Nagoya Journal of Medical Science最新文献

{"title":"Optimal surgical timing for non-urgent surgery patients with active infective endocarditis.","authors":"Tomonari Uemura, Hideki Ito, Ryota Yamamoto, Toshikuni Yamamoto, Sachie Terazawa, Tomo Yoshizumi, Yoshiyuki Tokuda, Yuji Narita, Masato Mutsuga","doi":"10.18999/nagjms.87.3.546","DOIUrl":"10.18999/nagjms.87.3.546","url":null,"abstract":"<p><p>While preoperative antibiotic therapy is generally recommended in non-emergency surgery cases of infective endocarditis, delaying surgery may lead to a deterioration in patient condition. This study examined deterioration of condition during preoperative antibiotic therapy and associated clinical characteristics to clarify the optimal timing for non-emergent infective endocarditis surgery. We retrospectively analyzed 65 patients (mean age 57.1 ± 16.9 years) with active left-sided infective endocarditis (57 with native valves, 8 with prosthetic valves) initially considered suitable for combined antibiotic therapy and non-emergent surgical treatment. Causative organisms were <i>Streptococcus</i> spp. (n=31), <i>Staphylococcus</i> spp. (n=15, including 5 resistant strains), and Gram-negative bacteria (n=4). Twelve patients (18%) required unexpected urgent operations shortly after starting antibiotics (median 5.5 days, interquartile range 3-8 days). Another 12 patients (18%) experienced deterioration of condition 20-30 days after starting antibiotics, including worsening heart failure (n=5), new embolic events (n=3), new perivalvular extension of infection (n=3), and worsening infection parameters (n=1). A leukocyte count >7900/μL one week after starting antibiotics predicted late deterioration (sensitivity 91%, specificity 76%, area under the receiver operating characteristic curve 0.866). Among patients with active infective endocarditis who initially received maximal antibiotic therapy and were considered for non-emergent surgery, 18% required urgent operation and another 18% experienced late deterioration. A high leukocyte count despite one week of antibiotic therapy was associated with late deterioration. For these patients, earlier surgical intervention might be beneficial to avoid a deterioration in conditions.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"546-557"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of bone regeneration in critical-sized defects using self-assembling peptide hydrogel-178, bone morphogenetic protein-2, and calcium phosphate scaffolds in a rat femur model.","authors":"Ippei Yamauchi, Hiroaki Nakashima, Sadayuki Ito, Naoki Segi, Jun Ouchida, Yoshinori Morita, Yukihito Ode, Yasuhiro Nagatani, Yuya Okada, Kei Ando, Shiro Imagama","doi":"10.18999/nagjms.87.3.421","DOIUrl":"10.18999/nagjms.87.3.421","url":null,"abstract":"<p><p>Bone regeneration is a highly demanded but challenging clinical endeavor in orthopedic surgery, necessitating the development of alternative bone grafting materials. This study aimed to evaluate the bone regenerative potential of self-assembling peptide hydrogel (0.8%), bone morphogenetic protein-2 (50 ng/μL), hydroxyapatite, and β-tricalcium phosphate, both individually and in combination with bone chips, in a rat femoral defect model. Ten-week-old female Wistar rats underwent surgical implantation of a polyetheretherketone cage into a 5-mm bony defect within the left femoral mid-shaft, maintained by an external fixator. Polyetheretherketone cages were filled with bone substitute materials alone in the first experiment and with bone substitute materials combined with bone chips in the second experiment. Radiographic and histological analyses were conducted following sacrifice at 56 weeks. While self-assembling peptide hydrogel alone exhibited moderate bone formation, with a bone-volume-to-total-volume ratio of 0.34 ± 0.09, this value was not significantly higher than that of the control group with an empty polyetheretherketone cage. Conversely, the combination of bone morphogenetic protein-2 with bone chips produced the highest level of bone regeneration, with a bone-volume-to-total-volume ratio of 0.78 ± 0.05, significantly surpassing bone chips alone (p < 0.01) and self-assembling peptide hydrogel with bone chips (p < 0.05). These findings suggest that while self-assembling peptide hydrogel holds potential as a scaffold material, particularly in minimally invasive applications, its efficacy in promoting robust bone regeneration may benefit from the inclusion of osteoinductive factors, such as bone morphogenetic protein-2.