{"title":"Investigations into the Dietary Pattern of Japanese Truck Drivers and Exploring Their Associations with Depressive Symptoms and Sleep Disturbances.","authors":"Takeichiro Tominaga, Kyoko Nomura","doi":"10.1620/tjem.2026.J022","DOIUrl":"https://doi.org/10.1620/tjem.2026.J022","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanqing Liu, Qiong Xiang, Shasha Mei, Jingyi Yang, Dan Ma, Bowen Wang, Enfeng Song, Hong Zhu
{"title":"Ligustilide Promotes Gastric Cancer Cell Apoptosis via Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction and Autophagy.","authors":"Hanqing Liu, Qiong Xiang, Shasha Mei, Jingyi Yang, Dan Ma, Bowen Wang, Enfeng Song, Hong Zhu","doi":"10.1620/tjem.2025.J082","DOIUrl":"10.1620/tjem.2025.J082","url":null,"abstract":"<p><p>Ligustilide is a natural benzoquinone derivative with many pharmacological properties, including anticancer and anti-inflammatory activities. Here, we investigated the antitumor efficacy of ligustilide in gastric cancer. MKN74 and AGS cells were treated with 20, 60, and 100 µM ligustilide. The antitumor efficacy of ligustilide was studied with MTT assays, colony formation assays, and flow cytometry. Apoptosis-, endoplasmic reticulum stress-, and autophagy-associated proteins were examined by immunoblotting and immunofluorescence. JC-1 staining was used to detect mitochondrial membrane potential in cancer cells. Tumor-bearing mice were intraperitoneally injected with 5 mg/kg ligustilide. Tumor weight and tumor volume were measured after 20 days of administration. We demonstrated that ligustilide suppressed gastric cancer cell proliferation by inducing cell cycle arrest and apoptosis. Mechanistically, ligustilide disrupted mitochondrial function by increasing the Bax/Bcl-2 ratio, triggering cytochrome c release into the cytoplasm, and activating caspase-3 and PARP cleavage, ultimately leading to mitochondrial membrane potential loss. Furthermore, ligustilide enhanced autophagy, as evidenced by elevated LC3-II/LC3-I ratio and ATG5 expression, accompanied by reduced p62 levels. This autophagic response was mediated through endoplasmic reticulum stress via the PERK-eIF2α-CHOP pathway. Notably, the proapoptotic effects of ligustilide were attenuated by 4-phenylbutyric acid (an ER stress inhibitor) or 3-methyladenine (an autophagy inhibitor). Consistent with in vitro findings, 4-phenylbutyric acid also abrogated the antitumor efficacy of ligustilidein vivo by concurrently suppressing apoptosis and autophagy.Overall, ligustilide triggers mitochondrial dysfunction, autophagy, and endoplasmic reticulum stress, collectively promoting gastric cancer cell death and suppressing survival.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"391-403"},"PeriodicalIF":1.6,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-TNF-α Treatment Improves the Live Birth Rate and Reduces the Risk of Premature Delivery in Patients with Recurrent Spontaneous Abortion.","authors":"Shuxia Chen, Yuan Li, Chao Sun, Jiecheng Yang, Shaoying Li, Qiang Feng, Xin Feng, Zhe Li, Kejuan Zhang, Yuejun Liu","doi":"10.1620/tjem.2025.J103","DOIUrl":"10.1620/tjem.2025.J103","url":null,"abstract":"<p><p>Immunity and inflammation contribute to the development of recurrent spontaneous abortion (RSA); tumor necrosis factor inhibitor (TNFi) is a well-known anti-inflammation treatment for immune diseases. This study aimed to investigate the effect of TNFi on pregnancy outcomes and tolerance in RSA patients. This retrospective, observational study analyzed 115 RSA patients. Forty-three patients received TNFi plus intravenous immunoglobin (IVIG) and low molecular weight heparin (LMWH) treatment (the TNFi group), whereas another 72 patients received IVIG plus LMWH or LMWH alone treatment (the Control group). TNFi agents included certolizumab, etanercept, and adalimumab. The live birth rate was greater in the TNFi group than in the Control group (72.1% vs. 45.8%, P = 0.006), whereas the premature delivery rate tended to be lower in the TNFi group vs. the Control group but did not reach statistical significance (9.7% vs. 24.2%, P = 0.123). Multivariable logistic regression revealed that treatment (TNFi vs. Control) was independently correlated with greater live birth achievement (P = 0.001, odds ratio = 5.470); furthermore, treatment (TNFi vs. Control) tended to be independently associated with a reduced premature delivery risk (P = 0.055, odds ratio = 0.178). The type of labor (P = 0.321), neonatal birth weight (P = 0.159), and newborn Apgar score (P = 0.233) did not differ between the TNFi group and the Control group. Furthermore, adverse events, including rash, gestational hypertension, abnormal liver function index, ecchymosis, fever, and abnormal renal function index were not different between the TNFi and Control groups (all P > 0.05). TNFi improves live birth rate and tends to reduce premature delivery risk in RSA patients, providing a potential treatment option.