of biopharmaceuticals., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Renal fibrosis is the final manifestation of chronic kidney disease (CKD); its prevention is vital for controlling CKD progression. Indoxyl sulfate (IS), a typical sulfate-conjugated uremic solute, is produced in the liver via the enzyme sulfotransferase (SULT) 1A1 and accumulates significantly during CKD. We investigated the toxicopathological role of IS in renal fibrosis using Sult1a1 -KO mice and the underlying mechanisms. The unilateral ureteral obstruction (UUO) model was created; kidney IS concentrations, inflammation, and renal fibrosis were assessed on day 14. After UUO treatment, inflammation and renal fibrosis were exacerbated in WT mice, with an accumulation of IS in the kidney. However, they were significantly suppressed in Sult1a1 -KO mice. CD206 + expression was upregulated, and β-catenin expression was downregulated in Sult1a1 -KO mice. To confirm the impact of erythropoietin (EPO) on renal fibrosis, we evaluated the time-dependent expression of EPO. In Sult1a1 -KO mice, EPO mRNA expression was improved considerably; UUO-induced renal fibrosis was further attenuated by recombinant human erythropoietin (rhEPO). Thus, UUO-induced renal fibrosis was alleviated in Sult1a1 -KO mice with a decreased accumulation of IS. Our findings confirmed the pathological role of IS in renal fibrosis and identified SULT1A1 as a new therapeutic target enzyme for preventing and attenuating renal fibrosis., Competing Interests: The authors declare no conflict of interest.

Society in eusocial insects is based on the reproductive division of labor, with a small number of reproductive individuals supported by a large number of nonreproductive individuals. Because inclusive fitness of all colony members depends on the survival and fertility of reproductive members, sterile members provide royals with special treatment. Here, we show that termite kings and queens each receive special food of a different composition from workers. Sequential analysis of feeding processes demonstrated that workers exhibit discriminative trophallaxis, indicating their decision-making capacity in allocating food to the kings and queens. Liquid chromatography tandem-mass spectrometry analyses of the stomodeal food and midgut contents revealed king- and queen-specific compounds, including diacylglycerols and short-chain peptides. Desorption electrospray ionization mass spectrometry imaging analyses of 13 C-labeled termites identified phosphatidylinositol and acetyl-l-carnitine in the royal food. Comparison of the digestive tract structure showed remarkable differences in the volume ratio of the midgut-to-hindgut among castes, indicating that digestive division of labor underlies reproductive division of labor. Our demonstration of king- and queen-specific foods in termites provides insight into the nutritional system that underpins the extraordinary reproduction and longevity of royals in eusocial insects., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Purpose: Vaginal progesterone (VP) alone has been used as luteal support (LS) in HRT-FET cycles without measuring serum progesterone concentrations (SPC) because it can achieve adequate intrauterine progesterone levels. However, several reports showed that the co-administration of progestin produced better outcomes than VP alone. We tried to address this discrepancy, focusing on SPC., Methods: VP was given to 180 women undergoing HRT-FET. We measured SPC when pregnancy was diagnosed on day 14 of LS. We compared assisted reproductive technology outcomes between VP alone versus VP + dydrogesterone (D)., Results: When using VP alone, average SPC in the miscarriage cases (9.6 ng/mL) were significantly lower compared with the ongoing pregnancy (OP) cases (14.7 ng/mL). The cut-off value for progesterone, 10.7 ng/mL, was a good predictor for the subsequent course of the pregnancy. Of 76 women receiving D ± VP from the start of LS and achieving a pregnancy, the numbers of OP were 44 (84.6%) in SPC ≥ 10.7 ng/mL and 20 (83.3%) in SPC ≤ 10.7 ng/mL with no significant difference., Conclusion: VP alone resulted in lower SPC in some pregnant women in HRT-FET cycles and exhibited a lower OP rate. The co-administration of D improved an OP rate of low progesterone cases to the level comparable with non-low progesterone cases., Competing Interests: All the authors state explicitly that there are no conflicts of interest in connection with this article., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl β-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl β-D-glucopyranoside arabinosylation to produce HexVic in planta., (© 2023. The Author(s).)

The plasma membrane (PM) serves multiple functions to support cell activities with its heterogeneous molecular distribution. Fatty acids (FAs) are hydrophobic components of the PM whose saturation and length determine the membrane's physical properties. The FA distribution contributes to the PM's lateral heterogeneity. However, the distribution of PM FAs is poorly understood. Here, we proposed the FA cluster hypothesis, which suggested that FAs on the PM exist as clusters. By the optogenetic tool translocating the endoplasmic reticulum (ER), we were able to manipulate the distribution of PM FAs. We used time-of-flight combined secondary ion mass spectrometry (TOF-SIMS) to image PM FAs and discovered that PM FAs were presented and distributed as clusters and are also manipulated as clusters. We also found the existence of multi-FA clusters formed by the colocalization of more than one FA. Our optogenetic tool also decreased the clustering degree of FA clusters and the formation probability of multi-FA clusters. This research opens up new avenues and perspectives to study PM heterogeneity from an FA perspective. This research also suggests a possible treatment for diseases caused by PM lipid aggregation and furnished a convenient tool for therapeutic development.

Background: Stem cells from human exfoliated deciduous teeth (SHED) are a mesenchymal stem cell type and have recently attracted attention for their high proliferative rate, multipotency, and immunosuppressive properties. However, SHED have not yet been investigated for anticancer properties. We therefore investigated whether SHED can be used as a treatment modality, particularly for anti-glioma therapy., Methods: In vitro , we examined the mobility of SHED and their ability to migrate towards glioma-conditioned medium and specific growth factors secreted by malignant gliomas. In vivo , we transplanted SHED into the left hemisphere of nude mice that had been previously implanted with human malignant glioma U87 cells into the right hemisphere. We assessed whether SHED had tumorigenic potential., Results: SHED exhibited strong migration ability towards malignant glioma in both in vitro and in vivo assays. In vitro , SHED migrated towards glioma-conditioned medium and specific growth factors such as stem cell factor, platelet-derived growth factor BB, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor. SHED were accumulated around tumor cells in the contralateral hemisphere 1 week after transplantation. Moreover, SHED remained in the brains of nude mice 150 days after transplantation. Finally, we verified that SHED had no malignant transformation or engraftment of SHED in the mouse brain., Conclusions: Our findings indicate that SHED can potentially be applied to track malignant glioma., Competing Interests: Kidswell Bio Corporation (formerly, Gene Techno Science Co., Ltd., Tokyo, Japan) generously provided SHED, and hMSC-AT cell as experimental materials. YM possesses stock options of Kidswell Bio Corporation. TA is serving as one of the Editorial Board members and the guest editor for the special issue titled Exploration of mechanisms in cortical plasticity of this journal. We declare that TA had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to RF. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2022 The Author(s). Published by IMR Press.)