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"421-430"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between maternal depression and smartphone use: a 1.5-year follow-up cohort study of Japanese mothers.","authors":"Haruka Tamura, Naoko Nishitani","doi":"10.18999/nagjms.87.3.498","DOIUrl":"10.18999/nagjms.87.3.498","url":null,"abstract":"<p><p>Maternal depression affects 17.7% of postpartum women and can emerge years after childbirth, impacting both mothers and their children. Social support plays an important role in preventing maternal depression. Family and community were traditional sources of social support, but the rise of digital media may impact social support and therefore maternal well-being. Mothers are accustomed to technology and often use digital devices for childcare and leisure activities. This study examined the association between screen time and the onset of depression two years postpartum. A cohort study was initiated in November 2020 (baseline) with follow-up in May-June 2022, employing an anonymous online questionnaire. Study participants were first-time mothers (n = 204) of children aged 5-8 months. Measures considered basic attributes, family environment, maternal depression (Edinburgh Postnatal Depression Scale [EPDS]), screen time, and sleep status. No baseline maternal depression (EPDS score < 9) was a requirement for participation. Maternal depression onset during a 1.5-year follow-up was the dependent variable. Screen time, sleep duration, and support services were independent variables. Their relationships were analyzed using Fisher's exact test, the Mantel-Haenszel test, and logistic regression. Twenty-six participants (12.7%) developed depression (EPDS ≥ 9) within two years of childbirth. Logistic regression revealed a significant association between smartphone use time and maternal depression (odds ratio [OR] = 1.89; 95% confidence interval [CI], 1.09-3.26). No association was found between social media or game use and maternal depression. Excessive smartphone use was related to depression two years after childbirth, indicating the need for health guidance on screen time for mothers.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"498-508"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of primary cutaneous diffuse large B-cell lymphoma, leg type with <i>MYC</i> rearrangement and high BCL2 protein expression due to trisomy 18.","authors":"Yosuke Matsui, Akira Katsumi, Ken Tanaka, Fumiya Ohara, Kenta Motegi, Akihiro Abe, Shogo Tamura, Katsuya Yamamoto, Tadashi Matsushita, Miwa Adachi, Yasuyuki Nagata, Masaki Hasegawa","doi":"10.18999/nagjms.87.3.582","DOIUrl":"10.18999/nagjms.87.3.582","url":null,"abstract":"<p><p>We report the case of an 80-year-old woman with a medial thigh nodule who was diagnosed with primary cutaneous diffuse large B-cell lymphoma, leg type. Further examination identified it as double-expressor lymphoma with elevated expression of both <i>MYC</i> and <i>BCL2</i>. This elevated expression has been linked to <i>MYC</i> translocation and is likely associated with trisomy 18. Our findings suggest that trisomy 18 plays a significant role in the development of double-expressor lymphoma. While cases of double-expressor lymphoma caused by extra copies of <i>BCL2</i> have been reported, we could not find any case of double-expressor lymphoma caused by trisomy 18. Therefore, this is an unique case of double-expressor lymphoma linked to <i>MYC</i> rearrangement and trisomy 18. Double-expressor lymphoma typically has a poor prognosis and is often resistant to standard treatments. The current findings may help refine diagnostic strategies for this condition.