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"405-410"},"PeriodicalIF":1.6,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Features and Surgical Management for Spinal Plexiform Schwannomas: Three Case Series and Literature Review.","authors":"Taishi Murakami, Takahiro Onoki, Ko Hashimoto, Yoshito Onoda, Kohei Takahashi, Kenichiro Yahata, Keisuke Ishikawa, Yuki Sato, Junya Kusakabe, Tomonori Kawaharada, Toshimi Aizawa","doi":"10.1620/tjem.2026.J026","DOIUrl":"https://doi.org/10.1620/tjem.2026.J026","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SALL4 Transcriptional Regulates CRIPTO to Boost the Stemness and Doxorubicin Hydrochloride Resistance of Colon Cancer Cells.","authors":"Rui Chen, Jianhui Chen, Chenqiao Ye, Jiaxin Yang, Shenkang Zhou, Pinlu Jiang","doi":"10.1620/tjem.2026.J002","DOIUrl":"https://doi.org/10.1620/tjem.2026.J002","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Memory-Phenotype CD4<sup>+</sup> T Lymphocytes: A Double-Edged Sword in Immune Responses.","authors":"Takeshi Kawabe","doi":"10.1620/tjem.2026.J040","DOIUrl":"10.1620/tjem.2026.J040","url":null,"abstract":"<p><p>CD4<sup>+</sup> T lymphocytes play an essential role in adaptive immune responses and comprise naïve, effector, and memory compartments. In pathogen infection, foreign antigen (Ag)-specific naïve T lymphocytes are activated to give rise to effector and memory cells to contribute to host protection from the pathogen. In addition to the conventional activation pathway, accumulating evidence suggests that some naïve cells can weakly respond to self-Ags to convert to \"memory-phenotype (MP) cells\" in steady state. Whereas newly generated MP cells adopt a rapidly proliferating, undifferentiated feature, they cease to divide with time while differentiating into distinct subsets including T helper type 1 (Th1)-like \"MP1,\" T helper type 17 (Th17)-like \"MP17,\" follicular helper T (Tfh)-like \"MPfh,\" and regulatory T cells. Functionally, these MP subsets can exert innate and adaptive immune responses to contribute to infectious and anti-tumor immunity as well as autoimmunity, demonstrating both physiological and pathological aspects of MP T lymphocytes. Furthermore, recent reports suggest that self-reactive MP cells are also existent in humans. In this article, I will review our current understanding on generation, maintenance, differentiation, and immunological functions of MP CD4<sup>+</sup> T lymphocytes and discuss their potential as a new therapeutic target in several disease contexts.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"287-297"},"PeriodicalIF":1.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Age-Specific Trends and Health Status of Children Aged 12-19 Years with Specified Chronic Pediatric Diseases in Japan - Insights from a National Database Study.","authors":"Erika Kuwahara, Akinori Moriichi, Hitoshi Kato","doi":"10.1620/tjem.2025.J073","DOIUrl":"10.1620/tjem.2025.J073","url":null,"abstract":"<p><p>Japan has a national financial assistance program called the \"Specified Chronic Pediatric Diseases of Japan\" (SCPDJ; also called \"Shouman\" in Japanese) for children with chronic diseases designated by the Japanese Ministry of Health, Labour and Welfare. The information of registrants in the system is digitized for research. We utilized the database to clarify the characteristics of children with diseases designated by the SCPDJ program. Analysis was performed with a particular focus on patients aged 12-19 years, which are considered the important ages for transition support from pediatric to adult medical care. The data included 69,061 cases aged 0 to 19 years from April 2016 to March 2017. The number of registrants showed a cumulative increase from 2 years toward adulthood. There were four distribution patterns for registered age and age at onset by disease category: 1) both age and age of onset peaked at age 0; 2) age distribution was mostly flat, while the most common age of onset was age 0; 3) age distribution peaked in older age groups, while age of onset of 0 was most common; and 4) both age and age of onset peaked at older ages. Approximately half of the patients aged 12-19 years were diagnosed after reaching school age. Although the disease condition of most patients remained good, some aged 12-19 years experienced exacerbation. The database was analyzed to provide an overview of children with diseases designated by the SCPDJ program and issues related to transition to adult care systems.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"379-389"},"PeriodicalIF":1.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wnt2 Expression in Cancer-Associated Fibroblasts Precedes Lymph Node Metastasis in Orthotopic Transplantation Mouse Model of Colorectal Cancer.","authors":"Hideaki Karasawa, Keigo Murakami, Koh Miura, Hiroyuki Sasaki, Tomoyuki Ono, Taiki Kajiwara, Akihiro Yamamura, Takashi Kamei, Shinobu Ohnuma, Toru Furukawa, Michiaki Unno","doi":"10.1620/tjem.2025.J039","DOIUrl":"10.1620/tjem.2025.J039","url":null,"abstract":"<p><p>Lymph node (LN) metastasis is one of the most common mechanisms underlying the spread of solid cancers. Mouse models of orthotopic tumor transplantation have been used to elucidate the metastatic mechanisms. Previous studies have mainly focused on metastasis in orthotopic models, and the correlation between histological findings of infiltrated cancer cells and tumor microenvironment has not been fully explored. Cancer-associated fibroblasts (CAFs) play a key role in metastasis, especially via secreting Wnt2, which plays a functional role in cancer progression. Here, we investigated the correlation between the incidence of LN metastases and histological findings in an orthotopic mouse model using 22 colorectal cancer cell lines. Lymphatic invasion was significantly associated with LN metastasis. Immunohistochemistry revealed that podoplanin and αSMA were highly expressed in the cancer stroma, thus suggesting that CAFs were also induced in the orthotopic implantation mouse model. Furthermore, Wnt2 positivity was mainly observed in the cancer stroma, and Wnt2 expression was significantly associated with the incidence of LN metastasis. Our results indicate that the orthotopic mouse model recapitulates cancer infiltration and the tumor microenvironment, including CAFs. The contribution of Wnt2 toward LN metastasis was also validated in an in vivo model. Thus, our findings provide new insights into the functional roles of CAFs and Wnt2 in metastasis.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"369-377"},"PeriodicalIF":1.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}