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"582-589"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative evaluation of upper gastrointestinal subepithelial lesions using endoscopic ultrasound-guided shear wave elastography.","authors":"Takahiro Marukawa, Kazuhiro Furukawa, Ryoji Miyahara, Kohei Funasaka, Takashi Hirose, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Yoshiki Hirooka, Hiroki Kawashima","doi":"10.18999/nagjms.87.3.462","DOIUrl":"10.18999/nagjms.87.3.462","url":null,"abstract":"<p><p>Shear wave elastography provides quantitative data on tissue stiffness, but was not available for endoscopic ultrasound until recently. The present study investigated the utility of a newly developed endoscopic ultrasound-guided shear wave measurement for diagnosing upper gastrointestinal subepithelial lesions. Shear wave velocity (Vs) was measured as an indicator of tissue stiffness, and the total amount of effective shear waves (VsN) was used as a reliability index for Vs values obtained by endoscopic ultrasound-guided shear wave measurements. Among the Vs values obtained, the five with the highest VsN were selected, and their median was defined as the median Vs (Vs-med). The median VsN of the five Vs values was defined as the median VsN (VsN-med). Endoscopic ultrasound-guided shear wave measurements were performed on 23 patients, with no complications occurring in any procedure. Histopathological diagnoses included 12 gastrointestinal stromal tumors, seven leiomyomas, and four schwannomas. Vs-med values for gastrointestinal stromal tumors, leiomyomas, and schwannomas were 2.46, 1.73, and 2.85 m/s, respectively, indicating that gastrointestinal stromal tumors and schwannomas were significantly stiffer than leiomyomas. VsN-med values for gastrointestinal stromal tumors, leiomyomas, and schwannomas were 40.5, 39, and 35.5%, respectively, with no significant differences. Endoscopic ultrasound-guided shear wave measurements are feasible for upper gastrointestinal subepithelial lesions and allow for the objective, non-invasive quantification of lesion stiffness. These results suggest the potential of endoscopic ultrasound-guided shear wave measurements as a valuable tool for the differential diagnosis of upper gastrointestinal subepithelial lesions.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"462-472"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of posterior lumbar interbody fusion in chronic renal failure patients on hemodialysis.","authors":"Hiroaki Nakashima, Sadayuki Ito, Naoki Segi, Jun Ouchida, Ippei Yamauchi, Koji Sato, Shiro Imagama","doi":"10.18999/nagjms.87.3.528","DOIUrl":"10.18999/nagjms.87.3.528","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) and its treatment with hemodialysis (HD) pose unique challenges for spinal surgery due to complications such as destructive spondyloarthropathy (DSA). This study retrospectively compared the surgical outcomes of posterior lumbar interbody fusion (PLIF) between 48 HD patients and 57 non-HD controls. Patients with tumors, infections, prior spinal surgery, or severe osteoporosis were excluded. HD patients had a mean dialysis duration of 16.2 years, while controls were treated for degenerative lumbar conditions. HD patients exhibited significantly higher intraoperative blood loss (415.8 ± 231.7 mL vs 293.4 ± 57.3 mL, <i>P</i> < 0.001) and lower 2-year bony fusion rates (72.9% vs 94.7%, <i>P</i> = 0.008). Pseudoarthrosis and adjacent segment disease (ASD) were more common in the HD group, necessitating reoperation in five cases versus one in controls. Neurological recovery at 2 years was worse in the HD group, with a mean Japanese Orthopaedic Association score of 19.6 ± 4.3 compared to 26.5 ± 2.2 in controls (<i>P</i> < 0.01). Despite facilitating initial neurological recovery, PLIF outcomes in HD patients were compromised by greater complication rates, including pseudoarthrosis and ASD. Thus, PLIF facilitates early neurological improvement in HD patients, but long-term functional outcomes are compromised due to higher rates of pseudoarthrosis and ASD, necessitating careful long-term management. Strategies minimizing mechanical stress and maintaining spinal alignment could further support long-term patient recovery.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"528-537"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical hemolytic uremic syndrome treated with anti-C5 antibody agent eculizumab, without genetic complement abnormalities.","authors":"Yuka Sato, Noritoshi Kato, Marina Asano, Hideaki Shimizu, Yoshitaka Tatematsu, Yuko Shimamura, Asuka Horinouchi, Kayaho Maeda, Sawako Kato, Tomoki Kosugi, Shoichi Maruyama","doi":"10.18999/nagjms.87.3.573","DOIUrl":"10.18999/nagjms.87.3.573","url":null,"abstract":"<p><p>Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease often complicated by end-stage renal disease. Anti-C5 antibody agents have been developed for the treatment of aHUS: these are highly effective but limited in use owing to the difficulty of diagnosing aHUS in the acute clinical phase. The pathophysiology of aHUS is a thrombotic microangiopathy (TMA) caused by complement dysregulation triggered by environmental factors in susceptible individuals with genetic factors. Although several germline variants associated with aHUS have been identified, approximately half of patients with aHUS lack known pathogenic variants. It is essential to recognize the characteristic clinical features of aHUS. These include the triad of hemolytic anemia, thrombocytopenia, and renal impairment, without the presence of Shiga toxin-producing <i>Escherichia coli</i> infection, thrombotic thrombocytopenic purpura associated with ADAMTS13 deficiency, or TMA from secondary cause. In this case, plasma exchange could not be continued owing to allergy. Early diagnosis allowed for prompt administration of eculizumab at the time of relapse, with favorable outcomes. Based on the finding of no genetic abnormalities, eculizumab was discontinued after 12 months, with no recurrence for 3 years. On day 27 of hospitalization, renal biopsy revealed endothelial damage. Since a definitive diagnosis cannot be made with genetic testing in the acute stage and approximately half of patients have no genetic abnormalities, it is suggested to diagnose the condition as per the clinical definition and commence treatment with plasma exchange. If thrombotic thrombocytopenic purpura is excluded, switching to eculizumab is another treatment option according to clinical conditions.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"573-581"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midterm results of aortic arch replacement with frozen elephant trunk for chronic dissecting aortic aneurysm involving the aortic arch.","authors":"Shunsuke Nakata, Masato Mutsuga, Yuji Narita, Yoshiyuki Tokuda, Sachie Terazawa, Tomo Yoshizumi, Hideki Ito, Ryo Emoto, Shigeyuki Matsui, Akihiko Usui","doi":"10.18999/nagjms.87.3.558","DOIUrl":"10.18999/nagjms.87.3.558","url":null,"abstract":"<p><p>We performed total aortic arch replacement (TAR) with a frozen elephant trunk (FET) for chronic dissecting aortic aneurysm (DAA) involving the aortic arch as the initial surgery and carefully observed these aortic findings with periodic computed tomography (CT) follow-up. Additional surgical interventions were considered when aortic events were observed. Midterm outcomes were evaluated to clarify the feasibility of this strategy. Thirty-seven patients underwent TAR with FET between 2014 and 2020. The median follow-up period was 48.6 months. There was 1 case of operative mortality (2.7%) and 11 late deaths, including five aortic-related deaths. Aortic events occurred in 26 patients (72.2%), including 14 cases of stent-induced new entry (SINE), eight cases of aneurysmal enlargement, two cases of graft infection, and one each of additional aortic dissection and aortic root enlargement. Thirty-one procedures were performed, including 14 open surgeries, 16 thoracic endovascular aortic repairs (TEVAR), and 1 endovascular aortic repair (EVAR) with coil embolization. The freedom rate from aortic events was 36.9% at three years and 22.8% at five years. The distal aortic arch showed significant shrinking (slope, -1.96; <i>P<</i>0.001), but the lower descending aorta showed significant enlargement (slope, 0.87; <i>P<</i>0.001). The diameter of the middle descending aorta was a predictor of SINE (>40.5 mm) and aneurysm enlargement (>40.2 mm). The present study showed acceptable early outcomes but frequent aortic events during follow-up. Cautious periodic CT is mandatory to perform additional reinterventions at the proper time, and scheduled surgical intervention, including TEVAR, is essential for cases with enlarged middle descending aortas.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"558-572"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential effects of microglia-vascular interactions during chronic systemic inflammation in the central nervous system of mice with systemic lupus erythematosus.","authors":"Mariko Shindo, Takahiro Tsuji, Rahadian Yudo Hartantyo, Yutaro Saito, Ayaka Ito, Shouta Sugio, Ikuko Takeda, Takayoshi Suganami, Hiroaki Wake","doi":"10.18999/nagjms.87.3.509","DOIUrl":"10.18999/nagjms.87.3.509","url":null,"abstract":"<p><p>Microglia are brain specific macrophages and the only immune cells in the brain. Microglia sense the systemic immune status and contribute to neurological and psychiatric disorders. We previously showed that systemic immune activation induces microglial migration on vessels that regulate the blood brain barrier permeability. In this study, using Toll like receptor 7 induced systemic lupus erythematosus model mice, we found microglia migration on vessels and significant T cell infiltration in the brain. Additionally, microglia interacting with T cell expressed MHC class II molecules in some cases, suggesting the antigen presentation of microglia in systemic lupus erythematosus model mice. This research provides insights on the autoimmune antibody expression in the brain.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"509-520"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>XXYLT1</i> inhibits NOTCH1 activation in Jurkat cells while promoting cell proliferation.","authors":"Weiwei Wang, Wataru Saiki, Yohei Tsukamoto, Sae Uchiyama, Yuji Kondo, Tetsuya Okajima, Hideyuki Takeuchi","doi":"10.18999/nagjms.87.3.431","DOIUrl":"10.18999/nagjms.87.3.431","url":null,"abstract":"<p><p>Glycosylation, a key post-translational modification, regulates protein function in many contexts. Epidermal growth factor-like repeats undergo domain-specific <i>O</i>-glycosylation such as <i>O-</i>glucosylation, <i>O-</i>fucosylation, and <i>O-</i>GlcNAc'ylation. <i>O-</i>Glucose glycans are attached to specific serine residues by the action of protein <i>O</i>-glucosyltransferase 1 (POGLUT1) and can be elongated with two xylose residues by glucoside α1-3xylosyltransferase 1 (GXYLT1) or glucoside α1-3xylosyltransferase 2 (GXYLT2) and xyloside α1-3xylosyltransferase 1 (XXYLT1) in mammals. The xylosyl elongation of <i>O-</i>glucose as a negative regulator of Notch in <i>Drosophila</i> has recently been reported, but its role in mammalian Notch signaling remains elusive. Here, we investigated the impact of terminal xylosylation by XXYLT1 on NOTCH1 signaling in Jurkat cells, a T-cell acute lymphoblastic leukemia cell line with cell-autonomous NOTCH1 activation due to the juxtamembrane expansion mutation. Mass spectrometry analysis of NOTCH1 fragments overexpressed in Jurkat cells demonstrated that the <i>O-</i>glucose site on NOTCH1 EGF10 was modified with various elongating patterns of <i>O-</i>glucose. Genetic deletion of <i>XXYLT1</i> in Jurkat cells led to enhanced activation of NOTCH1, suggesting that <i>XXYLT1</i> inhibited NOTCH1 activation in Jurkat cells, whereas the cell surface expression of NOTCH1 was not altered. Unexpectedly, the proliferation of Jurkat cells was impaired in <i>XXYLT1</i> knockout cells, with accompanying <i>MYC</i> downregulation, a Notch target gene. Our results revealed for the first time that mammalian Notch activation is fine-tuned by xylosylation in Jurkat cells, thus highlighting the potential of Notch agonism by the inhibition of xylosylation. Additionally, our findings regarding cell proliferation underscore the notion that there are possibly substrates other than NOTCH1 that XXYLT1 modifies, thereby regulating their functions in Jurkat cells.</p>","PeriodicalId":49014,"journal":{"name":"Nagoya Journal of Medical Science","volume":"87 3","pages":"431-450"},"PeriodicalIF":0.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}